Type 2 diabetes is a significant health problem because of its high prevalence and strong association with cardiovascular morbidity and mortality. An increase of type 2 diabetes is predicted due to increasing obesity and sedentary lifestyle habits. The development from latent to diagnostic disease spans many years and during this time it is possible to prevent or postpone type 2 diabetes using lifestyle and pharmacological interventions. The objective of this thesis is to investigate and describe early patterns and risk indicators of type 2 diabetes. The focus is on type 2 diabetes as one component in metabolic syndrome, i.e. the clustering of several cardiovascular risk markers. Two studies based on the Västerbotten Intervention Programme (VIP) provided the data; one case-referent study nested within VIP which includes 237 diabetes cases that were clinically diagnosed 5.4 years after the health survey, each with two referents; and one panel study with 5 consecutive annual cohorts including subjects that participated in VIP between1990 and 1994 and returned to a follow-up after 10 years, a total of 16 492 individuals. Associations between risk markers and type 2 diabetes or metabolic syndrome are evaluated by several statistical techniques. A model of metabolic syndrome is hypothesized. A prediction model for developing type 2 diabetes among middle-aged individuals is proposed, where high risk is defined as having at least two out of three risk criteria (fasting plasma glucose ≥6.1 mmol/L, HbA1c ≥4.7% (Swedish Mono-S standard) and BMI ≥27 in men and BMI ≥30 in women). With positive predictive values of 32% in men and 46% in women, this model performs at least as well as other published prediction models. Information on family history of diabetes does not improve the result and the cumbersome oral glucose tolerance test is not needed. Therefore this model should be feasible for use in routine care. A model of metabolic syndrome with five composite factors, based on 14 variables including markers produced by adipose tissue and b-cells, suggest that obesity with insulin resistance and b-cell decompensation are the core perturbations in the early stages of type 2 diabetes, while inflammation and dyslipidemia could not be shown to be independent early risk indicators. The composite factors do not improve the prediction as compared to the single markers of fasting glucose, BMI and proinsulin and, possibly blood pressure values. Stress (measured as passive or tense working conditions) and weak social support (measured as emotional support), are suggested to be strong risk indicators along with high BMI for type 2 diabetes in women. In men BMI is predictive, but the stress variables are not shown to be associated with future type 2 diabetes. A social gap is indicated by double risk of metabolic syndrome among subjects with low (≤ 9 years at school) compared to high education (≥ 13 years). High consumption of Swedish smokeless tobacco, snuff (>4 cans/week), is independently associated with metabolic syndrome, obesity and hypertriglyceridemia, but not with dysregulation of glucose. To conclude, single markers, that are commonly used in daily practice, are useful and sufficient for identification of subjects that are in the early stages of type 2 diabetes. Obesity with insulin resistance and b-cell decompensation are the core perturbations in early development to T2DM. Lifestyle, socioeconomic and psychosocial markers, in addition to biomarkers, are important determinants of future type 2 diabetes and metabolic syndrome, albeit not similarly among men and women.

