Showing papers by "University of Rennes published in 2005"
VU University Amsterdam1, University of Rennes2, Vita-Salute San Raffaele University3, University of Düsseldorf4, University of Basel5, Icahn School of Medicine at Mount Sinai6, Foothills Medical Centre7, National Institutes of Health8, University of Toronto9, Lund University10, Mayo Clinic11, University of Texas Health Science Center at Houston12
TL;DR: New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease.
Abstract: New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity.
4,862 citations
Kerstin Lindblad-Toh1, Claire M. Wade1, Claire M. Wade2, Tarjei S. Mikkelsen3 +238 more•Institutions (11)
TL;DR: A high-quality draft genome sequence of the domestic dog is reported, together with a dense map of single nucleotide polymorphisms (SNPs) across breeds, to shed light on the structure and evolution of genomes and genes.
Abstract: Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
2,431 citations
TL;DR: An analysis of the known ARE-binding proteins (ARE-BP) with respect to their mRNA targets and the consequences of their binding to the mRNA is presented and several hypotheses that could unify the published data are presented and suggest avenues for future research.
Abstract: The control of mRNA stability is an important process that allows cells to not only limit, but also rapidly adjust, the expression of regulatory factors whose over expression may be detrimental to the host organism. Sequence elements rich in A and U nucleotides or AU-rich elements (AREs) have been known for many years to target mRNAs for rapid degradation. In this survey, after briefly summarizing the data on the sequence characteristics of AREs, we present an analysis of the known ARE-binding proteins (ARE-BP) with respect to their mRNA targets and the consequences of their binding to the mRNA. In this analysis, both the changes in mRNA stability and the lesser studied effects on translation are considered. This analysis highlights the multitude of mRNAs bound by one ARE-BP and conversely the large number of ARE-BP that associate with any particular ARE-containing mRNA. This situation is discussed with respect to functional redundancies or antagonisms. The potential relationship between mRNA stability and translation is also discussed. Finally, we present several hypotheses that could unify the published data and suggest avenues for future research.
1,016 citations
TL;DR: In this article, the authors focus on reducing propagule loads on humans, and their food, cargo, and transport vessels, in order to reduce the risk of alien introductions to Antarctica and the sub-Antarctic.
Abstract: Alien microbes, fungi, plants and animals occur on most of the sub-Antarctic islands and some parts of the Antarctic continent. These have arrived over approximately the last two centuries, coincident with human activity in the region. Introduction routes have varied, but are largely associated with movement of people and cargo in connection with industrial, national scientific program and tourist operations. The large majority of aliens are European in origin. They have both direct and indirect impacts on the functioning of species-poor Antarctic ecosystems, in particular including substantial loss of local biodiversity and changes to ecosystem processes. With rapid climate change occurring in some parts of Antarctica, elevated numbers of introductions and enhanced success of colonization by aliens are likely, with consequent increases in impacts on ecosystems. Mitigation measures that will substantially reduce the risk of introductions to Antarctica and the sub-Antarctic must focus on reducing propagule loads on humans, and their food, cargo, and transport vessels.
644 citations
TL;DR: In this paper, the genome organizations of eight phylogenetically distinct species from five mammalian orders were compared in order to address fundamental questions relating to mammalian chromosomal evolution, and it was found that segmental duplications populate the majority of primate-specific breakpoints and often flank inverted chromosome segments, implicating their role in chromosomal rearrangement.
Abstract: The genome organizations of eight phylogenetically distinct species from five mammalian orders were compared in order to address fundamental questions relating to mammalian chromosomal evolution. Rates of chromosome evolution within mammalian orders were found to increase since the Cretaceous-Tertiary boundary. Nearly 20% of chromosome breakpoint regions were reused during mammalian evolution; these reuse sites are also enriched for centromeres. Analysis of gene content in and around evolutionary breakpoint regions revealed increased gene density relative to the genome-wide average. We found that segmental duplications populate the majority of primate-specific breakpoints and often flank inverted chromosome segments, implicating their role in chromosomal rearrangement.
