Substantial advantage of a combined Bayesian and genotyping approach in testosterone doping tests.

Testosterone abuse is conventionally assessed by the urinary testosterone/epitestosterone (T/E) ratio, levels above 4.0 being considered suspicious. A deletion polymorphism in the gene coding for UGT2B17 is strongly associated with reduced testosterone glucuronide (TG) levels in urine. Many of the individuals devoid of the gene would not reach a T/E ratio of 4.0 after testosterone intake. Future test programs will most likely shift from population based- to individual-based T/E cut-off ratios using Bayesian inference. A longitudinal analysis is dependent on an individual's true negative baseline T/E ratio. The aim was to investigate whether it is possible to increase the sensitivity and specificity of the T/E test by addition of UGT2B17 genotype information in a Bayesian framework. A single intramuscular dose of 500mg testosterone enanthate was given to 55 healthy male volunteers with either two, one or no allele (ins/ins, ins/del or del/del) of the UGT2B17 gene. Urinary excretion of TG and the T/E ratio was measured during 15 days. The Bayesian analysis was conducted to calculate the individual T/E cut-off ratio. When adding the genotype information, the program returned lower individual cut-off ratios in all del/del subjects increasing the sensitivity of the test considerably. It will be difficult, if not impossible, to discriminate between a true negative baseline T/E value and a false negative one without knowledge of the UGT2B17 genotype. UGT2B17 genotype information is crucial, both to decide which initial cut-off ratio to use for an individual, and for increasing the sensitivity of the Bayesian analysis.

A clonal Plasmodium falciparum population in an isolated outbreak of malaria in the Republic of Cabo Verde

We present the first parasitological, molecular and longitudinal analysis of an isolated outbreak of malaria. This outbreak occurred on Santiago Island (Republic of Cabo Verde), a region where malaria is hypoendemic and controlled, and thus the population is considered non-immune. Blood samples were collected from the inhabitants over 1 month and during cross-sectional surveys in the following year. The presence and nature of the parasites was determined by PCR. Plasmodium falciparum was the only species detected. Genetic analysis revealed that the circulating parasites were genetically homogeneous, and probably clonal. Gametocytes were found throughout this period. Our data suggest that this represented a focal outbreak, resulting in the infection of at least 40% of the villagers with a clonal parasite line. Thus, P. falciparum infections can persist for at least 1 year in a substantial proportion (10%) of the hosts. Implications for malaria control and the interpretation of epidemiological data are discussed.

Ammonia toxicity to the brain.

Hyperammonemia can be caused by various acquired or inherited disorders such as urea cycle defects. The brain is much more susceptible to the deleterious effects of ammonium in childhood than in adulthood. Hyperammonemia provokes irreversible damage to the developing central nervous system: cortical atrophy, ventricular enlargement and demyelination lead to cognitive impairment, seizures and cerebral palsy. The mechanisms leading to these severe brain lesions are still not well understood, but recent studies show that ammonium exposure alters several amino acid pathways and neurotransmitter systems, cerebral energy metabolism, nitric oxide synthesis, oxidative stress and signal transduction pathways. All in all, at the cellular level, these are associated with alterations in neuronal differentiation and patterns of cell death. Recent advances in imaging techniques are increasing our understanding of these processes through detailed in vivo longitudinal analysis of neurobiochemical changes associated with hyperammonemia. Further, several potential neuroprotective strategies have been put forward recently, including the use of NMDA receptor antagonists, nitric oxide inhibitors, creatine, acetyl-L-carnitine, CNTF or inhibitors of MAPKs and glutamine synthetase. Magnetic resonance imaging and spectroscopy will ultimately be a powerful tool to measure the effects of these neuroprotective approaches.

La pré-configuration des débats publics : apports d'une approche multimodale et longitudinale des dispositifs de catégorisation

Most linguistic and interactional studies on public and media debates focus on the way talk-in- interaction is locally managed by the moderator. For example, they analyze the extent to which the questions asked are both sequentially and categorically relevant. The present paper aims at enriching these studies by discussing the profitability of a multimodal and longitudinal approach to membership categorization practices. The approach is multimodal in the sense that it does not focus exclusively on verbal features. The approach is also longitudinal by considering the extent to which a debate is pre- configured. To this end, particular attention is paid to the posters promoting the encounters and to the way the participants are positioned in physical space.

Pediatric tracheotomy: a 30-year experience.