Abstract Although smoking in adolescents and young adults has been declining in the 21st century in Finland, about 17% of 18-year-olds still smoke on a daily basis. Young adults are in fact one of the age groups that are most likely to smoke in several countries. Nevertheless, a large proportion of them are known to want to quit smoking. Relatively little is known about the smoking habits of young adults. There are no evidence-based guidelines for smoking cessation in this age group. In many cases, they have been included within studies of adolescents or older adults without any separate analysis. Consequently, smoking cessation interventions demonstrated to be effective in middle-aged smokers are often adapted for young adults even though their culture, somatic features and smoking habits in many ways are different from those of middle-aged people. This study focused on 18–26-year-olds in northern parts of Finland. Specific aims were 1) to describe their smoking habits, 2) to compare health and lifestyle in tobacco users and non-tobacco users, 3) to study their nicotine dependence and motivation to quit smoking, and 4) to examine the use and effectiveness of smoking cessation pharmacotherapy in this age group. A total of 1163 male military recruits from northern parts of Finland filled in the study questionnaire. The survey study revealed that young adult males in northern parts of the country used tobacco products relatively often. Their smoking was associated with lower education, higher body mass index, inactivity in sports and impaired physical fitness. In addition, a great part of young smokers displayed symptoms of chronic bronchitis. Although most daily smokers were clearly dependent on nicotine and had previously tried to quit smoking, only 47% of the quitters had utilized any pharmacological aids in their attempts. Snus use seemed to be related to more severe nicotine dependence in smokers. The prospective study consisted of 314 voluntary young adult daily smokers who were motivated to quit smoking. The study was a randomised, placebo-controlled clinical trial, and the results indicated that varenicline might be more effective than nicotine patches in smoking cessation of young adult heavy smokers, at least in short term. Abstinence rates during the follow-up were similar when the nicotine patch and placebo patch were compared in young adult light smokers. / Tiivistelmä Suomessa nuorten keskuudessa tupakointi on ollut 2000-luvun aikana laskusuuntainen. Kuitenkin arviolta n. 17 % 18-vuotiaista tupakoi edelleen päivittäin. Nuoret aikuiset ovatkin useissa maissa yksi eniten tupakoivia ikäryhmiä. Silti suuren osan tupakoivista nuorista aikuisista on todettu olevan halukkaita llopettamaan tupakoinnin. Nuorten aikuisten tupakointia on tutkittu verrattain vähän. Heille suunnattuja tieteelliseen näyttöön perustuvia hoitomuotoja tupakoinnin lopettamiseen ei ole. He ovat usein osana teini-ikäisten tai vaihtoehtoisesti vanhempien aikuisten ryhmää tupakointiin liittyvissä tutkimuksissa, eikä heitä yleensä ole analysoitu erikseen. Usein heitä hoidetaankin keski-ikäisiltä aikuisilta saadun tutkimusnäytön pohjalta. Kuitenkin nuorten kulttuuri, biologinen pohja ja tupakointitavat eroavat merkittävästi vanhemmista tupakoitsijoista. Tämä työ on keskittynyt tutkimaan 18–26-vuotiaita nuoria aikuisia Pohjois-Suomessa. Sen tavoitteina on ollut 1) kuvata heidän tupakointitottumuksiaan, 2) selvittää tupakoinnin yhteyttä terveyteen ja elämäntapaan, 3) tutkia heidän nikotiiniriippuvuuttaan sekä motivaatiota lopettaa tupakointi, sekä 4) selvittää tupakkavieroituslääkkeiden käyttöä ja niiden tehoa tässä ikäryhmässä. Terveystottumuskyselyymme vastasi 1163 Pohjois-Suomen varusmiestä. Selvisi, että varusmiehet käyttivät tupakkatuotteita Pohjois-Suomessa valtakunnallisia arvioita enemmän. Tupakoinnin todettiin liittyvän varusmiehillä alempaan koulutustasoon, suurentuneeseen painoindeksiin, vähäisempään fyysiseen aktiivisuuteen ja huonompaan aerobiseen suorituskykyyn. Lisäksi tupakoivilla varusmiehillä kroonisen bronkiitin oireet olivat yleisiä. Vaikka valtaosa heistä oli selvästi nikotiiniriippuvaisia ja oli yrittänyt lopettaa tupakointinsa, vain 47% lopetusta yrittäneistä oli kokeillut tupakkavieroituslääkettä. Nuuskan käyttö vaikutti liittyvän vahvempaan nikotiiniriippuvuuteen tupakoitsijoilla. Prospektiiviseen, satunnaistettuun ja lumekontrolloituun kliiniseen kokeeseen osallistui 314 vapaaehtoista päivittäin tupakoivaa nuorta aikuista, jotka olivat halukkaita tupakoinnin lopetukseen. Tulokset viittasivat siihen, että varenikliini saattaa olla nikotiinilaastaria tehokkaampi tupakoinnista vieroituksessa vahvasti nikotiiniriippuvaisilla nuorilla aikuisilla ainakin lyhyellä aikavälillä. Kevyemmin tupakasta riippuvaisilla nikotiinilaastari ei ollut lumelaastaria tehokkaampi.