524 citations
TL;DR: Surprisingly, 30% of the parental methylation patterns are altered in the hybrids and the allopolyploid, and this high level of epigenetic regulation might explain the morphological plasticity of Spartina anglica and its larger ecological amplitude.
Abstract: To study the consequences of hybridization and genome duplication on polyploid genome evolution and adaptation, we used independently formed hybrids (Spartina x townsendii and Spartina x neyrautii) that originated from natural crosses between Spartina alterniflora, an American introduced species, and the European native Spartina maritima. The hybrid from England, S. x townsendii, gave rise to the invasive allopolyploid, salt-marsh species, Spartina anglica. Recent studies indicated that allopolyploid speciation may be associated with rapid genetic and epigenetic changes. To assess this in Spartina, we performed AFLP (amplified fragment length polymorphism) and MSAP (methylation sensitive amplification polymorphism) on young hybrids and the allopolyploid. By comparing the subgenomes in the hybrids and the allopolyploid to the parental species, we inferred structural changes that arose repeatedly in the two independently formed hybrids. Surprisingly, 30% of the parental methylation patterns are altered in the hybrids and the allopolyploid. This high level of epigenetic regulation might explain the morphological plasticity of Spartina anglica and its larger ecological amplitude. Hybridization rather than genome doubling seems to have triggered most of the methylation changes observed in Spartina anglica.
388 citations
TL;DR: The dynamics of compaction and its 'jamming' phenomena is focused on, outlining recent statistical mechanics approaches to describe it and their deep correspondence with thermal systems such as glass formers.
Abstract: Granular materials are of substantial importance in many industrial and natural processes, yet their complex behaviours, ranging from mechanical properties of static packing to their dynamics, rheology and instabilities, are still poorly understood. Here we focus on the dynamics of compaction and its 'jamming' phenomena, outlining recent statistical mechanics approaches to describe it and their deep correspondence with thermal systems such as glass formers. In fact, granular media are often presented as ideal systems for studying complex relaxation towards equilibrium. Granular compaction is defined as an increase of the bulk density of a granular medium submitted to mechanical perturbation. This phenomenon, relevant in many industrial processes and widely studied by the soil mechanics community, is simple enough to be fully investigated and yet reveals all the complex nature of granular dynamics, attracting considerable attention in a broad range of disciplines ranging from chemical to physical sciences.
384 citations
TL;DR: In this article, the spectral properties of the Ruelle-Perron-Frobenius operator associated to an Anosov map on classes of functions with high smoothness were studied.
Abstract: We study the spectral properties of the Ruelle-Perron-Frobenius operator associated to an Anosov map on classes of functions with high smoothness. To this end we construct anisotropic Banach spaces of distributions on which the transfer operator has a small essential spectrum. In the C ∞ case, the essential spectral radius is arbitrarily small, which yieldsa descriptionof the correlationswith arbitraryprecision. Moreover,we obtain sharp spectral stability results for deterministic and random perturbations. In particular, we obtain differentiability results for spectral data (which imply differentiability of the Sinai-Ruelle-Bowenmeasure, the variancefor the centrallimit theorem, the rates of decay for smooth observable, etc.).
317 citations
TL;DR: The recent developments in electrophilic activation of enynes are discussed and it is shown that simple catalysts such as [Ru(3)(CO)(12)], PtCl(2), and cationic gold complexes are efficient precursors to promote the formation of functional polyclic compounds.
Abstract: Transformations of enynes in the presence of transition-metal catalysts have played an important role in the preparation of a variety of cyclic compounds. Recent developments in the activation of triple carbon–carbon bonds by electrophilic metal centers have provided a new entry to the selective synthesis of cyclopropane derivatives from enynes. The mechanisms of these reactions involve catalytic species with both ionic and cyclopropylcarbenoid character. This type of activation will undoubtedly be further developed for application to other unsaturated hydrocarbons and inspire new catalytic cascade reaction sequences. This Minireview discusses the recent developments in electrophilic activation of enynes and shows that simple catalysts such as [Ru3(CO)12], PtCl2, and cationic gold complexes are efficient precursors to promote the formation of functional polyclic compounds.
