Cytoskeletal and DNA structure abnormalities result from bypass of requirement for the cdc10 start gene in the fission yeast Schizosaccharomyces pombe.

The cdc10 gene of the fission yeast S. pombe is required for traverse of the start control in late G1 and commitment to the mitotic cell cycle. To increase our understanding of the events which occur at start, a pseudoreversion analysis was undertaken to identify genes whose products may interact with cdc10 or bypass the requirement for it. A single gene, sct1+ (suppressor of cdc ten), has been identified, mutation of which suppresses all conditional alleles and a null allele of cdc10. Bypass of the requirement for cdc10+ function by sct1-1 mutations leads to pleiotropic defects, including microtubule, microfilament and nuclear structural abnormalities. Our data suggest that sct1 encodes a protein that is dependent upon cdc10+ either for its normal function or expression, or is a component of a checkpoint that monitors execution of p85cdc10 function.

Combining Internet Monitoring Processes, Packaging and Isotopic Analyses to Determine The Market Structure: Example of Gamma Butyrolactone

The Internet is becoming more and more popular among drug users. The use of websites and forums to obtain illicit drugs and relevant information about the means of consumption is a growing phenomenon mainly for new synthetic drugs. Gamma Butyrolactone (GBL), a chemical precursor of Gamma Hydroxy Butyric acid (GHB), is used as a "club drug" and also in drug facilitated sexual assaults. Its market takes place mainly on the Internet through online websites but the structure of the market remains unknown. This research aims to combine digital, physical and chemical information to help understand the distribution routes and the structure of the GBL market. Based on an Internet monitoring process, thirty-nine websites selling GBL, mainly in the Netherlands, were detected between January 2010 and December 2011. Seventeen websites were categorized into six groups based on digital traces (e.g. IP addresses and contact information). In parallel, twenty-five bulk GBL specimens were purchased from sixteen websites for packaging comparisons and carbon isotopic measurements. Packaging information showed a high correlation with digital data confirming the links previously established whereas chemical information revealed undetected links and provided complementary information. Indeed, while digital and packaging data give relevant information about the retailers, the supply routes and the distribution close to the consumer, the carbon isotopic data provides upstream information about the production level and in particular the synthesis pathways and the chemical precursors. A three-level structured market has been thereby identified with a production level mainly located in China and in Germany, an online distribution level mainly hosted in the Netherlands and the customers who order on the Internet.

Structure of the glycosyl-phosphatidylinositol membrane anchor of the Leishmania major promastigote surface protease.

In common with many other plasma membrane glycoproteins of eukaryotic origin, the promastigote surface protease (PSP) of the protozoan parasite Leishmania contains a glycosyl-phosphatidylinositol (GPI) membrane anchor. The GPI anchor of Leishmania major PSP was purified following proteolysis of the PSP and analyzed by two-dimensional 1H-1H NMR, compositional and methylation linkage analyses, chemical and enzymatic modifications, and amino acid sequencing. From these results, the structure of the GPI-containing peptide was found to be Asp-Gly-Gly-Asn-ethanolamine-PO4-6Man alpha 1-6Man alpha 1-4GlcN alpha 1-6myo-inositol-1-PO4-(1-alkyl-2-acyl-glycerol). The glycan structure is identical to the conserved glycan core regions of the GPI anchor of Trypanosoma brucei variant surface glycoprotein and rat brain Thy-1 antigen, supporting the notion that this portion of GPIs are highly conserved. The phosphatidylinositol moiety of the PSP anchor is unusual, containing a fully saturated, unbranched 1-O-alkyl chain (mainly C24:0) and a mixture of fully saturated unbranched 2-O-acyl chains (C12:0, C14:0, C16:0, and C18:0). This lipid composition differs significantly from those of the GPIs of T. brucei variant surface glycoprotein and mammalian erythrocyte acetylcholinesterase but is similar to that of a family of glycosylated phosphoinositides found uniquely in Leishmania.

