Synergism between a foldase and an unfoldase: reciprocal dependence between the thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaK.

The role of bacterial Hsp40, DnaJ, is to co-chaperone the binding of misfolded or alternatively folded proteins to bacterial Hsp70, DnaK, which is an ATP-fuelled unfolding chaperone. In addition to its DnaK targeting activity, DnaJ has a weak thiol-reductase activity. In between the substrate-binding domain and the J-domain anchor to DnaK, DnaJ has a unique domain with four conserved CXXC motives that bind two Zn(2+) and partly contribute to polypeptide binding. Here, we deleted in DnaJ this Zn-binding domain, which is characteristic to type I but not of type II or III J-proteins. This caused a loss of the thiol-reductase activity and strongly reduced the ability of DnaJ to mediate the ATP- and DnaK-dependent unfolding/refolding of mildly oxidized misfolded polypeptides, an inhibition that was alleviated in the presence of thioredoxin or DTT. We suggest that in addition to their general ability to target misfolded polypeptide substrates to the Hsp70/Hsp110 chaperone machinery, Type I J-proteins carry an ancillary protein dithiol-isomerase function that can synergize the unfolding action of the chaperone, in the particular case of substrates that are further stabilized by non-native disulfide bonds. Whereas the unfoldase can remain ineffective without the transient untying of disulfide bonds by the foldase, the foldase can remain ineffective without the transient ATP-fuelled unfolding of wrong local structures by the unfoldase.

Beyond Value-at-Risk : GlueVaR Distortion Risk Measures

We propose a new family of risk measures, called GlueVaR, within the class of distortion risk measures. Analytical closed-form expressions are shown for the most frequently used distribution functions in financial and insurance applications. The relationship between Glue-VaR, Value-at-Risk (VaR) and Tail Value-at-Risk (TVaR) is explained. Tail-subadditivity is investigated and it is shown that some GlueVaR risk measures satisfy this property. An interpretation in terms of risk attitudes is provided and a discussion is given on the applicability in non-financial problems such as health, safety, environmental or catastrophic risk management

The motivation to learn as a self-presentation tool among Swiss high school students : The moderating role of mastery goals' perceived social value on learning

Although it has been assumed that the motivation to learn - or mastery goal endorsement - positively predicts learning achievement, most empirical findings fail to demonstrate this relationship. In the present research, conducted in a Swiss high school, we adopted a social value approach to test the hypothesis that adolescent students' mastery goals do in fact predict learning, but only if these goals are perceived as highly useful for scholarly success (high social utility), and are not endorsed as a means to be appreciated by the teachers (low social desirability), a finding that has previously been observed among college students and on teacher-graded achievement measures only. Results demonstrate that in spite of potential peculiarities of an adolescent population, individual differences in mastery goals' perceived social utility and desirability moderate the mastery goal endorsement-learning achievement relation. Findings are discussed with regard to both theory development and educational practice.

Stochasticity in economic losses increases the value of reputation in indirect reciprocity.

Recent theory predicts harsh and stochastic conditions to generally promote the evolution of cooperation. Here, we test experimentally whether stochasticity in economic losses also affects the value of reputation in indirect reciprocity, a type of cooperation that is very typical for humans. We used a repeated helping game with observers. One subject (the "Unlucky") lost some money, another one (the "Passer-by") could reduce this loss by accepting a cost to herself, thereby building up a reputation that could be used by others in later interactions. The losses were either stable or stochastic, but the average loss over time and the average efficiency gains of helping were kept constant in both treatments. We found that players with a reputation of being generous were generally more likely to receive help by others, such that investing into a good reputation generated long-term benefits that compensated for the immediate costs of helping. Helping frequencies were similar in both treatments, but players with a reputation to be selfish lost more resources under stochastic conditions. Hence, returns on investment were steeper when losses varied than when they did not. We conclude that this type of stochasticity increases the value of reputation in indirect reciprocity.

Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis

Introduction: Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA. Methods: Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value. Results: With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity. Conclusions: CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.

