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Many drug candidates fail to complete the entire drug development process because of poor physicochemical properties. Solubility is an important physicochemical property which plays a vital role in various stages of drug discovery and development. Several methods have been proposed to enhance the solubility of drugs, and complex formation with cyclodextrins is among them. Beta-cyclodextrin (βCD) is a common excipient for solubilization of drugs. The aim of this study is to develop the mechanistic QSPR models to predict the solubility enhancement of a drug in the presence of βCD. In this study, the solubility enhancement of some drugs in the presence of 10mM βCD at 25°C was experimentally determined or collected from the literature. Two different models to predict the solubilization by βCD were developed by binary logistic regression using structural properties of drugs with more than 80% accuracy. Polar surface area and excess molar refraction are the main parameters for estimating solubilization by βCD. Moreover, other descriptors related to hydrophobicity and the capability of hydrogen bonding formation of molecules could improve the accuracy of the established models., (Published by Elsevier Masson SAS.)

Following the market trends, the consumption of fresh and cold-pressed juice in Europe is increasing. However, a primary concern - particularly in apple juice - is the related outbreaks caused by food-borne pathogens. One of the challenges is to find methods able to reduce pathogenic loads while avoiding deterioration of nutritional properties and bioactive compounds that occur in thermal pasteurization processes. In this study, the inactivation of Escherichia coli, Salmonella enterica and Listeria monocytogenes was evaluated under different ultraviolet C (UVC 254nm ) light treatments (up to 10,665.9 ± 28.1 mJ/cm 2 ), in two different steps of the production chain (before and after juice processing): on apple peel discs and in apple juice. The systems proposed were a horizontal chamber with UVC 254nm emitting lamps treating the product disposed at a distance of 12 cm, and a tank containing UVC 254nm lamps and in which the product is immersed and agitated. Final reductions ranged from 3.3 ± 0.5 to 5.3 ± 0.4 logarithmic units, depending on the microorganism, matrix and used device. The survival curves were adjusted to Weibull and biphasic models (R 2 -adj ≥ 0.852), and UVC doses needed for the first decimal reduction were calculated, being lower for the apple peel discs (0.20 to 83.83 mJ/cm 2 ) than they were for apple juice (174.60 to 1273.31 mJ/cm 2 ), probably for the low transmittance of the apple juice compared to the surface treatment occurring on the peels. Within the treatments evaluated, the UVC 254nm irradiation of apple peels immersed in water was the best option as it resulted in a reduction of the tested microorganisms of ca. 2-3 log units at lower UVC 254nm doses (< 500 mJ/cm 2 ) when compared to those occurring in apple peel treated with the UVC chamber and in juice. As contamination can proceed from apples, the sanitization of these fruit prior to juice production may be helpful in reducing the safety risks of the final product, reducing the drawbacks related to the poor transmittance of the fruit juices., (Copyright © 2022. Published by Elsevier B.V.)

