Should anti-malarial chemoprophylaxis be reimbursed in France? A cost-effectiveness analysis of different reimbursement strategies.

OBJECTIVES: France is the Western country with the highest number of imported malaria cases. This study evaluates the cost and effectiveness of the potential reimbursement of drugs for malaria chemoprophylaxis (CP). It targets travelers with medical insurance in France who are heading to endemic regions in sub-Saharan Africa (SSA), the cost of which is currently fully borne by these travelers. PATIENTS AND METHODS: A decision-tree model was built to assess the cost-effectiveness of three CP reimbursement strategies compared to the current strategy of non-reimbursement from the French National Health Insurance (NHI) perspective. The three strategies targeted either (1) all travelers to SSA (2) travelers of African origin traveling to visit friends and relatives (VFR) and (3) all travelers to West and Central Africa (WCA). Base-case analysis is complemented with deterministic and probabilistic sensitivity analyses (PSA). RESULTS: Reimbursement of CP would lead to a decrease in malaria cases. The base-case incremental cost per additional malaria case prevented (ICER) for strategies 1, 2 and 3 is estimated at € 34,623, € 15,136 and € 23,640, respectively. PSA confirms our results, showing that reimbursement has a very high probability of being cost-effective, especially under strategies 2 and 3. CONCLUSION: Reimbursement of malaria CP by the French NHI could be cost-effective and have a positive effect on malaria prevention in France. Restricting reimbursement to VFRs allows lower ICERs but does not seem feasible in the current French context, while targeting travelers to WCA, who are at higher risk for malaria, could be a reasonably efficient policy.

Reference microarchitectural values measured by HR-pQCT in a Franco-Swiss cohort of young adult women.

Bone microarchitecture assessed by high-resolution peripheral quantitative computed tomography varies across populations of different origin. The study presents a reference dataset of microarchitectural parameters in a homogeneous group of participants aged within 22-27 range determined by a discriminant analysis of a larger cross-sectional cohort of 339 women. INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) non-invasively measures three-dimensional bone microarchitectural parameters and volumetric bone mineral density. Previous studies established normative reference HR-pQCT datasets for several populations, but there were few data assessed in a reference group of young women with Caucasian ethnicity living in Western Europe. It is important to obtain different specific reference dataset for a valid interpretation of cortical and trabecular microarchitecture data. The aim of our study was to find the population with the most optimal bone status in order to establish a descriptive reference HR-pQCT dataset in a young and healthy normal-weight female cohort living in a European area including Geneva, Switzerland, Lyon and Saint-Etienne, France. METHODS: We constituted a cross-sectional cohort of 339 women aged 19-41 years with a BMI > 18 and < 30 kg/m2. All participants had HR-pQCT measurements at both non-dominant distal radius and tibia sites. RESULTS: We observed that microarchitectural parameters begin to decline before the age of 30 years. Based on a discriminant analysis, the optimal bone profile in this population was observed between the age range of 22 to 27 years. Consequently, we considered 43 participants aged 22-27 years to establish a reference dataset with median values and percentiles. CONCLUSION: This is the first study providing reference values of HR-pQCT measurements considering specific age bounds in a Franco-Swiss female cohort at the distal radius and tibia sites.

[First-line screening guidelines for renal stone disease patients: a CLAFU update]. / Bilan métabolique et prise en charge médicale de la lithiase: une mise au point du CLAFU.

This text summarizes the CLAFU first-line screening guidelines for renal stone disease patients. We have focused on the useful information provided by renal stone analysis and also the identification of relevant stone risk factors detected in a 24-hour urine collection. Indeed, evaluation of water, sodium and protein intake may be easily achieved in a current clinical setting and allows a useful pedagogic tool for patients' advices and follow-up: daily diuresis above 2000 mL, calcium intake between 800 mg and 1 g/day, a moderate daily sodium and proteins restricted diet (<9 g and <1.2 g/kg per day respectively). General therapeutical principles are reviewed, including circumstances requiring specialized management.