Qualitative structure-metabolism relationships in the hydrolysis of carbamates.

The aims of this review were 1) to compile a large number of reliable literature data on the metabolic hydrolysis of medicinal carbamates and 2) to extract from such data a qualitative relation between molecular structure and lability to metabolic hydrolysis. The compounds were classified according to the nature of their substituents (R³OCONR&supl;R²), and a metabolic lability score was calculated for each class. A trend emerged, such that the metabolic lability of carbamates decreased (i.e., their metabolic stability increased), in the following series: Aryl-OCO-NHAlkyl >> Alkyl-OCO-NHAlkyl ~ Alkyl-OCO-N(Alkyl)? ? Alkyl-OCO-N(endocyclic) ? Aryl-OCO-N(Alkyl)? ~ Aryl-OCO-N(endocyclic) ? Alkyl-OCO-NHAryl ~ Alkyl-OCO-NHAcyl?>> Alkyl-OCO-NH? > Cyclic carbamates. This trend should prove useful in the design of carbamates as drugs or prodrugs.

The use of external mesh reinforcement to reduce intimal hyperplasia and preserve the structure of human saphenous veins.

The saphenous vein is the conduit of choice in bypass graft procedures. Haemodynamic factors play a major role in the development of intimal hyperplasia (IH), and subsequent bypass failure. To evaluate the potential protective effect of external reinforcement on such a failure, we developed an ex vivo model for the perfusion of segments of human saphenous veins under arterial shear stress. In veins submitted to pulsatile high pressure (mean pressure at 100 mmHg) for 3 or 7 days, the use of an external macroporous polyester mesh 1) prevented the dilatation of the vessel, 2) decreased the development of IH, 3) reduced the apoptosis of smooth muscle cells, and the subsequent fibrosis of the media layer, 4) prevented the remodelling of extracellular matrix through the up-regulation of matrix metalloproteinases (MMP-2, MMP-9) and plasminogen activator type I. The data show that, in an experimental ex vivo setting, an external scaffold decreases IH and maintains the integrity of veins exposed to arterial pressure, via increase in shear stress and decrease wall tension, that likely contribute to trigger selective molecular and cellular changes.

Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment.

OBJECTIVE: To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects. METHOD: [¹⁸F]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested. RESULTS: The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline. CONCLUSION: The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

How to identify and recruit nurses to a survey 14 and 24 years after graduation in a context of scarce data : lessons learnt from the 2012 nurses at work pilot study on nurses' career paths

Nursing workforce data are scarce in Switzerland, with no active national registry of nurses. The worldwide nursing shortage is also affecting Switzerland, so that evidence-based results of the nurses at work project on career paths and retention are needed as part of the health care system stewardship; nurses at work is a retrospective cohort study of nurses who graduated in Swiss nursing schools in the last 30 years. Results of the pilot study are presented here (process and feasibility). The objectives are (1) to determine the size and structure of the potential target population by approaching two test-cohorts of nursing graduates (1988 and 1998); (2) to test methods of identifying and reaching them 14 and 24 years after graduation; (3) to compute participation rates, and identify recruitment and participation biases.

Vulnerability as a heuristic for interdisciplinary research: Assessing the thematic and methodological structure of empirical life-course studies

Changes in human lives are studied in psychology, sociology, and adjacent fields as outcomes of developmental processes, institutional regulations and policies, culturally and normatively structured life courses, or empirical accounts. However, such studies have used a wide range of complementary, but often divergent, concepts. This review has two aims. First, we report on the structure that has emerged from scientific life course research by focusing on abstracts from longitudinal and life course studies beginning with the year 2000. Second, we provide a sense of the disciplinary diversity of the field and assess the value of the concept of 'vulnerability' as a heuristic tool for studying human lives. Applying correspondence analysis to 10,632 scientific abstracts, we find a disciplinary divide between psychology and sociology, and observe indications of both similarities of-and differences between-studies, driven at least partly by the data and methods employed. We also find that vulnerability takes a central position in this scientific field, which leads us to suggest several reasons to see value in pursuing theory development for longitudinal and life course studies in this direction.

