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.

Duration of untreated psychosis: Impact of the definition of treatment onset on its predictive value over three years of treatment.

BACKGROUND: While reduction of DUP (Duration of Untreated Psychosis) is a key goal in early intervention strategies, the predictive value of DUP on outcome has been questioned. We planned this study in order to explore the impact of three different definition of "treatment initiation" on the predictive value of DUP on outcome in an early psychosis sample. METHODS: 221 early psychosis patients aged 18-35 were followed-up prospectively over 36 months. DUP was measured using three definitions for treatment onset: Initiation of antipsychotic medication (DUP1); engagement in a specialized programme (DUP2) and combination of engagement in a specialized programme and adherence to medication (DUP3). RESULTS: 10% of patients never reached criteria for DUP3 and therefore were never adequately treated over the 36-month period of care. While DUP1 and DUP2 had a limited predictive value on outcome, DUP3, based on a more restrictive definition for treatment onset, was a better predictor of positive and negative symptoms, as well as functional outcome at 12, 24 and 36 months. Globally, DUP3 explained 2 to 5 times more of the variance than DUP1 and DUP2, with effect sizes falling in the medium range according to Cohen. CONCLUSIONS: The limited predictive value of DUP on outcome in previous studies may be linked to problems of definitions that do not take adherence to treatment into account. While they need replication, our results suggest effort to reduce DUP should continue and aim both at early detection and development of engagement strategies.

Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL).

BACKGROUND: Most peripheral T-cell lymphoma (PTCL) patients have a poor outcome and the identification of prognostic factors at diagnosis is needed. PATIENTS AND METHODS: The prognostic impact of total metabolic tumor volume (TMTV0), measured on baseline [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography, was evaluated in a retrospective study including 108 PTCL patients (27 PTCL not otherwise specified, 43 angioimmunoblastic T-cell lymphomas and 38 anaplastic large-cell lymphomas). All received anthracycline-based chemotherapy. TMTV0 was computed with the 41% maximum standardized uptake value threshold method and an optimal cut-off point for binary outcomes was determined and compared with others prognostic factors. RESULTS: With a median follow-up of 23 months, 2-year progression-free survival (PFS) was 49% and 2-year overall survival (OS) was 67%. High TMTV0 was significantly associated with a worse prognosis. At 2 years, PFS was 26% in patients with a high TMTV0 (>230 cm(3), n = 53) versus 71% for those with a low TMTV0, [P < 0.0001, hazard ratio (HR) = 4], whereas OS was 50% versus 80%, respectively, (P = 0.0005, HR = 3.1). In multivariate analysis, TMTV0 was the only significant independent parameter for both PFS and OS. TMTV0, combined with PIT, discriminated even better than TMTV0 alone, patients with an adverse outcome (TMTV0 >230 cm(3) and PIT >1, n = 33,) from those with good prognosis (TMTV0 ≤230 cm(3) and PIT ≤1, n = 40): 19% versus 73% 2-year PFS (P < 0.0001) and 43% versus 81% 2-year OS, respectively (P = 0.0002). Thirty-one patients (other TMTV0-PIT combinations) had an intermediate outcome, 50% 2-year PFS and 68% 2-year OS. CONCLUSION: TMTV0 appears as an independent predictor of PTCL outcome. Combined with PIT, it could identify different risk categories at diagnosis and warrants further validation as a prognostic marker.

Value of renal cortical thickness as a predictor of renal function impairment in chronic renal disease patients

Objective: To determine the presence of linear relationship between renal cortical thickness, bipolar length, and parenchymal thickness in chronic kidney disease patients presenting with different estimated glomerular filtration rates (GFRs) and to assess the reproducibility of these measurements using ultrasonography. Materials and Methods: Ultrasonography was performed in 54 chronic renal failure patients. The scans were performed by two independent and blinded radiologists. The estimated GFR was calculated using the Cockcroft-Gault equation. Interobserver agreement was calculated and a linear correlation coefficient (r) was determined in order to establish the relationship between the different renal measurements and estimated GFR. Results: The correlation between GFR and measurements of renal cortical thickness, bipolar length, and parenchymal thickness was, respectively, moderate (r = 0.478; p < 0.001), poor (r = 0.380; p = 0.004), and poor (r = 0.277; p = 0.116). The interobserver agreement was considered excellent (0.754) for measurements of cortical thickness and bipolar length (0.833), and satisfactory for parenchymal thickness (0.523). Conclusion: The interobserver reproducibility for renal measurements obtained was good. A moderate correlation was observed between estimated GFR and cortical thickness, but bipolar length and parenchymal thickness were poorly correlated.

