Information Design

There are two ways of creating incentives for interacting agents to behave in a desired way. One is by providing appropriate payoff incentives, which is the subject of mechanism design. The other is by choosing the information that agents observe, which we refer to as information design. We consider a model of symmetric information where a designer chooses and announces the information structure about a payoff relevant state. The interacting agents observe the signal realizations and take actions which affect the welfare of both the designer and the agents. We characterize the general finite approach to deriving the optimal information structure for the designer - the one that maximizes the designer's ex ante expected utility subject to agents playing a Bayes Nash equilibrium. We then apply the general approach to a symmetric two state, two agent, and two actions environment in a parameterized underlying game and fully characterize the optimal information structure: it is never strictly optimal for the designer to use conditionally independent private signals; the optimal information structure may be a public signal or may consist of correlated private signals. Finally, we examine how changes in the underlying game affect the designer's maximum payoff. This exercise provides a joint mechanism/information design perspective.

Design and evaluation of a solid sampler for the monitoring of airborne 1,6-hexamethylene diisocyanate (HDI) and its prepolymers in 2-component spray painting

An active, solvent-free solid sampler was developed for the collection of 1,6-hexamethylene diisocyanate (HDI) aerosol and prepolymers. The sampler was made of a filter impregnated with 1-(2-methoxyphenyl)piperazine contained in a filter holder. Interferences with HDI were observed when a set of cellulose acetate filters and a polystyrene filter holder were used; a glass fiber filter and polypropylene filter cassette gave better results. The applicability of the sampling and analytical procedure was validated with a test chamber, constructed for the dynamic generation of HDI aerosol and prepolymers in commercial two-component spray paints (Desmodur(R) N75) used in car refinishing. The particle size distribution, temporal stability, and spatial uniformity of the simulated aerosol were established in order to test the sample. The monitoring of aerosol concentrations was conducted with the solid sampler paired to the reference impinger technique (impinger flasks contained 10 mL of 0.5 mg/mL 1-(2-methoxyphenyl)piperazine in toluene) under a controlled atmosphere in the test chamber. Analyses of derivatized HDI and prepolymers were carried out by using high-performance liquid chromatography and ultraviolet detection. The correlation between the solvent-free and the impinger techniques appeared fairly good (Y = 0.979X - 0.161; R = 0.978), when the tests were conducted in the range of 0.1 to 10 times the threshold limit value (TLV) for HDI monomer and up to 60-mu-g/m3 (3 U.K. TLVs) for total -N = C = O groups.

Experimental design for acquiring relevant data to address the issue of comparing consecutively manufactured tools and firearms

The comparison of consecutively manufactured tools and firearms has provided much, but not all, of the basis for the profession of firearm and toolmark examination. The authors accept the fundamental soundness of this approach but appeal to the experimental community to close two minor gaps in the experimental procedure. We suggest that "blinding" and attention to appropriateness of other experimental conditions that would consolidate the foundations of our profession. We do not suggest that previous work is unsound.

Intérêt de l'éthylglucuronide comme marqueur d'abus d'alcool, aspects analytiques, diagnostiques et médico-légaux

