Forensic intelligence framework. Part II: study of the main generic building blocks and challenges through the examples of illicit drugs and false identity documents monitoring

The development of forensic intelligence relies on the expression of suitable models that better represent the contribution of forensic intelligence in relation to the criminal justice system, policing and security. Such models assist in comparing and evaluating methods and new technologies, provide transparency and foster the development of new applications. Interestingly, strong similarities between two separate projects focusing on specific forensic science areas were recently observed. These observations have led to the induction of a general model (Part I) that could guide the use of any forensic science case data in an intelligence perspective. The present article builds upon this general approach by focusing on decisional and organisational issues. The article investigates the comparison process and evaluation system that lay at the heart of the forensic intelligence framework, advocating scientific decision criteria and a structured but flexible and dynamic architecture. These building blocks are crucial and clearly lay within the expertise of forensic scientists. However, it is only part of the problem. Forensic intelligence includes other blocks with their respective interactions, decision points and tensions (e.g. regarding how to guide detection and how to integrate forensic information with other information). Formalising these blocks identifies many questions and potential answers. Addressing these questions is essential for the progress of the discipline. Such a process requires clarifying the role and place of the forensic scientist within the whole process and their relationship to other stakeholders.

Tools in pharmacovigilance in psychiatry: therapeutic drug monitoring, pharmacogenetic tests and drug-drug interactions databases

