Accurate performance of a rat model of schizophrenia in the water maze depends on visual cue availability and stability: a distortion in cognitive mapping abilities?

Rats were treated postnatally (PND 5-16) with BSO (l-buthionine-(S,R)-sulfoximine) in an animal model of schizophrenia based on transient glutathione deficit. The BSO treated rats were impaired in patrolling a maze or a homing table when adult, yet demonstrated preserved escape learning, place discrimination and reversal in a water maze task [37]. In the present work, BSO rats' performance in the water maze was assessed in conditions controlling for the available visual cues. First, in a completely curtained environment with two salient controlled cues, BSO rats showed little accuracy compared to control rats. Secondly, pre-trained BSO rats were impaired in reaching the familiar spatial position when curtains partially occluded different portions of the room environment in successive sessions. The apparently preserved place learning in a classical water maze task thus appears to require the stability and the richness of visual landmarks from the surrounding environment. In other words, the accuracy of BSO rats in place and reversal learning is impaired in a minimal cue condition or when the visual panorama changes between trials. However, if the panorama remains rich and stable between trials, BSO rats are equally efficient in reaching a familiar position or in learning a new one. This suggests that the BSO accurate performance in the water maze does not satisfy all the criteria for a cognitive map based navigation on the integration of polymodal cues. It supports the general hypothesis of a binding deficit in BSO rats.

New roles for community pharmacists in modern health care systems: a challenge for pharmacy education and research.

The academic activities led by the Unit of Community Pharmacy can be classified as translational. Our group is interested in person-centered pharmaceutical services aimed at a more responsible use of drugs (effectiveness, safety, efficiency) in collaboration with physicians and other health care professionals in a primary care setting. The following domains of education and research are high priorities for our group: medication therapy management, medication adherence, integrated care, individualization of therapies, care management for the elderly and e-health.

Advances in Sequence Analysis: Theory, Methods, Applications

This book gives a general view of sequence analysis, the statistical study of successions of states or events. It includes innovative contributions on life course studies, transitions into and out of employment, contemporaneous and historical careers, and political trajectories. The approach presented in this book is now central to the life-course perspective and the study of social processes more generally. This volume promotes the dialogue between approaches to sequence analysis that developed separately, within traditions contrasted in space and disciplines. It includes the latest developments in sequential concepts, coding, atypical datasets and time patterns, optimal matching and alternative algorithms, survey optimization, and visualization. Field studies include original sequential material related to parenting in 19th-century Belgium, higher education and work in Finland and Italy, family formation before and after German reunification, French Jews persecuted in occupied France, long-term trends in electoral participation, and regime democratization. Overall the book reassesses the classical uses of sequences and it promotes new ways of collecting, formatting, representing and processing them. The introduction provides basic sequential concepts and tools, as well as a history of the method. Chapters are presented in a way that is both accessible to the beginner and informative to the expert.

Cereal mycorrhiza: an ancient symbiosis in modern agriculture.

The majority of terrestrial plants live in association with symbiotic fungi that facilitate mineral nutrient uptake. The oldest and most prevalent of these associations are the arbuscular mycorrhizal (AM) symbioses that first evolved approximately 400 million years ago, coinciding with the appearance of the first land plants. Crop domestication, in comparison, is a relatively recent event, beginning approximately 10000 years ago. How has the dramatic change from wild to cultivated ecosystems impacted AM associations, and do these ancient symbioses potentially have a role in modern agriculture? Here, we review recent advances in AM research and the use of breeding approaches to generate new crop varieties that enhance the agronomic potential of AM associations.

On the Schoenberg transformations in data analysis: theory and illustrations

The class of Schoenberg transformations, embedding Euclidean distances into higher dimensional Euclidean spaces, is presented, and derived from theorems on positive definite and conditionally negative definite matrices. Original results on the arc lengths, angles and curvature of the transformations are proposed, and visualized on artificial data sets by classical multidimensional scaling. A distance-based discriminant algorithm and a robust multidimensional centroid estimate illustrate the theory, closely connected to the Gaussian kernels of Machine Learning.

Nd and Sr isotope compositions in modern and fossil bones - Proxies for vertebrate provenance and taphonomy