314 citations
TL;DR: In this paper, the authors analyzed five arthropod taxa covering a broad range of functional aspects (wild bees, true bugs, carabid beetles, hoverflies and spiders) in 24 landscapes (4 x 4 km) across seven European countries along gradients of both land-use intensity and landscape structure.
Abstract: 1. In landscapes influenced by anthropogenic activities, such as intensive agriculture, knowledge of the relative importance and interaction of environmental factors on the composition and function of local communities across a range of spatial scales is important for maintaining biodiversity. 2. We analysed five arthropod taxa covering a broad range of functional aspects (wild bees, true bugs, carabid beetles, hoverflies and spiders) in 24 landscapes (4 x 4 km) across seven European countries along gradients of both land-use intensity and landscape structure. Species-environment relationships were examined in a hierarchical design of four main sets of environmental factors (country, land-use intensity, landscape structure, local habitat properties) that covered three spatial scales (region, landscape, local) by means of hierarchical variability partitioning using partial canonical correspondence analyses. 3. Local community composition and the distribution of body size classes and trophic guilds were most affected by regional processes, which highly confounded landscape and local factors. After correcting for regional effects, factors at the landscape scale dominated over local habitat factors. Land-use intensity explained most of the variability in species data, whereas landscape characteristics (especially connectivity) accounted for most of the variability in body size and trophic guilds. 4. Synthesis and applications. Our results suggest that management effort should be focused on land-use intensity and habitat connectivity in order to enhance diversity in agricultural landscapes. Since these factors are largely independent, specific conservation programmes may be developed with regards to socio-economic and agri-environmental requirements. Changes in either of these factors will enhance diversity but will also result in specific effects on local communities related to dispersal ability and the resource use of species.
301 citations
TL;DR: Dyssynchrony assessed by longitudinal motion is less sensitive to dyssynchrony, follows different time courses than those from circumferential motion, and may manifest CRT benefit during specific cardiac phases depending on pacing mode.
Abstract: Background— QRS duration is commonly used to select heart failure patients for cardiac resynchronization therapy (CRT). However, not all patients respond to CRT, and recent data suggest that direct assessments of mechanical dyssynchrony may better predict chronic response. Echo-Doppler methods are being used increasingly, but these principally rely on longitudinal motion (ell). It is unknown whether this analysis yields qualitative and/or quantitative results similar to those based on motion in the predominant muscle-fiber orientation (circumferential; ecc). Methods and Results— Both ell and ecc strains were calculated throughout the left ventricle from 3D MR-tagged images for the full cardiac cycle in dogs with cardiac failure and a left bundle conduction delay. Dyssynchrony was assessed from both temporal and regional strain variance analysis. CRT implemented by either biventricular (BiV) or left ventricular–only (LV) pacing enhanced systolic function similarly and correlated with improved dyssynchrony ...
TL;DR: Questions related to Aurora overexpression, which include why do polyploid cells containing abnormal centrosome numbers induced by Aurora not get eliminated at cell-cycle checkpoints, are addressed in this review.
TL;DR: In vitro binding assays indicate that one sRNA encoded within a pathogenicity island is a trans-encoded antisense RNA regulating the expression of target genes at the posttranscriptional level, suggesting that they are involved in the regulation of staphylococcal virulence.
Abstract: Small RNA (sRNA) genes are expressed in all organisms, primarily as regulators of translation and message stability. We have developed comparative genomic approaches to identify sRNAs that are expressed by Staphylococcus aureus, the most common cause of hospital-acquired infections. This study represents an in-depth analysis of the RNome of a Gram-positive bacterium. A set of sRNAs candidates were identified in silico within intergenic regions, and their expression levels were monitored by using microarrays and confirmed by Northern blot hybridizations. Two sRNAs were also detected directly from purification and RNA sequence determination. In total, at least 12 sRNAs are expressed from the S. aureus genome, five from the core genome and seven from pathogenicity islands that confer virulence and antibiotic resistance. Three sRNAs are present in multiple (two to five) copies. For the sRNAs that are conserved throughout the bacterial phylogeny, their secondary structures were inferred by phylogenetic comparative methods. In vitro binding assays indicate that one sRNA encoded within a pathogenicity island is a trans-encoded antisense RNA regulating the expression of target genes at the posttranscriptional level. Some of these RNAs show large variations of expression among pathogenic strains, suggesting that they are involved in the regulation of staphylococcal virulence.
