Changes in D-serine levels and localization during postnatal development of the rat vestibular nuclei.

The patterns of development of the vestibular nuclei (VN) and their main connections involving glutamate neurotransmission offer a good model for studying the function of the glial-derived neuromodulator D-serine in synaptic plasticity. In this study we show that D-serine is present in the VN and we analyzed its distribution and the levels of expression of serine racemase and D-amino acid oxidase (D-AAO) at different stages of postnatal (P) development. From birth to P21, high levels of D-serine were detected in glial cells and processes in all parts of the VN. This period corresponded to high expression of serine racemase and low expression of D-AAO. On the other hand, in the mature VN D-serine displayed very low levels and was mainly localized in neuronal cell bodies and dendrites. This drop of D-serine in adult stages corresponded to an increasing expression of D-AAO at mature stages. High levels of glial D-serine during the first 3 weeks of postnatal development correspond to an intense period of plasticity and synaptogenesis and maturation of VN afferents, suggesting that D-serine could be involved in these phenomena. These results demonstrate for the first time that changes in D-serine levels and distribution occur during postnatal development in the central nervous system. The strong decrease of D-serine levels and the glial-to-neuronal switch suggests that D-serine may have distinct functional roles depending on the developmental stage of the vestibular network.

Clinical Prognostic Factors Predicting Outcomes Of Patients With Recurrent Gbm And Nomograms

BACKGROUND: Prognostic models and nomograms were recently developed to predict survival of patients with newly diagnosed glioblastoma multiforme (GBM).1 To improve predictions, models should be updated with the most recent patient and disease information. Nomograms predicting patient outcome at the time of disease progression are required. METHODS: Baseline information from 299 patients with recurrent GBM recruited in 8 phase I or II trials of the EORTC Brain Tumor Group was used to evaluate clinical parameters as prognosticators of patient outcome. Univariate (log rank) and multivariate (Cox models) analyses were made to assess the ability of patients' characteristics (age, sex, performance status [WHO PS], and MRC neurological deficit scale), disease history (prior treatments, time since last treatment or initial diagnosis, and administration of steroids or antiepileptics) and disease characteristics (tumor size and number of lesions) to predict progression free survival (PFS) and overall survival (OS). Bootstrap technique was used for models internal validation. Nomograms were computed to provide individual patients predictions. RESULTS: Poor PS and more than 1 lesion had a significant prognostic impact for both PFS and OS. Antiepileptic drug use was significantly associated with worse PFS. Larger tumors (split by the median of the largest tumor diameter >42.5 mm) and steroid use had shorter OS. Age, sex, neurologic deficit, prior therapies, and time since last therapy or initial diagnosis did not show independent prognostic value for PFS or OS. CONCLUSIONS: This analysis confirms that PS but not age is a major prognostic factor for PFS and OS. Multiple or large tumors and the need to administer steroids significantly increase the risk of progression and death. Nomograms at the recurrence could be used to obtain accurate predictions for the design of new targeted therapy trials or retrospective analyses. (1. T. Gorlia et al., Nomograms for predicting survival of patients with newly diagnosed glioblastoma. Lancet Oncol 9 (1): 29-38, 2008.)

Development of Concepts for Pavement Management, MLR-79-04, 1979

Sufficient evidence was not discovered in this brief search to alter the general opinion that the Serviceability (Present Serviceability Index-PSI) - Performance Concepts developed by the AASHO Road Test provides the optimum engineering basis for pavement management. Use of these concepts in Iowa has the additional advantage in that we have a reasonable quantity of historical data over a period of time on the change in pavement condition as measured by PSI's. Some additional benefits would be the ability to better assess our needs with respect to those being recommended to Congress by AASHTO Committees. These concepts have been the basis used for developing policies on dimensions and weight of vehicles and highway needs which the AASHTO Transport Committees have recommended to the United States House Committee on Ways and Means. The first recommendation based on these concepts was made in the mid 1960's. Iowa's participation in the evaluation for this recommendation was under the direction of our present Director of Transportation, Mr. Raymond Kassel. PSI Indexes had to be derived from subjective surface ratings at that time. The most recent recommendation to Congress was made in November of 1977. Based on the rationale expressed above, a pilot study of the major part of the rural interstate system was conducted. The Objective of the study was to measure pavement performance through the use of the Present Serviceability Index (PSI) - Pavement Performance concepts as developed by the AASHO Road Test and to explore the usefulness of this type of data as a pavement management tool. Projects in the vicinity of the major urban centers were not included in this study due to the extra time that would be required to isolate accurate traffic data in these areas. Projects consisting of asphalt surface courses on crushed stone base sections were not included.

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[Jeune homme endormi, profil gauche] : [estampe] / [gravé par Weisbrod]

Destinataire de l'envoi : Bentinck, Charlotte Sophie von Aldenburg (1715-1800 ; comtesse de)