Novel psychoactive substances (NPS) are synthetic drugs that pose serious public health and safety concerns as their ingestion by recreational drug users continues to cause adverse events and death. A multitude of NPS have been implicated in forensic investigations in the United States, but the identification of these emerging substances is challenging and complex, requiring advanced analytical capabilities and novel analysis workflows. The most common and effective manner for identifying NPS is by the use of mass spectrometry, while the true utility of this technology lies within non-targeted acquisition techniques. This research sought to utilize novel drug screening technologies and customized methodologies to characterize current NPS use in high risk populations through the analysis of biological sample extracts discarded from a partnering forensic toxicology reference laboratory. Specifically, NPS detection, identification, and characterization were the primary foci to produce increased awareness and education on a national level. To accomplish these goals, two novel workflows were developed: sample mining and data mining. A liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) assay was developed, validated, and implemented for forensic toxicology analytical testing. A SCIEX TripleTOF™ 5600+ QTOF-MS with SWATH® acquisition coupled to a Shimadzu Nexera XR UHPLC was used. Resulting data were compared against an extensive in-house library database containing more than 800 analytes. The LC-QTOF-MS assay was applied to the re-analysis of biological sample extracts to discover emergent NPS, their metabolites, and trends in use patterns. In total, 3,543 biological sample extracts were analyzed during this research and 21 emerging NPS were detected, some for the first time, through sample mining. Among these emerging substances were the NPS opioids: isopropyl-U-47700, 3,4-methylenedioxy-U-47700, and fluorofuranylfentanyl; the NPS opioid precursors: N-methyl norfentanyl and benzylfuranylfentanyl; the NPS hallucinogens: 2F-deschloroketamine, methoxy-PCP, and hydroxy-PCP; the NPS stimulants: 3,4-methylenedioxy-alpha-PHP, eutylone, and N-ethyl hexedrone; and the NPS benzodiazepine: flualprazolam. With respect to trends, NPS opioid positivity declined over time during this research; however, fentanyl positivity was persistent. Heroin and 3,4-methylenedioxymethamphetamine (MDMA) positivity appeared to decline slightly, but further temporal evaluation is necessary. NPS were less likely to be found in combination with other NPS; only one NPS substance was found in 82.5% of NPS-positive samples. Fentanyl poly-drug use was common, including concurrent or proximate use with traditional opioids (42.8%), NPS opioids (27.3%), cocaine (26.4%), methamphetamine (13.1%), NPS stimulants (4.2%), and other substances. The evaluation of in vitro metabolism for five emerging NPS detected for the first time during this research (3,4-methylenedioxy-U-47700, ortho-fluorofuranylfentanyl, 2F-deschloroketamine, eutylone, and N-ethyl hexedrone) resulted in the characterization of major metabolic pathways and the identification of metabolites presence in vivo by data mining of extract datafiles. These major metabolites provide utility for forensic laboratories to prolong detection windows for NPS. The primary metabolite identified for 3,4-methylenedioxy-U-47700 was N-demethyl-3,4-methylenedioxy-U-47700; the primary metabolite identified for ortho-fluorofuranylfentanyl was fluoro-4-ANPP; the primary metabolite identified for 2F-deschloroketamine was 2F-deschloro-norketamine; and the primary metabolites identified for eutylone and N-ethyl hexedrone were products of hydrogenation to the beta-ketone. As shown through this research, NPS continue to appear in forensic toxicology casework and novel assays for their detection and characterization are critical to remaining at the forefront of emerging drug trends and recreational drug use. LC-QTOF-MS was a vital piece of the analytical puzzle for discovering and characterizing emerging NPS and their metabolites. Analytical chemists must continue research involving NPS to broaden our understanding of synthetic drugs and their public health and safety impacts. / Chemistry