TL;DR: The two approaches to induce noncentrosymmetry at the macroscopic level, either by supramolecular organization or by the all optical poling procedure are shown.
Abstract: Coordination compounds are of particular interest for the design of new chromophores with large nonlinear optical (NLO) susceptibilities. They offer a wide range of metals with different oxidation states and ligands, which can give rise to tunable electronic properties. Metal ions are excellent templates to build 2D and 3D octupolar NLO-phores. Their associations with functionalized bipyridyl ligands give rise to octahedral and tetrahedral metal complexes with large first-order hyperpolarizabilities. The ability to functionalize these octupoles allows their incorporation into macromolecular architectures such as polymers and metallodendrimers, We also show in this Account two approaches to induce noncentrosymmetry at the macroscopic level, either by supramolecular organization or by the all optical poling procedure.
TL;DR: Nocturnal production of melatonin is reduced in autism, and was significantly negatively correlated with severity of autistic impairments in verbal communication and play.
TL;DR: In this article, the authors investigated the relationship between steepness and incision rate and showed that the relationship is always a power law whose exponent depends on the channel cross-sectional geometry and runoff variability.
Abstract: Long-term bedrock incision is driven by daily discharge events of variable magnitude and frequency, with ineffective events below an incision threshold. We explore theoretically how this short-term stochastic behavior controls long-term steady state incision rates and bedrock channel profiles, combining a realistic frequency-magnitude distribution of discharge with a deterministic, detachment-limited incision model in which incision rate is a power function of basal shear stress above a critical shear stress. Our model predicts a power law relationship between steady state slope and drainage area consistent with observations. The exponent of this power law is independent of discharge mean and variability, while the amplitude factor, which controls mountain belt relief, is a power law function of mean runoff (with an exponent of -0.5) and a complex function of runoff variability. In accordance with evidence that incision occurs between 6 and 20% of time in rapidly incising rivers (>1 mm/yr) our model predicts that channel steepness is virtually insensitive to runoff variability. Runoff variability can only decrease channel steepness for very slow incision rates and/or weak lithologies. The relationship between channel steepness and incision rate is always a power law whose exponent depends on the channel cross-sectional geometry and runoff variability. This contradicts models neglecting discharge stochasticity in which the steepness-incision scaling is set by the incision law exponent. Our results suggest that changes in climate variability cannot explain an increase in bedrock incision rates during the Late Cenozoic within the context of a detachment limited model.
Journal Article•
TL;DR: Electrophysiologic patterns typically observed during the transition from interictal to ictal activity in human mesial temporal lobe epilepsy are related to mechanisms (at a neuronal population level) involved in seizure generation through a computational model of EEG activity.
