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PubMed2005

Radiation effectiveness factors for use in calculating probability of causation of radiogenic cancers.

This paper presents so-called radiation effectiveness factors that are intended to represent the biological effectiveness of different radiation types, relative to high-energy Co gamma rays, for the purpose of estimating cancer risks and probability of causation of radiogenic cancers in identified individuals. Radiation effectiveness factors are expressed as subjective probability distributions to represent uncertainty that arises from uncertainties in estimates of relative biological effectiveness obtained from radiobiological studies of stochastic endpoints, limited data on biological effectiveness obtained from human epidemiological studies, and other judgments involved in evaluating the applicability of available information to induction of cancers in humans. Primarily on the basis of reviews and evaluations of available data by experts, probability distributions of radiation effectiveness factors are developed for the following radiation types: neutrons of energy less than 10 keV, 10-100 keV, 0.1-2 MeV (including fission neutrons), 2-20 MeV, and greater than 20 MeV; alpha particles of any energy emitted by radionuclides; photons of energy 30-250 keV and less than 30 keV; and electrons of energy less than 15 keV. Photons of energy greater than 250 keV and electrons of energy greater than 15 keV are assumed to have the same biological effectiveness as reference Co gamma rays and are assigned a radiation effectiveness factor of unity, without uncertainty. For neutrons and alpha particles, separate probability distributions of radiation effectiveness factors are developed for solid tumors and leukemias, and small corrections to represent an inverse dose-rate effect are applied to those distributions in cases of chronic exposure. A radiation effectiveness factor different from unity for 15-60 keV electrons is discussed but is not adopted due to a lack of relevant radiobiological data. Radiation effectiveness factors presented in this paper are incorporated in the Interactive RadioEpidemiological Program and were developed for use by The National Institute for Occupational Safety and Health and U.S. Department of Labor in evaluating claims for compensation for radiogenic cancers by workers at U.S. Department of Energy facilities.

Algorithms↗

PubMed2006

Is cataract surgery cost-effective among older patients with a low predicted probability for improvement in reported visual functioning?

INTRODUCTION: Although cataract surgery has been demonstrated to be effective and cost-effective, 5% to 20% of patients do not benefit functionally from the procedure. This study examines the cost-effectiveness of cataract surgery versus watchful waiting in a subgroup of patients who had less than a 30% predicted probability of reporting improvements in visual function after surgery. METHODS: Randomized trial (first eye surgery vs. watchful waiting) of 250 patients who based on a cataract surgery index (CSI) were felt to have less than a 30% probability of reporting improvements in visual functioning after surgery. Cost was estimated using monthly resource utilization surveys and Medicare billing and payment data. Effectiveness was evaluated at 6 months using the Activities of Daily Vision Scale (ADVS) and the Health Utilities Index, Mark 3 (HUI3). RESULTS: In terms of overall utility, the incremental cost-effectiveness of surgery was Dollars 38,288/QALY. In the subgroup of patients with a CSI score > 11 (< 20% probability of improvement), the cost-effectiveness of cataract surgery was Dollars 53,500/QALY. Sensitivity analysis demonstrated that often this population of patients may not derive a utility benefit with surgery. CONCLUSION: Cataract surgery is cost-effective even in a subpopulation of patient with a lower, < 30%, predicted probability of reporting improved visual functioning after surgery. There may be a subgroup of patients, CSI > 11, for whom a strategy of watchful waiting may be equally effective and considerably less expensive.

Activities of Daily Living↗

PubMed2004

Television images and probable posttraumatic stress disorder after September 11: the role of background characteristics, event exposures, and perievent panic.

Television viewing has been associated with posttraumatic stress disorder (PTSD) symptoms after disasters and traumas; we examined characteristics that may explain this association among New Yorkers after September 11, 2001. Among 2001 respondents to a random-digit dial telephone survey conducted 4 months after September 11, people who viewed more television images in the 7 days after September 11 had more probable PTSD. People in the highest third of viewing had a 2.32 times greater odds of probable PTSD after September 11 compared with people in the lowest third of viewing; after adjustment for explanatory variables, the relative odds of probable PTSD were 1.66. Adjustment for perievent panic accounted for 44% of the reduction in association between television and probable PTSD, suggesting that perievent emotional reactions may play an important role in the television and psychopathology association. Television may merit consideration as a potential exposure to a traumatic event.