Customer driven business model – connecting customer value to firm resources in ICT value networks

The objective of this thesis is to provide a business model framework that connects customer value to firm resources and explains the change logic of the business model. Strategic supply management and especially dynamic value network management as its scope, the dissertation is based on basic economic theories, transaction cost economics and the resource-based view. The main research question is how the changing customer values should be taken into account when planning business in a networked environment. The main question is divided into questions that form the basic research problems for the separate case studies presented in the five Publications. This research adopts the case study strategy, and the constructive research approach within it. The material consists of data from several Delphi panels and expert workshops, software pilot documents, company financial statements and information on investor relations on the companies’ web sites. The cases used in this study are a mobile multi-player game value network, smart phone and “Skype mobile” services, the business models of AOL, eBay, Google, Amazon and a telecom operator, a virtual city portal business system and a multi-play offering. The main contribution of this dissertation is bridging the gap between firm resources and customer value. This has been done by theorizing the business model concept and connecting it to both the resource-based view and customer value. This thesis contributes to the resource-based view, which deals with customer value and firm resources needed to deliver the value but has a gap in explaining how the customer value changes should be connected to the changes in key resources. This dissertation also provides tools and processes for analyzing the customer value preferences of ICT services, constructing and analyzing business models and business concept innovation and conducting resource analysis.

Statistical hypothesis testing and common misinterpretations: should we abandon p-value in forensic science applications?

Many people regard the concept of hypothesis testing as fundamental to inferential statistics. Various schools of thought, in particular frequentist and Bayesian, have promoted radically different solutions for taking a decision about the plausibility of competing hypotheses. Comprehensive philosophical comparisons about their advantages and drawbacks are widely available and continue to span over large debates in the literature. More recently, controversial discussion was initiated by an editorial decision of a scientific journal [1] to refuse any paper submitted for publication containing null hypothesis testing procedures. Since the large majority of papers published in forensic journals propose the evaluation of statistical evidence based on the so called p-values, it is of interest to expose the discussion of this journal's decision within the forensic science community. This paper aims to provide forensic science researchers with a primer on the main concepts and their implications for making informed methodological choices.

Comparison of the prognostic value of pretreatment measurements of systemic inflammatory response in patients undergoing curative resection of clear cell renal cell carcinoma.

PURPOSE: Pretreatment measurements of systemic inflammatory response, including the Glasgow prognostic score (GPS), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) and the prognostic nutritional index (PNI) have been recognized as prognostic factors in clear cell renal cell carcinoma (CCRCC), but there is at present no study that compared these markers. METHODS: We evaluated the pretreatment GPS, NLR, MLR, PLR and PNI in 430 patients, who underwent surgery for clinically localized CCRCC (pT1-3N0M0). Associations with disease-free survival were assessed with Cox models. Discrimination was measured with the C-index, and a decision curve analysis was used to evaluate the clinical net benefit. RESULTS: On multivariable analyses, all measures of systemic inflammatory response were significant prognostic factors. The increase in discrimination compared with the stage, size, grade and necrosis (SSIGN) score alone was 5.8 % for the GPS, 1.1-1.4 % for the NLR, 2.9-3.4 % for the MLR, 2.0-3.3 % for the PLR and 1.4-3.0 % for the PNI. On the simultaneous multivariable analysis of all candidate measures, the final multivariable model contained the SSIGN score (HR 1.40, P < 0.001), the GPS (HR 2.32, P < 0.001) and the MLR (HR 5.78, P = 0.003) as significant variables. Adding both the GPS and the MLR increased the discrimination of the SSIGN score by 6.2 % and improved the clinical net benefit. CONCLUSIONS: In patients with clinically localized CCRCC, the GPS and the MLR appear to be the most relevant prognostic measures of systemic inflammatory response. They may be used as an adjunct for patient counseling, tailoring management and clinical trial design.

The pedagogical value of games and songs : The perceptions of teachers

Aquest estudi intenta explorar i descobrir les actituds i creences d’alguns mestres de llengua anglesa de Catalunya sobre la naturalesa dels jocs i les cançons, així com el paper que juguen en les seves aules per ensenyar l’anglès als infants. Les opinions dels mestres de llengua anglesa van ser recollides mitjançant un qüestionari que contenia preguntes sobre els jocs i les cançons i els resultats s’analitzen i s’exposen en aquest estudi.

