Formal Modeling and Analysis Techniques for High Level Petri Nets

Petri Nets are a formal, graphical and executable modeling technique for the specification and analysis of concurrent and distributed systems and have been widely applied in computer science and many other engineering disciplines. Low level Petri nets are simple and useful for modeling control flows but not powerful enough to define data and system functionality. High level Petri nets (HLPNs) have been developed to support data and functionality definitions, such as using complex structured data as tokens and algebraic expressions as transition formulas. Compared to low level Petri nets, HLPNs result in compact system models that are easier to be understood. Therefore, HLPNs are more useful in modeling complex systems. There are two issues in using HLPNs - modeling and analysis. Modeling concerns the abstracting and representing the systems under consideration using HLPNs, and analysis deals with effective ways study the behaviors and properties of the resulting HLPN models. In this dissertation, several modeling and analysis techniques for HLPNs are studied, which are integrated into a framework that is supported by a tool. For modeling, this framework integrates two formal languages: a type of HLPNs called Predicate Transition Net (PrT Net) is used to model a system's behavior and a first-order linear time temporal logic (FOLTL) to specify the system's properties. The main contribution of this dissertation with regard to modeling is to develop a software tool to support the formal modeling capabilities in this framework. For analysis, this framework combines three complementary techniques, simulation, explicit state model checking and bounded model checking (BMC). Simulation is a straightforward and speedy method, but only covers some execution paths in a HLPN model. Explicit state model checking covers all the execution paths but suffers from the state explosion problem. BMC is a tradeoff as it provides a certain level of coverage while more efficient than explicit state model checking. The main contribution of this dissertation with regard to analysis is adapting BMC to analyze HLPN models and integrating the three complementary analysis techniques in a software tool to support the formal analysis capabilities in this framework. The SAMTools developed for this framework in this dissertation integrates three tools: PIPE+ for HLPNs behavioral modeling and simulation, SAMAT for hierarchical structural modeling and property specification, and PIPE+Verifier for behavioral verification.

Bullying Victimization and Perpetration Among Adolescent Sport Teammates

Purpose: Bullying is a specific pattern of repeated victimization explored with great frequency in school-based literature, but receiving little attention within sport. The current study explored the prevalence of bullying in sport, and examined whether bullying experiences were associated with perceptions about relationships with peers and coaches. Method: Adolescent sport team members (n = 359, 64% female) with an average age of 14.47 years (SD = 1.34) completed a pen-and-paper or online questionnaire assessing how frequently they perpetrated or were victimized by bullying during school and sport generally, as well as recent experiences with 16 bullying behaviors on their sport team. Participants also reported on relationships with their coach and teammates. Results: Bullying was less prevalent in sport compared with school, and occurred at a relatively low frequency overall. However, by identifying participants who reported experiencing one or more act of bullying on their team recently, results revealed that those victimized through bullying reported weaker connections with peers, whereas those perpetrating bullying only reported weaker coach relationships. Conclusion: With the underlying message that bullying may occur in adolescent sport through negative teammate interactions, sport researchers should build upon these findings to develop approaches to mitigate peer victimization in sport.

Time series wind power forecasting based on variant Gaussian process and TLBO

Due to the variability and stochastic nature of wind power system, accurate wind power forecasting has an important role in developing reliable and economic power system operation and control strategies. As wind variability is stochastic, Gaussian Process regression has recently been introduced to capture the randomness of wind energy. However, the disadvantages of Gaussian Process regression include its computation complexity and incapability to adapt to time varying time-series systems. A variant Gaussian Process for time series forecasting is introduced in this study to address these issues. This new method is shown to be capable of reducing computational complexity and increasing prediction accuracy. It is further proved that the forecasting result converges as the number of available data approaches innite. Further, a teaching learning based optimization (TLBO) method is used to train the model and to accelerate
the learning rate. The proposed modelling and optimization method is applied to forecast both the wind power generation of Ireland and that from a single wind farm to show the eectiveness of the proposed method.

