The place preference task: a new tool for studying the relation between behavior and place cell activity in rats

This study describes a task that combines random searching with goal directed navigation. The testing was conducted on a circular elevated open field (80 cm in diameter), with an unmarked target area (20 cm in diameter) in the center of 1 of the 4 quadrants. Whenever the rat entered the target area, the computerized tracking system released a pellet to a random point on the open field. Rats were able to learn the task under light and in total darkness, and on a stable or a rotating arena. Visual information was important in light, but idiothetic information became crucial in darkness. Learning of a new position was quicker under light than in total darkness on a rotating arena. The place preference task should make it possible to study place cells (PCs) when the rats use an allothetic (room frame) or idiothetic (arena frame) representation of space and to compare the behavioral response with the PCs' activity.

SwissParam: a fast force field generation tool for small organic molecules.

The drug discovery process has been deeply transformed recently by the use of computational ligand-based or structure-based methods, helping the lead compounds identification and optimization, and finally the delivery of new drug candidates more quickly and at lower cost. Structure-based computational methods for drug discovery mainly involve ligand-protein docking and rapid binding free energy estimation, both of which require force field parameterization for many drug candidates. Here, we present a fast force field generation tool, called SwissParam, able to generate, for arbitrary small organic molecule, topologies, and parameters based on the Merck molecular force field, but in a functional form that is compatible with the CHARMM force field. Output files can be used with CHARMM or GROMACS. The topologies and parameters generated by SwissParam are used by the docking software EADock2 and EADock DSS to describe the small molecules to be docked, whereas the protein is described by the CHARMM force field, and allow them to reach success rates ranging from 56 to 78%. We have also developed a rapid binding free energy estimation approach, using SwissParam for ligands and CHARMM22/27 for proteins, which requires only a short minimization to reproduce the experimental binding free energy of 214 ligand-protein complexes involving 62 different proteins, with a standard error of 2.0 kcal mol(-1), and a correlation coefficient of 0.74. Together, these results demonstrate the relevance of using SwissParam topologies and parameters to describe small organic molecules in computer-aided drug design applications, together with a CHARMM22/27 description of the target protein. SwissParam is available free of charge for academic users at www.swissparam.ch.

Quantitative Assessment of T1 Relaxation and Diffusion as a Prognostic Tool for Brain Development: A Longitudinal Preliminary Study on Preterm Babies

BACKGROUND: Despite major advances in care of premature infants, survivors exhibit mild cognitive deficits in around 40%. Beside severe intraventricular haemorrhages (IVH) and cystic periventricular leucomalacia (PVL), more subtle patterns such as grade I and II IVH, punctuate WM lesions and diffuse PVL might be linked to the cognitive deficits. Grey matter disease is also recognized to contribute to long-term cognitive impairment.¦OBJECTIVE: We intend to use novel MR techniques to study more precisely the different injury patterns. In particular MP2RAGE (magnetization prepared dual rapid echo gradient) produces high-resolution quantitative T1 relaxation maps. This contrast is known to reflect tissue anomalies such as white matter injury in general and dysmyelination in particular. We also used diffusion tensor imaging, a quantitative technique known to reflect white matter maturation and disease.¦DESIGN/METHODS: All preterm infants born under 30 weeks of GA were included. Serial 3T MR-imaging using a neonatal head-coil at DOL 3, 10 and at term equivalent age (TEA), using DTI and MP2RAGE sequences was performed. MP2RAGE generates a T1 map and allows calculating the relaxation time T1. Multiple measurements were performed for each exam in 12 defined white and grey matter ROIs.¦RESULTS: 16 patients were recruited: mean GA 27 2/7 w (191,2d SD±10,8), mean BW 999g (SD±265). 39 MRIs were realized (12 early: mean 4,83d±1,75, 13 late: mean 18,77d±8,05 and 14 at TEA: 88,91d±8,96). Measures of relaxation time T1 show a gradual and significant decrease over time (for ROI PLIC mean±SD in ms: 2100.53±102,75, 2116,5±41,55 and 1726,42±51,31 and for ROI central WM: 2302,25±79,02, 2315,02±115,02 and 1992,7±96,37 for early, late and TEA MR respectively). These trends are also observed in grey matter area, especially in thalamus. Measurements of ADC values show similar monotonous decrease over time.¦CONCLUSIONS: From these preliminary results, we conclude that quantitative MR imaging in very preterm infants is feasible. On the successive MP2RAGE and DTI sequences, we observe a gradual decrease over time in the described ROIs, representing the progressive maturation of the WM micro-structure and interestingly the same evolution is observed in the grey matter. We speculate that our study will provide normative values for T1map and ADC and might be a predictive factor for favourable or less favourable outcome.

