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PubMed1978

The relationship between the transition probability and oscillator concepts of the cell cycle and the nature of the commitment to replication.

The oscillator concept of the cell cycle predicts the existence of threshold conditions within the cell which must be exceeded before replication is initiated. It is shown (a) that if the conditions are subthreshold, random disturbances can trigger a cycle of the oscillation (round of replication) and (b) that the probability of this occurring increases as the state of the system approaches the threshold. It is concluded that the oscillator concept explains the data on which the transition probability model is based. It also accounts for the ability of cells to replicate even when the mitogen is present for a limited period only.

Cell Cycle↗

PubMed1993

Local control in medically inoperable lung cancer: an analysis of its importance in outcome and factors determining the probability of tumor eradication.

PURPOSE: For patients who are medically unable to tolerate a surgical resection for technically resectable non-small-cell lung carcinoma, radiation therapy is an acceptable alternative. We report on the effect of achieving local control of the primary tumor on survival end-points, and analyze factors that may influence local control. METHODS AND MATERIALS: We reviewed the records of 152 patients with medically inoperable non-small-cell lung carcinoma treated at our institutions. All patients had technically resectable lesions and no evidence of metastatic disease. Treatment was delivered using megavoltage irradiation to doses ranging from 45 to 75 Gy. RESULTS: For patients with tumors 3 cm or less, locally controlling the tumor significantly improved survival (p = .0371). Patients with T1 tumors had a higher probability of survival and disease-free-survival than patients with larger tumors if the primary tumor was locally controlled, but this survival advantage disappeared if the tumor was not controlled. Overall, patients with smaller tumors had a lower incidence of distant spread, but this association was maintained only when the primary tumor was controlled (36 month risk of 10%, 23%, and 57% for tumors < 3 cm, 3-4.9 cm, 5 cm or greater, respectively, p = .0027). For patients whose tumors were not controlled, there was no significant difference in the risk of distant dissemination by tumor size. Higher radiation doses influenced local control and metastatic spread. We observed no influence of the initial field size in the risk of local control and in the probability of survival. CONCLUSION: Radical radiation therapy is an effective treatment for small (T1 or < 3 cm) tumors when treated to doses of 65 Gy or more, and should be offered as an alternative to surgery in elderly or infirm patients. New therapeutic strategies to improve the local control rate should be considered for larger tumors, through the use of hyperfractionated treatment, endobronchial "boost" irradiation, and sensitizing chemotherapy agents.

Carcinoma, Non-Small-Cell Lung↗

PubMedDate not supplied

Ninety-five percent probability of paternity with HLA, ABO and haptoglobins.

Using HLA tissue typing as the basic genetic test along with ABO and haptoglobin typing, it is generally possible either to exclude a putative father conclusively or, in nonexclusion cases, to assign a greater than 95% probability of paternity. In 22 of 53 nonexclusion cases, the putative father had a probability of paternity above 99% based on these genetic tests.

ABO Blood-Group System↗

PubMedDate not supplied

Adverse events following immunization: assessing probability of causation.

The Monitoring System for Adverse Events Following Immunization of the Centers for Disease Control collects data on events temporally related to immunization. Occasionally, reports are received of neurologic disturbances temporally related to receipt of vaccine. Most of these disturbances are events that regularly occur in the absence of immunization. It is then difficult to determine whether the relationship between the immunization and illness is causal or coincidental. We developed a method to assess causation of serious neurologic events by probability theory. By combining epidemiologic information on disease incidence with specific elements of the patient history, an estimate of the odds of vaccine causation can be derived, based on rational assumptions rather than observer bias. The result is not a diagnosis but an estimate of probability.

Brain Diseases↗

PubMed1989

Accuracy curves: an alternative graphical representation of probability data.

