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Highly diverse radiolarian faunas of latest Maastrichtian to early Eocene age have been recovered from the low latitude realm in order to contribute to the clarification of radiolarian taxonomy, construct a zonation based on a discrete sequence of co-existence intervals of species ranging from the late Paleocene to early Eocene and to describe a rich low latitude latest Cretaceous to late Paleocene fauna. 225 samples of late Paleocene to early Eocene age have been collected from ODP Leg 171 B-Hole 1051 A (Blake Nose), DSDP Leg 43-Site 384 (Northwest Atlantic) and DSDP Leg 10-Sites 86, 94, 95, 96. Sequences consist of mainly pelagic oozes and chalks, with some clay and ash layers. A new imaging technique is devised to perform (in particular on topotypic material) both transmitted light microscopy and SEM imaging on individual radiolarian specimens. SEM precedes transmitted light imaging. Radiolarians are adhered to a cover slip (using nail varnish) which is secured to a stub using conductive levers. Specimens are then photographed in low vacuum (40-50Pa; 0.5mbar), which enables charge neutralization by ionized molecules of the chamber atmosphere. Thus gold coating is avoided and subsequently this allows transmitted light imaging to follow. The conductive levers are unscrewed and the cover slip is simply overturned and mounted with Canada balsam. In an attempt towards a post-Haeckelian classification, the initial spicule (Entactinaria), micro- or macrosphere (Spumellaria) and initial spicule and cephalis (Nassellaria) have been studied by slicing Entactinaria and Spumellaria, and by tilting Nassellaria in the SEM chamber. A new genus of the family Coccodiscidae is erected and Spongatractus HAECKEL is re-located to the subfamily Axopruinae. The biochronology has been carried out using the Unitary Association Method (Guex 1977, 1991). A database recording the occurrences of 112 species has been used to establish a succession of 22 Unitary Associations. Each association is correlated to chronostratigraphy via calcareous microfossils that were previously studied by other authors. The 22 UAs have been united into seven Unitary Associations Zones (UAZones) (JP10- JE4). The established zones permit to distinguish supplementary subdivisions within the existing zonation. The low-latitude Paleocene radiolarian zonation established by Sanfilippo and Nigrini (1998a) is incomplete due to the lack of radiolarian-bearing early Paleocene sediments. In order to contribute to the study of sparsely known low latitude early Paleocene faunas, 80 samples were taken from the highly siliceous Guayaquil Formation (Ecuador). The sequence consists of black cherts, shales, siliceous limestones and volcanic ash layers. The carbonate content increases up section. Age control is supplied by sporadic occurrences of silicified planktonic foraminifera casts. One Cretaceous zone and seven Paleocene zones have been identified. The existing zonation for the South Pacific can be applied to the early-early late Paleocene sequence, although certain marker species have significantly shorter ranges (notably Buryella foremanae and B. granulata). Despite missing marker species in the late Paleocene, faunal distribution correlates reasonably to the Low-Latitude zonation. An assemblage highly abundant in Lithomelissa, Lophophaena and Cycladophora in the upper RP6 zone (correlated by the presence of Pterocodon poculum, Circodiscus circularis, Pterocodon? sp. aff. P. tenellus and Stylotrochus nitidus) shows a close affinity to contemporaneous faunas reported from Site 1121, Campbell Plateau. Coupled with a high diatom abundance (notably Aulacodiscus spp. and Arachnoidiscus spp.), these faunas are interpreted as reflecting a period of enhanced biosiliceous productivity during the late Paleocene. The youngest sample is void of radiolarians, diatoms and sponge spicules yet contains many pyritized infaunal benthic foraminifera which are akin to the midway-type fauna. The presence of this fauna suggests deposition in a neritic environment. This is in contrast to the inferred bathyal slope depositional environment of the older Paleocene sediments and suggests a shoaling of the depositional environment which may be related to a coeval major accretionary event. RESUME DE LA THESE Des faunes de radiolaires de basses latitudes très diversifiées d'âge Maastrichtien terminal à Eocène inférieur, ont été étudiées afin de contribuer à la clarification de leur taxonomie, de construire une biozonation basée sur une séquence discrète d'intervalles de coexistence des espèces d'age Paléocène supérieur à Eocène inférieur et de décrire une riche faune de basse latitude allant du Crétacé terminal au Paléocène supérieur. L'étude de cette faune contribue particulièrement à la connaissance des insaisissables radiolaires de basses latitudes du Paléocène inférieur. 