Patterns of care and treatment outcomes of patients with astroblastoma: A National Cancer Database analysis

AIM: To evaluate the use of chemotherapy and radiation, and their outcomes for patients with astroblastoma. PATIENTS & METHODS: This is a retrospective review of patients extracted from the National Cancer Database. We investigated overall survival (OS) using Kaplan-Meier curves. Cox proportional hazards models were used to correlate OS with risk variables and treatments. RESULTS: OS at 5 years was 79.5%. Patients with high-grade tumors were more likely to receive chemotherapy and radiation. Patients with high-grade astroblastoma who did not receive adjuvant radiation had poor survival. CONCLUSION: Patients with astroblastoma should be treated with curative intent. Radiation is likely beneficial in high-grade astroblastoma. The exact role of radiation and chemotherapy following surgical resection warrant further investigation

Parametric enhancement of flavor oscillation in a three-neutrino framework

When neutrinos travel through matter with a periodic density profile, the neutrino oscillation probability can be enhanced if certain conditions are satisfied. In a two-neutrino framework, the condition for parametric resonance is known. Herein, we consider the analogous parametric resonance condition within the context of a full three-neutrino framework with two oscillation scales. For energies in the range of hundreds of MeV to a few GeV, we find that neutrino oscillation can be parametrically enhanced if two approximate relations are satisfied. The first is similar to the two-neutrino parametric resonance condition while the second involves the other oscillation scale. Treating the Earth's density as piecewise constant, we show that oscillations in this energy range can be enhanced between two- and threefold

Vestibular Perception following Acute Unilateral Vestibular Lesions.

Little is known about the vestibulo-perceptual (VP) system, particularly after a unilateral vestibular lesion. We investigated vestibulo-ocular (VO) and VP function in 25 patients with vestibular neuritis (VN) acutely (2 days after onset) and after compensation (recovery phase, 10 weeks). Since the effect of VN on reflex and perceptual function may differ at threshold and supra-threshold acceleration levels, we used two stimulus intensities, acceleration steps of 0.5°/s(2) and velocity steps of 90°/s (acceleration 180°/s(2)). We hypothesised that the vestibular lesion or the compensatory processes could dissociate VO and VP function, particularly if the acute vertiginous sensation interferes with the perceptual tasks. Both in acute and recovery phases, VO and VP thresholds increased, particularly during ipsilesional rotations. In signal detection theory this indicates that signals from the healthy and affected side are still fused, but result in asymmetric thresholds due to a lesion-induced bias. The normal pattern whereby VP thresholds are higher than VO thresholds was preserved, indicating that any 'perceptual noise' added by the vertigo does not disrupt the cognitive decision-making processes inherent to the perceptual task. Overall, the parallel findings in VO and VP thresholds imply little or no additional cortical processing and suggest that vestibular thresholds essentially reflect the sensitivity of the fused peripheral receptors. In contrast, a significant VO-VP dissociation for supra-threshold stimuli was found. Acutely, time constants and duration of the VO and VP responses were reduced - asymmetrically for VO, as expected, but surprisingly symmetrical for perception. At recovery, VP responses normalised but VO responses remained shortened and asymmetric. Thus, unlike threshold data, supra-threshold responses show considerable VO-VP dissociation indicative of additional, higher-order processing of vestibular signals. We provide evidence of perceptual processes (ultimately cortical) participating in vestibular compensation, suppressing asymmetry acutely in unilateral vestibular lesions

Improving Sensorimotor Function and Adaptation using Stochastic Vestibular Stimulation