Dinuclear vs. mononuclear complexes: accelerated, metal-dependent ring-opening polymerization of lactide.

Dinuclear complexes of aluminum and indium with a bis(phenoxy-imine) platform have been synthesized and used in the polymerization of lactide. Kinetic studies demonstrate that the dialuminum precursor provides a more favorable reaction pathway in terms of activation free energy than that of directly related monoaluminum systems. No similar trend is observed with the corresponding diindium-monoindium systems, which is attributed to a dissimilar ROP mechanism.

How do children acquire early grammar and build multiword utterances? A corpus study of French children aged 2 to 4.

In the last 50 years, researchers have debated over the lexical or grammatical nature of children's early multiword utterances. Due to methodological limitations, the issue remains controversial. This corpus study explores the effect of grammatical, lexical, and pragmatic categories on mean length of utterances (MLU). A total of 312 speech samples from high-low socioeconomic status (SES) French-speaking children aged 2-4 years were annotated with a part-of-speech-tagger. Multiple regression analyses show that grammatical categories, particularly the most frequent subcategories, were the best predictors of MLU both across age and SES groups. These findings support the view that early language learning is guided by grammatical rather than by lexical words. This corpus research design can be used for future cross-linguistic and cross-pathology studies.

Extracting survival parameters from isothermal, isobaric, and "iso-concentration" inactivation experiments by the "3 end points method".

Theoretically, if an organism's resistance can be characterized by 3 survival parameters, they can be found by solving 3 simultaneous equations that relate the final survival ratio to the lethal agent's intensity. (For 2 resistance parameters, 2 equations will suffice.) In practice, the inevitable experimental scatter would distort the results of such a calculation or render the method unworkable. Averaging the results obtained with more than 3 final survival ratio triplet combinations, determined in four or more treatments, can remove this impediment. This can be confirmed by the ability of a kinetic inactivation model derived from the averaged parameters to predict survival patterns under conditions not employed in their determination, as demonstrated with published isothermal survival data of Clostridium botulinum spores, isobaric data of Escherichia coli under HPP, and Pseudomonas exposed to hydrogen peroxide. Both the method and the underlying assumption that the inactivation followed a Weibull-Log logistic (WeLL) kinetics were confirmed in this way, indicating that when an appropriate survival model is available, it is possible to predict the entire inactivation curves from several experimental final survival ratios alone. Where applicable, the method could simplify the experimental procedure and lower the cost of microbial resistance determinations. In principle, the methodology can be extended to deteriorative chemical reactions if they too can be characterized by 2 or 3 kinetic parameters.

Perturbative theory and modeling of electronic-resonance-enhanced coherent anti-Stokes Raman scattering spectroscopy of nitric oxide.

A theory is developed for three-laser electronic-resonance-enhanced (ERE) coherent anti-Stokes Raman scattering (CARS) spectroscopy of nitric oxide (NO). A vibrational Q-branch Raman polarization is excited in the NO molecule by the frequency difference between visible Raman pump and Stokes beams. An ultraviolet probe beam is scattered from the induced Raman polarization to produce an ultraviolet ERE-CARS signal. The frequency of the ultraviolet probe beam is selected to be in electronic resonance with rotational transitions in the A (2)Sigma(+)<--X (2)Pi (1,0) band of NO. This choice results in a resonance between the frequency of the ERE-CARS signal and transitions in the (0,0) band. The theoretical model for ERE-CARS NO spectra has been developed in the perturbative limit. Comparisons to experimental spectra are presented where either the probe laser was scanned with fixed Stokes frequency or the Stokes laser was scanned with fixed probe frequency. At atmospheric pressure and an NO concentration of 100 ppm, good agreement is found between theoretical and experimental spectral peak locations and relative intensities for both types of spectra. Factors relating to saturation in the experiments are discussed, including implications for the theoretical predictions.

Two-color planar laser-induced fluorescence thermometry in aqueous solutions.

