La consultation systémique: une interface entre recherche et clinique

Le but de la consultation systémique est l'évaluation des interactions familiales à des fins cliniques aussi bien qu'à des fins de recherche, avec mise en lumière des ressources aussi bien que des difficultés de la famille. Elle est soit demandée spontanément par les parents soit par le(s) thérapeute(s) qui sui(ven)t la famille. Lors d'une première rencontre, nous proposons d'une part à la famille de faire des jeux familiaux standardisés que nous filmons et d'autre part de poser les questions qui motivent les parents ou thérapeute(s) à nous consulter. Lors d'une deuxième rencontre, un visionnement des films avec la famille (et les thérapeutes) permet une discussion ainsi que l'élaboration de réponses aux questions posées. Après une description de la pratique de la consultation systémique, avec ses objectifs et ses principes, les situations utilisées dans ce contexte sont présentées (comme le Lausanne Trilogue Play). Enfin, une vignette clinique en illustre la richesse et l'utilité, aussi bien pour la recherche que pour la clinique. The aim of the systems consultation is to assess the family interaction in order to enlighten, in a clinical perspective, the resources as well as the difficulties of the family. The family itself or a therapist may request it. During the first session, we propose to the family, on the one hand, to play standardized games which are recorded and, on the other hand, to ask the questions they (or the therapist/s) may have. During the second session, a video feedback takes place to discuss and elaborate on the questions. After a description of the practice of the systems consultation, including aims and principles, the observational situations used in this context will be presented (e.g. the Lausanne Trilogue Play). Finally a case illustration will show its richness and usefulness for research as well as for clinical purposes, in particular as a bridge between research and clinical domains.

Representing diffusion MRI in 5D for segmentation of white matter tracts with a level set method.

We present a method for segmenting white matter tracts from high angular resolution diffusion MR. images by representing the data in a 5 dimensional space of position and orientation. Whereas crossing fiber tracts cannot be separated in 3D position space, they clearly disentangle in 5D position-orientation space. The segmentation is done using a 5D level set method applied to hyper-surfaces evolving in 5D position-orientation space. In this paper we present a methodology for constructing the position-orientation space. We then show how to implement the standard level set method in such a non-Euclidean high dimensional space. The level set theory is basically defined for N-dimensions but there are several practical implementation details to consider, such as mean curvature. Finally, we will show results from a synthetic model and a few preliminary results on real data of a human brain acquired by high angular resolution diffusion MRI.

Application of synthetic peptides in development of a serologic method for laboratory diagnosis of schistosomiasis mansoni

The immunoreactivity of seven peptides synthesized from Schistosoma mansoni proteins, was evaluated by dot-blot and ELISA assays using two different sensitization methodologies. The best results were obtained on wells of the Costar 3590 microplates coated with peptides P1, P2, P3, P6, and P7 using conventional methodology. The signals increased considerably (p < 0.0003) on wells sensitized with P1 to P6 using alternative methodology. In contrast, the well coated with peptide P7 presented lower signal when compared with conventional methodology (p = 0.0019). These results, establish the basis for the application of synthetic peptides for laboratory diagnosis of schistosomiasis mansoni.

Mejora diagnóstica de hepatopatías de afectación difusa mediante técnicas de inteligencia artificial

The automatic diagnostic discrimination is an application of artificial intelligence techniques that can solve clinical cases based on imaging. Diffuse liver diseases are diseases of wide prominence in the population and insidious course, yet early in its progression. Early and effective diagnosis is necessary because many of these diseases progress to cirrhosis and liver cancer. The usual technique of choice for accurate diagnosis is liver biopsy, an invasive and not without incompatibilities one. It is proposed in this project an alternative non-invasive and free of contraindications method based on liver ultrasonography. The images are digitized and then analyzed using statistical techniques and analysis of texture. The results are validated from the pathology report. Finally, we apply artificial intelligence techniques as Fuzzy k-Means or Support Vector Machines and compare its significance to the analysis Statistics and the report of the clinician. The results show that this technique is significantly valid and a promising alternative as a noninvasive diagnostic chronic liver disease from diffuse involvement. Artificial Intelligence classifying techniques significantly improve the diagnosing discrimination compared to other statistics.

Quantification of nicotine, cotinine, trans-3'-hydroxycotinine and varenicline in human plasma by a sensitive and specific UPLC-tandem mass-spectrometry procedure for a clinical study on smoking cessation.

