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Probability of finding HLA-mismatched related or unrelated marrow or cord blood donors.

Given recent improvements in the technology of transplantation and histocompatibility testing, it is now possible to contemplate using related or unrelated allogeneic hematologic stem cell donors with high degrees of HLA disparity. This paper is a follow-up of an earlier publication on the probability of finding a matched donor (Transplantation 60:778-783, 1995) and addresses the probability of finding a partially mismatched donor. Assuming that a four of six antigen HLA-A, -B, -DR match is acceptable, it is possible to find unrelated donors for patients of any race from a putative registry with fewer than 10,000 potential donors. Further, storing cord blood from newborns in families with a known genetic disease would yield an acceptable future stem cell transplant product in nearly 40% of cases. These results show the potential impact of cord blood donors and emphasize the importance of improvements in transplantation using partially mismatched donors.

Blood Donors↗

Probability of cell hits in selected organs and tissues by high-LET particles at the ISS orbit.

The fluence of high-LET particles (HLP) with LET infinity H2O greater than 15 keV micrometers-1 in selected organs and tissues were measured with plastic nuclear track detectors using a life-size human phantom on the 9th Shuttle-Mir Mission (STS-91). The planar-track fluence of HLP during the 9.8-day mission ranged from 1.9 x 10(3) n cm-2 (bladder) to 5.1 x 10(3) n cm-2 (brain) by a factor of 2.7. Based on these data, a probability of HLP hits to a matured cell of each organ or tissue was roughly estimated for a 90-day ISS mission. In the calculation, all cells were assumed to be spheres with a geometric cross-sectional area of 500 micrometers2 and the cell-hit frequency from isotropic space radiation can be described by the Poisson-distribution function. As results, the probability of one or more than 1 hit to a single cell by HLP for 90 days ranged from 17% to 38%; that of two or more than 2 hits was estimated to be 1.3-8.2%.

Brain↗

DNA probability profiles: examples from the Treponema pallidum genome.

In this paper we apply an algorithm developed by Poland (Biopolymers 13 (1974) 1859) to treat the statistical mechanics of the thermal unwinding of DNA to the genome of Treponema pallidum, the syphilis spirochete. We calculate probability profiles (giving the probability that each unit in the molecule is in the helix-state) and other statistical distributions for genes and sequences of genes, the longest containing 100 genes and 107,139 base pairs (approximately 10% of the genome).

Algorithms↗

The effects of probability and relative direction on human somatomotor electroencephalographic rhythms.

Classical views on the preparation of voluntary movement involve separate motor and cognitive processes. Recent neurophysiological evidence challenges this dichotomy. Recordings from within the motor cortices have demonstrated that cognitive factors modulate neural activity. This issue was examined in event-related desynchronizations (ERDs) by using a goal-directed pointing paradigm. The ERD, which is typically recorded in response to self-paced finger movements, has been demonstrated to reflect specific movement parameters. Cognitive factors were introduced by manipulating probability and the relative direction of the responses in a choice reaction time task. The results demonstrated that probability influences the 20 Hz ERD.

Cognition↗

[Paternity index. Application to a sample of 48 trios presumptive father-mother-child. Study of the relationship between the probability of paternity and the percentage of exclusion].

Two different indices are of interest in paternity diagnosis. 1. The proportion of men whose paternity is excluded by mother and child phenotypes. 2. The posterior probability of paternity, obtained by a bayesian process from the phenotypes of putative father, mother and child. These two indices are different, and it is proposed that the first one be used for gauging the value of the second. Two examples of the method are given: first, a sample of 48 putative father-mother-child trios, observed in the probability of paternity versus proportion of excluded men plane at different steps on the laboratory examinations, second, the figure obtained for a child for whom two putative fathers were at examination.

Paternity↗

Calculation of cranial nerve complication probability for acoustic neuroma radiosurgery.