Receiver operating characteristic (ROC) curves have been frequently used to compare probability models applied to medical problems. Though the curves are a measure of the discriminatory power of a model, they do not reflect the model's accuracy. A supplementary accuracy curve is derived which will be coincident with the ROC curve if the model is reliable, will be above the ROC curve if the model's probabilities are too high or below if they are too low. A clinical example of this new graphical presentation is given.

Bayes Theorem↗

PubMed1996

Applying the realized probability of dying to cancer survival.

Age comparisons of survival in cancer cohorts generally utilize relative survival rates, which are based on indicators of the probability of survival for a given number of years after diagnosis. Cancer relative survival rates for the same number of years tend to decline as age at diagnosis increases. However, the same number of years of survival reflects higher relative longevity at older ages than at younger ages. The realized probability of dying (RPD) is a survival measure that expresses individual survival time after diagnosis relative to the survival distribution of an age-, race-, and sex-specific reference population, in effect weighing individual survival time more heavily as age at diagnosis increases. The purpose of this study was to apply the RPD as a survival measure in cancer epidemiology. Two cohorts of cancer patients, white males with prostate cancer and white females with breast cancer, aged 55 years and over at diagnosis, were followed for 15 years. Although older subjects survived less time after diagnosis than younger subjects, they achieved more favorable RPD values. We present survival analysis methods for analyzing the RPD in this population, an approach not previously used with this measure. The implications for use of the RPD in cancer epidemiology are discussed.

Breast Neoplasms↗

PubMed1991

Differences in the probability of cloning specific DNA between primary and amplified libraries: theoretical considerations.

We present a theoretical study of the probability of isolating a particular clone from a DNA library. There are differences in this probability between primary and amplified libraries even if the desired clone represents the same fraction of both libraries. As the result, we must screen severalfold more phage or bacteria in an amplified library than in a primary library.

Cloning, Molecular↗

PubMed2006

Evaluating the probability of previously unknown carriage of MRSA at hospital admission.

PURPOSE: We determined the prevalence and risk profile of patients with previously unknown carriage of methicillin-resistant Staphylococcus aureus (MRSA) at hospital admission. SUBJECTS AND METHODS: We conducted a 7-month, prospective case-controlled study in adult inpatients admitted to a university hospital with endemic MRSA. Multivariate conditional logistic regression for data sets matched 1:4 was performed to identify the risk profile of newly identified MRSA carriers. RESULTS: Overall, 399 of 12072 screened admissions (prevalence, 3.3%) were found colonized (n = 368, 92%) or infected (n = 31, 8%) with MRSA. In 204 cases (prevalence, 1.7%), MRSA carriage was newly identified. Without screening on admission, 49% (196/399) of MRSA carriers would have been missed. We identified nine independent risk factors for newly identified MRSA carriage at admission (adjusted odds ratio): male sex (1.9); age greater than 75 years (2.0); receipt of fluoroquinolones (2.7), cephalosporins (2.1), and carbapenems (3.2) in the last 6 months; previous hospitalization (1.9) or intravenous therapy (1.7) during the last 12 months; urinary catheter at admission (2.0); and intrahospital transfer (2.4). A risk score (range, 0-13) was calculated by adding points assigned to these variables. On the basis of analysis of 1006 patients included in the case-controlled study, the probability of MRSA carriage was 8% (28/342) in patients with a low score (< or =1), 19% (92/482) in patients with an intermediate score (2-4), and 46% (84/182) in patients with a high score (> or =5). The risk score had good discrimination (c-statistic, 0.73) and showed excellent calibration (P = .88). CONCLUSIONS: On-admission prevalence of previously unknown MRSA carriers was high. Applying the risk score to newly admitted patients with an intermediate or high probability of MRSA carriage could allow a more effective MRSA control strategy.

Aged↗

PubMed2006

Value transfer across odor stimuli using probability of reinforcement in the rat.