SUMMARYIn order to increase drug safety we must better understand how medication interacts with the body of our patients and this knowledge should be made easily available for the clinicians prescribing the medication. This thesis contributes to how the knowledge of some drug properties can increase and how to make information readily accessible for the medical professionals. Furthermore it investigates the use of Therapeutic drug monitoring, drug interaction databases and pharmacogenetic tests in pharmacovigilance.Two pharmacogenetic studies in the naturalistic setting of psychiatric in-patients clinics have been performed; one with the antidepressant mirtazapine, the other with the antipsychotic clozapine. Forty-five depressed patients have been treated with mirtazapine and were followed for 8 weeks. The therapeutic effect was as seen in other previous studies. Enantioselective analyses could confirm an influence of age, gender and smoking in the pharmacokinetics of mirtazapine; it showed a significant influence of the CYP2D6 genotype on the antidepressant effective S-enantiomer, and for the first time an influence of the CYP2B6 genotype on the plasma concentrations of the 8-OH metabolite was found. The CYP2B6*/*6 genotype was associated to better treatment response. A detailed hypothesis of the metabolic pathways of mirtazapine is proposed. In the second pharmacogenetic study, analyses of 75 schizophrenic patients treated with clozapine showed the influence of CYP450 and ABCB1 genotypes on its pharmacokinetics. For the first time we could demonstrate an in vivo effect of the CYP2C19 genotype and an influence of P-glycoprotein on the plasma concentrations of clozapine. Further we confirmed in vivo the prominent role of CYP1A2 in the metabolism of clozapine.Identifying risk factors for the occurrence of serious adverse drug reactions (SADR) would allow a more individualized and safer drug therapy. SADR are rare events and therefore difficult to study. We tested the feasibility of a nested matched case-control study to examine the influence of high drug plasma levels and CYP2D6 genotypes on the risk to experience an SADR. In our sample we compared 62 SADR cases with 82 controls; both groups were psychiatric patients from the in-patient clinic Königsfelden. Drug plasma levels of >120% of the upper recommended references could be identified as a risk factor with a statistically significant odds ratio of 3.5, a similar trend could be seen for CYP2D6 poor metaboliser. Although a matched case-control design seems a valid method, 100% matching is not easy to perform in a relative small cohort of one in-patient clinic. However, a nested case-control study is feasible.On the base of the experience gained in the AMSP+ study and the fact that we have today only sparse data indicating that routine drug plasma concentration monitoring and/or pharmacogenetic testing in psychiatry are justified to minimize the risk for ADR, we developed a test algorithm named "TDM plus" (TDM plus interaction checks plus pharmacogenetic testing).Pharmacovigilance programs such as the AMSP project (AMSP = Arzneimittelsicherheit in der Psychiatrie) survey psychiatric in-patients in order to collect SADR and to detect new safety signals. Case reports of such SADR are, although anecdotal, valuable to illustrate rare clinical events and sometimes confirm theoretical assumptions of e.g. drug interactions. Seven pharmacovigilance case reports are summarized in this thesis.To provide clinicians with meaningful information on the risk of drug combinations, during the course of this thesis the internet based drug interaction program mediQ.ch (in German) has been developed. Risk estimation is based on published clinical and pharmacological information of single drugs and alimentary products, including adverse drug reaction profiles. Information on risk factors such as renal and hepatic insufficiency and specific genotypes are given. More than 20'000 drug pairs have been described in detail. Over 2000 substances with their metabolic and transport pathways are included and all information is referenced with links to the published scientific literature or other information sources. Medical professionals of more than 100 hospitals and 300 individual practitioners do consult mediQ.ch regularly. Validations with comparisons to other drug interaction programs show good results.Finally, therapeutic drug monitoring, drug interaction programs and pharmacogenetic tests are helpful tools in pharmacovigilance and should, in absence of sufficient routine tests supporting data, be used as proposed in our TDM plus algorithm.RESUMEPour améliorer la sécurité d'emploi des médicaments il est important de mieux comprendre leurs interactions dans le corps des patients. Ensuite le clinicien qui prescrit une pharmacothérapie doit avoir un accès simple à ces informations. Entre autres, cette thèse contribue à mieux connaître les caractéristiques pharmacocinétiques de deux médicaments. Elle examine aussi l'utilisation de trois outils en pharmacovigilance : le monitorage thérapeutique des taux plasmatiques des médicaments (« therapeutic drug monitoring »), un programme informatisé d'estimation du risque de combinaisons médicamenteuses, et enfin des tests pharmacogénétiques.Deux études cliniques pharmacogénétiques ont été conduites dans le cadre habituel de clinique psychiatrique : l'une avec la mirtazapine (antidépresseur), l'autre avec la clozapine (antipsychotique). On a traité 45 patients dépressifs avec de la mirtazapine pendant 8 semaines. L'effet thérapeutique était semblable à celui des études précédentes. Nous avons confirmé l'influence de l'âge et du sexe sur la pharmacocinétique de la mirtazapine et la différence dans les concentrations plasmatiques entre fumeurs et non-fumeurs. Au moyen d'analyses énantiomères sélectives, nous avons pu montrer une influence significative du génotype CYP2D6 sur l'énantiomère S+, principalement responsable de l'effet antidépresseur. Pour la première fois, nous avons trouvé une influence du génotype CYP2B6 sur les taux plasmatiques de la 8-OH-mirtazapine. Par ailleurs, le génotype CYP2B6*6/*6 était associé à une meilleure réponse thérapeutique. Une hypothèse sur les voies métaboliques détaillées de la mirtazapine est proposée. Dans la deuxième étude, 75 patients schizophrènes traités avec de la clozapine ont été examinés pour étudier l'influence des génotypes des iso-enzymes CYP450 et de la protéine de transport ABCB1 sur la pharmacocinétique de cet antipsychotique. Pour la première fois, on a montré in vivo un effet des génotypes CYP2C19 et ABCB1 sur les taux plasmatiques de la clozapine. L'importance du CYP1A2 dans le métabolisme de la clozapine a été confirmée.L'identification de facteurs de risques dans la survenue d'effets secondaire graves permettrait une thérapie plus individualisée et plus sûre. Les effets secondaires graves sont rares. Dans une étude de faisabilité (« nested matched case-control design » = étude avec appariement) nous avons comparé des patients avec effets secondaires graves à des patients-contrôles prenant le même type de médicaments mais sans effets secondaires graves. Des taux plasmatiques supérieurs à 120% de la valeur de référence haute sont associés à un risque avec « odds ratio » significatif de 3.5. Une tendance similaire est apparue pour le génotype du CYP2D6. Le « nested matched case-control design » semble une méthode valide qui présente cependant une difficulté : trouver des patients-contrôles dans le cadre d'une seule clinique psychiatrique. Par contre la conduite d'une « nested case-control study » sans appariement est recommandable.Sur la base de notre expérience de l'étude AMSP+ et le fait que nous disposons que de peux de données justifiant des monitorings de taux plasmatiques et/ou de tests pharmacogénétiques de routine, nous avons développé un test algorithme nommé « TDMplus » (TDM + vérification d'interactions médicamenteuses + tests pharmacogénétique).Des programmes de pharmacovigilances comme celui de l'AMSP (Arzneimittelsicherheit in der Psychiatrie = pharmacovigilance en psychiatrie) collectent les effets secondaires graves chez les patients psychiatriques hospitalisés pour identifier des signaux d'alertes. La publication de certains de ces cas même anecdotiques est précieuse. Elle décrit des événements rares et quelques fois une hypothèse sur le potentiel d'une interaction médicamenteuse peut ainsi être confirmée. Sept publications de cas sont résumées ici.Dans le cadre de cette thèse, on a développé un programme informatisé sur internet (en allemand) - mediQ.ch - pour estimer le potentiel de risques d'une interaction médicamenteuse afin d'offrir en ligne ces informations utiles aux cliniciens. Les estimations de risques sont fondées sur des informations cliniques (y compris les profils d'effets secondaires) et pharmacologiques pour chaque médicament ou substance combinés. Le programme donne aussi des informations sur les facteurs de risques comme l'insuffisance rénale et hépatique et certains génotypes. Actuellement il décrit en détail les interactions potentielles de plus de 20'000 paires de médicaments, et celles de 2000 substances actives avec leurs voies de métabolisation et de transport. Chaque information mentionne sa source d'origine; un lien hypertexte permet d'y accéder. Le programme mediQ.ch est régulièrement consulté par les cliniciens de 100 hôpitaux et par 300 praticiens indépendants. Les premières validations et comparaisons avec d'autres programmes sur les interactions médicamenteuses montrent de bons résultats.En conclusion : le monitorage thérapeutique des médicaments, les programmes informatisés contenant l'information sur le potentiel d'interaction médicamenteuse et les tests pharmacogénétiques sont de précieux outils en pharmacovigilance. Nous proposons de les utiliser en respectant l'algorithme « TDM plus » que nous avons développé.

