967 resultados para Van Young, Eric


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Genotypic, developmental, and environmental factors converge to determine the degree of Crassulacean acid metabolism (CAM) expression. To characterize the signaling events controlling CAM expression in young pineapple (Ananas comosus) plants, this photosynthetic pathway was modulated through manipulations in water availability. Rapid, intense, and completely reversible up-regulation in CAM expression was triggered by water deficit, as indicated by the rise in nocturnal malate accumulation and in the expression and activity of important CAM enzymes. During both up-and down-regulation of CAM, the degree of CAM expression was positively and negatively correlated with the endogenous levels of abscisic acid (ABA) and cytokinins, respectively. When exogenously applied, ABA stimulated and cytokinins repressed the expression of CAM. However, inhibition of water deficit-induced ABA accumulation did not block the up-regulation of CAM, suggesting that a parallel, non-ABA-dependent signaling route was also operating. Moreover, strong evidence revealed that nitric oxide (NO) may fulfill an important role during CAM signaling. Up-regulation of CAM was clearly observed in NO-treated plants, and a conspicuous temporal and spatial correlation was also evident between NO production and CAM expression. Removal of NO from the tissues either by adding NO scavenger or by inhibiting NO production significantly impaired ABA-induced up-regulation of CAM, indicating that NO likely acts as a key downstream component in the ABA-dependent signaling pathway. Finally, tungstate or glutamine inhibition of the NO-generating enzyme nitrate reductase completely blocked NO production during ABA-induced up-regulation of CAM, characterizing this enzyme as responsible for NO synthesis during CAM signaling in pineapple plants.

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Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4 alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappa B signalling in Group 4, suggest future avenues for rational, targeted therapy.

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Children and adolescents infected with HIV typically have a lower response to immunization than do those in the general population. In most developed countries, meningococcal serogroup C conjugate vaccine is one of the recommended vaccines for such individuals. However, there have been no studies evaluating the antibody response to this vaccine in HIV-infected children, adolescents or young adults. In this study, we evaluated that response using serum bactericidal antibody (SBA) and enzyme-linked immunosorbent assay, comparing HIV-infected with non-HIV-infected patients, as well as analysing the occurrence of side effects. In non-responders, we assessed the antibody response to revaccination. This clinical trial involved 92 patients between 10 and 20 years of age: 43 HIV-infected patients (HIV+ group) and 49 non-HIV-infected patients (HIV- group). After one dose of the vaccine, 72.1% of the HIV+ group patients and 100% of the HIV- group patients were considered protected. Of the HIV+ group patients who received a second dose of the vaccine, only 40% acquired protection. Overall, 81.4% of the HIV+ group patients acquired protection (after one or two doses of the vaccine). Side effects occurred in 16.3% and 44% of the HIV+ group and HIV- group patients, respectively. Therefore, the meningococcal serogroup C conjugate vaccine proved to be safe and effective for use in HIV-infected children, adolescents, and young adults, although their antibody response was weaker than that shown by non-HIV-infected patients. This indicates the need to discuss changes to the immunization schedule for children, adolescents, and young adults infected with HIV, in order to ensure more effective protection against meningococcal disease. (c) 2012 Elsevier Ltd. All rights reserved.

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We report the discovery of two low-mass companions to the young A0V star HD 1160 at projected separations of 81 +/- 5 AU (HD 1160 B) and 533 +/- 25 AU (HD 1160 C) by the Gemini NICI Planet-Finding Campaign. Very Large Telescope images of the system taken over a decade for the purpose of using HD 1160 A as a photometric calibrator confirm that both companions are physically associated. By comparing the system to members of young moving groups and open clusters with well-established ages, we estimate an age of 50(-40)(+50) Myr for HD 1160 ABC. While the UVW motion of the system does not match any known moving group, the small magnitude of the space velocity is consistent with youth. Near-IR spectroscopy shows HD 1160 C to be an M3.5 +/- 0.5 star with an estimated mass of 0.22(-0.04)(+0.03) M-circle dot, while NIR photometry of HD 1160 B suggests a brown dwarf with a mass of 33(-9)(+12) M-Jup. The very small mass ratio (0.014) between the A and B components of the system is rare for A star binaries, and would represent a planetary-mass companion were HD 1160 A to be slightly less massive than the Sun.

