"INTERMED": a method to assess health service needs. I. Development and reliability.

The purpose of this paper is to describe the development and to test the reliability of a new method called INTERMED, for health service needs assessment. The INTERMED integrates the biopsychosocial aspects of disease and the relationship between patient and health care system in a comprehensive scheme and reflects an operationalized conceptual approach to case mix or case complexity. The method is developed to enhance interdisciplinary communication between (para-) medical specialists and to provide a method to describe case complexity for clinical, scientific, and educational purposes. First, a feasibility study (N = 21 patients) was conducted which included double scoring and discussion of the results. This led to a version of the instrument on which two interrater reliability studies were performed. In study 1, the INTERMED was double scored for 14 patients admitted to an internal ward by a psychiatrist and an internist on the basis of a joint interview conducted by both. In study 2, on the basis of medical charts, two clinicians separately double scored the INTERMED in 16 patients referred to the outpatient psychiatric consultation service. Averaged over both studies, in 94.2% of all ratings there was no important difference between the raters (more than 1 point difference). As a research interview, it takes about 20 minutes; as part of the whole process of history taking it takes about 15 minutes. In both studies, improvements were suggested by the results. Analyses of study 1 revealed that on most items there was considerable agreement; some items were improved. Also, the reference point for the prognoses was changed so that it reflected both short- and long-term prognoses. Analyses of study 2 showed that in this setting, less agreement between the raters was obtained due to the fact that the raters were less experienced and the scoring procedure was more susceptible to differences. Some improvements--mainly of the anchor points--were specified which may further enhance interrater reliability. The INTERMED proves to be a reliable method for classifying patients' care needs, especially when used by experienced raters scoring by patient interview. It can be a useful tool in assessing patients' care needs, as well as the level of needed adjustment between general and mental health service delivery. The INTERMED is easily applicable in the clinical setting at low time-costs.

Designing phase III or IV trials for vaccines: choosing between individual or cluster randomised trial designs.

The choice of design between individual randomisation, cluster or pseudo-cluster randomisation is often made difficult. Clear methodological guidelines have been given for trials in general practice, but not for vaccine trials. This article proposes a decisional flow-chart to choose the most adapted design for evaluating the effectiveness of a vaccine in large-scale studies. Six criteria have been identified: importance of herd immunity or herd protection, ability to delimit epidemiological units, homogeneity of transmission probability across sub-populations, population's acceptability of randomisation, availability of logistical resources, and estimated sample size. This easy to use decisional method could help sponsors, trial steering committees and ethical committees adopt the most suitable design.

Geographic variation in sex-chromosome differentiation in the common frog (Rana temporaria).

In sharp contrast with birds and mammals, sex-determination systems in ectothermic vertebrates are often highly dynamic and sometimes multifactorial. Both environmental and genetic effects have been documented in common frogs (Rana temporaria). One genetic linkage group, mapping to the largest pair of chromosomes and harbouring the candidate sex-determining gene Dmrt1, associates with sex in several populations throughout Europe, but association varies both within and among populations. Here, we show that sex association at this linkage group differs among populations along a 1500-km transect across Sweden. Genetic differentiation between sexes is strongest (FST  = 0.152) in a northern-boreal population, where male-specific alleles and heterozygote excesses (FIS  = -0.418 in males, +0.025 in females) testify to a male-heterogametic system and lack of X-Y recombination. In the southernmost population (nemoral climate), in contrast, sexes share the same alleles at the same frequencies (FST  = 0.007 between sexes), suggesting unrestricted recombination. Other populations show intermediate levels of sex differentiation, with males falling in two categories: some cluster with females, while others display male-specific Y haplotypes. This polymorphism may result from differences between populations in the patterns of X-Y recombination, co-option of an alternative sex-chromosome pair, or a mixed sex-determination system where maleness is controlled either by genes or by environment depending on populations or families. We propose approaches to test among these alternative models, to disentangle the effects of climate and phylogeography on the latitudinal trend, and to sort out how this polymorphism relates to the 'sexual races' described in common frogs in the 1930s.

