Health Universities - Konzept, Relevanz und Best Practice : Mit regionaler Versorgung und interprofessioneller Bildung zu bedarfsgerechten Gesundheitsfachleuten

Das Konzept der Health Universities entstand als eine Antwort auf die Herausforderungen des Gesundheitswesens in den 1960er und 1970er Jahren. Es vereint bildungs- und versorgungspolitische Ansprüche, die schwierig unter einen Hut zu bringen sind. Wie hat sich dieses Konzept in Europa weiter entwickelt? Welche Bedeutung hat es für die Herausforderungen von heute? Dieser Bericht zeigt das Potential der Health Universities für eine bedarfsgerechte Ausbildung von Gesundheitsfachleuten zu Beginn des 21. Jahrhunderts, indem Konzept, Relevanz und Best Practice beschrieben werden

Semiautomatic mammographic parenchymal patterns classification using multiple statistical features.

RATIONALE AND OBJECTIVES: Our project was to investigate a complete methodology for the semiautomatic assessment of digital mammograms according to their density, an indicator known to be correlated to breast cancer risk. The BI-RADS four-grade density scale is usually employed by radiologists for reporting breast density, but it allows for a certain degree of subjective input, and an objective qualification of density has therefore often been reported hard to assess. The goal of this study was to design an objective technique for determining breast BI-RADS density. MATERIALS AND METHODS: The proposed semiautomatic method makes use of complementary pattern recognition techniques to describe manually selected regions of interest (ROIs) in the breast with 36 statistical features. Three different classifiers based on a linear discriminant analysis or Bayesian theories were designed and tested on a database consisting of 1408 ROIs from 88 patients, using a leave-one-ROI-out technique. Classifications in optimal feature subspaces with lower dimensionality and reduction to a two-class problem were studied as well. RESULTS: Comparison with a reference established by the classifications of three radiologists shows excellent performance of the classifiers, even though extremely dense breasts continue to remain more difficult to classify accurately. For the two best classifiers, the exact agreement percentages are 76% and above, and weighted kappa values are 0.78 and 0.83. Furthermore, classification in lower dimensional spaces and two-class problems give excellent results. CONCLUSION: The proposed semiautomatic classifiers method provides an objective and reproducible method for characterizing breast density, especially for the two-class case. It represents a simple and valuable tool that could be used in screening programs, training, education, or for optimizing image processing in diagnostic tasks

Inferring the effective thickness of polyelectrolytes from stretching measurements at various ionic strengths: applications to DNA and RNA

By resorting to the thick-chain model we discuss how the stretching response of a polymer is influenced by the self-avoidance entailed by its finite thickness. The characterization of the force versus extension curve for a thick chain is carried out through extensive stochastic simulations. The computational results are captured by an analytic expression that is used to fit experimental stretching measurements carried out on DNA and single-stranded RNA (poly-U) in various solutions. This strategy allows us to infer the apparent diameter of two biologically-relevant polyelectrolytes, namely DNA and poly-U, for different ionic strengths. Due to the very different degree of flexibility of the two molecules, the results provide insight into how the apparent diameter is influenced by the interplay between the (solution-dependent) Debye screening length and the polymers' ``bare'' thickness. For DNA, the electrostatic contribution to the effective radius, $\Delta$, is found to be about 5 times larger than the Debye screening length, consistently with previous theoretical predictions for highly-charged stiff rods. For the more flexible poly-U chains the electrostatic contribution to $\Delta$ is found to be significantly smaller than the Debye screening length.Comment: iopart, 14 pages, 13 figures, to appear in J. Phys.: Condens. Matte

Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration

BACKGROUND: Recombinant human erythropoietin (rHuEpo) can improve human performance and is therefore frequently abused by athletes. As a result, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) as an indirect method to detect blood doping. Despite this progress, challenges remain to detect blood manipulations such as the use of microdoses of rHuEpo. METHODS: Forty-five whole-blood transcriptional markers of rHuEpo previously derived from a high-dose rHuEpo administration trial were used to assess whether microdoses of rHuEpo could be detected in 14 trained subjects and whether these markers may be confounded by exercise (n = 14 trained subjects) and altitude training (n = 21 elite runners and n = 4 elite rowers, respectively). Differential gene expression analysis was carried out following normalisation and significance declared following application of a 5% false discovery rate (FDR) and a 1.5 fold-change. Adaptive model analysis was also applied to incorporate these markers for the detection of rHuEpo. RESULTS: ALAS2, BCL2L1, DCAF12, EPB42, GMPR, SELENBP1, SLC4A1, TMOD1 and TRIM58 were differentially expressed during and throughout the post phase of microdose rHuEpo administration. The CD247 and TRIM58 genes were significantly up- and down-regulated, respectively, immediately following exercise when compared with the baseline both before and after rHuEpo/placebo. No significant gene expression changes were found 30 min after exercise in either rHuEpo or placebo groups. ALAS2, BCL2L1, DCAF12, SLC4A1, TMOD1 and TRIM58 tended to be significantly expressed in the elite runners ten days after arriving at altitude and one week after returning from altitude (FDR > 0.059, fold-change varying from 1.39 to 1.63). Following application of the adaptive model, 15 genes showed a high sensitivity (≥ 93%) and specificity (≥ 71%), with BCL2L1 and CSDA having the highest sensitivity (93%) and specificity (93%). CONCLUSIONS: Current results provide further evidence that transcriptional biomarkers can strengthen the ABP approach by significantly prolonging the detection window and improving the sensitivity and specificity of blood doping detection. Further studies are required to confirm, and if necessary, integrate the confounding effects of altitude training on blood doping

Adherence to intermittent preventive treatment for malaria in Papua New Guinean infants: A pharmacological study alongside the randomized controlled trial.