We demonstrate a two-color planar laser-induced fluorescence technique for obtaining two-dimensional temperature images in water. For this method, a pulsed Nd:YAG laser at 532 nm excites a solution of temperature-sensitive rhodamine 560 and temperature-insensitive sulforhodamine 640. The resulting emissions are optically separated through filters and detected via a charged-couple device (CCD) camera system. A ratio of the two images yields temperature images independent of incident irradiance. An uncertainty in temperature of +/- 1.4 degrees C is established at the 95% confidence interval.

Two-point time-series measurementsof hydroxyl concentration in a turbulent nonpremixed flame.

Quantitative two-point hydroxyl time-series measurements have been performed in a turbulent nonpremixed flame by using two-point picosecond time-resolved laser-induced fluorescence. The current diagnostic system has been improved from its preliminary version to address optical aberrations and fluorescence lifetime fluctuations. In particular, with a newly designed collection system, the aberration-limited blur spot is reduced from 6 mm to 180 microm. Additional photon-counting channels enable the recovery of absolute OH concentrations through a triple-bin integration method. The present research represents what we believe to be the first application of this two-point technique to turbulent flames. Two independent schemes have been applied to remove uncorrelated noise in the derived two-point statistics. We show that optical aberrations can have a significant effect on space-time correlations. However, the sampling rate and fluctuations in the fluorescence lifetime barely affect the spatial autocorrelation function and thus the integral length scale. Such length scales for hydroxyl are found to rise linearly with increasing axial distance at peak [OH] locations. Along the jet centerline, the integral length scale varies slightly below the flame tip but increases rapidly above the flame tip. In addition, the OH length scale demonstrates the same trend as the OH time scale along the jet centerline, but the opposite trend at peak [OH] locations.

Measurement of nitric oxide concentrations in flames by using electronic-resonance-enhanced coherent anti-Stokes Raman scattering.

We have measured nitric oxide (NO) concentrations in flames by using electronic-resonance-enhanced coherent anti-Stokes Raman spectroscopy (ERE-CARS). Visible pump and Stokes beams were tuned to a Q-branch vibrational Raman resonance of NO. A UV probe beam was tuned into resonance with specific rotational transitions in the (v"=1,v'=0) vibrational band in the A(2)Sigma(+)-X(2)Pi electronic transition, thus providing a substantial electronic-resonance enhancement of the resulting CARS signal. NO concentrations were measured at levels down to 50 parts in 10(6) in H(2)/air flames at atmospheric pressure. NO was also detected in heavily sooting C(2)H(2)/air flames at atmospheric pressure with minimal background interference.

Microsatellite profile in hormonal receptor genes associated with breast cancer.

Given that breast cancer is depending on multiple hormonal influences, the nuclear receptors, estrogen receptor alpha, estrogen receptor beta and androgen receptor, are candidates for cancer susceptibility markers. We conducted an association study in a case-control population (139 cases and 145 controls) by genotyping three potentially functional microsatellites (TA)n, (CA)n and (CAG)n in the ERa, ERb and AR genes respectively. For (CAG)n polymorphism, a significant difference was observed using a cut-off 15 repeats CAG between genotypes short-short/short-long/long-long in cases and control subjects (p = 0.009) and also between the distribution of short/long allele in the two groups of individuals (p = 0.001). Genotypes comprising one or two short (CAG)n sequences had higher risk of breast cancer compared to genotypes with two long allele (odds ratio = 1,93; confidence interval = 1.05-3.55; p = 0.03). No significant difference was observed in allele frequency or in short/long allele percentage for (CA)n or (TA)n polymorphism (cut-off 22 CA and 19 TA repeats), neither in genotype frequencies (short-short, short-long or long-long). When the three microsatellite genotype were taken in analysis, the profile short CA-long TA-short CAG could clearly discriminate between cases and controls (p = 0.006). Also, this combined genotype profile has greater predictive values for breast cancer than (CAG)n genotype alone (predictive positive value 57,1% versus 53,7% and predictive negative value 53% versus 23% respectively). Our results sustain a polygenic model of breast cancer with gene-gene interactions; combined effects of three low-risk polymorphisms conferred significant genetic predisposition. Genotyping hormonal receptor genes ERa, ERb and AR could be a useful genetic marker for defining disease risk.

