1,047 research outputs found
Investigational Chemotherapy and Novel Pharmacokinetics for the Treatment of Cancers of the CNS
Investigation of Reduced-Order Modeling for Aircraft Stability and Control Prediction
High-fidelity computational fluid dynamics tools offer the potential to approximate increments for ground-to-flight scaling effects, as well as to augment the dynamic damping derivative data for motion-based flight simulators. Unfortunately, the computational expense is currently prohibitive for populating a complete simulator database. This work investigates an existing surrogate-based, indicial response reduced-order model methodology as a means to efficiently augment a flight simulator database with high-fidelity nonlinear aerodynamic damping derivatives. Creation of the reduced-order model is based on the superposition integrals of the step response with the derivative of its corresponding input signal. Step responses are calculated using a computational grid motion approach that separates the effects of angle of attack and sideslip angle from angular rates, and rates from angle of attack and sideslip. It is demonstrated that the transients produced during the start of a forced-oscillation motion are captured by the reduced-order model to the level of fidelity of a comparable computational solution. Aerodynamic coefficients computed within minutes by the reduced-order model for an aircraft undergoing an 18-second half Lazy-8 maneuver and a 25-second Immelmann turn maneuver are compared with those from full computational flight solutions that required days to complete. Finally, a cost-benefit assessment is included that demonstrates a compelling advantage for this approach.
d for maneuvering, flexible vehicles
Unsteady Model Estimation for Generic T-Tail Transport Aircraft Using Computational Data
Models including nonlinear and unsteady behaviors are developed for the longitudinal axis of the NASA Generic T-Tail Aircraft over a large range of angle of attack. These models are based on computational simulations of forced-oscillation tests in a wind tunnel. This work continues a recent study and an ongoing effort by NASA to improve aircraft simulations for pilot training in loss-of-control and stalled conditions. The objective of this work is to develop appropriate aerodynamic models that provide representative responses in simulation for a given class of aircraft. In the stall region, nonlinear unsteady responses are often present and may require an extended aerodynamic model compared to that used in the conventional flight envelope. In this study, two objectives are addressed. The first is to obtain representative models for the NASA Generic T-Tail aircraft over a wide range of angle of attack and the second is to continue development of a specialized CFD test technique that uses Schroeder sweeps to create information rich responses for unsteady aerodynamic model identification
Efficient Unsteady Model Estimation Using Computational and Experimental Data
Improving aircraft simulations for pilot training in loss-of-control and stalled conditions is one goal of NASA research in the System Wide Safety Program. One part of this effort is to develop appropriate generic aerodynamic models that provide representative responses in simulation for a given class of aircraft. In this part of the flight envelope nonlinear unsteady responses are often present and may require an extended aerodynamic model compared to that used in the conventional flight envelope. In this preliminary study, two objectives are addressed. First, to obtain a representative model for a NASA generic aircraft at an unsteady condition in the flight envelope and second, to evaluate the techniques involved. To meet these objectives, two different generic aircraft configurations are modeled using both experimental and analytical data. With these results, an initial assessment of the efficiency and quality of the tools and test techniques are evaluated to develop guidance for analytical and experimental approaches to unsteady modeling
Computational Study of a Generic T-tail Transport
This paper presents a computational study on the static and dynamic stability characteristics of a generic transport T-tail configuration under a NASA research program to improve stall models for civil transports. The NASA Tetrahedral Unstructured Software System (TetrUSS) was used to obtain both static and periodic dynamic solutions at low speed conditions for three Reynolds number conditions up to 60 deg angle of attack. The computational results are compared to experimental data. The dominant effects of Reynolds number for the static conditions were found to occur in the stall region. The pitch and roll damping coefficients compared well to experimental results up to up to 40 deg angle of attack whereas yaw damping coefficient agreed only up to 20 deg angle of attack
PP19. TEVAR in Female Patients: Increased Aortic Coverage is Associated with a Higher Risk of Spinal Cord Ischemia
Portion, package or tableware size for changing selection and consumption of food, alcohol and tobacco.