In a series of experiments value transfer across odor stimuli using probability of reinforcement was demonstrated in rats. Rats were trained with the following pairs of simple simultaneous discriminations A(100) B(0) and C(50) D(0) where the letter represents a particular scent mixed with sand presented in a cup and the number in parentheses represents the probability of reinforcement given that the rats dug to the bottom of the cup. In test, the rats were confronted with a choice between the B and D stimuli and (in experiments 2 and 3) the rats preferred to dig in the B stimulus providing evidence for value transfer using procedures similar to those that have been used in the pigeon literature.

Animals↗

PubMed2006

The relation between worrying and concerns: the importance of perceived probability and cost.

The relation between worrying and individuals' concerns was examined in a sample of 197 college students. Participants described the five undesirable outcomes that they thought about most often, indicated how likely they thought the outcomes were, and how upset they would be by them. Worry severity was measured using the Penn State Worry Questionnaire. The relation between worry severity and the life domains about which individuals were concerned was quite weak. In contrast, as predicted, greater worry was associated with higher probability and cost estimates. In addition, cost estimates moderated the relation between worry severity and probability estimates. The potential importance of perceived threat for understanding worrying is discussed.

Achievement↗

PubMed2004

Contrast, probability, and saccadic latency; evidence for independence of detection and decision.

Many factors influence how long it takes to respond to a visual stimulus. The lowest-level factors, such as luminance and contrast, determine how easily different elements of a target can be detected. Higher-level factors are to do with whether these elements constitute a stimulus requiring a response; they include prior probability and urgency. It is natural to think of these two processes, detection and decision, as occurring in series, so that overall reaction time is essentially the sum of the contributions of each stage. Here, measurements of saccadic latency to visual targets whose contrast and prior probability are systematically manipulated demonstrate that there are indeed separable stages of detection and decision. Both can be quantitatively described by rise-to-threshold mechanisms; the average rate of rise of the first is a simple logarithmic function of target contrast, whereas the second shows the linear rise characteristic of the LATER model of neural decision making. The implication is that under normal, high-contrast conditions, in which detection is very fast, the random variability that is characteristic of all reaction times is not caused by sensory noise but is gratuitously introduced by the brain itself; paradoxically, by conferring unpredictability it may aid an organism's survival.

Contrast Sensitivity↗

PubMed2004

The recognition potential during sentence presentation: stimulus probability, background stimuli, and SOA.

Recognition potential (RP) is an electrical brain response that has proved its usefulness for studying semantic processing of isolated words, and appears when subjects view meaningful stimuli embedded in a stream of background images at a high rate of presentation: the rapid stream stimulation paradigm (RSS). The present technical study is aimed at testing the validity of this procedure in the study of words within sentences. For this purpose, we varied word and background probability of appearance, the number of background stimuli preceding each word, and stimulus onset asynchrony. Probability did not have significant effects on RP, but it was found that a minimum number of two background stimuli preceding each word and a high rate (250 ms) of presentation are preferable for enhancing RP amplitude. The RSS paradigm would therefore improve the visibility-and, hence, refine the analysis-of a component that can nevertheless be obtained with more standard paradigms, such as rapid serial visual presentation, devoid of interspersed background stimuli.

Adult↗

PubMed2006

Rectal bleeding, fecal incontinence, and high stool frequency after conformal radiotherapy for prostate cancer: normal tissue complication probability modeling.

PURPOSE: To analyze whether inclusion of predisposing clinical features in the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model improves the estimation of late gastrointestinal toxicity. METHODS AND MATERIALS: This study includes 468 prostate cancer patients participating in a randomized trial comparing 68 with 78 Gy. We fitted the probability of developing late toxicity within 3 years (rectal bleeding, high stool frequency, and fecal incontinence) with the original, and a modified LKB model, in which a clinical feature (e.g., history of abdominal surgery) was taken into account by fitting subset specific TD50s. The ratio of these TD50s is the dose-modifying factor for that clinical feature. Dose distributions of anorectal (bleeding and frequency) and anal wall (fecal incontinence) were used. RESULTS: The modified LKB model gave significantly better fits than the original LKB model. Patients with a history of abdominal surgery had a lower tolerance to radiation than did patients without previous surgery, with a dose-modifying factor of 1.1 for bleeding and of 2.5 for fecal incontinence. The dose-response curve for bleeding was approximately two times steeper than that for frequency and three times steeper than that for fecal incontinence. CONCLUSIONS: Inclusion of predisposing clinical features significantly improved the estimation of the NTCP. For patients with a history of abdominal surgery, more severe dose constraints should therefore be used during treatment plan optimization.