The Antibiotic Resistance and Prescribing in European Children Project: A Neonatal and Pediatric Antimicrobial Web-based Point Prevalence Survey in 73 Hospitals Worldwide

BACKGROUND: The neonatal and pediatric antimicrobial point prevalence survey (PPS) of the Antibiotic Resistance and Prescribing in European Children project (http://www.arpecproject.eu/) aims to standardize a method for surveillance of antimicrobial use in children and neonates admitted to the hospital within Europe. This article describes the audit criteria used and reports overall country-specific proportions of antimicrobial use. An analytical review presents methodologies on antimicrobial use.

METHODS: A 1-day PPS on antimicrobial use in hospitalized children was organized in September 2011, using a previously validated and standardized method. The survey included all inpatient pediatric and neonatal beds and identified all children receiving an antimicrobial treatment on the day of survey. Mandatory data were age, gender, (birth) weight, underlying diagnosis, antimicrobial agent, dose and indication for treatment. Data were entered through a web-based system for data-entry and reporting, based on the WebPPS program developed for the European Surveillance of Antimicrobial Consumption project.

RESULTS: There were 2760 and 1565 pediatric versus 1154 and 589 neonatal inpatients reported among 50 European (n = 14 countries) and 23 non-European hospitals (n = 9 countries), respectively. Overall, antibiotic pediatric and neonatal use was significantly higher in non-European (43.8%; 95% confidence interval [CI]: 41.3-46.3% and 39.4%; 95% CI: 35.5-43.4%) compared with that in European hospitals (35.4; 95% CI: 33.6-37.2% and 21.8%; 95% CI: 19.4-24.2%). Proportions of antibiotic use were highest in hematology/oncology wards (61.3%; 95% CI: 56.2-66.4%) and pediatric intensive care units (55.8%; 95% CI: 50.3-61.3%).

CONCLUSIONS: An Antibiotic Resistance and Prescribing in European Children standardized web-based method for a 1-day PPS was successfully developed and conducted in 73 hospitals worldwide. It offers a simple, feasible and sustainable way of data collection that can be used globally.

Swellable polymer films containing Au nanoparticles for point-of-care therapeutic drug monitoring using surface-enhanced Raman spectroscopy

Large (10 × 10 cm) sheets of surface-enhanced Raman spectroscopy (SERS) active polymer have been prepared by stabilising metal nanoparticle aggregates within dry hydroxyethylcellulose (HEC) films. In these films the aggregates are protected by the polymer matrix during storage but in use they are released when aqueous analyte droplets cause the films to swell to their gel form. The fact that these "Poly-SERS" films can be prepared in bulk but then cut to size and stored in air before use means that they provide a cost effective and convenient method for routine SERS analysis. Here we have tested both Ag and Au Poly-SERS films for use in point-of-care monitoring of therapeutic drugs, using phenytoin as the test compound. Phenytoin in water could readily be detected using Ag Poly-SERS films but dissolving the compound in phosphate buffered saline (PBS) to mimic body fluid samples caused loss of the drug signal due to competition for metal surface sites from Cl^- ions in the buffer solution. However, with Au Poly-SERS films there was no detectable interference from Cl^- and these materials allowed phenytoin to be detected at 1.8 mg L^-1, even in PBS. The target range of detection of phenytoin in therapeutic drug monitoring is 10-20 mg L^-1. With the Au Poly-SERS films, the absolute signal generated by a given concentration of phenytoin was lower for the films than for the parent colloid but the SERS signals were still high enough to be used for therapeutic monitoring, so the cost in sensitivity for moving from simple aqueous colloids to films is not so large that it outweighs the advantages which the films bring for practical applications, in particular their ease of use and long shelf life.

