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Diffusion weighted imaging sequences are now widely available on Magnetic Resonance Imaging (MRI) scanners. Diffusion Tensor Imaging (DTI) of the brain is able to show white matter tracts and is now commonly used in human medicine to study brain anatomy, tumors, structural pathways,... The purpose of this study was to show the interest of DTI to reveal the white matter fibers in the dogs' brain. DTI MR Images for this study were obtained with a 3 T system of 4 dogs euthanized for other reasons than neurological disorders. Combined fractional anisotropic (FA) and directional maps were obtained in the first 2 hours after death. The heads were amputated immediately after scanning and stored in 10% formalin until preparation for dissection. An experienced anatomist tracked white matter tracts with clinical relevance using the scanner software. The selected tracts were REFVIDume rendered and correlated with gross dissection. Using DTI we were able to track relevant neurological connections, such as the corticospinal tract, the optic and the cerebellar tract. The three dimensional anatomy is better presented using modern visualization techniques. DTI seems to be a valuable tool in order to present clinically relevant white matter tracts to neurological clinicians and researchers.

Objectives: In recent years schizophrenia trials suffer from diminishing differences in effects of drug and placebo treatment even for established antipsychotics [1]. While there are multiple factors which can lead to difficulties in differentiating between placebo and drug treatment, one of them could be that the available rating scales, e.g. Positive and Negative Syndrome Scale (PANSS) [2] are not optimal for measuring the effect of drug treatment. The goal of this study was to analyse the responses of the individual items of PANSS and item subscales to drug and placebo treatment in order to find the ones which are most sensitive to differentiate between placebo and drug effect. Methods: We analysed data from seven clinical trials of different antipsychotics. “Mini-PANSS” scales consisting of the most sensitive items identified in exploratory analysis were created and analysed statistically. The power of these scales to show a statistically significant difference between the placebo and drug treatment was then compared with the power of total PANSS and its positive, negative and general psychopathology subscales. Additionally, pharmacokinetic-pharmacodynamic analysis was performed in order to determine which of these (sub)scales shows the highest drug effect on top of the placebo effect. Results: All 30 items of the PANSS scale show a therapeutic drug effect. Mini-PANSS scales consisting of items with the largest drug treatment response are somewhat better in differentiating between placebo and drug treatment than the total PANSS. However, the difference between the tested mini-PANSS scales and total PANSS is generally very small. Conclusions: None of the studied scales can replace PANSS total in the analysis of primary endpoints. References: [1] Kemp AS, Schooler NR, Kalali AH, Alphs L, Anand R, Awad G, et al. What is causing the reduced drug-placebo difference in recent schizophrenia clinical trials and what can be done about it? Schizophrenia Bulletin. 2010;36(3):504-9. [2] Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrom Scale (PANSS) for schizophrenia. Schizophrenia Bulletin. 1987;13(2):261-76.

For the calibration of any model, measurements are necessary. As measurements are expensive, it is of interest to determine beforehand which kind of samples will provide the maximum of information. Using a criterion related to the Fisher information matrix, it is possible to design a sampling scheme that will enable the most precise model parameter estimates. This approach was applied to a reactive transport model (based on SLIM) of Escherichia coli in the Scheldt Estuary. As this estuary is highly influenced by the tide, it is expected that careful timing of the samples with respect to the tidal cycle will have an effect on the quality of the data. The timing and also the positioning of samples were optimised according to the proposed criterion. In the investigated case studies the precision of the estimated parameters could be improved by up to a factor of ten, confirming the usefulness of this approach to maximize the amount of information that can be retrieved from a fixed number of samples.