Chemical labelling of oyster shells used for time-calibrated high-resolution Mg/Ca ratios: A tool for estimation of past seasonal temperature variations

The geochemical compositions of biogenic carbonates are increasingly used for palaeoenvironmental reconstructions. The skeletal delta O-18 temperature relationship is dependent on water salinity, so many recent studies have focused on the Mg/Ca and Sr/Ca ratios because those ratios in water do not change significantly on short time scales. Thus, those elemental ratios are considered to be good palaeotemperature proxies in many biominerals, although their use remains ambiguous in bivalve shells. Here, we present the high-resolution Mg/Ca ratios of two modern species of juvenile and adult oyster shells, Crassostrea gigas and Ostrea edulis. These specimens were grown in controlled conditions for over one year in two different locations. In situ monthly Mn-marking of the shells has been used for day calibration. The daily Mg/Ca.ratios in the shell have been measured with an electron microprobe. The high frequency Mg/Ca variation of all specimens displays good synchronism with lunar cycles, suggesting that tides strongly influence the incorporation of Mg/Ca into the shells. Highly significant correlation coefficients (0.70<R<0.83, p<0.0001) between the Mg/Ca ratios and the seawater temperature are obtained only for juvenile C. gigas samples, while metabolic control of Mg/Ca incorporation and lower shell growth rates preclude the use of the Mg/Ca ratio in adult shells as a palaeothermometer. Data from three juvenile C. gigas shells from the two study sites are selected to establish a relationship: T = 3.77Mg/Ca + 1.88, where T is in degrees C and Mg/Ca in mmol/mol. (c) 2012 Elsevier B.V. All rights reserved.

1st radiometric dating of a paleontologically dated Bathonian level from Georgia (USSR) - Use of the cathodoluminescence for selection of suitable plagioclases

Jurassic volcanic formations interlayered with (ammonite-bearing) sediments are common in the Caucasus area; this situation is of interest for the numerical calibration of the poorly documented Jurassic portion of the time scale. However, following petrographic study on thin sections no whole-rocks can be considered reliable geochronometers due to subsequent alteration; from about 20 samples, two were selected for plagioclase dating; one (V134) is probably early Kimmeridgian in age; the other (V136) is probably located in the Lower Bathonian stage according to diagnostic ammonites. Cathodoluminescence (CTL) study has shown that sample V136 was similar to usual volcanic feldspars (blue to green colour); however, the lack of CTL of the V134 plagioclase is a character common to diagenetic feldspars; consequently, in spite of a good optical preservation, this geo-chronometer cannot give an age representative of the time of emplacement of the lava flow. We have combined CTL observation with microprobe analysis in order to document the poorly known CTL behaviour of volcanic feldspars; cations Ti4+ and Fe2+ play a major role in the CTL colour of plagioclases and are able to document the growing history of these feldspars ; phenocrysts are initially rich in Fe2+ (core of the crystals, green in colour), then richer in Ti toward the exterior; microcrysts are even richer in Ti (blue to bright blue). We have also observed that natural CTL colour was modified resulting from acid ``cleaning'' of the separated feldspars : the initial blue or green colour tends to change to yellow or violet, respectively, after acid treatment probably due to oxydation of Fe2+ toward Fe3+. X-ray and microprobe analyses both indicated that plagioclases from sample V134 was near the sodic end member (albite) suggesting a diagenetic origin in this andesitic basalt; In contrast, sample V136 contains a calcic plagioclase of common composition for a doleritic basalt. The K-Ar conventional technique was applied as a preliminary tool for radiometric analysis. The Kimmeridgian Na-plagioclase sample gave a ``rejuvenated'' (85 Ma) apparent age which confirms a late genesis for the separated plagioclase phase; this interpretation is based on CTL observation, X-ray analysis, and microprobe analysis ; these techniques are able to distinguish samples which have been submitted to diagenetic alteration from those which have not. An age consistent with the stratigraphic location has been obtained from sample V136. This age of 161 +/- 3 (2-sigma) Ma, is the first one available from a sample palaeontologically located with reasonable precision within the mid Jurassic time.

Use of the FACTS solvation model for protein-ligand docking calculations. Application to EADock.

Protein-ligand docking has made important progress during the last decade and has become a powerful tool for drug development, opening the way to virtual high throughput screening and in silico structure-based ligand design. Despite the flattering picture that has been drawn, recent publications have shown that the docking problem is far from being solved, and that more developments are still needed to achieve high successful prediction rates and accuracy. Introducing an accurate description of the solvation effect upon binding is thought to be essential to achieve this goal. In particular, EADock uses the Generalized Born Molecular Volume 2 (GBMV2) solvent model, which has been shown to reproduce accurately the desolvation energies calculated by solving the Poisson equation. Here, the implementation of the Fast Analytical Continuum Treatment of Solvation (FACTS) as an implicit solvation model in small molecules docking calculations has been assessed using the EADock docking program. Our results strongly support the use of FACTS for docking. The success rates of EADock/FACTS and EADock/GBMV2 are similar, i.e. around 75% for local docking and 65% for blind docking. However, these results come at a much lower computational cost: FACTS is 10 times faster than GBMV2 in calculating the total electrostatic energy, and allows a speed up of EADock by a factor of 4. This study also supports the EADock development strategy relying on the CHARMM package for energy calculations, which enables straightforward implementation and testing of the latest developments in the field of Molecular Modeling.

The use of 3D planning in facial surgery: Preliminary observations.

Three-dimensional (3D) planning is becoming a more commonly used tool in maxillofacial surgery. At first used only virtually, 3D planning now also enables the creation of useful intraoperative aids such as cutting guides, which decrease the operative difficulty. In our center, we have used 3D planning in various domains of facial surgery and have investigated the advantages of this technique. We have also addressed the difficulties associated with its use. 3D planning increases the accuracy of reconstructive surgery, decreases operating time, whilst maintaining excellent esthetic results. However, its use is restricted to osseous reconstruction at this stage and once planning has been undertaken, it cannot be reversed or altered intraoperatively. Despite the attractive nature of this new tool, its uses and practicalities must be further evaluated. In particular, cost-effectiveness, hospital stay, and patient perceived benefits must be assessed.

Toxoplasma gondii: flat-mounting of retina as a new tool for the observation of ocular infection in mice.

Ocular toxoplasmosis is the principal cause of posterior uveitis and a leading cause of blindness. Animal models are required to improve our understanding of the pathogenesis of this disease. The method currently used for the detection of retinal cysts in animals involves the observation, under a microscope, of all the sections from infected eyes. However, this method is time-consuming and lacks sensitivity. We have developed a rapid, sensitive method for observing retinal cysts in mice infected with Toxoplasma gondii. This method involves combining the flat-mounting of retina - a compromise between macroscopic observation and global analysis of this tissue - and the use of an avirulent recombinant strain of T. gondii expressing the Escherichia coli beta-galactosidase gene, visually detectable at the submacroscopic level. Single cyst unilateral infection was found in six out of 17 mice killed within 28 days of infection, whereas a bilateral infection was found in only one mouse. There was no correlation between brain cysts number and ocular infection.

Recommendations for the use of ultrasound in rheumatoid arthritis: literature review and SONAR score experience.

Ultrasound (US) has become a useful tool in the detection of early disease, differential diagnosis, guidance of treatment decisions and treatment monitoring of rheumatoid arthritis (RA). In 2008, the Swiss Sonography in Arthritis and Rheumatism (SONAR) group was established to promote the use of US in inflammatory arthritis in clinical practice. A scoring system was developed and taught to a large number of Swiss rheumatologists who already contributed to the Swiss Clinical Quality Management (SCQM) database, a national patient register. This paper intends to give a Swiss consensus about best clinical practice recommendations for the use of US in RA on the basis of the current literature knowledge and experience with the Swiss SONAR score. Literature research was performed to collect data on current evidence. The results were discussed among specialists of the Swiss university centres and private practice, following a structured procedure. Musculoskelatal US was found to be very helpful in establishing the diagnosis and monitoring the evolution of RA, and to be a reliable tool if used by experienced examiners. It influences treatment decisions such as continuing, intensifying or stepping down therapy. The definite modalities of integrating US into the diagnosis and monitoring of RA treatments will be defined within a few years. There are, however, strong arguments to use US findings as of today in daily clinical care. Some practical recommendations about the use of US in RA, focusing on the diagnosis and the use of the SONAR score, are proposed.