The risk factors for fractures and trabecular bone-score value in patients with endogenous Cushing's syndrome.

In a cohort study of 182 consecutive patients with active endogenous Cushing's syndrome, the only predictor of fracture occurrence after adjustment for age, gender bone mineral density (BMD) and trabecular bone score (TBS) was 24-h urinary free cortisol (24hUFC) levels with a threshold of 1472 nmol/24 h (odds ratio, 3.00 (95 % confidence interval (CI), 1.52-5.92); p = 0.002). INTRODUCTION: The aim was to estimate the risk factors for fracture in subjects with endogenous Cushing's syndrome (CS) and to evaluate the value of the TBS in these patients. METHODS: All enrolled patients with CS (n = 182) were interviewed in relation to low-traumatic fractures and underwent lateral X-ray imaging from T4 to L5. BMD measurements were performed using a DXA Prodigy device (GEHC Lunar, Madison, Wisconsin, USA). The TBS was derived retrospectively from existing BMD scans, blinded to clinical outcome, using TBS iNsight software v2.1 (Medimaps, Merignac, France). Urinary free cortisol (24hUFC) was measured by immunochemiluminescence assay (reference range, 60-413 nmol/24 h). RESULTS: Among enrolled patients with CS (149 females; 33 males; mean age, 37.8 years (95 % confidence interval, 34.2-39.1); 24hUFC, 2370 nmol/24 h (2087-2632), fractures were confirmed in 81 (44.5 %) patients, with 70 suffering from vertebral fractures, which were multiple in 53 cases; 24 patients reported non-vertebral fractures. The mean spine TBS was 1.207 (1.187-1.228), and TBS Z-score was -1.86 (-2.07 to -1.65); area under the curve (AUC) was used to predict fracture (mean spine TBS) = 0.548 (95 % CI, 0.454-0.641)). In the final regression model, the only predictor of fracture occurrence was 24hUFC levels (p = 0.001), with an increase of 1.041 (95 % CI, 1.019-1.063), calculated for every 100 nmol/24-h cortisol elevation (AUC (24hUFC) = 0.705 (95 % CI, 0.629-0.782)). CONCLUSIONS: Young patients with CS have a low TBS. However, the only predictor of low traumatic fracture is the severity of the disease itself, indicated by high 24hUFC levels.

Areas of high conservation value in Georgia: present and future threats by invasive alien plants

Georgia is known for its extraordinary rich biodiversity of plants, which may now be threatened due to the spread of invasive alien plants (IAP). We aimed to identify (i) the most prominent IAP out of 9 selected potentially invasive and harmful IAP IAP by predicting thetheir distribution of 9 selected IAP under current and future climate conditions in Georgia as well as in its 43 Protected Areas, as a proxy for areas of high conservation value and (ii) the Protected Areas most at risk due to these IAP. We used species distribution models based on 6 climate variables and then filtered the obtained distributions based on maps of soil and vegetation types, and on recorded occurrences, resulting into the predicted ecological distribution of the 9 IAP's at a resolution of 1km2. We foundOur habitat suitability analysis showed that Ambrosia artemisiifolia, (24% and 40%) Robinia pseudoacaia (14% and 19%) and Ailanthus altissima (9% and 11%) have the largest potential distribution are the most abundant (predicted % area covered)d) IAP, with Ailanthus altissima the potentially most increasing one over the next fifty years (from 9% to 13% and from 11% to 25%), for Georgia and the Protected Areas, respectively. Furthermore, our results show indicate two areas in Georgia that are under specifically high threat, i.e. the area around Tbilisi and an area in the western part of Georgia (Adjara), both at lower altitudes. Our procedure to identify areas of high conservation value most at risk by IAP has been applied for the first time. It will help national authorities in prioritizing their measures to protect Georgia's outstanding biodiversity from the negative impact of IAP.

Prognostic value of PCSK9 levels in patients with acute coronary syndromes.

