Passive Coherent Location (PCL), eller Passiv Radar som det populärt kallas, är enteknologi inom radarlära som innefattar radartyper som inte själva skickar ut elektromagnetiska vågor för att finna och undersöka ett mål. Istället använder sig dessa radartyper av befintliga signaler, såsom radio- och TV-sändningar för att detektera mål. På så vis är det betydligt svårare att upptäcka en passiv radar jämfört med en traditionell aktiv radar. SAAB utvecklar teknologi och metoder för passiva radarsystem. För att få en förståelse för ett av deras PCL-systems prestanda behöver SAAB utveckla en enkel metod för att fastställa radartäckningen. Som ett steg till detta har SAAB därför givit författaren till denna rapport i uppgift att skapa ett gränssnitt som kombinerar och jämför PCL-systemet med detektioner från en automatic dependent surveillance broadcast (ADS-B). Detektionerna från ADS-B kan då fungera som ett facit för hur väl PCLsystemet tar upp detektioner. Vilket ger gränssnittets användare en god indikationför PCL-systemets utsträckning och reliabilitet. Intervjuer hölls med anställda på SAAB som har erfarenhet av att arbeta med likvärdiga system och dess gränssnitt. Intervjuerna var semistrukturerade med frågor som syftade att utforska vilka funktioner som uppskattas och vilka svårigheter deltagarna ser i nuvarande gränssnitt. Utefter deltagarnas svar på intervjuerna byggdes en behovsanalys som tillsammans med teorier inom området låg till grund för utformningen av gränssnittsprototypen. Lösningsförslaget är en gränssnittsprotyp som visar datapunkter där detektion av mål visas från PCL-systemet och ADS-B. / Passive Coherent Location (PCL), or more popularly known as Passive Radar, is a subgenre within the field of radartechnology which includes radar types that does not transmit electromagnetic signals by themselves to find and investigate targets. Instead, they use already existing transmission, such as radio and TV broadcasts, to detect a target. Thus, it is much harder to discover a passive radar compared to a traditional active radar. SAAB is developing technologies and methods for passive radar systems. To get an understanding of the performance of one of their PCL systems, SAAB is looking for a simple method to determine the coverage of the radar. As part of this SAAB has given the author of this report the task of developing an interface which combines and compares the PCL-system with the detections of an automatic dependent surveillance broadcast (ADS-B). The detections from the ADS-B can then act as an answer key for how well the PCL-system detects targets. Thus, giving the interfaces user a good indication for the PCL-systems coverage and reliability. Interviews were conducted with SAAB employees experienced in working with similar systems and their interfaces. These interviews were semi-structured, with questions aiming to explore appreciated features and identified challenges in the current interfaces. A needs analysis was constructed based on the participants answers in the interviews, which, combined with theories within the field served as the foundation for designing the interface prototype. The proposed solution is an interface prototype, displaying data points from the PCL system and ADS-B.

The sexual abuse of children is an issue that society must address with urgency and commitment, given the profoundly damaging effects and widespread occurrence of this kind of crime. Providing psychological treatment to identified offenders is an important endeavour of the criminal justice system, with the aim of reducing recidivism and thereby preventing future victims. This dissertation explores a number of areas relevant to the treatment of sexual offenders on a sample of 223 adult males who completed a prison-based programme for child sexual offenders in New Zealand. Specifically, the assessment of treatment outcome and its relationship with recidivism, risk assessment, and the influence of specific offender factors on estimates of treatment outcome and risk were investigated. Study 1 (N = 218) is an independent validation of the validity of the Violence Risk Scale: Sexual Offender Version (VRS:SO; Olver, Wong, Nicholaichuk, & Gordon, 2007), a recently developed risk assessment instrument for sexual offenders that incorporates both static and dynamic risk factors and contains protocols for the assessment of change as a result of treatment. Results indicate support for the inter-rater reliability, concurrent validity, and predictive validity of