PURPOSE: Estimations of complications from stereotactic radiosurgery usually rely simply on dose-volume or dose-diameter isoeffect curves. Due to the sparse clinical data available, these curves have typically not considered the target location in the brain, target histology, or treatment plan conformality as parameters in the calculation. In this study, a predictive model was generated to estimate the probability of cranial neuropathies as a result of acoustic schwannoma radiosurgery. METHODS AND MATERIALS: The dose-volume histogram reduction scheme was used to calculate the normal tissue complication probability (NTCP) from brainstem dose-volume histograms. The model's fitting parameters were optimized to provide the best fit to the observed complication data for acoustic neuroma patients treated with stereotactic radiosurgery at the University of Florida. The calculation was then applied to the remainder of the patients in the database. RESULTS: The best fit to our clinical data was obtained using n = 0.04, m = 0.15, and alpha/beta = 2.1 Gy(-1). Although the fitting parameter m is relatively consistent with ranges found in the literature, both the volume parameter, n, and alpha/beta are much smaller than the values quoted in the literature. The fit to our clinical data indicates that brainstem, or possibly a specific portion of the brainstem, is more radiosensitive than the parameters in the literature indicate, and that there is very little volume effect; in other words, irradiation of a small fraction of the brainstem yields NTCPs that are nearly as high as those calculated for entire volume irradiation. These new fitting parameters are specific to acoustic neuroma radiosurgery, and the small volume effect that we observe may be an artifact of the fixed relationship of acoustic tumors to specific regions of the brainstem. Applying the model to our patient database, we calculate an average NTCP of 7.2% for patients who had no cranial nerve complications, and the average NTCP for was 66% for patients who sustained a cranial neuropathy. For the entire patient population, the actual percentage of patients suffering either facial or trigeminal neuropathy was 14.7%, whereas the calculated average NTCP was 14.8%. DISCUSSION: NTCP calculations using brainstem dose-volume histograms can be used to estimate the rate of cranial neuropathies from acoustic neuroma radiosurgery. More clinical data and further study will lead to refinement of the model with time.

Brain Stem↗

Calculation of the uncertainty in complication probability for various dose-response models, applied to the parotid gland.

PURPOSE: Usually, models that predict normal tissue complication probability (NTCP) are fitted to clinical data with the maximum likelihood (ML) method. This method inevitably causes a loss of information contained in the data. In this study, an alternative method is investigated that calculates the parameter probability distribution (PD), and, thus, conserves all information. The PD method also allows the calculation of the uncertainty in the NTCP, which is an (often-neglected) prerequisite for the intercomparison of both treatment plans and NTCP models. The PD and ML methods are applied to parotid gland data, and the results are compared. METHODS AND MATERIALS: The drop in salivary flow due to radiotherapy was measured in 25 parotid glands of 15 patients. Together with the parotid gland dose-volume histograms (DVH), this enabled the calculation of the parameter PDs for three different NTCP models (Lyman, relative seriality, and critical volume). From these PDs, the NTCP and its uncertainty could be calculated for arbitrary parotid gland DVHs. ML parameters and resulting NTCP values were calculated also. RESULTS: All models fitted equally well. The parameter PDs turned out to have nonnormal shapes and long tails. The NTCP predictions of the ML and PD method usually differed considerably, depending on the NTCP model and the nature of irradiation. NTCP curves and ML parameters suggested a highly parallel organization of the parotid gland. CONCLUSIONS: Considering the substantial differences between the NTCP predictions of the ML and PD method, the use of the PD method is preferred, because this is the only method that takes all information contained in the clinical data into account. Furthermore, PD method gives a true measure of the uncertainty in the NTCP.

Confidence Intervals↗

Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability.

PURPOSE: To compare different normal tissue complication probability (NTCP) models to predict the incidence of radiation pneumonitis on the basis of the dose distribution in the lung. METHODS AND MATERIALS: The data from 382 breast cancer, malignant lymphoma, and inoperable non-small-cell lung cancer patients from two centers were studied. Radiation pneumonitis was scored using the Southwestern Oncology Group criteria. Dose-volume histograms of the lungs were calculated from the dose distributions that were corrected for dose per fraction effects. The dose-volume histogram of each patient was reduced to a single parameter using different local dose-effect relationships. Examples of single parameters were the mean lung dose (MLD) and the volume of lung receiving more than a threshold dose (V(Dth)). The parameters for the different NTCP models were fit to patient data using a maximum likelihood analysis. RESULTS: The best fit resulted in a linear local dose-effect relationship, with the MLD as the resulting single parameter. The relationship between the MLD and NTCP could be described with a median toxic dose (TD(50)) of 30.8 Gy and a steepness parameter m of 0.37. The best fit for the relationship between the V(Dth) and the NTCP was obtained with a D(th) of 13 Gy. The MLD model was found to be significantly better than the V(Dth) model (p <0.03). However, for 85% of the studied patients, the difference in NTCP calculated with both models was <10%, because of the high correlation between the two parameters. For dose distributions outside the range of the studied dose-volume histograms, the difference in NTCP, using the two models could be >35%. For arbitrary dose distributions, an estimate of the uncertainty in the NTCP could be determined using the probability distribution of the parameter values of the Lyman-Kutcher-Burman model. CONCLUSION: The maximum likelihood method revealed that the underlying local dose-effect relation for radiation pneumonitis was linear (the MLD model), rather than a step function (the V(Dth) model). Thus, for the studied patient population, the MLD was the most accurate predictor for the incidence of radiation pneumonitis.

