BackgroundSurvivors of pediatric brain tumors are at risk for impaired development in multiple neuropsychological domains. The purpose of this study was to compare neuropsychological outcomes of pediatric brain tumor patients who underwent X-ray radiotherapy (XRT) versus proton radiotherapy (PRT).MethodsPediatric patients who underwent either XRT or PRT and received posttreatment age-appropriate neuropsychological evaluation—including measures of intelligence (IQ), attention, memory, visuographic skills, academic skills, and parent-reported adaptive functioning—were identified. Multivariate analyses were performed to assess differences in neuropsychological outcomes and included tests for interaction between treatment cohort and follow-up time.ResultsBetween 1998 and 2017, 125 patients with tumors located in the supratentorial (17.6%), midline (28.8%), or posterior fossa (53.6%) compartments received radiation and had posttreatment neuropsychological evaluation. Median age at treatment was 7.4 years. The PRT patient cohort had higher estimated SES and shorter median time from radiotherapy completion to last neuropsychological evaluation (6.7 vs 2.6 y, P < 0.001). On multivariable analysis, PRT was associated with higher full-scale IQ (β = 10.6, P = 0.048) and processing speed (β = 14.4, P = 0.007) relative to XRT, with trend toward higher verbal IQ (β = 9.9, P = 0.06) and general adaptive functioning (β = 11.4, P = 0.07). Planned sensitivity analyses truncating follow-up interval in the XRT cohort re-demonstrated higher verbal IQ (P = 0.01) and IQ (P = 0.04) following PRT, with trend toward improved processing speed (P = 0.09).ConclusionsPRT is associated with favorable outcomes for intelligence and processing speed. Combined with other strategies for treatment de-intensification, PRT may further reduce neuropsychological morbidity of brain tumor treatment.

Background Glioblastoma (GBM; WHO grade IV) assumes a variable appearance on magnetic resonance imaging owing to heterogeneous proliferation and infiltration of its cells. As a result, the neurovascular units responsible for functional connectivity (FC) may exist within gross tumor boundaries, albeit with altered magnitude. Therefore, we hypothesize that the strength of functional connectivity within GBMs is predictive of overall survival. Methods We used pre-defined FC regions of interest (ROIs) in denovo GBM patients to characterize the presence of within-tumor FC observable via resting-state fMRI and its relationship to survival outcomes. Results 57 GBM patients (mean age 57.8 ± 13.9 years) were analyzed. Functionally connected voxels, not identifiable on conventional structural images, can be routinely found within the tumor mass and was not significantly correlated to tumor size. In patients with known survival times (n = 31), higher intra-network FC strength within GBM tumors was associated with better overall survival even after accounting for clinical and demographic covariates. Conclusions These findings suggest the possibility that functionally intact regions may persist within GBMs and that the extent to which FC is maintained may carry prognostic value and inform treatment planning.

Regional nodal irradiation for women with breast cancer is an important risk factor for upper extremity lymphedema, but tools to accurately predict lymphedema risk for individuals are lacking. In this analysis of the National Cancer Institute of Canada Clinical Trials Group MA.20 randomized trial, 3 risk factors were predictive of lymphedema risk: body mass Purpose: Regional nodal irradiation for women with breast cancer is known to be an important risk factor for the development of upper extremity lymphedema, but tools to accurately predict lymphedema risks for individual patients are lacking. This study sought to develop and validate a nomogram to predict lymphedema risk after axillary surgery and radiation therapy in women with breast cancer. Methods and Materials: Data from 1832 women accrued on the MA.20 trial between March 2000 and February 2007 were used to create a prognostic model with National Cancer Institute Common Toxicity Criteria Version 2.0 grade 2 or higher lymphedema as the primary endpoint. Multivariable logistic regression estimated model performance. External validation was performed on data from a single large academic cancer center (N Z 785). Results: In the MA.20 trial cohort, 3 risk factors were predictive of lymphedema risk: body mass index

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Ever since Abraham Flexner formalized the idea of premedical education in 1910, medical educators have argued about how best to prepare students for medical school. This back-and-forth about the premedical years has focused almost exclusively on the range and content of the required course work; noticeably absent from the debate is consideration of the ways in which the experience of the premedical years-including the curricular and noncurricular demands placed on students-shape the moral education of the next generation of physicians. The authors review the century-long conversation about premedical education, highlighting the themes of that discussion and the important aspects of being a "premed" that have not been a part of the conversation. From their systematic review of college and university Web sites designed for premedical students and from comments collected from a symposium on the premedical years, the authors describe how life as a premedical student, and not just curricular content, teaches important lessons about what it means to be a professional. The authors also report important disparities in attitudes about premedical education; for example, premedical advisors regard the "sifting process" of premedical education as a "journey of discovery," whereas students describe their premedical years as a competition. The authors' work suggests a new approach to premedical education, an approach that combines the coursework needed to succeed in medical school with formal opportunities to reflect on both the positive and pernicious effects of the premedical years.

Cocaine addicts have a number of cognitive deficits that persist following prolonged abstinence. These include impairments in executive functions dependent on the prefrontal cortex, as well as deficits on learning and memory tasks sensitive to hippocampal function. Recent preclinical studies using non-human animals have demonstrated that cocaine treatment can produce persistent deficits in executive functions, but there is relatively little evidence that treatment with cocaine produces persistent deficits in performance on hippocampal-dependent tasks. We recently demonstrated that extended (but not limited) access to self-administered cocaine is especially effective in producing persistent deficits on a test of cognitive vigilance, and therefore, we used this procedure to examine the effects of limited or extended access to cocaine self-administration on recognition memory performance, which is sensitive to hippocampal function. We found that extended access to cocaine produced deficits in recognition memory that persisted for at least 2 weeks after the cessation of drug use. We conclude that the deficits in learning and memory observed in cocaine addicts may be at least in part due to repeated drug use, rather than just due to a pre-existing condition, and that in studying the neural basis of such deficits procedures involving extended access to self-administered cocaine may be especially useful. Keywordsself-administration; memory; cocaine; object recognition Cocaine addicts present with a number of cognitive deficits even following prolonged abstinence. These include impaired performance on tasks involving attention and cognitive flexibility that are thought to be mediated by the medial and orbital prefrontal cortex, as well as spatial, verbal, and recognition memory impairments on tasks thought to be mediated by the hippocampus (Manschreck et al. 1990;Ardila et al. 1991;Berry et al. 1993;Beatty et al. 1995;Hoff et al. 1996;Bolla et al. 2003). Given that cognitive deficits are known to negatively impact treatment outcomes (Aharonovich et al. 2003;Aharonovich et al. 2006), the development of an animal model of persistent cocaine-induced cognitive deficits would be useful in exploring the nature of the deficit. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2009 July 31. Published in final edited form as:Neuroscience. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptA number of preclinical studies have reported that treatment with cocaine produces cognit...

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Purpose-This study aimed to assess the association between pretreatment c-Met overexpression in local-regional advanced cervical cancer patients treated definitively with concurrent chemoradiation (CRT) and treatment outcomes including overall survival (OS), progression free survival (PFS), distant metastases control (DM), and local-regional control (LC).Patients and Methods-This IRB approved study included cervical cancer patients treated definitively and consecutively with CRT. Evaluation of cytoplasmic immunoreactivity for c-Met was performed and scored semi-quantitatively by three pathologists, blinded to the treatment outcomes, and incorporated both the intensity and percentage of immunoreactivity in invasive