BACKGROUND/PURPOSE: The aim of this study was to investigate changes of pediatric tracheotomy practice over time. METHODS: A retrospective analysis of all tracheotomies at the University Children's Hospital Zurich from January 1990 to December 2009 was performed. Data analyzed included the indication for tracheotomy, patient comorbidities, age, duration of cannulation, and complications. The second part of the study consisted of comparing our results with data from an earlier study done at the same institution by Simma et al. (Eur J Pediatr 1994;153:291-296) reviewing the patients with tracheotomies treated from 1979 to 1989. RESULTS: Between 1990 and 2009, 119 patients were included. The indication for tracheotomy was airway obstruction in 70% and prolonged ventilation in 30%. 70% of the patients were operated on before 1 year of age. Serious postoperative complications occurred in 25 patients (23%). There was one death related to tracheotomy. Successful decannulation was achieved in 60%, on average 28 months after tracheotomy. The decannulation rate in patients with airway obstruction was 74% compared to 52% for the patients in prolonged ventilation group; a statistically significant difference was observed (p < 0.05). The longitudinal analysis showed an increase of indications for prolonged ventilation and a trend toward decreased tracheotomy complications. CONCLUSION: Over 30 years, a shift in the indications of pediatric tracheotomy, with an increasing number of procedures performed for prolonged ventilation, was found. The tracheotomy-related mortality was under 1%. Tracheotomy remains a valid and safe option for pediatric patients. Level of evidence 2c.

Towards a dynamic model of e-commerce: environmental, technological and organisational drivers of B2C along time

Despite the important benefits for firms of commercial initiatives on the Internet, e-commerce is still an emerging distribution channel, even in developed countries. Thus, more needs to be known about the mechanisms affecting its development. A large number of works have studied firms¿ e-commerce adoption from technological, intraorganizational, institutional, or other specific perspectives, but there is a need for adequately tested integrative frameworks. Hence, this work proposes and tests a model of firms¿ business-to-consumer (called B2C) e-commerce adoption that is founded on a holistic vision of the phenomenon. With this integrative approach, the authors analyze the joint influence of environmental, technological, and organizational factors; moreover, they evaluate this effect over time. Using various representative Spanish data sets covering the period 1996-2005, the findings demonstrate the suitability of the holistic framework. Likewise, some lessons are learned from the analysis of the key building blocks. In particular, the current study provides evidence for the debate about the effect of competitive pressure, since the findings show that competitive pressure disincentivizes e-commerce adoption in the long term. The results also show that the development or enrichment of the consumers¿ consumption patterns, the technological readiness of the market forces, the firm¿s global scope, and its competences in innovation continuously favor e-commerce adoption.

Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study

High blood pressure (BP) has been ranked as the most important risk factor worldwide regarding attributable deaths. Dietary habits are major determinants of BP. Among them, frequent intake of low-fat dairy products may protect against hypertension. Our aim was to assess the relationship between low-fat dairy product intake and BP levels and their changes after 12 month follow-up in a cohort of asymptomatic older persons at high cardiovascular risk recruited into a large-scale trial assessing the effects of Mediterranean diets on cardiovascular outcomes. Data from 2290 participants, including 1845 with hypertension, were available for analyses. Dairy products were not a specific part of the intervention; thus, data were analysed as an observational cohort. Dietary information was collected with validated semi-quantitative FFQ and trained personnel measured BP. To assess BP changes, we undertook cross-sectional analyses at baseline and at the end of follow-up and longitudinal analyses. A statistically significant inverse association between low-fat dairy product intake and systolic BP was observed for the 12-month longitudinal analysis. In the longitudinal analysis, the adjusted systolic and diastolic BP were significantly lower in the highest quintile of low-fat dairy product intake ( 2 4·2 (95% CI 2 6·9, 2 1·4) and 2 1·8 (95% CI 2 3·2, 2 0·4) mmHg respectively), whereas the point estimates for the difference in diastolic BP indicated a modest non-significant inverse association. Intake of low-fat dairy products was inversely associated with BP in an older population at high cardiovascular risk, suggesting a possible protective effect against hypertension.

Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study

High blood pressure (BP) has been ranked as the most important risk factor worldwide regarding attributable deaths. Dietary habits are major determinants of BP. Among them, frequent intake of low-fat dairy products may protect against hypertension. Our aim was to assess the relationship between low-fat dairy product intake and BP levels and their changes after 12 month follow-up in a cohort of asymptomatic older persons at high cardiovascular risk recruited into a large-scale trial assessing the effects of Mediterranean diets on cardiovascular outcomes. Data from 2290 participants, including 1845 with hypertension, were available for analyses. Dairy products were not a specific part of the intervention; thus, data were analysed as an observational cohort. Dietary information was collected with validated semi-quantitative FFQ and trained personnel measured BP. To assess BP changes, we undertook cross-sectional analyses at baseline and at the end of follow-up and longitudinal analyses. A statistically significant inverse association between low-fat dairy product intake and systolic BP was observed for the 12-month longitudinal analysis. In the longitudinal analysis, the adjusted systolic and diastolic BP were significantly lower in the highest quintile of low-fat dairy product intake ( 2 4·2 (95% CI 2 6·9, 2 1·4) and 2 1·8 (95% CI 2 3·2, 2 0·4) mmHg respectively), whereas the point estimates for the difference in diastolic BP indicated a modest non-significant inverse association. Intake of low-fat dairy products was inversely associated with BP in an older population at high cardiovascular risk, suggesting a possible protective effect against hypertension.

Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study

High blood pressure (BP) has been ranked as the most important risk factor worldwide regarding attributable deaths. Dietary habits are major determinants of BP. Among them, frequent intake of low-fat dairy products may protect against hypertension. Our aim was to assess the relationship between low-fat dairy product intake and BP levels and their changes after 12 month follow-up in a cohort of asymptomatic older persons at high cardiovascular risk recruited into a large-scale trial assessing the effects of Mediterranean diets on cardiovascular outcomes. Data from 2290 participants, including 1845 with hypertension, were available for analyses. Dairy products were not a specific part of the intervention; thus, data were analysed as an observational cohort. Dietary information was collected with validated semi-quantitative FFQ and trained personnel measured BP. To assess BP changes, we undertook cross-sectional analyses at baseline and at the end of follow-up and longitudinal analyses. A statistically significant inverse association between low-fat dairy product intake and systolic BP was observed for the 12-month longitudinal analysis. In the longitudinal analysis, the adjusted systolic and diastolic BP were significantly lower in the highest quintile of low-fat dairy product intake ( 2 4·2 (95% CI 2 6·9, 2 1·4) and 2 1·8 (95% CI 2 3·2, 2 0·4) mmHg respectively), whereas the point estimates for the difference in diastolic BP indicated a modest non-significant inverse association. Intake of low-fat dairy products was inversely associated with BP in an older population at high cardiovascular risk, suggesting a possible protective effect against hypertension.

Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study

High blood pressure (BP) has been ranked as the most important risk factor worldwide regarding attributable deaths. Dietary habits are major determinants of BP. Among them, frequent intake of low-fat dairy products may protect against hypertension. Our aim was to assess the relationship between low-fat dairy product intake and BP levels and their changes after 12 month follow-up in a cohort of asymptomatic older persons at high cardiovascular risk recruited into a large-scale trial assessing the effects of Mediterranean diets on cardiovascular outcomes. Data from 2290 participants, including 1845 with hypertension, were available for analyses. Dairy products were not a specific part of the intervention; thus, data were analysed as an observational cohort. Dietary information was collected with validated semi-quantitative FFQ and trained personnel measured BP. To assess BP changes, we undertook cross-sectional analyses at baseline and at the end of follow-up and longitudinal analyses. A statistically significant inverse association between low-fat dairy product intake and systolic BP was observed for the 12-month longitudinal analysis. In the longitudinal analysis, the adjusted systolic and diastolic BP were significantly lower in the highest quintile of low-fat dairy product intake ( 2 4·2 (95% CI 2 6·9, 2 1·4) and 2 1·8 (95% CI 2 3·2, 2 0·4) mmHg respectively), whereas the point estimates for the difference in diastolic BP indicated a modest non-significant inverse association. Intake of low-fat dairy products was inversely associated with BP in an older population at high cardiovascular risk, suggesting a possible protective effect against hypertension.

Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study

High blood pressure (BP) has been ranked as the most important risk factor worldwide regarding attributable deaths. Dietary habits are major determinants of BP. Among them, frequent intake of low-fat dairy products may protect against hypertension. Our aim was to assess the relationship between low-fat dairy product intake and BP levels and their changes after 12 month follow-up in a cohort of asymptomatic older persons at high cardiovascular risk recruited into a large-scale trial assessing the effects of Mediterranean diets on cardiovascular outcomes. Data from 2290 participants, including 1845 with hypertension, were available for analyses. Dairy products were not a specific part of the intervention; thus, data were analysed as an observational cohort. Dietary information was collected with validated semi-quantitative FFQ and trained personnel measured BP. To assess BP changes, we undertook cross-sectional analyses at baseline and at the end of follow-up and longitudinal analyses. A statistically significant inverse association between low-fat dairy product intake and systolic BP was observed for the 12-month longitudinal analysis. In the longitudinal analysis, the adjusted systolic and diastolic BP were significantly lower in the highest quintile of low-fat dairy product intake ( 2 4·2 (95% CI 2 6·9, 2 1·4) and 2 1·8 (95% CI 2 3·2, 2 0·4) mmHg respectively), whereas the point estimates for the difference in diastolic BP indicated a modest non-significant inverse association. Intake of low-fat dairy products was inversely associated with BP in an older population at high cardiovascular risk, suggesting a possible protective effect against hypertension.