Sensitive and specific detection of viable Mycobacterium avium subsp. paratuberculosis in raw milk by the Peptide-mediated magnetic separation (PMS)-phage assay

This study describes further validation of a previously described Peptide-mediated magnetic separation (PMS)-Phage assay, and its application to test raw cows’ milk for presence of viable Mycobacterium avium subsp. paratuberculosis (MAP). The inclusivity and exclusivity of the PMS-phage assay were initially assessed, before the 50% limit of detection (LOD50) was determined and compared with those of PMS-qPCR (targeting both IS900 and f57) and PMS-culture. These methods were then applied in parallel to test 146 individual milk samples and 22 bulk tank milk samples from Johne’s affected herds. Viable MAP were detected by the PMS-phage assay in 31 (21.2%) of 146 individual milk samples (mean plaque count of 228.1 PFU/50 ml, range 6-948 PFU/50 ml), and 13 (59.1%) of 22 bulk tank milks (mean plaque count of 136.83 PFU/50 ml, range 18-695 PFU/50 ml). In contrast, only 7 (9.1%) of 77 individual milks and 10 (45.4%) of 22 bulk tank milks tested PMS-qPCR positive, and 17 (11.6%) of 146 individual milks and 11 (50%) of 22 bulk tank milks tested PMS-culture positive. The mean 50% limits of detection (LOD50) of the PMS-phage, PMS-IS900 qPCR and PMS-f57 qPCR assays, determined by testing MAP-spiked milk, were 0.93, 135.63 and 297.35 MAP CFU/50 ml milk, respectively. Collectively, these results demonstrate that, in our laboratory, the PMS-phage assay is a sensitive and specific method to quickly detect the presence of viable MAP cells in milk. However, due to its complicated, multi-step nature, the method would not be a suitable MAP screening method for the dairy industry.

Evaluating New Matrix Pooled Testing Methods for Detecting HIV Treatment Failure with and without Covariate Information

Thesis (Master's)--University of Washington, 2016-08

Coupled diusion and mechanics in battery electrodes

Thesis (Ph.D.)--University of Washington, 2016-08

Seasonality Shows Evidence for Polygenic Architecture and Genetic Correlation With Schizophrenia and Bipolar Disorder

OBJECTIVE: To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. METHOD: Genome-wide association studies (GWASs) were conducted in Australian (between 1988 and 1990 and between 2010 and 2013) and Amish (between May 2010 and December 2011) samples in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered, and the results were meta-analyzed in a total sample of 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder, major depressive disorder (MDD), and schizophrenia were calculated to test for overlap in risk between psychiatric disorders and seasonality. RESULTS: The most significant association was with rs11825064 (P = 1.7 × 10⁻⁶, β = 0.64, standard error = 0.13), an intergenic single nucleotide polymorphism (SNP) found on chromosome 11. The evidence for overlap in risk factors was strongest for schizophrenia and seasonality, with the schizophrenia genetic profile scores explaining 3% of the variance in log-transformed global seasonality scores. Bipolar disorder genetic profile scores were also associated with seasonality, although at much weaker levels (minimum P value = 3.4 × 10⁻³), and no evidence for overlap in risk was detected between MDD and seasonality. CONCLUSIONS: Common SNPs of large effect most likely do not exist for seasonality in the populations examined. As expected, there were overlapping genetic risk factors for bipolar disorder (but not MDD) with seasonality. Unexpectedly, the risk for schizophrenia and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and schizophrenia.

Preschoolers’ Executive Control and Diurnal Cortisol as Mediators of the Relations of Prenatal Stress to Child Adjustment

Thesis (Ph.D.)--University of Washington, 2016-08

Convective Cold Pools over the Atlas Mountains and Their Influence on the Saharan Heat Low