Evolution of intraspecific variation : a comparative phylogenetic approach

Understanding the evolution of intraspecific variance is a major research question in evolutionary biology. While its importance to processes operating at individual and population levels is well-documented, much less is known about its role in macroevolutionary patterns. Nevertheless, both experimental and theoretical evidence suggest that the intraspecific variance is susceptible to selection, can transform into interspecific variation and, therefore, is crucial for macroevolutionary processes. The main objectives of this thesis were: (l) to investigate which factors impact evolution of intraspecific variation in Polygonaceae and determine if evolution of intraspecific variation influences species diversification; and (2) to develop a novel comparative phylogenetic method to model evolution of intraspecific variation. Using the buckwheat family, Polygonaceae, as a study system, I demonstrated which life-history and ecological traits are relevant to the evolution of intraspecific variation. I analyzed how differential intraspecific variation drives species diversification patterns. I showed with computer simulations the shortcomings of existing comparative methods with respect to intraspecific variation. I developed a novel comparative model that readily incorporates the intraspecific variance into phylogenetic comparative methods. The obtained results are complimentary, because they affect both empirical and methodological aspects of comparative analysis. Overall, I highlight that intraspecific variation is an important contributor to the macroevolutionary patterns and it should be explicitly considered in the comparative phylogenetic analysis. - En biologie évolutive comprendre l'évolution de la variance intraspécifique est un axe de recherche majeur. Bien que l'importance de cette variation soit bien documentée au niveau individuel et populationnel, on en sait beaucoup moins sur son rôle au niveau macroévolutif. Néanmoins, des preuves expérimentales et théoriques suggèrent que la variance intraspécifique est sensible à la sélection et peut se transformer en variation interspécifique. Par conséquent, elle est cruciale pour mieux comprendre les processus macroévolutifs. Les principaux objectifs de ma thèse étaient : (i) d'enquêter sur les facteurs qui affectent l'évolution de la variation intraspécifique chez les Polygonaceae et de déterminer si l'évolution de cette dernière influence la diversification des espèces, et (2) de développer une nouvelle méthode comparative permettant de modéliser l'évolution de la variation intraspécifique dans un cadre phylogénétique. En utilisant comme système d'étude la famille du sarrasin, les Polygonacées, je démontre que les traits d'histoire de vie sont pertinents pour comprendre l'évolution de la variation intraspécifique. J'ai également analysé l'influence de la variation intraspécifique au niveau de la diversification des espèces. J'ai ensuite démontré avec des données simulées les limites des méthodes comparatives existantes vis à vis de la variation intraspécifique. Finalement, j'ai développé un modèle comparatif qui intègre facilement la variance intraspécifique dans les méthodes comparatives phylogénétiques existantes. Les résultats obtenus lors de ma thèse sont complémentaires car ils abordent aspects empiriques et méthodologiques de l'analyse comparative. En conclusion, je souligne que la variation intraspécifique est un facteur important en macroévolution et qu'elle doit être explicitement considérée lors d'analyses comparatives phylogénétiques.

A new alternative method for testing skin irritation using a human skin model: a pilot study.

Studies assessing skin irritation to chemicals have traditionally used laboratory animals; however, such methods are questionable regarding their relevance for humans. New in vitro methods have been validated, such as the reconstructed human epidermis (RHE) model (Episkin®, Epiderm®). The comparison (accuracy) with in vivo results such as the 4-h human patch test (HPT) is 76% at best (Epiderm®). There is a need to develop an in vitro method that better simulates the anatomo-pathological changes encountered in vivo. To develop an in vitro method to determine skin irritation using human viable skin through histopathology, and compare the results of 4 tested substances to the main in vitro methods and in vivo animal method (Draize test). Human skin removed during surgery was dermatomed and mounted on an in vitro flow-through diffusion cell system. Ten chemicals with known non-irritant (heptylbutyrate, hexylsalicylate, butylmethacrylate, isoproturon, bentazon, DEHP and methylisothiazolinone (MI)) and irritant properties (folpet, 1-bromohexane and methylchloroisothiazolinone (MCI/MI)), a negative control (sodiumchloride) and a positive control (sodiumlaurylsulphate) were applied. The skin was exposed at least for 4h. Histopathology was performed to investigate irritation signs (spongiosis, necrosis, vacuolization). We obtained 100% accuracy with the HPT model; 75% with the RHE models and 50% with the Draize test for 4 tested substances. The coefficients of variation (CV) between our three test batches were <0.1, showing good reproducibility. Furthermore, we reported objectively histopathological irritation signs (irritation scale): strong (folpet), significant (1-bromohexane), slight (MCI/MI at 750/250ppm) and none (isoproturon, bentazon, DEHP and MI). This new in vitro test method presented effective results for the tested chemicals. It should be further validated using a greater number of substances; and tested in different laboratories in order to suitably evaluate reproducibility.