Selective attention to emotional stimuli: What IQ and Openness do, and emotional intelligence does not

We examined how general intelligence, personality, and emotional intelligence-measured as an ability using the MSCEIT-predicted performance on a selective-attention task requiring participants to ignore distracting emotion information. We used a visual prime in which participants saw a pair of faces depicting emotions; their task was to focus on one of the faces (the target) while ignoring the other (the distractor). Next, participants categorized a string of letters (word or nonword), which was either congruent to the target or the distractor. The speed of response to categorizing the string was recorded. Given the emotional nature of the stimuli and the emotional information processing involved in the task, we were surprised to see that none of the MSCEIT branches predicted performance. However, general intelligence and openness to experience reduced response time.

Eosinophilic oesophagitis: latest intelligence.

Eosinophilic oesophagitis (EoE), first described in the early 1990s, has rapidly evolved as a distinctive chronic inflammatory oesophageal disease with increasing incidence and prevalence in the westernized countries. Currently, EoE represents the main cause of dysphagia in adult patients. This disease is more prevalent in males and is frequently associated with allergies. The diagnosis is established based on the presence of oesophageal symptoms and dense eosinophilic oesophageal infiltration once other conditions leading to oesophageal eosinophilia are excluded. It is currently under discussion to what extent and by which methods allergic testing should be performed. Topical corticosteroids lead to a rapid improvement of active EoE clinically and histologically. Especially in children, elimination diets can have similar efficacy as topical corticosteroids. Oesophageal dilation of EoE-induced oesophageal strictures can also be effective in improving symptoms, but this therapy has no effect on the underlying inflammation. Neither the diagnostic nor the long-term therapeutic strategies are as yet defined. Cite this as: A. M. Schoepfer, D. Simon and A. Straumann, Clinical & Experimental Allergy, 2011 (41) 630-639.

Pédiatrie. 3. Le score de McIsaac: une aide à l'indication des tests de diagnostic rapide dans tes angines à streptocoques A [Pediatrics. Using the McIsaac score for the indication of rapid diagnostic testing in children with streptococcal pharyngitis].

The McIsaac scoring system is a tool designed to predict the probability of streptococcal pharyngitis in children aged 3 to 17 years with a sore throat. Although it does not allow the physician to make the diagnosis of streptococcal pharyngitis, it enables to identify those children with a sore throat in whom rapid antigen detection tests have a good predictive value.

Les tests génétiques peuvent-ils être utiles pour la prévention cardiovasculaire? [Are genetic tests useful for cardiovascular prevention?].