Two-dimensional probabilistic inversion of plane-wave electromagnetic data: Methodology, model constraints and joint inversion with electrical resistivity data

Probabilistic inversion methods based on Markov chain Monte Carlo (MCMC) simulation are well suited to quantify parameter and model uncertainty of nonlinear inverse problems. Yet, application of such methods to CPU-intensive forward models can be a daunting task, particularly if the parameter space is high dimensional. Here, we present a 2-D pixel-based MCMC inversion of plane-wave electromagnetic (EM) data. Using synthetic data, we investigate how model parameter uncertainty depends on model structure constraints using different norms of the likelihood function and the model constraints, and study the added benefits of joint inversion of EM and electrical resistivity tomography (ERT) data. Our results demonstrate that model structure constraints are necessary to stabilize the MCMC inversion results of a highly discretized model. These constraints decrease model parameter uncertainty and facilitate model interpretation. A drawback is that these constraints may lead to posterior distributions that do not fully include the true underlying model, because some of its features exhibit a low sensitivity to the EM data, and hence are difficult to resolve. This problem can be partly mitigated if the plane-wave EM data is augmented with ERT observations. The hierarchical Bayesian inverse formulation introduced and used herein is able to successfully recover the probabilistic properties of the measurement data errors and a model regularization weight. Application of the proposed inversion methodology to field data from an aquifer demonstrates that the posterior mean model realization is very similar to that derived from a deterministic inversion with similar model constraints.

Évaluation d'une structure gériatrique entre l'ambulatoire et l'hospitalier [Geriatric institutions, between ambulatory and hospital care: patients' description and performance assessment].

Introduction : Décrire les patients d'une structure gériatrique offrant des hospitalisations de courte durée, dans un contexte ambulatoire, pour des situations gériatriques courantes dans le canton de Genève (Suisse). Mesurer les performances de cette structure en termes de qualité des soins et de coûts. Méthodes : Des données relatives au profil des 100 premiers patients ont été collectées (huit mois), ainsi qu'aux prestations, aux ressources et aux effets (réadmissions, décès, satisfaction, complications) de manière à mesurer différents indicateurs de qualité et de coûts. Les valeurs observées ont été systématiquement comparées aux valeurs attendues, calculées à partir du profil des patients. Résultats : Des critères d'admission ont été fixés pour exclure les situations dans lesquelles d'autres structures offrent des soins mieux adaptés. La spécificité de cette structure intermédiaire a été d'assurer une continuité des soins et d'organiser d'emblée le retour à domicile par des prestations de liaison ambulatoire. La faible occurrence des réadmissions potentiellement évitables, une bonne satisfaction des patients, l'absence de décès prématurés et le faible nombre de complications suggèrent que les soins médicaux et infirmiers ont été délivrés avec une bonne qualité. Le coût s'est révélé nettement plus économique que des séjours hospitaliers après ajustement pour la lourdeur des cas. Conclusion : L'expérience-pilote a démontré la faisabilité et l'utilité d'une unité d'hébergement et d'hospitalisation de court séjour en toute sécurité. Le suivi du patient par le médecin traitant assure une continuité des soins et évite la perte d'information lors des transitions ainsi que les examens non pertinents. INTRODUCTION: To describe patients admitted to a geriatric institution, providing short-term hospitalizations in the context of ambulatory care in the canton of Geneva. To measure the performances of this structure in terms of quality ofcare and costs. METHOD: Data related to the clinical,functioning and participation profiles of the first 100 patients were collected. Data related to effects (readmission, deaths, satisfaction, complications), services and resources were also documented over an 8-month period to measure various quality and costindicators. Observed values were systematically compared to expected values, adjusted for case mix. RESULTS: Explicit criteria were proposed to focus on the suitable patients, excluding situations in which other structures were considered to be more appropriate. The specificity of this intermediate structure was to immediately organize, upon discharge, outpatient services at home. The low rate of potentially avoidable readmissions, the high patient satisfaction scores, the absence of premature death and the low number of iatrogenic complications suggest that medical and nursing care delivered reflect a good quality of services. The cost was significantly lower than expected, after adjusting for case mix. CONCLUSION: The pilot experience showed that a short-stay hospitalization unit was feasible with acceptable security conditions. The attending physician's knowledge of the patients allowed this system tofocus on essential issues without proposing inappropriate services.