225 échantillons d'âge Paléocène supérieur à Eocène inférieur provenant des ODP Leg 171B-Site 1051A (Blake Nose), Leg DSDP 43-Site 384 (Atlantique Nord -Ouest) et des DSDP Leg 10 -Sites 86, 94, 95, 96, ont été étudiés. Ces séquences sont constituées principalement de « ooze » et de « chalks »pélagiques ainsi que de quelques niveaux de cendres et d'argiles. Une nouvelle technique d'imagerie a été conçue afin de pouvoir prendre conjointement des images en lumière transmise et au Microscope Electronique à Balayage (MEB) de spécimens individuels. Ceci à été particulièrement appliqué à l'étude des topotypes. L'imagerie MEB précède l'imagerie en lumière transmise. Les radiolaires sont collés sur une lame pour micropaléontologie (au moyen de vernis à ongles) qui est ensuite fixée à un porte-objet à l'aide de bras métalliques conducteurs. Les spécimens sont ensuite photographiés en vide partiel (40-50Pa; 0.5mbar), ce qui permet la neutralisation des charges électrostatiques dues à la présence de molécules ionisées dans l'atmosphère de la chambre d'observation. Ainsi la métallisation de l'échantillon avec de l'or n'est plus nécessaire et ceci permet l'observation ultérieure en lumière transmise. Les bras conducteurs sont ensuite dévissés et la lame est simplement retournée et immergée dans du baume du Canada. Dans une approche de classification post Haeckelienne, le spicule initial (Entactinaires), la micro- ou macro -sphère (Spumellaires) et le spicule initial et cephalis (Nassellaires) ont été étudiés. Ceci a nécessité le sectionnement d'Entactinaires et de Spumellaires, et de pivoter les Nassellaires dans la chambre d'observation du MEB. Un nouveau genre de la Famille des Coccodiscidae a été érigé et Spongatractus HAECKEL à été réassigné à la sous-famille des Axopruninae. L'analyse biostratigraphique à été effectuée à l'aide de la méthode des Associations Unitaires {Guex 1977, 1991). Une base de données enregistrant les présences de 112 espèces à été utilisée poux établir une succession de 22 Associations Unitaires. Chaque association est corrélée à la chronostratigraphie au moyen de microfossiles calcaires précédemment étudiés par d'autres auteurs. Les 22 UAs ont été combinées en sept Zones d'Associations Unitaires (UAZones) (JP10- JE4). Ces Zones permettent d'insérer des subdivisions supplémentaires dans la zonation actuelle. La zonation de basses latitudes du Paléocène établie par Sanfilippo et Nigrini (1998a) est incomplète due au manque de sédiments du Paléocène inférieur contenant des radiolaires. Afin de contribuer à l'étude des faunes peu connues des basses latitudes du Paléocène inférieur, 80 échantillons ont été prélevés d'une section siliceuse de la Formation de Guayaquil (Equateur). La séquence est composée de cherts noirs, de shales, de calcaires siliceux et de couches de cendres volcaniques. La fraction carbonatée augmente vers le haut de la section. Des contraintes chronologiques sont fournies par la présence sporadique de moules de foraminifères planctoniques. Une zone d'intervalles du Crétacé et sept du Paléocène ont été mises en évidence. Bien que certaines espèces marqueur ont des distributions remarquablement plus courtes (notamment Buryella foremanae et B. granulata), la zonation existante pour le Pacifique Sud est applicable à la séquence d'age Paléocène inférieure à Paléocène supérieur basal étudiée. Malgré l'absence d'espèces marqueur du Paléocène supérieur, la succession faunistique se corrèle raisonnablement avec la zonation pour les basses latitudes. Un assemblage contenant d'abondants représentant du genre Lithomelissa, Lophophaena et Cycladophora dans la zone RP6 (correlée par la présence de Pterocodon poculum, Circodiscus circularis, Pterocodon? sp. aff. P. tenellus et Stylotrochus nitidus) montre une grande similitude avec certaines faunes issues des hauts latitudes et d'age semblable décrites par Hollis (2002, Site 1121, Campbell Plateau). Ceci, en plus d'une abondance importante en diatomés (notamment Aulacodiscus spp. et Arachnoidiscus spp.) nous mènent à interpréter cette faune comme