A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma.

PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.

Alpha rhythm and hypofrontality in schizophrenia.

OBJECTIVE: To reveal the EEG correlates of resting hypofrontality in schizophrenia (SZ). METHOD: We analyzed the whole-head EEG topography in 14 patients compared to 14 matched controls by applying a new parameterization of the multichannel EEG. We used a combination of power measures tuned for regional surface mapping with power measures that allow evaluation of global effects. RESULTS: The SZ-related EEG abnormalities include i) a global decrease in absolute EEG power robustly manifested in the alpha and beta frequency bands, and ii) a relative increase in the alpha power over the prefrontal brain regions against its reduction over the posterior regions. In the alpha band both effects are linked to the SZ symptoms measured with Positive and Negative Symptom Scales and to chronicity. CONCLUSION: As alpha activity is related to regional deactivation, our findings support the concept of hypofrontality in SZ and expose the alpha rhythm as a sensitive indicator of it.

Singular homoclinic bifurcations in tritrophic food chains.

The Rosenzweig-MacArthur food chain model is proved to have homoclinic orbits. The proof is in two steps. First, we use a geometric approach based on singular perturbation and detect singular homoclinic orbits as well as parameter combinations for which these orbits exist. Second, we show, numerically, that for slightly different parameter values there exist also nonsingular homoclinic orbits that tend toward the singular ones when the time responses of the three trophic levels are extremely diversified. The analysis is performed without exploiting too deeply the mathematical structure of the Rosenzweig-MacArthur model. This is done intentionally, to assist readers interested more in the methodology than in the application to food chains.

Yield and dynamics of tritrophic food chains.

Strong relationships between yield and dynamic behavior of tritrophic food chains are pointed out by analyzing the classical Rosenzweig-MacArthur model. On the one hand, food chains are subdivided into undersupplied and oversupplied categories, the first being those in which a marginal increase of nutrient supply to the bottom produces a marginal increase of mean yield at the top. On the other hand, a detailed bifurcation analysis proves that dynamic complexity first increases with nutrient supply (from stationary to a low-frequency cyclic regime and, finally, to chaos) and then decreases (from chaos to a high-frequency cyclic regime). A careful comparison of the two analyses supports the conclusion that food chains cycling at high frequency are oversupplied, while all others are undersupplied. A straightforward consequence of this result is that maximization of food yield requires a chaotic regime. This regime turns out to be very often on the edge of a potential catastrophic collapse of the top component of the food chain. In other words, optimality implies very complex and dangerous dynamics, as intuitively understood long ago for ditrophic food chains by Rosenzweig in his famous article on the paradox of enrichment.

Neurobehavioural evaluation of Venezuelan workers exposed to inorganic lead.

OBJECTIVES: To assess neurobehavioural effects of low exposure to lead, 43 workers from a lead smelter and 45 workers from a glass factory were evaluated with the World Health Organisation neurobehavioural core test battery (NCTB) in a cross sectional study. METHODS: The NCTB comprises a questionnaire and seven tests that measure simple reaction time, short-term memory (digit span, Benton), mood (profile of mood states), eye-hand coordination (Santa Ana pegboard, pursuit aiming II), and perceptual speed (digit-symbol). RESULTS: Smelter workers were employed on average for four years, and had a mean blood lead concentration of 2.0 mumol/l (42 micrograms/dl). Glass factory workers had a mean of 0.72 mumol/l (15 micrograms/dl). Historical blood lead concentrations were used to classify exposure based on current, peak, and time weighted average. Although the exposed workers performed less well than the non-exposed in 10 of 14 response variables, only profile of mood states tension-anxiety, hostility, and depression mood scales showed a significantly poorer dose-response relation with blood lead concentration in multiple linear regression models that included age, education, and alcohol intake as covariates. The frequency of symptoms of anger, depression, fatigue, and joint pain were also significantly increased in the exposed group. CONCLUSION: This study is consistent with the larger body of neurobehavioural research of low occupational exposure to lead. The small effects found in this study occurred at blood lead concentrations slightly lower than those reported in several previous studies.

Neurobehavioral evaluation of Venezuelan workers exposed to organic solvent mixtures.

To assess the applicability of the World Health Organization (WHO) Neurobehavioral Core Test Battery (NCTB), we evaluated 53 male and 29 female Venezuelan workers exposed to mixtures of organic solvents in an adhesive factory, and 56 male and 11 female workers unexposed to any type of neurotoxic chemical. The average age of unexposed workers was 30 years and 33 years for those exposed, average schooling for both groups was 8 years, and the mean duration of exposure was 7 years. The NCTB, which assesses central nervous system functions, is composed of seven tests that measure simple motor function, short-term memory, eye-hand coordination, affective behavior, and psychomotor perception and speed. The battery includes: profile of mood states (POMS); Simple Reaction Time for attention and response speed; Digit Span for auditory memory; Santa Ana manual dexterity; Digit-Symbol for perceptual motor speed; the Benton visual retention for visual perception and memory; and Pursuit Aiming II for motor steadiness. In each of 13 subtests, the exposed group had a poorer performance than the nonexposed group. The range of differences in mean performance was between 5% and 89%, particularly in POMS (tension-anxiety, anger-hostility, depression-rejection, fatigue-inertia, confusion-bewilderment), Simple Reaction Time, Digit-Symbol, and Santa Ana Pegboard (p < .05). In multivariate regression analyses, controlling for the effects of age, sex, and education, significantly poorer performance in the exposed was found for tension-anxiety, hostility, depression, and confusion moods in the POMS, and in digit-symbol and simple reaction time (p < .05). These alterations were also dose-related using years of exposure in analyses of covariance. Compared to the nonexposed, the exposed subjects demonstrated an increased frequency of subjective symptoms of fatigue, difficulties with memory, confusion, paresthesias in upper and lower extremities, and sleep disturbances. We conclude that the methodology is applicable to the population studied. The tests of the NCTB were accepted by the subjects and were administered satisfactorily, except for occasional difficulties in verbal comprehension in subtests of POMS, which is the only test that requires more demanding verbal skills. The magnitude of the behavioral deficits is consistent with the probable high level of exposure and with the range of deficits previously reported in workers with long-term solvent exposures.