Abstract: In human partial epilepsies and in experimental models of chronic and/or acute epilepsy, the role of inhibition and the relationship between the inhibition and excitation and epileptogenesis has long been questioned. Besides experimental methods carried out either in vitro (human or animal tissue) or in vivo (animals), pathophysiologic mechanisms can be approached by direct recording of brain electrical activity in human epilepsy. Indeed, in some clinical presurgical investigation methods like stereoelectroencephalography, intracerebral electrodes are used in patients suffering from drug resistant epilepsy to directly record paroxysmal activities with excellent temporal resolution (in the order of 1 millisecond). The study of neurophysiologic mechanisms underlying such depth-EEG activities is crucial to progress in the understanding of the interictal to ictal transition. In this study, the authors relate electrophysiologic patterns typically observed during the transition from interictal to ictal activity in human mesial temporal lobe epilepsy (MTLE) to mechanisms (at a neuronal population level) involved in seizure generation through a computational model of EEG activity. Intracerebral EEG signals recorded from hippocampus in five patients with MTLE during four periods (during interictal activity, just before seizure onset, during seizure onset, and during ictal activity) were used to identify the three main parameters of a model of hippocampus EEG activity (related to excitation, slow dendritic inhibition and fast somatic inhibition). The identification procedure used optimization algorithms to minimize a spectral distance between real and simulated signals. Results demonstrated that the model generates very realistic signals for automatically identified parameters. They also showed that the transition from interictal to ictal activity cannot be simply explained by an increase in excitation and a decrease in inhibition but rather by time-varying ensemble interactions between pyramidal cells and local interneurons projecting to either their dendritic or perisomatic region (with slow and fast GABAA kinetics). Particularly, during preonset activity, an increasing dendritic GABAergic inhibition compensates a gradually increasing excitation up to a brutal drop at seizure onset when faster oscillations (beta and low gamma band, 15 to 40 Hz) are observed. These faster oscillations are then explained by the model feedback loop between pyramidal cells and interneurons targeting their perisomatic region. These findings obtained from model identification in human temporal lobe epilepsy are in agreement with some results obtained experimentally, either on animal models of epilepsy or on the human epileptic tissue.
TL;DR: Evidence is supported that aggregation relies on mechanisms of amplification, supported by interactions between individuals that follow simple rules based on local information and without knowledge of the global structure.
TL;DR: Results obtained indicates that USF factors are key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism, and in melanocytes USF-1 has been implicated as a key UV-activated regulator of genes associated with pigmentation.
Abstract: Upstream stimulating factors (USF), USF-1 and USF-2, are members of the eucaryotic evolutionary conserved basic-Helix-Loop-Helix-Leucine Zipper transcription factor family. They interact with high affinity to cognate E-box regulatory elements (CANNTG), which are largely represented across the whole genome in eucaryotes. The ubiquitously expressed USF-transcription factors participate in distinct transcriptional processes, mediating recruitment of chromatin remodelling enzymes and interacting with co-activators and members of the transcription pre-initiation complex. Results obtained from both cell lines and knock-out mice indicates that USF factors are key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism, and in melanocytes USF-1 has been implicated as a key UV-activated regulator of genes associated with pigmentation. This review will focus on general characteristics of the USF-transcription factors and their place in some regulatory networks.
TL;DR: It is demonstrated that COPD patients produce greater quantities of MMP-12 than controls, which may be a critical step in the pathogenesis of COPD and emphysema.
Abstract: Objective and design: Chronic obstructive pulmonary disease (COPD) is characterized by an inflammatory process and airway remodeling involving matrix metalloproteinases (MMPs). Thus, we analyzed the expression and release of MMP-12 (macrophage metalloelastase) in bronchoalveolar lavage (BAL) and lung tissue from COPD patients and control subjects. Methods: Immunocytochemistry and immunochemistry were performed to analyze the expression of MMP-12 in BAL cells and bronchial biopsies. Western blotting was used for the evaluation of MMP-12 in BAL fluids. Results: The number of MMP-12 expressing macrophages together with the staining intensity was higher in BAL samples from COPD patients than in controls subjects. Similar results were noted in bronchial biopsies with higher MMP-12 expression in COPD subjects than in controls. Enhanced MMP-12 level was also observed in BAL fluids from patient with COPD in comparison to control subjects. Conclusion: This study demonstrated that COPD patients produce greater quantities of MMP-12 than controls, which may be a critical step in the pathogenesis of COPD and emphysema.
TL;DR: The description and the implementation of a formal framework for the on-line decentralised diagnosis of large discrete event systems, framework which is based on the ''divide and conquer'' principle and does not require the global model computation is described.
TL;DR: In this article, three-dimensional images of Vickers indentations on several glasses, including silicate glasses and bulk metallic glass (BMG), were obtained before and after annealing using an atomic force microscope.