RESUMEUne consommation excessive et chronique d'alcool est associée à une augmentation significative de la morbidité et de la mortalité. L'identification de marqueurs biologiques fiables, permettant de mettre en évidence une consommation excessive et chronique, présente donc un intérêt certain pour prévenir les conséquences néfastes de l'abus d'alcool. L'approche couramment employée consiste à mesurer les marqueurs biologiques indirects dans le sang, tels que les marqueurs hépatiques dont l'augmentation peut résulter d'une consommation chronique et excessive d'alcool. Cependant, leur valeur diagnostique est souvent limitée par leur manque de sensibilité et/ou de spécificité et leur combinaison est généralement recommandée pour améliorer le diagnostic. A ce jour, il n'existe pas de marqueur biologique permettant le diagnostic fiable d'une consommation chronique et excessive d'alcool.L'objectif principal de cette thèse était d'évaluer la pertinence de l'éthylglucuronide (EtG), un métabolite direct de l'éthanol présentant la particularité d'être incorporé dans les cheveux, comme marqueur d'une consommation chronique et excessive d'alcool. Dans un premier temps, une revue de la littérature a permis de dresser un état des lieux de l'usage de l'EtG et d'identifier les axes de réflexion. L'EtG s'est révélé être un marqueur efficace pour identifier une consommation chronique et excessive d'alcool. Cependant, l'absence de seuil de positivité fiable et une méconnaissance des facteurs influençant l'incorporation de l'EtG dans les cheveux ont été mises en évidence. Afin d'investiguer ces différents points, deux études ont été conduites : (1) une étude chez le rat pour tenter de comprendre les facteurs influençant l'incorporation de l'EtG dans les cheveux et étudier la relation entre la quantité d'alcool administrée et la concentration d'EtG mesurée dans les cheveux; et (2) une étude clinique afin de déterminer les performances diagnostiques de l'EtG comme marqueur d'une consommation excessive et chronique d'alcool. Une méthode analytique sensible et sélective par chromatographic gazeuse couplée à la spectrométrie de masse en tandem a été développée et appliquée à l'analyse de l'EtG dans les cheveux.Le sang semblait jouer un rôle majeur dans l'incorporation de l'EtG dans les poils. Son incorporation n'était pas influencée par la pigmentation. La concentration d'EtG mesurée dans les poils de rats reflétait la dose d'éthanol administrée. De plus, la mesure de l'EtG dans les cheveux humains a démontré de très bonnes performances diagnostiques pour détecter une consommation excessive et chronique d'alcool. Les performances diagnostiques de l'EtG surpassaient celles des marqueurs hépatiques usuels seuls ou combinés. L'EtG n'était pas influencé par l'âge, le sexe ou l'indice de masse corporelle. Un seuil de positivité de 25 pg/mg permettait de détecter les consommateurs à usage nocif avec une grande fiabilité. Un seuil de positivité de 9 pg/mg permettait de détecter les consommateurs à risque.SUMMARYChronic and excessive alcohol consumption is associated with a significant increase of morbidity and mortality. The identification of a reliable biomarker to detect chronic and excessive alcohol consumers would be valuable to prevent alcohol's harmful effects. The combined analysis of 2 or more hepatic biomarkers, which are known to be increased following sustained alcohol consumption, is usually applied to enhance the diagnostic performance in identifying chronic and excessive alcohol consumers. However, their diagnostic value is often limited by their lack of sensitivity and / or specificity and their combination is generally recommended to improve diagnosis. To date, there are no reliable biomarkers available for diagnosing chronic and excessive alcohol consumption.The main objective of this research was to evaluate the relevance of EtG, a direct alcohol metabolite, as a biomarker of chronic and excessive alcohol consumption, thanks to its characteristic to incorporate into hair. First, a review of literature on the use of EtG was carried out. EtG demonstrated strong potential in detecting chronic and excessive alcohol consumption. However, the lack of reliable cutoff and the unawareness of factors that affect the EtG incorporation into hair were stressed. To investigate these points, two studies have been conducted: (1) a nonclinical study in rats to determine the factors affecting the incorporation of EtG into hair as well as to investigate the relationship between the amount of alcohol administered and the EtG concentration measured in hair; and (2) a clinical study to determine the diagnostic performance of EtG as a biomarker for the identification of chronic and excessive alcohol consumers. A sensitive and specific Gas Chromatography-Mass Spectrometry coupled to tandem Mass Spectrometry method has been developed and applied to hair EtG analysis.Bloodstream seemed to play a major role in the EtG incorporation into hair. EtG incorporation into rat hair was not affected by hair pigmentation. EtG concentration in rat hair appeared to reflect the EtG concentration in blood. Besides, EtG demonstrated strong diagnostic performance in detecting both heavy alcohol consumption and at-risk alcohol consumption, and clearly outperformed diagnostic performance of hepatic biomarkers. In contrast with hepatic biomarkers, EtG was not associated with age, gender or body mass index. A reliable cutoff value of 25 pg/mg allowed to detect heavy drinkers; a reliable cutoff value of 9 pg/mg allowed to detect at-risk drinkers.