the VRS:SO with regard to sexual recidivism, with pre-treatment and post-treatment scores showing superior predictive validity relative to a widely used measure of static risk (Static-99; Hanson & Thornton, 1999) and a measure of "Deviance" based on a 4-factor battery of relevant psychometric tests (Allan, Grace, Rutherford, & Hudson, 2007). In Study 2 (N = 218), three separate methods of assessing proximal treatment outcome (representative of three categories of treatment outcome measures that have previously been applied in the literature) are applied and compared in terms of their predictive validity with regard to sexual recidivism, and the relative advantages and disadvantages of their use. These measures are: change on a battery of relevant psychometric tests administered prior to and following treatment; change across treatment on the VRS:SO; and post-treatment ratings of the attainment of treatment goals as measured by a modified version of Hogue’s (1994) Standard Goal Attainment Scaling for Sexual Offenders (SGAS). Results indicate that positive treatment outcomes as measured by all of these methods are associated with reduced sexual recidivism. SGAS scores are identified as being relatively simple and efficient to obtain, however the VRS:SO and the psychometric battery are both able to provide useful pre-treatment clinical information regarding potential treatment targets for a particular offender. Study 3 (N = 223) and Study 4 (N = 216) are explorations of the influence of particular offender characteristics on response to treatment and risk of recidivism. Of particular interest was the personality construct of psychopathy (measured using the Psychopathy Checklist-Revised, PCL-R; Hare, 1991), and both studies are attempted replications and extensions of previously reported interaction effects involving this construct (Heilbrun, 1979; Seto & Barbaree, 1999). The results of Study 3 indicate that there is no interaction effect between PCL-R scores and treatment outcome (as measured by the SGAS) on sexual recidivism, in contrast to an influential study by Seto and Barbaree (1999). Study 4 reports an interaction effect between PCL-R scores and intelligence on recidivism, such that higher than average IQ scores appear to moderate the well-known association between psychopathy and risk. Overall, the findings reported in this dissertation suggest the importance of considering dynamic factors as well as static factors in sex offender risk assessments, and support the premise that dynamic factors are changeable, with change being associated with changes in recidivism. The potential for certain offender characteristics to influence treatment response and risk of recidivism is highlighted, and several areas for further exploration are identified.

O câncer de próstata é o tipo de câncer mais incidente no sexo masculino, sendo estimados 68.220 novos casos no Brasil para cada ano do biênio 2018-2019. Embora tenha-se observado um enorme progresso no tratamento do câncer de próstata nas últimas décadas, esta doença continua sendo a segunda maior causa de mortes relacionadas ao câncer em homens. Entre os fármacos indicados para o seu tratamento, o docetaxel aparece como escolha de primeira-linha dada sua grande eficácia terapêutica. Entretanto, efeitos adversos severos estão relacionados ao uso deste fármaco. Para superar estes problemas, a veiculação de quimioterápicos em sistemas de liberação nanoestruturados vem sendo amplamente estudada nos últimos anos, dados os diversos benefícios que oferece. Deste modo, o presente trabalho visou desenvolver, caracterizar e avaliar biologicamente nanopartículas poliméricas a base de um copolímero de policaprolactona-DL-?-tocoferol-polietilenoglicol-1000 (PCL-TPGS) contendo docetaxel para uso na terapia do câncer de próstata. As nanopartículas foram obtidas pela técnica de nanoprecipitação e caracterizadas por suas características físico-químicas, morfológicas e biológicas. Os sistemas foram obtidos com sucesso e possuem distribuição de tamanhos adequada para os objetivos propostos (PSD 130 ± 18 nm, PDI 0,10 ± 0,04 e ZP -30,1 ± 2,3 mV), alto rendimento, eficiência de encapsulação e capacidade de carga (98,7 ± 3,2%, 96,2 ± 1,1% e 5,01 ± 0,32%, respectivamente). Os estudos calorimétricos e espectroscópicos permitiram avaliar o estado físico do fármaco na nanopartícula e sugerir a encapsulação. Ensaios biológicos demonstraram elevada capacidade dos nanocarreadores contendo docetaxel em causar dano celular em linhagem de