Three-dimensional (3D) culture of organoids from primary cells (wild type) or tumoroids from tumor cells, is used to study the physiological mechanisms in vivo, in order to model normal or tumor tissues more accurately than conventional two-dimensional (2D) culture. The features of this 3D culture, such as the three-dimensional structure, the self-renewal capacity and differentiation are preserved and appropriate to cancer study since their cellular characteristics are very similar to in vivo models. Here, we summarize the recent advances in the rapidly evolving field of organoids and their applications to cancer biology, clinical research and personalized medicine., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: One diagnosis of cystic fibrosis involves measuring the nasal transepithelial potential difference (NPD) as a complementary technique in the forms of the disease, where the sweat test is non-discriminating. The NPD is measured using solutions with and without chlorides, containing a variety of substances whose activities on nasal mucus membranes are studied or assessed. Among the solutions described in the literature and used in specialized centers, none seems to be best adapted for industrial production for reasons of stability (formulas of the international consensus of Rowe et al. and formulas of Knowles et al.) and/or potential toxicity (formulas of Middleton et al.)., Objective(s): Defining new formulas, according to those of the international consensus, with greater physicochemical and microbiological stability., Methods: The reformulation tests were conducted on the formulas of Rowe et al., using CHESS® (CHemical Equilibrium of Species and Surfaces) software for modeling aqueous systems that substantially reduced the number of experiments. CHESS® software was first validated using models of ideal and non-ideal solutions. Thereafter, experimentation was carried out for the sake of comparison with theoretical data., Results: CHESS® software using models of ideal and non-ideal solutions were validated. The experimentation confirmed the theoretical data, and new formulas were assessed based on their physicochemical (pH, content, Osmolality) and microbiological stability., Conclusion: The new formulas defined here guarantee excellent physicochemical and microbiological stability of diagnostic solutions, indispensable criteria for harmonizing and comparing results from different specialized centers using NPD measurements. These new formulas apply to the harmonization approach of techniques for measuring the nasal transepithelial potential difference., (Copyright © 2021 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Sport climbing is increasingly popular and consultations by climbers in hand surgery departments are on the increase. The pathologies related to this sport concern essentially the pulley system, tendons being rarely affected. We report the case of a male climber who presented an atypical rupture of the flexor superficialis tendon in his left middle finger sustained when using an atypical climbing grip technique: the "hook grip". This consists in extension of the metacarpophalangeal joints and maximal flexion of the proximal interphalangeal joints with force exerted only on middle phalanx of the middle finger. A biomechanical analysis using finger musculoskeletal modeling was performed to compare the hook grip to other grips, and the patient's recovery performance was assessed. Adapted functional treatment with physiotherapy seems to have been a good option for the treatment of this atypical lesion since the patient recovered normal use of his finger in daily life. He recovered maximal force in climbing holds. The biomechanical analysis confirmed that the atypical "hook grip" was likely at the origin of the rupture, since flexor digitorum superficialis tendon force for this grip is greater than in other climbing grip techniques. The "hook grip" seems to be dangerous and should be used cautiously by climbers to prevent similar pathology. Additionally, the patient should henceforth be careful when climbing, since the biomechanical model showed that the remaining flexor digitorum profundus tendon was overused., (Copyright © 2021 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

The Sustainable Development Goals (SDGs) encourage nations to substantially increase food production to achieve zero hunger (SDG 2) while preserving life on land (SDG 15). A key question is how to reconcile these potentially competing goals spatially. We use integer linear programming to develop an 'integrated land use planning framework' that identifies the optimal allocation of 17 crops under different hypothetical conservation targets while meeting agricultural demands by 2030. Intensifying existing cropland to maximum yield before allocating new cropland would reduce land requirement by 43% versus cropland expansion without intensification. Even with yield gap closure, tropical and sub-tropical crops still require expansion, primarily allocated to Venezuela, eastern Brazil, Congo Basin, Myanmar and Indonesia. Enforcement of protected areas, via avoiding conversion in 75% of Key Biodiversity Areas and 65% of intact areas, is vital to attain biodiversity targets but bears large opportunity costs, with agricultural rents dropping from $4.1 to $2.8 trillion. Although nationally constrained forest conservation efforts would earn 9% less agricultural rents compared to globally coordinated conservation solutions, they were also able to reduce intact habitat and forest loss (43% and 35% reduction). Our results demonstrate that careful choice of the allocation of future cropland expansion, could dramatically reduce-but not eliminate-the tradeoffs between the SDGs for food production and land biodiversity conservation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Whole-body vibration is a major cause of lower back pain among employees, and the medical and preventive care teams of occupational health departments are often confronted with lower back pain problems among machine operators., Objectives: The objectives of this research are to determine the number of excavator drivers exposed to whole-body vibration levels above 0.5m/s2, identify other exposure factors that may contribute to back pain, and propose corrective measures., Methods: Vibration measurements were carried out on individual excavator drivers while they were observed carrying out working tasks, after which prevention advice is given. Factors which determine vibration levels are logged on to a database., Results: The multivariate analysis of several determining factors shows vibration exposure levels vary depending on the varied work tasks being carried out., Conclusion: This study identifies exposed employees among excavator operators. For each workstation, the determining factors that could explain the high exposures to vibrations are identified. This work shows the important role of tasks on exposure levels. A better adaptation of the tools used to carry out work tasks would allow a decrease in the vibration level of this type of machine.