Structure-Based, Rational Design of T Cell Receptors.

Adoptive cell transfer using engineered T cells is emerging as a promising treatment for metastatic melanoma. Such an approach allows one to introduce T cell receptor (TCR) modifications that, while maintaining the specificity for the targeted antigen, can enhance the binding and kinetic parameters for the interaction with peptides (p) bound to major histocompatibility complexes (MHC). Using the well-characterized 2C TCR/SIYR/H-2K(b) structure as a model system, we demonstrated that a binding free energy decomposition based on the MM-GBSA approach provides a detailed and reliable description of the TCR/pMHC interactions at the structural and thermodynamic levels. Starting from this result, we developed a new structure-based approach, to rationally design new TCR sequences, and applied it to the BC1 TCR targeting the HLA-A2 restricted NY-ESO-1157-165 cancer-testis epitope. Fifty-four percent of the designed sequence replacements exhibited improved pMHC binding as compared to the native TCR, with up to 150-fold increase in affinity, while preserving specificity. Genetically engineered CD8(+) T cells expressing these modified TCRs showed an improved functional activity compared to those expressing BC1 TCR. We measured maximum levels of activities for TCRs within the upper limit of natural affinity, K D = ∼1 - 5 μM. Beyond the affinity threshold at K D < 1 μM we observed an attenuation in cellular function, in line with the "half-life" model of T cell activation. Our computer-aided protein-engineering approach requires the 3D-structure of the TCR-pMHC complex of interest, which can be obtained from X-ray crystallography. We have also developed a homology modeling-based approach, TCRep 3D, to obtain accurate structural models of any TCR-pMHC complexes when experimental data is not available. Since the accuracy of the models depends on the prediction of the TCR orientation over pMHC, we have complemented the approach with a simplified rigid method to predict this orientation and successfully assessed it using all non-redundant TCR-pMHC crystal structures available. These methods potentially extend the use of our TCR engineering method to entire TCR repertoires for which no X-ray structure is available. We have also performed a steered molecular dynamics study of the unbinding of the TCR-pMHC complex to get a better understanding of how TCRs interact with pMHCs. This entire rational TCR design pipeline is now being used to produce rationally optimized TCRs for adoptive cell therapies of stage IV melanoma.

Divergence with gene flow and fine-scale phylogeographical structure in the wedge-billed woodcreeper, Glyphorynchus spirurus, a Neotropical rainforest bird.

Determining the relative roles of vicariance and selection in restricting gene flow between populations is of central importance to the evolutionary process of population divergence and speciation. Here we use molecular and morphological data to contrast the effect of isolation (by mountains and geographical distance) with that of ecological factors (altitudinal gradients) in promoting differentiation in the wedge-billed woodcreeper, Glyphorynchus spirurus, a tropical forest bird, in Ecuador. Tarsus length and beak size increased relative to body size with altitude on both sides of the Andes, and were correlated with the amount of moss on tree trunks, suggesting the role of selection in driving adaptive divergence. In contrast, molecular data revealed a considerable degree of admixture along these altitudinal gradients, suggesting that adaptive divergence in morphological traits has occurred in the presence of gene flow. As suggested by mitochondrial DNA sequence data, the Andes act as a barrier to gene flow between ancient subspecific lineages. Genome-wide amplified fragment length polymorphism markers reflected more recent patterns of gene flow and revealed fine-scale patterns of population differentiation that were not detectable with mitochondrial DNA, including the differentiation of isolated coastal populations west of the Andes. Our results support the predominant role of geographical isolation in driving genetic differentiation in G. spirurus, yet suggest the role of selection in driving parallel morphological divergence along ecological gradients.