BACKGROUND: Overeating and harmful alcohol and tobacco use have been linked to the aetiology of various non-communicable diseases, which are among the leading global causes of morbidity and premature mortality. As people are repeatedly exposed to varying sizes and shapes of food, alcohol and tobacco products in environments such as shops, restaurants, bars and homes, this has stimulated public health policy interest in product size and shape as potential targets for intervention. OBJECTIVES: 1) To assess the effects of interventions involving exposure to different sizes or sets of physical dimensions of a portion, package, individual unit or item of tableware on unregulated selection or consumption of food, alcohol or tobacco products in adults and children.2) To assess the extent to which these effects may be modified by study, intervention and participant characteristics. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, PsycINFO, eight other published or grey literature databases, trial registries and key websites up to November 2012, followed by citation searches and contacts with study authors. This original search identified eligible studies published up to July 2013, which are fully incorporated into the review. We conducted an updated search up to 30 January 2015 but further eligible studies are not yet fully incorporated due to their minimal potential to change the conclusions. SELECTION CRITERIA: Randomised controlled trials with between-subjects (parallel-group) or within-subjects (cross-over) designs, conducted in laboratory or field settings, in adults or children. Eligible studies compared at least two groups of participants, each exposed to a different size or shape of a portion of a food (including non-alcoholic beverages), alcohol or tobacco product, its package or individual unit size, or of an item of tableware used to consume it, and included a measure of unregulated selection or consumption of food, alcohol or tobacco. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methods to select eligible studies for inclusion and to collect data and assess risk of bias. We calculated study-level effect sizes as standardised mean differences (SMDs) between comparison groups, measured as quantities selected or consumed. We combined these results using random-effects meta-analysis models to estimate summary effect sizes (SMDs with 95% confidence intervals (CIs)) for each outcome for size and shape comparisons. We rated the overall quality of evidence using the GRADE system. Finally, we used meta-regression analysis to investigate statistical associations between summary effect sizes and variant study, intervention or participant characteristics. MAIN RESULTS: The current version of this review includes 72 studies, published between 1978 and July 2013, assessed as being at overall unclear or high risk of bias with respect to selection and consumption outcomes. Ninety-six per cent of included studies (69/72) manipulated food products and 4% (3/72) manipulated cigarettes. No included studies manipulated alcohol products. Forty-nine per cent (35/72) manipulated portion size, 14% (10/72) package size and 21% (15/72) tableware size or shape. More studies investigated effects among adults (76% (55/72)) than children and all studies were conducted in high-income countries - predominantly in the USA (81% (58/72)). Sources of funding were reported for the majority of studies, with no evidence of funding by agencies with possible commercial interests in their results.A meta-analysis of 86 independent comparisons from 58 studies (6603 participants) found a small to moderate effect of portion, package, individual unit or tableware size on consumption of food (SMD 0.38, 95% CI 0.29 to 0.46), providing moderate quality evidence that exposure to larger sizes increased quantities of food consumed among children (SMD 0.21, 95% CI 0.10 to 0.31) and adults (SMD 0.46, 95% CI 0.40 to 0.52). The size of this effect suggests that, if sustained reductions in exposure to larger-sized food portions, packages and tableware could be achieved across the whole diet, this could reduce average daily energy consumed from food by between 144 and 228 kcal (8.5% to 13.5% from a baseline of 1689 kcal) among UK children and adults. A meta-analysis of six independent comparisons from three studies (108 participants) found low quality evidence for no difference in the effect of cigarette length on consumption (SMD 0.25, 95% CI -0.14 