The aryl hydrocarbon receptor (AhR) binds a wide range of structurally diverse compounds such as halogenated dibenzo-p-dioxins, dibenzofurans and biphenyls which are abundant in the environment. Activation of AhR leads to the regulation of a battery of xenobiotic enzymes including cytochrome P4501A1 (CYP1A1). The purely chlorinated compounds feature in the World Health Organisation’s (WHO) evaluation of dioxin-like compounds derived from a meta-analysis of previous potency data (toxic equivalency factors; TEFs), which is used to calculate the total toxic equivalence (TEQ). The first aim of this work was to fully characterise the three most environmentally abundant mono-ortho-substituted polychlorinated biphenyls (PCBs; PCB 105, 118 and 156) including a re-evaluation of their putative antagonistic effects on AhR. Secondly, the effects of mixed halogenated compounds, currently not included in the TEQ estimation, were investigated as AhR agonists based on their environmental exposure and potency. Quantitative real-time PCR (qRT-PCR) was used to measure the AhR mediated induction of CYP1A1 mRNA in rat H4IIE and human MCF-7 cells. The three mono-ortho-substituted PCBs were shown to be antagonists of rat and human AhRs, an effect which is not currently included in the TEQ calculation. 2-bromo-3,7,8-trichlorodibenzo-p-dioxin (2-B-3,7,8-TriCDD) was found to be an AhR agonist that was 2-fold more potent than 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; considered one of the most potent in the environment). The majority of the other tested compounds were found to be within 10-fold less potent than TCDD and could therefore have a significant impact on the TEQ. A family of putative AhR agonists from AstraZencea were investigated and one of the compounds was shown to be a highly potent AhR agonist, 5-fold more potent than TCDD at inducing CYP1A1. The results indicate approximately a 15-fold higher sensitivity of the rat cell line to the AhR agonists compared with the human cell line. It is not currently understood what confers these differences whether it is a difference in the mechanism of activation or purely as a result of differences in the AhR sequence. The mechanism of action is thought to be the same in both species and the associated proteins are both comparable. The amino acid sequences of the AhR, in both human and rat are quite similar but may play a significant role in the differences observed between species. Therefore in order to directly compare the rat and human AhRs, two novel cell line models were created using an inducible expression system to infect an AhR-deficient mouse cell line with a replication-defective virus containing either the rat or human AhR. The AhRs were activated with various compounds to induce mouse CYP1A1. The CYP1A1 mRNA was measured using qRT-PCR but showed that the two AhR genes were not expressed enough to produce a response detectable above the background CYP1A1 induction by the low levels of mouse AhR. This research has shown that these dioxin-like compounds can have very different potencies at AhRs in different species so it is not always possible to predict the potency in humans from in vitro or rat in vivo toxicity data. Furthermore, it has identified compounds, such as 5F-203, which are significantly more potent in human compared to rat. This thesis provides information on the AhR species differences between human and rat that can be applied to risk assessment.