câncer de próstata (PC-3), atingindo EC50 de 0,4760 ± 0,092 nM. A avaliação da internalização celular resultou em 97,64 ± 1,21%, coerentes com os resultados de citotoxicidade. Estudos in vivo demonstraram eficácia do sistema desenvolvido em modelo animal, cuja capacidade de redução tumoral foi superior à formulação comercial de docetaxel. O sistema desenvolvido tem potencial para o aprimoramento da terapia citotóxica convencional em humanos, sendo necessários estudos posteriores para a assegurar sua segurança clínica. / Prostate cancer is the most common type of cancer in men, with an estimated 68,220 new cases in Brazil for each year of the 2018-2019 biennium. Although tremendous progress has been made in the treatment of prostate cancer in recent decades, this disease remains the second leading cause of cancer-related deaths in men. Among the drugs indicated for its treatment, docetaxel appears as a first-line choice given its great therapeutic efficacy. However, severe adverse effects are related to the use of this drug. To overcome these problems, the delivery of chemotherapy in nanostructured release systems has been widely studied in recent years, given the several benefits it offers. Thus, the present work aimed to develop, characterize and biologically asses polymeric nanoparticles based on a copolymer of polycaprolactone- DL-?-tocopherol-polyethylene glycol-1000 (PCL-TPGS) containing docetaxel for use in prostate cancer therapy. The nanoparticles were obtained by the nanoprecipitation technique and characterized by their physical-chemical, morphological and biological characteristics. The systems were successfully obtained and have suitable size distribution for the proposed objectives (PSD 130 ± 18 nm, PDI 0.10 ± 0.04 and ZP- 30.1 ± 2.3 mV), high yield, encapsulation efficiency and loading capacity (98.7 ± 3.2%, 96.2 ± 1.1% and 5.01 ± 0.32%, respectively). Calorimetric and spectroscopic studies allowed the evaluation of drug physical state within the nanoparticle and suggest the encapsulation. Biological assays demonstrated a high ability of docetaxel-containing nanocarriers to cause cell damage in prostate cancer cell line (PC-3), reaching EC50 of 0.4760 ± 0.092 nM. The evaluation of the cellular internalization resulted in 97.64 ± 1.21%, consistent with the results of cytotoxicity. In vivo studies demonstrated efficacy of the system developed in an animal model, whose tumor reduction capacity was superior to the commercial formulation of docetaxel. The developed system has potential for the improvement of conventional cytotoxic therapy in humans, and further studies are needed to ensure its clinical safety.

Ce travail de thèse s’inscrit dans le cadre d’une collaboration entre Sanofi à Vitry-sur-Seine et le Laboratoire Hétérochimie Fondamentale et Appliquée (LHFA) à Toulouse, et a pour but de développer de nouveaux nanovecteurs à base de conjugués polymériques biodégradables et biocompatibles capables d’encapsuler, de transporter et de libérer des agents thérapeutiques. Les travaux précédemment réalisés au laboratoire, ont montré que la libération de principes actifs hydrophobes, tels que le Cabazitaxel de la famille des taxanes, pouvait être contrôlée grâce à l’architecture de conjugués de nature PEG-PLA. Dans le premier chapitre, une étude a été menée afin d’améliorer la cinétique de libération du principe actif, en tirant profit de la différence de pH qui réside entre les tissus sains et les tissus cancéreux. Différents liens (reliant le principe actif au copolymère) ayant un comportement pH dépendant ont été étudiés, comme l’hydrazone, l’acétal et le β-thiopropionate. La liaison ester boronique, dynamique en fonction du pH, a aussi été étudiée dans le but de déstructurer la NP et permettre indirectement d’améliorer la libération du principe actif. La synthèse et l’évaluation des divers conjugués ont montré que la structure polymérique amphiphile des conjugués inhibait considérablement le comportement pH dépendant attendu. Dans le second chapitre, plusieurs technologies comme le ciblage, permettant de diriger la NP dans l’organisme, ou l’imagerie permettant de les visualiser, ont été étudiées. L’influence de la structure des conjugués de forme Y et L sur les propriétés de reconnaissance et d’imagerie a été analysée. La structure Y offre quelques avantages quant à la quantité de ligand requise pour obtenir un ciblage actif optimal ainsi qu’une meilleure visualisation, en comparaison des résultats obtenus avec les conjugués L. La méthode