New concepts for the design of dermal substitutes

Objectives: Skin can be partially regenerated after full thickness defects by collagen matrices, In this study, we identified the main limitations of induced regeneration aiming to improve the design of dermal matrices. Methods: Single mice received a 1 cm2, full thickness skin wound on the dorsum, which were grafted with collagen-GAG matrices or left ungrafted. The healing modulation induced by the collagen-GAG matrices was compared to spontaneous healing and to custom designed, bioactive, poly-N-Acetyl- Glucosamine (NAG) matrices. Wound staging was based on macroscopic, histological and immunhistochemical analysis on days 3, 7, 10 and 21 post wounding. Results: Cell density was higher in spontaneously granulating wounds compared to grafted wounds. While grafted wounds exhibited increased levels of cell proliferation on days 7 and 10, vascularity was dramatically reduced. NAG scaffolds accelerated both angiogenesis and wound re-epithelialization. Conclusions: Since slow integration and revascularization severely limit the engraftment of clinically used dermal scaffolds, the design of dermal matrices using bioactive materials represent the next step in skin regeneration.

The impact of iron supplementation efficiency in female blood donors with a decreased ferritin level and no anaemia. Rationale and design of a randomised controlled trial: a study protocol.

ABSTRACT: BACKGROUND: There is no recommendation to screen ferritin level in blood donors, even though several studies have noted the high prevalence of iron deficiency after blood donation, particularly among menstruating females. Furthermore, some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation. Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia, but with a mean serum ferritin </= 30 ng/ml. METHODS/DESIGN: In a double blind randomised controlled trial, we will measure blood count and ferritin level of women under age 50 yr, who donate blood to the University Hospital of Lausanne Blood Transfusion Department, at the time of the donation and after 1 week. One hundred and forty donors with a ferritin level </= 30 ng/ml and haemoglobin level >/= 120 g/l (non-anaemic) a week after the donation will be included in the study and randomised. A one-month course of oral ferrous sulphate (80 mg/day of elemental iron) will be introduced vs. placebo. Self-reported fatigue will be measured using a visual analogue scale. Secondary outcomes are: score of fatigue (Fatigue Severity Scale), maximal aerobic power (Chester Step Test), quality of life (SF-12), and mood disorders (Prime-MD). Haemoglobin and ferritin concentration will be monitored before and after the intervention. DISCUSSION: Iron deficiency is a potential problem for all blood donors, especially menstruating women. To our knowledge, no other intervention study has yet evaluated the impact of iron supplementation on subjective symptoms after a blood donation. TRIAL REGISTRATION: NCT00689793.

Design and analysis of ChIP-Seq experiments for nuclear factor I DNA-binding proteins