Abstract: To estimate the ratio of densification to Vickers indentation volume, three-dimensional images of Vickers indentations on several glasses, including silicate glasses and bulk metallic glass (BMG), were obtained before and after annealing using an atomic force microscope. Large volume recovery of Vickers indentation by annealing was observed for all glasses but BMG. Following previous studies, this recovered volume almost corresponded to the densified volume under a Vickers indenter, and the compositional dependence of densification was discussed. The ratios of densification to the total indentation volume for silica and soda-lime glasses were 92% and 61%, respectively. It was concluded that densification was a general property for silicate glasses and that the ratios of densification to the total indentation volume for all the glasses correlated well with Poisson’s ratios of the glasses.
TL;DR: The luminescence of trivalent lanthanide ions has found applications in lighting, lasers, optical telecommunications, medical diagnostics, and various other fields and two recent developments in the field of luminescent materials are addressed.
Abstract: The luminescence of trivalent lanthanide ions has found applications in lighting, lasers, optical telecommunications, medical diagnostics, and various other fields. This introductory review present...
TL;DR: The presence of a member of the aquaporin family of water channels, AQP8, is shown and the strikingly high water permeability (Pf) characterizing the rat liver IMM is demonstrated, suggesting that AQP 8-mediated water transport may be particularly important for rapid expansions of mitochondrial volume.
TL;DR: The objective of the current study was to compare the discriminating accuracy of four prognostic models developed to predict the survival of patients undergoing nephrectomy for nonmetastatic renal cell carcinoma (RCC).
Abstract: BACKGROUND
The objective of the current study was to compare, in a large multicenter study, the discriminating accuracy of four prognostic models developed to predict the survival of patients undergoing nephrectomy for nonmetastatic renal cell carcinoma (RCC).
METHODS
A total of 2404 records of patients from 6 European centers were retrospectively reviewed. For each patient, prognostic scores were calculated according to four models: the Kattan model, the University of California at Los Angeles integrated staging system (UISS) model, the Yaycioglu model, and the Cindolo model. Survival curves were estimated by the Kaplan–Meier method and compared by the log-rank test. Discriminating ability was assessed by the Harrell c-index for censored data. The primary end point was overall survival (OS), and the secondary end points were cancer-specific survival (CSS) and disease recurrence-free survival (RFS).
RESULTS
At last follow-up, 541 subjects had died of any causes, with a 5-year OS rate of 80%. The 5-year CSS and RFS rates were 85% and 78%, respectively. All models discriminated well (P < 0.0001). The c-indexes for OS were 0.706 for the Kattan nomogram, 0.683 for the UISS model, and 0.589 and 0.615 for the Yaycioglu and Cindolo models, respectively. The Kattan nomogram was found to improve discrimination substantially in the UISS intermediate-risk patients.
CONCLUSIONS
The current study appears to better define the general applicability of prognostic models for predicting survival in patients with nonmetastatic RCC treated with nephrectomy. The results suggest that postoperative models discriminate substantially better than preoperative ones. The Kattan model was consistently found to be the most accurate, although the UISS model was only slightly less well performing. The Kattan model can be useful in the UISS intermediate-risk patients. Cancer 2005. © 2005 American Cancer Society.
TL;DR: In this paper, the authors investigated the effects of habitat type, landscape context of habitats and farming intensity on carabid beetles assemblages in hedgerow network landscapes in western France.
TL;DR: In this paper, the importance of plant uptake and denitrification in litter for N retention in riparian buffers was investigated, showing that annual nitrogen retention in the vegetation and litter compartment is substantial, making up 13-99% of the total N mitigation.
02 Oct 2005
TL;DR: The language adopts a declarative paradigm, wherein users may concern themselves solely with the relations between the models rather than needing to deal explicitly with issues such as order of rule execution and pattern searching/traversal of input models.
Abstract: We present Tefkat, an implementation of a language designed specifically for the transformation of MOF models using patterns and rules. The language adopts a declarative paradigm, wherein users may concern themselves solely with the relations between the models rather than needing to deal explicitly with issues such as order of rule execution and pattern searching/traversal of input models. In this paper, we demonstrate the language using a provided example and highlight a number of language features used in solving the problem, a simple object-to-relational mapping.