SOARES, A.T.C. Perfil antropológico das ossadas analisadas no Centro de Medicina Legal (CEMEL) da Faculdade de Medicina de Ribeirão Preto USP. 2007. 169 p. Dissertação (Mestrado) Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, 2007. A Antropologia Forense é uma área do conhecimento que aplica os métodos da antropologia física e arqueologia para coleta e análise de evidências legais, buscando estabelecer a identidade de um ser. O Centro de Medicina Legal (CEMEL) da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP) possui um Laboratório de Antropologia Forense, criado em 2005 durante o desenvolvimento de um projeto em parceria com a University of Sheffield (UK) e financiado pelo British Foreign and Commonwealth Office Global Opportunities Fund. Durante esse projeto, um protocolo para análise de ossadas foi implementado dentro de uma estrutura científica atualizada para aplicação em contextos de importância social. Após dois anos de funcionamento, constatou-se que muitas das ossadas encaminhadas ao CEMEL estavam incompletas, tornando a realização de um perfil biológico difícil e postergando a sua identificação devido à ausência de informações e literatura nacional recente sobre Antropologia Forense. Assim, 42 ossadas humanas examinadas no CEMEL desde sua inauguração em 1999 foram analisadas e revisadas. Os resultados mostraram que a maioria dos casos era de indivíduos do sexo masculino, de ancestralidade caucasiana, com idade entre 32,71 e 46,29 anos, estatura entre 1,64 e 1,73m, destros, sem achados patológicos, com elementos odontológicos informativos, mas sem roupas ou outros pertences. Observou-se que 61,90% das ossadas possuíam menos de 50% dos ossos, com média de 79,64±52,40 ossos por caso. Os ossos mais encaminhados foram occipital, parietal esquerdo, temporal esquerdo, parietal direito, temporal direito, fêmur direito e vértebras torácicas de um a 12. Os ossos menos encaminhados foram hióide, piramidal esquerdo, falange distal superior um direita, falanges distais superiores dois a cinco direitas e falanges médias superiores dois a cinco esquerdas. Os dentes mais encaminhados foram o 2º molar superior direito e o 1º molar superior direito, enquanto que os dentes menos encaminhados foram o incisivo central superior direito, os incisivos centrais inferiores direito e esquerdo. Roupas e outros pertences estavam presentes em 20 casos, totalizando 66 itens. Trinta e um casos têm potencial para identificação somente através de técnicas de Antropologia Forense. Para os demais 11 casos provavelmente será necessário utilizar DNA para identificação. Diante dos resultados observados, discute-se a necessidade de melhorias na capacitação técnica e infra-estrutura, assim como a forma de coleta e o transporte, de forma a aumentar o número de elementos ósseos coletados e, conseqüentemente, de informações úteis para identificação. Dois crânios apresentaram evidência de craniotomia realizada durante necropsia e um apresentou resíduos de vela, o que sugere que podem ter sido retirados indevidamente do local de sepultamento, ou até mesmo vendidos, além da sua utilização em rituais religiosos. Conclui-se que campanhas de conscientização e melhorias na fiscalização dos cemitérios podem reduzir os casos de roubos e comércio de elementos ósseos. / SOARES, A.T.C. Anthropological profile of the skeletons analyzed at the Medico Legal Centre (CEMEL) of the Faculty of Medicine of Ribeirão Preto USP. 2007. 169 p. Dissertation (Masters Degree) Faculty of Medicine of Ribeirão Preto, Ribeirão Preto, 2007. Forensic Anthropology is an area of knowledge that applies the methods of physical anthropology and archeology to the collection and analysis of legal evidence, including the search for individual identity. The Medico Legal Centre (CEMEL) of the Faculty of Medicine of Ribeirão Preto of University of São Paulo (FMRP-USP) has a Laboratory of Forensic Anthropology, created in 2005 during a development project in partnership with the University of Sheffield (UK) and financed by the British Foreign and Commonwealth Office Global Opportunities Fund. During this project, a protocol for skeletal analysis was implemented within an upgraded scientific infrastructure for application in a socially important context. After two years of work, it was noticed that many skeletons forwarded to CEMEL were incomplete, making completion of a biological profile difficult and postponing identification due to the lack of information and recent national literature about Forensic Anthropology. Therefore, 42 human skeletons examined at CEMEL since its inauguration in 1999 were analyzed and reviewed. The results showed most cases to be of male individuals, of Caucasian ethnic origin, aged between 32.71 and 46.29 y.o., of height between 1.64 and 1.73 m, right handed, without any pathological findings, with informative odontological findings, but with no clothes or other belongings. It was observed that 61.90% of the skeletons were less than 50% complete, with a mean of 79.64±52.40 bones per case. The most frequently found bones were the occipital, left parietal, left temporal, right parietal, right temporal, right femur and one to 12 thoracic vertebrae. The least frequent bones were the hyoid, left triquetral, 1st right superior distal phalanx, two to five right superior distal phalanges and two to five left superior intermediate phalanges. The most frequently found teeth were the right superior 2nd molar and right superior 1st molar, while the least frequent teeth were the right superior central incisor, and right and left inferior central incisors. Clothes or other belongings were present in 20 cases, totaling 66 items. Thirty one cases have potential to be identified only via forensic anthropological analysis. For the remaining 11 cases it will be probably necessary to use DNA for identification. In view of these observations the necessity for improvements in technical qualifications and infrastructure are discussed, as well as recovery and transport, in order to maximize the number of skeletal elements recovered andas a consequenceof information useful in identification. Two skulls presented evidence of a craniotomy conducted during autopsy and one of candle residue, suggesting that it may have been taken improperly from the place of burial, or even sold, for its use in religious rituals. It is concluded that public awareness campaigns and better inspection of cemeteries may reduce cases of robbery and trade in skeletal remains.