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We have carried out high contrast imaging of 70 young, nearby B and A stars to search for brown dwarf and planetary companions as part of the Gemini NICI Planet-Finding Campaign. Our survey represents the largest, deepest survey for planets around high-mass stars (≈1.5-2.5 M ☉) conducted to date and includes the planet hosts β Pic and Fomalhaut. We obtained follow-up astrometry of all candidate companions within 400 AU projected separation for stars in uncrowded fields and identified new low-mass companions to HD 1160 and HIP 79797. We have found that the previously known young brown dwarf companion to HIP 79797 is itself a tight (3 AU) binary, composed of brown dwarfs with masses 58$^{+21}_{-20}$ M Jup and 55$^{+20}_{-19}$ M Jup, making this system one of the rare substellar binaries in orbit around a star. Considering the contrast limits of our NICI data and the fact that we did not detect any planets, we use high-fidelity Monte Carlo simulations to show that fewer than 20% of 2 M ☉ stars can have giant planets greater than 4 M Jup between 59 and 460 AU at 95% confidence, and fewer than 10% of these stars can have a planet more massive than 10 M Jup between 38 and 650 AU. Overall, we find that large-separation giant planets are not common around B and A stars: fewer than 10% of B and A stars can have an analog to the HR 8799 b (7 M Jup, 68 AU) planet at 95% confidence. We also describe a new Bayesian technique for determining the ages of field B and A stars from photometry and theoretical isochrones. Our method produces more plausible ages for high-mass stars than previous age-dating techniques, which tend to underestimate stellar ages and their uncertainties.

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Long-term dietary exposures to lead in young children were calculated by combining food consumption data of 11 European countries categorised using harmonised broad food categories with occurrence data on lead from different Member States (pan-European approach). The results of the assessment in children living in the Netherlands were compared with a long-term lead intake assessment in the same group using Dutch lead concentration data and linking the consumption and concentration data at the highest possible level of detail. Exposures obtained with the pan-European approach were higher than the national exposure calculations. For both assessments cereals contributed most to the exposure. The lower dietary exposure in the national study was due to the use of lower lead concentrations and...

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There is a shortage of empirical applications of the capability approach that employ closed survey instruments to assess self-reported capabilities. However, for those few instruments that have been designed and administered through surveys until now, no psychometric properties (reliability, validity, and factor structure) were reported. The purpose of this study is the assessment of the psychometric properties of three new language versions (German, French, and Italian) of an established (English) set of eight self-reported capability items. The set of items is taken from a previously published British study by Anand and van Hees (J Soc Econ 35(2):268–284, 2006). Our sample consists of 17,152 young male adults aged 18–25 years from the three major language regions in Switzerland. The results indicate good reliability of the three language versions. The results from the exploratory factor analyses suggest a one-dimensional factor structure for seven domain specific items. Furthermore, the results from multiple regression analyses suggest that a global summary item on overall capabilities represents a measurement alternative to the set of seven domain specific capability items. Finally, the results confirm the applicability of the closed capability instrument in a large scale survey questionnaire and represent the first attempt to measure self-reported capabilities in Switzerland.

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INTRODUCTION We report the first findings of functional magnetic resonance imaging of the auditory cortex in a young woman with a bilateral cochleovestibular deficit as first manifestation of Brown-Vialetto-Van Leare syndrome. The patient had no open speech discrimination, even with hearing aids, and is depending on lip reading for communication. METHODS To evaluate the possible efficiency of a cochlear implantation, we investigated hemodynamic responses within the central auditory pathways using an auditory functional magnetic resonance imaging paradigm. RESULTS Blood oxygen level-dependent correlates were detected bilaterally along the auditory pathways after exposure to intermittent clicking tone stimulation at 2 kHz. CONCLUSION These results suggest integrity of the central auditory pathways and represent a positive argument to propose a cochlear implantation with the aim to restore hearing.

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AIMS To estimate physical activity trajectories for people who quit smoking, and compare them to what would have been expected had smoking continued. DESIGN, SETTING AND PARTICIPANTS A total of 5115 participants in the Coronary Artery Risk Development in Young Adults Study (CARDIA) study, a population-based study of African American and European American people recruited at age 18-30 years in 1985/6 and followed over 25 years. MEASUREMENTS Physical activity was self-reported during clinical examinations at baseline (1985/6) and at years 2, 5, 7, 10, 15, 20 and 25 (2010/11); smoking status was reported each year (at examinations or by telephone, and imputed where missing). We used mixed linear models to estimate trajectories of physical activity under varying smoking conditions, with adjustment for participant characteristics and secular trends. FINDINGS We found significant interactions by race/sex (P = 0.02 for the interaction with cumulative years of smoking), hence we investigated the subgroups separately. Increasing years of smoking were associated with a decline in physical activity in black and white women and black men [e.g. coefficient for 10 years of smoking: -0.14; 95% confidence interval (CI) = -0.20 to -0.07, P < 0.001 for white women]. An increase in physical activity was associated with years since smoking cessation in white men (coefficient 0.06; 95% CI = 0 to 0.13, P = 0.05). The physical activity trajectory for people who quit diverged progressively towards higher physical activity from the expected trajectory had smoking continued. For example, physical activity was 34% higher (95% CI = 18 to 52%; P < 0.001) for white women 10 years after stopping compared with continuing smoking for those 10 years (P = 0.21 for race/sex differences). CONCLUSIONS Smokers who quit have progressively higher levels of physical activity in the years after quitting compared with continuing smokers.

