Impulsivity may be induced by therapeutic interventions (dopamine replacement therapies and sub‐thalamic nucleus (STN) stimulation) in patients with Parkinson's disease (PD). The present review has two goals. First, to describe the most frequently encountered facets of cognitive impulsivity and to stress the links between cognitive impulsivity and aspects such as reward‐related decision making, risk‐taking, and time‐processing in healthy population. The most widely used related cognitive impulsivity paradigms are presented. Second, to review the results of studies on cognitive impulsivity in healthy volunteers and in patients with PD, the latter support the applicability and clinical relevance of this construct in PD population. Data show that PD treatments may favor impulsivity via different mechanisms. Suggestions on the roles of dopamine and STN in the pathophysiology of cognitive impulsivity are proposed. © 2009 Movement Disorder Society
The objective of this paper is to examine how current techniques for flash‐flood monitoring and forecasting can meet the needs of the population at risk to evaluate the flood severity and anticipate its danger. To this end, the social response time for different social actions in the course of two well studied flash flood events which occurred in France and Italy is identified. The event management activities are broadly characterized into three types according to their main objective (information, organisation and protection). The activities are also classified into three other types according to the scale and nature of the human group involved (individuals, communities and institutions). The conclusions reached relate to (1) the characterisation of the social responses according to watershed scale and to the information available, and (2) to the appropriateness of the existing surveillance and forecasting tools to support the social responses. Results suggest that representing the dynamics of the social response with just one number representing the average time for warning a population is an oversimplification. It appears that the social response time exhibits a parallel with the hydrological response time, by diminishing in time with decreasing size of the relevant watershed. A second result is that the human groups have different capabilities of anticipation, apparently based on the nature of information they use. Comparing watershed response times and social response times shows clearly that at scales of less than 100 km 2 , a number of actions were taken with response times comparable to the catchment response time. The implications for adapting the warning processes to social scales (individual or organisational scales) are considerable. At small scales, and for the implied anticipation times, the reliable and high‐resolution description of the actual rainfall field becomes the major source of information for decision‐making processes such as deciding between evacuations or advising to stay home. This points to the need to improve the accuracy and quality control of real time radar rainfall data, especially for extreme flash flood‐generating storms. Copyright © 2009 Royal Meteorological Society
From one‐ to two‐ and three‐dimensional MAS NMR solid‐state experiments involving 31 P and 27 Al, we show that the structure of microporous alumino‐phosphate AlPO 4 ‐40 contains at least four times more sites than expected, and we attribute two types of Al IV sites. The newly described 27 Al‐ 31 P MQ‐HMQC opens new possibilities of describing details of three‐dimensional bounded networks. Copyright © 2009 John Wiley & Sons, Ltd.
Ovarian carcinoma has the highest mortality rate among gynaecological malignancies. In this project, we investigated the hypothesis that molecular markers are able to predict outcome of ovarian cancer independently of classical clinical predictors, and that these molecular markers can be validated using independent data sets. We applied a semi‐supervised method for prediction of patient survival. Microarrays from a cohort of 80 ovarian carcinomas (TOC cohort) were used for the development of a predictive model, which was then evaluated in an entirely independent cohort of 118 carcinomas (Duke cohort). A 300‐gene ovarian prognostic index (OPI) was generated and validated in a leave‐one‐out approach in the TOC cohort (Kaplan‐Meier analysis, p = 0.0087). In a second validation step, the prognostic power of the OPI was confirmed in an independent data set (Duke cohort, p = 0.0063). In multivariate analysis, the OPI was independent of the post‐operative residual tumour, the main clinico‐pathological prognostic parameter with an adjusted hazard ratio of 6.4 (TOC cohort, CI 1.8–23.5, p = 0.0049) and 1.9 (Duke cohort, CI 1.2–3.0, p = 0.0068). We constructed a combined score of molecular data (OPI) and clinical parameters (residual tumour), which was able to define patient groups with highly significant differences in survival. The integrated analysis of gene expression data as well as residual tumour can be used for optimized assessment of the prognosis of platinum‐taxol‐treated ovarian cancer. As traditional treatment options are limited, this analysis may be able to optimize clinical management and to identify those patients who would be candidates for new therapeutic strategies. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Background Chemotherapy is accepted as first‐line conservative treatment of optic pathway tumors in patients younger than 5. Limited data are available on the outcome of patients with recurrence/progression after initial chemotherapy. Procedure Data on 68 children with Optic Pathway Tumors (OPT) treated with first‐line Baby Brain (BBSFOP) chemotherapy at the Gustave Roussy Institute in Villejuif between 1990 and 2005 were reviewed. Results During a median follow‐up of 6 years, 44 (65%) patients were diagnosed with one or more relapses. Most of the relapses occurred during the first 6 years of life. Overall and progression‐free survival rates at 5 years after first relapse were 64% and 14%, respectively. First relapse was treated with chemotherapy, radiotherapy or surgery in 28, 9, and 6 patients, respectively. Best response to second‐line chemotherapy was partial response in 10, stable disease in 10, and progressive disease in 8 patients. Patients with objective radiologic response to first‐line chemotherapy, had a greater chance to respond again to second‐line chemotherapy (RR = 90% vs. 15%, P = 0.003). Median time to progression after first relapse was 1.7, 2.5, and 3.1 years after surgery, chemotherapy and radiotherapy, respectively. Finally, 25 (37%) patients received radiotherapy at a median age of 6.7 years. Conclusions Second‐line chemotherapy can be effective in the treatment of relapses after first‐line chemotherapy and delay further the need for RT, especially in patients whose tumor initially responded to chemotherapy. Despite the desire to avoid irradiation in treatment of young patients with OPT, radiotherapy was used for 37% of patients, usually before the age of 10. Pediatr Blood Cancer 2009;52:575–580. © 2009 Wiley‐Liss, Inc.
– Maize mutants deficient for the expression of two genes encoding cytosolic glutamine syntehtase (GS) isoenzymes GS1.3 and GS1.4 displayed reduced kernel number and kernel size, respectively, the effect of the mutation being cumulative in the double mutant. However, at maturity, shoot biomass production was not modified in all the mutants, indicating that the reaction catalysed by the enzyme is specifically involved in the control of grain yield. Objective – To examine the physiological impact of the GS mutations on the leaf metabolic profile during the kernel filling period, during which nitrogen is remobilised from the shoots to be further exported to the kernels. Methodology – An 1 H‐NMR spectroscopy metabolomic was applied to the investigation of metabolic change of the gln1.3 , gln1.4 and gln1.3/1.4 double mutant. Results – In the three GS mutants, an increase in the amount of several N‐containing metabolites such as asparagine, alanine, threonine and phophatidylcholine was observed whatever the level of nitrogen fertilisation. In addition, we found an accumulation of phenylalanine and tyrosine, two metabolites involved the primary steps of the phenylpropanoid pathway. Conclusion – Changes in the metabolic profile of the GS mutants suggest that, when cytosolic GS activity is strongly reduced, either alternative metabolic pathways participate in the reassimilation of ammonium released during leaf protein remobilisation or that premature leaf senescence is induced when kernel set and kernel filling are affected. The accumulation of phenylalanine and tyrosine in the mutant plants indicates that lignin biosynthesis is altered, thus possibly affecting ear development. Copyright © 2009 John Wiley & Sons, Ltd.
We assessed the impact of subcellular targeting on the heterologous expression of a clinically useful protease inhibitor, bovine aprotinin, in leaves of potato, Solanum tuberosum . Transgenic potato lines targeting aprotinin to the cytosol, the ER or the apoplast were first generated, and then assessed for their ability to accumulate the recombinant protein. On‐chip detection and quantitation of aprotinin variants by SELDI TOF MS showed the inhibitor to be absent in the cytosol, but present under different forms in the ER and the apoplast. No visible phenotypic effects of aprotinin were observed for the transgenic lines, but aprotinin retention in the ER was associated with a significant decrease of leaf soluble protein content. A 2‐D gel assessment of control and transgenic lines revealed a possible link between this altered protein content and the down‐regulation of proteins implicated in protein synthesis and maturation. These observations, supported by complementary 2‐DE analyses with potato lines targeting aprotinin to the apoplast, suggest an aprotinin‐mediated feedback in planta negatively altering protein anabolism. From a practical viewpoint, these data illustrate the importance of taking into account not only the characteristics of recombinant proteins expressed in heterologous environments, but also their possible effects on protein accumulation in the host plant factory.