Introduction : l’estimation du délai post mortem (délai entre la découverte d’un cadavre et le moment du décès) est un élément important dans une enquête de police. Cette estimation est difficile lorsque le corps retrouvé est à l’état de squelette. Il existe peu d’outil pour effectuer cela.Ce travail s’inscrit dans la volonté d’élaborer des méthodes d’estimation de l’intervalle post mortem sur des restes osseux. Cette thèse s’attache à apporter des données nouvelles à l’aide de la micro-imagerie en taphonomie osseuse. Plus particulièrement, nous tentons de mettre en évidence les interactions entre l’os humain post mortem et son environnement.Matériels et méthodes : Des os humains issus de plusieurs dons du corps à la science ont été étudiés au micro-scanner. Ces os ont été conservés prospectivement pendant des périodes connues de temps connues. Les os ont été examinés au décours d’une conservation dans un environnement contrôlé et stable en température et en hygrométrie. Quatre axes d’expérimentation ont été retenus.Un premier axe de travail a porté sur la mesure de la précision du micro-scanner lors de mesures répétées. Ce travail a été réalisé sur des fragments de voûtes crâniennes et des phalanges.Un deuxième axe de travail a été réalisé sur l’impact du mode de conservation initiale de l’échantillon. Nous avons comparé l’évolution architecturale au micro-scanner de fragments de voûte crânienne conservés dans du formol à 10% ou en congélation à -20°C. Chaque échantillon a été conservé pendant 12 mois.Un troisième axe de travail s’est attaché à décrire l’évolution micro-scannographique de fragments osseux conservés en milieu standard sur diverse période (fragments de voûte crânienne sur 4 semaines et 10 semaines - fragments de côtes sur 6 et 36 mois).Résultats : Il a été mis en évidence que les acquisitions faites au micro-scanner sont précises et reproductibles.Nous avons montré qu’il existe de nombreuses variations architecturales lors de la mise en conservation d’os en milieu formolé ou en congélation. Cela montre l’importance du travail sur os frais dans un contexte taphonomique.Il a été mis en évidence des modifications architecturales significatives lors de la conservation d’os en milieu dit standard et contrôlé. Ces modifications surviennent dès les deux premières semaines de conservations pour les fragments de voûtes et sont également observées après 6 et 36 mois de conservation pour les fragments de côtes.Discussion et conclusion : Ce travail a permis de mettre en évidence l’intérêt que représente la micro-imagerie pour l’étude de l’architecture osseuse. Il s’agit d’une technologie précise et non destructrice de l’échantillon. L’apport du micro-scanner réside dans la capacité d’analyse architecturale de volumes importants. Nos résultats confirment l’influence du milieu de conservation et du temps sur le substrat osseux. Des modifications architecturales sont déjà observables après des temps de conservation variables (de quelques semaines plusieurs mois). Ces délais sont très courts au regard du délai de prescription en matière pénale et de la taphonomie en archéologie. Ces résultats méritent d’être confrontés à des données sur un plus grand nombre d’individus, sur des durées de conservation plus longues et avec de nombreux milieux de conservation. / Introduction: Estimating post-mortem delay (the time between the discovery of a dead body and the time of death) is an important element in a police investigation. This estimate is difficult when the body found is in the skeleton state. There is little tool to do this.This work is part of the desire to develop methods for estimating the post mortem interval on bone remains. This thesis focuses on providing new data using micro-imaging in bone taphonomy. In particular, we try to highlight the interactions between post mortem human bone and its environment.Materials and methods: Human bones from several body donations to science were studied by micro-scanning. These bones have been conserved prospectively for known periods of time. The bones were examined during conservation in a controlled environment and stable in temperature and hygrometry. Four axes of experimentation were retained.A first line of work focused on measuring the precision of the micro-scanner during repeated measurements. This work was done on fragments of cranial vaults and phalanges.A second line of work was carried out on the impact of the initial mode of preservation of the sample. We compared the architectural evolution with micro-scanning of cranial vault fragments preserved in 10% formalin or freezing at -20 ° C. Each sample was kept for 12 months.A third line of work focused on describing the microCT evolution of bone fragments preserved in standard medium over various periods (cranial vault fragments over 4 weeks and 10 weeks - rib fragments over 6 and 36 months).Results: It has been shown that micro-scanner acquisitions are accurate and reproducible.We have shown that there are many architectural variations in the storage of bone in formaldehyde or freezing. This