The past environment is often reconstructed by measuring a certain proxy (e.g. delta O-18) in an environmental archive, i.e. a biogenic or abiogenic accreting structure which gradually accumulates mass and records the current environment during this mass formation (e.g. corals, shells, trees, ice cores, speleothems, etc.). Proxy analysis usually yields a record along a distance axis. However, to relate the data to environmental variations, the date associated with each data point has to be known too. This transformation from distance to time is not straightforward to solve, since accretion mostly proceeds at a varying and unknown rate. To solve this problem some hypotheses about the growth rate or the time series must be made. Depending on the application, different assumptions may be appropriate, resulting in or requiring a particular method to perform this transformation. The actual method used can hugely influence the final result and hence the interpretation of the data in terms of frequency and timing of events. However, no comparative study has been made so far, and most of the existing methods haven't been thoroughly assessed. Therefore, this paper aims to evaluate and compare the most popular methods. To keep the review manageable the scope was limited to those records where it can be assumed that the time series is periodic. Examples of periods include tidal, seasonal and ENSO (El Nino Southern Oscillation) cycles, and even cycles of thousands of years could be considered, as long as they are resolved in the measured record. Six methods to reconstruct the time base for periodic proxy records are compared in this review. Their performance in the presence of stochastic and systematic errors is tested on simulations and linked to the methods' underlying assumptions. As a final comparison, all methods are applied to a real world example. The goal of this overview is to provide an objective structure and comparison of the methods mostly used, so that the users are aware of the underlying assumptions and their consequences.

In this study we have explored to what extend the mean borefield and fluid outlet temperature of a borehole thermal energy storage system (BTESS) can be predicted with simple linear models. This is necessary to solve the optimal control problem for a BTESS by means of conventional optimization tools. The study shows that both fast transients (with a time-scale of one hour) and slow transients (with a time-scale of a year) can be predicted with a fifth order linear model resulting in an accuracy of ± 1°C if hourly measurements over the time span of half a year are available. ispartof: Proceedings of the Heat Pump Platform Symposium ispartof: Heat Pump Platform Symposium location:Sint-Katelijne-Waver, Belgium date:17 Sep - 17 Sep 2008 status: published