SUMMARY : Eukaryotic DNA interacts with the nuclear proteins using non-covalent ionic interactions. Proteins can recognize specific nucleotide sequences based on the sterical interactions with the DNA and these specific protein-DNA interactions are the basis for many nuclear processes, e.g. gene transcription, chromosomal replication, and recombination. New technology termed ChIP-Seq has been recently developed for the analysis of protein-DNA interactions on a whole genome scale and it is based on immunoprecipitation of chromatin and high-throughput DNA sequencing procedure. ChIP-Seq is a novel technique with a great potential to replace older techniques for mapping of protein-DNA interactions. In this thesis, we bring some new insights into the ChIP-Seq data analysis. First, we point out to some common and so far unknown artifacts of the method. Sequence tag distribution in the genome does not follow uniform distribution and we have found extreme hot-spots of tag accumulation over specific loci in the human and mouse genomes. These artifactual sequence tags accumulations will create false peaks in every ChIP-Seq dataset and we propose different filtering methods to reduce the number of false positives. Next, we propose random sampling as a powerful analytical tool in the ChIP-Seq data analysis that could be used to infer biological knowledge from the massive ChIP-Seq datasets. We created unbiased random sampling algorithm and we used this methodology to reveal some of the important biological properties of Nuclear Factor I DNA binding proteins. Finally, by analyzing the ChIP-Seq data in detail, we revealed that Nuclear Factor I transcription factors mainly act as activators of transcription, and that they are associated with specific chromatin modifications that are markers of open chromatin. We speculate that NFI factors only interact with the DNA wrapped around the nucleosome. We also found multiple loci that indicate possible chromatin barrier activity of NFI proteins, which could suggest the use of NFI binding sequences as chromatin insulators in biotechnology applications. RESUME : L'ADN des eucaryotes interagit avec les protéines nucléaires par des interactions noncovalentes ioniques. Les protéines peuvent reconnaître les séquences nucléotidiques spécifiques basées sur l'interaction stérique avec l'ADN, et des interactions spécifiques contrôlent de nombreux processus nucléaire, p.ex. transcription du gène, la réplication chromosomique, et la recombinaison. Une nouvelle technologie appelée ChIP-Seq a été récemment développée pour l'analyse des interactions protéine-ADN à l'échelle du génome entier et cette approche est basée sur l'immuno-précipitation de la chromatine et sur la procédure de séquençage de l'ADN à haut débit. La nouvelle approche ChIP-Seq a donc un fort potentiel pour remplacer les anciennes techniques de cartographie des interactions protéine-ADN. Dans cette thèse, nous apportons de nouvelles perspectives dans l'analyse des données ChIP-Seq. Tout d'abord, nous avons identifié des artefacts très communs associés à cette méthode qui étaient jusqu'à présent insoupçonnés. La distribution des séquences dans le génome ne suit pas une distribution uniforme et nous avons constaté des positions extrêmes d'accumulation de séquence à des régions spécifiques, des génomes humains et de la souris. Ces accumulations des séquences artéfactuelles créera de faux pics dans toutes les données ChIP-Seq, et nous proposons différentes méthodes de filtrage pour réduire le nombre de faux positifs. Ensuite, nous proposons un nouvel échantillonnage aléatoire comme un outil puissant d'analyse des données ChIP-Seq, ce qui pourraient augmenter l'acquisition de connaissances biologiques à partir des données ChIP-Seq. Nous avons créé un algorithme d'échantillonnage aléatoire et nous avons utilisé cette méthode pour révéler certaines des propriétés biologiques importantes de protéines liant à l'ADN nommés Facteur Nucléaire I (NFI). Enfin, en analysant en détail les données de ChIP-Seq pour la famille de facteurs de transcription nommés Facteur Nucléaire I, nous avons révélé que ces protéines agissent principalement comme des activateurs de transcription, et qu'elles sont associées à des modifications de la chromatine spécifiques qui sont des marqueurs de la chromatine ouverte. Nous pensons que lés facteurs NFI interagir uniquement avec l'ADN enroulé autour du nucléosome. Nous avons également constaté plusieurs régions génomiques qui indiquent une éventuelle activité de barrière chromatinienne des protéines NFI, ce qui pourrait suggérer l'utilisation de séquences de liaison NFI comme séquences isolatrices dans des applications de la biotechnologie.

Basic biochemical investigations as rationale for the design of original antimalarial drugs. An example of phospholipid metabolism

The future of antimalarial chemotherapy is particulary alarming in view of the spread of parasite cross-resistances to drugs that are not even structurally related. Only the availability of new pharmacological models will make it possible to select molecules with novel mechanisms of action, thus delaving resistance and allowing the development of new chemotherapeutic strategies. We reached this objective in mice. Our approach is hunged on fundamental and applied research begun in 1980 to investigate to phospholipid (PL) metabolism of intraerythrocytic Plasmodium. This metabolism is abundant, specific and indispensable for the production of Plasmodium membranes. Any drug to interfere with this metabolism blocks parasitic development. The most effective interference yet found involves blockage of the choline transporter, which supplies Plasmodium with choline for the synthesis of phosphatidylcholine, its major PL, this is a limiting step in the pathway. The drug sensitivity thereshold is much lower for the parasite, which is more dependent on this metabolism than host cells. The compounds show in vitro activity against P. falciparum at 1 to 10 nM. They show a very low toxicity against a lymphblastoid cell line, demonstrating a total abscence of correlation between growth inhibition of parasites and lymphoblastoid cells. They show antimalarial activity in vivo, in the P. berghei or P. chabaudi/mouse system, at doses 20-to 100-fold lower than their in acute toxicity limit. The bioavailability of a radiolabeled form of the product seemed to be advantageous (slow blood clearance and no significant concentration in tissues). Lastly, the compounds are inexpensive to produce. They are stable and water-soluble.