Les matériaux méso-structurés sont des matériaux à porosité contrôlée, issus de synthèses de chimie sol/gel entre micelles de tensioactifs et précurseur inorganique, le plus souvent de silice. Parmi ces matériaux, le SBA-15, formé en milieu super-acide à partir de P123 (un copolymère tribloc) comme tensioactif et de TEOS comme précurseur inorganique de silice, est un des plus étudiés. La synthèse de ce matériau a été étudiée par diffusion des rayons X à petits angles (SAXS) in situ, et a permis de décrire qualitativement et quantitativement les mécanismes d’auto-assemblages entre micelles de tensioactifs et particules silicatées. Spécifiquement, nos résultats ont montré que l’hydrolyse-condensation du TEOS en solution a permis la formation d’oligomères de silice, qui interagissent avec la couronne des micelles sphériques de P123, pour progressivement former des micelles hybrides cylindriques organiques/inorganiques, qui vont ensuite précipiter en une mésophase hybride 2D-hexagonale. Ce modèle de synthèse est appelé « transition sphères-cylindres ». De plus, afin de comprendre les mécanismes de formation du matériau à toutes les échelles, nous avons étudié l’influence des conditions de synthèse sur la morphologie des grains de matériau méso-structurés. En effet, nous avons montré que sans agitation pendant la synthèse, les grains de matériaux présentent une forme d’équilibre qui dépend fortement de la température de synthèse. En fonction de la température, il est donc possible de former des matériaux hybrides de forme grains de riz, bâtons (courts ou longs) ou mêmes sous forme de tores. Nous proposons un modèle théorique qui permet d’expliquer l’ensemble des morphologies observées, en fonction des tensions de surfaces et des énergies de courbures de cristal-liquide 2D-hexagonal lors de la précipitation de la mésophase hybride. Nous appuyons ce modèle théorique sur des études en diffusion des rayons X à très petits angles (USAXS), qui permettent d’étudier la croissance des grains. Grâce à ces études, nous proposons une description très complète de la formation du matériau SBA-15. Fort de ces connaissances, nous avons pu, grâce à de nouvelles études de SAXS in situ, appliquer le modèle de précipitation de type « transition sphères-cylindres » à d’autres matériaux, issus de tensioactifs non-ioniques fluorés, et ainsi expliquer la formation de matériaux dits « bimodaux », c’est-à-dire issus d’un mélange entre P123 et un tensioactif fluoré(Rf₈(EO)₉ et qui présentent deux ordres poreux bien définis. Enfin, nous avons cherché à utiliser nos connaissances pour la fabrication de matériaux innovants, en remplaçant la solution micellaire par des émulsions dopées en nanoparticules d’or (NPs), afin de fabriquer des matériaux hybrides dopés en NPs. / Meso-structured materials are materials with a well-controlled porosity, designed from sol/gel syntheses between surfactant micelles and an inorganic precursor, most often a silica precursor. Among them, the SBA-15 material, formed in super-acid solution from P123 (a tri-block copolymer) as surfactant and TEOS a silica precursor, is one of the most studied. Synthesis of this material has been studied by in situ Small Angle X-Ray Scattering (SAXS), which allowed to describe both qualitatively and quantitatively the self-assembly mechanisms between surfactant micelles and silica particles. In details, our results showed that TEOS hydrolysis-condensation allow the formation of silica oligomers that interact with the corona of the spherical micelles of P123, and progressively the micelles reshape in hybrid organic/inorganic cylindrical micelles. The hybrid micelles, first free in solution, eventually precipitate in a hybrid 2D-hexagonal mesophase. This model of synthesis is called “sphere-to-rod transition”. Moreover, in order to understand the material mechanisms of formation at every length scales, we studied the influence of the synthesis conditions on the morphology of the meso-structured material grains. Indeed, in agreement with a previous study, our results show that if the synthesis is made without stirring, the material grains has an equilibrium shape that strongly depends on the synthesis temperature. By changing the temperature, one can form hybrid materials with a “rice grain” shape, or a (short or long) rod shape, or even a torus shape. We propose a theoretical model to explain all the observed morphologies, model that takes into account surface tensions and curvature energy of the newly formed 2D-hexagonal liquid-crystal at the precipitation of the hybrid mesophase. We measured the nucleation and growth of the grains by Ultra Small Angle X-Ray Scattering (USAXS). Thanks to all these studies, we present a complete description of the formation of the SBA-15 material. Our knowledge were used to describe new in situ SAXS measurements of new materials: our “sphere-to-rod transition” model was able to describe the formation of two materials, form two fluorinated surfactants and allowed to explain the formation of a “bimodal” material, which means a material with two well-defined porous order, that is synthesized from a mix of two surfactant (P123 and (Rf₈(EO)₉). Finally, we tried to use our knowledge to form innovative materials, by replacing the micellar solution as template by an emulsion doped in gold nanoparticles (NPs) to form hybrid materials doped in NPs.