The goal of this project was to develop a rapid separation and detection method for analyzing organic compounds in smokeless powders and then test its applicability on gunshot residue (GSR) samples. In this project, a total of 20 common smokeless powder additives and their decomposition products were separated by ultra performance liquid chromatography (UPLC) and confirmed by tandem mass spectrometry (MS/MS) using multiple reaction monitoring mode (MRM). Some of the targeted compounds included diphenylamines, centralites, nitrotoluenes, nitroglycerin, and various phthalates. The compounds were ionized in the MS source using simultaneous positive and negative electrospray ionization (ESI) with negative atmospheric pressure chemical ionization (APCI) in order to detect all compounds in a single analysis. The developed UPLC/MS/MS method was applied to commercially available smokeless powders and gunshot residue samples recovered from the hands of shooters, spent cartridges, and smokeless powder retrieved from unfired cartridges. Distinct compositions were identified for smokeless powders from different manufacturers and from separate manufacturing lots. The procedure also produced specific chemical profiles when tested on gunshot residues from different manufacturers. Overall, this thesis represents the development of a rapid and reproducible procedure capable of simultaneously detecting the widest possible range of components present in organic gunshot residue.

U.S. Air Force (USAF) active duty Airmenshowunusually high tobacco prevalence rates (TPR); i.e., smoke, smokeless, both(SSL-B), when compared to civilian publics in the United States. Tobacco control efforts have proven largely ineffective inlowering nicotine habits among Airmen, while outdoor designated tobacco areas (DTAs) sited near worksites and popular localeson USAF bases (USAFBs) likelyswayAirmen to continue riskynicotine habits. The aim of this inquiry was to assess whetherquantities of DTAs on USAFBs and U.S. airbases (USABs) with 4 mediator variables(quality of DTAs,sites of DTAs, execution of a tobacco cessation program, and types of tobacco cessation programs) wereassociated with TPR (SSL-B) among Airmen at 21 sampled USAF installations worldwide. Organizational cultural theory was the theoretical outline chosen. One USAF surveillance system was accessed,and a survey tool was providedby15 USAF health promotion coordinators and6base civil engineer staff.Correlation assessments and regression analyses were conducted to analyze the survey data. The results of the study revealed that there was a moderate positive correlation among quantities of DTAs and TPR(SSL-B) withAirmen across sampled USAF installations(r= .56, p< .01), and there was a low positive correlation between quantities of DTAs on lower security threat USABs and Airmenpopulace numbers(r= .10, p< .048). Quantities of DTAs were also the strongest predictor of TPR (SSL-B) among Airmen[F(2, 18) = .00, p< .013].Results indicate that fewer or no DTAs on USAFBsand USABs could positively improve the health statuses of active duty USAF Airmen and civilian forces, improve mission duties, lessen health care costs, and foster tobacco-free lifestyles as the normalized behavior on U.S. military installations, and thus promote social change.

<p>  </p> <p>With bombings in the United States on the rise for the first time since 2016, the detection and identification of explosives remains of pertinent interest to law enforcement agencies. This work presents two soon-to-be published research articles that focus on the detection and identification of explosives by both chemical instrumentation and canines. The first article, <em>Quantitative Analysis of Smokeless Powder Particles in Post-Blast Debris via Gas Chromatography/Vacuum Ultraviolet Spectroscopy (GC/VUV)</em>, utilizes gas chromatography/vacuum ultraviolet spectroscopy (GC/VUV) to determine the difference in chemical composition of two smokeless powders in both pre- and post-blast conditions. The compounds of interest in this study were nitroglycerin, 2,4-dinitrotoluene, diphenylamine, ethyl centralite, and di-n-butyl phthalate. Concentration changes between pre- and post-blast smokeless powder particles were determined as well as microscopic differences between pre- and post-blast debris for both smokeless powders in all devices. To our knowledge, this is the first use of GC/VUV for the quantification of explosives. The second article, <em>An Odor-Permeable Membrane Device for the Storage of Canine Training Aids</em>, proposes the use of an odor-permeable membrane device (OPMD) as a standardized storage method for canine training aids. It is hypothesized that the OPMD would minimize cross-contamination between training aids, and that the OPMD could be used for canine training as well as storage. The goal of this research is to use flux and evaporation rate to quantify the explosive odor that escapes from the OPMD compared to unconfined explosives. Preliminary data suggests that there is an exponential relationship between relative boiling point and evaporation rate. It has been determined that compounds with higher boiling points have lower evaporation rates than compounds that have lower boiling points. The materials studied thus far are known odor compounds produced by explosive formulations. These include nitromethane, nitroethane, 1-nitropropane, r-limonene, and toluene. </p>