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OBJECTIVE In patients with a long life expectancy with high-risk (HR) prostate cancer (PCa), the chance to die from PCa is not negligible and may change significantly according to the time elapsed from surgery. The aim of this study was to evaluate long-term survival patterns in young patients treated with radical prostatectomy (RP) for HRPCa. MATERIALS AND METHODS Within a multiinstitutional cohort, 600 young patients (≤59 years) treated with RP between 1987 and 2012 for HRPCa (defined as at least one of the following adverse characteristics: prostate specific antigen>20, cT3 or higher, biopsy Gleason sum 8-10) were identified. Smoothed cumulative incidence plot was performed to assess cancer-specific mortality (CSM) and other cause mortality (OCM) rates at 10, 15, and 20 years after RP. The same analyses were performed to assess the 5-year probability of CSM and OCM in patients who survived 5, 10, and 15 years after RP. A multivariable competing risk regression model was fitted to identify predictors of CSM and OCM. RESULTS The 10-, 15- and 20-year CSM and OCM rates were 11.6% and 5.5% vs. 15.5% and 13.5% vs. 18.4% and 19.3%, respectively. The 5-year probability of CSM and OCM rates among patients who survived at 5, 10, and 15 years after RP, were 6.4% and 2.7% vs. 4.6% and 9.6% vs. 4.2% and 8.2%, respectively. Year of surgery, pathological stage and Gleason score, surgical margin status and lymph node invasion were the major determinants of CSM (all P≤0.03). Conversely, none of the covariates was significantly associated with OCM (all P≥ 0.09). CONCLUSIONS Very long-term cancer control in young high-risk patients after RP is highly satisfactory. The probability of dying from PCa in young patients is the leading cause of death during the first 10 years of survivorship after RP. Thereafter, mortality not related to PCa became the main cause of death. Consequently, surgery should be consider among young patients with high-risk disease and strict PCa follow-up should enforce during the first 10 years of survivorship after RP.

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Background: Finding the right mentor in medical education is challenging, especially if you are relatively new to the field. However, a mentor that is fit for purpose offers great potential. The workshop will explore strategies and pitfalls for successfully finding the best available mentor. Intended Outcomes: At the end of the workshop participants will be able to: (1) identify practical strategies for successfully finding the right mentor in medical education; (2) give feedback on a proposed idea of a platform for matching mentees and mentors within AMEE; (3) establish an electronic network for continued dialogue and support within the online platform of AMEE (MedEdWorld). Structure: After an introduction to mentorship in medical education and characteristics of effective mentors, participants will have the opportunity to develop their own concepts and questions and discuss them with other participants and facilitators. Senior mentors will give advice from their experience. Furthermore, a proposal of an online platform to help young medical educators find a mentor will be presented and discussed. Who Should Attend: Young medical educators interested in finding the right mentor and in exchanging ideas with colleagues in a similar situation. Level: Introductory

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BACKGROUND Racial disparities in kidney transplantation in children have been found in the United States, but have not been studied before in Europe. STUDY DESIGN Cohort study. SETTING & PARTICIPANTS Data were derived from the ESPN/ERA-EDTA Registry, an international pediatric renal registry collecting data from 36 European countries. This analysis included 1,134 young patients (aged ≤19 years) from 8 medium- to high-income countries who initiated renal replacement therapy (RRT) in 2006 to 2012. FACTOR Racial background. OUTCOMES & MEASUREMENTS Differences between racial groups in access to kidney transplantation, transplant survival, and overall survival on RRT were examined using Cox regression analysis while adjusting for age at RRT initiation, sex, and country of residence. RESULTS 868 (76.5%) patients were white; 59 (5.2%), black; 116 (10.2%), Asian; and 91 (8.0%), from other racial groups. After a median follow-up of 2.8 (range, 0.1-3.0) years, we found that black (HR, 0.49; 95% CI, 0.34-0.72) and Asian (HR, 0.54; 95% CI, 0.41-0.71) patients were less likely to receive a kidney transplant than white patients. These disparities persisted after adjustment for primary renal disease. Transplant survival rates were similar across racial groups. Asian patients had higher overall mortality risk on RRT compared with white patients (HR, 2.50; 95% CI, 1.14-5.49). Adjustment for primary kidney disease reduced the effect of Asian background, suggesting that part of the association may be explained by differences in the underlying kidney disease between racial groups. LIMITATIONS No data for socioeconomic status, blood group, and HLA profile. CONCLUSIONS We believe this is the first study examining racial differences in access to and outcomes of kidney transplantation in a large European population. We found important differences with less favorable outcomes for black and Asian patients. Further research is required to address the barriers to optimal treatment among racial minority groups.