Purpose: Radiomics are a set of methods used to leverage medical imaging and extract quantitative features that can characterize a patient's phenotype. All modalities can be used with several different software packages. Specific informatics methods can then be used to create meaningful predictive models. In this review, we will explain the major steps of a radiomics analysis pipeline and then present the studies published in the context of radiation therapy., Methods: A literature review was performed on Medline using the search engine PubMed. The search strategy included the search terms "radiotherapy", "radiation oncology" and "radiomics". The search was conducted in July 2019 and reference lists of selected articles were hand searched for relevance to this review., Results: A typical radiomics workflow always includes five steps: imaging and segmenting, data curation and preparation, feature extraction, exploration and selection and finally modeling. In radiation oncology, radiomics studies have been published to explore different clinical outcome in lung (n=5), head and neck (n=5), esophageal (n=3), rectal (n=3), pancreatic (n=2) cancer and brain metastases (n=2). The quality of these retrospective studies is heterogeneous and their results have not been translated to the clinic., Conclusion: Radiomics has a great potential to predict clinical outcome and better personalize treatment. But the field is still young and constantly evolving. Improvement in bias reduction techniques and multicenter studies will hopefully allow more robust and generalizable models., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Our work has been carried out with the aim of providing a solution to decision-making problems encountered in information systems for supply chains in crisis situation. The supply chain represents a competitive advantage that companies seek to perpetuate. It aims to optimize the exchanges, or flows, that the company maintains with its suppliers and its customers. These flows can be of various natures. It can be information flows relating to supplies or product design, financial flows linked to purchases, or even flows of goods. The crisis management logistics is getting more and more attention, especially in the current context of the COVID-19 pandemic. For these systems, where it is never very easy to anticipate the evolution of the environment, the forms of changes undergone are varied and rapid. We aim to provide an answer to these challenges, in an approach that links optimization methods to the paradigm of artificial intelligence. We therefore propose to find mathematical models, and inter-agent cooperation protocols, to minimize the risk of stock shortage in any area of ​​the supply chain., (© 2020 The Author(s). Published by Elsevier B.V.)

Objectives: Hospital-based studies of community-onset bloodstream infections (CO-BSI) are less resource-intensive to carry out than population-based incidence studies. We examined several metrics capturing the potential role of Salmonella Typhi as a cause of CO-BSI for making inferences about incidence., Methods: We systematically reviewed three databases for hospital-based studies of CO-BSI. We determined, by study, the prevalence and rank order of Salmonella among pathogenic bloodstream isolates, and the prevalence ratio of Salmonella Typhi to Escherichia coli (S:E ratio). We then describe these hospital-based study metrics in relation to population-based typhoid fever incidence data from a separate systematic review., Results: Forty-four studies met the inclusion criteria, of which 23 (52.3%) isolated Salmonella Typhi at least once. Among studies isolating Salmonella Typhi, the median (interquartile range) prevalence and rank order of Salmonella Typhi compared to other pathogens isolated in BSI was 8.3% (3.2-37.9%) and 3 (1-6), respectively. The median (interquartile range) S:E ratio was 1.0 (0.4-3.0). With respect to incidence, in Pemba Island, Tanzania, prevalence, rank order, S:E ratio, and incidence was 64.8%, 1, 9.2 and 110 cases per 100 000, respectively, and in Boulkiemdé, Burkina Faso, was 13.3%, 3, 2.3 and 249 cases per 100 000., Conclusions: We describe considerable variation in place and time for Salmonella Typhi prevalence, rank order, and S:E ratio among hospital-based studies of CO-BSI. Data from simultaneous typhoid prevalence