The West African Monsoon (WAM) and its representation in numerical models are strongly influenced by the Saharan Heat Low (SHL), a low-pressure system driven by radiative heating over the central Sahara and ventilated by the cold and moist inflow from adjacent oceans. It has recently been shown that a significant part of the southerly moisture flux into the SHL originates from convective cold pools over the Sahel. These density currents driven by evaporation of rain are largely absent in models with parameterized convection. This crucial issue has been hypothesized to contribute to the inability of many climate models to reproduce the variability of the WAM. Here, the role of convective cold pools approaching the SHL from the Atlas Mountains, which are a strong orographic trigger for deep convection in Northwest Africa, is analyzed. Knowledge about the frequency of these events, as well as their impact on large-scale dynamics, is required to understand their contribution to the variability of the SHL and to known model uncertainties. The first aspect is addressed through the development of an objective and automated method for the generation of multi-year climatologies not available before. The algorithm combines freely available standard surface observations with satellite microwave data. Representativeness of stations and influence of their spatial density are addressed by comparison to a satellite-only climatology. Applying this algorithm to data from automated weather stations and manned synoptic stations in and south of the Atlas Mountains reveals the frequent occurrence. On the order of 6 events per month are detected from May to September when the SHL is in its northernmost position. The events tend to cluster into several-days long convectively active periods, often with strong events on consecutive days. This study is the first to diagnose dynamical impacts of such periods on the SHL, based on simulations of two example cases using the Weather Research and Forecast (WRF) model at convection-permitting resolution. Sensitivity experiments with artificially removed cold pools as well as different resolutions and parameterizations are conducted. Results indicate increases in surface pressure of more than 1 hPa and significant moisture transports into the desert over several days. This moisture affects radiative heating and thus the energy balance of the SHL. Even though cold pool events north of the SHL are less frequent when compared to their Sahelian counterparts, it is shown that they gain importance due to their temporal clustering on synoptic timescale. Together with studies focusing on the Sahel, this work emphasizes the need for improved parameterization schemes for deep convection in order to produce more reliable climate projections for the WAM.

Prepuce-sparing plasty and simple running suture for phimosis

Aim. Circumcision is the most common procedure for phimosis. In recent years, the value of foreskin properties as well as aesthetic reasons determined to other operations preserving the foreskin. We report 5-years experience with a technique that preserve the physical foreskin appearance intact. Patients and methods. Fifty-two patients, eligible to undergo phimosis surgery, underwent prepuce-sparing plasty and simple running suture. Evaluation of results was made with photos comparative and verified by using presence/absence of recurrence, scarring evaluation, and VAS for patient satisfaction. Results. Forty-eight patients reported no complications. There were no cases of bleeding, infection, pathological scarring, phimosis recurrence. The scar showed a good pliability and a thin thickness. Patient satisfaction was high. Conclusions. The association of prepuce-sparing plasty and simple running suture highlighted an effective and easy method for the correction of acquired phimosis in adult patients, with excellent functional and cosmetic results.

Patients' satisfaction and quality of life in coronary artery disease

OBJECTIVES: To assess satisfaction of survivors of coronary artery diseases (CAD) with healthcare services and to determine whether specific components of standard health-related quality of life (HRQL) assessment tools might identify areas of satisfaction and dissatisfaction. METHOD: A specific tool developed to provide a comprehensive assessment of healthcare needs was administered concomitantly with generic and specific HRQL instruments, on 242 patients with CAD, admitted to an acute coronary unit during a single year. RESULTS: 92.5% of patients confirmed their trust in and satisfaction with the care given by their General Practitioner; even so, one third experienced difficulty getting an appointment and a quarter wanted more time for each consultation or prompt referral to a specialist when needed. Around a third expressed dissatisfaction with advice from the practice nurse or hospital consultant. Overall 54% were highly satisfied with services, 33% moderately satisfied and 13% dissatisfied.Cronbach's alpha was 0.87; the corrected total-item correlation ranged between 0.55-0.75, with trivial 'floor' score and low 'ceiling' effect. Several domains in all three HRQL tools correlated with items relating to satisfaction. The Seattle Angina Questionnaire Treatment Score correlated significantly with all satisfaction items and with the global satisfaction score. CONCLUSION: Cardiac patients' demanded better services and advice from, and more time with, health professionals and easier surgery access. The satisfaction tool showed acceptable psychometric properties. In this patient group, disease-specific HRQL tools seem more appropriate than generic tools for surveys of patient satisfaction

Study and investigation of the various reactions of Mazandaran Province shoreline against wind waves