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

Analysis of space-time environmental data in complex regions

This thesis develops a comprehensive and a flexible statistical framework for the analysis and detection of space, time and space-time clusters of environmental point data. The developed clustering methods were applied in both simulated datasets and real-world environmental phenomena; however, only the cases of forest fires in Canton of Ticino (Switzerland) and in Portugal are expounded in this document. Normally, environmental phenomena can be modelled as stochastic point processes where each event, e.g. the forest fire ignition point, is characterised by its spatial location and occurrence in time. Additionally, information such as burned area, ignition causes, landuse, topographic, climatic and meteorological features, etc., can also be used to characterise the studied phenomenon. Thereby, the space-time pattern characterisa- tion represents a powerful tool to understand the distribution and behaviour of the events and their correlation with underlying processes, for instance, socio-economic, environmental and meteorological factors. Consequently, we propose a methodology based on the adaptation and application of statistical and fractal point process measures for both global (e.g. the Morisita Index, the Box-counting fractal method, the multifractal formalism and the Ripley's K-function) and local (e.g. Scan Statistics) analysis. Many measures describing the space-time distribution of environmental phenomena have been proposed in a wide variety of disciplines; nevertheless, most of these measures are of global character and do not consider complex spatial constraints, high variability and multivariate nature of the events. Therefore, we proposed an statistical framework that takes into account the complexities of the geographical space, where phenomena take place, by introducing the Validity Domain concept and carrying out clustering analyses in data with different constrained geographical spaces, hence, assessing the relative degree of clustering of the real distribution. Moreover, exclusively to the forest fire case, this research proposes two new methodologies to defining and mapping both the Wildland-Urban Interface (WUI) described as the interaction zone between burnable vegetation and anthropogenic infrastructures, and the prediction of fire ignition susceptibility. In this regard, the main objective of this Thesis was to carry out a basic statistical/- geospatial research with a strong application part to analyse and to describe complex phenomena as well as to overcome unsolved methodological problems in the characterisation of space-time patterns, in particular, the forest fire occurrences. Thus, this Thesis provides a response to the increasing demand for both environmental monitoring and management tools for the assessment of natural and anthropogenic hazards and risks, sustainable development, retrospective success analysis, etc. The major contributions of this work were presented at national and international conferences and published in 5 scientific journals. National and international collaborations were also established and successfully accomplished. -- Cette thèse développe une méthodologie statistique complète et flexible pour l'analyse et la détection des structures spatiales, temporelles et spatio-temporelles de données environnementales représentées comme de semis de points. Les méthodes ici développées ont été appliquées aux jeux de données simulées autant qu'A des phénomènes environnementaux réels; nonobstant, seulement le cas des feux forestiers dans le Canton du Tessin (la Suisse) et celui de Portugal sont expliqués dans ce document. Normalement, les phénomènes environnementaux peuvent être modélisés comme des processus ponctuels stochastiques ou chaque événement, par ex. les point d'ignition des feux forestiers, est déterminé par son emplacement spatial et son occurrence dans le temps. De plus, des informations tels que la surface bru^lée, les causes d'ignition, l'utilisation du sol, les caractéristiques topographiques, climatiques et météorologiques, etc., peuvent aussi être utilisées pour caractériser le phénomène étudié. Par conséquent, la définition de la structure spatio-temporelle représente un outil puissant pour compren- dre la distribution du phénomène et sa corrélation avec des processus sous-jacents tels que les facteurs socio-économiques, environnementaux et météorologiques. De ce fait, nous proposons une méthodologie basée sur l'adaptation et l'application de mesures statistiques et fractales des processus ponctuels d'analyse global (par ex. l'indice de Morisita, la dimension fractale par comptage de boîtes, le formalisme multifractal et la fonction K de Ripley) et local (par ex. la statistique de scan). Des nombreuses mesures décrivant les structures spatio-temporelles de phénomènes environnementaux peuvent être trouvées dans la littérature. Néanmoins, la plupart de ces mesures sont de caractère global et ne considèrent pas de contraintes spatiales com- plexes, ainsi que la haute variabilité et la nature multivariée des événements. A cet effet, la méthodologie ici proposée prend en compte les complexités de l'espace géographique ou le phénomène a lieu, à travers de l'introduction du concept de Domaine de Validité et l'application des mesures d'analyse spatiale dans des données en présentant différentes contraintes géographiques. Cela permet l'évaluation du degré relatif d'agrégation spatiale/temporelle des structures du phénomène observé. En plus, exclusif au cas de feux forestiers, cette recherche propose aussi deux nouvelles méthodologies pour la définition et la cartographie des zones périurbaines, décrites comme des espaces anthropogéniques à proximité de la végétation sauvage ou de la forêt, et de la prédiction de la susceptibilité à l'ignition de feu. A cet égard, l'objectif principal de cette Thèse a été d'effectuer une recherche statistique/géospatiale avec une forte application dans des cas réels, pour analyser et décrire des phénomènes environnementaux complexes aussi bien que surmonter des problèmes méthodologiques non résolus relatifs à la caractérisation des structures spatio-temporelles, particulièrement, celles des occurrences de feux forestières. Ainsi, cette Thèse fournit une réponse à la demande croissante de la gestion et du monitoring environnemental pour le déploiement d'outils d'évaluation des risques et des dangers naturels et anthro- pogéniques. Les majeures contributions de ce travail ont été présentées aux conférences nationales et internationales, et ont été aussi publiées dans 5 revues internationales avec comité de lecture. Des collaborations nationales et internationales ont été aussi établies et accomplies avec succès.