The Design and efficiency of loyalty rewards

The goal of this paper is to reexamine the optimal design and efficiency of loyalty rewards in markets for final consumption goods. While the literature has emphasized the role of loyalty rewards as endogenous switching costs (which distort the efficient allocation of consumers), in this paper I analyze the ability of alternative designs to foster consumer participation and increase total surplus. First, the efficiency of loyalty rewards depend on their specific design. A commitment to the price of repeat purchases can involve substantial efficiency gains by reducing price-cost margins. However, discount policies imply higher future regular prices and are likely to reduce total surplus. Second, firms may prefer to set up inefficient rewards (discounts), especially in those circumstances where a commitment to the price of repeat purchases triggers Coasian dynamics.

Study design for technology assessment: critical issues.

The epidemiological methods have become useful tools for the assessment of the effectiveness and safety of health care technologies. The experimental methods, namely the randomized controlled trials (RCT), give the best evidence of the effect of a technology. However, the ethical issues and the very nature of the intervention under study sometimes make it difficult to carry out an RCT. Therefore, quasi-experimental and non-experimental study designs are also applied. The critical issues concerning these designs are discussed. The results of evaluative studies are of importance for decision-makers in health policy. The measurements of the impact of a medical technology should go beyond a statement of its effectiveness, because the essential outcome of an intervention or programme is the health status and quality of life of the individuals and populations concerned.

Docking, virtual high throughput screening and in silico fragment-based drug design.

ABSTRACT The drug discovery process has been profoundly changed recently by the adoption of computational methods helping the design of new drug candidates more rapidly and at lower costs. In silico drug design consists of a collection of tools helping to make rational decisions at the different steps of the drug discovery process, such as the identification of a biomolecular target of therapeutical interest, the selection or the design of new lead compounds and their modification to obtain better affinities, as well as pharmacokinetic and pharmacodynamic properties. Among the different tools available, a particular emphasis is placed in this review on molecular docking, virtual high throughput screening and fragment-based ligand design.

Discursos y representaciones médico-sanitarias en el cine documental colonial español de la posguerra (1939-1950)

El objetivo de este estudio es contribuir al entendimiento, desde un punto de vista histórico, del papel que juega el cine en los procesos de popularización de la ciencia, la medicina y la tecnología. El punto de partida es la consideración de la medicina y del cine como conjuntos complejos y multidimensionales de “prácticas y discursos” de carácter científico-tecnológico y, por tanto, como formas particulares de acción e interacción cotidiana entre personas, colectivos e instituciones que juegan un papel básico en los procesos de construcción y funcionamiento de las sociedades contemporáneas. Así, mediante el análisis de la representación y articulación de las prácticas y los discursos médico-sanitarios en el cine documental colonial español del primer franquismo, es decir, en el caso particular de la construcción, legitimación y consolidación de un régimen totalitario, se aportan algunas claves explicativas sobre las múltiples relaciones entre diferentes colectivos (expertos y no-expertos) en cuanto a la naturaleza y el nivel de intervención en los procesos de generación y gestión de conocimiento científico-tecnológico. Como resultado, el cine se revela como un espacio no sólo de evasión y entretenimiento, sino también de ciencia y educación, donde la capacidad de definir y solucionar problemas cotidianos de la población, y por tanto, su impacto en la construcción de la arquitectura social, ideológica, económica, política y cultural de las sociedades contemporáneas, se fundamenta en la combinación de sus aspectos como espectáculo narrativo y científico-tecnológico.