Adolescent↗

PubMed2003

Scintigraphic probability and angiographic diagnostic certainty in acute pulmonary embolism.

The objectives of this study were to determine if diagnostic certainty on angiography correlates with scintigraphic probability for the diagnosis of pulmonary embolism. From a total of 160 consecutive patients who underwent both nuclear imaging and invasive selective pulmonary angiography, we reviewed the xenon-133 ventilation images in 2 posterior oblique views and the Tc-99m macroaggregated serum albumin perfusion scans and angiograms of 40 patients (15 men, 25 women; average age 57 years) who were discharged from the hospital on anticoagulants with a diagnosis of pulmonary embolism. The angiograms were reviewed and the diagnosis of embolism was considered certain in the presence of an intraluminal filling defect, a trailing embolus, or a branch occlusion equal to or larger than a segmental branch (n=29; 73%), and uncertain when the studies were reinterpreted as either equivocal or negative or in the presence of a single, small subsegmental filling defect of questionable clinical significance. The ventilation-perfusion scans were read as high (n=18; 45%), intermediate (n=10; 25%), or low (n=12; 30%) probability. The proportion of patients with diagnostic certainty on angiography in the high-, intermediate-, and low-probability scintigraphic subgroups was, respectively, 100% (18 of 18), 70% (7 of 10), and 33% (4 of 12) (P=0.004). In patients diagnosed with pulmonary embolism based on selective angiography, a lower probability of pulmonary embolism on ventilation-perfusion scintigraphy correlates with a lesser degree of diagnostic certainty on angiography and a higher incidence of single subsegmental emboli.

Acute Disease↗

PubMed2003

The effect of foraging parameters on the probability that a dive is successful.

In this paper, we investigate the foraging decisions of an animal that dives to obtain its food. It might seem reasonable to use the probability that the diver is successful in any dive as an indicator of habitat quality. We use a dynamic model of optimal prey choice to show that this interpretation of diving success is not generally valid. In particular, we show that diving success is not directly proportional to the overall rate of gain that can be achieved in an environment. Furthermore, some environmental factors can have a non-monotonic effect on the probability of success. For example, as the travel time to the foraging area increases, the probability of success may first increase and then decrease. We point out that the same conclusions are likely to apply in the context of mate choice, i.e. the probability of getting a mate may not be an indicator of the quality of the environment in terms of reproductive success.

Animals↗

PubMed2003

Power-law tail probabilities of drainage areas in river basins.

We examine the appearance of power-law behavior in rooted tree graphs in the context of river networks. It has long been observed that the tails of statistical distributions of upstream areas in river networks, measured above every link, obey a power-law relationship over a range of scales. We examine this behavior by considering a subset of all links, defined as those links which drain complete Strahler basins, where the Strahler order defines a discrete measure of scale, for self-similar networks with both deterministic and random topologies. We find an excellent power-law structure in the tail probabilities for complete Strahler basin areas, over many ranges of scale. We show analytically that the tail probabilities converge to a power law under the assumptions of (1) simple scaling of the distributions of complete Strahler basin areas and (2) application of Horton's law of stream numbers. The convergence to a power law does not occur for all underlying distributions, but for a large class of statistical distributions which have specific limiting properties. For example, underlying distributions which are exponential and gamma distributed, while not power-law scaling, produce power laws in the tail probabilities when rescaled and sampled according to Horton's law of stream numbers. The power-law exponent is given by the expression phi=ln(R(b))/ln(R(A)), where R(b) is the bifurcation ratio and R(A) is the Horton area ratio. It is commonly observed that R(b) approximately equal R(A) in many river basins, implying that the tail probability exponent for complete Strahler basins is close to 1.0.

Journal Article↗

PubMed2004

Optimal paths and the calculation of state selection probabilities.

