The role of fitness in the association between fatness and cardiometabolic risk from childhood to adolescence

Background Fatness and fitness both influence cardiometabolic risk. Objective The purpose of this study was to investigate whether childhood fatness and increasing fatness from childhood to adolescence are associated with cardiometabolic risk during adolescence and how fitness affects this association. Subjects and methods Of 565 adolescents (283 boys and 282 girls) from the TRacking Adolescents Individual Life Survey (TRAILS) data on anthropometric parameters (age 11 and 16), metabolic parameters, and fitness (age 16) were available. Body mass index and skinfolds were used as measures for fatness. Increasing fatness was calculated by subtracting Z-scores for fatness at age 11 from Z-score fatness at age 16. Cardiometabolic risk was calculated as the average of the standardized means of mean arterial pressure, fasting serum triglycerides, high-density lipoprotein-cholesterol, glucose, and waist circumference. Insulin resistance was calculated by homeostasis model assessment-insulin resistance (HOMA-IR). Fitness was estimated as maximal oxygen consumption (VO2max) during a shuttle run test. Results Boys showed a higher clustered cardiometabolic risk when compared to girls (p < 0.01). Childhood fatness (age 11) and increasing fatness were independently associated with cardiometabolic risk during adolescence. In boys, high fitness was related to a reduced effect of increasing fatness on clustered cardiometabolic risk. Childhood fatness, increasing fatness, and fitness were independently associated with HOMA-IR. Moreover, in boys this association was dependent of fatness. Conclusions Childhood fatness and increasing fatness are associated with increased cardiometabolic risk and HOMA-IR during adolescence, but a good fitness attenuates this association especially in fat boys

Balancing equity and efficiency in the Dutch basic benefits package using the principle of proportional shortfall

Economic evaluations are increasingly used to inform decisions regarding the allocation of scarce health care resources. To systematically incorporate societal preferences into these evaluations, quality-adjusted life year gains could be weighted according to some equity principle, the most suitable of which is a matter of frequent debate. While many countries still struggle with equity concerns for priority setting in health care, the Netherlands has reached a broad consensus to use the concept of proportional shortfall. Our study evaluates the concept and its support in the Dutch health care context. We discuss arguments in the Netherlands for using proportional shortfall and difficulties in transitioning from principle to practice. In doing so, we address universal issues leading to a systematic consideration of equity concerns for priority setting in health care. The article thus has relevance to all countries struggling with the formalization of equity concerns for priority setting

Peroxiredoxin 4, a novel circulating biomarker for oxidative stress and the risk of incident cardiovascular disease and all-cause mortality

BACKGROUND: Oxidative stress has been suggested to play a key role in the development of cardiovascular disease (CVD). The aim of our study was to investigate the associations of serum peroxiredoxin 4 (Prx4), a hydrogen peroxide-degrading peroxidase, with incident CVD and all-cause mortality. We subsequently examined the incremental value of Prx4 for the risk prediction of CVD compared with the Framingham risk score (FRS). METHODS AND RESULTS: We performed Cox regression analyses in 8141 participants without history of CVD (aged 28 to 75 years; women 52.6%) from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study in Groningen, The Netherlands. Serum Prx4 was measured by an immunoluminometric assay in baseline samples. Main outcomes were: (1) incident CVD events or CVD mortality and (2) all-cause mortality during a median follow-up of 10.5 years. In total, 708 participants (7.8%) developed CVD events or CVD mortality, and 517 participants (6.3%) died. Baseline serum Prx4 levels were significantly higher in participants with incident CVD events or CVD mortality and in those who died than in participants who remained free of outcomes (both P<0.001). In multivariable models with adjustment for Framingham risk factors, hazard ratios were 1.16 (95% CI 1.06 to 1.27, P<0.001) for incident CVD events or CVD mortality and 1.17 (95% CI 1.06 to 1.29, P=0.003) for all-cause mortality per doubling of Prx4 levels. After the addition of Prx4 to the FRS, the net reclassification improvement was 2.7% (P=0.01) using 10-year risk categories of CVD. CONCLUSIONS: Elevated serum Prx4 levels are associated with a significantly higher risk of incident CVD events or CVD mortality and all-cause mortality after adjustment for clinical risk factors. The addition of Prx4 to the FRS marginally improved risk prediction of future CVD

The Pharmaceutical Sciences in 2020: Report of a Conference Organized by the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation (FIP)

The Board of Pharmaceutical Sciences (BPS) of the International Pharmaceutical Federation (FIP) has developed a view on the future of pharmaceutical sciences in 2020. This followed an international conference with invited participants from various fields (academicians, scientists, regulators, industrialists, venture capitalists) who shared their views on the forces that might determine how the pharmaceutical sciences will look in 2020. The commentary here provides a summary of major research activities that will drive drug discovery and development, enabling technologies for pharmaceutical sciences, paradigm shifts in drug discovery, development and regulations, and changes in education to meet the demands of academia, industry and regulatory institutions for pharmaceutical sciences in 2020