Breast Neoplasms↗

Tumor control probability of nasopharyngeal carcinoma: a comparison of different mathematical models.

PURPOSE: Radiation dose and tumor volume are factors known to affect the local control of a given type of tumor. Local tumor control is a major factor to consider when a treatment plan is evaluated. This article reports the correlation between tumor control probability, dose, and volume in a retrospective study of 142 patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The tumor volume was outlined and calculated from a computed tomographic scan. Patients were categorized according to tumor volume and radiation dose received in treatment. Local control rate was calculated for each category by the Kaplan-Meier method. Mathematical models were fitted to correlate the local control rate, dose, and volume. Both empirical and mechanistic approaches were attempted; the former included logistic models with two and three parameters, and the latter, the formulation from Brenner and Bentzen with a radiobiological basis. RESULTS: Brenner's model estimated alpha at 0.041 Gy(-1) with 95% confidence limits (-0.032, 0.113) Gy(-1). The volume dependent constant h was estimated at 0.160 cm(-3) with 95% confidence limits (-0.729, 1.048) cm(-3). The Pearson correlation coefficient was 0.64. The magnitude and sign of the fitted parameters were reasonable and consistent with reported clinical experience. The other models were fitted with slightly better goodness of fit (r = 0.65 - 0.68), but with less interpretable parameters. CONCLUSION: Brenner's model is considered appropriate for a description of the dose and volume effect on the local control of the NPC. It could be used in combination with normal tissue complication probability for treatment plan evaluation to optimize treatment results.

Adult↗

Comparison of radiosurgery treatment modalities based on complication and control probabilities.

PURPOSE: The relative efficacy of Gamma Knife, Linac, and Proton treatment modalities for stereotactic radiosurgery (SRS) was investigated on the basis of normal tissue complication probability (NTCP) and tumor control probability (TCP), calculated for representative test cases. METHODS AND MATERIALS: Five radiosurgery patient cases were selected to cover a range of treatment-planning situations from small spherical volumes to large irregular volumes. A target volume consisting of contours drawn on CT transverse slices was prepared for each case. Plans were developed using the three treatment modalities for each case, with the objective of encompassing the target as closely as possible with a prescription isodose line and minimizing dose to normal tissue, within the constraints of current clinical practice. Dose-volume histograms (DVH) were calculated for the target and for normal tissue, and these histograms were used to calculate NTCP and TCP values for each plan. RESULTS AND CONCLUSIONS: Differences in NTCP and TCP values were found to depend on treatment modality, size, shape, and location of the target, the amount of effort devoted to treatment planning, and the complexity of the plan.

Algorithms↗

Normal tissue complication probabilities: dependence on choice of biological model and dose-volume histogram reduction scheme.

PURPOSE: To evaluate the impact of dose-volume histogram (DVH) reduction schemes and models of normal tissue complication probability (NTCP) on ranking of radiation treatment plans. METHODS AND MATERIALS: Data for liver complications in humans and for spinal cord in rats were used to derive input parameters of four different NTCP models. DVH reduction was performed using two schemes: "effective volume" and "preferred Lyman". DVHs for competing treatment plans were derived from a sample DVH by varying dose uniformity in a high dose region so that the obtained cumulative DVHs intersected. Treatment plans were ranked according to the calculated NTCP values. RESULTS: Whenever the preferred Lyman scheme was used to reduce the DVH, competing plans were indistinguishable as long as the mean dose was constant. The effective volume DVH reduction scheme did allow us to distinguish between these competing treatment plans. However, plan ranking depended on the radiobiological model used and its input parameters. CONCLUSIONS: Dose escalation will be a significant part of radiation treatment planning using new technologies, such as 3-D conformal radiotherapy and tomotherapy. Such dose escalation will depend on how the dose distributions in organs at risk are interpreted in terms of expected complication probabilities. The present study indicates considerable variability in predicted NTCP values because of the methods used for DVH reduction and radiobiological models and their input parameters. Animal studies and collection of standardized clinical data are needed to ascertain the effects of non-uniform dose distributions and to test the validity of the models currently in use.

Animals↗

Need probability effects in animal short-term memory.

Five pigeons performed in a delayed matching-to-sample (DMTS) procedure with five delay durations (0.5, 2.5, 5, 10 and 20 s) mixed within sessions. Contrary to the predictions of need probability theory, discriminability decreased when fewer short than long delays were included in each session. To test whether the decrease in discriminability was due to a decrease in obtained reinforcement at short delays, the number of trials at each delay was held constant and reinforcer probability was increased with increasing delay. This manipulation produced a similar decrease in discriminability as when the frequency of delays was manipulated. It was concluded that the effect of delay frequency on the forgetting function is mediated by the effect of the reinforcer distribution, which influences discriminability by weakening stimulus control.

