We write to draw readers’ attention to a little recognised form of bias that can influence conclusions which are drawn from the study of patient treatment response subgroups derived after the treatment results become known [ [1] Sylvestre M.-P. Huszti E. Hanley J.A. Do Oscar winners live longer than less successful peers? A reanalysis of the evidence. Ann Intern Med. 2006; 145: 361-363 Crossref PubMed Scopus (111) Google Scholar ]. We use some of our own data to illustrate the issue.

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 chemotherapy, fraction size). A wide 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.

Most elderly want to age in place. Yet, most elderly live in suburban and rural communities ill-suited to meet the changing aging-related demands. This paper discusses various issues communities need to address when balancing the demands of aging baby boomers against those of younger households. Accommodating changes in life stage needs requires revising building and zoning codes to permit mixed use and mixed density development incorporating greater varieties of housing units and easier accessibility. Developing support arrangements for naturally occurring retirement communities will become important for state and local governments. A significant number of aging adults will move to locales with natural and augmented civic amenities. Such migration is double-edged; features that attract gray gold also attract needy elderly. Finally, affordable housing will be an issue for a growing number of elderly, calling for targeted tax and financial assistance policies for lower income elderly homeowners.

Clinical trials and oncology data management have undergone considerable change in the past decade. Imaging has become a key tool for clinical trials management and a biomarker for clinical trial validation as imaging technologies improve and become more precise. Images have become extremely helpful in determining staging/eligibility, treatment response, and outcome determination including disease recurrence and progression. In modern protocols, images are often reviewed in real time to validate these points in order to improve compliance to study requirements and create uniform patient populations for clinical trials analysis. Data acquisition and management systems are currently in use to acquire and display images in electronic digital formats for view by both on site and off site radiology reviewers. As clinical trials become more global in focus, the ability for databases to accommodate diverse imaging acquisition strategies will become increasingly important for information review.

Purpose: To test the Washington University (WU) patient dataset, analysis of which suggested that superior-to-inferior tumor position, maximum dose, and D35 (minimum dose to the hottest 35% of the lung volume) were valuable to predict radiation pneumonitis (PP), against the patient database from Radiation Therapy Oncology Group (RTOG) trial 9311.Methods and Materials: The entire dataset consisted of 324 patients receiving definitive conformal radiotherapy for non-small-cell lung cancer (WU = 219, RTOG 9311 = 129). Clinical, dosimetric, and tumor location parameters were modeled to predict RP in the individual datasets and in a combined dataset. Association quality with RP was assessed using Spearman's rank correlation (r) for univariate analysis and multivariate analysis; comparison between subgroups was tested using the Wilcoxon rank sum test.Results: The WU model to predict RP performed poorly for the RTOG 9311 data. The most predictive model in the RTOG 9311 dataset was a single-parameter model, D15 (r = 0.28). Combining the datasets, the best derived model was a two-parameter model consisting of mean lung dose and superior-to-inferior gross tumor volume position (r = 0.303). An equation and nomogram to predict the probability of RP was derived using the combined patient population.Conclusions: Statistical models derived from a large pool of candidate models resulted in well-tuned models for each subset (WU or RTOG 9311), which did not perform well when applied to the other dataset. However, when the data were combined, a model was generated that performed well on each data subset. The final model incorporates two effects: greater risk due to inferior lung irradiation, and greater risk for increasing normal lung mean dose. This formula and nomogram may aid clinicians during radiation treatment planning for lung cancer. (c) 2007 Elsevier Inc.

This paper evaluates how consumers value differences in neighborhood composition and street layout, factors not previously included in empirical studies of house value. Highly connected street patterns are important to New Urbanism. We use measures of neighborhood street connectivity and their interaction with other neighborhood attributes to evaluate how street layout affects property values. We employ two different methods of indexing street layout. Both methods show layout has a significant impact on price, but conclusions are sensitive to the method used. In pedestrian oriented neighborhoods, a more gridiron-like street pattern increases house value using one measure, but greater connectivity decreases house value using the other. In auto-oriented developments, a more gridiron-like street pattern reduces house value using either measure.

The author looks at the volatility of sales, property, and income taxes in Georgia and concludes that a property tax is the best way to fund public schools. Sales and income taxes are more volatile than the property tax, the author says.