de co-nanoformulation a permis de faire varier la quantité de ligand ou de sonde d’imagerie au sein des NPs. Dans le troisième chapitre, la synthèse et l’efficacité de sels de (bi)pyridinium comme catalyseurs pour la ROP de l’ε-caprolactone sont présentées. Un phénomène de coopérativité avec des bipyridiniums, dications donneurs de deux liaisons hydrogènes (IHBD) a été mis en évidence pour l’activation de l’ε-caprolactone, avec des activités en ROP plus importante en comparaison des systèmes impliquant la participation d’une seule liaison H. Les meilleurs systèmes ont pu être évalués plus en détail et ont permis d’accéder à des polymères de masses définies allant jusqu’à 13 000 g/mol. / This PhD thesis is based on a joint between Sanofi in Vitry-sur-Seine and LHFA. This work consists in the development of new nanovectors based on biodegradable and biocompatible polymerics conjugate that enable to encapsulate, transport and deliver therapeutic agents. Previous works in the laboratory have shown that the release of hydrophobic drugs, such as Cabazitaxel, a taxane derivative, could be controlled by the architecture of the conjugated PEG-PLA. In the first chapter, a study was realized to improve the release kinetics of the drug, taking advantage of the difference of pH between healthy and cancerous tissue. Different linkers (linking the drug to the copolymer) having a pH dependent behavior have been studied, such as hydrazone, acetal and β-thiopropionate. The boronic ester bonding, dynamic function of pH, was also studied in order to destroy the NP and indirectly improve the release of drug. The synthesis and the evaluation of various conjugates have shown that the amphiphilic polymeric structure of the conjugates significantly inhibited the expected pH-dependent behavior. In the second chapter, several technologies such as targeting or imaging were studied. The influence of the Y and L-shape on the recognition and imaging properties was analyzed. The Y-shape offers advantages like the amount of ligand required for optimal active targeting and better visualization, in comparison with the results obtained with the L conjugates. The method of co-nanoformulation allowed to adjust the ligand amount or imaging probe within the NPs. In the third chapter, the synthesis and efficiency of (bi)pyridinium salts as catalysts for the ROP of ε-caprolactone are presented. A collaborative behavior with dication bipyridiniums is bearing two hydrogen bonds (IHBD) was demonstrated for the activation of the ε-caprolactone, with greater ROP activities compared to systems involving the participation of only one H bond. The best systems were evaluated in more details and allowed access to polymers with a molecular weight of up to 13 000 g / mol.

<p>Forskning har visat att förekomst av riskfaktorer för brottsrecidiv skiljer sig mellan vålds- och sexualbrottslingar. Ytterligare forskning behövs dock om skillnader mellan mer specifika brottskategorier. Syftet var att undersöka skillnader mellan män dömda för mord (n=363), dråp (n=110), rån (n=238), sexualbrott mot vuxen (n=71) respektive sexualbrott mot barn (n=57) avseende ålder, psykopatiprofil enligt PCL-R samt riskkaraktäristika bedömt med HCR-20. Resultatet visade att personer dömda för sexualbrott mot barn hade lägre förekomst av historiska riskfaktorer, lägre grad av psykopati, samt var äldre än övriga grupper. Gruppen dömda för dråp hade en lägre grad av psykopatisk personlighet (faktor 1) än de andra våldsbrottsgrupperna, mord och rån, medan de hade den antisociala livsstilen typisk för psykopater (faktor 2). Det omvända gällde för gruppen sexualbrott mot vuxen. Grupperna rån och mord liknade varandra på flertalet variabler, dock var personer dömda för rån yngre än samtliga grupper. Resultaten har betydelse för utformande av åtgärder avsedda att minska recidivrisken.</p>