témoin d'un épisode de productivité biosiliceuse accrue dans le Paléocène supérieur. L'échantillon le plus jeune, dépourvu de radiolaires, de diatomés et de spicules d'éponge contient de nombreux foraminifères benthiques infaunaux pyritisés. Les espèces identifiées sont caractéristiques d'une faune de type midway. La présence de ces foraminifères suggère un environnement de type néritique. Ceci est en contraste avec l'environnement de pente bathyale caractérisent les sédiments sous-jacent. Cette séquence de diminution de la tranche d'eau peut être associée à un événement d'accrétion majeure. RESUME DE LA THESE (POUR LE GRAND PUBLIC) Les radiolaires constituent le groupe de plancton marin le plus divers et le plus largement répandu de l'enregistrement fossile. Un taux d'évolution rapide et une variation géographique considérable des populations font des radiolaires un outil de recherche sans égal pour la biostratigraphie et la paléocéanographie. Néanmoins, avant de pouvoir les utiliser comme outils de travail, il est essentiel d'établir une solide base taxonomique. L'étude des Radiolaires peut impliquer plusieurs techniques d'extraction, d'observation et d'imagerie qui sont dépendantes du degré d'altération diagénétique des spécimens. Le squelette initial, qu'il s'agisse d'un spicule initial (Entactinaria), d'une micro- ou macro -sphère (Spumellaria) ou d'un spicule initial et d'un cephalis (Nassellaria), est l'élément le plus constant au cours de l'évolution et devrait représenter le fondement de la systématique. Des échantillons provenant de carottes de basses latitudes du Deep Sea Drilling Project et de l' Ocean Drilling ont été étudiés. De nouvelles techniques d'imagerie et de sectionnement ont été développées sur des topotypes de radiolaires préservés en opale, dans le but d'étudier les caractéristiques de leur squelette initial qui n'étaient pas visibles dans leur illustration originale. Ceci aide entre autre à comparer des spécimens recristallisés en quartz, provenant de terrains accrétés, avec les holotypes en opale de la littérature. La distribution des espèces étudiés a fourni des données biostratigraphiques qui ont été compilées à l'aide de la méthode des Associations Unitaires (Guez 1977, 1991). Il s'agit d'un modèle mathématique déterministe conçu pour exploiter la totalité de l'assemblage plutôt que de se confiner à l'utilisation de taxons marqueurs individuels. Une séquence de 22 Associations Unitaires a été établie pour la période allant du Paléocène supérieur à l'Éocène inférieur. Chaque Association Unitaire a été corrélée à l'échelle de temps absolue à l'aide de microfossiles calcaires. Les 22 UAs ont été combinées en sept Zones d'Associations Unitaires (JP10- JE4). Ces Zones permettent d'insérer des subdivisions supplémentaires dans la zonation actuelle. Les radiolaires du Paléocène inférieur à moyen des basses latitudes sont rares. Les meilleures sections connues se trouvent dans les hautes latitudes (Nouvelle Zélande). Quelques assemblages épars ont été mentionnés par le passé en Californie, en Équateur et en Russie. Une séquence siliceuse de 190 mètres dans la Formation de Guayaquil (Équateur), s'étendant du Maastrichtien supérieur au Paléocène supérieur, a fourni des faunes relativement bien préservées. L'étude de ces faunes a permis de mettre en évidence la première séquence complète de radiolaires de basses latitudes dans le Paléocène inférieure. Huit zones allant du Crétacé terminal au Paléocène supérieur ont pu être appliqués et la présence de foraminifères planctoniques a fournie plusieurs points d'attache chronologiques. Dans le Paléocène supérieur, un riche assemblage contenant d'abondants diatomés et radiolaires ayant des similitudes faunistiques marquantes avec des assemblages de hautes latitudes de Nouvelle Zélande, témoigne d'un épisode de productivité biosiliceuse accrue pendant cette période. Étant donné que la pointe du continent sud-américain et l'Antarctique étaient plus proches au cours du Paléocène, ce phénomène peut être expliqué par le transport, le long de la côte ouest de l'Amérique du Sud, d'eaux riches en nutriments en provenance de l'Océan Antarctique. Suite à cet épisode, l'enregistrement en radiolaires est interrompu. Ceci peut être associé à des événements tectoniques régionaux qui ont eu pour effet de diminuer la tranche d'eau relative, rendant l'environnement plus favorable aux foraminifères benthiques qui sont abondamment présents dans l'échantillon le plus jeune de la séquence.