shows the importance of fresh bone work in a taphonomic context.Significant architectural modifications have been demonstrated during bone conservation in a standard and controlled environment. These changes occur as early as the first two weeks of storage for the vault fragments and are also observed after 6 and 36 months of storage for the rib fragments.Discussion and conclusion: This work has made it possible to highlight the interest that micro-imaging represents for the study of bone architecture. This is a precise and non-destructive technology of the sample. The contribution of the micro-scanner lies in the capacity of architectural analysis of large volumes. Our results confirm the influence of conservation medium and time on the bone substrate. Architectural modifications are already observable after variable conservation times (from a few weeks to several months). These delays are very short with regard to the limitation period in criminal cases and taphonomy in archeology. These results deserve to be confronted with data on a larger number of individuals, longer storage periods, and many conservation environments.

This thesis aims to provide a detailed understanding of treatment engagement amongst forensic populations. Following an introduction outlining the current theoretical thinking in the area, Chapter 2 presents a systematic literature review exploring reasons for completion/non-completion of treatment from an offender's perspective. Consensus regarding reasons for treatment completion/non-completion was found. Reasons provided supported the majority of factors outlined in the Multifactor Offender Readiness Model (MORM), a model of treatment readiness. Research in this area was limited; no papers exploring adolescents' perspectives were identified. Implications for practice are discussed and areas for future research highlighted. Furthering existing research, Chapter 3 presents a mixed methods research study exploring the reasons why young people, detained in a secure hospital setting choose to attend/not attend sessions. Using thematic analysis several themes were identified. Factors relating to the young person, treatment and the organisation were identified, supporting the MORM. Chapter 4 presents a critical review of the Corrections Victoria Treatment Readiness Questionnaire (CVTRQ), a measure of treatment readiness developed using the internal factors of the MORM. This chapter explores the overall development and psychometric properties of the CVTRQ, highlighting its strengths and limitations. An overall discussion of the work presented is provided in Chapter 5.

This thesis explores facial affect processing in violent offenders, with a specific focus on how patterns of impairment seen in Intimate Partner Violent (IPV) prisoners differ to those of other violent prisoners. Chapter one introduces IPV as a serious public health concern with inadequate treatment efficacy. It discusses the overlap between IPV and non-IPV violence and highlights the need for further research elucidating how the treatment needs of IPV prisoners differ to those of non-IPV prisoners. The role of facial affect processing is then discussed in relation to empathy and violent offending. Chapter two reviews the literature on facial affect processing in violent offenders. The review found deficits in violent offenders’ recognition of negative affect, with deficits in fear, anger and disgust most reliably reported, across indices of accuracy, sensitivity and response bias. Subtleties in processing patterns were observed between violent offenders and non-violent offenders, and between violent offenders and sexually-violent offenders. The review highlighted a dearth of research exploring facial affect processing in IPV prisoners. Chapter three presents a study investigating facial affect processing among IPV and non-IPV violent prisoners and nonoffending controls. It investigated the role of eye-scan paths as a mechanism underpinning recognition deficits in violent offenders and explored the influence of psychopathology on visual scanning behaviour. Groups did not differ in their recognition accuracy but they did differ in their eye-scan paths as a function of intensity and sex of the expression; with nonoffenders demonstrating different visual scanning behaviour relative to offender groups, who did not differ from each other. There was little evidence to suggest that eye-scan paths were influenced by psychopathological profiles of the groups. Chapter four presents a critique of the revised Conflict Tactics Scales (CTS2, Straus, Hamby, Boney-McCoy & Sugarman, 1996), a widely used measure of IPV. The review highlights the objectivity of the measure as both a strength, in terms of its limiting denial, minimisation and cognitive distortions but also a limitation in its failure to take into consideration the context in which the behaviour occurred. The scales’ psychometric properties are also discussed. The thesis conclusions are presented in Chapter five, alongside recommendations for practice and research.