Macromolecular engineering is one of the most powerful tools to control the molecular parameters, including architecture of polymers, and to improve their performances or to impart them new properties. This contribution aims at reporting on a novel strategy for the macromolecular engineering of poly-ε-caprolactone (PCL) which is based on the use of functional ε-caprolactone, the α-chloro-ε-caprolactone (αClεCL). Indeed, αClεCL is a precursor of polymers and copolymers with εCL that bear pendant activated chlorides well suited to grafting from reaction. These (co)polyesters have been used as macroinitiators for the Atom Transfer Radical Polymerization (ATRP) of methyl methacrylate leading to the corresponding graft copolymer. They have also been involved in an Atom Transfer Radical Addition (ATRA) reaction with a series of olefins bearing different functional groups (hydroxyl, carboxylic acid and epoxy group) in order to functionalize the polyester backbone without deleterious degradation. ATRA of PEO chains with an unsaturation end groups has also been carried out in order to prepare PCL-g-PEO of different compositions to be used as stabilizers of polyester nanoparticles. Combination of ring-opening polymerization of ε-caprolactone and the copper-catalyzed Huisgens [3+2] cycloaddition is a novel strategy for going a step further in the macromolecular engineering of poly-ε-caprolactone (PCL). This click reaction is very well-suited to the chemical modification of aliphatic polyesters because, its implementation under very mild conditions prevents chain degradation from occurring. Indeed, alkynes were cycloadded onto azide containing PCL at low temperature (35°C) in an organic solvent (DMF or THF). Originally, α-chloro-ε-caprolactone and ε-caprolactone were randomly copolymerized in toluene at room temperature followed by reaction of the activated chlorides with sodium azide. In order to make a wide range of functional aliphatic polyesters available, poly(α-azide-ε-caprolactone-co-ε-caprolactone) copolyesters were reacted with a series of alkynes substituted by a functional group, e.g., hydroxyl, acrylate and quaternary ammonium salts, This strategy turned out to be efficient to synthesize for instance hydrophilic, photo-cross-linkable and hydrosoluble PCL. Moreover, a variety of graft copolymers were prepared by both the grafting from and the grafting onto techniques. Indeed, an ATRP initiator was attached onto PCL followed by polymerization of vinyl monomers, whereas alkyne endcapped PEO was cycloadded onto azide-containing PCL with formation of amphiphilic PCL-g-PEO copolymers. Last but not least, the click chemistry was very instrumental in imparting an antimicrobial activity to PCL or for the preparation of new functionalized caprolactones.

Forskning har visat att förekomst av riskfaktorer för brottsrecidiv skiljer sig mellan vålds- och sexualbrottslingar. Ytterligare forskning behövs dock om skillnader mellan mer specifika brottskategorier. Syftet var att undersöka skillnader mellan män dömda för mord (n=363), dråp (n=110), rån (n=238), sexualbrott mot vuxen (n=71) respektive sexualbrott mot barn (n=57) avseende ålder, psykopatiprofil enligt PCL-R samt riskkaraktäristika bedömt med HCR-20. Resultatet visade att personer dömda för sexualbrott mot barn hade lägre förekomst av historiska riskfaktorer, lägre grad av psykopati, samt var äldre än övriga grupper. Gruppen dömda för dråp hade en lägre grad av psykopatisk personlighet (faktor 1) än de andra våldsbrottsgrupperna, mord och rån, medan de hade den antisociala livsstilen typisk för psykopater (faktor 2). Det omvända gällde för gruppen sexualbrott mot vuxen. Grupperna rån och mord liknade varandra på flertalet variabler, dock var personer dömda för rån yngre än samtliga grupper. Resultaten har betydelse för utformande av åtgärder avsedda att minska recidivrisken.

This thesis presents a finite element method based comparative study of linear and geometrically non-linear progressive failure analysis of thin walled composite aerospace structures, which are typically subjected to combined in-plane and out-of-plane loadings. Different ply and constituent based failure criteria and material property degradation schemes have been included in a PCL code to be executed in MSC Nastran. As case studies, progressive failure analyses of sample composite laminates with cut-outs under combined loading are executed to study the effect of geometric non-linearity on the first ply failure and progression of failure. Ply and constituent based failure criteria and different material property degradation schemes are also compared in terms of predicting the first ply failure and failure progression. For mode independent failure criteria, a method is proposed for the determination of separate material property degradation factors for fiber and matrix failures which are assumed to occur simultaneously. The results of the present study show that under combined out-of-plane and in-plane loading, linear analysis can significantly underestimate or overestimate the failure progression compared to geometrically non-linear analysis even at low levels of out-of-plane loading.