The addition of noise to a dynamical system means that initial states near points of instability may no longer decay to a unique stable state. A common example of this behavior occurs in a dynamical system with two degrees of freedom and with two or more stable states. If the initial state of the system is near the separatrices bounding the basins of attraction of these stable states, then the addition of noise to the system means that there is a nonzero probability that the stable state selected is in a different basin of attraction to that of the initial state. We discuss a method of calculating these state-selection probabilities based on a path-integral representation of the stochastic dynamics. The relationship of this approach to a method based on the solution of the backward Fokker-Planck equation is particularly stressed, since this was used in previous studies of problems of this type. However, while the method based on the backward Fokker-Planck equation is a powerful one for systems with one degree of freedom, in systems with more degrees of freedom it is much less useful. Since the standard method of solution in this case involves a series of mappings onto a deterministic dynamics which is simply the classical dynamics associated with the path-integral formulation, we argue that for systems with more than one degree of freedom, the path-integral method is a very natural way of calculating state-selection probabilities. We illustrate this on a simple example taken from population biology, and find that the state-selection probabilities are in excellent agreement with Monte Carlo simulations.

Journal Article↗

PubMed2004

Spatial persistence and survival probabilities for fluctuating interfaces.

We report the results of numerical investigations of the steady-state (SS) and finite-initial-conditions (FIC) spatial persistence and survival probabilities for (1+1) -dimensional interfaces with dynamics governed by the nonlinear Kardar-Parisi-Zhang equation and the linear Edwards-Wilkinson (EW) equation with both white (uncorrelated) and colored (spatially correlated) noise. We study the effects of a finite sampling distance on the measured spatial persistence probability and show that both SS and FIC persistence probabilities exhibit simple scaling behavior as a function of the system size and the sampling distance. Analytical expressions for the exponents associated with the power-law decay of SS and FIC spatial persistence probabilities of the EW equation with power-law correlated noise are established and numerically verified.

Journal Article↗

PubMed2005

Joint probability distributions for a class of non-Markovian processes.

We consider joint probability distributions for the class of coupled Langevin equations introduced by Fogedby [H. C. Fogedby, Phys. Rev. E 50, 1657 (1994)]. We generalize well-known results for the single-time probability distributions to the case of N -time joint probability distributions. It is shown that these probability distribution functions can be obtained by an integral transform from distributions of a Markovian process. The integral kernel obeys a partial differential equation with fractional time derivatives reflecting the non-Markovian character of the process.

Journal Article↗

PubMed2005

Tails of the crossing probability.

The scaling of the tails of the probability of a system to percolate only in the horizontal direction pi(hs) was investigated numerically for the correlated site-bond percolation model (q -state Potts model) for q=1 , 2, 3, 4 (where q is the number of spin states). We have to demonstrate that the crossing probability pi(hs) (p) far from the critical point p(c) has the shape pi(hs) (p) similar to D exp [cL (p- p(c) )(nu) ] where nu is the correlation length index, and p=1-exp (-beta) is the probability of a bond to be closed. For the tail region the correlation length is smaller than the lattice size. At criticality the correlation length reaches the sample size and we observe crossover to another scaling pi(hs) (p) similar to A exp {-b [L (p- p(c) )(nu)](x)}. Here x is a scaling index describing the central part of the crossing probability.

Journal Article↗

PubMed2006

Probability distribution of residence times of grains in models of rice piles.

We study the probability distribution of residence time of a grain at a site, and its total residence time inside a pile, in different rice pile models. The tails of these distributions are dominated by the grains that get deeply buried in the pile. We show that, for a pile of size L, the probabilities that the residence time at a site or the total residence time is greater than t, both decay as 1/t(ln t)x for L(omega) << t << exp(L(gamma)) where gamma is an exponent > or = 1, and values of x and omega in the two cases are different. In the Oslo rice pile model we find that the probability of the residence time T(i) at a site i being greater than or equal to t is a nonmonotonic function of L for a fixed t and does not obey simple scaling. For model in d dimensions, we show that the probability of minimum slope configuration in the steady state, for large L, varies as exp(-kappaL(d+2)) where kappa is a constant, and hence gamma=d+2.

Journal Article↗

PubMed1999

A new approach to modeling daily probabilities of conception.

