Influence of the implanted pulse generator as reference electrode in finite element model of monopolar deep brain stimulation.

Electrical deep brain stimulation (DBS) is an efficient method to treat movement disorders. Many models of DBS, based mostly on finite elements, have recently been proposed to better understand the interaction between the electrical stimulation and the brain tissues. In monopolar DBS, clinically widely used, the implanted pulse generator (IPG) is used as reference electrode (RE). In this paper, the influence of the RE model of monopolar DBS is investigated. For that purpose, a finite element model of the full electric loop including the head, the neck and the superior chest is used. Head, neck and superior chest are made of simple structures such as parallelepipeds and cylinders. The tissues surrounding the electrode are accurately modelled from data provided by the diffusion tensor magnetic resonance imaging (DT-MRI). Three different configurations of RE are compared with a commonly used model of reduced size. The electrical impedance seen by the DBS system and the potential distribution are computed for each model. Moreover, axons are modelled to compute the area of tissue activated by stimulation. Results show that these indicators are influenced by the surface and position of the RE. The use of a RE model corresponding to the implanted device rather than the usually simplified model leads to an increase of the system impedance (+48%) and a reduction of the area of activated tissue (-15%).

Cumulative Costs of Caries Prevention and Treatment in Children - with Special Reference to Work Division and Cohort Effect

Lapsen karieshoidon kustannuskertymän muutokset ja karieshoidon toimintakäytäntöjen yhteys kustannuksiin Tutkimuksen tavoitteena oli mitata terveyskeskuksessa hoidettavien lasten karieshoidon kumulatiivisia kustannuksia ja verrata niitä kahden erilaisen toimintatavan välillä. Lisäksi tarkasteltiin lasten hampaiden terveyttä. Tutkimus tehtiin julkisen palvelutuottajan näkökulmasta. Tutkimusaineisto kerättiin Kemin ja Tornion terveyskeskusten suun terveydenhuollon potilaskertomuksista. Kemin kohortit 1980, 1983 ja 1986 (n = 600) ja Tornion kohortit 1980 ja 1992 (n = 400) edustivat perinteistä ja Kemin kohortit 1989, 1992 ja 1995 (n = 600) uutta toimintatapaa työnjaon ja ehkäisyn ajoituksen suhteen. Kohortteja ja kaupunkeja verrattiin hampaiden terveyden (dmft/DMFT = 0 ja dmft ja DMFT keskiarvot 5 ja 12 vuoden iässä) ja voimavarojen käytön suhteen. Panoskäyttö johdettiin käyntimäärien avulla laskennallisen työajan kautta. Kustannuskertymät muodostettiin käyttämällä henkilöstömenoista laskettuja suorittajakohtaisia yksikkökustannuksia. Panoskäytön ja yksikkökustannusten kautta muodostettiin kustannuskertymät. Kustannusten ja terveysvaikutusten suhteita arvioitiin kustannus-vaikuttavuusanalyysissä. Suuhygienistien työpanosta hyödyntävällä varhaisen ehkäisyn toimintamallilla saavutettiin vähäisemmin kustannuksin alle kouluiässä parempi ja kouluiässä yhtä hyvä hammasterveys kuin perinteisellä, enemmän hammaslääkärien työpanokseen perustuvalla tavalla. Karieksen hoitoon liittyvien käyntien määrä oli nuorimmissa syntymävuosikohorteissa pienempi kuin vanhimmissa kohorteissa. Käynnit hammaslääkärissä vähenivät eniten. Toimintatavalla oli merkittävä vaikutus lapsen karieshoidon kokonaiskustannuksiin. Herkkyysanalyysin mukaan karieshoidon kustannukset olivat työnjakoa hyödyntämällä kolmanneksen pienemmät, kuin jos hoidon suorittajana olisi ollut ainoastaan hammaslääkäri-hoitaja työpari. Lasten karieshoidon kustannusvaikuttavuus kohentui molemmissa terveyskeskuksissa nuoremmissa kohorteissa vanhempiin verrattuna. Suun terveydenhuollon potilaskertomuksia olisi hyödynnettävä toiminnan kehittämisessä. Varhaisen ehkäisyn avulla voitaisiin kaikkien suun terveydenhuollon ammattihenkilöiden työpanos kohdentaa kustannustehokkaasti.