Seasonal and spatial species richness variation of dung beetle (Coleoptera, Scarabaeidae s. str.) in the Atlantic Forest of southeastern Brazil

The knowledge on Atlantic Forest scarab beetle fauna is quite limited. This biome is strongly degraded and these insects can be used as bioindicators since they are sensitive to forest destruction and show distinct organizational patterns in forest fragments or in areas that have been deteriorated by human activity. Thus, a study of the Scarabaeidae (sensu stricto) dung beetles fauna that inhabit Serra do Japi, São Paulo, Brazil (23º12'-23º22' S and 46º53'-47º03'W) was carried out; the monthly species richness was analyzed in six areas during one year and the vegetation's structural physiognomy was described. The areas included a conserved and a degraded valley, a northward and a southward hillside, a hilltop, and an area of secondary forest growing under eucalyptus trees. The specimens were collected using four pitfall traps baited with human feces, which remained at each spot during 48 hours. Between September, 1997 and August, 1998, 3524 individuals of 39 species were collected; the most abundant were: Canthidium trinodosum, Eurysternus cyanescens, Uroxys kratochvili, Scybalocanthon nigriceps, Uroxys lata, Canthonella sp., Dichotomius assifer, Deltochilum furcatum, Canthidium sp.2, Canthon latipes, Deltochilum rubripenne, Eurysternus sp., and Dichotomius sp.1. The number of individuals and species was greater in the hot, rainy season, when there was a correlation between the number of species and the mean annual temperature [r²= 0.69; p<0.01]. The lower winter richness was most pronounced in the conserved valley, while richness remained relatively constant in the degraded valley; abundance was much higher in the degraded valley. The cluster analysis showed that the valleys and hillsides are the most similar in relation to species composition and abundance, yet different from the secondary forest with eucalypts and the hilltop.

Evaluation of oviposition traps as an entomological surveillance method for Aedes aegypti (Diptera, Culicidae)

This study aimed to describe the behavior of oviposition traps for Aedes aegypti over time, to compare it with the larval survey and to investigate the association with climatic variables. It was conducted in São José do Rio Preto city, São Paulo. Daily climatic data and fortnightly measurements for oviposition traps and larval infestation were collected from October 2003 to September 2004. Three different periods were identified in the behavior of oviposition traps' positivity and mean number of eggs: increase, plateau and decrease in values. These measurements followed the variation of climatic data from the first and third periods. High correlation was obtained between the positivity and the mean number of eggs. The oviposition traps showed higher capacity to detect the vector than did larval survey. It was observed that the first (October to December) and third (May to September) periods were considered to be the most suitable to use oviposition traps than larval surveys.

Geographical and temporal body size variation in a reptile: roles of sex, ecology, phylogeny and ecology structured in phylogeny.

Geographical body size variation has long interested evolutionary biologists, and a range of mechanisms have been proposed to explain the observed patterns. It is considered to be more puzzling in ectotherms than in endotherms, and integrative approaches are necessary for testing non-exclusive alternative mechanisms. Using lacertid lizards as a model, we adopted an integrative approach, testing different hypotheses for both sexes while incorporating temporal, spatial, and phylogenetic autocorrelation at the individual level. We used data on the Spanish Sand Racer species group from a field survey to disentangle different sources of body size variation through environmental and individual genetic data, while accounting for temporal and spatial autocorrelation. A variation partitioning method was applied to separate independent and shared components of ecology and phylogeny, and estimated their significance. Then, we fed-back our models by controlling for relevant independent components. The pattern was consistent with the geographical Bergmann's cline and the experimental temperature-size rule: adults were larger at lower temperatures (and/or higher elevations). This result was confirmed with additional multi-year independent data-set derived from the literature. Variation partitioning showed no sex differences in phylogenetic inertia but showed sex differences in the independent component of ecology; primarily due to growth differences. Interestingly, only after controlling for independent components did primary productivity also emerge as an important predictor explaining size variation in both sexes. This study highlights the importance of integrating individual-based genetic information, relevant ecological parameters, and temporal and spatial autocorrelation in sex-specific models to detect potentially important hidden effects. Our individual-based approach devoted to extract and control for independent components was useful to reveal hidden effects linked with alternative non-exclusive hypothesis, such as those of primary productivity. Also, including measurement date allowed disentangling and controlling for short-term temporal autocorrelation reflecting sex-specific growth plasticity.

Common genetic variation and the control of HIV-1 in humans.

To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians.

Photometric and Spectroscopic Observations of the Cluster of Galaxies Abell 2390

Spectroscopic and photometric observations in a 6 arcmin x 6 arcmin field centered on the rich cluster of galaxies Abell 2390 are presented. The photometry concerns 700 objects and the spectroscopy 72 objects. The redshift survey shows that the mean redshift of the cluster is 0.232. An original method for automatic determination of the spectral type of galaxies is presented.

Genetic diversity and ecological success of Staphylococcus aureus strains colonizing humans.