Understanding environmental proxies stored in biogenic carbonates has become a major task and a multidisciplinary endeavour. The CALMARs project (CALcareous MARine Skeletons as recorders of global climate changes) involved reading these records stored in biogenic carbonates and aimed at validating the skeletons of sclerosponges, bivalves and echinoderms as environmental proxies. The first aim was to determine the growth rates of two hyper calcified sponges: Ceratoporella nicholsoni and Petrobiona massiliana. Accumulative data for all specimens of C. nicholsoni collected and measured showed the mean average growth rate to be 198.25μm/yr (9 specimens: n=557, σ=15.23 μm/yr). The mean growth rate of Petrobiona massiliana was 242.76 μm/yr (13 specimens, n=189, σ=161.42 μm/yr). However, the growth rate of this species shows much variation between and within specimens, but falls within the range observed in other hyper calcified sponges. Secondly, we investigated the uptake route of elements into the tissues of Petrobiona massiliana. Transmission Electron Microscopy (TEM) observations showed uptake and accumulation of particles inside endocytic vesicles of specific cell types. Bacteria marked with strontium were also accumulated within phagosomes of the same cells and retained their strontium after incorporation. Incubations with the dissolved elements (up to 10 mM) did not allow the location of elements to be determined within the sponge tissue. However, supersaturated incubations (providing particulate ions) allowed element hotspots to be discovered using Scanning Electron Microscopy (SEM) + Energy Dispersive X-ray analysis (EDX). Focused Ion Beam-cut sections from the element hotspots enabled positive analysis using the Scanning TEM + EDX, but the exact cellular locations are still to be determined at the ultrastructural level. Thirdly, lead profiles from several sclerosponge skeletons were investigated. Nine lead profiles covering more than 130 years from eight sclerosponges of two different species, Ceratoporella nicholsoni and Stromatospongia vermicola, collected off Jamaica, Acklins Island and Turks and Caicos Island are compared. All the profiles display i) the rise in lead around 1950 linked with the atmospheric pollution due to the increasing use of leaded gasoline, and ii) the decrease in lead content during the eighties following the introduction of unleaded gasoline. It is demonstrated that lead curves from sclerosponges are reproducible within single specimens as well as between different specimens from similar locations. In addition, the study reveals information on the physiological functioning of sclerosponges and suggests non-linearity of the lead partitioning coefficient. Bivalve shells offer a great potential as environmental proxies, since they have a wide geographical range and are well represented in the fossil record since the Cretaceous. Nevertheless, they are much less studied than corals and foraminifera and are largely limited to isotopic studies. The general aim of this project was to increase our knowledge of δ18O, δ13C, Sr/Ca, Mg/Ca, U/Ca, Ba/Ca, and Pb/Ca in bivalve aragonite and calcite. The most well studied proxy of sea surface temperature (SST) in bivalve carbonate is δ18O, and it is well known that in addition to SST, the δ18O of the water dictates the δ18O value of the shell. This study clearly demonstrates that unknown δ18O of the water can cause severe errors when calculating SST from estuarine bivalve shells; with the example presented here providing calculated SSTs 1.7 to 6.4 °C warmer than measured. Therefore, a salinity independent or salinity proxy would greatly benefit SST reconstructions. In estuaries, shell δ13C has long been regarded as a potential salinity indicator. However, this study highlights the problems associated with the incorporation of light metabolic CO2 in the shell. Therefore, interpreting δ13C values in bivalve carbonate should be done with caution. In addition to δ13C, Ba/Ca ratios were investigated as a salinity proxy as well. In the calcite shells of M. edulis a strong linear relationship between shell ‘background’ Ba/Ca and water Ba/Ca was found in both the laboratory and field. Although each estuary will have different relationships between salinity and water Ba/Ca, shell Ba/Ca can be used as an indicator of salinity within one estuary. Similar patterns of relatively stable background levels interrupted with sharp episodic peaks were also found in the aragonite shells of S. giganteus, and appear nearly ubiquitous to all bivalves. However, there was an ontogenic decrease in S. giganteus background Ba/Ca ratios, illustrating that these proxies can be species specific. The ratios of Sr/Ca, Mg/Ca and U/Ca were investigated as salinity independent SST proxies, but none were correlated to SST in the two aragonitic and one calcitic bivalve studied. Finally, the use of bivalve shells as recorders of pollution was also assessed. There was both large inter- and intra-specimen variability in Pb/Ca ratios of M. mercenaria shells, but when enough shells were averaged, the typical anthropogenic Pb profile from 1949 to 2003 was evident. Biomineralization is obviously a biological process, and therefore, understanding the pathway of elemental incorporation is vital to understanding proxy incorporation under different temperature and salinity regimes. Results for the mussel, Mytilus edulis, showed uptake of Ca, Cd, Co, Cu and Hg displayed saturation kinetics. Because steady-state was observed at all the different metal exposure levels, it was unlikely that either internal metal binding sites or membrane transporters were saturated under those conditions. Our results indicate that uptake of trace elements and further processing in mussels involves different combinations of the general pathways including those intended for homeostasis of major ions such as Ca and Mg. There was no clear distinction between uptakes of essential and non- essential metals. Through uptake of trace elements is dependent mainly on free ion activity in the exposure water, our results have shown that there are cases when other chemical species may also be important predominantly taken up via the dietary route. Also the effect of temperature and salinity clearly shows deviations from the free ion activity model indicative for physiological regulation. Echinoderms are abundant in a wide geographical range from equatorial to Polar Regions and several species are rather long-lived (60 to 100y). In the present study, we investigated the effects of temperature on the incorporation of minor and trace elements and on the δ18O and δ13C in the skeleton of the wide-ranged temperate starfish Asterias rubens and in closely related sea urchin species collected from boreal to tropical latitudes. A highly significant temperature effect on the Mg incorporation in the skeleton in both experimental and field conditions was evidenced and matches the relation obtained in benthic foraminifera. This effect was independent of growth rate, contrary to previous statements. The slope of relative δ18O versus temperature in skeletons of starfish is also highly significant and neatly matches slopes measured in corals or molluscs. The Mg/Ca ratios of museum specimens are below those of present day specimens indicating a general warming trend.