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Much attention has been given to the negative d13C anomaly nearly coincident with the Permian-Triassic boundary. New data indicate a stepwise decline in d13C initiating before the Latest Permian extinction event followed by highly variable d13C values during the remaining Early Triassic. d13C values appear much less erratic as global metazoan diversity increased in the Middle Triassic. Given the previously unappreciated magnitude of isotopic change and the number of large d13C excursions that occurred during the Early Triassic, catastrophic mechanisms like methane release/bolide impact become less attractive to explain the Early Triassic carbon isotopic record as a whole.

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OBJECTIVES: EEG and serum neuron-specific enolase (NSE) are used for outcome prognostication in patients with postanoxic coma; however, it is unclear if EEG abnormalities reflect transient neuronal dysfunction or neuronal death. To assess this question, EEG abnormalities were correlated with NSE. Moreover, NSE cutoff values and hypothermic EEG features related with poor outcome were explored.¦METHODS: In a prospective cohort of 61 adults treated with therapeutic hypothermia (TH) after cardiac arrest (CA), multichannel EEG recorded during TH was assessed for background reactivity and continuity, presence of epileptiform transients, and correlated with serum NSE collected at 24-48 hours after CA. Demographic, clinical, and functional outcome data (at 3 months) were collected and integrated in the analyses.¦RESULTS: In-hospital mortality was 41%, and 82% of survivors had good neurologic outcome at 3 months. Serum NSE and EEG findings were strongly correlated (Spearman rho = 0.45; p < 0.001). Median NSE peak values were higher in patients with unreactive EEG background (p < 0.001) and discontinuous patterns (p = 0.001). While all subjects with nonreactive EEG died, 5 survivors (3 with good outcome) had NSE levels >33 μg/L.¦CONCLUSION: The correlation between EEG during TH and serum NSE levels supports the hypothesis that early EEG alterations reflect permanent neuronal damage. Furthermore, this study confirms that absent EEG background reactivity and presence of epileptiform transients are robust predictors of poor outcome after CA, and that survival with good neurologic recovery is possible despite serum NSE levels> 33 μg/L. This underscores the importance of multimodal assessments in this setting.

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DNA double strand breaks (DSBs) are mainly repaired via homologous recombination (HR) or nonhomologous end joining (NHEJ). These breaks pose severe threats to genome integrity but can also be necessary intermediates of normal cellular processes such as immunoglobulin class switch recombination (CSR). During CSR, DSBs are produced in the G1 phase of the cell cycle and are repaired by the classical NHEJ machinery. By studying B lymphocytes derived from patients with Cornelia de Lange Syndrome, we observed a strong correlation between heterozygous loss-of-function mutations in the gene encoding the cohesin loading protein NIPBL and a shift toward the use of an alternative, microhomology-based end joining during CSR. Furthermore, the early recruitment of 53BP1 to DSBs was reduced in the NIPBL-deficient patient cells. Association of NIPBL deficiency and impaired NHEJ was also observed in a plasmid-based end-joining assay and a yeast model system. Our results suggest that NIPBL plays an important and evolutionarily conserved role in NHEJ, in addition to its canonical function in sister chromatid cohesion and its recently suggested function in HR.

