Predictors and Correlates of Substance Use among Young Men. The Longitudinal “From a Boy to a Man” Birth Cohort Study.

Substance use is one of our most important public health problems. Studying risk factors in a longitudinal study setting helps to identify subgroups of young people at greater risk for substance-use-related problems, and to facilitate targeted prevention efforts. The aim of this thesis was to study childhood predictors and correlates of substance-use-related outcomes among young men in a longitudinal, nationwide birth cohort study. The study population included 10% of all Finnish-speaking boys born in Finland in 1981 (n=2946, 97% of the target population). In 1989, at age eight, valid measures of psychiatric symptoms (Rutter questionnaires and Children’s Depression Inventory) were obtained from parents, teachers and the boys themselves. In 1999, at age 18, boys were reached at their obligatory military call-up (n=2348, 80% of the boys attending the study in 1989). Self-reports of substance use, psychopathology, adaptive functioning (Young Adult Self-Report), and mental health service use were obtained through questionnaires. Information about psychiatric diagnoses from the Military Register (age 18-23 years) and information about offending from the National Police Register (age 16-20 years) were collected in early adulthood (92% of the 1989sample). Boys with childhood conduct, hyperactive, and comorbid conduct-emotional problems had elevated rates of substance use and substance-use-related crime in early adulthood. Depressive symptoms predicted daily smoking, especially among boys of low-educated fathers. Emotional problems predicted lower occurrence of drunkenness-related alcohol use and smoking. Teacher reports on boys’ problem behaviour had the best predictive power for later substance use. At age 18, frequent drunkenness associated with delinquency, smoking and illicit drug use, and having friends. Occasional drunkenness associated with better psychosocial functioning in general compared to boys with frequent drunkenness or without drunkenness-related alcohol use. Illicit drug use without drug offending was not predicted by childhood psychiatric symptoms, but 22% of boys with illicit drug use had a psychiatric diagnosis in early adulthood. Drug offenders, in turn, had psychiatric problems both in childhood and in adulthood. Psychiatric disorders were common among young men with substance-use-related crime. Recidivist crime associated strongly with having a substance use disorder diagnosis according to the Military Register. At age 18, frequent drunkenness was common among boys entering mental health services, but entering substance use treatment was non-existent. According to the findings of this thesis, substance-use-related outcomes accumulate in boys having psychiatric problems both in childhood and in early adulthood. Targeted early interventions in school health care systems, particularly for boys with childhood hyperactive, conduct, and comorbid conduct-emotional problems are recommended. Psychiatric problems and risky behaviours, such as delinquency should always be assessed alongside substance use. Specialized and multidisciplinary care are required for young men who have multiple or complex needs, for instance, for young men with drug offending and recidivist crime. Integrating a substance use treatment perspective with other services where young men are encountered is emphasized.

Dietary intake according to gender and education : a twenty-year trend in a Swiss adult population

We assessed trends in dietary intake according to gender and education using repeated cross-sectional, population-based surveys conducted between 1993 and 2012 in Geneva, Switzerland (17,263 participants, 52.0 ± 10.6 years, 48% male). In 1993-1999, higher educated men had higher monounsaturated fatty acids (MUFA), carotene and vitamin D intakes than lower educated men, and the differences decreased in 2006-2012. In 1993-1999, higher educated women had higher fiber, iron, carotene, vitamin D and alcohol intakes than lower educated women, and the differences decreased in 2006-2012. Total energy, polyunsaturated fatty acids, retinol and alcohol intakes decreased, while mono/disaccharides, MUFA and carotene intake increased in both genders. Lower educated men had stronger decreases in saturated fatty acid (SFA) and calcium intakes than higher educated men: multivariate-adjusted slope and 95% confidence interval -0.11 (-0.15; -0.06) vs. -0.03 (-0.08; 0.02) g/day/year for SFA and -5.2 (-7.8; -2.7) vs. -1.03 (-3.8; 1.8) mg/day/year for calcium, p for interaction <0.05. Higher educated women had a greater decrease in iron intake than lower educated women: -0.03 (-0.04; -0.02) vs. -0.01 (-0.02; 0.00) mg/day/year, p for interaction = 0.002. We conclude that, in Switzerland, dietary intake evolved similarly between 1993 and 2012 in both educational groups. Educational differences present in 1993 persisted in 2012.