Studies using oxygen isotopes (δ18O) of mollusk shells to determine paleotemperature need to assume water δ18O values, which could severely influence calculated temperatures. We analyzed aragonitic shells of the Butter Clam, Saxidomus giganteus (DeShayes, 1839), to determine the reproducibility of the isotopic signal between individuals and to assess how precisely temperature could be calculated given known salinity and temperature. Furthermore, carbon isotopes are also investigated as an environmental proxy. The abundance of well-preserved S. giganteus shells in archeological and geological deposits in northwestern North America makes them a particularly suitable species for paleoclimate studies. Seasonally resolved stable oxygen isotope profiles in three S. giganteus shells collected from the same site in Puget Sound (Washington, USA) were well correlated (0.77 < R2 < 0.87). Although there were differences up to 0.58‰ in high resolution δ18O profiles of the three shells, the difference between the average δ18O of each shell was less than half of this (0.19‰) and half of what has been reported for between-colony coral variability. δ13C profiles on the other hand were more complex, with shell δ13C being about 2.5‰ lower than expected equilibrium values. However, this roughly conforms to the idea that about 10% of the shell carbon originates from metabolic CO2. Both δ18O and δ13C indicate that S. giganteus do not grow during periods of reduced salinity. Despite the excellent reproducibility of δ18O between shells, and the fact that salinity effects were duly considered, calculated temperature still differed from instrumental temperature. Applying different salinity-δ18O water relationships to average shell δ18O, and considering salinity from the shell collection site and a nearby offshore station resulted in calculated average water temperatures ranging from 1.7 to 6.4 °C warmer than measured. Although we could not determine if S. giganteus precipitate their shells in isotopic equilibrium, we believe that the difficulty in predicting temperature arose from not being able to accurately determine δ18O of the water at the time of shell precipitation. These data highlight the difficulties inherent to using stable isotope profiles of estuarine biogenic carbonates as environmental proxies.

Tropical trees are often excluded from dendrochronological investigations because of a lack of distinct growth ring boundaries, causing a gap in paleoclimate reconstructions from tropical regions. The potential use of time series of vessel features (density, diameter, surface area and hydraulic conductivity) combined with spectral analysis as a proxy for environmental conditions in the mangrove Rhizophora mucronata was investigated. Intra-annual differences in the vessel features revealed a trade-off between hydraulic efficiency (large vessels) during the rainy season and hydraulic safety (small, more numerous vessels) during the dry season. In addition to the earlywood-latewood variations, a semiannual signal was discovered in the vessel density and diameters after Fourier transformation. The similarity in the Fourier spectra of the vessel features and the climate data, in particular mean relative humidity and precipitation, provides strong evidence for a climatic driving force for the intra-annual variability of the vessel features. The high-resolution approach used in this study, in combination with spectral analysis, may have great potential for the study of climate variability in tropical regions.

The record of an environmental proxy along a growth axis in biogenic carbonates can reflect changing environmental conditions experienced during the lifetime of the organism. When a chronology of the growth axis is not available, a method based on anchor points is commonly used to introduce a time grid. Between these anchor points a constant growth rate is generally assumed, despite the fact that growth rates change during life in most organisms. Here, we present a method which refines the constant growth rate assumption, at least in situations where the environmental proxy has a periodic component in its signal. A nonlinear growth rate can then be estimated, enabling the construction of a more realistic time base. The anchor point method and the method proposed here are first compared on a synthetic record. It is shown that the choice of the anchor points, which is always a subjective one, is largely influenced by the stochastic noise on the data record. This results in biased growth rate profiles and biased time grids. Next we apply the method on the Mg record in the bivalve Isognomon ephippium, on three samples of the clam Saxidomus giganteus from Washington State and on the Vanuatu coral stable isotope record. The method developed is applicable to a wide range of proxy records, which are measured along an indirect time grid and are complicated by nonlinear accretion rates. Furthermore, this method which takes variable growth rates into account opens perspectives on quantitative modeling of the relationship between environmental proxies recorded by accretive archives and the instrumental record, like temperature or salinity.