TL;DR: Whether atrophy of the EC evaluated by the quantitative magnetic resonance imaging (MRI) method is correlated with the epileptogenicity of this structure in TLE is determined.
Abstract: Summary: Purpose: Several studies have demonstrated diminution in the volume of entorhinal cortex (EC) ipsilateral to the pathologic side in patients with temporal lobe epilepsy (TLE). The relation between the degree of EC atrophy and the epileptogenicity of this structure has never been directly studied. The purpose of the study was to determine whether atrophy of the EC evaluated by the quantitative magnetic resonance imaging (MRI) method is correlated with the epileptogenicity of this structure in TLE.
Methods: Intracerebral recordings (SEEG method) of seizures from 11 patients with mesial TLE were analyzed. Seizures were classified according to patterns of onset: pattern 1 was the emergence of a low-frequency, high-amplitude rhythmic spiking followed by a tonic discharge, and pattern 2 was the emergence of a tonic discharge in the mesial structures. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between hippocampus (Hip) and EC at seizure onset. MRI volumetric analysis was performed by using a T1-weighted three-dimensional gradient-echo sequence in TLE patients and 12 healthy subjects.
Results: Significant interactions between Hip and Ec were quantified at seizure onset. The EC was found to be the leader structure in most of the pattern 2 seizures. Volumetric measurements of EC demonstrated an atrophy in 63% of patients ipsilateral to the epileptic side. A significant correlation between the strength of EC–Hip coupling and the degree of atrophy was found. In addition, in those patients that had a normal EC volume, the EC was never the leader structure in Ec–Hip coupling.
Conclusions: These results validate the potential role of volumetry to predict the epileptogenesis of the EC in patients with hippocampal sclerosis and MTLE.
TL;DR: Data obtained in laboratory settings, where confounding factors can be eliminated, prove that benzodiazepine-1 (BZ1) receptors are the most deleterious hypnotics at least in terms of their effects on body sway.
Abstract: The aim of this review is to establish the relationship between treatment with hypnotics and the risk of postural instability and as a consequence, falls and hip fractures, in the elderly. A review of the literature was performed through a search of the MEDLINE, Ingenta and PASCAL databases from 1975 to 2005. We considered as hypnotics only those drugs approved for treating insomnia, i.e. some benzodiazepines and the more recently launched 'Z'-compounds, i.e. zopiclone, zolpidem and zaleplon. Large-scale surveys consistently report increases in the frequency of falls and hip fractures when hypnotics are used in the elderly (2-fold risk). Benzodiazepines are the major class of hypnotics involved in this context; falls and fractures in patients taking Z-compounds are less frequently reported, and in this respect, zolpidem is considered as at risk in only one study. It is important to note, however, that drug adverse effect relationships are difficult to establish with this type of epidemiological data-mining. On the other hand, data obtained in laboratory settings, where confounding factors can be eliminated, prove that benzodiazepines are the most deleterious hypnotics at least in terms of their effects on body sway. Z-compounds are considered safer, probably because of their pharmacokinetic properties as well as their selective pharmacological activities at benzodiazepine-1 (BZ(1)) receptors. The effects of hypnotics on balance, gait and equilibrium are the consequence of differential negative impacts on vigilance and cognitive functions, and are highly dose- and time-dependent. Z-compounds have short half-lives and have less cognitive and residual effects than older medications. Some practical rules need to be followed when prescribing hypnotics in order to prevent falls and hip fractures as much as possible in elderly insomniacs, whether institutionalised or not. These are: (i) establish a clear diagnosis of the sleep disorder; (ii) take into account chronic conditions leading to balance and gait difficulties (motor and cognitive status); (iii) search for concomitant prescription of psychotropics and sedatives; (iv) use half the recommended adult dosage; and (v) declare any adverse effect to pharmacovigilance centres. Comparative pharmacovigilance studies focused on the impact of hypnotics on postural stability are very much needed.