The practice of three-dimensional conformai radiation therapy (3DCRT) is heavily dependent on the use of image, geometric, and dosimetric data for treatment planning and verification. Several Radiation Therapy Oncology Group (RTOG) multi-institutional clinical protocols involving relationships of radiation dose and response in 3DCRT have been designed to acquire and collect both these treatment planning and verification (TPV) data as well as clinical endpoints. These TPV data have been evaluated by the 3DQA Center at Washington University in an effort (a) to evaluate the consistency of data and (b) to establish a database which can be linked to clinical outcomes for evaluating response statistics and developing dose-response models. To address these aims, two databases have been developed in the 3DQA Center. The first is a quality-assurance process-tracking database, the second a repository for evaluated TPV data for protocol cases.

PurDose/Obieclive: For treatment of lung cancer, dose heterogeneity corrections and subsequent prescription alteration remain controversial.Previous dosimetry studies based on slab geometry and single beam geometry may not adequately represent the clinical situation of a circumscribed tumor within lung.Energy choice also remains a controversy.The objective of this study was to perform dose measurements for a tumor in lung in an anthropomorphic phantom using a clinically relevant beam arrangement for both 6 and 18 MV photons.Measured and calculated dose distributions were compared, using several different dose calculation algorithms.Methods &Materials: An anthropomorphic phantom was modified by replacing lung cylinders (2.5 and 5.0 cm diameter) with muscle-equivalent cylinders.The phantom was scanned on a CT simulator.Gross, clinical, and planning target volumes (GTV, CTV, PTV1 -tumor and regional nodes plus one cm margin, PTV2 -tumor only plus one cm margin) were delineated slice-by-slice.3D planning was performed with large fields (AP/PA/RPO) covering PTV1 and boost fields optimized for each PTV2 for 6 and 18 MV photons.Ratio-TAR (RTAR) both with and without heterogeneity corrections, convolution adapted RTAR (CARTAR), and superposition convolution dose calculation algorithms were tested.Film was placed in between phantom slices at the 'tumor' levels.The phantom was irradiated using homogeneous monitor unit calculations.Measured and calculated dose distributions were compared by isodoses and dose volume histograms.One test case (2.5 cm.cylinder) compared film and TLD dose measurements with similar results.Lung tissue ratio (LTR) measurements with an ion chamber imbedded in a 3 X 3 cm 2 muscle-equivalent rectangular solid, surrounded by either lung or muscle-equivalent material, were also performed.Results: The three heterogenei W correction algorithms, compared with the measured iscdoses, overpredicted the minimum dose to PTV2 by 11-18% for the smaller tumor, and by 5-8% for the larger tumor.None of the algorithms predicted the diffuse penumbra associated with 18 MV photons in lung.For the 2.5 cm diameter tumor, the measured minimum dose covering GTV and PTV2 was 98% and 95% of the homogeneous prescription dose, respectively, for 6 MV photons.GTV and PTV2 received a minimum dose of 95% and 89% of the homogeneous prescription dose, respectively, for 18 MV.For the 5.0 cm tumor, both the 6 and 18 MV beams provided approximately 100% of the homogeneous prescription dose to both GTV and PTV2.The measured LTR for 6 MV was 1.11 versus 1.17 calculated by RTAR with heterogeneity corrections.The 18 MV measured LTR was 1.01 compared with a calculated value of 1.09.Conclusion: Our studies indicate strong caution must be exercised before reducing dose prescriptions for lung cancer based on simplistic dose calculation algorithms An institution must validate their algorithms' accuracy by performing realistic phantom studies.The LTR value of unity for 18 MV photons indicates that increased transmission is offset by reduced local scatter.High energy beams provide deficient coverage of small target volumes within lung and 6 MV photons may be preferable despite slightly increased hot spots. 2035