A sensitive and specific ultra performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of nicotine, its metabolites cotinine and trans-3'-hydroxycotinine and varenicline in human plasma was developed and validated. Sample preparation was realized by solid phase extraction of the target compounds and of the internal standards (nicotine-d4, cotinine-d3, trans-3'-hydroxycotinine-d3 and CP-533,633, a structural analog of varenicline) from 0.5mL of plasma, using a mixed-mode cation exchange support. Chromatographic separations were performed on a hydrophilic interaction liquid chromatography column (HILIC BEH 2.1×100mm, 1.7μm). A gradient program was used, with a 10mM ammonium formate buffer pH 3/acetonitrile mobile phase at a flow of 0.4mL/min. The compounds were detected on a triple quadrupole mass spectrometer, operated with an electrospray interface in positive ionization mode and quantification was performed using multiple reaction monitoring. Matrix effects were quantitatively evaluated with success, with coefficients of variation inferior to 8%. The procedure was fully validated according to Food and Drug Administration guidelines and to Société Française des Sciences et Techniques Pharmaceutiques. The concentration range was 2-500ng/mL for nicotine, 1-1000ng/mL for cotinine, 2-1000ng/mL for trans-3'-hydroxycotinine and 1-500ng/mL for varenicline, according to levels usually measured in plasma. Trueness (86.2-113.6%), repeatability (1.9-12.3%) and intermediate precision (4.4-15.9%) were found to be satisfactory, as well as stability in plasma. The procedure was successfully used to quantify nicotine, its metabolites and varenicline in more than 400 plasma samples from participants in a clinical study on smoking cessation.

New insights in carbohydrate-deficient transferrin analysis with capillary electrophoresis-mass spectrometry

Capillary zone electrophoresis (CZE) with UV detection has been widely used for the determination of carbohydrate-deficient transferrin (CDT), an indirect marker of the chronic alcohol consumption (≥60-80g/day). A commercially available method (CEofix? CDT kit), containing a bilayer anionic coating, allows for the analysis of CDT with a high resolution between transferrin (Tf) glycoforms with reduced protein adsorption onto the capillary wall. Although widely used in routine analysis, this procedure presents some limitations in terms of selectivity and sensitivity which may be overcome with mass spectrometry (MS). However, the available method is not MS-compatible due to the non-volatile coating as well as the phosphate and borate buffers present in the background electrolyte (BGE). This study firstly consisted in developing MS-compatible separation conditions, i.e., coating and BGE compositions. Numerous cationic, neutral, and anionic coatings were evaluated in combination with BGEs covering a broad range of pH values. A bilayer coating composed of a cationic layer of 10% polybrene (m/v) and an anionic layer of 10% dextran sulfate (m/v) combined with a BGE composed of 20mM ammonium acetate at pH 8.5 provided the best results in terms of glycoforms' resolution, efficiency, adsorption reduction, migration times' repeatability, and coating stability. The method was then transferred to CZE-MS after investigations of the electrospray ionization (ESI) source, equipped with a sheath-flow interface, and the time-of-flight (TOF/MS) parameters. A successful MS detection of tetrasialo-Tf was obtained during infusion, while the experiments highlighted the challenges and issues encountered with intact glycoprotein analysis by CZE-ESI-MS.

Risk-based modelling of diffuse land use impacts from rural landscapes upon salmonid fry abundance

Research has demonstrated that landscape or watershed scale processes can influence instream aquatic ecosystems, in terms of the impacts of delivery of fine sediment, solutes and organic matter. Testing such impacts upon populations of organisms (i.e. at the catchment scale) has not proven straightforward and differences have emerged in the conclusions reached. This is: (1) partly because different studies have focused upon different scales of enquiry; but also (2) because the emphasis upon upstream land cover has rarely addressed the extent to which such land covers are hydrologically connected, and hence able to deliver diffuse pollution, to the drainage network However, there is a third issue. In order to develop suitable hydrological models, we need to conceptualise the process cascade. To do this, we need to know what matters to the organism being impacted by the hydrological system, such that we can identify which processes need to be modelled. Acquiring such knowledge is not easy, especially for organisms like fish that might occupy very different locations in the river over relatively short periods of time. However, and inevitably, hydrological modellers have started by building up piecemeal the aspects of the problem that we think matter to fish. Herein, we report two developments: (a) for the case of sediment associated diffuse pollution from agriculture, a risk-based modelling framework, SCIMAP, has been developed, which is distinct because it has an explicit focus upon hydrological connectivity; and (b) we use spatially distributed ecological data to infer the processes and the associated process parameters that matter to salmonid fry. We apply the model to spatially distributed salmon and fry data from the River Eden, Cumbria, England. The analysis shows, quite surprisingly, that arable land covers are relatively unimportant as drivers of fry abundance. What matters most is intensive pasture, a land cover that could be associated with a number of stressors on salmonid fry (e.g. pesticides, fine sediment) and which allows us to identify a series of risky field locations, where this land cover is readily connected to the river system by overland flow. (C) 2010 Elsevier B.V. All rights reserved.