Aged↗

PubMed2004

Voxel-based homogeneity probability maps of gray matter in groups: assessing the reliability of functional effects.

A subject of increasing importance in magnetic resonance imaging (MRI) is the analysis of intersubject structural differences, particularly when comparing groups of subjects with different conditions or diagnoses. On the other hand, determining structural homogeneity across subjects using voxel-based morphological (VBM) methods has become even more important to investigators who test for group brain activation using functional magnetic resonance images (fMRI) or positron emission tomography (PET). In the absence of methods that evaluate structural differences, one does not know how much reliability to assign to the functional differences. Here, we describe a voxel-based method for quantitatively assessing the homogeneity of tissues from structural magnetic resonance images of groups. Specifically, this method determines the homogeneity of gray matter for a group of subjects. Homogeneity probability maps (HPMs) of a given tissue type (e.g., gray matter) are generated by using a confidence interval based on binomial distribution. These maps indicate for each voxel the probability that the tissue type is gray for the population being studied. Therefore, HPMs can accompany functional analyses to indicate the confidence one can assign to functional difference at any given voxel. In this paper, examples of HPMs generated for a group of control subjects are shown and discussed. The application of this method to functional analysis is demonstrated.

Adult↗

PubMed2004

MR-based automatic delineation of volumes of interest in human brain PET images using probability maps.

The purpose of this study was to develop and validate an observer-independent approach for automatic generation of volume-of-interest (VOI) brain templates to be used in emission tomography studies of the brain. The method utilizes a VOI probability map created on the basis of a database of several subjects' MR-images, where VOI sets have been defined manually. High-resolution structural MR-images and 5-HT(2A) receptor binding PET-images (in terms of (18)F-altanserin binding) from 10 healthy volunteers and 10 patients with mild cognitive impairment were included for the analysis. A template including 35 VOIs was manually delineated on the subjects' MR images. Through a warping algorithm template VOI sets defined from each individual were transferred to the other subjects MR-images and the voxel overlap was compared to the VOI set specifically drawn for that particular individual. Comparisons were also made for the VOI templates 5-HT(2A) receptor binding values. It was shown that when the generated VOI set is based on more than one template VOI set, delineation of VOIs is better reproduced and shows less variation as compared both to transfer of a single set of template VOIs as well as manual delineation of the VOI set. The approach was also shown to work equally well in individuals with pronounced cerebral atrophy. Probability-map-based automatic delineation of VOIs is a fast, objective, reproducible, and safe way to assess regional brain values from PET or SPECT scans. In addition, the method applies well in elderly subjects, even in the presence of pronounced cerebral atrophy.

Aged↗

PubMed2005

Brain activations associated with probability matching.

Previously, in a simple probability-matching experiment with two split-brain patients that involved having the participant predict which of two events will happen on the next trial, we found that the left hemisphere tended to look for patterns and match the frequency of previous occurrences but not the right hemisphere [Wolford, G., Miller, M. B., & Gazzaniga, M. S. (2000). The left hemisphere's role in hypothesis formation. Journal of Neuroscience, 20(RC64), 1-4]. In this study, we examined those findings in normal subjects using fMRI. Subjects alternated between blocks of trials in which they predicted the location of a stimulus and those in which they detected the location of a stimulus. Previous investigators using similar paradigms reported mostly right hemisphere activations, including activations in the right dorsolateral and ventrolateral prefrontal cortex, the medial prefrontal cortex, and the right lateral parietal lobe. We also found mostly right hemisphere activations, but we found that some of the activations in the dorsolateral prefrontal and parietal cortices were sensitive to individual differences in the tendency to look for patterns in random sequences. Further, we found that, by controlling for the working memory component of the predicting task, all brain activations in the normal brain associated with looking for patterns were related to the task demands of working memory processes underlying probability matching and predicting.