Indiana University-Purdue University Indianapolis (IUPUI) / Pipe bombs are a common form of improvised explosive device, due in part to their ease of construction. Despite their simplistic nature, the lethality of pipe bombs should not be dismissed. Due to the risk of harm and their commonality, research into the pipe bomb deflagration process and subsequent chemical analysis is necessary. The laboratory examination of pipe bomb fragments begins with a visual examination. While this is presumptive in nature, hypotheses formed here can lead to subsequent confirmatory exams. The purpose of this study was to measure the mass and velocity of pipe bomb fragments using high speed video. These values were used to discern any trends in container type (PVC or black/galvanized steel), energetic filler (Pyrodex or double base smokeless powder), and ambient temperature (13°C and -8°C). The results show patterns based on container type, energetic filler, and temperature. The second stage of a laboratory exam is chemical analysis to identify any explosive that may be present. Legality calls for identification only, not quantitation. The purpose of this study is to quantitate the amount of explosive residue on post-blast pipe bomb fragments. By doing so, the instrumental sensitivities required for this type of analysis will be known. Additionally, a distribution of the residue will be mapped to provide insight into the deflagration process of a device. This project used a novel sampling technique called total vaporization solid phase microextraction. The method was optimized for nitroglycerin, the main energetic in double base smokeless powder. Detection limits are in the part per billion range. Results show that the concentration of residue is not uniform, and the highest concentration is located on the endcaps regardless of container type. Total vaporization solid phase microextraction was also applied to automotive racing samples of interest to the National Hot Rod Association. The purpose of this project is two-fold; safety of the race teams in the form of dragstrip adhesive consistency and monitoring in the form of fuel testing for illegal adulteration. A suite of analyses, including gas chromatography mass spectrometry, infrared spectroscopy, and evaporation rate, were developed for the testing of dragstrip adhesives. Gas chromatography mass spectrometry methods were developed for both nitromethane based fuel as well as racing gasolines. Analyses of fuel from post-race cars were able to detect evidence of adulteration. Not only was a novel technique developed and optimized, but it was successfully implemented in the analysis of two different analytes, explosive residue and racing gasoline. TV-SPME shows tremendous promise for the future in its ability to analyze a broad spectrum of analytes.

The growing need for fast sampling of explosives in high throughput areas has increased the demand for improved technology for the trace detection of illicit compounds. Detection of the volatiles associated with the presence of the illicit compounds offer a different approach for sensitive trace detection of these compounds without increasing the false positive alarm rate. This study evaluated the performance of non-contact sampling and detection systems using statistical analysis through the construction of Receiver Operating Characteristic (ROC) curves in real-world scenarios for the detection of volatiles in the headspace of smokeless powder, used as the model system for generalizing explosives detection. A novel sorbent coated disk coined planar solid phase microextraction (PSPME) was previously used for rapid, non-contact sampling of the headspace containers. The limits of detection for the PSPME coupled to IMS detection was determined to be 0.5-24 ng for vapor sampling of volatile chemical compounds associated with illicit compounds and demonstrated an extraction efficiency of three times greater than other commercially available substrates, retaining >50% of the analyte after 30 minutes sampling of an analyte spike in comparison to a non-detect for the unmodified filters. Both static and dynamic PSPME sampling was used coupled with two ion mobility spectrometer (IMS) detection systems in which 10-500 mg quantities of smokeless powders were detected within 5-10 minutes of static sampling and 1 minute of dynamic sampling time in 1-45 L closed systems, resulting in faster sampling and analysis times in comparison to conventional solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) analysis. Similar real-world scenarios were sampled in low and high clutter environments with zero false positive rates. Excellent PSPME-IMS detection of the volatile analytes were visualized from the ROC curves, resulting with areas under the curves (AUC) of 0.85-1.0 and 0.81-1.0 for portable and bench-top IMS systems, respectively. Construction of ROC curves were also developed for SPME-GC-MS resulting with AUC of 0.95-1.0, comparable with PSPME-IMS detection. The PSPME-IMS technique provides less false positive results for non-contact vapor sampling, cutting the cost and providing an effective sampling and detection needed in high-throughput scenarios, resulting in similar performance in comparison to well-established techniques with the added advantage of fast detection in the field.