Fibroblast Growth Factor 8 and its Receptors in The Growth and Angiogenesis of Experimental Breast Cancer . With Special Reference to Thrombospondin-1 as a Novel Target Gene for FGF-8

The growth of breast cancer is regulated by hormones and growth factors. Recently, aberrant fibroblast growth factor (FGF) signalling has been strongly implicated in promoting the progression of breast cancer and is thought to have a role in the development of endocrine resistant disease. FGFs mediate their auto- and paracrine signals through binding to FGF receptors 1-4 (FGFR1-4) and their isoforms. Specific targets of FGFs in breast cancer cells and the differential role of FGFRs, however, are poorly described. FGF-8 is expressed at elevated levels in breast cancer, and it has been shown to act as an angiogenic, growth promoting factor in experimental models of breast cancer. Furthermore, it plays an important role in mediating androgen effects in prostate cancer and in some breast cancer cell lines. We aimed to study testosterone (Te) and FGF-8 regulated genes in Shionogi 115 (S115) breast cancer cells, characterise FGF-8 activated intracellular signalling pathways and clarify the role of FGFR1, -2 and -3 in these cells. Thrombospondin-1 (TSP-1), an endogenous inhibitor of angiogenesis, was recognised as a Te and FGF-8 regulated gene. Te repression of TSP-1 was androgen receptor (AR)-dependent. It required de novo protein synthesis, but it was independent of FGF-8 expression. FGF-8, in turn, downregulated TSP-1 transcription by activating the ERK and PI3K pathways, and the effect could be reversed by specific kinase inhibitors. Differential FGFR1-3 action was studied by silencing each receptor by shRNA expression in S115 cells. FGFR1 expression was a prerequisite for the growth of S115 tumours, whereas FGFR2 expression alone was not able to promote tumour growth. High FGFR1 expression led to a growth advantage that was associated with strong ERK activation, increased angiogenesis and reduced apoptosis, and all of these effects could be reversed by an FGFR inhibitor. Taken together, the results of this thesis show that FGF-8 and FGFRs contribute strongly to the regulation of the growth and angiogenesis of experimental breast cancer and support the evidence for FGF-FGFR signalling as one of the major players in breast cancers.

Animal models of anxiety: an ethological perspective

In the field of anxiety research, animal models are used as screening tools in the search for compounds with therapeutic potential and as simulations for research on mechanisms underlying emotional behaviour. However, a solely pharmacological approach to the validation of such tests has resulted in distinct problems with their applicability to systems other than those involving the benzodiazepine/GABAA receptor complex. In this context, recent developments in our understanding of mammalian defensive behaviour have not only prompted the development of new models but also attempts to refine existing ones. The present review focuses on the application of ethological techniques to one of the most widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh approach to an established test has revealed a hitherto unrecognized multidimensionality to plus-maze behaviour and, as it yields comprehensive behavioural profiles, has many advantages over conventional methodology. This assertion is supported by reference to recent work on the effects of diverse manipulations including psychosocial stress, benzodiazepines, GABA receptor ligands, neurosteroids, 5-HT1A receptor ligands, and panicolytic/panicogenic agents. On the basis of this review, it is suggested that other models of anxiety may well benefit from greater attention to behavioural detail

Experimental Studies on Non-Metallic Composite Bone Implants With a Special Reference to Staphylococcal Biofilm Infection

Non-metallic implants made of bioresorbable or biostable synthetic polymers are attractive options in many surgical procedures, ranging from bioresorbable suture anchors of arthroscopic surgery to reconstructive skull implants made of biostable fiber-reinforced composites. Among other benefits, non-metallic implants produce less interference in imaging. Bioresorbable polymer implants may be true multifunctional, serving as osteoconductive scaffolds and as matrices for simultaneous delivery of bone enhancement agents. As a major advantage for loading conditions, mechanical properties of biostable fiber-reinforced composites can be matched with those of the bone. Unsolved problems of these biomaterials are related to the risk of staphylococcal biofilm infections and to the low osteoconductivity of contemporary bioresorbable composite implants. This thesis was focused on the research and development of a multifunctional implant model with enhanced osteoconductivity and low susceptibility to infection. In addition, the experimental models for assessment, diagnostics and prophylaxis of biomaterial-related infections were established. The first experiment (Study I) established an in vitro method for simultaneous evaluation of calcium phosphate and biofilm formation on bisphenol-Aglycidyldimethacrylate and triethylenglycoldimethacrylate (BisGMA-TEGDMA) thermosets with different content of bioactive glass 45S5. The second experiment (Study II) showed no significant difference in osteointegration of nanostructured and microsized polylactide-co-glycolide/β-tricalcium phosphate (PLGA /β-TCP) composites in a minipig model. The third experiment (Study III) demonstrated that positron emission tomography (PET) imaging with the novel 68Ga labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) CD33 related sialic-acid immunoglobulin like lectins (Siglec-9) tracer was able to detect inflammatory response to S. epidermidis and S. aureus peri-implant infections in an intraosseous polytetrafluoroethylene catheter model. In the fourth experiment (Study IV), BisGMATEGDMA thermosets coated with lactose-modified chitosan (Chitlac) and silver nanoparticles exhibited antibacterial activity against S. aureus and P. aeruginosa strains in an in vitro biofilm model and showed in vivo biocompatibility in a minipig model. In the last experiment (Study V), a selective androgen modulator (SARM) released from a poly(lactide)-co-ε-caprolactone (PLCL) polymer matrix failed to produce a dose-dependent enhancement of peri-implant osteogenesis in a bone marrow ablation model.