and incidence studies are limited. We propose that hospital-based study metrics warrant evaluation for making inference about typhoid incidence and as covariates in typhoid incidence models., (© 2019 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Advances in electroencephalography help identify the epileptic zone. It is now possible to locate the source of abnormalities on the patient's magnetic resonance imaging. For this, high resolution electroencephalogram is required. The software for this type of reconstruction are still being developed. If it is only one tool, research is progressing through simulations., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: The National Lung Screening Trial found that, in a selected population with a high risk of lung cancer, an annual low-dose CT-scan decreased lung cancer mortality by 20% and overall mortality by 7% compared to annual chest X-Ray. In France, a work group stated that individual screening should be considered in this setting. However, the economic impact of an organized and generalized (to all eligible individuals) screening in France was never reported., Methods: This is a modeling study using French population demographic data and published data from randomized screening trials. We used the same selection criteria as NLST: 55-74-year-old smokers for at least 30 pack-years, current smoker or quit less than 15 years. We computed a second model including also 50-54-year-old individuals. Then, we used different participation rates: 65%, 45%, and 32%., Results: According to the considered model, there would be 1,650,588 to 2,283,993 subjects eligible to screening in France. According to the model and participation rate, lung cancer screening would diagnose 3600 to 10,118 stages 1/2 lung cancer each year. There would be 5991 to 16,839 false-positives, of whom 1416 to 3981 would undergo unnecessary surgery. Screening policy would cost 105 to 215 € million per year. However, increasing the price of a cigarette pack by 0.05 to 0.10 € would fully cover the screening costs., Conclusion: Participation rate is a key point for screening impact. Screening could be easily funded by a small increase in cigarette prices., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Chronic kidney disease causes hyperphosphatemia, which is associated with increased cardiovascular risk and mortality. In patients with end-stage renal disease, haemodialysis allows the control of hyperphosphatemia. During a 4-h haemodialysis session, between 600 and 700mg of phosphate are extracted from the plasma, whereas the latter contains only 90mg of inorganic phosphate. The precise origin of phosphates remains unknown. The modelling of phosphorus transfers allows to predict the outcome after changes in dialysis prescription (duration, frequency) with simple two-compartment models and to describe the transfers between the different body compartments with more complex models. Work using 31 P nuclear magnetic resonance spectroscopy performed in animals showed an increase in intracellular phosphate concentration and a decrease in intracellular ATP during a haemodialysis session suggesting an intracellular origin of phosphates., (Copyright © 2017. Published by Elsevier Masson SAS.)

Drug development of new compounds implies to define the dosage as well as the conditions of their use (indication, treatment duration, drug interactions, warnings …). This information requires the identification of the time course response. The decisions made during the clinical phases are now based on mathematical models. These models are continuously described and improved during all phases of the drug development using data collected in healthy volunteers and patients. Their objectives are to describe the most precisely, the link between the compound characteristics (pharmacology), the patient demographics and the effects. Further, the natural history of the disease, the placebo effect and the probability of dropping out will be integrated into the model to optimize the evaluation of the compound. These technical improvements are not only statistical, in the sense that they allow a better understanding of the advantages and pitfalls of the new drug. This article presents these methods used in psychiatry and which will become the new standard of drug evaluation., (© L’Encéphale, Paris, 2016.)