Chemical profiling: a tool to decipher the structure and organisation of illicit drugs markets: an 8-year study in Western Switzerland

Illicit drug analyses usually focus on the identification and quantitation of questioned material to support the judicial process. In parallel, more and more laboratories develop physical and chemical profiling methods in a forensic intelligence perspective. The analysis of large databases resulting from this approach enables not only to draw tactical and operational intelligence, but may also contribute to the strategic overview of drugs markets. In Western Switzerland, the chemical analysis of illicit drug seizures is centralised in a laboratory hosted by the University of Lausanne. For over 8 years, this laboratory has analysed 5875 cocaine and 2728 heroin specimens, coming from respectively 1138 and 614 seizures operated by police and border guards or customs. Chemical (major and minor alkaloids, purity, cutting agents, chemical class), physical (packaging and appearance) as well as circumstantial (criminal case number, mass of drug seized, date and place of seizure) information are collated in a dedicated database for each specimen. The study capitalises on this extended database and defines several indicators to characterise the structure of drugs markets, to follow-up on their evolution and to compare cocaine and heroin markets. Relational, spatial, temporal and quantitative analyses of data reveal the emergence and importance of distribution networks. They enable to evaluate the cross-jurisdictional character of drug trafficking and the observation time of drug batches, as well as the quantity of drugs entering the market every year. Results highlight the stable nature of drugs markets over the years despite the very dynamic flows of distribution and consumption. This research work illustrates how the systematic analysis of forensic data may elicit knowledge on criminal activities at a strategic level. In combination with information from other sources, such knowledge can help to devise intelligence-based preventive and repressive measures and to discuss the impact of countermeasures.