Effect of Erythrina velutina and Erythrina mulungu in rats submitted to animal models of anxiety and depression

Erythrina velutina (EV) and Erythrina mulungu (EM), popularly used in Brazil as tranquilizing agents, were studied. The effects of acute and chronic oral treatment with a water:alcohol extract of EV (7:3, plant grounded stem bark; acute = 100, 200, 400 mg/kg; chronic = 50, 100, 200 mg/kg) were evaluated in rats (N = 11-12) submitted to the elevated T-maze (for avoidance and escape measurements) model of anxiety. This model was selected for its presumed capacity to elicit specific subtypes of anxiety disorders recognized in clinical practice: avoidance has been related to generalized anxiety and escape to panic. Additionally, animals were treated with the same doses of EV and EM (water:alcohol 7:3, inflorescence extract) and submitted to the forced swim test for the evaluation of antidepressant activity (N = 7-10). Both treatment regimens with EV impaired elevated T-maze avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (avoidance 1, mean ± SEM, acute study: 131.1 ± 45.5 (control), 9.0 ± 3.3 (diazepam), 12.7 ± 2.9 (200 mg/kg), 28.8 ± 15.3 (400 mg/kg); chronic study: 131.7 ± 46.9 (control), 35.8 ± 29.7 (diazepam), 24.4 ± 10.4 (50 mg/kg), 29.7 ± 11.5 (200 mg/kg)). Neither EV nor EM altered measurements performed in the forced swim test, in contrast to the reference drug imipramine that significantly decreased immobility time after chronic treatment. These results were not due to motor alterations since no significant effects were detected in an open field. These observations suggest that EV exerts anxiolytic-like effects on a specific subset of defensive behaviors which have been associated with generalized anxiety disorder.

Studies on energy exchange between sea and atmosphere from the indian ocean with special reference to arabian sea and bay of bengal

There are only a few attempts in the Indian ocean to evolve reliable climatic models of energy exchange fluxes and to study their inter annul variations. Large space scale and time history of the flux fields could be estimated by the bulk aerodynamic exchange and radiation equation, making use of the climatic normal’s of the related parameters derived from the remarkably good amount of surface marine observations compiled and made available on magnetic tape TDF II by the national climatic centre of NOAA for the period of years 1854 –early 1973. In this thesis the author has made an attempt to calculate the thermal energy exchange fluxes in a meaningful way, using the bulk aerodynamic coefficients which depend on the changes in the wind speed. The spatial and temporal distribution of the exchanges of energy between the ocean and atmosphere , are presented and their impact on the climatic variations of the Indian ocean are discussed from the point of view of predominating air sea interaction processes.

Nuclear curvature energy in relativistic models

The difficulties arising in the calculation of the nuclear curvature energy are analyzed in detail, especially with reference to relativistic models. It is underlined that the implicit dependence on curvature of the quantal wave functions is directly accessible only in a semiclassical framework. It is shown that also in the relativistic models quantal and semiclassical calculations of the curvature energy are in good agreement.