Cheap, rapid and efficient DNA extraction method to perform multilocus microsatellite genotyping on all Schistosoma mansoni stages

Schistosomes are endoparasites causing a serious human disease called schistosomiasis. The quantification of parasite genetic diversity is an essential component to understand the schistosomiasis epidemiology and disease transmission patterns. In this paper, we propose a novel assay for a rapid, low costly and efficient DNA extraction method of egg, larval and adult stages of Schistosoma mansoni. One euro makes possible to perform 60,000 DNA extraction reactions at top speed (only 15 min of incubation and 5 handling steps).

A Method and Tool to Support the Analysis and Enhance the Understanding of Peer-to-Peer Learning Experiences

In this paper we look at how a web-based social software can be used to make qualitative data analysis of online peer-to-peer learning experiences. Specifically, we propose to use Cohere, a web-based social sense-making tool, to observe, track, annotate and visualize discussion group activities in online courses. We define a specific methodology for data observation and structuring, and present results of the analysis of peer interactions conducted in discussion forum in a real case study of a P2PU course. Finally we discuss how network visualization and analysis can be used to gather a better understanding of the peer-to-peer learning experience. To do so, we provide preliminary insights on the social, dialogical and conceptual connections that have been generated within one online discussion group.

Standardisation of 18F by a coincidence method using full solid angle detectors.

A solution of (18)F was standardised with a 4pibeta-4pigamma coincidence counting system in which the beta detector is a one-inch diameter cylindrical UPS89 plastic scintillator, positioned at the bottom of a well-type 5''x5'' NaI(Tl) gamma-ray detector. Almost full detection efficiency-which was varied downwards electronically-was achieved in the beta-channel. Aliquots of this (18)F solution were also measured using 4pigamma NaI(Tl) integral counting and Monte Carlo calculated efficiencies as well as the CIEMAT-NIST method. Secondary measurements of the same solution were also performed with an IG11 ionisation chamber whose equivalent activity is traceable to the Système International de Référence through the contribution IRA-METAS made to it in 2001; IRA's degree of equivalence was found to be close to the key comparison reference value (KCRV). The (18)F activity predicted by this coincidence system agrees closely with the ionisation chamber measurement and is compatible within one standard deviation of the other primary measurements. This work demonstrates that our new coincidence system can standardise short-lived radionuclides used in nuclear medicine.

F+0 renography in neonates and infants younger than 6 months: an accurate method to diagnose severe obstructive uropathy.

