TEMPOS: A Platform for Developing Temporal Applications on Top of Object DBMS

This paper presents TEMPOS: a set of models and languages supporting the manipulation of temporal data on top of object DBMS. The proposed models exploit object-oriented technology to meet some important, yet traditionally neglected design criteria related to legacy code migration and representation independence. Two complementary ways for accessing temporal data are offered: a query language and a visual browser. The query language, namely TempOQL, is an extension of OQL supporting the manipulation of histories regardless of their representations, through fully composable functional operators. The visual browser offers operators that facilitate several time-related interactive navigation tasks, such as studying a snapshot of a collection of objects at a given instant, or detecting and examining changes within temporal attributes and relationships. TEMPOS models and languages have been formalized both at the syntactical and the semantical level and have been implemented on top of an object DBMS. The suitability of the proposals with regard to applications' requirements has been validated through concrete case studies

Metabolic Activity and mRNA Levels of Human Cardiac CYP450s Involved in Drug Metabolism

Tissue-specific expression of CYP450s can regulate the intracellular concentration of drugs and explain inter-subject variability in drug action. The overall objective of our study was to determine in a large cohort of samples, mRNA levels and CYP450 activity expressed in the human heart.CYP450 mRNA levels were determined by RTPCR in left ventricular samples (n = 68) of explanted hearts from patients with end-stage heart failure. Samples were obtained from ischemic and non-ischemic hearts. In some instances (n = 7), samples were available from both the left and right ventricles. A technique for the preparation of microsomes from human heart tissue was developed and CYP450-dependent activity was determined using verapamil enantiomers as probe-drug substrates.Our results show that CYP2J2 mRNA was the most abundant isoform in all human heart left ventricular samples tested. Other CYP450 mRNAs of importance were CYP4A11, CYP2E1, CYP1A1 and CYP2C8 mRNAs while CYP2B6 and CYP2C9 mRNAs were present at low levels in only some of the hearts analyzed. CYP450 mRNAs did not differ between ischemic and non-ischemic hearts and appeared to be present at similar levels in the left and right ventricles. Incubation of verapamil with heart microsomes led to the formation of nine CYP450-dependent metabolites: a major finding was the observation that stereoselectivity was reversed compared to human liver microsomes, in which the R-enantiomer is metabolized to a greater extent.This study determined cardiac mRNA levels of various CYP450 isozymes involved in drug metabolism and demonstrated the prevalent expression of CYP2J2 mRNA. It revealed that cardiomyocytes can efficiently metabolize drugs and that cardiac CYP450s are highly relevant with regard to clearance of drugs in the heart. Our results support the claim that drug metabolism in the vicinity of a drug effector site can modulate drug effects

Higher Toxicity with 42 Gy in 10 Fractions as a Total Dose for 3D-Conformal Accelerated Partial Breast Irradiation: Results from a Dose Escalation Phase II Trial

Objective: Recent recommendations regarding indications of accelerated partial breast irradiation (APBI) have been put forward for selected breast cancer (BC) patients. However, some treatment planning parameters, such as total dose, are not yet well defined. The Institut Gustave Roussy has initiated a dose escalation trial at the 40 Gy/10 fractions/5 days and at a further step of total dose (TD) of 42 Gy/10 fractions/5 days. Here, we report early results of the latest step compared with the 40 Gy dose level. Methods and materials: From October 2007 to March 2010, a total of 48 pT1N0 BC patients were enrolled within this clinical trial: 17 patients at a TD of 42 Gy/10f/5d and 31 at a TD of 40 Gy/10f/5d. Median follow-up was 19 months (min-max, 12–26). All the patients were treated by APBI using a technique with 2 minitangents and an “enface” electrons delivering 20% of the total dose. Toxicities were systematically assessed at 1; 2; 6 months and then every 6 months. Results: Patients’ recruitment of 42 Gy step was ended owing to persistent grade 3 toxicity 6 months after APBI completion (n = 1). Early toxicities were statistically higher after a total dose of 42 Gy regarding grade ≥2 dry (p = 0.01) and moist (p = 0.05) skin desquamation. Breast pain was also statistically higher in the 42 Gy step compared to 40 Gy step (p = 0.02). Other late toxicities (grade ≥2 fibrosis and telangectasia) were not statistically different between 42 Gy and 40 Gy. Conclusions: Early toxicities were more severe and higher rates of late toxicities were observed after 42 Gy/10 fractions/5 days when compared to 40 Gy/10 fractions/5 days. This data suggest that 40 Gy/10 fractions/5 days could potentially be the maximum tolerance for PBI although longer follow-up is warranted to better assess late toxicities

Occup Environ Med

OBJECTIVES: Asthma has significant occupational consequences. The objective of our study was to investigate the links between asthma and the career path, taking into account gender and age at asthma onset. METHODS: Using cross-sectional data collected at inclusion in the French CONSTANCES cohort in 2013-2014, we studied the links between each career path indicator (number of job periods, total duration of employment, numbers of part-time jobs and work interruptions due to unemployment or health issues, employment status at inclusion) on the one hand, and current asthma and asthma symptom score in the last 12 months on the other hand, as reported by the participants. Multivariate analyses were performed separately for men and women using logistic and negative binomial regression models adjusted for age, smoking status, body mass index and educational level. RESULTS: When the asthma symptom score was used, significant associations were observed with all of the career path indicators studied: a high symptom score was associated with a shorter total duration of employment as well as a greater number of job periods, part-time jobs and work interruptions due to unemployment or health issues. These associations were of similar magnitude in men and women. When current asthma was used, the associations were more pronounced in women for some career path indicators. CONCLUSION: The career path of asthmatic adults is more often unfavourable than that of those without asthma. Efforts should be made to support people with asthma in the workplace, in order to maintain employment and facilitate the return to work.La cohorte CONSTANCES - Infrastructure épidémiologique ouverte pour la recherche et la surveillanc

Management of multi-language business processes with "AProMoRe"

International audienceAPROMORE (Advanced PROocess MOdel REpository) is an open and extensible plat- form meant to face the challenge of how to deal with an increasing number of business process models within or accross organisations

Management of multi-language business processes with "AProMoRe"

International audienceAPROMORE (Advanced PROocess MOdel REpository) is an open and extensible plat- form meant to face the challenge of how to deal with an increasing number of business process models within or accross organisations

Improvement of the Trivalent Inactivated Flu Vaccine Using PapMV Nanoparticles

Commercial seasonal flu vaccines induce production of antibodies directed mostly towards hemaglutinin (HA). Because HA changes rapidly in the circulating virus, the protection remains partial. Several conserved viral proteins, e.g., nucleocapsid (NP) and matrix proteins (M1), are present in the vaccine, but are not immunogenic. To improve the protection provided by these vaccines, we used nanoparticles made of the coat protein of a plant virus (papaya mosaic virus; PapMV) as an adjuvant. Immunization of mice and ferrets with the adjuvanted formulation increased the magnitude and breadth of the humoral response to NP and to highly conserved regions of HA. They also triggered a cellular mediated immune response to NP and M1, and long-lasting protection in animals challenged with a heterosubtypic influenza strain (WSN/33). Thus, seasonal flu vaccine adjuvanted with PapMV nanoparticles can induce universal protection to influenza, which is a major advancement when facing a pandemic

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery