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PubMed2000

The probability of correct target dosage: dose-population histograms for deriving treatment margins in radiotherapy.

PURPOSE: To provide an analytical description of the effect of random and systematic geometrical deviations on the target dose in radiotherapy and to derive margin rules. METHODS AND MATERIALS: The cumulative dose distribution delivered to the clinical target volume (CTV) is expressed analytically. Geometrical deviations are separated into treatment execution (random) and treatment preparation (systematic) variations. The analysis relates each possible preparation (systematic) error to the dose distribution over the CTV and allows computation of the probability distribution of, for instance, the minimum dose delivered to the CTV. RESULTS: The probability distributions of the cumulative dose over a population of patients are called dose-population histograms in short. Large execution (random) variations lead to CTV underdosage for a large number of patients, while the same level of preparation (systematic) errors leads to a much larger underdosage for some of the patients. A single point on the histogram gives a simple "margin recipe." For example, to ensure a minimum dose to the CTV of 95% for 90% of the patients, a margin between CTV and planning target volume (PTV) is required of 2.5 times the total standard deviation (SD) of preparation (systematic) errors (Sigma) plus 1.64 times the total SD of execution (random) errors (sigma') combined with the penumbra width, minus 1.64 times the SD describing the penumbra width (sigma(p)). For a sigma(p) of 3.2 mm, this recipe can be simplified to 2.5 Sigma + 0.7 sigma'. Because this margin excludes rotational errors and shape deviations, it must be considered as a lower limit for safe radiotherapy. CONCLUSION: Dose-population histograms provide insight into the effects of geometrical deviations on a population of patients. Using a dose-probability based approach, simple algorithms for choosing margins were derived.

Algorithms↗

PubMed1996

Tumor volume and local control probability: clinical data and radiobiological interpretations.

PURPOSE: It is well established for certain human tumor histologies that increasing tumor volume leads to a decreasing probability of tumor control. The simplest explanation for these findings is that the number of tumor clonogens that must be sterilized to control a tumor increases with tumor volume. In this investigation we consider whether clinical evidence favors a further hypothesis, namely, that clonogen number increases in direct proportion to tumor volume. METHODS AND MATERIALS: Previously published data on the volume-cure relationship for breast tumors, neck nodes, malignant melanoma, and squamous cell carcinomas of the oropharynx and the uterine cervix were analyzed. RESULTS: We found in all these data sets evidence that the effect of tumor volume on tumor control probability was less than what would be expected under the assumption of proportionality between number of clonogens and volume. We describe good reasons to believe that this is the result of patient-to-patient variability in radiocurability, and possibly other factors as well. CONCLUSIONS: Clinical data do provide evidence for a highly significant reduction of tumor control probability with increasing tumor volume. However, because of heterogeneity in patient and tumor characteristics, the volume effect is less pronounced than would be expected from a simple proportionality between number of clonogens and volume. In principle this simple proportionality does hold in individual patients, so that standard approaches for treatment plan optimization in individuals may still be valid.

Humans↗

PubMed2002

Treatment of pancreatic cancer tumors with intensity-modulated radiation therapy (IMRT) using the volume at risk approach (VARA): employing dose-volume histogram (DVH) and normal tissue complication probability (NTCP) to evaluate small bowel toxicity.

The emergent use of a combined modality approach (chemotherapy and radiation) in pancreatic cancer is associated with increased gastrointestinal toxicity. Intensity-modulated radiation therapy (IMRT) has the potential to deliver adequate dose to the tumor volume while decreasing the dose to critical structures such as the small bowel. We evaluated the influence of IMRT with inverse treatment planning on the dose-volume histograms (DVHs) of normal tissue compared to standard 3-dimensional conformal radiation treatment (3D-CRT) in patients with pancreatic cancer. Between July 1999 and May 2001, 10 randomly selected patients with adenocarcinoma of the pancreatic head were planned simultaneously with 3D-CRT and inverse-planned IMRT using the volume at risk approach (VaRA) and compared for various dosimetric parameters. DVH and normal tissue complication probability (NTCP) were calculated using IMRT and 3D-CRT plans. The aim of the treatment plan was to deliver 61.2 Gy to the gross tumor volume (GTV) and 45 Gy to the clinical treatment volume (CTV) while maintaining critical normal tissues to below specified tolerances. IMRT plans were more conformal than 3D-CRT plans. The average dose delivered to one third of the small bowel was lower with the IMRT plan compared to 3D-CRT. The IMRT plan resulted in one third of the small bowel receiving 30.2+/-12.9 Gy vs. 38.5+/-14.2 Gy with 3D-CRT (p = 0.006). The median volume of small bowel that received greater than either 50 or 60 Gy was reduced with IMRT. The median volume of small bowel exceeding 50 Gy was 19.2+/-11.2% (range 3% to 45%) compared to 31.4+/-21.3 (range 7% to 70%) for 3D-CRT (p = 0.048). The median volume of small bowel that received greater than 60 Gy was 12.5+/-4.8% for IMRT compared to 19.8+/-18.6% for 3D-CRT (p = 0.034). The VaRA approach employing IMRT techniques resulted in a lower dose per volume of small bowel that exceeded 60 Gy. We used the Lyman-Kutcher models to compare the probability of small bowel injury employing IMRT compared to 3D-CRT. The BIOPLAN model predicted a small bowel complication probability of 9.3+/-6% with IMRT compared to 24.4+/-18.9% with 3D-CRT delivery of dose (p = 0.021). IMRT with an inverse treatment plan has the potential to significantly improve radiation therapy of pancreatic cancers by reducing normal tissue dose, and simultaneously allow escalation of dose to further enhance locoregional control.

Adenocarcinoma↗

PubMedDate not supplied

Emission probabilities of the KX-rays following the decay of 237Np in equilibrium with 233Pa.

Following international EUROMET Project No. 416 and our recent measurement of the emission probabilities of the main gamma-rays of 237Np in equilibrium with 233Pa, a complementary work has been undertaken to determine the photon emission probabilities of the KX-rays associated with the decay of these nuclides. Two different analysis methods have been used: the KX-rays region was analyzed by fitting both Voigt and full response functions. Photon emission probabilities were determined with a relative uncertainty of about 2%.

Journal Article↗

PubMed1997

Surveillance mammography and stereotactic core breast biopsy for probably benign lesions: a cost comparison analysis.

RATIONALE AND OBJECTIVES: The authors compared the economic effect of stereotactic core needle biopsy (CNB) with that of short-term unilateral surveillance mammography in the management of probably benign breast lesions detected during routine screening mammography. METHODS: Published data with regard to the cost of stereotactic CNB and unilateral mammography were applied to 3,184 patients who underwent surveillance mammography; including 161 patients who underwent biopsy. Costs of immediate tissue diagnosis were compared with costs of surveillance with use of ratios of published reimbursement scales to minimize geographic variations. Sensitivity analyses were applied to this ratio. RESULTS: The cost of managing probably benign breast lesions with surveillance mammography was $3,307,575 less than if all lesions had been managed with CNB. The ratio of the cost of CNB to the cost of surveillance mammography was 8:1. This ratio is more sensitive to the frequency of use of CNB than to reimbursement schedules. CONCLUSION: With similar false-negative rates, CNB is more costly than surveillance and has a negative effect in the management of probably benign breast lesions, unless interval change during surveillance prompts tissue diagnosis.

Biopsy, Needle↗

PubMed2001

[Estimation of the probability of mediastinal involvement: a statistical definition of the clinical target volume for 3-dimensional conformal radiotherapy in non-small-cell lung cancer?].

PURPOSE: Conformal irradiation of non-small cell lung carcinoma (NSCLC) is largely based on a precise definition of the nodal clinical target volume (CTVn). The reduction of the number of nodal stations to be irradiated would render tumor dose escalation more achievable. The aim of this work was to design an mathematical tool based on documented data, that would predict the risk of metastatic involvement for each nodal station. METHODS AND MATERIAL: From the large surgical series published in the literature we looked at the main pre-treatment parameters that modify the risk of nodal invasion. The probability of involvement for the 17 nodal stations described by the American Thoracic Society (ATS) was computed from all these publications and then weighted according to the French epidemiological data. Starting from the primitive location of the tumour as the main characteristic, we built a probabilistic tree for each nodal station representing the risk distribution as a function of each tumor feature. From the statistical point of view, we used the inversion of probability trees method described by Weinstein and Feinberg. RESULTS: Taking into account all the different parameters of the pre-treatment staging relative to each level of the ATS map brings up to 20,000 different combinations. The first chosen parameters in the tree were, depending on the tumour location, the histological classification, the metastatic stage, the nodal stage weighted in function of the sensitivity and specificity of the diagnostic examination used (PET scan, CAT scan) and the tumoral stage. A software is proposed to compute a predicted probability of involvement of each nodal station for any given clinical presentation. CONCLUSION: To better define the CTVn in NSCLC 3DRT, we propose a software that evaluates the mediastinal nodal involvement risk from easily accessible individual pre-treatment parameters.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Effects of rivastigmine treatment on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable Alzheimer's disease: a 26-week, multicenter, open-label study.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and is characterized clinically by a gradual decline in cognitive performance, an increasingly impaired ability to perform activities of daily living, and neuropsychiatric and behavioral disturbances. OBJECTIVE: The goal of this study was to assess the effect of rivastigmine on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable AD and to evaluate the safety and tolerability of rivastigmine in this population. METHODS: This prospective, 26-week, open-label study was conducted in 13 centers in the United States and involved a total of 29 nursing homes. The effects of rivastigmine 3 to 12 mg/d for 26 weeks were assessed in nursing home residents with moderate to severe probable AD. Efficacy was evaluated using the Neuropsychiatric Inventory-Nursing Home (NPI-NH) scale for neuropsychiatric and behavioral disturbances; the Mini-Mental State Examination and the naming subset of the Alzheimer's Disease Assessment Scale-Cognitive subscale for cognitive performance; and the simplified Clinician's Interview-Based Impression of Change Plus Caregiver Input for global functioning. RESULTS: A total of 173 patients (141 women, 32 men; mean [SD]age, 82.6 [5.9] years) were enrolled. After 26 weeks of rivastigmine treatment, the mean (SD) change from baseline for all treated patients in the observed cases population was -2.5 (16.4) (n = 100; P = 0.138); it was -0.8 (16.5) (n = 149; P = 0.576) for the last-observation-carried-forward population. Patients with at least 1 neuropsychiatric symptom present at baseline showed a 3.2-point mean improvement in NPI-NH total score (n = 92; P = 0.062), with 49% of these patients demonstrating a clinically meaningful (ie, > or = 30%) reduction from baseline. At 26 weeks, scores for 8 of the 12 neuropsychiatric and behavioral disturbances in patients with the specific symptom present at baseline showed statistically significant improvements from baseline (delusions [n = 32; P = 0.007], hallucinations [n = 15; P < 0.001], agitation [n = 58; P = 0.044], apathy/indifference [n = 37; P < 0.001], irritability/lability [n = 50; P < 0.001], aberrant motor behavior [n = 32; P < 0.001], nighttime disturbances [n = 22; P < 0.001], and appetite/eating changes [n = 28; P = 0.002]) in the observed cases population. Limitations of this study include that it was open label and not restricted to patients with behavioral disturbances at baseline. CONCLUSION: In the current study, rivastigmine treatment for 26 weeks in nursing home residents with moderate to severe probable AD was associated with decreased NPI-NH item scores for a wide range of behavioral disturbances in the subgroup of patients with behavioral symptoms at baseline.

Aged↗

PubMed2005

Clinical characteristics, management and prognostic factors in patients with probable severe acute respiratory syndrome (SARS) in a SARS center in Taiwan.

BACKGROUND: Severe acute respiratory syndrome (SARS) is an emerging viral infectious disease. We report our experience in treating SARS patients. METHODS: From April 27 to May 24, 2003, a total of 36 patients with probable SARS were admitted and treated in a hospital rearranged as a special center for the management of SARS patients. Medical records for the patients were retrospectively reviewed. Univariate and multivariate analyses were performed to determine factors associated with respiratory failure and intubation. RESULTS: Of the 36 patients with probable SARS (median age, 37 years; range, 22-66 years), 9 were male and 27 were female. Thirty-two patients (88.9%) were infected in the hospital setting. All patients presented with fever, and 33 eventually developed lymphopenia during hospitalization. Chest radiography showed no unique pattern, but pleural effusion was not seen. All patients initially received empiric antibacterial therapy against common causative pathogens of atypical pneumonia. Ribavirin was given to all except 1 patient. Twenty-two patients received immunoglobulin therapy, and 32 were given corticosteroids. A total of 20 patients (55.6%) required supplemental oxygen, and 8 (22.2%) were intubated with mechanical ventilatory support. Two of these patients died. A higher body temperature at presentation (median 39.5 vs 38.6 degrees C), and higher peak values of lactate dehydrogenase (410 vs 282 U/L) and C-reactive protein (10.2 vs 2.5 mg/dL), were associated with subsequent respiratory failure. Multivariate analysis showed that peak level of C-reactive protein was the only independent predictor of respiratory failure and intubation (odds ratio for every increment of 1 mg/dL = 1.45; 95% confidence interval = 1.003, 2.097; p = 0.048). CONCLUSION: All patients with probable SARS who were admitted to hospital presented with fever and lymphopenia. While the efficacy of different treatments could not be evaluated from this retrospective study, a higher value of C-reactive protein was associated with the development of respiratory failure and subsequent intubation.

Adult↗

PubMed2001

Two-locus identity probabilities and identity disequilibrium in a partially selfing subdivided population.

Measures of association of genes at different loci (linkage disequilibrium) are widely used to determine whether the structure of natural populations is clonal or not, to map genes from population data, or to test for the homogeneity of response of molecular markers to background selection, for example. However, the usual definitions of parameters for gametic associations may not be suitable for all these purposes. In this paper, we derive the recursion equations for one- and two-locus identity probabilities in an infinite island model. We study the role of drift, gene flow, partial selfing and mutation model on the expected association of genes across loci. We define the 'within-subpopulation identity disequilibrium' as the difference between the joint two-locus probability of identity in state and the expected product of one-locus identity probabilities. We evaluate this parameter as a function of recombination rate, effective size, gene flow and selfing rate. Within-subpopulation identity disequilibrium attains maximum values for intermediate immigration rates, whatever the selfing rate. Moreover, identity disequilibrium may be very small, even for high selfing rates. We discuss the implications of these findings for the analysis of data from natural populations.

Alleles↗

PubMed2002

A haplotypic approach to founder-origin probabilities and outbred QTL analysis.

Founder-origin probability methods are used to trace specific chromosomal segments in individual offspring. A haplotypic method was developed for calculating founder-origin probabilities in three-generation outbred pedigrees suited to quantitative trait locus (QTL) analysis. Estimators for expected founder-origin proportions were derived for a linkage group segment, an entire linkage group and a complete haplotype. If the founders are truly outbred, the haplotypic method gives a close approximation when compared with the Haley et al. (1994) method that simultaneously uses all marker information for QTL analysis, and it is less computationally demanding. The chief limitation of the haplotypic method is that some information in two-allele intercross marker-type configurations is ignored. Informativeness of marker arrays is discussed in the framework of founder-origin probabilities and proportions. The haplotypic method can be extended to more complex pedigrees with additional generations.

Founder Effect↗

PubMed2005

Host specificity and the probability of discovering species of helminth parasites.

Different animal species have different probabilities of being discovered and described by scientists, and these probabilities are determined to a large extent by the biological characteristics of these species. For instance, species with broader geographical ranges are more likely to be encountered by collectors than species with restricted distributions; indeed, the size of the geographical range is often the best predictor of a species' date of description. For parasitic organisms, host specificity may be similarly linked to the probability of a species being found. Here, using data on 170 helminth species parasitic in freshwater fishes, we show that host specificity is associated with the year in which the helminths were described. Helminths that exploit more host species, and to a lesser degree those that exploit a broader taxonomic range of host species, tend to be discovered earlier than the more host-specific helminths. This pattern was observed across all helminth species, as well as within the different helminth taxa (trematodes, cestodes, nematodes and acanthocephalans). Our results demonstrate that the parasite species known at any given point in time are not a random subset of existing species, but rather a biased subset with respect to the parasites' biological properties.

Animals↗

PubMedDate not supplied

Chloride efflux inhibits single calcium channel open probability in vertebrate photoreceptors: chloride imaging and cell-attached patch-clamp recordings.

The present study uses cell-attached patch-recording techniques to study the single-channel properties of Ca2+ channels in isolated salamander photoreceptors and investigate their sensitivity to reductions in intracellular Cl-. The results show that photoreceptor Ca2+ channels possess properties similar to L-type Ca2+ channels in other preparations, including (1) enhancement of openings by the dihydropyridine agonist, (-)BayK8644; (2) suppression by a dihydropyridine antagonist, nisoldipine; (3) single-channel conductance of 22 pS with 82 mM Ba2+ as the charge carrier; (4) mean open probability of 0.1; (5) open-time distribution fit with a single exponential (tau0 = 1.1 ms) consistent with a single open state; and (6) closed time distribution fit with two exponentials (tau(c1) = 0.7 ms, tau(c2) = 25.4 ms) consistent with at least two closed states. Using a Cl- -sensitive dye to measure intracellular [Cl-], it was found that perfusion with gluconate-containing, low Cl- medium depleted intracellular [Cl-]. It was therefore possible to reduce intracellular [Cl-] by perfusion with a low Cl- solution while maintaining the extracellular channel surface in high Cl- pipette solution. Under these conditions, the single-channel conductance was unchanged, but the mean open probability fell to 0.03. This reduction can account for the 66% reduction in whole-cell Ca2+ currents produced by perfusion with low Cl- solutions. Examination of the open and closed time distributions suggests that the reduction in open probability arises from increases in closed-state dwell times. Changes in intracellular [Cl-] may thus modulate photoreceptor Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2002

Probability of nitrate contamination of recently recharged groundwaters in the conterminous United States.

A new logistic regression (LR) model was used to predict the probability of nitrate contamination exceeding 4 mg/L in predominantly shallow, recently recharged groundwaters of the United States. The new model contains variables representing (1) N fertilizer loading (p < 0.001), (2) percent cropland-pasture (p < 0.001), (3) natural log of human population density (p < 0.001), (4) percent well-drained soils (p < 0.001), (5) depth to the seasonally high water table (p < 0.001), and (6) presence or absence of unconsolidated sand and gravel aquifers (p = 0.002). Observed and average predicted probabilities associated with deciles of risk are well correlated (r2 = 0.875), indicating that the LR model fits the data well. The likelihood of nitrate contamination is greater in areas with high N loading and well-drained surficial soils over unconsolidated sand and gravels. The LR model correctly predicted the status of nitrate contamination in 75% of wells in a validation data set. Considering all wells used in both calibration and validation, observed median nitrate concentration increased from 0.24 to 8.30 mg/L as the mapped probability of nitrate exceeding 4 mg/L increased from < or =0.17 to >0.83.

Forecasting↗

PubMed2000

Comparison of different procedures to identify probable cases of myocardial infarction and stroke in two Swedish prospective cohort studies using local and national routine registers.

In prospective cohort studies, person-time time is calculated from baseline until the first definite event occurs or until censoring. A way to correctly identify and date definite events when only routine registers are available is to retrieve all hospital discharge notes and death certificates with a diagnosis of probable event and perform a consecutive revision. It is important to detect all possible hospital stays as they may contain useful information for the revision study. Furthermore, loss to follow-up can be avoided by extending the retrieval outside the specific geographical area where the cohort was defined. The aims of this study were (i) to describe a comprehensive retrieval of probable myocardial infarctions (diagnosis with International Classification of Diseases 8th and 9th revisions codes 410-414) or stroke (codes 430-438), (ii) to quantify the relative efficiency of different local and national routine registers or their combination compared with the use of all available registers together, and (iii) to audit local and national registers by comparing their outcome at the county level. The study was performed in two prospective cohorts studies i.e., 'Men-born-1914' (n = 500) from Skåne (period 1982-1993), and Skara-1 (n = 683) from Skaraborg (period 1988-1994.). All available routine registers were linked to the cohorts. The use of all available routine registers improved retrieval of both individual and hospital stays with a discharge diagnosis of probable event and gave an enhanced basis for a future validation study. Local registers were not completely covered by the national register, but the accessible combination of national inpatient and mortality registers was an efficient alternative.

Aged↗

PubMed2001

Delayed motherhood increases the probability of sons to be infertile.

PURPOSE: To ascertain whether advanced maternal age at birth is associated with offspring infertility. METHODS: A written questionnaire was completed by infertile couples attending our clinic in the presence of a researcher. RESULTS: Maternal age at birth (odds ratio 1.236, 95% CI 1.100-1.388) and birth order of all respondents and their respective siblings (odds ratio 0.551, 95% CI 0.351-0.865) were significant predictors of male infertility. The probability of a man being infertile increased as mother's age at birth increased (regression coefficient +/- standard error 0.212 +/- 0.059; P < 0.001), but decreased as birth order increased (regression coefficient +/- standard error -0.596 +/- 0.230; P = 0.010). CONCLUSIONS: Delayed motherhood may enhance the probability of sons to be infertile. The probability of a man being infertile would be greater if he comes from a small family than if he comes from a large family.

Female↗

PubMed2004

Combined psychophysiological assessment of ADHD: a pilot study of Bayesian probability approach illustrated by appraisal of ADHD in female college students.

Manifestations of ADHD are observed at both psychological and physiological levels and assessed via various psychometric, EEG, and imaging tests. However, no test is 100% accurate in its assessment of ADHD. This study introduces a stochastic assessment combining psychometric tests with previously reported (Consistency Index) and newly developed (Alpha Blockade Index) EEG-based physiological markers of ADHD. The assessment utilizes classical Bayesian inference to refine after each step the probability of ADHD of each individual. In a pilot study involving six college females with ADHD and six matched controls, the assessment achieved correct classification for all ADHD and non-ADHD participants. In comparison, the classification of ADHD versus non-ADHD participants was < 85% for any one of the tests separately. The procedure significantly improved the score separation between ADHD versus non-ADHD groups. The final average probabilities for ADHD were 76% for the ADHD group and 8% for the control group. These probabilities correlated (r = .87) with the Brown ADD scale and (r = .84) with the ADHD-Symptom Inventory used for the screening of the participants. We conclude that, although each separate test was not completely accurate, a combination of several tests classified correctly all ADHD and all non-ADHD participants. The application of the proposed assessment is not limited to the specific tests used in this study--the assessment represents a general paradigm capable of accommodating a variety of ADHD tests into a single diagnostic assessment.

Adult↗

PubMed1976

Fear appeals and attitude change: effects of a threat's noxiousness, probability of occurrence, and the efficacy of coping responses.

Three factorial experiments examined the persuasive effects of the noxiousness of threatened event, its probability of occurrence, and the efficacy of recommended protective measures. A total of 176 students participated in separate studies on the topics of cigarette smoking, driving safety, and venereal disease. The results disclosed that increments in the efficacy variable increased intentions to adopt the efficacy variable increased intentions to adopt the recommended practices. Interaction effects revealed that when the preventive practices were effective, increments in the noxiousness and probability variables facilitated attitude change; however, when the coping responses were the preventive practices were effective, increments in the noxiousness and probability either had no effect or a deleterious effect, respectively. These interaction effects were discussed in terms of a defensive avoidance hypothesis, the crucial component of which was an inability to ward off the danger. Furthermore, the effect of the emotion of fear upon intentions was found to be mediated by the cognitive appraisal of severity of the threat. Finally, similarities with and extensions of previous studies were reviewed.

Accidents, Traffic↗

PubMed2002

Do desirability ratings moderate the validity of probability ratings on the Smoking Consequences Questionnaire-Adult? A reanalysis using regression.

Smokers' responses to the Smoking Consequences Questionnaire-Adult (A. L. Copeland, T. H. Brandon, & E. P. Quinn, 1995) were used to determine whether smoking outcome expectancies are moderated by subjective evaluations (desirability ratings) in their effect on smoking-related variables. Hierarchical regression in a reanalysis of data from A. L. Copeland et al. indicated that the product of probability and desirability ratings accounted for a significant amount of variance in smoking rate, nicotine dependence, saliva cotinine, and posttreatment smoking status above that accounted for by probability and desirability ratings alone. Results indicate that desirability ratings serve as moderators to probability ratings in explaining current smoking, nicotine dependence, and continued smoking. Effects were modest in magnitude but suggest that it may be important to address subjective evaluations of outcomes in smoking cessation and relapse prevention efforts.

Adult↗