Added value of SPECT/CT in addition to whole-body scintigraphy augmented with prone lateral views in patients with well-differentiated thyroid carcinoma

Purpose: We aimed to determine the impact of SPECT/CT performed in addition to whole-­‐body scintigraphy augmented with prone lateral views in patients with well-­‐differentiated thyroid carcinoma. Methods and Materials: This retrospective study included 141 patients (87 female, 54 male, mean age 47 years) with well-­‐differentiated thyroid carcinoma (105 papillary, 31 follicular, 1 Hürthle cell and 4 poorly differentiated) treated with radioiodine therapy (1000-7400 MBq). Patients were referred for either first postsurgical therapy (n=76) or further treatment (n=65). Two nuclear medicine physicians interpreted the scans in consensus (first whole-­‐body scintigraphy with prone lateral view, then SPECT/CT) reporting abnormal iodine uptake in the thyroid bed, lymph nodes and distant metastasis. The corresponding ATA risk score was calculated for each patient before and after SPECT/CT, as well as change in disease extension Results: The analysis showed a difference between scintigraphy and SPECT/CT in n=17 lesions in 14 patients (9.9%): 12 were described as suspicious on scintigraphy and could be considered as benign on SPECT/CT (3 corresponded to local iodine uptake, 6 to lymph nodes metastases and 3 to distant metastases). The others 5 corresponded to metastases (4 lymph nodes and 1 distant) that were not seen on whole-­‐body scintigraphy augmented with prone lateral views. In 10 of 141 (7.1%) patients, we observed a change in ATA risk stratification, with a risk increase in 4 of them (2.8%). Conclusion: SPECT/CT allowed detecting 5 focal lesions missed on planar scintigraphy, and to precise benignity of 12 suspicious lesions on planar scintigraphy. Moreover, SPECT/CT improved the risk stratification in 10 patients with a significant change in the patient management

Expanding the Customer Relationship Management scope to the non-profit organizations : an analysis focused on the e-university domain

Peer-reviewed

Market orientation and performance in entrepreneurial SMEs

Market orientation is the organizational culture that creates the necessary behaviors for continuous additional value for customers and thus continuous superior performance for the business. The field of market orientation has been studied repeatedly during the past two decades. Yet research has concentrated on large firms in large domestic markets creating a need for diversifying research. The master’s thesis at hand examined the general incidence of market orientation among SMEs from five different industries as well as its consequences on SME performance. The empirical part of the thesis was conducted with a web-based survey that resulted in 255 responses. The data of the survey was analyzed by statistical analysis. The incidence of market orientation varied among dimensions and market orientation did not show any direct effect on firm performance. Customer orientation was the only dimension that showed a direct (positive) effect. On the contrary, moderating effects were found which indicate that the effect of market orientation in SMEs is influenced by other factors that should receive further attention. Also industry specific differences were discovered and should be further examined.

Estimating extreme value cumulative distribution functions using bias-corrected kernel approaches

We propose a new kernel estimation of the cumulative distribution function based on transformation and on bias reducing techniques. We derive the optimal bandwidth that minimises the asymptotic integrated mean squared error. The simulation results show that our proposed kernel estimation improves alternative approaches when the variable has an extreme value distribution with heavy tail and the sample size is small.

Combining Customer Requirements and Modularity in Complete Tap Water Solution

This thesis studies forming a complete solution concept for tap water systems in project business environment. The aim of the study is to find tools and means for the target company to determine the scope of their tap water solution offering and to research what kind of organizational capabilities and resources are needed to supply such system solutions. With the help of literature, the characteristics of systems selling and project business and thematics of systems integration and integrated solutions are examined, and the significance of modularity and customer requirements in the given operational environment is discussed. After this, a checklist tool for customer requirements management is developed for the tap water system along with a module allocation method. The study proposes that with the checklist and module allocation the technical specifications can be extensively and innovatively defined for the system. The tools developed are a part of a complete tap water solution concept, which suggests that integrated solutions might constitute possibilities for the company to outperform its competitors when the traditional business methods of the industry are becoming obsolete.

Developing the environmental marketing of an industrial company

The objective of this study was to examine how the customers of Larox Flowsys value environmental issues and how environmental issues affect their purchasing behaviour. A comparison between Larox peristaltic pumps and competing pump brands and types was also made in order to find out whether LPP pumps possess some more environmentally beneficial features that other pumps do not have. Finally, if the answers to the first two research questions show that a need for a new marketing message does exist, then the final stage is to select the most appropriate environmental arguments for Larox Flowsys. The empirical data in the study was collected from several different sources, but the main sources were the customer interviews and the outsourced market research. The data was analysed mainly by using content analysis, but theme formation and quantification were also utilized. The results showed that the customers do not consider environmental issues as a main purchasing criterion, but they may well be the criterion that differentiates the product from competing ones. The comparison proved that LPP pumps do possess some significant environmental benefits over competing pumps and therefore, the prerequisite for the use of environmental arguments exists. The final stage in the study was to select the proper environmental arguments for Larox Flowsys.