Purpose: We recently replaced our university developed CT simulator prototype with a commercial grade spiral CT simulator (Picker AcQsim) that is networked with three independent virtual simulation workstations and our 3D radiation therapy planning (3D-RTP) system multiple workstations.This presentation will report our initial experience with this CT simulation device and define criteria for optimum clinical use as well as describe some potential drawbacks of the current system.Methods & Materials: Over a 10 month period, 210 patients underwent CT simulation using the AcQsim.An additional 127 patients had a volumetric CT scan done on the device with their CT data and target and normal tissue contours ultimately transferred to our 3D-RTP system.We currently perform the initial patient localization and immobilization in the CT simulation suite by using CT topograms and a fiducial laser marking system.Immobilization devices, required for all patients undergoing CT simulation, are constructed and registered to a device that defines the treatment table coordinates.Orthogonal anterior and lateral CT topograms document patient alignment and the position of a reference coordinate center.The volumetric CT scan with appropriate CT contrast materials administered is obtained while the patient is in the immobilization device.On average, more than 100 CT slices are obtained per study.Contours defining tumor, target, and normal tissues are drawn on a slice by slice basis.lsocenter definition can be automatically defined within the target volume and marked on the patient and immobilizauon device before leaving the initial CT simulation session.Virtual simulation is then performed on the patient data set with the assistance of predefined target volumes and normal tissue contours displayed on rapidly computed digital reconstructed radiographs (DRRs) in a manner similar to a conventional fluoroscopic radiotherapy simulator.Lastly.a verification simulation is performed with the patient on a conventional simulator in which portal radiographs are compared against

The introduction of nonlinear damping into computational simulations of stable active cochlear mechanical models has introduced instability in computational simulations of models used here. Nonlinear dynamical systems theory provides tools that give insight into the possible sources of such instability. Analysis of differential equations for a simplified cochlear mechanical model with a computer program (“AUTO” by Eusebius Doedel) suggests that the unstable behavior of earlier simulations is an artifact of the computations rather than an inherent feature of the differential equation model. [Work supported by NIH grants NS21592 and RR01379.]

In modeling the propagation of signals produced in the cochlea, the effects of the middle ear must be included. We present a linear two-port network model of the middle ear of cat with air cavities open. Effects of the eardrum, ossicular chain, oval and round windows, and fluid in the vestibule are included. The two ports represented are: 1) the ear canal; and 2) the basal end of the cochlear spiral. The model parameters were selected to fit experimental data measuring various aspects of forward transmission only. However, we have used the model to reproduce acoustic distortion signals observed in the ear canal. Three significant findings are that: 1) The design of an acoustic coupler can have a large effect on signals measured in the ear canal; 2) The middle ear and acoustic coupler affect the reflection of distortion signals back into the cochlea and therefore affect distortion signals observed within the cochlea as well as in the ear canal; 3) The reverse transmission properties of the middle ear circuit model are highly frequency dependent.

Amplitude and phase characteristics of the two most audible combination tones (2f1 − f2) and (f2 − f1) were measured psychoacoustically on four subjects using the cancellation method. Digital stimulus generation allowed for exact phase control and continuous phase shifting. For equal level stimulus tones (f1 and f2) in cosine phase, the results generally corroborate earlier findings. That is, the amplitude of (2f1 − f2) and (f2 − f1) both decrease with increasing f2/f1 with slight changes as a function of stimulus level; (f2 − f1) phase remains relatively constant with respect to stimulus phase as a function of f2/f1, while (2f1 − f2) phase increases dramatically with increasing f2/f1. The present study covers a wide range of primary frequencies and frequency ratios; it also presents data for both (2f1 − f2) and (f2 − f1) from the same subject. Previously unreported combination-tone pitch shift as a function of cancellation-tone phase is also described.

The response characteristics of a Markov process model for neuron activity [Frederick C. Moses et al., Biophys. Soc. Abstracts 9, 115 (A) (1969)] are investigated. The input to the model is the intensity function of a Poisson process and the output is the intensity function for the firing of the neuron model. The model and its implementation are described by Clark and Molnar in Computers in Biomedical Research [Stacy and Waxman, Eds., (1974), Vol. IV]. In the current study, the input intensity function is modulated with sinusoids and, after the process reaches steady state, the output intensity function is plotted versus time for one period of the stimulus. In the case of a real neuron, a period histogram would be an estimate of this intensity function. Fourier analysis of the intensity function waveforms indicates that the model has considerable frequency selectivity. This frequency selectivity appears to be related to the tendency of the model to oscillate when there is a step in the input intensity function. This model has been previously applied to the study of cochlear nucleus neurons; it is less apparent how model parameters might be related to cochlear nerve fibers. [This work has been supported in part by grants from the United States Public Health Service.]