Standard conception probabilities models assume that different acts of intercourse make independent contributions to the probability of conception in viable cycles. We propose an alternative, approximate model based on the assumption that the act of intercourse closest to the time of maximum fertility is the one most likely to have caused conception. We describe an adaptive algorithm [the most fertile intercourse day (MFID) algorithm] that estimates the most fertile intercourse day in each cycle. The approach is easily extended to include covariates and random between-couple differences in fecundability that affect the probability of conception in a given cycle. Reanalyses of two data sets reported in the literature are presented. Estimates of the probability of conception during the most fertile period of the cycle and of the effects of covariates are similar to estimates found using standard models.

Algorithms↗

PubMed2005

Cell-mediated immunity predicts the probability of local recruitment in nestling blue tits.

We investigated whether the variation in T-cell-mediated immune function of blue tit nestlings affected their fledgling success and the probability of local survival. We studied the relationship between immune function and survival under two rearing conditions: control, unmanipulated, and experimentally enlarged broods. Brood enlargement had negative effects on nestling immune response. Immune response was positively related to fledgling success and it predicted the probability of local recruitment. However, the relationship between immune response and the probability of recruitment was significantly positive only among control broods and nonsignificant among enlarged broods. The effect of immune response on the recruitment probability was not affected by variation in body mass. Our study suggests that selection for immune responsiveness seems to be weak or even absent under unfavourable rearing conditions as simulated by brood size enlargement. Therefore, year-to-year environmental variation and environmental heterogeneity may constrain evolution towards higher immune responsiveness.

Animals↗

PubMed2000

Release probability modulates short-term plasticity at a rat giant terminal.

1. Modulation of release probability is a major factor underlying short-term synaptic plasticity in the central nervous system. We have investigated the relationship between release probability ((Pr) and paired-pulse modulation at a large auditory calyceal synapse containing many transmitter release sites. Whole-cell patch electrode recordings were made of excitatory postsynaptic currents (EPSCs), evoked by stimulation of auditory nerve fibres giving rise to the endbulbs of Held. 2. Quantitative estimates of Pr and quantal amplitude were obtained using the recently developed variance-mean analysis technique. Release probability conditions were modulated by bath application of cadmium, elevated calcium and protein kinase C activation by phorbol esters. 3. Our results show that, under physiological conditions, most sites released neurotransmitter following a single presynaptic nerve impulse, with a mean Pr of 0.6. The mean quantal amplitude was 44 pA, which was consistent with the mean amplitude of miniature EPSCs (47 pA). 4. Under high release probability conditions with elevated calcium or phorbol esters, Pr at all sites approached 1.0. At these high Pr values, variance-mean analysis indicated a significant postsynaptic contribution to paired-pulse depression. The miniature EPSC amplitudes were decreased following stimulation in elevated calcium, confirming a postsynaptic component of paired-pulse depression at this glutamatergic connection. 5. A notable feature was the large variability between neurons in the relationship between paired-pulse ratio and Pr. Based on current models of vesicle release and ultrastructural evidence, we suggest that this variability may be partly due to morphological differences between endbulb specializations, particularly in the ratio of fusion-ready to reserve populations of vesicles at endbulb release sites.

Animals↗

PubMed1998

Risk of left ventricular dysfunction in patients with probable Alzheimer's disease with APOE*4 allele.

OBJECTIVE: To examine the association between the APOE genotype and cardiovascular disease in Alzheimer's disease (AD) patients. DESIGN: Case register study of 100 consecutive referrals to a Memory Clinic where type of dementia and cardiovascular comorbidity were diagnosed and APOE genotype was determined. SETTING: The Memory Clinic, University Hospital Rotterdam Dijkzigt. PARTICIPANTS: One hundred Memory Clinic patients, 59 to 91 years of age, who attended the Memory Clinic in the period between January 1994 and March 1996. MEASUREMENTS: Relative risk of cardiovascular morbidity in probable AD, based on clinical and ECG findings. RESULTS: The diagnosis of probable AD was more frequent in APOE*4 allele-carrying AD patients. When comparing homozygotes for APOE*4 with homozygotes for APOE*3, a nine-fold increase in prevalence of cardiac ischemia on ECG was found in the former. When grouping parameters of left ventricular dysfunction, the prevalence was 7.2 (95% confidence interval 1.2-42.6) times greater in probable Alzheimer patients with APOE4/4. CONCLUSIONS: In patients with probable AD, APOE*4 is associated with cardiac disease indicative of left ventricular dysfunction.