The intermittent preventive treatment in infants (IPTi) trial that took place in Papua New Guinea showed an overall reduction of 29% of the risk of malaria when delivering single-dose sulfadoxine-pyrimethamine (SP) associated to 3 days of amodiaquine (AQ) every three months to children during the first year of life. The aim of the present study was to assess if the last two doses of AQ were truly administered as prescribed by the parents at home based on drug level measurement and PK modelling, which is a good proxy of medication adherence. It provides also important information to discuss the efficacy of the intervention and on feasibility of self-administered preventive malaria treatment. During the three-arm randomized double-blinded IPTi trial, each child was prescribed one dose of SP (day 0) and 3 doses of either AQ or artesunate (AS) at day 0, 1 & 2 adjusted to weight or placebo. Treatments were given at 3, 6, 9 and 12 months of age. The first day of treatment was delivered by nursing staff (initiation under directly observed treatment (DOT)) and the two last doses of AQ or AS by parents at home without supervision. For this cross-sectional study, 206 consecutive children already involved in the IPTi trial were enrolled over a 2-month period. At the time of the survey, allocation of the children to one of the three arms was not known. Blood samples for drug level measurement were collected from finger pricks one day after the planned last third dose intake. Only children allocated to the SP-AQ arm were included in the present analysis. Indeed, the half-life of AS is too short to assess if drugs were given on not. Because of the short half-life of AQ, desethyl-AQ (metabolite of AQ (DAQ)) measurements were used to investigate AQ medication adherence. Two PK (PK) models from previously published studies in paediatric populations were applied to the dataset using non-linear mixed effect modelling (NONMEM) to estimate the number of doses really given by the parents. The study nurse reported the administration time for the first AQ dose while it was estimated by the parents for the remaining two doses. Out of 206 children, 64 were in the SP-AQ arm. The adjusted dosing history for each individual was identified as the one with the lowest difference between observed and individual predicted concentrations estimated by the two PK models for all the possible adherence schemes. The median (range) blood concentration AQ in AQ arm was 9.3 ng/mL (0-1427.8 ng/mL), (Quartiles 1-3: 2.4 ng/mL -22.2 ng/mL). The median (range) for DAQ was 162.0 ng/mL (0-712 ng/mL), (Quartiles 1-3: 80.4 ng/mL-267.7 ng/mL). Under the assumption of full adherence for all participants, a marked underprediction of concentrations was observed using both PK models. Our results suggest that only 39-50% of children received the three scheduled doses of AQ as prescribed, 33-37% two doses and 17-24% received only the first dose administered by the study nurse. Both models were highly congruent to classify adherence patterns. Considering the IPTi intervention, our results seem to indicate that medication adherence is low in the ideal trial research setting and is likely to be even lower if given in day-to-day practice, questioning the real impact that this intervention might have. More generally, the estimation of the number of doses truly administered, a proxy measure of adherence and an assessment of the feasibility of the mode of administration, should be more thoroughly studied when discussing the efficacy of the interventions in trials investigating self-administered malaria preventive treatments

Integrating Human Indoor Air Pollutant Exposure within Life Cycle Impact Assessment

Neglecting health effects from indoor pollutant emissions and exposure, as currently done in Life Cycle Assessment (LCA), may result in product or process optimizations at the expense of workers’ or consumers’ health. To close this gap, methods for considering indoor exposure to chemicals are needed to complement the methods for outdoor human exposure assessment already in use. This paper summarizes the work of an international expert group on the integration of human indoor and outdoor exposure in LCA, within the UNEP/SETAC Life Cycle Initiative. A new methodological framework is proposed for a general procedure to include human-health effects from indoor exposure in LCA. Exposure models from occupational hygiene and household indoor air quality studies and practices are critically reviewed and recommendations are provided on the appropriateness of various model alternatives in the context of LCA. A single-compartment box model is recommended for use as a default in LCA, enabling one to screen occupational and household exposures consistent with the existing models to assess outdoor emission in a multimedia environment. An initial set of model parameter values was collected. The comparison between indoor and outdoor human exposure per unit of emission shows that for many pollutants, intake per unit of indoor emission may be several orders of magnitude higher than for outdoor emissions. It is concluded that indoor exposure should be routinely addressed within LCA

Évolution des recommandations de nutrition artificielle en soins intensifs et observation de leur application sur 2 périodes (2000-2001 et 2015)

Le traitement nutritionnel des patients de soins intensifs (SI) a considérablement évolué au cours de ces dernières décennies. De nombreuses études ont été menées depuis le milieu des années 60 soutenant de multiples théories à différents niveaux de la nutrition. Certains de leurs résultats, parfois contradictoires, ont abouti à une confusion intense parmi les cliniciens. En effet, il est difficile d’étudier et d’analyser le statut nutritionnel d’un individu car de nombreux biais peuvent entrer en jeu et cela d’autant plus dans le domaine des SI. Les objectifs de l’étude sont l’analyse de l’évolution des recommandations des guidelines et de l’observance des SI du CHUV à celles-ci