Smokeless powders are a set of energetic materials, known as low explosives, which are typically utilized for reloading ammunition. There are three types which differ in their primary energetic materials; where single base powders contain nitrocellulose as their primary energetic material, double and triple base powders contain nitroglycerin in addition to nitrocellulose, and triple base powders also contain nitroguanidine. Additional organic compounds, while not proprietary to specific manufacturers, are added to the powders in varied ratios during the manufacturing process to optimize the ballistic performance of the powders. The additional compounds function as stabilizers, plasticizers, flash suppressants, deterrents, and opacifiers. Of the three smokeless powder types, single and double base powders are commercially available, and have been heavily utilized in the manufacture of improvised explosive devices. Forensic smokeless powder samples are currently analyzed using multiple analytical techniques. Combined microscopic, macroscopic, and instrumental techniques are used to evaluate the sample, and the information obtained is used to generate a list of potential distributors. Gas chromatography – mass spectrometry (GC-MS) is arguably the most useful of the instrumental techniques since it distinguishes single and double base powders, and provides additional information about the relative ratios of all the analytes present in the sample. However, forensic smokeless powder samples are still limited to being classified as either single or double base powders, based on the absence or presence of nitroglycerin, respectively. In this work, the goal was to develop statistically valid classes, beyond the single and double base designations, based on multiple organic compounds which are commonly encountered in commercial smokeless powders. Several chemometric techniques were applied to smokeless powder GC-MS data for determination of the classes, and for assignment of test samples to these novel classes. The total ion spectrum (TIS), which is calculated from the GC-MS data for each sample, is obtained by summing the intensities for each mass-to-charge (m/z) ratio across the entire chromatographic profile. A TIS matrix comprising data for 726 smokeless powder samples was subject to agglomerative hierarchical cluster (AHC) analysis, and six distinct classes were identified. Within each class, a single m/z ratio had the highest intensity for the majority of samples, though the m/z ratio was not always unique to the specific class. Based on these observations, a new classification method known as the Intense Ion Rule (IIR) was developed and used for the assignment of test samples to the AHC designated classes. Discriminant models were developed for assignment of test samples to the AHC designated classes using k-Nearest Neighbors (kNN) and linear and quadratic discriminant analyses (LDA and QDA, respectively). Each of the models were optimized using leave-one-out (LOO) and leave-group-out (LGO) cross-validation, and the performance of the models was evaluated by calculating correct classification rates for assignment of the cross-validation (CV) samples to the AHC designated classes. The optimized models were utilized to assign test samples to the AHC designated classes. Overall, the QDA LGO model achieved the highest correct classification rates for assignment of both the CV samples and the test samples to the AHC designated classes. In forensic application, the goal of an explosives analyst is to ascertain the manufacturer of a smokeless powder sample. In addition, knowledge about the probability of a forensic sample being produced by a specific manufacturer could potentially decrease the time invested by an analyst during investigation by providing a shorter list of potential manufacturers. In this work, Bayes* Theorem and Bayesian Networks were investigated as an additional tool to be utilized in forensic casework. Bayesian Networks were generated and used to calculate posterior probabilities of a test sample belonging to specific manufacturers. The networks were designed to include manufacturer controlled powder characteristics such as shape, color, and dimension; as well as, the relative intensities of the class associated ions determined from cluster analysis. Samples were predicted to belong to a manufacturer based on the highest posterior probability. Overall percent correct rates were determined by calculating the percentage of correct predictions; that is, where the known and predicted manufacturer were the same. The initial overall percent correct rate was 66%. The dimensions of the smokeless powders were added to the network as average diameter and average length nodes. Addition of average diameter and length resulted in an overall prediction rate of 70%.