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Purpose: We intended to determine whether the need for retreatmentwith intravitreal ranibizumab follows an individual rhythm in patientswith exudative AMD. Setting: Prospective mono-centre cohort study.Methods: Prospective study. 48 patients with exudative AMD. 3 loadingdoses of ranibizumab, followed by a 12 months PRN regimen guided byearly exudative signs on SD-OCT. An intensified follow-up allowed todetect recurrences early.Results:Mean VA improved by 6.4 letters at month 3 and by 13.1 letters atmonth 12, with a mean of 8.0 injections (range 0-12) during the maintenancephase. The intra-individual variance of the intervals was relativelysmall and ranged within 20% of themean interval in 91% of patients.Thefirst interval was within 1 week of the mean interval in 84% of patients.The retreatment criteria were stable in 89% of patients.Conclusion: The relative stability of the intra-individual intervalsmay allowsimplifying the care for AMDpatients.Theremay be a predictive role for thefirst interval after the loading phase. The functional results of this PRNregimenwith early retreatmentwere excellent. Financial disclosure:None.

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To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.

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PURPOSE: Attention deficit and hyperactivity disorder (ADHD) is one of the most frequent disorders in childhood and adolescence. Both neurocognitive and environmental factors have been related to ADHD. The current study contributes to the documentation of the predictive relation between early attachment deprivation and ADHD. METHOD: Data were collected from 641 adopted adolescents (53.2 % girls) aged 11-16 years in five countries, using the DSM oriented scale for ADHD of the Child Behavior Checklist (CBCL) (Achenbach and Rescorla, Manual for the ASEBA school-age forms and profiles. University of Vermont, Research Center for Children, Youth and Families, Burlington, 2001). The influence of attachment deprivation on ADHD symptoms was initially tested taking into consideration several key variables that have been reported as influencing ADHD at the adoptee level (age, gender, length of time in the adoptive family, parents' educational level and marital status), and at the level of the country of origin and country of adoption (poverty, quality of health services and values). The analyses were computed using the multilevel modeling technique. RESULTS: The results showed that an increase in the level of ADHD symptoms was predicted by the duration of exposure to early attachment deprivation, estimated from the age of adoption, after controlling for the influence of adoptee and country variables. The effect of the age of adoption was also demonstrated to be specific to the level of ADHD symptoms in comparison to both the externalizing and internalizing behavior scales of the CBCL. CONCLUSION: Deprivation of stable and sensitive care in infancy may have long-lasting consequences for children's development.

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New plate-tectonic reconstructions of the Gondwana margin suggest that the location of Gondwana-derived terranes should not only be guided by the models, but should also consider the possible detrital input from some Asian blocks (Hunia), supposed to have been located along the Cambrian Gondwana margin, and accreted in the Silurian to the North-Chinese block. Consequently, the Gondwana margin has to be subdivided into a more western domain, where the future Avalonian blocks will be separated from Gondwana by the opening Rheic Ocean, whereas in its eastern continuation, hosting the future basement areas of Central Europe, different periods of crustal extension should be distinguished. Instead of applying a rather cylindrical model, it is supposed that crustal extension follows a much more complex pattern, where local back-arcs or intra-continental rifts are involved. Guided by the age data of magmatic rocks and the pattern of subsidence curves, the following extensional events can be distinguished: During the early to middle Cambrian, a back-arc setting guided the evolution at the Gondwana margin. Contemporaneous intra-continental rift basins developed at other places related to a general post-PanAfrican extensional phase affecting Africa Upper Cambrian formation of oceanic crust is manifested in the Chamrousse area, and may have lateral cryptic relics preserved in other places. This is regarded as the oceanisation of some marginal basins in a context of back-arc rifting. These basins were closed in a mid-Ordovician tectonic phase, related to the subduction of buoyant material (mid-ocean ridge?) Since the Early Ordovician, a new phase of extension is observed, accompanied by a large-scale volcanic activity, erosion of the rift shoulders generated detritus (Armorican Quartzite) and the rift basins collected detrital zircons from a wide hinterland. This phase heralded the opening of Palaeotethys, but it failed due to the Silurian collision (Eo-Variscan phase) of an intra-oceanic arc with the Gondwana margin. During this time period, at the eastern wing of the Gondwana margin begins the drift of the future Hunia microcontinents, through the opening of an eastern prolongation of the already existing Rheic Ocean. The passive margin of the remaining Gondwana was composed of the Galatian superterranes, constituents of the future Variscan basement areas. Remaining under the influence of crustal extension, they will start their drift to Laurussia since the earliest Devonian during the opening of the Palaeotethys Ocean. (C) 2008 Elsevier B.V. All rights reserved.