Determining of beach states and study of manner sediment transmission in beach profile, involves the evaluating the actions of hydrodynamic forces dominated over the beaches, in this research through determining the beach states by the help of Hanson and short method, different reactions of Mazandaran’s shoreline against wind waves was studied and investigated. For this reason, First, the kind of hydrodynamic forces dominated over the beaches of this province was studied and beaches of the this province was distinguished as wave–dominated beaches, afterwards eight stations are chosen throughout the shoreline and the waves qualities and the sediments regarding to different depth was evaluated in these stations by using software and laboratory actions. In this way the parameter of dimensionless fall velocity each station was calculated and the beach states and their changes according to time was studied. Finally, the gained information is located in the software area of Arc GIS, and the waves dynamics and the way of erosion and accretion was evaluated in each station. In this research by study of air photographs during a thirty years period we found that was no remarkable changes at shoreline in western and central parts and each type of change depends upon the delta, while eastern part of coast at the location of breakwaters in neighbouring of Farahabad Station, accretion features is quiet evident. In the main results of this research, it became obvious that the beach state in the stations Neca, Farahabad, Larim, Naftchal, Mazandaran university, Babolsar, Noor is dissipative and the beach in Nashtarood station is in intermediate (ridge and runnel) state to the extend that in the dissipation beaches from east to west, the degree of dissipation of the beaches is decreased continuously.

The analysis and detection of new psychoactive substances in biological matrices

New psychoactive substances (NPSs) have appeared on the recreational drug market at an unprecedented rate in recent years. Many are not new drugs but failed products of the pharmaceutical industry. The speed and variety of drugs entering the market poses a new complex challenge for the forensic toxicology community. The detection of these substances in biological matrices can be difficult as the exact compounds of interest may not be known. Many NPS are sold under the same brand name and therefore users themselves may not know what substances they have ingested. The majority of analytical methods for the detection of NPSs tend to focus on a specific class of compounds rather than a wide variety. In response to this, a robust and sensitive method was developed for the analysis of various NPS by solid phase extraction (SPE) with gas chromatography mass spectrometry (GCMS). Sample preparation and derivatisation were optimised testing a range of SPE cartridges and derivatising agents, as well as derivatisation incubation time and temperature. The final gas chromatography mass spectrometry method was validated in accordance with SWGTOX 2013 guidelines over a wide concentration range for both blood and urine for 23 and 25 analytes respectively. This included the validation of 8 NBOMe compounds in blood and 10 NBOMe compounds in urine. This GC-MS method was then applied to 8 authentic samples with concentrations compared to those originally identified by NMS laboratories. The rapid influx of NPSs has resulted in the re-analysis of samples and thus, the stability of these substances is crucial information. The stability of mephedrone was investigated, examining the effect that storage temperatures and preservatives had on analyte stability daily for 1 week and then weekly for 10 weeks. Several laboratories identified NPSs use through the cross-reactivity of these substances with existing screening protocols such as ELISA. The application of Immunalysis ketamine, methamphetamine and amphetamine ELISA kits for the detection of NPS was evaluated. The aim of this work was to determine if any cross-reactivity from NPS substances was observed, and to determine whether these existing kits would identify NPS use within biological samples. The cross- reactivity of methoxetamine, 3-MeO-PCE and 3-MeO-PCP for different commercially point of care test (POCT) was also assessed for urine. One of the newest groups of compounds to appear on the NPS market is the NBOMe series. These drugs pose a serious threat to public health due to their high potency, with fatalities already reported in the literature. These compounds are falsely marketed as LSD which increases the chance of adverse effects due to the potency differences between these 2 substances. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was validated in accordance with SWGTOX 2013 guidelines for the detection for 25B, 25C and 25I-NBOMe in urine and hair. Long-Evans rats were administered 25B-, 25C- and 25I-NBOMe at doses ranging from 30-300 µg/kg over a period of 10 days. Tail flick tests were then carried out on the rats in order to determine whether any analgesic effects were observed as a result of dosing. Rats were also shaved prior to their first dose and reshaved after the 10-day period. Hair was separated by colour (black and white) and analysed using the validated LC-MS/MS method, assessing the impact hair colour has on the incorporation of these drugs. Urine was collected from the rats, analysed using the validated LC-MS/MS method and screened for potential metabolites using both LC-MS/MS and quadrupole time of flight (QToF) instrumentation.