Judges are often reluctant to interact with medical ethics when deciding cases with an inherently ethical content. They sometimes even transfer decision-making responsibilities to medical ethics groups. At times this unwillingness is based on the presumption that medical ethics will be able to perform an effective regulatory function. The problem is there is a wide range of ethical discourse, both official and unofficial; so much it can cancel itself out. Therefore, as a regulatory tool for the medical profession, medical ethics is insufficient for the job. Judges, on the other hand, could arbitrate between competing ethical conclusions. Indeed, there is a strong argument they \(should\). This thesis addresses this timely and complex issue. Judges need to be willing and able to rely on the soundness of their own moral convictions to recognise and deal appropriately with the inherent ethical content in certain cases. In order to do this, they need a decision-making framework that recognises the ethical nature of judicial decision-making, so as to provide judges with confidence in applying moral principles and medical ethics. This thesis will provide such an integrated framework.

The main aim of this thesis is to advocate a more scientifically informed approach towards epidemiological evidence in disease litigation. It analyses the judicial scepticism about epidemiology in UK tort law, and finds that the myth of scientific certainty lies at the heart of the devaluation of epidemiology as proof of specific causation. It traces misconceptions about epidemiology to broader misconceptions about science as a whole (including medical science and disease), and confused legal approaches to causation. To explain why legal objections to epidemiology are erroneous, the thesis clarifies fundamental aspects of science and disease causation that lawyers need to better grasp. Scientific reasoning is inherently probabilistic. Further, medical research indicates that disease causation is usually multifactorial and stochastic. Rigid and deterministic ‘but for’ questions are thus fundamentally unsuited for assessing disease causation. The mismatch between legal and medical causal models makes courts resort to normative, ‘backwards’ causal reasoning or haphazard exceptional approaches to disease causation, where the most difficult dilemmas around causation arise. This thesis argues that courts need a better test for causation for disease that can take account of probabilistic scientific and epidemiological evidence, and suggests one such principled approach. Epidemiology can be invaluable in such an assessment of disease causation.

Dialectical Behaviour Therapy (DBT) is a type of “talking therapy”, developed from cognitive behavioural therapy; it has been adapted to help people who experience emotions, often females diagnosed with Borderline Personality Disorder (BPD). With its growth in popularity, DBT has been adapted and used with other populations - not just adult females with BPD – to include forensic populations (i.e. people who are in contact with services due to criminal behaviour) and adolescent populations. This thesis contains a systematic literature review investigating the use of DBT in Forensic Services and an empirical study that utilised a qualitative design to explore adolescents and parents’ experiences of DBT.