Generic utilities in chronic obstructive pulmonary disease patients stratified according to different staging systems.

Background To determine generic utilities for Spanish chronic obstructive pulmonary disease (COPD) patients stratified by different classifications: GOLD 2007, GOLD 2013, GesEPOC 2012 and BODEx index. Methods Multicentre, observational, cross-sectional study. Patients were aged ≥40 years, with spirometrically confirmed COPD. Utility values were derived from EQ-5D-3 L. Means, standard deviations (SD), medians and interquartile ranges (IQR) were computed based on the different classifications. Differences in median utilities between groups were assessed by non-parametric tests. Results 346 patients were included, of which 85.5% were male with a mean age of 67.9 (SD = 9.7) years and a mean duration of COPD of 7.6 (SD = 5.8) years; 80.3% were ex-smokers and the mean smoking history was 54.2 (SD = 33.2) pack-years. Median utilities (IQR) by GOLD 2007 were 0.87 (0.22) for moderate; 0.80 (0.26) for severe and 0.67 (0.42) for very-severe patients (p < 0.001 for all comparisons). Median utilities by GOLD 2013 were group A: 1.0 (0.09); group B: 0.87 (0.13); group C: 1.0 (0.16); group D: 0.74 (0.29); comparisons were statistically significant (p < 0.001) except A vs C. Median utilities by GesEPOC phenotypes were 0.84 (0.33) for non exacerbator; 0.80 (0.26) for COPD-asthma overlap; 0.71 (0.62) for exacerbator with emphysema; 0.72 (0.57) for exacerbator with chronic bronchitis (p < 0.001). Comparisons between patients with or without exacerbations and between patients with COPD-asthma overlap and exacerbator with chronic bronchitis were statistically-significant (p < 0.001). Median utilities by BODEx index were: group 02: 0.89 (0.20); group 34: 0.80 (0.27); group 56: 0.67 (0.29); group 79: 0.41 (0.31). All comparisons were significant (p < 0.001) except between groups 34 and 56. Conclusion Irrespective of the classification used utilities were associated to disease severity. Some clinical phenotypes were associated with worse utilities, probably related to a higher frequency of exacerbations. GOLD 2007 guidelines and BODEx index better discriminated patients with a worse health status than GOLD 2013 guidelines, while GOLD 2013 guidelines were better able to identify a smaller group of patients with the best health.

A relational approach to the geography of innovation: a typology of regions

The aim of this study was to devise a method for computing a composite indicator that measures the regional degree of exposure to external knowledge sources. On the basis of this indicator, we propose a typology of regions according to their potential capacity to access extra-local items of knowledge, which might help them to recombine complementary elements of such an asset to produce a higher number of new ideas. Building on various research streams that have been relatively independent to date, we summarize a non-exhaustive instrumental list of recent studies that motivates our approach and the construction of our complex indicator, which can be used to appraise the extent to which each region is in an optimal position to access external innovative resources.

A novel approach to analysing the regimes of temporary streams in relation to their controls on the composition and structure of aquatic biota

Temporary streams are those water courses that undergo the recurrent cessation of flow or the complete drying of their channel. The structure and composition of biological communities in temporary stream reaches are strongly dependent on the temporal changes of the aquatic habitats determined by the hydrological conditions. Therefore, the structural and functional characteristics of aquatic fauna to assess the ecological quality of a temporary stream reach cannot be used without taking into account the controls imposed by the hydrological regime. This paper develops methods for analysing temporary streams' aquatic regimes, based on the definition of six aquatic states that summarize the transient sets of mesohabitats occurring on a given reach at a particular moment, depending on the hydrological conditions: Hyperrheic, Eurheic, Oligorheic, Arheic, Hyporheic and Edaphic. When the hydrological conditions lead to a change in the aquatic state, the structure and composition of the aquatic community changes according to the new set of available habitats. We used the water discharge records from gauging stations or simulations with rainfall-runoff models to infer the temporal patterns of occurrence of these states in the Aquatic States Frequency Graph we developed. The visual analysis of this graph is complemented by the development of two metrics which describe the permanence of flow and the seasonal predictability of zero flow periods. Finally, a classification of temporary streams in four aquatic regimes in terms of their influence over the development of aquatic life is updated from the existing classifications, with stream aquatic regimes defined as Permanent, Temporary-pools, Temporary-dry and Episodic. While aquatic regimes describe the long-term overall variability of the hydrological conditions of the river section and have been used for many years by hydrologists and ecologists, aquatic states describe the availability of mesohabitats in given periods that determine the presence of different biotic assemblages. This novel concept links hydrological and ecological conditions in a unique way. All these methods were implemented with data from eight temporary streams around the Mediterranean within the MIRAGE project. Their application was a precondition to assessing the ecological quality of these streams.