Interviewer and Respondent Survey Quality Effects in a CATI Panel

Especially in panel surveys, respondent attrition, respondent learning, and interviewer experience effects play a crucial role with respect to data quality. We examine three interview survey quality indicators in the same survey in a cross sectional as well as in a longitudinal way. In the cross sectional analysis we compare data quality in the mature original sample with that in a refreshment sample, surveyed in the same wave. Because in the same wave an interviewer survey was conducted, collecting attitudes on their socio demography, survey attitudes and burden measures, we are able to consider interviewer fixed effects as well. The longitudinal analysis gives more insight in the respondent learning effects with respect to the quality indicators considered by considering the very same respondents across waves. The Swiss Household Panel, a CATI survey representative of the Swiss residential population, forms an ideal modelling database: the interviewer - respondent assignment is random, both within and across waves. This design avoids possible confusion with other effects stemming from a non-random assignment of interviewers, e.g. area effects or effects from assigning the best interviewers to the hard cases. In order to separate interviewer, respondent and wave effects, we build cross-classified multilevel models.

Diffusion of Administrative Innovation: TQM Implementation and Effectiveness in a Global

The main objective of this dissertation is to create new knowledge on an administrative innovation, its adoption, diffusion and finally its effectiveness. In this dissertation the administrative innovation is approached through a widely utilized management philosophy, namely the total quality management (TQM) strategy. TQM operationalizes a self-assessment procedure, which is based on continual improvement principles and measuring the improvements. This dissertation also captures the theme of change management as it analyzes the adoption and diffusion of the administrative innovation. It identifies innovation characteristics as well as organisational and individual factors explaining the adoption and implementation. As a special feature, this study also explores the effectiveness of the innovation based on objective data. For studying the administrative innovation (TQM model), a multinational Case Company provides a versatile ground for a deep, longitudinal analysis. The Case Company started the adoption systematically in the mid 1980s in some of its units. As part of their strategic planning today, the procedure is in use throughout the entire global company. The empirical story begins from the innovation adoption decision that was made in the Case Company over 22 years ago. In order to be able to capture the right atmosphere and backgrounds leading to the adoption decision, key informants from that time were interviewed, since the main target was to clarify the dynamics of how an administrative innovation develops. In addition, archival material was collected and studied, available memos and data relating to the innovation, innovation adoption and later to the implementation contained altogether 20500 pages of documents. A survey was furthermore conducted at the end of 2006 focusing on questions related to the innovation, organization and leadership characteristics and the response rate totalled up to 54%. For measuring the effectiveness of the innovation implementation, the needed longitudinal objective performance data was collected. This data included the profit unit level experience of TQM, the development of the self assessment scores per profit unit and performance data per profit unit measured with profitability, productivity and customer satisfaction. The data covered the years 1995-2006. As a result, the prerequisites for the successful adoption of an administrative innovation were defined, such as the top management involvement, support of the change agents and effective tools for implementation and measurement. The factors with the greatest effect on the depth of the implementation were the timing of the adoption and formalization. The results also indicated that the TQM model does have an effect on the company performance measured with profitability, productivity and customer satisfaction. Consequently this thesis contributes to the present literature (i) by taking into its scope an administrative innovation and focusing on the whole innovation implementation process, from the adoption, through diffusion until its consequences, (ii) because the studied factors with an effect on the innovation adoption and diffusion are multifaceted and grouped into individual, organizational and environmental factors, and a strong emphasis is put on the role of the individual change agents and (iii) by measuring the depth and consistency of the administrative innovation. This deep analysis was possible due to the availability of longitudinal data with triangulation possibilities.

Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study

High blood pressure (BP) has been ranked as the most important risk factor worldwide regarding attributable deaths. Dietary habits are major determinants of BP. Among them, frequent intake of low-fat dairy products may protect against hypertension. Our aim was to assess the relationship between low-fat dairy product intake and BP levels and their changes after 12 month follow-up in a cohort of asymptomatic older persons at high cardiovascular risk recruited into a large-scale trial assessing the effects of Mediterranean diets on cardiovascular outcomes. Data from 2290 participants, including 1845 with hypertension, were available for analyses. Dairy products were not a specific part of the intervention; thus, data were analysed as an observational cohort. Dietary information was collected with validated semi-quantitative FFQ and trained personnel measured BP. To assess BP changes, we undertook cross-sectional analyses at baseline and at the end of follow-up and longitudinal analyses. A statistically significant inverse association between low-fat dairy product intake and systolic BP was observed for the 12-month longitudinal analysis. In the longitudinal analysis, the adjusted systolic and diastolic BP were significantly lower in the highest quintile of low-fat dairy product intake ( 2 4·2 (95% CI 2 6·9, 2 1·4) and 2 1·8 (95% CI 2 3·2, 2 0·4) mmHg respectively), whereas the point estimates for the difference in diastolic BP indicated a modest non-significant inverse association. Intake of low-fat dairy products was inversely associated with BP in an older population at high cardiovascular risk, suggesting a possible protective effect against hypertension.