Recent progresses in genetics have opened new avenues to further our understanding of the pathophysiological mechanisms underlying cardiovascular disease, raising, new expectations in the field of personalized medicine. Genetic tests may have a high predictive value for rare monogenic diseases. The situation is very different for common polygenic diseases, such as myocardial infarction, type 2 diabetes or stroke. The results from recent genome-wide association studies have provided useful information for research, but have not yet been proven to be clinically useful. It is therefore currently not recommended to conducted genetic testing to guide cardiovascular prevention neither in clinical nor in public health settings.

L'intelligence-led policing: un cadre pertinent pour soutenir la lutte contre les incendies volontaires répétitifs

Agir efficacement contre les incendies volontaires répétitifs représente un défi de taille pour la société et la police. Nous proposons d'utiliser l'intelligence-led policing et le cycle du renseignement comme cadre à une approche permettant une gestion et un suivi global et systématique de ces événements. Mais avant de pouvoir lancer ce processus, un certain nombre de défis doit être surmonté tel que la nature non spécifique des données. Il sera alors possible de mettre en place un processus qui permettra de faire des analyses pour obtenir une vision des incendies, détecter des situations répétitives et des liens entre les événements mettant en évidence des séries. Le renseignement obtenu par l'analyse des données rassemblées peut ensuite être utilisé pour mettre en place des moyens complémentaires d'enquête ou pour prendre des mesures préventives ou répressives.

Substantial advantage of a combined Bayesian and genotyping approach in testosterone doping tests.

Testosterone abuse is conventionally assessed by the urinary testosterone/epitestosterone (T/E) ratio, levels above 4.0 being considered suspicious. A deletion polymorphism in the gene coding for UGT2B17 is strongly associated with reduced testosterone glucuronide (TG) levels in urine. Many of the individuals devoid of the gene would not reach a T/E ratio of 4.0 after testosterone intake. Future test programs will most likely shift from population based- to individual-based T/E cut-off ratios using Bayesian inference. A longitudinal analysis is dependent on an individual's true negative baseline T/E ratio. The aim was to investigate whether it is possible to increase the sensitivity and specificity of the T/E test by addition of UGT2B17 genotype information in a Bayesian framework. A single intramuscular dose of 500mg testosterone enanthate was given to 55 healthy male volunteers with either two, one or no allele (ins/ins, ins/del or del/del) of the UGT2B17 gene. Urinary excretion of TG and the T/E ratio was measured during 15 days. The Bayesian analysis was conducted to calculate the individual T/E cut-off ratio. When adding the genotype information, the program returned lower individual cut-off ratios in all del/del subjects increasing the sensitivity of the test considerably. It will be difficult, if not impossible, to discriminate between a true negative baseline T/E value and a false negative one without knowledge of the UGT2B17 genotype. UGT2B17 genotype information is crucial, both to decide which initial cut-off ratio to use for an individual, and for increasing the sensitivity of the Bayesian analysis.

Comparison of three acellular tests for assessing the oxidation potential of nanomaterials

Great effort is put into developing reliable, predictive, high-throughput, and low-cost screening approaches for the toxicity evaluation of ambient and manufactured nanoparticles (NP). These tests often consider oxidative reactivity, as oxidative stress is a well-documented pathway in particle toxicology. Based on a panel of six carbonaceous and five metal/metal oxide (Me/MeOx) nanoparticles, we: (i) compared the specifications (linearity, detection limits, repeatability) of three acellular reactivity tests using either dithiothreitol (DTT assay), dichlorofluorescein (DCFH assay), or ascorbic acid (AA-assay) as the reducing agent; and (ii) evaluated which physicochemical properties were important for explaining the observed reactivity. The selected AA assay was found to be neither sensitive nor robust enough to be retained. For the other tests, the surface properties of carbonaceous NP were of utmost importance for explaining their reactivity. In particular, the presence of "strongly reducing" surface functions explained most of its DCFH reactivity and a large part of its DTT reactivity. For the selected Me/MeOx, a different picture emerged. Whereas all particles were able to oxidize DCFH, dissolution and complexation processes could additionally influence the measured reactivity, as observed using the DTT assay. This study suggests that a combination of the DTT and DCFH assays provides complementary information relative to the quantification of the oxidative capacity of NP.