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Fast track concrete has proven to be successful in obtaining high early strengths. This benefit does not come without cost. Type III cement and insulation blankets to accelerate the cure add to its expense when compared to conventional paving. This research was intended to determine the increase in time required to obtain opening strength when a fast track mix utilized conventional Type I cement and also used a conventional cure. Standard concrete mixes also were tested to determine the acceleration of strength gain when cured with insulation blankets. The goal was to determine mixes and procedures which would result in a range of opening times. This would allow the most economical design for a particular project and tailor it to that projects time restraint. Three mixes were tested: Class F, Class C, and Class B. Each mix was tested with one section being cured with insulation blankets and another section without. All used Type I cement. Iowa Department of Transportation specifications required 500 psi of flexural strength before a pavement can be opened to traffic. The Class F mix with Type I cement and using insulation blankets reached that strength in approximately 36 hours, the Class C mix using the blankets in approximately 48 hours, and the Class F mix without covers in about 60 hours. (Note: Class F concrete pavement is opened at 400 psi minimum and Class F bonded overlay pavement at 350 psi.) The results showed a significant improvement in early strength gain by the use of insulation blankets. The Type I cement could be used in mixes intended for early opening with sacrifices in time when compared to fast track but are still much sooner than conventional pavement. It appears a range of design alternatives is possible using Type I cement both with and without insulating blankets.

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In 1990, early distress had shown up on US 20 in Hamilton/Webster counties, three years after paving. Since that time, over a dozen more projects, constructed between 1984 and 1994, have been found to exhibit similar early distress. Several changes to the concrete and Portland cement specifications occurred in 1994 and 1996. This study was undertaken to investigate in place concrete pavements before and after specification changes were implemented. The objective of this research is to evaluate the impact of Portland cement and concrete specification changes made in 1994 and 1996 on PCC durability. Cores were obtained in 1998 and 2003 from projects constructed in 1992, before specification changes, and 1997 after specification changes. The following is a brief summary of the conclusions: 1. The pavements in the study constructed under the new specifications are performing much better after 5 years of service than the pavements constructed under the old specifications. 2. According to ISU, micro-cracking is evident in all concrete that has been in service, due to thermal stresses and loading stresses. Also, the low vacuum SEM will desiccate the concrete enough to cause micro-cracking. The SEM should not be used as a tool to indicate micro-cracking. 3. Use of Type II cement (C3A <8%) and a 3.0% SO3 limit does not completely eliminate ettringite infilling in air voids, as indicated in the bottom of the 1997 cores. 4. In areas of high moisture (bottom of the core), infilling is present in most of the 1997 cores. 5. Low air content and high spacing factor in the top of 1992 cores apparently causes F/T cycling cracking and then increased moisture paths from cracking causes infilling. 6. Use of ground granulated blast furnace slag (GGBFS) and fly ash reduces ettringite infilling either by diluting the aluminate (C3A) or lowering permeability, which slows ingress of moisture. 7. The specification changes that made the biggest impact on pavement durability are the limits on vibration and increase in air content in September 1994. 8. Investigations of cores from pavements placed in 2002 and 2003 indicate improved air contents and spacing factors. In-place air content and spacing factors should be monitored to determine if appropriate air void parameters are being met.