Prevalence of sleep apnoea syndrome in the middle to old age general population.

On the basis of a large populationbased sample who underwent full polysomnography at home (HypnoLaus cohort), we recently reported that 49·7% of men and 23·4% of women aged 40 years or older had an apnoea-hypopnoea index of 15 events per h or more1 according to the American Academy of Sleep Medicine (AASM) 2013 scoring criteria. When excessive daytime sleepiness (ie, Epworth score >10 [maximum score 24]) was included in the definition with an apnoea-hypopnoea index of 5 events per h or more, the prevalence was 12·5% in men and 5·9% in women. This high prevalence of sleep disordered breathing reinforced the idea that the treatment decision should not only be based the apnoeahypopnoea index, but should also take into account associated symptoms and cardiovascular and metabolic comorbidities. After this Article was published, several readers contacted us to ask for the prevalence of sleep apnoea syndrome in our sample according to the International Classification of Sleep Disorders (ICSD-3) criteria. These criteria include either the presence of an apnoea-hypopnoea index of 5 events per h or more associated with obstructive sleep apnoearelated symptoms or cardiovascular and metabolic comorbidities, or an apnoea-hypopnoea index of 15 events per h or more (figure).

Bosniak classification of renal cystic lesions according to multidetector computed tomography findings

Renal cystic lesions are usually diagnosed in the radiologists' practice and therefore their characterization is crucial to determine the clinical approach to be adopted and prognosis. The Bosniak classification based on computed tomography findings has allowed for standardization and categorization of lesions in increasing order of malignancy (I, II, IIF, III and IV) in a simple and accurate way. The present iconographic essay developed with multidetector computed tomography images of selected cases from the archives of the authors' institution, is aimed at describing imaging findings that can help in the diagnosis of renal cysts.

Most and Least Preferred Colours Differ According to Object Context : New Insights from an Unrestricted Colour Range

Humans like some colours and dislike others, but which particular colours and why remains to be understood. Empirical studies on colour preferences generally targeted most preferred colours, but rarely least preferred (disliked) colours. In addition, findings are often based on general colour preferences leaving open the question whether results generalise to specific objects. Here, 88 participants selected the colours they preferred most and least for three context conditions (general, interior walls, t-shirt) using a high-precision colour picker. Participants also indicated whether they associated their colour choice to a valenced object or concept. The chosen colours varied widely between individuals and contexts and so did the reasons for their choices. Consistent patterns also emerged, as most preferred colours in general were more chromatic, while for walls they were lighter and for t-shirts they were darker and less chromatic compared to least preferred colours. This meant that general colour preferences could not explain object specific colour preferences. Measures of the selection process further revealed that, compared to most preferred colours, least preferred colours were chosen more quickly and were less often linked to valenced objects or concepts. The high intra- and inter-individual variability in this and previous reports furthers our understanding that colour preferences are determined by subjective experiences and that most and least preferred colours are not processed equally.

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

Urinary 2,5-hexanedione in workers exposed to n-hexane: influence of the sample treatment

The aim of the present study was to determine 2,5-hexanedione (2,5-HD), a metabolite of n-hexane, by gas chromatography/flame ionization detection in 31 workers exposed to n-hexane after two types of sample pretreatment, i.e., with (total 2,5-HD) and without (free 2,5-HD) acid hydrolysis. The mean urinary 2,5-HD was 0.52 mg/L (free) and 2.88 mg/L (total), this difference being significant (Student t-test, p < 0.05). The differences in the results according to the sample treatment support the need to modify the current Brazilian legislation, which proposes the analysis of 2,5-HD without indicating whether it is the free or total metabolite.

Validation of an instrument to evaluate quality of life in the aging population: WHOQOL-AGE.