Recovering Euclidean deformable models from stereo-motion

In this paper we present a novel structure from motion (SfM) approach able to infer 3D deformable models from uncalibrated stereo images. Using a stereo setup dramatically improves the 3D model estimation when the observed 3D shape is mostly deforming without undergoing strong rigid motion. Our approach first calibrates the stereo system automatically and then computes a single metric rigid structure for each frame. Afterwards, these 3D shapes are aligned to a reference view using a RANSAC method in order to compute the mean shape of the object and to select the subset of points on the object which have remained rigid throughout the sequence without deforming. The selected rigid points are then used to compute frame-wise shape registration and to extract the motion parameters robustly from frame to frame. Finally, all this information is used in a global optimization stage with bundle adjustment which allows to refine the frame-wise initial solution and also to recover the non-rigid 3D model. We show results on synthetic and real data that prove the performance of the proposed method even when there is no rigid motion in the original sequence

Global models for concrete realities

This paper intends to analyze the evolution of the Ecomuseums from their early appearance in the seventies until the present, emphasizing the characteristics which make them unique and different from all the other museums. This analysis will be used to show the Japanese landscape on ecomuseums and how the ecomuseum evolution might be a reference at internatioal level.

Japan ecomuseums: global models for concrete realities

The present document intends to analyze the different ecomuseums visited and studied in Japan trying to describe the reality of Japanese ecomuseology. From the descriptions of Japanese ecomuseums extrapolate the main features to build a model that is a possible reference for the XXI century ecomuseums.

Mesozoic climates: General circulation models and the rock record

General circulation models (GCMs) use the laws of physics and an understanding of past geography to simulate climatic responses. They are objective in character. However, they tend to require powerful computers to handle vast numbers of calculations. Nevertheless, it is now possible to compare results from different GCMs for a range of times and over a wide range of parameterisations for the past, present and future (e.g. in terms of predictions of surface air temperature, surface moisture, precipitation, etc.). GCMs are currently producing simulated climate predictions for the Mesozoic, which compare favourably with the distributions of climatically sensitive facies (e.g. coals, evaporites and palaeosols). They can be used effectively in the prediction of oceanic upwelling sites and the distribution of petroleum source rocks and phosphorites. Models also produce evaluations of other parameters that do not leave a geological record (e.g. cloud cover, snow cover) and equivocal phenomena such as storminess. Parameterisation of sub-grid scale processes is the main weakness in GCMs (e.g. land surfaces, convection, cloud behaviour) and model output for continental interiors is still too cold in winter by comparison with palaeontological data. The sedimentary and palaeontological record provides an important way that GCMs may themselves be evaluated and this is important because the same GCMs are being used currently to predict possible changes in future climate. The Mesozoic Earth was, by comparison with the present, an alien world, as we illustrate here by reference to late Triassic, late Jurassic and late Cretaceous simulations. Dense forests grew close to both poles but experienced months-long daylight in warm summers and months-long darkness in cold snowy winters. Ocean depths were warm (8 degrees C or more to the ocean floor) and reefs, with corals, grew 10 degrees of latitude further north and south than at the present time. The whole Earth was warmer than now by 6 degrees C or more, giving more atmospheric humidity and a greatly enhanced hydrological cycle. Much of the rainfall was predominantly convective in character, often focused over the oceans and leaving major desert expanses on the continental areas. Polar ice sheets are unlikely to have been present because of the high summer temperatures achieved. The model indicates extensive sea ice in the nearly enclosed Arctic seaway through a large portion of the year during the late Cretaceous, and the possibility of sea ice in adjacent parts of the Midwest Seaway over North America. The Triassic world was a predominantly warm world, the model output for evaporation and precipitation conforming well with the known distributions of evaporites, calcretes and other climatically sensitive facies for that time. The message from the geological record is clear. Through the Phanerozoic, Earth's climate has changed significantly, both on a variety of time scales and over a range of climatic states, usually baldly referred to as "greenhouse" and "icehouse", although these terms disguise more subtle states between these extremes. Any notion that the climate can remain constant for the convenience of one species of anthropoid is a delusion (although the recent rate of climatic change is exceptional). (c) 2006 Elsevier B.V. All rights reserved.

Multi-model assessment of stratospheric ozone return dates and ozone recovery in CCMVal-2 models