En raison de leur diffusion sauvage sur le e-commerce, leur soi-disant sécurité d’usage et l’alternative légale aux stupéfiants habituels qu’ils constituent, les nouvelles substances psychoactives (NPS) sont un phénomène mondial émergeant. Au-delà de différents défis dans nos sociétés (législation, prévention,... ), la capacité d'identifier les NPS dans des échantillons biologiques présente de nombreux challenges analytiques : ces nouvelles substances ne sont pas référencées dans les bibliothèques habituelles de spectrométrie de masse commerciales, leur métabolisme est inconnu (avec parfois des métabolites actifs), les doses actives sont parfois très faibles et par conséquent, les concentrations dans le sang ou l'urine sont également faibles. Dans ce contexte, notre laboratoire effectue régulièrement des analyses toxicologiques dans un contexte clinique, et pour les forces de l’ordre, dans des échantillons biologiques à l'aide de deux principaux types d’analyseurs : la chromatographie liquide couplée à la spectrométrie de masse tandem (CL-SM/SM) pour le criblage ciblé et la chromatographie liquide couplée à la spectrométrie de masse haute résolution (CL-SMHR) pour le criblage non ciblé. Cette dernière technique est basée sur la masse exacte (mais également, le profil isotopique et le temps de rétention) des composés de l’échantillon à partir de laquelle la formule chimique est déterminée et recherchée dans une base de données spectrales en utilisant un logiciel dédié. L’objectif de ma thèse est de caractériser des NPS et leurs métabolites (afin d’alimenter cette base de données) en utilisant une stratégie combinant des approches in vitro, in silico et in vivo. Il s’agit, en particulier, d’augmenter la sensibilité de détection de la prise de NPS en se focalisant sur les métabolites qui sont le plus souvent les produits majeurs d’élimination des NPS.A cet effet, une méthode in vitro destinée à produire les métabolites des NPS et utilisant des microsomes hépatiques humains a été mise en oeuvre. Les métabolites obtenus, comparés aux prédictions in silico, ont été enregistrés dans la base de données. Cette approche a été confrontée à l’analyses de comprimés et d’autres produits non biologiques contenant des NPS, mais également, à des données in vivo d’exposition aux NPS : cas d’intoxications, études expérimentales et études épidémiologiques prospectives et rétrospectives dans des populations ciblées, ou non…Au total, ce travail basé sur cette stratégie in vitro, in silico, in vivo m’a permis d’enrichir notre base de données de spectres de masse haute résolution (SMHR) pour le criblage non ciblé et également notre base de données de criblage ciblé (SM/SM). Notre méthode en haute résolution, qui s’est enrichie au cours de ces 3 années de thèse de 83 nouveaux NPS et 281 métabolites, constitue aujourd’hui un outil analytique efficient pour la détection d’une exposition aux NPS. / Owing to wild e-commerce diffusion, alleging safety and legal alternative to usual drugs of abuse arguments, the new psychoactive substances (NPS) are emerging phenomenon in the world. In our societies, through various consecutive challenges (legislation, prevention, …), the ability to identify NPS in biological samples exhibits numerous analytical pitfalls: new substances which are not referenced in the usual commercial mass spectrometric libraries, unknown metabolism (with sometimes active metabolites), sometimes very low active dosages and consecutively low concentrations in blood or urine. In this context, clinical and forensic toxicological analyses in biological samples are routinely performed in our laboratory using two main analytical devices: liquid chromatography-tandem mass spectrometry (LC-MS/MS) for targeted screening and liquid chromatography-high resolution mass spectrometry (LC-HRMS) for non-targeted screening. This last technique is based on the accurate mass (together with isotopic pattern and retention time) of sample components, from which the chemical formula is calculated and searched against a database of mass spectra using dedicated software. The aim of my thesis is to characterize NPS and metabolites (in order to increase the spectral database) using a strategy combining in vitro, in silico, and in vivo approaches. Therefore, the main goal is to increase the detection sensitivity of the NPS use by focusing on the metabolites that are most often the major products of NPS elimination. For this purpose, an in vitro method designed to produce NPS metabolites using human liver microsomes incubations was applied. Obtained metabolites, after confrontation with metabolites in silico predicted, were saved in database. This approach was subsequently confronted with analysis of tablets or other non-biological product containing NPS, but also, with in vivo observed data from NPS exposure: intoxication cases, experimental studies and prospective and retrospective epidemiological studies in targeted population or not … All in all, this work based on this in vitro, in silico and in vivo strategy allowed me to enhance our high resolution spectra database (HRMS) for non-targeted screening and also our spectra database for targeted screening (MS/MS). Today, our HRMS device, with a database that was increased with 83 new NPS and 281 metabolites for the duration of my thesis, is an efficient analytical tool for NPS use detection.