BACKGROUND: There is a need for short, specific instruments that assess quality of life (QOL) adequately in the older adult population. The aims of the present study were to obtain evidence on the validity of the inferences that could be drawn from an instrument to measure QOL in the aging population (people 50+ years old), and to test its psychometric properties. METHODS: The instrument, WHOQOL-AGE, comprised 13 positive items, assessed on a five-point rating scale, and was administered to nationally representative samples (n = 9987) from Finland, Poland, and Spain. Cronbach's alpha was employed to assess internal consistency reliability, whereas the validity of the questionnaire was assessed by means of factor analysis, graded response model, Pearson's correlation coefficient and unpaired t-test. Normative values were calculated across countries and for different age groups. RESULTS: The satisfactory goodness-of-fit indices confirmed that the factorial structure of WHOQOL-AGE comprises two first-order factors. Cronbach's alpha was 0.88 for factor 1, and 0.84 for factor 2. Evidence supporting a global score was found with a second-order factor model, according to the goodness-of-fit indices: CFI = 0.93, TLI = 0.91, RMSEA = 0.073. Convergent validity was estimated at r = 0.75 and adequate discriminant validity was also found. Significant differences were found between healthy individuals (74.19 ± 13.21) and individuals with at least one chronic condition (64.29 ± 16.29), supporting adequate known-groups validity. CONCLUSIONS: WHOQOL-AGE has shown good psychometric properties in Finland, Poland, and Spain. Therefore, considerable support is provided to using the WHOQOL-AGE to measure QOL in older adults in these countries, and to compare the QOL of older and younger adults.

Mechanical closing of the paperboard package and the effect of the shape of paperboard package to its manufacturability

The main objective of this thesis was to design a hinge and a closing mechanism for the plastic rim of a paperboard package. Of the hinge and closing mechanisms the 3D-models were designed using SolidWorks program and the functionality of the mechanisms was tested with rapid prototype models. When a mechanism that worked was found, the manufacturability of the mechanisms was tested in an injection molding machine with changeable inserts. Another objective of this thesis was to test the effect of the shape of paperboard package to its manufacturability. The effect of the packages shape was tested with plastic tools made for three different shaped trays. Suggestions for further research were made according to the results of the thesis.

The concept of solution: Industry’s insights compared to theoretical views

Many manufacturing companies have started to offer complete solutions to their customers’ unique needs due to toughening competition and customer demand. Discourse on this kind of solution business is still developing, hence, there is not an established definition for the concept of solution. The aim of the study is to profoundly identify the concept of solution and to understand how the industry’s current views differ from the theoretical concepts. The describing dimensions are identified from selected 13 theoretical notions, and from responses, that the employees of five different companies have given. The 32 interview transcripts are analyzed with thematic analysis and qualitative content analysis. According to the findings, the concept of solution is characterized by integration, customization, risk-sharing, value co-creation, long-term orientation, and desired outcomes. The industry’s insights differ in terms of them all. The results illustrate, that a solution is a bundle, and the whole solution is customized on some level for a client. A solution supplier needs to be customer-focused, in which value co-creation is only a part. The solution solves the customer’s problem, and improves both the customer’s, and the supplier’s business. Neither long-term focus nor risks-sharing were directly employed to characterize the concept of solution. Differences are mainly due to the different approaches to the definitions and inexperience of the companies.

Computational Evaluation of Print Unevenness According to Human Vision

Print quality and the printability of paper are very important attributes when modern printing applications are considered. In prints containing images, high print quality is a basic requirement. Tone unevenness and non uniform glossiness of printed products are the most disturbing factors influencing overall print quality. These defects are caused by non ideal interactions of paper, ink and printing devices in high speed printing processes. Since print quality is a perceptive characteristic, the measurement of unevenness according to human vision is a significant problem. In this thesis, the mottling phenomenon is studied. Mottling is a printing defect characterized by a spotty, non uniform appearance in solid printed areas. Print mottle is usually the result of uneven ink lay down or non uniform ink absorption across the paper surface, especially visible in mid tone imagery or areas of uniform color, such as solids and continuous tone screen builds. By using existing knowledge on visual perception and known methods to quantify print tone variation, a new method for print unevenness evaluation is introduced. The method is compared to previous results in the field and is supported by psychometric experiments. Pilot studies are made to estimate the effect of optical paper characteristics prior to printing, on the unevenness of the printed area after printing. Instrumental methods for print unevenness evaluation have been compared and the results of the comparison indicate that the proposed method produces better results in terms of visual evaluation correspondence. The method has been successfully implemented as ail industrial application and is proved to be a reliable substitute to visual expertise.