We studied the response to F+0 renography and the relative and absolute individual kidney function in neonates and &lt; 6-mo-old infants before and after surgery for unilateral ureteropelvic junction obstruction (UJO). METHODS: The results obtained at diagnosis and after pyeloplasty for 9 children (8 boys, 1 girl; age range, 0.8-5.9 mo; mean age +/- SD, 2.4 +/- 1.5 mo) with proven unilateral UJO (i.e., affected kidney [AK]) and an unremarkable contralateral kidney (i.e., normal kidney [NK]) were evaluated and compared with a control group of 10 children (6 boys, 4 girls; age range, 0.8-2.8 mo; mean age, 1.5 +/- 0.7 mo) selected because of symmetric renal function, absence of vesicoureteral reflux or infection, and an initially dilated but not obstructed renal pelvis as proven by follow-up. Renography was performed for 20 min after injection of (123)I-hippuran (OIH) (0.5-1.0 MBq/kg) immediately followed by furosemide (1 mg/kg). The relative and absolute renal functions and the response to furosemide were measured on background-subtracted and depth-corrected renograms. The response to furosemide was quantified by an elimination index (EI), defined as the ratio of the 3- to 20-min activities: An EI &gt; or = 3 was considered definitively normal and an EI &lt; or = 1 definitively abnormal. If EI was equivocal (1 &lt; EI &lt; 3), the response to gravity-assisted drainage was used to differentiate AKs from NKs. Absolute separate renal function was measured by an accumulation index (AI), defined as the percentage of (123)I-OIH (%ID) extracted by the kidney 30-90 s after maximal cardiac activity. RESULTS: All AKs had definitively abnormal EIs at diagnosis (mean, 0.56 +/- 0.12) and were significantly lower than the EIs of the NKs (mean, 3.24 +/- 1.88) and of the 20 control kidneys (mean, 3.81 +/- 1.97; P &lt; 0.001). The EIs of the AKs significantly improved (mean, 2.81 +/- 0.64; P &lt; 0.05) after pyeloplasty. At diagnosis, the AIs of the AKs were significantly lower (mean, 6.31 +/- 2.33 %ID) than the AIs of the NKs (mean, 9.43 +/- 1.12 %ID) and of the control kidneys (mean, 9.05 +/- 1.17 %ID; P &lt; 0.05). The AIs of the AKs increased at follow-up (mean, 7.81 +/- 2.23 %ID) but remained lower than those of the NKs (mean, 10.75 +/- 1.35 %ID; P &lt; 0.05). CONCLUSION: In neonates and infants younger than 6 mo, (123)I-OIH renography with early furosemide injection (F+0) allowed us to reliably diagnose AKs and to determine if parenchymal function was normal or impaired and if it improved after surgery.

Use of high-resolution geophysical data to characterize heterogeneous aquifers: influence of data integration method on hydrological predictions

The integration of geophysical data into the subsurface characterization problem has been shown in many cases to significantly improve hydrological knowledge by providing information at spatial scales and locations that is unattainable using conventional hydrological measurement techniques. The investigation of exactly how much benefit can be brought by geophysical data in terms of its effect on hydrological predictions, however, has received considerably less attention in the literature. Here, we examine the potential hydrological benefits brought by a recently introduced simulated annealing (SA) conditional stochastic simulation method designed for the assimilation of diverse hydrogeophysical data sets. We consider the specific case of integrating crosshole ground-penetrating radar (GPR) and borehole porosity log data to characterize the porosity distribution in saturated heterogeneous aquifers. In many cases, porosity is linked to hydraulic conductivity and thus to flow and transport behavior. To perform our evaluation, we first generate a number of synthetic porosity fields exhibiting varying degrees of spatial continuity and structural complexity. Next, we simulate the collection of crosshole GPR data between several boreholes in these fields, and the collection of porosity log data at the borehole locations. The inverted GPR data, together with the porosity logs, are then used to reconstruct the porosity field using the SA-based method, along with a number of other more elementary approaches. Assuming that the grid-cell-scale relationship between porosity and hydraulic conductivity is unique and known, the porosity realizations are then used in groundwater flow and contaminant transport simulations to assess the benefits and limitations of the different approaches.

Molecular design of the Calphabeta interface favors specific pairing of introduced TCRalphabeta in human T cells.

A promising approach to adoptive transfer therapy of tumors is to reprogram autologous T lymphocytes by TCR gene transfer of defined Ag specificity. An obstacle, however, is the undesired pairing of introduced TCRalpha- and TCRbeta-chains with the endogenous TCR chains. These events vary depending on the individual endogenous TCR and they not only may reduce the levels of cell surface-introduced TCR but also may generate hybrid TCR with unknown Ag specificities. We show that such hybrid heterodimers can be generated even by the pairing of human and mouse TCRalpha- and TCRbeta-chains. To overcome this hurdle, we have identified a pair of amino acid residues in the crystal structure of a TCR that lie at the interface of associated TCR Calpha and Cbeta domains and are related to each other by both a complementary steric interaction analogous to a "knob-into-hole" configuration and the electrostatic environment. We mutated the two residues so as to invert the sense of this interaction analogous to a charged "hole-into-knob" configuration. We show that this inversion in the CalphaCbeta interface promotes selective assembly of the introduced TCR while preserving its specificity and avidity for Ag ligand. Noteworthily, this TCR modification was equally efficient on both a Mu and a Hu TCR. Our data suggest that this approach is generally applicable to TCR independently of their Ag specificity and affinity, subset distribution, and species of origin. Thus, this strategy may optimize TCR gene transfer to efficiently and safely reprogram random T cells into tumor-reactive T cells.