Understanding communicative actions:A repetitive TMS study

Previous work has shown that the right posterior superior temporal sulcus (RpSTS) is involved in inferring both instrumental goals and communicative intentions of observed actions (1, 2), using previous knowledge to generate perceptual and/or conceptual inferences (3, 4). Here, we disturb neural activity in RpSTS to test whether this region is necessary for understanding the meaning of novel communicative actions. Thirteen subjects received two 20 min sessions of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS), either over RpSTS (50,-42,14) or over a control region (area MT+, -43,-70,10), before performance of a communicative game and a control task. The game involved controlled non-verbal communicative interactions between pairs of subjects (40 trials). Each pair was asked to jointly create a goal configuration of two geometrical tokens, using the movements of the tokens on a gameboard as the only available communicative channel (5). One participant (a confederate) knew the goal configuration, and she moved her token on the gameboard to inform an addressee (a participant) where and how to position his token. The control task was a visual search paradigm that involved the same stimuli, responses, joint attention, and inter-subjects dependencies, but no communicative necessities. Performance was indexed by Task Efficiency, defined as the number of correct responses per unit of planning time, and by Efficiency Rate, defined as the rate of change (across trials) in Task Efficiency. After rTMS over RpSTS, but not left MT+, the Efficiency Rate of the addresses was reduced in the communicative game, but not in the visual search. In contrast, after rTMS over left MT+, subjects were not able to benefit from experience gained during the previous trials of the visual search task (Task X Site interaction, p<0.05). There were no corresponding interactions between tasks and site of rTMS intervention on the Task Efficiency parameter. These findings qualify how RpSTS contributes to understanding the meaning of non-verbal communicative actions. Repetitive TMS over RpSTS did not disrupt the ability of addressees to interpret novel communicative actions. Rather, this region appears to be necessary for incorporating previous knowledge, accumulated during interactions with a communicative partner, to constrain the inferential process that leads to action understanding

Structural Uncertainty in Onchocerciasis Transmission Models Influences the Estimation of Elimination Thresholds and Selection of Age Groups for Seromonitoring

Background. The World Health Organization recommends monitoring Ov16 serologyin children aged <10 years for stopping mass ivermectin administration. Transmission models can help to identify the most informative age groups for serological monitoring and investigate the discriminatory power of serology-based elimination thresholds.Model predictions will depend on assumed age-exposure patterns and transmission efficiency at low infection levels. Methods. The individual-based transmission model, EPIONCHO-IBM, was used toassess: i) the most informative age groups for serological monitoring using receiveroperator characteristic curves for different elimination thresholds under various age-dependent exposure assumptions, including those of ONCHOSIM (another widely-used model), and ii) the influence of within-human density-dependent parasite establishment (included in EPIONCHO-IBM but not in ONCHOSIM) on positive predictive values for different serological thresholds.Results. When assuming EPIONCHO-IBM exposure patterns, under-10s are themost informative age group for seromonitoring; when assuming ONCHOSIM’s exposure patterns, 5–15-year olds are the most informative (as published elsewhere).Omitting density-dependent parasite establishment results in more lenientseroprevalence thresholds, even for higher baseline infection prevalence and shorter treatment durations.Conclusions. Selecting appropriate seromonitoring age groups depends critically onage-dependent exposure patterns. The role of density dependence on elimination thresholds largely explains differing EPIONCHO-IBM and ONCHOSIM elimination predictions

The effects of lead time and visual aids in TTO valuation: a study of the EQ-VT framework

__Abstract__ __Background__ The effect of lead time in time trade-off (TTO) valuation is not well understood. The purpose of this study was to investigate the effects on health-state valuation of the length of lead time and the way the lead-time TTO task is displayed visually. __Methods__ Using two general population samples, we compared three lead-time TTO variants: 10 years of lead time in full health preceding 5 years of unhealthy time (standard); 5 years of lead time preceding 5 years of unhealthy time (experimental); and 10 years of lead time and 5 years of unhealthy time, presented with a visual aid to highlight the point where the lead time ends (experimental). Participants were randomized to receive one of the lead-time variants, as administered by a computer software program. __Results__ Health-state values generated by TTO valuation tasks using a longer lead time were slightly lower than those generated by tasks using a shorter lead time. When lead time and unhealthy time were presented with visual aids highlighting the difference between the lead time and unhealthy time, respondents spent more time considering health states with a value close to 0. __Conclusions__ Different lead-time time trade-off variants should be carefully studied in order to achieve the best measurement of health-state values using this new method

Thermally activated reorientation of di-interstitial defects in silicon

We propose a di-interstitial model for the P6 center commonly observed in ion implanted silicon. The di-interstitial structure and transition paths between different defect orientations can explain the thermally activated transition of the P6 center from low-temperature C1h to room-temperature D2d symmetry. The activation energy for the defect reorientation determined by ab initio calculations is 0.5 eV in agreement with the experiment. Our di-interstitial model establishes a link between point defects and extended defects, di-interstitials providing the nuclei for the growth.Comment: 12 pages, REVTeX, Four figures, submitted to Phys. Rev. Let