Estimating the value of the metal-ligand bond dissociation enthalpy<D> (M-L) for adducts using empirical equations supported by TG data

In this work is presented and tested (for 106 adducts, mainly of the zinc group halides) two empirical equations supported in TG data to estimate the value of the metal-ligand bond dissociation enthalpy for adducts: <D> (M-O) = t i / g if t i < 420 K and <D> (M-O) = (t i / g ) - 7,75 . 10-2 . t i if t i > 420 K. In this empirical equations, t i is the thermodynamic temperature of the beginning of the thermal decomposition of the adduct, as determined by thermogravimetry, andg is a constant factor that is function of the metal halide considered and of the number of ligands, but is not dependant of the ligand itself. To half of the tested adducts the difference between experimental and calculated values was less than 5%. To about 80% of the tested adducts, the difference between the experimental (calorimetric) and the calculated (using the proposed equations) values are less than 15%.

Factors of customer project profitability in an engineering industrial enterprise

The purpose of the study is to find factors affecting projects' profitability in project business. The issue is approached from customer profitability and project management point of view. The study has been made for a big Finnish company acting in a global market place. The research method is quantitative. Research hypotheses are based on the literature. The used database is originated from the company's ERP- (enterprise resource planning) and project financial follow-up —system. The findings of the study supported the hypotheses weakly. Obviously profitability fluctuated depending on a customer and a project manager. The reasons could not be justified with the variables used in the research.

Drivers and Barriers of Collaboration in the Value Chain of Paperboard-Packed Consumer Goods

Value chain collaboration has been a prevailing topic for research, and there is a constantly growing interest in developing collaborative models for improved efficiency in logistics. One area of collaboration is demand information management, which enables improved visibility and decrease of inventories in the value chain. Outsourcing of non-core competencies has changed the nature of collaboration from intra-enterprise to cross-enterprise activity, and this together with increasing competition in the globalizing markets have created a need for methods and tools for collaborative work. The retailer part in the value chain of consumer packaged goods (CPG) has been studied relatively widely, proven models have been defined, and there exist several best practice collaboration cases. The information and communications technology has developed rapidly, offering efficient solutions and applications to exchange information between value chain partners. However, the majority of CPG industry still works with traditional business models and practices. This concerns especially companies operating in the upstream of the CPG value chain. Demand information for consumer packaged goods originates at retailers' counters, based on consumers' buying decisions. As this information does not get transferred along the value chain towards the upstream parties, each player needs to optimize their part, causing safety margins for inventories and speculation in purchasing decisions. The safety margins increase with each player, resulting in a phenomenon known as the bullwhip effect. The further the company is from the original demand information source, the more distorted the information is. This thesis concentrates on the upstream parts of the value chain of consumer packaged goods, and more precisely the packaging value chain. Packaging is becoming a part of the product with informative and interactive features, and therefore is not just a cost item needed to protect the product. The upstream part of the CPG value chain is distinctive, as the product changes after each involved party, and therefore the original demand information from the retailers cannot be utilized as such – even if it were transferred seamlessly. The objective of this thesis is to examine the main drivers for collaboration, and barriers causing the moderate adaptation level of collaborative models. Another objective is to define a collaborative demand information management model and test it in a pilot business situation in order to see if the barriers can be eliminated. The empirical part of this thesis contains three parts, all related to the research objective, but involving different target groups, viewpoints and research approaches. The study shows evidence that the main barriers for collaboration are very similar to the barriers in the lower part of the same value chain; lack of trust, lack of business case and lack of senior management commitment. Eliminating one of them – the lack of business case – is not enough to eliminate the two other barriers, as the operational model in this thesis shows. The uncertainty of the future, fear of losing an independent position in purchasing decision making and lack of commitment remain strong enough barriers to prevent the implementation of the proposed collaborative business model. The study proposes a new way of defining the value chain processes: it divides the contracting and planning process into two processes, one managing the commercial parts and the other managing the quantity and specification related issues. This model can reduce the resistance to collaboration, as the commercial part of the contracting process would remain the same as in the traditional model. The quantity/specification-related issues would be managed by the parties with the best capabilities and resources, as well as access to the original demand information. The parties in between would be involved in the planning process as well, as their impact for the next party upstream is significant. The study also highlights the future challenges for companies operating in the CPG value chain. The markets are becoming global, with toughening competition. Also, the technology development will most likely continue with a speed exceeding the adaptation capabilities of the industry. Value chains are also becoming increasingly dynamic, which means shorter and more agile business relationships, and at the same time the predictability of consumer demand is getting more difficult due to shorter product life cycles and trends. These changes will certainly have an effect on companies' operational models, but it is very difficult to estimate when and how the proven methods will gain wide enough adaptation to become standards.