AIMS: Proprotein convertase subtilisin kexin 9 (PCSK9) is an emerging target for the treatment of hypercholesterolaemia, but the clinical utility of PCSK9 levels to guide treatment is unknown. We aimed to prospectively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospective cohort. At 1 year, the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events (GRACE) variables, as well as the achievement of LDL cholesterol targets of <1.8 mmol/L. Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia (rate ratio, RR 1.21, 95% confidence interval, CI 1.09-1.53), be treated with lipid-lowering therapy (RR 1.46, 95% CI 1.30-1.63), present with longer time interval of chest pain (RR 1.29, 95% CI 1.09-1.53) and higher C-reactive protein levels (RR 1.22, 95% CI 1.16-1.30). PCSK9 increased 12-24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001). At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI 0.69-1.85) for all-cause death and remained similar after adjustment for the GRACE score. Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets (RR 0.81, 95% CI 0.66-0.99). CONCLUSION: In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year.

Reciprocal preening and food sharing in colour-polymorphic nestling barn owls.

Barn owl (Tyto alba) siblings preen and offer food items to one another, behaviours that can be considered prosocial because they benefit a conspecific by relieving distress or need. In experimental broods, we analysed whether such behaviours were reciprocated, preferentially exchanged between specific phenotypes, performed to avoid harassment and food theft or signals of hierarchy status. Three of the results are consistent with the hypothesis of direct reciprocity. First, food sharing was reciprocated in three-chick broods but not in pairs of siblings, that is when nestlings could choose a partner with whom to develop a reciprocating interaction. Second, a nestling was more likely to give a prey item to its sibling if the latter individual had preened the former. Third, siblings matched their investment in preening each other. Manipulation of age hierarchy showed that food stealing was directed towards older siblings but was not performed to compensate for a low level of cooperation received. Social behaviours were related to melanin-based coloration, suggesting that animals may signal their propensity to interact socially. The most prosocial phenotype (darker reddish) was also the phenotype that stole more food, and the effect of coloration on prosocial behaviour depended upon rank and sex, suggesting that colour-related prosociality is state dependent.

Assessing the added value of wastewater-based epidemiology to monitor illicit drug use