While forensic psychiatric inpatient violence is a serious problem, research on risk assessment for this outcome is limited; the current research investigated the predictive validity of a number of structured risk/forensic instruments for inpatient violence. Research objectives included: 1) observing the profile of dynamic changes in violence risk detected by existing violence risk assessment instruments; 2) assessing whether existing violence risk assessment instruments could be used to assess risk for inpatient violence; 3) evaluating the contribution of dynamic risk measures to the prediction of inpatient violence; and 4) assessing the relationship between dynamic changes in risk and inpatient violence. Instruments included: the Historical Clinical Risk Management 20 - Version 3 (HCR-20V3), the Psychopathy Checklist Revised (PCL-R), the Short-Term Assessment of Risk and Treatability (START), the Revised Violence Risk Appraisal Guide (VRAG-R), and the Violence Risk Scale (VRS). Two studies were conducted on a maximum-security forensic psychiatric unit at Alberta Hospital Edmonton. Study 1 was a pseudo-prospective archival investigation (n = 99), while Study 2 was a prospective investigation (n = 19); all risk assessment scores were based on information available in institutional files. Instruments designed to capture dynamic/clinical risk variables (HCR-20V3, START, VRS) detected dynamic changes in risk in this setting over longer follow-ups (i.e., between admission and discharge), but not over shorter follow-ups (i.e., 28 day periods). Predictive validity analyses indicated that specialized measures designed to capture relevant dynamic/clinical variables were significant predictors of inpatient violence; instruments that were not designed for this purpose (PCL-R and VRAG-R), did not demonstrate predictive validity for inpatient violence. Dynamic measures consistently demonstrated incremental predictive validity for inpatient violence, beyond the static measures. Additionally, change scores demonstrated incremental relationships with decreased inpatient violence, beyond pretreatment scores. Put another way, positive risk change was associated with decreased violence over the course of the patients’ stays in hospital. Reliable and valid risk assessments are a necessary component of effective offender programming (Risk-Need-Responsivity Model) and the current results indicated that valid violence risk assessments for forensic psychiatric inpatient violence are possible. Implications for clinical practice and the reduction/mitigation of inpatient violence are discussed.

Tissue engineering is a multidisciplinary field that is rapidly emerging as a promising approach for tissue repair and regeneration. In this approach, scaffolds which allow cells to invade the construct and guide the cells grow into specific tissue play a pivotal role. Electrospinning has gained popularity recently as a simple and versatile method to produce fibrous structures with nano- to microscale dimensions. These electrospun fibers have been extensively applied to create nanofiber scaffolds for tissue engineering applications. Specifically for bone and cartilage tissue engineering, polymeric materials have some attractive properties such as the biodegradability. Ceramic scaffolds and implant coatings, such as hydroxyapatite and silica-based bioglass have also been considered as bone graft substitutes for bone repair because of their bioactivity and, in some cases, tunable resorbability. Besides tissue engineering scaffolds, for clinical application, especially for load-bearing artificial implants, metallic materials such as titanium are the most commonly used material. Osseointegration between bone and implants is very essential for implant success. To achieve better osseointegration between bone and the implant surface, three dimensional porous structures can provide enhanced fixation with bone by allowing tissue to grow into the pores. In this study, pre-3D electrospun polymer and ceramic scaffolds with peptide conjugation and 3D titanium scaffolds with different surface morphology were fabricated to testify the osteoblast and mensechymal stem cell attachment and differentiation. The overall goal of this thesis is to determine if the peptide functionalization of polymeric scaffolds and physical parameters of ceramic and metallic scaffold can promote osteoblast maturation and mesenchymal stem cell differentiation in vitro to achieve an optimal scaffold design for greater osseointegration. The results of the studies showed with functionalization of MSC- specific peptide, polymer scaffolds behaved with higher biocompatibility and MSC affinity. For the ceramic and metallic scaffolds, microstructures and nanostructures can synergistically promote osteoblast maturation and 3D micro-environment with micro-roughness is a promising design for osteoblast maturation and MSC differentiation in vitro compared to 2D surfaces.