To assess the validity of postexercise measurements in estimating peak oxygen uptake (V̇O2peak) in swimming, we compared oxygen uptake (V̇O2) measurements during supramaximal exercise with various commonly adopted methods, including a recently developed heart rate - V̇O2 modelling procedure. Thirty-one elite swimmers performed a 200-m maximal swim where V̇O2 was measured breath-by-breath using a portable gas analyzer connected to a respiratory snorkel, 1 min before, during, and 3 min postexercise. V̇O2peak(-20-0) was the average of the last 20 s of effort. The following postexercise measures were compared: (i) first 20-s average (V̇O2peak(0-20)); (ii) linear backward extrapolation (BE) of the first 20 s (BE(20)), 30 s, and 3 × 20-, 4 × 20-, and 3 or 4 × 20-s averages; (iii) semilogarithmic BE at 20 s (LOG(20)) and at the other same time intervals as in linear BE; and (iv) predicted V̇O2peak using mathematical modelling (pV̇O2(0-20)]. Repeated-measures ANOVA and post-hoc Bonferroni tests compared V̇O2peak (criterion) and each estimated value. Pearson's coefficient of determination (r(2)) was used to assess correlation. Exercise V̇O2peak(-20-0) (mean ± SD 3531 ± 738 mL·min(-1)) was not different (p > 0.30) from pV̇O2(0-20) (3571 ± 735 mL·min(-1)), BE(20) (3617 ± 708 mL·min(-1)), or LOG(20) (3627 ± 746 mL·min(-1)). pV̇O2(0-20) was very strongly correlated with exercise V̇O2peak (r(2) = 0.962; p < 0.001), and showed a low standard error of the estimate (146 mL·min(-1), 4.1%) and the lowest mean difference (40 mL·min(-1); 1.1%). We confirm that the new modelling procedure based on postexercise V̇O2 and heart rate measurements is a valid and accurate procedure for estimating V̇O2peak in swimmers and avoids the estimation bias produced by other methods.

The role of the families of persons with severe psychiatric disorders (schizophrenia in particular) in the care of their relatives has recently evolved: once seen as pathogenic to be kept at a distance, the family is now recognised by professionals as a partner in the care process. The links between families and psychiatric institutions remain complex and marked by ambivalence and paradoxes., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Amino acid-based fertilisers increase the bioavailability of nitrogen in plants and help withstand stress conditions. Additionally, porcine blood protein hydrolysates are able to supply iron, which is involved in chlorophyll synthesis and improves the availability of nutrients in soil. A high degree of hydrolysis is desirable when producing a protein hydrolysate intended for fertilisation, since it assures a high supply of free amino acids. Given the complexity of enzyme reactions, empirical approaches such as artificial neural networks (ANNs) are preferred for modelisation., Results: Porcine blood meal was hydrolysed for 3 h with subtilisin. The time evolution of the degree of hydrolysis was successfully modelled by means of a feedforward ANN comprising 10 neurons in the hidden layer and trained by the Levenberg-Marquardt algorithm. The ANN model described adequately the influence of pH, temperature, enzyme concentration and reaction time upon the degree of hydrolysis, and was used to estimate the optimal operation conditions (pH 6.67, 56.9 °C, enzyme to substrate ratio of 10 g kg(-1) and 3 h of reaction) leading to the maximum degree of hydrolysis (35.12%)., Conclusions: ANN modelling was a useful tool to model enzymatic reactions and was successfully employed to optimise the degree of hydrolysis., (© 2015 Society of Chemical Industry.)

Background: Few studies have analyzed the cost of treatment of chronic angina pectoris, especially in European countries., Aim: To determine, using a modeling approach, the cost of care in 2012 for 1year of treatment of patients with stable angina, according to four therapeutic options: optimal medical therapy (OMT); percutaneous coronary intervention with bare-metal stent (PCI-BMS); PCI with drug-eluting stent (PCI-DES); and coronary artery bypass graft (CABG)., Methods: Six different clinical scenarios that could occur over 1year were defined: clinical success; recurrence of symptoms without hospitalization; myocardial infarction (MI); subsequent revascularization; death from non-cardiac cause; and cardiac death. The probability of a patient being in one of the six clinical scenarios, according to the therapeutic options used, was determined from a literature search. A direct medical cost for each of the therapeutic options was calculated from the perspective of French statutory health insurance., Results: The annual costs per patient for each strategy, according to their efficacy