Wastewater-based epidemiology consists in acquiring relevant information about the lifestyle and health status of the population through the analysis of wastewater samples collected at the influent of a wastewater treatment plant. Whilst being a very young discipline, it has experienced an astonishing development since its firs application in 2005. The possibility to gather community-wide information about drug use has been among the major field of application. The wide resonance of the first results sparked the interest of scientists from various disciplines. Since then, research has broadened in innumerable directions. Although being praised as a revolutionary approach, there was a need to critically assess its added value, with regard to the existing indicators used to monitor illicit drug use. The main, and explicit, objective of this research was to evaluate the added value of wastewater-based epidemiology with regards to two particular, although interconnected, dimensions of illicit drug use. The first is related to trying to understand the added value of the discipline from an epidemiological, or societal, perspective. In other terms, to evaluate if and how it completes our current vision about the extent of illicit drug use at the population level, and if it can guide the planning of future prevention measures and drug policies. The second dimension is the criminal one, with a particular focus on the networks which develop around the large demand in illicit drugs. The goal here was to assess if wastewater-based epidemiology, combined to indicators stemming from the epidemiological dimension, could provide additional clues about the structure of drug distribution networks and the size of their market. This research had also an implicit objective, which focused on initiating the path of wastewater- based epidemiology at the Ecole des Sciences Criminelles of the University of Lausanne. This consisted in gathering the necessary knowledge about the collection, preparation, and analysis of wastewater samples and, most importantly, to understand how to interpret the acquired data and produce useful information. In the first phase of this research, it was possible to determine that ammonium loads, measured directly in the wastewater stream, could be used to monitor the dynamics of the population served by the wastewater treatment plant. Furthermore, it was shown that on the long term, the population did not have a substantial impact on consumption patterns measured through wastewater analysis. Focussing on methadone, for which precise prescription data was available, it was possible to show that reliable consumption estimates could be obtained via wastewater analysis. This allowed to validate the selected sampling strategy, which was then used to monitor the consumption of heroin, through the measurement of morphine. The latter, in combination to prescription and sales data, provided estimates of heroin consumption in line with other indicators. These results, combined to epidemiological data, highlighted the good correspondence between measurements and expectations and, furthermore, suggested that the dark figure of heroin users evading harm-reduction programs, which would thus not be measured by conventional indicators, is likely limited. In the third part, which consisted in a collaborative study aiming at extensively investigating geographical differences in drug use, wastewater analysis was shown to be a useful complement to existing indicators. In particular for stigmatised drugs, such as cocaine and heroin, it allowed to decipher the complex picture derived from surveys and crime statistics. Globally, it provided relevant information to better understand the drug market, both from an epidemiological and repressive perspective. The fourth part focused on cannabis and on the potential of combining wastewater and survey data to overcome some of their respective limitations. Using a hierarchical inference model, it was possible to refine current estimates of cannabis prevalence in the metropolitan area of Lausanne. Wastewater results suggested that the actual prevalence is substantially higher compared to existing figures, thus supporting the common belief that surveys tend to underestimate cannabis use. Whilst being affected by several biases, the information collected through surveys allowed to overcome some of the limitations linked to the analysis of cannabis markers in wastewater (i.e., stability and limited excretion data). These findings highlighted the importance and utility of combining wastewater-based epidemiology to existing indicators about drug use. Similarly, the fifth part of the research was centred on assessing the potential uses of wastewater-based epidemiology from a law enforcement perspective. Through three concrete examples, it was shown that results from wastewater analysis can be used to produce highly relevant intelligence, allowing drug enforcement to assess the structure and operations of drug distribution networks and, ultimately, guide their decisions at the tactical and/or operational level. Finally, the potential to implement wastewater-based epidemiology to monitor the use of harmful, prohibited and counterfeit pharmaceuticals was illustrated through the analysis of sibutramine, and its urinary metabolite, in wastewater samples. The results of this research have highlighted that wastewater-based epidemiology is a useful and powerful approach with numerous scopes. Faced with the complexity of measuring a hidden phenomenon like illicit drug use, it is a major addition to the panoply of existing indicators. -- L'épidémiologie basée sur l'analyse des eaux usées (ou, selon sa définition anglaise, « wastewater-based epidemiology ») consiste en l'acquisition d'informations portant sur le mode de vie et l'état de santé d'une population via l'analyse d'échantillons d'eaux usées récoltés à l'entrée des stations d'épuration. Bien qu'il s'agisse d'une discipline récente, elle a vécu des développements