BACKGROUND: Tools are lacking to assess the individual risk of severe toxicity from chemotherapy. Such tools would be especially useful for older patients, who vary considerably in terms of health status and functional reserve. METHODS: The authors conducted a prospective, multicentric study of patients aged !70 years who were starting chemotherapy. Grade 4 hematologic (H) or grade 3/4 nonhematologic (NH) toxicity according to version 3.0 of the Common Terminology Criteria for Adverse Events was defined as severe. Twenty-four parameters were assessed. Toxicity of the regimen (Chemotox) was adjusted using an index to estimate the average per-patient risk of chemotherapy toxicity (the MAX2 index). In total, 562 patients were accrued, and 518 patients were evaluable and were split randomly (2:1 ratio) into a derivation cohort and a validation cohort. RESULTS: Severe toxicity was observed in 64% of patients. The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score was constructed along 2 subscores: H toxicity and NH toxicity. Predictors of H toxicity were lymphocytes, aspartate aminotransferase level, Instrumental Activities of Daily Living score, lactate dehydrogenase level, diastolic blood pressure, and Chemotox. The best model included the 4 latter predictors (risk categories: low, 7%; medium-low, 23%; medium-high, 54%; and high, 100%, respectively; P trend < .001). Predictors of NH toxicity were hemoglobin, creatinine clearance, albumin, selfrated health, Eastern Cooperative Oncology Group performance, Mini-Mental Status score, Mini-Nutritional Assessment score, and Chemotox. The 4 latter predictors provided the best model (risk categories: 33%, 46%, 67%, and 93%, respectively; P trend < .001). The combined risk categories were 50%, 58%, 77%, and 79%, respectively; P trend < .001). Bootstrap internal validation and independent sample validation demonstrated stable risk categorization and P trend < .001. CONCLUSIONS: The CRASH score distinguished several risk levels of severe toxicity. The split score discriminated better than the combined score. To the authors' knowledge, this is the first score systematically integrating both chemotherapy and patient risk for older patients and has a potential for future clinical application. Cancer 2012;118:3377-

What neural mechanisms support our conscious perception of briefly presented stimuli? Some theories of conscious access postulate a key role of top-down amplification loops involving prefrontal cortex (PFC). To test this issue, we measured the visual backward masking threshold in patients with focal prefrontal lesions, using both objective and subjective measures while controlling for putative attention deficits. In all conditions of temporal or spatial attention cueing, the threshold for access to consciousness was systematically shifted in patients, particular after a lesion of the left anterior PFC. The deficit affected subjective reports more than objective performance, and objective performance conditioned on subjective visibility was essentially normal. We conclude that PFC makes a causal contribution to conscious visual perception of masked stimuli, and outline a dual-route signal detection theory of objective and subjective decision making.

To study the effect of education on the performance in the Mini-Mental State Examination (MMSE) domains, we included 2,861 Mexican Americans aged 65 and older from the Hispanic Established Populations for Epidemiologic Studies of the Elderly (EPESE) followed from 1993-1994 until 2004-2005. The MMSE was examined as total score (0-30) or divided in two global domains: 1) no-memory (score 0-24): Orientation, attention, and language; and 2) memory (score 0-6): working and delayed memory. Mean age and total MMSE were 72.7 and 24.6 at wave 1, and 81.7 and 20.5 at wave 5. Spanish speaking subjects had lower years of education (4.1 vs. 7.4, p<. 0001), they had significantly higher adjusted (by age, education, and gender) mean scores for memory, no-memory and the total MMSE compared with English speaking subjects across the five waves of follow-up. In multivariate longitudinal analyses over 11 years of follow-up, subjects with more years of education performed better than those less educated, especially in no-memory and the total MMSE. Spanish speaking subjects with 4-6 years of education had higher memory scores than those speaking English (estimate 0.40, standard error [SE] = 0.14, p<.001), [7][8][9][10][11] SE= 0.13, p<.01) or 12+ (estimate 0.44, SE= 0.13, p<.001). This suggests that cultural factors and factors related to preferred language use may determine variations in MMSE performance. Since the memory domain of the MMSE is less affected by education, it may be used along with other cognitive tests in older populations with low education.

Biomarkers represent a critical research area in neurodegeneration disease as they can contribute to studying potential disease-modifying agents, fostering timely therapeutic interventions, and alleviating associated financial costs. Functional connectivity (FC) analysis represents a promising approach to identify early biomarkers in specific diseases. Yet, virtually no study has tested whether potential FC biomarkers prove to be reliable and reproducible across different centers. As such, their implementation remains uncertain due to multiple sources of variability across studies: the numerous international centers capable conducting FC research vary in their scanning equipment and their samples' socio-cultural background, and, more troublingly still, no gold-standard method exists to analyze FC. In this unprecedented study, we aim to address both issues by performing the first multicenter FC research in the behavioral-variant frontotemporal dementia (bvFTD), and by assessing multiple FC approaches to propose a gold-standard method for analysis. We enrolled 52 bvFTD patients and 60 controls from three international clinics (with different fMRI recording parameters), and three additional neurological patient groups. To evaluate FC, we focused on seed analysis, inter-regional connectivity, and several graph-theory approaches. Only graph-theory analysis, based on weighted-matrices, yielded consistent differences between bvFTD and controls across centers. Also, graph metrics robustly discriminated bvFTD from the other neurological conditions. The consistency of our findings across heterogeneous contexts highlights graph-theory as a potential gold-standard approach for brain network analysis in bvFTD. Hum Brain Mapp 38:3804-3822, 2017. © 2017 Wiley Periodicals, Inc.