Projections of stratospheric ozone from a suite of chemistry-climate models (CCMs) have been analyzed. In addition to a reference simulation where anthropogenic halogenated ozone depleting substances (ODSs) and greenhouse gases (GHGs) vary with time, sensitivity simulations with either ODS or GHG concentrations fixed at 1960 levels were performed to disaggregate the drivers of projected ozone changes. These simulations were also used to assess the two distinct milestones of ozone returning to historical values (ozone return dates) and ozone no longer being influenced by ODSs (full ozone recovery). The date of ozone returning to historical values does not indicate complete recovery from ODSs in most cases, because GHG-induced changes accelerate or decelerate ozone changes in many regions. In the upper stratosphere where CO2-induced stratospheric cooling increases ozone, full ozone recovery is projected to not likely have occurred by 2100 even though ozone returns to its 1980 or even 1960 levels well before (~2025 and 2040, respectively). In contrast, in the tropical lower stratosphere ozone decreases continuously from 1960 to 2100 due to projected increases in tropical upwelling, while by around 2040 it is already very likely that full recovery from the effects of ODSs has occurred, although ODS concentrations are still elevated by this date. In the midlatitude lower stratosphere the evolution differs from that in the tropics, and rather than a steady decrease in ozone, first a decrease in ozone is simulated from 1960 to 2000, which is then followed by a steady increase through the 21st century. Ozone in the midlatitude lower stratosphere returns to 1980 levels by ~2045 in the Northern Hemisphere (NH) and by ~2055 in the Southern Hemisphere (SH), and full ozone recovery is likely reached by 2100 in both hemispheres. Overall, in all regions except the tropical lower stratosphere, full ozone recovery from ODSs occurs significantly later than the return of total column ozone to its 1980 level. The latest return of total column ozone is projected to occur over Antarctica (~2045–2060) whereas it is not likely that full ozone recovery is reached by the end of the 21st century in this region. Arctic total column ozone is projected to return to 1980 levels well before polar stratospheric halogen loading does so (~2025–2030 for total column ozone, cf. 2050–2070 for Cly+60×Bry) and it is likely that full recovery of total column ozone from the effects of ODSs has occurred by ~2035. In contrast to the Antarctic, by 2100 Arctic total column ozone is projected to be above 1960 levels, but not in the fixed GHG simulation, indicating that climate change plays a significant role.

The impact of uncertainty in satellite data on the assessment of flood inundation models

The performance of flood inundation models is often assessed using satellite observed data; however these data have inherent uncertainty. In this study we assess the impact of this uncertainty when calibrating a flood inundation model (LISFLOOD-FP) for a flood event in December 2006 on the River Dee, North Wales, UK. The flood extent is delineated from an ERS-2 SAR image of the event using an active contour model (snake), and water levels at the flood margin calculated through intersection of the shoreline vector with LiDAR topographic data. Gauged water levels are used to create a reference water surface slope for comparison with the satellite-derived water levels. Residuals between the satellite observed data points and those from the reference line are spatially clustered into groups of similar values. We show that model calibration achieved using pattern matching of observed and predicted flood extent is negatively influenced by this spatial dependency in the data. By contrast, model calibration using water elevations produces realistic calibrated optimum friction parameters even when spatial dependency is present. To test the impact of removing spatial dependency a new method of evaluating flood inundation model performance is developed by using multiple random subsamples of the water surface elevation data points. By testing for spatial dependency using Moran’s I, multiple subsamples of water elevations that have no significant spatial dependency are selected. The model is then calibrated against these data and the results averaged. This gives a near identical result to calibration using spatially dependent data, but has the advantage of being a statistically robust assessment of model performance in which we can have more confidence. Moreover, by using the variations found in the subsamples of the observed data it is possible to assess the effects of observational uncertainty on the assessment of flooding risk.

RAMI4PILPS: An intercomparison of formulations for the partitioning of solar radiation in land surface models

[1] Remotely sensed, multiannual data sets of shortwave radiative surface fluxes are now available for assimilation into land surface schemes (LSSs) of climate and/or numerical weather prediction models. The RAMI4PILPS suite of virtual experiments assesses the accuracy and consistency of the radiative transfer formulations that provide the magnitudes of absorbed, reflected, and transmitted shortwave radiative fluxes in LSSs. RAMI4PILPS evaluates models under perfectly controlled experimental conditions in order to eliminate uncertainties arising from an incomplete or erroneous knowledge of the structural, spectral and illumination related canopy characteristics typical for model comparison with in situ observations. More specifically, the shortwave radiation is separated into a visible and near-infrared spectral region, and the quality of the simulated radiative fluxes is evaluated by direct comparison with a 3-D Monte Carlo reference model identified during the third phase of the Radiation transfer Model Intercomparison (RAMI) exercise. The RAMI4PILPS setup thus allows to focus in particular on the numerical accuracy of shortwave radiative transfer formulations and to pinpoint to areas where future model improvements should concentrate. The impact of increasing degrees of structural and spectral subgrid variability on the simulated fluxes is documented and the relevance of any thus emerging biases with respect to gross primary production estimates and shortwave radiative forcings due to snow and fire events are investigated.