The genetic determinants and phenotypic traits which make a Staphylococcus aureus strain a successful colonizer are largely unknown. The genetic diversity and population structure of 133 S. aureus isolates from healthy, generally risk-free adult carriers were investigated using four different typing methods: multilocus sequence typing (MLST), amplified fragment length polymorphism analysis (AFLP), double-locus sequence typing (DLST), and spa typing were compared. Carriage isolates displayed great genetic diversity which could only be revealed fully by DLST. Results of AFLP and MLST were highly concordant in the delineation of genotypic clusters of closely related isolates, roughly equivalent to clonal complexes. spa typing and DLST provided considerably less phylogenetic information. The resolution of spa typing was similar to that of AFLP and inferior to that of DLST. AFLP proved to be the most universal method, combining a phylogeny-building capacity similar to that of MLST with a much higher resolution. However, it had a lower reproducibility than sequencing-based MLST, DLST, and spa typing. We found two cases of methicillin-resistant S. aureus colonization, both of which were most likely associated with employment at a health service. Of 21 genotypic clusters detected, 2 were most prevalent: cluster 45 and cluster 30 each colonized 24% of the carrier population. The number of bacteria found in nasal samples varied significantly among the clusters, but the most prevalent clusters were not particularly numerous in the nasal samples. We did not find much evidence that genotypic clusters were associated with different carrier characteristics, such as age, sex, medical conditions, or antibiotic use. This may provide empirical support for the idea that genetic clusters in bacteria are maintained in the absence of adaptation to different niches. Alternatively, carrier characteristics other than those evaluated here or factors other than human hosts may exert selective pressure maintaining genotypic clusters.

Semi-supervised remote sensing image classification with cluster kernels

A semisupervised support vector machine is presented for the classification of remote sensing images. The method exploits the wealth of unlabeled samples for regularizing the training kernel representation locally by means of cluster kernels. The method learns a suitable kernel directly from the image and thus avoids assuming a priori signal relations by using a predefined kernel structure. Good results are obtained in image classification examples when few labeled samples are available. The method scales almost linearly with the number of unlabeled samples and provides out-of-sample predictions.

A new accelerometric method to assess the daily walking practice.

OBJECTIVE: To describe a method to obtain a profile of the duration and intensity (speed) of walking periods over 24 hours in women under free-living conditions. DESIGN: A new method based on accelerometry was designed for analyzing walking activity. In order to take into account inter-individual variability of acceleration, an individual calibration process was used. Different experiments were performed to highlight the variability of acceleration vs walking speed relationship, to analyze the speed prediction accuracy of the method, and to test the assessment of walking distance and duration over 24-h. SUBJECTS: Twenty-eight women were studied (mean+/-s.d.) age: 39.3+/-8.9 y; body mass: 79.7+/-11.1 kg; body height: 162.9+/-5.4 cm; and body mass index (BMI) 30.0+/-3.8 kg/m(2). RESULTS: Accelerometer output was significantly correlated with speed during treadmill walking (r=0.95, P<0.01), and short unconstrained walks (r=0.86, P<0.01), although with a large inter-individual variation of the regression parameters. By using individual calibration, it was possible to predict walking speed on a standard urban circuit (predicted vs measured r=0.93, P<0.01, s.e.e.=0.51 km/h). In the free-living experiment, women spent on average 79.9+/-36.0 (range: 31.7-168.2) min/day in displacement activities, from which discontinuous short walking activities represented about 2/3 and continuous ones 1/3. Total walking distance averaged 2.1+/-1.2 (range: 0.4-4.7) km/day. It was performed at an average speed of 5.0+/-0.5 (range: 4.1-6.0) km/h. CONCLUSION: An accelerometer measuring the anteroposterior acceleration of the body can estimate walking speed together with the pattern, intensity and duration of daily walking activity.

Effects of thresholding level variation in fringe binarization of multiobject joint transform correlation

It is possible to improve the fringe binarization method of joint transform correlation by choosing a suitable threshold level.

Revisiting Field Capacity (FC): variation of definition of FC and its estimation from pedotransfer functions

Taking into account the nature of the hydrological processes involved in in situ measurement of Field Capacity (FC), this study proposes a variation of the definition of FC aiming not only at minimizing the inadequacies of its determination, but also at maintaining its original, practical meaning. Analysis of FC data for 22 Brazilian soils and additional FC data from the literature, all measured according to the proposed definition, which is based on a 48-h drainage time after infiltration by shallow ponding, indicates a weak dependency on the amount of infiltrated water, antecedent moisture level, soil morphology, and the level of the groundwater table, but a strong dependency on basic soil properties. The dependence on basic soil properties allowed determination of FC of the 22 soil profiles by pedotransfer functions (PTFs) using the input variables usually adopted in prediction of soil water retention. Among the input variables, soil moisture content θ (6 kPa) had the greatest impact. Indeed, a linear PTF based only on it resulted in an FC with a root mean squared residue less than 0.04 m³ m-3 for most soils individually. Such a PTF proved to be a better FC predictor than the traditional method of using moisture content at an arbitrary suction. Our FC data were compatible with an equivalent and broader USA database found in the literature, mainly for medium-texture soil samples. One reason for differences between FCs of the two data sets of fine-textured soils is due to their different drainage times. Thus, a standardized procedure for in situ determination of FC is recommended.