The video streaming business has grown substantially during the last decades. To optimize the user experience in video streaming, it is important to know how the user satisfaction relates to the technical qualities for the video streaming services, such as bufferings and startup times.  The Net Promoter Score (NPS) is a widely used management tool used in surveys to measure customer satisfaction and loyalty. The users are categorized into three user groups based on a survey question. This thesis investigates whether it is possible to find correlations between the three user groups based on NPS ratings and measured technical qualities from video streams. Initial data exploring through information visualization suggested that the data should be separated into live streams and video-on-demand. Statistical analysis showed that the NPS user groups have no correlations to how long the users are watching the streams, nor to how long the video takes to start. The results showed, that the users watching live streams seem to be more sensitive to lower qualities than those watching video- on-demand. However, this could also be due to the fact that the measured technical qualities during live streams are generally lower. The buffering and the seek time proved to have correlations to the measured user satisfaction, but several other factors such as the actual video content could also have big impacts on the user’s ratings. The users which had experienced more buffering and longer seek times were more likely to rate the service with a lower score, than the average user. / Mängden videor som streamas över Internet har ökat väsentligt under de senaste årtiondena. För att kunna optimera upplevelsen för de som streamar videor är det viktigt för företagen som erbjuder dessa tjänster att veta hur kundnöjdheten relaterar till de tekniska egenskaperna. Dessa kan inkludera faktorer såsom buffring och starttider. Net Promoter Score (NPS) är ett verktyg som används inom många olika branscher för att mäta kundnöjdhet och lojalitet. Användarna delas in i tre grupper beroende på hur de svarar på en enkätfråga. Detta examensarbete undersöker huruvida det är möjligt att hitta korrelationer mellan kundnöjdhet baserad på de tre användargrupperna från NPS-verktyget och uppmätta tekniska kvaliteter från en streamingtjänst. Efter att inledande informationsvisualiseringar påvisade skillnader mellan live-strömmar och video-on-demand har dessa grupper hanterats separat. Statistisk analys visade att de tre NPS-grupperna inte har några korrelationer med starttiden eller hur länge användarna tittar på videor. Resultatet visade även att användarna som tittar på live-strömmar verkar vara känsligare för lägre tekniska kvaliteter än de som tittar på video-on-demand. Detta kan dock även bero på att de uppmätta tekniska egenskaperna under live-strömmarna generellt är lite lägre. Buffringen och söktiden visade sig ha samband med den uppmätta kundnöjdheten, men flera andra faktorer, såsom det faktiska videoinnehållet, kan också ha en inverkan på användarnas betyg. Användarna som hade upplevt mer buffring och längre söktider var mer benägna att ge tjänsten ett lägre betyg än den genomsnittliga användaren.