Animals↗

Evaluation of DNA match probability in criminal case.

The new emphasis on quantification of evidence has led to perplexing courtroom decisions and it has been difficult for forensic scientists to pursue logical arguments. Especially, for evaluating DNA evidence, though both the genetic relationship for two compared persons and the examined locus system should be considered, the understanding for this has not yet drawn much attention. In this paper, we suggest to calculate the match probability by using coancestry coefficient when the family relationship is considered, and thus the performances of the identification values depending on the calculation of match probability are compared under various situations.

Bias↗

Pulsed field gradient NMR measurements of probability distribution of displacement under flow in sphere packings.

In this work we used the PFG NMR displacement technique to investigate the transport of water particles under flow through a model porous media. Using different sizes of sphere for monodisperse glass sphere packings, we measured the probability distribution of displacement for mean displacements ranging from 0.08 to 7.3 times the characteristic length of the porous media. We observed, therefore, the transition between the velocity probability distribution and the Gaussian-shaped distribution of classical dispersion.

Glass↗

A preliminary comparison of guided compliance and high-probability instructional sequences as treatment for noncompliance in children with developmental disabilities.

The efficacy of guided compliance and high-probability instructional sequences was compared with two children referred to an outpatient clinic for treatment of noncompliance. Parents were taught to implement the procedures in their homes, and parent-training outcomes for the two interventions were compared in terms of treatment effectiveness, procedural integrity, and parent satisfaction. Levels of compliance were higher under guided compliance than under high-probability instructional sequences. Nevertheless, parents rapidly learned to implement both treatments with a high degree of accuracy and reported equal satisfaction with the procedures.

Adult↗

Efficient diagnostic test sequence: applications of the probability-modifying plot.

Excessive diagnostic testing rarely leads to complete certainty of the disease status of a patient. Because of constraints of health care budgets, physicians should be aware of the diminishing marginal gain of each subsequent test in a testing strategy related to costs. We developed the probability-modifying plot to determine economically efficient sequence of testing without losing clinical effectiveness. Two applications of the model are presented: diagnosis of Helicobacter pylori and diagnosis of benign prostatic hyperplasia. The probability-modifying plots are drawn to visualize and calculate the economic efficiency of all possible test sequences, meaning that although the different test sequences are equally accurate, some have even lower costs than others.

Decision Support Techniques↗

Evaluation of diagnostic imaging tests: diagnostic probability estimation.

In the evaluation of a diagnostic imaging test for the diagnosis of a particular illness in a particular category of patients, the test should be construed as leading to a test result in the sense of a set of descriptive readings from the image(s), not interpretation of these; and in the evaluation of the test, therefore, the first challenge is the translation of each test result (set of readings) into the corresponding probability that the illness is present. This interpretive translation should not be subjective, nor should it be based on an objective algorithm founded on clinical judgments. Instead, a suitable diagnostic probability function (of the elements in the test result) should be derived empirically by logistic regression analysis of suitable data. We illustrate this alternative outlook by reanalysis of the data from the Prospective Investigation of Pulmonary Embolism Diagnosis.

Adult↗

Gender differences in the probability of alcohol treatment.

Interview data from 7,359 adults 18 years of age and over who met the DSM-IV criteria for alcohol abuse or dependence at some point during their lives revealed that 23.0% of the men and 15.1% of the women ever received treatment for alcohol problems. The median interval from onset of disorder to first treatment was between 2 and 3 years longer for men than women. This difference did not result from women being more likely than men to initiate treatment shortly after onset of an alcohol use disorder, but rather from men being more likely than women to initiate treatment in the period well after onset. Excluding treatment initiated prior to the clinical onset of the disorders or after cessation of drinking, men's and women's cumulative conditional probabilities of having initiated treatment by 30 years after onset of alcohol abuse or dependence were .424 and .356, respectively. Within the first 8 years after onset of abuse or dependence, men's and women's probabilities of initiating treatment were about the same, but men were 13% to 20% more likely to initiate treatment in the period from 8 to 25 years after onset. Use of proportional hazards models to adjust for factors including sociodemographic characteristics, prior consumption, severity of disorder, and comorbid drug use and depression revealed that men's and women's likelihoods of ever having received treatment did not differ for the most severely affected, those with 20 or more symptoms of abuse or dependence. Among those less severely affected, the male-to-female ratio in the likelihood of treatment declined with severity from 1.75 (1 symptom) to 1.24 (15 symptoms).

Adolescent↗