results, were, in our models, €1567 with OMT, €5908 with PCI-BMS, €6623 with PCI-DES and €16,612 with CABG. These costs were significantly different (P<0.05). A part of these costs was related to management of complications (recurrence of symptoms, MI and death) during the year (between 3% and 38% depending on the therapeutic options studied); this part of the expenditure was lowest with the CABG therapeutic option., Conclusion: OMT appears to be the least costly option, and, if reasonable from a clinical point of view, might achieve appreciable savings in health expenditure., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: In the psychological literature, two concepts are often used to approach psychological and social adaptation: defense mechanisms and coping strategies. Many empirical studies deal with these strategies independently of each other. However, the nature of their relationship is still debated, making empirical studies necessary jointly evaluating these two types of strategies to better reflect the adaptive process., Objective: To test Chabrol and Callahan's theoretical model of the relationship between defence mechanisms and coping strategies. According to theses authors, defence mechanisms and coping strategies are distinct mechanisms, functionally organized: defenses appear first and modulate the emergence of coping strategy defenses through threat representation., Method: Ninety-four young adult volunteers completed the Coping Inventory for Stressful Situations (CISS), the Defense Style Questionnaire (DSQ-40) and the Perceived Stress Scale (PSS14). The data were treated according to the structural equation modeling method., Results: Overall, the results support the theoretical model proposed by Chabrol and Callahan. The statistical model provides a good fit to the data (chi(2)/df=18.62/22=.85, P=.67, RMSEA=.00 (90% CI: .00-.07), CFI=1, TLI=1.04). It explains from 7 to 24% of coping variability scores (Avoidant Coping: R(2)=.07, P<.01; emotional coping and problem-focused coping: R(2)=24, P<.01). Results also show that the relationships between defence mechanisms and copings strategies are mediated by perceived distress and perceived controllability. Defence impact on coping strategies is not the same whether one considers problem-focused coping or emotional and avoidant coping. Immature and mature defences' impact on problem-focused coping is underpinned by a simple mediation: perceived controllability. Defences' impact on emotional coping and avoidant coping is more complex and underpinned by a double mediation: first by the perceived controllability and then, in a second time, the perceived distress. Finally, the results show the existence of a feedback loop from emotional copings to immature defences., Conclusion: It is now clearly relevant for the therapist to simultaneously work on defence mechanisms and coping strategies without assimilating these two categories of processes. Such work involves being able to identify them in their specificities. One of the crucial therapeutic targets is to understand the role of defences on the mental construction of reality in order to maximize adaptive reactions, critical in stress management., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Swimming and training are carried out with wide variability in distances and intensities. However, oxygen uptake kinetics for the intensities seen in swimming has not been reported. The purpose of this study was to assess and compare the oxygen uptake kinetics throughout low-moderate to severe intensities during incremental swimming exercise. We hypothesized that the oxygen uptake kinetic parameters would be affected by swimming intensity. Twenty male trained swimmers completed an incremental protocol of seven 200-m crawl swims to exhaustion (0.05 m·s(-1) increments and 30-s intervals). Oxygen uptake was continuously measured by a portable gas analyzer connected to a respiratory snorkel and valve system. Oxygen uptake kinetics was assessed using a double exponential regression model that yielded both fast and slow components of the response of oxygen uptake to exercise. From low-moderate to severe swimming intensities changes occurred for the first and second oxygen uptake amplitudes (P ≤ 0.04), time constants (P = 0.01), and time delays (P ≤ 0.02). At the heavy and severe intensities, a notable oxygen uptake slow component (>255 mL·min(-1)) occurred in all swimmers. Oxygen uptake kinetics whilst swimming at different intensities offers relevant information regarding cardiorespiratory and metabolic stress that might be useful for appropriate performance diagnosis and training prescription.