Astronauts experience sensorimotor changes during adaption to G-transitions that occur when entering and exiting microgravity. Post space flight, these sensorimotor disturbances can include postural and gait instability, visual performance changes, manual control disruptions, spatial disorientation, and motion sickness, all of which can hinder the operational capabilities of the astronauts. Crewmember safety would be significantly increased if sensorimotor changes brought on by gravitational changes could be mitigated and adaptation could be facilitated. The goal of this research is to investigate and develop the use of electrical stochastic vestibular stimulation (SVS) as a countermeasure to augment sensorimotor function and facilitate adaptation. For this project, SVS will be applied via electrodes on the mastoid processes at imperceptible amplitude levels. We hypothesize that SVS will improve sensorimotor performance through the phenomena of stochastic resonance, which occurs when the response of a nonlinear system to a weak input signal is optimized by the application of a particular nonzero level of noise. In line with the theory of stochastic resonance, a specific optimal level of SVS will be found and tested for each subject [1]. Three experiments are planned to investigate the use of SVS in sensory-dependent tasks and performance. The first experiment will aim to demonstrate stochastic resonance in the vestibular system through perception based motion recognition thresholds obtained using a 6-degree of freedom Stewart platform in the Jenks Vestibular Laboratory at Massachusetts Eye and Ear Infirmary. A range of SVS amplitudes will be applied to each subject and the subjectspecific optimal SVS level will be identified as that which results in the lowest motion recognition threshold, through previously established, well developed methods [2,3,4]. The second experiment will investigate the use of optimal SVS in facilitating sensorimotor adaptation to system disturbances. Subjects will adapt to wearing minifying glasses, resulting in decreased vestibular ocular reflex (VOR) gain. The VOR gain will then be intermittently measured while the subject readapts to normal vision, with and without optimal SVS. We expect that optimal SVS will cause a steepening of the adaptation curve. The third experiment will test the use of optimal SVS in an operationally relevant aerospace task, using the tilt translation sled at NASA Johnson Space Center, a test platform capable of recreating the tilt-gain and tilt-translation illusions associated with landing of a spacecraft post-space flight. In this experiment, a perception based manual control measure will be used to compare performance with and without optimal SVS. We expect performance to improve in this task when optimal SVS is applied. The ultimate goal of this work is to systematically investigate and further understand the potential benefits of stochastic vestibular stimulation in the context of human space flight so that it may be used in the future as a component of a comprehensive countermeasure plan for adaptation to G-transitions

Exhibition of Stochastic Resonance in Vestibular Perception

Astronauts experience sensorimotor changes during spaceflight, particularly during G-transitions. Post flight sensorimotor changes include spatial disorientation, along with postural and gait instability that may degrade operational capabilities of the astronauts and endanger the crew. A sensorimotor countermeasure that mitigates these effects would improve crewmember safety and decrease risk. The goal of this research is to investigate the potential use of stochastic vestibular stimulation (SVS) as a technology to improve sensorimotor function. We hypothesize that low levels of SVS will improve sensorimotor perception through the phenomenon of stochastic resonance (SR), when the response of a nonlinear system to a weak input signal is enhanced by the application of a particular nonzero level of noise. This study aims to advance the development of SVS as a potential countermeasure by 1) demonstrating the exhibition of stochastic resonance in vestibular perception, a vital component of sensorimotor function, 2) investigating the repeatability of SR exhibition, and 3) determining the relative contribution of the semicircular canals (SCC) and otolith (OTO) organs to vestibular perceptual SR. A constant current stimulator was used to deliver bilateral bipolar SVS via electrodes placed on each of the mastoid processes, as previously done. Vestibular perceptual motion recognition thresholds were measured using a 6-degree of freedom MOOG platform and a 150 trial 3-down/1-up staircase procedure. In the first test session, we measured vestibular perceptual thresholds in upright roll-tilt at 0.2 Hz (SCC+OTO) with SVS ranging from 0-700 A. In a second test session a week later, we re-measured roll-tilt thresholds with 0, optimal (from test session 1), and 1500 A SVS levels. A subset of these subjects, plus naive subjects, participated in two additional test sessions in which we measured thresholds in supine roll-rotation at 0.2 Hz (SCC) and upright y-translation at 1 Hz (OTO) with SVS up to 700 A. A sinusoidal galvanic vestibular stimulation (GVS) perceptual threshold was also measured on each test day and used to normalize the SVS levels across subjects. In roll-tilt thresholds with SVS, the characteristic SR curve was qualitatively exhibited in 10 of 12 subjects, and the improvement in motion threshold was significant in 6 subjects, indicating that optimal SVS improved passive body motion perception in a way that is consistent with classical SR theory. A probabilistic comparison to numeric simulations further validated these experimental results. On the second test session, 4 out of the 10 SR exhibitors showed repeated improvement with SVS compared to the no SVS condition. Data collection is ongoing for the last two test sessions in which SCC and OTO only perceptual motion recognition thresholds are being measured with SVS. The final results of these test sessions will give insight into whether vestibular perceptual SR can occur when only one type of vestibular sensor is sensing motion or if it is more evident when sensory integration between the SCC and OTO is occurring during the motion. The overall purpose of this research is to further quantify the effects of SVS on various sensorimotor tasks and to gain a more fundamental understanding of how SVS causes SR in the vestibular system. In the context of human space flight, results from this research will help in understanding how SVS may be practically implemented in the future as a component of a comprehensive countermeasure plan for G-transition adaptation

Quality of Life Associated with Physical Activity but not Sedentary Time in Youth