Development of a Sensitive Resource Use Questionnaire

Alcoholism is a chronic disease and the evaluation of its burden usually focuses on long-term co-morbidity and mortality. Clinical Trials evaluating new interventions for alcohol-dependent patients rarely last more than 12 to 24 months. OBJECTIVES: Develop a questionnaire capable of capturing principal resource use yet sensitive enough to show short-term economic benefit of drugs developed to reduce consump¬tion in alcohol-dependent patients. METHODS: Comprehensive Medline literature search using keywords: Alcohol-related-disorders, economics, cost of illness. Further, experts panel discussions provided additional data. RESULTS: Two key cost drivers, hospitalisation and sick leaves were identified by the literature review. Expert findings related to costs of social consequences were incorporated. These three important resources were included in the questionnaire in addition to standard medical resource use consumption input. Finally, the following items were included: consultation visits, hospitalisations, sick leaves and working situation, living situation, social environ¬ment, accidents, arrests and domestic violence. The recall period is 3 months. DISCUSSION: A great deal of information is collected in this questionnaire in order to capture all relevant resources. Tests to validate the questionnaire in a real-life setting will be conducted (face validity, concurrent validity, and test-retest) in a cohort of dependent patients initiated at Lausanne University hospital ( Switzerland). Items not sensitive enough to capture short-term costs and consequences will be removed. Translation into other major languages and adaptation to different settings after cultural validation is planned. CONCLUSIONS: Publication of this tool should facilitate additional knowledge about resource utilisation at the patient level and enable evaluation of short-term economic impact of pharmacological and non-pharmacological interventions.

Exposure to bioaerosols in poultry houses at different stages of fattening; use of real-time PCR for airborne bacterial quantification

Previous studies have demonstrated that poultry house workers are exposed to very high levels of organic dust and consequently have an increased prevalence of adverse respiratory symptoms. However, the influence of the age of broilers on bioaerosol concentrations has not been investigated. To evaluate the evolution of bioaerosol concentration during the fattening period, bioaerosol parameters (inhalable dust, endotoxin and bacteria) were measured in 12 poultry confinement buildings in Switzerland, at three different stages of the birds' growth; samples of air taken from within the breathing zones of individual poultry house employees as they caught the chickens ready to be transported for slaughter were also analysed. Quantitative polymerase chain reaction (Q-PCR) was used to assess the quantity of total airborne bacteria and total airborne Staphylococcus species. Bioaerosol levels increased significantly during the fattening period of the chickens. During the task of catching mature birds, the mean inhalable dust concentration for a worker was 26 +/- 1.9 mg m(-3) and endotoxin concentration was 6198 +/- 2.3 EU m(-3) air, >6-fold higher than the Swiss occupational recommended value (1000 EU m(-3)). The mean exposure level of bird catchers to total bacteria and Staphylococcus species measured by Q-PCR is also very high, respectively, reaching values of 53 (+/-2.6) x 10(7) cells m(-3) air and 62 (+/-1.9) x 10(6) m(-3) air. It was concluded that in the absence of wearing protective breathing apparatus, chicken catchers in Switzerland risk exposure beyond recommended limits for all measured bioaerosol parameters. Moreover, the use of Q-PCR to estimate total and specific numbers of airborne bacteria is a promising tool for evaluating any modifications intended to improve the safety of current working practices

INdividual SUrveys in RAllies (INSURA), A new tool for exploring transnational activism?

Prior the middle of the 90', interviewing participants in protest events was quiet rare. INdividual SUrveys in RAllies (INSURA) did enter the social researcher's usual toolkit only in the following decade after Favre, Fillieule and Mayer (1997) conducted such a survey with as a primary ambition to build a solid methodological framework that could be subsequently applied by other researchers. After some years of intensive use of INSURA, one is entitled to wonder whether that technique has fulfilled social researchers' hopes or not. In that paper, results of a collective work on alter-global rallies in Evian and Saint- Denis are used to answer three interrelated questions. Firstly, some basic methodological questions about how to collect data on crowds are adressed. What are the specific constraints of interviewing people at the very moment they are "expressing" a political opinion? What specific constraints result from the morphology of the covered events, that is to say, how to build a valid sampling frame? The authors then turn to a more general point about the questions that can be solved, or not, using that technique. Secondly it is the strenghts and weaknesses of INSURA in exploring the transnational dimension of alter global protests that is adressed. The authors show that INSURA is certainly well suited to explore the demographics of alter-global events, as well as relational networks of individuals and multiple belongings. On the contrary, it is assumed that organization networks and movement's boundaries are far more difficult to explore through that method, a fact that seriously limits international cross comparisons of events and movements based on that tool.