Master of Science / Department of Biological & Agricultural Engineering / Stacy L. Hutchinson / Soil erosion is a serious problem resulting in degradation of soil systems and nonpoint source (NPS) pollution of water resources. Concentrated overland flow is the primary transport mechanism for many NPS pollutants including soil, and locating areas where sheet flow transitions into concentrated flow is useful for assessing the potential for soil erosion. The ability to predict areas where overland flow transitions to concentrated flow and soil erosion potential is high assists land managers in implementing best management practices (BMPs) to reduce soil erosion and NPS. An erosion model, called the nLS model, was developed to identify transitional overland flow regions. The model is based on the kinematic wave overland flow theory and uses Manning’s n values, flow length, and slope as inputs to determine where overland flow transitions to sheet flow and soil erosion potential increases. Currently, the model has only been tested and validated for watersheds within Kansas. In order to assess model uncertainties and evaluate the model’s applicability to other regions, a sensitivity analysis on key input parameters was conducted. To assess model operations, several sensitivity analyses were performed on model inputs, including digital elevation models (DEMs) and landuse/landcover data (LULC). The impact of slope was assessed using two methods. First, by modifying the DEMs in a stepwise fashion from flatter to steeper terrains, and second, by modifying the elevation of each DEM cell based on the associated elevation error. To assess difficulties that might arise from the parameterization of surface roughness, LULC classes were assigned Manning’s n values within the suggested range using a Monte Carlo simulation. In addition, the critical threshold value used for locating erosion potential sites was modified, and alternative model calculations were used to assess the potential for improving model accuracy. Finally, the model was run using data from multiple sites, including two study areas in Hawaii and two in Kansas. The outputs for each site were analyzed in an attempt to identify any trends caused by site characteristics. Results from this study showed that the nLS model was sensitive to all of the inputs. Modifying the Manning’s roughness coefficient significantly altered the final nLS values and shifted the critical threshold points, especially in areas of the upper watershed. Changes in the slope value modified the nLS model outputs in a predictable manner, but there was some variability, especially in areas with lower slope values. In addition, discrepancies in the DEM, which may be present due to measurement or processing error, were shown to significantly alter the flow paths of a watershed. These findings suggest that accurate roughness coefficients and LULC data are especially important for regions with a steeper topography, and accurate elevation data is important for regions with lower slope values. The results also suggest that the threshold value for the model plays a vital role in locating potential soil erosion sites, and adjustments to this value could possibly be used as a method for calibrating the nLS model. Finally, the alternative model calculations used in this study did not significantly improve the accuracy of the nLS model, so the existing model is sufficient for obtaining accurate nLS estimates. The information gained from this study can improve the assessment of soil erosion processes due to concentrated overland flow. By successfully implementing a land management program that makes use of the nLS models, it should be possible to improve BMP placement and design, helping to improve water and soil quality.

International Telemetering Conference Proceedings / October 20-23, 2003 / Riviera Hotel and Convention Center, Las Vegas, Nevada / Unmanned Telemetry Ground System (UTGS) was implemented in Defense System Test Center (DSTC), Agency for Defense Development (ADD). The components of UTGS are Antenna, NPS (Network Power Switch), RCB (Receiver/Combiner/Bit synchronizer) and microwave link. We have installed RCB which is composed of receiver, combiner and bit synchronizer. RCB can be controlled and monitored by RS232 serial communication and microwave network. NPS controls its power supplies. UTGS sends PCM stream to local site using E1-class HDSL and microwave link. This system is possible the signal acquisition and reduction of man power at remote site. The usability and performance of UTGS was proved in flight tests. This paper describes the hardware, software design and an implementation of UTGS.