Two-point time-series measurements of minor-species concentrations in a turbulent nonpremixed flame.

We report a technique that is capable of making simultaneous two-point time-series measurements of minor-species concentrations in turbulent flames. The experimental setup, which incorporates picosecond time-resolved laser-induced fluorescence, has a spatial resolution of less than 250 microm and a temporal resolution of less than 100 micros, which spatially and temporally resolve microscales in many turbulent flows. Two-point time-series data are given for a standard turbulent nonpremixed flame at Re= 10,000, including a discussion of potential implications.

Generating microbial survival curves during thermal processing in real time.

AIMS: To develop a method to calculate and record theoretical microbial survival curves during thermal processing of foods and pharmaceutical products simultaneously with the changing temperature. Moreover, to demonstrate that the method can be used to calculate nonisothermal survival curves, with widely available software such as Microsoft Excel. METHODS AND RESULTS: It has been assumed that the targeted organism's isothermal survival curves are not log linear and hence, the inactivation rate in nonisothermal processes is a function of the momentary temperature and the corresponding survival ratio. This could be expressed by a difference equation, which is an approximation to the continuous rate model. The concept was tested with the isothermal survival parameters of Clostridium botulinum and Bacillus sporothermodurans spores, and Salmonella enteritidis cells, using different kinds of survival models and under temperature profiles resembling those of commercial processes. As expected, there was an excellent agreement between the curves produced by solving the differential equation of the continuous model and by the incremental method, which has been posted on the web as freeware. CONCLUSIONS: It is possible to calculate nonisothermal survival curves, in real time, with an algorithm that can be written in the language of general purpose software, to follow the inactivation of one or more targeted organisms simultaneously and to simulate microbial survival patterns under existing or planned industrial thermal processes. SIGNIFICANCE AND IMPACT OF THE STUDY: Replacement of the traditional 'F0-value', which requires the log linearity of the organism's isothermal survival curves, by the more realistic theoretical survival ratio estimate as a measure of the thermal process efficacy.

Measurements of absolute CH concentrations by cavity ring-down spectroscopy and linear laser-induced fluorescence in laminar, counterflow partially premixed and nonpremixed flames at atmospheric pressure.

We report quantitative, spatially resolved measurements of methylidyne concentration ([CH]) in laminar, counterflow partially premixed and nonpremixed flames at atmospheric pressure by using both cavity ring-down spectroscopy (CRDS) and linear laser-induced fluorescence (LIF) in the A-X (0, 0) band. Three partially premixed (phiB = 1.45, 1.6, 2.0) flames plus a single nonpremixed methane-air flame are investigated at a global strain rate of 20 s(-1). These quantitative measurements are compared with predictions from an opposed-flow flame code when utilizing two GRI chemical kinetic mechanisms (versions 2.11 and 3.0). The LIF measurements of [CH] are corrected for variations in the electronic quenching rate coefficient by using predicted major species concentrations and temperatures along with quenching cross sections for CH that are available in the literature. The peak CH concentration obtained by CRDS is used to calibrate the quenching-corrected LIF measurements. Excellent agreement is obtained between CH concentration profiles measured by using the CRDS and LIF techniques. The spatial location of the CH layer is very well predicted by GRI 3.0; moreover, the measured and predicted CH concentrations are in good agreement for all the flames of this study.

Productivity of lexical categories in French-speaking children with cochlear implants.