The second chapter handles the measurement. These are often collected with a Laser Ablation Inductively Coupled Mass Spectrometer (LA-ICP-MS) and the first problem we encountered was the calibration of this instrument. It is used to measure trace elements with an incredibly high spatial resolution. Of course, it has also some major disadvantages. One of these is that the laser, which is used to ablate the solid substrate, has a variable intensity. In addition several other internal instrumental parameters seem to vary over time in an unpredictable manner. Therefore, people use internal standards for more than twenty years. Such internal standards are elements whose concentration does not vary over the sample. Consequently,all variation detected in these internal standards must be due to artificial variation in the instrument. Because the drift of the instrument is reflected in the measurementofthe internal standard, all other concentrationscan be calibratedaccordingto this internal standard. This simple idea seems to work quite well. Unfortunately, the calibration algorithm does not take into account measurement noise in the signal of the internal standards. This is exactly the improvement that we made: imagine two internal standards, each consisting of the same drift pattern, and disturbed by a different noise pattern. A better approximation of the true drift pattern can be reached by the arithmetic mean of both internal standards.Hereinthe drift remains and the noise cancels out. This idea is further refined, so that the uncertainty on the internal standards can be taken into account as well, and an a priori and an a posteriori verification of the model used is given. Further, the myth of mass dependent internal standards is ruled out and finally a real world example is processed. An additional important property of the proposed calibration is that an internal quality check is performed, which warns the investigator if some artefacts or problems occurred during the measurement. The remaining part of this work is devoted to the reconstruction of time series. One of the major problems with data-processing of proxy records (e.g. stable isotope ratios of oxygen or carbon, or trace elements in shells, sponges, corals, sediment cores, etc ) is the dating of individual observations. All these proxy records are measured as function of a distance, while generally the time series are desired. Due to variations and differences in accretion rate, each record has its unique distance series, which cannot be compared with other records or models. Therefore, distance series are transformed into time series. However, this is only possible if additional information about the accretion rate is available. Unfortunately, this is mostly not the case and thus additional assumptions are necessary. Such assumption can be made about the signal and formally written down in the signal model. In addition,the concept of a time base distortion is introduced.As will be shown,this enables us to estimate variations in accretion rate. For this, we started from a previously estimated time base (if this is unknown, we initialize the time base assuming a constant accretion rate). Next, we allow this base to be distorted due to nonlinear accretion rates or hiatuses and we will show how such a distortion can be estimated. In the third chapter, we have illustrated how the time series can be reconstructed, assuming a periodic proxy-record. Therefore, the concept of time base distortions is introduced. First, we propose a model for variations in accretion rate. Next, we illustrate how this accretion rate can be identified and estimated in the Fourier spectrum of the proxy. This approach is compared with the widely used anchor point method in two manners: the assumptions made are compared and next the sensitivity of both methods w.r.t. stochastic noise is illustrated on a simulation. Three case studies are incorporated to validate the method and to illustrate its usef

The reproductive behaviour of the longleaved sundew Drosera intermedia Hayne was studied in three hydrologically differing heathland habitats: a pool edge, an old path through the wet heath and a seepage area. Sexual reproductive allocation (SRA) (the slope of thc regression of sexual on vegetative biomass in a given season) differed strongly between years (related to temperature and precipitation) and habitats. Averaged over years. path plants had a higher SRA than plants in the seepage area and at the pool edge. Asexual reproductive allocation. expressed as thc size-dependent probability of reproducing asexually, did not differ between habitats in most years. The observations agreed with general life history theory. SRA was high in the path habitat where adult survival chances were low and juvenile (= seed, first year seedling) survival was high. SRA was lower in the seepage area where adult survival chances were higher and juvenile survival lower. At the pool edge, a habitat with high adult mortality and low juvenile establishment, the predicted optimal reproductive behaviour, a high SRA, was not observed due to environmental constraints (inundation).

The effect of naturally caught insects, measured as the number of prey caught over the whole growing season, on growth and flowering of the carnivorous plant Drosera intermedia Hayne was investigated in four populations in two different heathland habitats : (1) a path through the wet heath where the plants root in a podzol, (2) a seepage area where plants root in a peaty soil or among Sphagnum. There was a positive correlation between vegetative growth during the growing season 1987 and the number of prey caught that season in all populations. No relationship between prey number and next year's vegetative growth was found. The number of prey caught in May and June 1987 was positively related to the probability to flower that year in the path populations (trend in the seepage area). The number of prey caught between May and August 1987 was positively related to flowering the following year in the seepage area, but not in the path populations. Overall, the data show that D. intermedia in the two contrasting habitats, benefits from insect prey both in terms of vegetative growth and flowering.