Purpose: It has been reported that youth who engaged in more screen time had lower quality of life scores compared to those that were more physically active. Furthermore, increased sedentary behavior increases health risks particularly the risk for obesity. A cross-sectional analysis was completed to examine the relationship between healthrelated quality-of-life (HRQOL) and accelerometer-measured sedentary time (ST) and physical activity (PA) in 9-10-yearold youth who were recruited for the family-based, childhood obesity intervention, iCook 4-H. It was hypothesized that objectively measured ST would be negatively correlated and PA would be positively correlated with HRQOL.Methods: A subset of participants (n=118) wore Actigraph GT3X+ accelerometers for 7 days and completed the Pediatric Quality of Life survey (PedsQLTM, version 4.0) to assess HRQOL. Mean daily minutes of accelerometermeasured ST (547 ± 60) and PA including light-intensity (LPA=240 ± 49), moderate-intensity (MPA=35 ± 11), vigorous-intensity (VPA=17 ± 9), and moderate-to vigorousintensity (MVPA=52 ± 19) were evaluated during waking hours. Multiple linear regressions were used to assess relationship between ST and PA intensities with HRQOL. Statistical significance was set at p ≤ 0.05.Results: There were no significant associations between ST or LPA with HRQOL. MPA, VPA and MVPA were positively associated with multiple HRQOL domains.Conclusion: The lack of relationship between objectively measured ST and LPA with the total HRQOL score and subscales merits further investigation. The findings of the current study support the need for lifestyle interventions that engage families in behavior that increases MVPA

Assessing the Permeability of Engineered Capillary Networks in a 3D Culture

Many pathologies are characterized by poor blood vessel growth and reduced nutrient delivery to the surrounding tissue, introducing a need for tissue engineered blood vessels. Our lab has developed a 3D co-culture method to grow interconnected networks of pericyte-invested capillaries, which can anastamose with host vasculature following implantation to restore blood flow to ischemic tissues. However, if the engineered vessels contain endothelial cells (ECs) that are misaligned or contain wide junctional gaps, they may function improperly and behave more like the pathologic vessels that nourish tumors. The purpose of this study was to test the resistance to permeability of these networks in vitro, grown with different stromal cell types, as a metric of vessel functionality. A fluorescent dextran tracer was used to visualize transport across the endothelium and the pixel intensity was quantified using a customized MATLAB algorithm. In fibroblast-EC co-cultures, the dextran tracer easily penetrated through the vessel wall and permeability was high through the first 5 days of culture, indicative of vessel immaturity. Beyond day 5, dextran accumulated at the periphery of the vessel, with very little transported across the endothelium. Quantitatively, permeability dropped from initial levels of 61% to 39% after 7 days, and to 7% after 2 weeks. When ECs were co-cultured with bone marrow-derived mesenchymal stem cells (MSCs) or adipose-derived stem cells (AdSCs), much tighter control of permeability was achieved. Relative to the EC-fibroblast co-cultures, permeabilities were reduced 41% for the EC-MSC co-cultures and 50% for the EC-AdSC co-cultures after 3 days of culture. By day 14, these permeabilities decreased by 68% and 77% over the EC-fibroblast cultures. Co-cultures containing stem cells exhibit elevated VE-cadherin levels and more prominent EC-EC junctional complexes when compared to cultures containing fibroblasts. These data suggest the stromal cell identity influences the functionality and physiologic relevance of engineered capillary networks

Non-linear stimulus-response behavior of the human stance control system is predicted by optimization of a system with sensory and motor noise

We developed a theory of human stance control that predicted (1) how subjects re-weight their utilization of proprioceptive and graviceptive orientation information in experiments where eyes closed stance was perturbed by surface-tilt stimuli with different amplitudes, (2) the experimentally observed increase in body sway variability (i.e. the “remnant” body sway that could not be attributed to the stimulus) with increasing surface-tilt amplitude, (3) neural controller feedback gains that determine the amount of corrective torque generated in relation to sensory cues signaling body orientation, and (4) the magnitude and structure of spontaneous body sway. Responses to surface-tilt perturbations with different amplitudes were interpreted using a feedback control model to determine control parameters and changes in these parameters with stimulus amplitude. Different combinations of internal sensory and/or motor noise sources were added to the model to identify the properties of noise sources that were able to account for the experimental remnant sway characteristics. Various behavioral criteria were investigated to determine if optimization of these criteria could predict the identified model parameters and amplitude-dependent parameter changes. Robust findings were that remnant sway characteristics were best predicted by models that included both sensory and motor noise, the graviceptive noise magnitude was about ten times larger than the proprioceptive noise, and noise sources with signal-dependent properties provided better explanations of remnant sway. Overall results indicate that humans dynamically weight sensory system contributions to stance control and tune their corrective responses to minimize the energetic effects of sensory noise and external stimuli