Rare earth elements (REE), while not essential for the physiologic functions of animals, are ingested and incorporated in ppb concentrations in bones and teeth. Nd isotope compositions of modern bones of animals from isotopically distinct habitats demonstrate that the (143)Nd/(144)Nd of the apatite can be used as a fingerprint for bedrock geology or ambient water mass. This potentially allows the provenance and migration of extant vertebrates to be traced, similar to the use of Sr isotopes. Although REE may be enriched by up to 5 orders of magnitude during diagenesis and recrystallization of bone apatite, in vivo (143)Nd/(144)Nd may be preserved in the inner cortex of fossil bones or enamel. However, tracking the provenance of ancient or extinct vertebrates is possible only for well-preserved archeological and paleontological skeletal remains with in vivo-like Nd contents at the ppb-level. Intra-bone and -tooth REE analysis can be used to screen for appropriate areas. Large intra-bone Nd concentration gradients of 10(1)-10(3) are often measured. Nd concentrations in the inner bone cortex increase over timescales of millions of years, while bone rims may be enriched over millenial timescales. Nevertheless, epsilon(Nd) values are often similar within one epsilon(Nd) unit within a single bone. Larger intra-bone differences in specimens may either reflect a partial preservation of in vivo values or changing epsilon(Nd) values of the diagenetic fluid during fossilization. However, most fossil specimens and the outer rims of bones will record taphonomic (143)Nd/(144)Nd incorporated post mortem during diagenesis. Unlike REE patterns, (143)Nd/(144)Nd are not biased by fractionation processes during REE-uptake into the apatite crystal lattice, hence the epsilon(Nd) value is an important tracer for taphonomy and reworking. Bones and teeth from autochthonous fossil assemblages have small variations of +/- 1 epsilon(Nd) unit only. In contrast, fossil bones and teeth from over 20 different marine and terrestrial fossil sites have a total range of epsilon(Nd) values from -13.0 to 4.9 (n = 80), often matching the composition of the embedding sediment. This implies that the surrounding sediment is the source of Nd in the fossil bones and that the specimens of this study seem not to have been reworked. Differences in epsilon(Nd) values between skeletal remains and embedding sediment may either indicate reworking of fossils and/or a REE-uptake from a diagenetic fluid with non-sediment derived epsilon(Nd) values. The latter often applies to fossil shark teeth, which may preserve paleo-seawater values. Complementary to epsilon(Nd) values, (87)Sr/(86)Sr can help to further constrain the fossil provenance and reworking. (C) 2011 Elsevier Ltd. All rights reserved.

Implementation of bayesian therapeutic drug monitoring in modern patient care

The variability observed in drug exposure has a direct impact on the overall response to drug. The largest part of variability between dose and drug response resides in the pharmacokinetic phase, i.e. in the dose-concentration relationship. Among possibilities offered to clinicians, Therapeutic Drug Monitoring (TDM; Monitoring of drug concentration measurements) is one of the useful tool to guide pharmacotherapy. TDM aims at optimizing treatments by individualizing dosage regimens based on blood drug concentration measurement. Bayesian calculations, relying on population pharmacokinetic approach, currently represent the gold standard TDM strategy. However, it requires expertise and computational assistance, thus limiting its large implementation in routine patient care. The overall objective of this thesis was to implement robust tools to provide Bayesian TDM to clinician in modern routine patient care. To that endeavour, aims were (i) to elaborate an efficient and ergonomic computer tool for Bayesian TDM: EzeCHieL (ii) to provide algorithms for drug concentration Bayesian forecasting and software validation, relying on population pharmacokinetics (iii) to address some relevant issues encountered in clinical practice with a focus on neonates and drug adherence. First, the current stage of the existing software was reviewed and allows establishing specifications for the development of EzeCHieL. Then, in close collaboration with software engineers a fully integrated software, EzeCHieL, has been elaborated. EzeCHieL provides population-based predictions and Bayesian forecasting and an easy-to-use interface. It enables to assess the expectedness of an observed concentration in a patient compared to the whole population (via percentiles), to assess the suitability of the predicted concentration relative to the targeted concentration and to provide dosing adjustment. It allows thus a priori and a posteriori Bayesian drug dosing individualization. Implementation of Bayesian methods requires drug disposition characterisation and variability quantification trough population approach. Population pharmacokinetic analyses have been performed and Bayesian estimators have been provided for candidate drugs in population of interest: anti-infectious drugs administered to neonates (gentamicin and imipenem). Developed models were implemented in EzeCHieL and also served as validation tool in comparing EzeCHieL concentration predictions against predictions from the reference software (NONMEM®). Models used need to be adequate and reliable. For instance, extrapolation is not possible from adults or children to neonates. Therefore, this work proposes models for neonates based on the developmental pharmacokinetics concept. Patients' adherence is also an important concern for drug models development and for a successful outcome of the pharmacotherapy. A last study attempts to assess impact of routine patient adherence measurement on models definition and TDM interpretation. In conclusion, our results offer solutions to assist clinicians in interpreting blood drug concentrations and to improve the appropriateness of drug dosing in routine clinical practice.

The Implied Book and the Narrative Text. On a Blind Spot in Narratological Theory - from a Media Studies Perspective

The article is concerned with the formal definition of a largely unnoticed factor in narrative structure. Based on the assumptions that (1) the semantics of a written text depend, among other factors, directly on its visual alignment in space, that (2) the formal structure of a text has to meet that of its spatial presentation and that (3) these assumptions hold true also for narrative texts (which, however, in modern times typically conceal their spatial dimensions by a low-key linear layout), it is argued that, how ever low-key, the expected material shape of a given narrative determines the configuration of its plot by its author. The ,implied book' thus denotes an author's historically assumable, not necessarily conscious idea of how his text, which is still in the process of creation, will be dimensionally presented and under these circumstances visually absorbed. Assuming that an author's knowledge of this later (potentially) substantiated material form influences the composition, the implied book is to be understood as a text-genetically determined, structuring moment of the text. Historically reconstructed, it thus serves the methodical analysis of structural characteristics of a completed text.

Identification of muscle-specific calpain and beta-sarcoglycan genes in progressive autosomal recessive muscular dystrophies.

The autosomal recessive forms of limb-girdle muscular dystrophies are encoded by at least five distinct genes. The work performed towards the identification of two of these is summarized in this report. This success illustrates the growing importance of genetics in modern nosology.