Aged↗

PubMed2005

MLE and Bayesian inference of age-dependent sensitivity and transition probability in periodic screening.

This article extends previous probability models for periodic breast cancer screening examinations. The specific aim is to provide statistical inference for age dependence of sensitivity and the transition probability from the disease free to the preclinical state. The setting is a periodic screening program in which a cohort of initially asymptomatic women undergo a sequence of breast cancer screening exams. We use age as a covariate in the estimation of screening sensitivity and the transition probability simultaneously, both from a frequentist point of view and within a Bayesian framework. We apply our method to the Health Insurance Plan of Greater New York study of female breast cancer and give age-dependent sensitivity and transition probability density estimates. The inferential methodology we develop is also applicable when analyzing studies of modalities for early detection of other types of progressive chronic diseases.

Adult↗

PubMed2006

Fragment length distributions and collision probabilities for AFLP markers.

AFLP is a DNA fingerprinting technique frequently used in plant and animal sciences. A drawback of the technique is the occurrence of multiple DNA fragments of the same length in a single AFLP lane, which we name a collision. In this article we quantify the problem. The well-known birthday problem plays a role. Calculation of collision probabilities requires a fragment length distribution (fld). We discuss three ways to estimate the fld: based on theoretical considerations, on in-silico determination using DNA sequence data from Arabidopsis thaliana, or on direct estimation from AFLP data. In the latter case we use a generalized linear model with monotone smoothing of the fragment length probabilities. Collision probabilities are calculated from two perspectives, assuming known fragment counts and assuming known band counts. We compare results for a number of fld's, ranging from uniform to highly skewed. The conclusion is that collisions occur often, with higher probabilities for higher numbers of bands, for more skewed distributions, and, to a lesser extent, for smaller scoring ranges. For a typical plant genome an AFLP with 19 bands is likely to contain the first collision. Practical implications of collisions are discussed. AFLP examples from lettuce and chicory are used for illustration.

Animals↗

PubMed1999

Kaplan-Meier tumor probability as a starting point for dose-response modeling provides accurate lifetime risk estimates from rodent carcinogenicity studies.

In rodent carcinogenicity studies the linearized multistage model for modelling the dose-response for specific tumor incidence has limitations in accuracy. This note provides an alternative basic method for analyzing the dose-response relationship. It is based on an actuarial analysis of mortality and specific tumor incidence. The survival and the Kaplan-Meier specific tumor probability are fitted to a Weibull model, in which exposure level, exposure period, and observation period are independent variables. The mortality from specific cancers at a certain time is simulated by means of the product of survival and specific tumor rate (derivative of Kaplan-Meier tumor probability) as function of exposure level, exposure duration, and observation period, integrated over the observation period. The model is demonstrated by means of fitting the mortality and tumor incidence data from the second NTP mice study on butadiene to a Weibull model and to the linear, so-called, one-hit model. It will be shown that, in the experimental exposure range, the Weibull model is far superior to the one-hit model and predicts the specific tumor incidence with a high accuracy over the total dose range. The Kaplan-Meier probability model for a specific tumor is also useful for regulatory risk estimation. It is proposed that to develop a specific tumor a risk level of 1 in 1,000 over a lifetime is about equal to 5 in 10,000 at 50% survival of the population. The Kaplan-Meier probability may be estimated at the time of 50% survival of the exposed population, which can be deduced from the all mortality data. This estimation method provides meaningful data, using exposure level, exposure duration, and observation period properly. The advantage of the actuarial analysis method for interpreting rodent studies is that allowance is made for competition between death causes, which is essential in case of considerable difference in mortality and specific mortality between dose groups. Integrating the product of survival and specific tumor rate is the proper way to predict, comparatively, mortality and specific mortality in exposed and unexposed rodent populations.

Animals↗