Over the last five years, we have studied spatial distributions of cochlear responses to single- and two-tone stimuli by recording sequentially from as many as 418 cochlear nerve fibers in each cat and obtaining plots of amplitude and phase of response components at primary and distortion frequencies. We have observed: (1) that such responses to two-tone stimuli of sound pressure levels (SPL) as low as 34 dB re 20 μN/m2 rms show noticeable deviations from linear behavior; (2) that two major forms of nonlinear behavior in responses to two-tone stimuli are distortion products and two-tone suppression; (3) that the spatial distributions of amplitude and phase of (2f1-f2) and (f2-f1) components in response to two-tone stimuli are similar, in the region near and apical to the distortion-frequency place, to those of the fs component in response to a single-tone stimulus whose frequency fs is equal to the particular distortion frequency, and dissimilar in the more basal region; and (4) that each of the f1 and f2 components in the response is mutually suppressed in regions where the other response component is large. By examining acoustic signals near the eardrum of the cat and the chinchilla with a closed acoustic system containing a probe microphone, we have observed, with SPL of the primary frequencies ranging from 40 to 95 dB, that the levels of the acoustic distortion signals (2f1-f2) and (f2-f1) can be as large as −30 and −43 dB, respectively, relative to the primary levels. Our results from a model for the peripheral auditory system consisting of a two-dimensional model for cochlear mechanics (with nonlinear equivalent basilar-membrane damping) coupled to a linear model for middle ear and acoustic coupler show qualitative agreement with our animal data. These animal and model studies support the following interpretations: (1) mechanical distortion signals (2f1-f2) and (f2-f1) are generated in the cochlear region where the f1 and f2 components are both large; (2) these distortion signals propagate both apically toward the distortion-frequency place and basally toward the stapes, through the middle ear and into the ear canal; and (3) mutual suppression of the f1 and f2 components and generation of the propagating distortion products are likely to be present concurrently in cochlear-partition motion. We have also found that both neurally observed and acoustically observed distortion products are reversibly reduced by exposing the ear for 1 or 2 min to a fatiguing single tone at SPL of 80 to 90 dB at a frequency near or slightly below the primary frequencies. Observations of the effects of the single-tone fatiguing and of anoxia on acoustic distortion signals demonstrate physiological vulnerability of mechanically present nonlinear behavior of the ear. Our results support the hypothesis that, in the mechanoelectrophysiological transduction occurring in the normal organ of Corti, response variables of the mechanical domain (e.g., basilar-membrane motion) and of the electrophysiological domain (e.g., hair-cell mambrane potential) are bidirectionally coupled such that nonlinear behavior originating from either domain produces effects that can also be observed in the other domain. One of the functionally useful effects of cochlear nonlinearity appears to be an increase in the dynamic range by compression of the amplitude of cochlear-partition motion.

Background-A previous analysis of our institutional database (WU) suggested that the superiorto-inferior tumor position, maximum dose, and D35 were valuable. We tested our institutional model against the RTOG 9311 patient database.

The natural history and treatment landscape of primary brain tumours are complicated by the varied tumour behaviour of primary or secondary gliomas (high-grade transformation of low-grade lesions), as well as the dilemmas with identification of radiation necrosis, tumour progression, and pseudoprogression on MRI. Radiomics and radiogenomics promise to offer precise diagnosis, predict prognosis, and assess tumour response to modern chemotherapy/immunotherapy and radiation therapy. This is achieved by a triumvirate of morphological, textural, and functional signatures, derived from a high-throughput extraction of quantitative voxel-level MR image metrics. However, the lack of standardisation of acquisition parameters and inconsistent methodology between working groups have made validations unreliable, hence multi-centre studies involving heterogenous study populations are warranted. We elucidate novel radiomic and radiogenomic workflow concepts and state-of-the-art descriptors in sub-visual MR image processing, with relevant literature on applications of such machine learning techniques in glioma management.

New Urbanism, Space syntax, Neighborhood design, Housing prices, R14, R29, R52,

Purpose To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non–small-cell lung cancer. Methods and Materials The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemo-therapy, fraction size). Awide range of dose–volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUD (generalized equivalent uniform dose) values. Results The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior–inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 * MED+1.50 * ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis risk in combined-data WUSTL and RTOG 93-11 trial datasets.