The productivity of lexical categories was studied longitudinally in a sample of 17 young hearing-impaired French-speaking children with cochlear implants. Age of implantation ranged from 22 months to 76 months. Spontaneous speech samples were collected at six-month intervals over a period of 36 months, starting at the one-word stage. Four general measures of their linguistic production (number of utterances, verbal fluency, vocabulary, and grammatical production) as well as 36 specific lexical categories, according to the CHILDES codes, were computed in terms of tokens, i.e., total number of words. Cochlear-implanted children (CI) were compared to a French database of normally hearing children aged 2-4 compiled by the first author. Follow-up results indicate that, at the two-year post-implantation follow-up, noun, and verb morphology was significantly impaired. At the three-year follow-up, the cochlear-implanted group had recovered on adjectives, determiners and nouns, main verbs, and auxiliaries. The two groups differed significantly in processing locative adverbs, prepositions, pronouns, and verbs (infinitive verb, modal, and modal lexical), but individual variability within the cochlear-implanted group was substantial. Results are discussed in terms of recovery and developmental trends and variability in the acquisition of lexical categories by French children two years and three years post-implantation.

A model of microbial contamination of a water reservoir.

A three year record of daily fecal coliform counts in a Massachusetts water reservoir has the appearance of an irregular time series punctuated by outbursts of varying duration. The pattern is described in terms of a probabilistic model where the fluctuations in the 'regular' and 'explosive' regimes are governed by two sets of probabilities. It has been assumed that the random oscillations has a lognormal distribution, and that once an explosion threshold has been exceeded the increments or decrements in the population size have fixed probability distributions. The threshold for triggering an outburst was estimated by examining the randomness of the autocorrelation function of the record after it is filtered to eliminate peaks of progressively increasing magnitude. Once the threshold has been identified, the mean and standard deviation of the underlying lognormal distribution could be estimated directly from remains found in the record after all the peaks were removed. The probabilities of an increment and decrement during the outbursts and their relative magnitudes could also be estimated using simple formulas. These estimated parameter values were then used to generate realistic records with known threshold levels, which were subsequently used to assess the procedure's feasibility and sensitivity.

Postcesarean infection.

In 1998, 20.2% of the approximately 4 million births in the United States occurred via cesarean delivery. Routine antibiotic prophylaxis has significantly reduced morbidity, yet each year between 41,000 and 206,000 women develop a subsequent infection of the uterus or surgical incision. A thorough understanding of the pathophysiology and complex interaction of risk factors for metritis and wound infection is vital for perinatal nurses. Nurses have a critical role in the identification and treatment of postcesarean infection.

Language evolution in children with cochlear implants.

The capacity to incorporate significant words into the existing vocabulary and to use these words to form sentences with more mature syntactic structures emerges over a considerable time course in young deaf children who have undergone a cochlear implantation. The purpose of this follow-up study is to document the nature and time span of language production--in morphosyntactic and lexical skills--when a child's first experience with language sounds is provided artificially through electrical stimulation. To examine the development of these two aspects of linguistic processing, five deaf French children, all enrolled in similar postimplantation educational settings, were individually assessed at 6-month intervals over a period of 18 months. Computerized analyses were derived from their spontaneous speech in a 20-min standardized play session. Results for mean length of utterance and vocabulary revealed gradually improving performance for most children, in spite of the generally low starting point. Both measures of production nevertheless remained well below the norms established for normally hearing children. Although the achievement of higher production scores, which underlies more effective interpersonal exchanges, is evident after only 1 year of device use, it is clear that improvement does not always occur at the same pace, as shown by two of the children. This emphasizes the importance of longitudinal studies in documenting intersubject variability and intrasubject stability throughout the experience with an implant.

Acquisition of lexical morphology in simple partial epilepsy.

In the study of language acquisition following early brain damage, results have been divergent. On one hand, some studies claim that language eventually resumes to normal, whereas, on the other hand, studies show lasting deficits throughout development. Discrepancies in the results could arise from different etiologies and tests used. This study attempts to determine the extent to which the development of verb production is affected in later development in children who had simple partial epilepsy (SPE). Measures of diversity and fluency of three verb types, namely main verbs, auxiliary and copula verbs, and nonfinite verbs were used on three children diagnosed as SPE and compared to control groups. Our main results show a limited production of auxiliary verbs. Further analysis of their productions suggest a telegraphic style of speech, as reflected by a superior production of nonfinite verb type compared with normal children. These findings are interpreted as reflecting long-lasting consequences of early brain damage with respect to language development.