Drug manufacturer seeking authorization to bring a newly medicinal compound to the market (Market Authorization Application) have to undertake various studies, each of them providing a specific report. It is however essential to know how to pool results in order to understand the behavior of the drug in all the situations likely to be encountered in clinical practice. The exploitation of these data is now carried out through pharmacometric analyzes which aim at quantifying the exposure and the response of a drug over time. These methods (named "population approach") are based on non-linear mixed effects model and therefore, on the identification of a mathematical model. A first step is to model the variations in concentrations over time by integrating the physio-pathological characteristics of the patients. At this stage, the Bayesian analysis is essential to identify and select the factors of interindividual variability. This pharmacokinetic (PK) modeling allows us to obtain the prescribed dose for each patient, but also their exposure. The second step consists in defining the relationship between exposure and effect: pharmacodynamic (PD) modeling. In psychiatry, the response can be the receptors' occupancy rate or the evolution of a clinical score (BPRS, PANSS…) over time. The final PK-PD model defines the target exposure, that is to say, the concentration values required to achieve maximum effect on the score studied without risking over-exposure. Ultimately, a Monte Carlo simulation will be conducted which will test the expected response for different doses and will facilitate a rational choice in dosage. Assessing the process behind the transition from an oral to a long-acting injectable form of an active ingredient such as aripiprazole can be done by following the same protocol. A 10- to 30-mg per day therapeutic range has thus been identified. The model incorporates all the identified factors of variability of aripiprazole (drug interactions and genetic polymorphism of the P450 2D6 cytochrome) and showed that with an injectable sustained release form, a monthly dose of 400mg would allow 90% of patients to gain exposure in the therapeutic range. In case of a drug inhibition and/or of a slow metabolizing profile, dosage adjustment is necessary., (Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

A model devoted to the modelling of the field evaporation of a tip is presented in this paper. The influence of length scales from the atomic scale to the macroscopic scale is taken into account in this approach. The evolution of the tip shape is modelled at the atomic scale in a three dimensional geometry with cylindrical symmetry. The projection law of ions is determined using a realistic representation of the tip geometry including the presence of electrodes in the surrounding area of the specimen. This realistic modelling gives a direct access to the voltage required to field evaporate, to the evolving magnification in the microscope and to the understanding of reconstruction artefacts when the presence of phases with different evaporation fields and/or different dielectric permittivity constants are modelled. This model has been applied to understand the field evaporation behaviour in bulk dielectric materials. In particular the role of the residual conductivity of dielectric materials is addressed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: Brain growth plays likely an important role for the skull growth. In the fetus, there exists an heterochrony for the growth of supratentorial (forebrain) and infratentorial regions (brainstem and cerebellum). The aim of the study was thus to model geometrically the growth of these two regions and to compare it with the inflection of the base of skull., Material and Methods: Brain growth measurements were performed from midsagittal photographs of fetal brains obtained from an Anatomical Atlas over a period from 10 to 40 amenorrhea weeks (AW). After countouring and pointing anatomical and geometrical landmarks, we have developed a linear growth model based on principal component analysis (PCA). Besides, the variation of the sphenoidal and clivo-foraminal angles was studied from anatomical midsagittal slices of fetal heads sampled over a period from 16 to 39 AW., Results: The PCA model brings to light the radial expansion of the forebrain growth (first component) associated with an inferior and posterior rotation of the occipital lobe. The growth of the infratentoriel region presents an inferior and posterior expansion associated with a second component corresponding to inferior and anterior expansions. From the 17 AW, appears an heterochrony between the supra- and infratentorial growths and an inversion of the ratio between the infra- and supratentorial dimensions after 30 AW. The sphenoidal and clivo-foraminal angles decrease slightly until 25 AW, and then increase quickly until the 39 AW., Conclusions: The growth of brain is accompanied by morphological change between the compartments supra- and infratentoriel but also on the level of the base of skull. The possible interactions will be discussed., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

The aim of this work, undertaken in the framework of QWeCI (Quantifying Weather and Climate Impacts on health in the developing countries) project, is to study how climate variability could influence malaria seasonal incidence. It will also assess the evolution of vector-borne diseases such as malaria by simulation analysis of climate models according to various climate scenarios for the next years. Climate variability seems to be determinant for the risk of malaria development (Freeman and Bradley, 1996 [1], Lindsay and Birley, 1996 [2], Kuhn et al., 2005 [3]). Climate can impact on the epidemiology of malaria by several mechanisms, directly, via the development rates and survival of both pathogens and vectors, and indirectly, through changes in vegetation and land surface characteristics such as the variability of breeding sites like ponds., (Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.)