The future of patient safety: Surgical trainees accept virtual reality as a new training tool.

BACKGROUND: The use of virtual reality (VR) has gained increasing interest to acquire laparoscopic skills outside the operating theatre and thus increasing patients' safety. The aim of this study was to evaluate trainees' acceptance of VR for assessment and training during a skills course and at their institution. METHODS: All 735 surgical trainees of the International Gastrointestinal Surgery Workshop 2006-2008, held in Davos, Switzerland, were given a minimum of 45 minutes for VR training during the course. Participants' opinion on VR was analyzed with a standardized questionnaire. RESULTS: Fivehundred-twenty-seven participants (72%) from 28 countries attended the VR sessions and answered the questionnaires. The possibility of using VR at the course was estimated as excellent or good in 68%, useful in 21%, reasonable in 9% and unsuitable or useless in 2%. If such VR simulators were available at their institution, most course participants would train at least one hour per week (46%), two or more hours (42%) and only 12% wouldn't use VR. Similarly, 63% of the participants would accept to operate on patients only after VR training and 55% to have VR as part of their assessment. CONCLUSION: Residents accept and appreciate VR simulation for surgical assessment and training. The majority of the trainees are motivated to regularly spend time for VR training if accessible.

Use of a dynamic foot pressure index to monitor the effects of treatment for equinus gait in children with cerebral palsy.

The purpose of this study is to introduce and describe a newly developed index using foot pressure analysis to quantify the degree of equinus gait in children with cerebral palsy before and after injection with botulinum toxin. Data were captured preinjection and 12 weeks postinjection. Ten children aged 2(1/2) to 6(1/2) years took part (5 boys and 5 girls). Three of them had a diagnosis of spastic diplegia and 7 of congenital hemiplegia. In total, 13 limbs were analyzed. After orientation and segmentation of raw pedobarographic data, we determined a dynamic foot pressure index graded 0 to 100 that quantified the relative degree of heel and forefoot contact during stance. These data were correlated (Pearson correlation) with clinical measurements of dorsiflexion at the ankle (on a slow and fast stretch) and video observation (using the Observational Gait Scale). Pedobarograph data were strongly correlated with both the Observational Gait Scale scores (R = 0.79, P < 0.005) and clinical measurements of dorsiflexion on a fast stretch, which is reflective of spasticity (R = 0.70, P < 0.005). We demonstrated the index's sensitivity in detecting changes in spasticity and good correlation with video observations seems to indicate this technique's potential validity. When manipulated and segmented appropriately, and with the development of a simple ordinal index, we found that foot pressure data provided a useful tool in tracking changes in patients with spastic equinus.

Optimization of HS-SPME/GC-MS analysis and its use in the profiling of illicit ecstasy tablets (Part 1)

A headspace solid-phase microextraction procedure (HS-SPME) was developed for the profiling of traces present in 3,4-methylenedioxymethylampethamine (MDMA). Traces were first extracted using HS-SPME and then analyzed by gas chromatography-mass spectroscopy (GC-MS). The HS-SPME conditions were optimized using varying conditions. Optimal results were obtained when 40 mg of crushed MDMA sample was heated at 80 °C for 15 min, followed by extraction at 80 °C for 15 min with a polydimethylsiloxane/divinylbenzene coated fibre. A total of 31 compounds were identified as traces related to MDMA synthesis, namely precursors, intermediates or by-products. In addition some fatty acids used as tabletting materials and caffeine used as adulterant, were also detected. The use of a restricted set of 10 target compounds was also proposed for developing a screening tool for clustering samples having close profile. 114 seizures were analyzed using an SPME auto-sampler (MultiPurpose Samples MPS2), purchased from Gerstel GMBH & Co. (Germany), and coupled to GC-MS. The data was handled using various pre-treatment methods, followed by the study of similarities between sample pairs based on the Pearson correlation. The results show that HS-SPME, coupled with the suitable statistical method is a powerful tool for distinguishing specimens coming from the same seizure and specimens coming from different seizures. This information can be used by law enforcement personnel to visualize the ecstasy distribution network as well as the clandestine tablet manufacturing.