Adult↗

PubMed2005

Competition between simultaneous stimuli modulated by location probability in hemispatial neglect.

Many aspects of spatial neglect can be explained as arising from competition for attentional selection, with salient ipsilesional stimuli emerging as the winner more often than contralesional stimuli. The outcome of the competition, however, can be affected both by bottom-up perceptual factors such as the gestalt properties of the display and by top-down factors such as expectancy or stimulus blocking. This study examines whether the competition for attentional selection can be modulated by manipulating the probability of the target's location in hemispatial neglect. Five patients with left-sided hemispatial neglect and a group of control participants performed a visual target discrimination task. In equal probability blocks, the target appeared randomly in any of six possible horizontal locations (three left, three right) whereas in biased blocks, the target appeared in the mid-location on the left on 50% of the trials and in each of the other locations on 10% of the trials. The target appeared either alone or was accompanied by a distractor on the opposite side. The results showed that the spatial bias facilitated detection of all left-sided targets in the neglect group, but was more spatially specific in the control group. Furthermore, while distractors on either side interfered with target processing in both groups, the patterns differed across the visual field. Finally, the magnitude of facilitation due to the bias was greatest in the condition with the most inhibition, i.e. a left-sided target accompanied by a right-sided distractor in the neglect group. These data underscore the competitive push-pull relationship between different bottom-up and top-down attentional factors, particularly within neglect patients, in whom a strong ipsilesional attentional bias already exists.

Aged↗

PubMed2005

Normal tissue complication probability modeling for acute esophagitis in patients treated with conformal radiation therapy for non-small cell lung cancer.

PURPOSE: To evaluate the ability of a well-known normal tissue complication probability (NTCP) model to predict radiation esophagitis by determining updated model parameters and then comparing these results with the predictive value of other dosimetric parameters. MATERIAL AND METHODS: Clinical and dosimetric data regarding esophagitis were analyzed in 101 inoperable/unresectable non-small-cell lung cancer patients treated by external beam irradiation. Grade 2 or higher esophagitis counted as events. Parameters (TD50, n, and m) of the Lyman normal tissue complication probability (NTCP) model were determined using maximum likelihood analysis, and compared to other dose/volume threshold values including: percentage of esophagus receiving > 40 Gy (V40) to > 75 Gy (V75), and maximum esophageal doses. RESULTS: Sixteen patients developed grade 2-3 acute esophagitis (no G4 or 5). The maximum likelihood analysis produced new Lyman model parameters of: TD50 = 51 Gy, n = 0.44 and m = 0.32. The mean NTCP value is significantly lower (P < 0.001) in the group of patients without esophagitis (13.5%) than with esophagitis (27.2%). The rates of esophagitis are 2.5, 7, 9 and 13.4%, respectively, when the NTCP values are <10%, <15%, <20% and <25%. A significant association is found between esophagitis and dose/volume parameters V40 (P = 0.001) to V70 (P = 0.024). CONCLUSIONS: New values of TD50, n and m offer a good description of the esophagitis distribution in our population. Compared to the use of this model with previously published parameters (associated with late toxicity) predictions of the model for acute esophagitis using the new parameters would indicate that, for a population of patients, the distribution of events as a function of uniform dose would occur with a lower mean uniform dose value (smaller TD50), over a wider range of uniform doses (larger m), while also exhibiting a bigger volume effect (larger n). These new parameter values are supported in essence by the correlations found for the dose/volume threshold parameters.

Acute Disease↗