Forensic science is defined as the application of scientific or technical practices to the recognition, collection, analysis, and interpretation of evidence for criminal and civil law or regulatory issues. A combination of computer science in the field of 3D reconstruction and molecular biology science and techniques were employed in this research aims to document and record a complete picture of the body decomposition process including the changes of the microbiome over the decomposition process. In this thesis, the possibility to reconstruct the crime scene and the decomposition process was investigated. In addition, a 3D model aiming to integrate the biological and thanatological information was generated. The possibility of utilising Autodesk 123D Catch software as a new tool for 3D reconstruction of a crime scene was thoroughly evaluated. First experiments demonstrated that the number of photos required to obtain the best result was specified to be from 20 to 30 photos as a minimum. In addition, significant experiments were performed in different conditions of sizes, locations, and different involved materials. The measurements were obtained from the models using the same software were compared with the real measurements of the tested objects. The result of the correlation between real and estimated measurements showed a very strong agreement ranging from 0.994 to 1.000. With reference to the documentation of the decomposition process, there are different factors, intrinsic and extrinsic, have been reported affecting the decomposition of a carrion/body. These factors mainly interact with the rates of the biological and chemical reaction happening after death. The biological reactions are mainly due to the activity of microorganism and insects. Pigs (Sus scrofa domesticus) were used as a model for human studies and the results obtained have been applied to other mammals without considering the effect of fur on the decomposition process and on the insect and microbial colonisation. In order to investigate this point, rabbits (Oryctolagus cuniculus) with and without fur were used in two sets of experiments at Huddersfield in summer 2014 and in spring 2015. The results obtained in this study showed a similarity of the decomposition stages between animals with and without fur. However, the decomposition process was faster during the summer due to the fast of insect colonisation and activity. In addition, the entomological data collected during the summer and spring experiments were demonstrated that the same taxa nearly were present in both seasons, except Hydrotaea (Diptera, Muscidae), which was presented only in the summer experiment, moreover, only one sample of Lucilia sericata (Calliphoridae) was detected in the spring season. Differences in colonisation time were observed only in spring experiment; animals without fur were colonised two days before animals with fur. The season could have affected the insect’s activity and the spread of the decomposition volatiles. The microbial communities during the decomposition process were investigated using BIOLOG EcoPlateTM and the hypervariable V1-3 region of 16S rRNA gene was used for their molecular identification based on pyrosequencing. Eurofins Genomic Operon using 454-GS Junior pyrosequencing platform (Roche) carried out these analyses. The functional diversity of the bacterial communities on all carcasses samples showed a considerable variability depending on the stage of the decomposition and the sampling region (Oral cavity, skin and interface-sand-carrion) in both seasons. Furthermore, over the molecular analyses of bacterial communities at the phylum level, four main phyla of bacteria were detected among analysed carrion during the decomposition process. These phyla were changed significantly during the stages of the decomposition and between sampling regions. While no difference was observed due to presence or absence of fur. On the other hand, the analysis at the family level was able to highlight differences at the temporal scale but as well as carrion with and without fur. The statistical analysis results showed a significant difference in the bacterial community family distribution among the presence of fur and among the decomposition stages, with significant differences among sampling regions and seasons.

This thesis explores the work carried out by forensic specialists employed by the International Commission on Missing Persons (ICMP). Headquartered in Sarajevo, Bosnia and Herzegovina (BiH), ICMP assists the work of local governments around the world in addressing the issue of missing persons following armed conflict, atrocities, and natural disasters. This thesis focuses on ICMP's efforts to aid the Bosnian government in locating, exhuming, and identifying the remains of the individuals who went missing during the country's recent war (1992-1995). Utilising data obtained via interviews with and observations of ICMP staff members, it primarily represents a study of the management of professional identity in emotionally charged situations, examining the experiences of the forensic specialists who work in the organisation's three mortuary facilities throughout BiH. It explores forensic specialists' work with human remains, their interactions with victims' family members, and their attendance at events in which victims are commemorated and/or buried. Discussion of forensic specialists' experiences with the deceased brings into consideration their varying responses to the remains, emphasising the prevalence and perceived importance of emotional detachment. Situations in which emotional detachment from the remains may prove challenging are considered, as are the varying techniques forensic specialists utilise in managing emotional responses to their work. Examination of forensic specialists' interactions with the living suggests their general dislike of these encounters, although the positive aspects of these interactions are also examined. Exploration of forensic specialists' opinions of attending burials and/or commemorations brings into further consideration the balance between emotional attachment and detachment. While respondents noted the importance of maintaining an emotional connection to their work, they nevertheless emphasised the importance of avoiding such responses while in the mortuary. Commemorations and/or burials become ‘safe spaces' for forensic specialists to express and experience emotional responses to their work that are not overtly professional.