I detta examensarbete har vi undersökt vilket område klasslärare ansåg att det krävdes mest kompetens inom. Vi har även undersökt vad som är den största utmaningen och inom vilket område klasslärarna önskar mer utbildning då de har en elev med NPS-diagnos i klassrummet som tilldelats ett digitalt verktyg som kompensatoriskt hjälpmedel. Då tidigare forskning pekar på att pedagoger har brister på kompetens inom IT, ville vi undersöka om det fortfarande var så med tanke på att den digitala utvecklingen är snabb. Vi har med hjälp av deltagande klasslärare i en enkätundersökning och tre korta semistrukturerade intervjuer analyserat och presenterat resultatet samt satt det i relation till forskningsbakgrunden i vårt arbete. Resultatet från vår undersökning pekar på att klasslärarna anser att lärarrollens betydelse för relationer och motivation är det område det krävs störst komptens inom då de har en NPS-diagnostiserad elev som tilldelats ett digitalt verktyg som kompensatoriskt hjälpmedel. De anser även att det relationella perspektivet är den största utmaningen då man har dessa elever i klassrummet. Motiveringen till dessa två svar var i stort sett desamma. Klasslärarna menade att om man inte har någon god relation så spelar det digitala kompensatoriska hjälpmedlet ingen roll. Vi fick även en indikation på att klasslärarna trots detta, önskade utbildning inom IT.

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In Taiwan, non-point source (NPS) pollution is one of the major causes of the impairment of surface waters. NPS pollutants, which are associated with stormwater runoff from agricultural land uses can be quite diffuse and difficult to treat. The I-Liao Creek Basin, located in southern Taiwan, flows through approximately 90-km and drains towards the Kaoping River. It is one of the major sub-basin in the Kaoping River watershed, which is the largest and the most intensively used watershed in Taiwan. Field investigation results indicate that the main water pollution sources in the I-Liao Creek Basin are domestic wastewater and NPS pollutants from agricultural activities. In this study, an Integrated Watershed Management Model (IWMM) was applied for simulating the water quality in the I-Liao Creek watershed. The model includes a global atmosphere module, a land module, a human impact module, a canopy module, and a global ocean module. Those modules can be linked and managed by a graphic user-interface. The model was calibrated and verified with field data, and was used to investigate potential NPS pollution management plans. Moreover, the Storm Water Management Model (SWMM) was used to verify the accuracy of the simulated results of flow and water qualities. Results from this study show that geographical information system (GIS) is an important mean for land-use identification and waste load estimation in the catchment. Linking the information of land utilization with the NPS pollution simulation model may further provide essential information of pollution potential of NPS pollution for all sub-regions in the river basin. Results and experience obtained from this study will be helpful in designing the watershed management and NPS pollution control strategies for other similar river basins.

This thesis investigates and design innovative concepts of noise protection solutions (NPS) for the Swedish high-speed railway (HSR) that is planned to be built between Stockholm and Gothenburg in the near future. The planned traffic will start in 2035. The concepts have been developed through a design process, starting with a research phase of existing solutions for the problem, theory about noise and absorbing materials. Following by an analysis of all researched data to narrow down the project and the interviews with the Swedish transport administration, this in order to pinpoint the requirements for the NPS. To get opinions from people who are exposed to low frequency noise, two questionnaires were conducted with a total of 80 respondents. Because of the difficulty to find the exact target group of people who are only exposed to the noise from high speed trains, the first questionnaire was open for all people who are exposed to low frequency noise (traffic noise). The second questionnaire was published at Trafikverket Facebook page, and because of their high number of followers, people who are exposed to train noise could easily be reached. From the answers and the analyzed data, a requirement specification for the NPS was created with all the requirements that the NPS needed to have according to Trafikverkets standards and from the questionnaire. These requirements were the prerequisite used in the synthesis phase. Different brainstorming methods were used to develop a large amount of ideas. A workshop with people from the society was held to keep the creativity alive. From the first synthesis phase, six ideas out of 160 ideas were chosen by a dot evaluation, and in order to narrow down the ideas even more, a matrix evaluation was used. The matrix was built from the requirement specification to verify which ideas fit most of the requirements for a new NPS. From this evaluation, two concepts were chosen to be developed further. After a validation from Trafikverket, the two concepts were further developed, this by an open brainstorming session. Via discussions and sketching, new ideas for the concepts arose. We found solutions for the problems that arose with each concept and made final decisions about the design and material. Three concepts were 3D visualized in the CAD program Rhinoceros. Final touches of the concepts were made in Keyshot. Throughout this thesis, three concepts for noise protections for the HSR have been developed and the research question “How can innovation be created by using a design process?” have been discussed and answered.