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Eighteen patients with acetabular fractures, with a mean age of 76 years, were treated with cable fixation and acute total hip arthroplasty. Nine were T-shaped fractures, 4 associated transverse and posterior wall, 2 transverse, 2 posterior column and posterior wall, and 1 anterior and posterior hemitransverse fractures. One patient experienced 3 episodes of hip dislocation within 10 months after surgery. All the others had a good outcome at a mean follow-up time of 36 months. Radiographic assessment showed healing of the fracture and a satisfactory alignment of the cup without loosening. This option provides good primary fixation, stabilizes complex acetabular fractures in elderly patients, and permits early postoperative mobilization.

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Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD. Many studies suggest that modifications of prenatal and/or early postnatal lung development will have important implications for future lung function and risk of CLD throughout life. This view represents a fundamental change of current pathophysiological concepts and treatment paradigms, and holds the potential to develop novel preventative and/or therapeutic strategies. However, for the successful development of such approaches, key questions, such as a clear understanding of underlying mechanisms of impaired lung development, the identification and validation of relevant preclinical models to facilitate translational research, and the development of concepts for correction of aberrant development, all need to be solved. Accordingly, a European Science Foundation Exploratory Workshop was held where clinical, translational and basic research scientists from different disciplines met to discuss potential mechanisms of developmental origins of CLD, and to identify major knowledge gaps in order to delineate a roadmap for future integrative research.

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An increased oxidative stress and alteration of the antioxidant systems have been observed in schizophrenia. Glutathione (GSH), a major redox regulator, is decreased in patients' cerebrospinal fluid, prefrontal cortex in vivo and striatum post-mortem tissue. Most importantly, there is genetic and functional evidence for the implication of the gene of the glutamate cysteine ligase (GCL) catalytic subunit, the key GSH-synthesizing enzyme. We have developed animal models for a GSH deficit to study the consequences of such deficit on the brain development. A GSH deficit combined with elevated dopamine (DA) during development leads to reduced parvalbumin (PV) expression in a subclass of GABA interneurons in rat anterior cingulate cortex (ACC). Similar changes are observed in postmortem brain tissue of schizophrenic patients. GSH dysregulation increases vulnerability to oxidative stress, that in turn could lead to cortical circuit anomalies in the schizophrenic brain. In the present study, we use a GCL modulatory subunit (GCLM) knock-out (KO) mouse model that presents up to 80% decreased brain GSH levels. During postnatal development, a subgroup of animals from each genotype is exposed to elevated oxidative stress induced by treatment with the DA reuptake inhibitor GBR12909. Results reveal a significant genotype-specific delay International Congress on Schizophrenia Research 136 10. 10. Neuroanatomy, Animal Downloaded from http://schizophreniabulletin.oxfordjournals.org at Bibliotheque Cantonale et Universitaire on June 18, 2010 in cortical PV expression at postnatal day P10 in GCLM-KO mice, as compared to wild-type. This effect seems to be further exaggerated in animals treated with GBR12909 from P5 to P10. At P20, PV expression is no longer significantly reduced in GCLM-KO ACC without GBR but is reduced if GBR is applied from P10 to P20. However, our result show that GCLM-KO mice exhibit increased oxidative stress, cortical altered myelin development as shown by MBP marker, and more specifically impairment of the peri-neuronal net known to modulate PV connectivity. In addition, we also observe a reduced PV expression in the ventro-temporal hippocampus of adult GCLM-KO mice, suggesting that anomalies of the PV interneurons prevail at least in some brain regions throughout the adulthood. Interestingly, the power of kainate-induced gamma oscillations, known to be dependent on proper activation of PV interneuron's, is also lower in hippocampal slices of adult GCLM KO mice. These results suggest that the PV positive GABA interneurons is particularly vulnerable to increased oxidative stress