importants depuis sa première mise en oeuvre en 2005, notamment dans le domaine de l'analyse des résidus de stupéfiants. Suite aux retombées médiatiques des premiers résultats de ces analyses de métabolites dans les eaux usées, de nombreux scientifiques provenant de différentes disciplines ont rejoint les rangs de cette nouvelle discipline en développant plusieurs axes de recherche distincts. Bien que reconnu pour son coté objectif et révolutionnaire, il était nécessaire d'évaluer sa valeur ajoutée en regard des indicateurs couramment utilisés pour mesurer la consommation de stupéfiants. En se focalisant sur deux dimensions spécifiques de la consommation de stupéfiants, l'objectif principal de cette recherche était focalisé sur l'évaluation de la valeur ajoutée de l'épidémiologie basée sur l'analyse des eaux usées. La première dimension abordée était celle épidémiologique ou sociétale. En d'autres termes, il s'agissait de comprendre si et comment l'analyse des eaux usées permettait de compléter la vision actuelle sur la problématique, ainsi que déterminer son utilité dans la planification des mesures préventives et des politiques en matière de stupéfiants actuelles et futures. La seconde dimension abordée était celle criminelle, en particulier, l'étude des réseaux qui se développent autour du trafic de produits stupéfiants. L'objectif était de déterminer si cette nouvelle approche combinée aux indicateurs conventionnels, fournissait de nouveaux indices quant à la structure et l'organisation des réseaux de distribution ainsi que sur les dimensions du marché. Cette recherche avait aussi un objectif implicite, développer et d'évaluer la mise en place de l'épidémiologie basée sur l'analyse des eaux usées. En particulier, il s'agissait d'acquérir les connaissances nécessaires quant à la manière de collecter, traiter et analyser des échantillons d'eaux usées, mais surtout, de comprendre comment interpréter les données afin d'en extraire les informations les plus pertinentes. Dans la première phase de cette recherche, il y pu être mis en évidence que les charges en ammonium, mesurées directement dans les eaux usées permettait de suivre la dynamique des mouvements de la population contributrice aux eaux usées de la station d'épuration de la zone étudiée. De plus, il a pu être démontré que, sur le long terme, les mouvements de la population n'avaient pas d'influence substantielle sur le pattern de consommation mesuré dans les eaux usées. En se focalisant sur la méthadone, une substance pour laquelle des données précises sur le nombre de prescriptions étaient disponibles, il a pu être démontré que des estimations exactes sur la consommation pouvaient être tirées de l'analyse des eaux usées. Ceci a permis de valider la stratégie d'échantillonnage adoptée, qui, par le bais de la morphine, a ensuite été utilisée pour suivre la consommation d'héroïne. Combinée aux données de vente et de prescription, l'analyse de la morphine a permis d'obtenir des estimations sur la consommation d'héroïne en accord avec des indicateurs conventionnels. Ces résultats, combinés aux données épidémiologiques ont permis de montrer une bonne adéquation entre les projections des deux approches et ainsi démontrer que le chiffre noir des consommateurs qui échappent aux mesures de réduction de risque, et qui ne seraient donc pas mesurés par ces indicateurs, est vraisemblablement limité. La troisième partie du travail a été réalisée dans le cadre d'une étude collaborative qui avait pour but d'investiguer la valeur ajoutée de l'analyse des eaux usées à mettre en évidence des différences géographiques dans la consommation de stupéfiants. En particulier pour des substances stigmatisées, telles la cocaïne et l'héroïne, l'approche a permis d'objectiver et de préciser la vision obtenue avec les indicateurs traditionnels du type sondages ou les statistiques policières. Globalement, l'analyse des eaux usées s'est montrée être un outil très utile pour mieux comprendre le marché des stupéfiants, à la fois sous l'angle épidémiologique et répressif. La quatrième partie du travail était focalisée sur la problématique du cannabis ainsi que sur le potentiel de combiner l'analyse des eaux usées aux données de sondage afin de surmonter, en partie, leurs limitations. En utilisant un modèle d'inférence hiérarchique, il a été possible d'affiner les actuelles estimations sur la prévalence de l'utilisation de cannabis dans la zone métropolitaine de la ville de Lausanne. Les résultats ont démontré que celle-ci est plus haute que ce que l'on s'attendait, confirmant ainsi l'hypothèse que les sondages ont tendance à sous-estimer la consommation de cannabis. Bien que biaisés, les données récoltées par les sondages ont permis de surmonter certaines des limitations liées à l'analyse des marqueurs du cannabis dans les eaux usées (i.e., stabilité et manque de données sur l'excrétion). Ces résultats mettent en évidence l'importance et l'utilité de combiner les résultats de l'analyse des eaux usées aux indicateurs existants. De la même façon, la cinquième partie du travail était centrée sur l'apport de l'analyse des eaux usées du point de vue de la police. Au travers de trois exemples, l'utilisation de l'indicateur pour produire du renseignement concernant la structure et les activités des réseaux de distribution de stupéfiants, ainsi que pour guider les choix stratégiques et opérationnels de la police, a été mise en évidence. Dans la dernière partie, la possibilité d'utiliser cette approche pour suivre la consommation de produits pharmaceutiques dangereux, interdits ou contrefaits, a été démontrée par l'analyse dans les eaux usées de la sibutramine et ses métabolites. Les résultats de cette recherche ont mis en évidence que l'épidémiologie par l'analyse des eaux usées est une approche pertinente et puissante, ayant de nombreux domaines d'application. Face à la complexité de mesurer un phénomène caché comme la consommation de stupéfiants, la valeur ajoutée de cette approche a ainsi pu être démontrée.