to 0.65).One included study (50 participants) estimated a large effect on consumption of exposure to differently shaped tableware (SMD 1.17, 95% CI 0.57 to 1.78), rated as very low quality evidence that exposure to shorter, wider bottles (versus taller, narrower bottles) increased quantities of water consumed by young adult participants.A meta-analysis of 13 independent comparisons from 10 studies (1164 participants) found a small to moderate effect of portion or tableware size on selection of food (SMD 0.42, 95% CI 0.24 to 0.59), rated as moderate quality evidence that exposure to larger sizes increased the quantities of food people selected for subsequent consumption. This effect was present among adults (SMD 0.55, 95% CI 0.35 to 0.75) but not children (SMD 0.14, 95% CI -0.06 to 0.34).In addition, a meta-analysis of three independent comparisons from three studies (232 participants) found a very large effect of exposure to differently shaped tableware on selection of non-alcoholic beverages (SMD 1.47, 95% CI 0.52 to 2.43), rated as low quality evidence that exposure to shorter, wider (versus taller, narrower) glasses or bottles increased the quantities selected for subsequent consumption among adults (SMD 2.31, 95% CI 1.79 to 2.83) and children (SMD 1.03, 95% CI 0.41 to 1.65). AUTHORS' CONCLUSIONS: This review found that people consistently consume more food and drink when offered larger-sized portions, packages or tableware than when offered smaller-sized versions. This suggests that policies and practices that successfully reduce the size, availability and appeal of larger-sized portions, packages, individual units and tableware can contribute to meaningful reductions in the quantities of food (including non-alcoholic beverages) people select and consume in the immediate and short term. However, it is uncertain whether reducing portions at the smaller end of the size range can be as effective in reducing food consumption as reductions at the larger end of the range. We are unable to highlight clear implications for tobacco or alcohol policy due to identified gaps in the current evidence base.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/14651858.CD011045.pub
Permeability changes and effect of chemotherapy in brain adjacent to tumor in an experimental model of metastatic brain tumor from breast cancer
Abstract
Background: Brain tumor vasculature can be significantly compromised and leakier than that of normal brain blood vessels. Little is known if there are vascular permeability alterations in the brain adjacent to tumor (BAT). Changes in BAT permeability may also lead to increased drug permeation in the BAT, which may exert toxicity on cells of the central nervous system. Herein, we studied permeation changes in BAT using quantitative fluorescent microscopy and autoradiography, while the effect of chemotherapy within the BAT region was determined by staining for activated astrocytes.
Methods: Human metastatic breast cancer cells (MDA-MB-231Br) were injected into left ventricle of female NuNu mice. Metastases were allowed to grow for 28 days, after which animals were injected fluorescent tracers Texas Red (625 Da) or Texas Red dextran (3 kDa) or a chemotherapeutic agent 14C-paclitaxel. The accumulation of tracers and 14C-paclitaxel in BAT were determined by using quantitative fluorescent microscopy and autoradiography respectively. The effect of chemotherapy in BAT was determined by staining for activated astrocytes.
Results: The mean permeability of texas Red (625 Da) within BAT region increased 1.0 to 2.5-fold when compared to normal brain, whereas, Texas Red dextran (3 kDa) demonstrated mean permeability increase ranging from 1.0 to 1.8-fold compared to normal brain. The Kin values in the BAT for both Texas Red (625 Da) and Texas Red dextran (3 kDa) were found to be 4.32 ± 0.2 × 105 mL/s/g and 1.6 ± 1.4 × 105 mL/s/g respectively and found to be significantly higher than the normal brain. We also found that there is significant increase in accumulation of 14C-Paclitaxel in BAT compared to the normal brain. We also observed animals treated with chemotherapy (paclitaxel (10 mg/kg), erubilin (1.5 mg/kg) and docetaxel (10 mg/kg)) showed activated astrocytes in BAT.
Conclusions: Our data showed increased permeation of fluorescent tracers and 14C-paclitaxel in the BAT. This increased permeation lead to elevated levels of activated astrocytes in BAT region in the animals treated with chemotherapy
- …