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PubMed1996

The probability distribution of the amount of an individual's genome surviving to the following generation.

The probability that at least p% of an individual's genome is passed on collectively to his children is calculated. With data availability the consideration of the chromosome as a whole rather than discrete loci becomes of increasing practical importance. Assuming the genomic continuum model, which allows for recombination, the crossover process in a chromosome pedigree is viewed as a continuous-time Markov random walk on the vertices of a hypercube with time parameter map distance along the chromosome. The desired probability corresponds to the probability of sojourn times of the process in a small set of vertices, which are well approximated via the Poisson clumping heuristic. Results are given for the human genome. It is very likely that an individual with at least four children passes on at least 90% of his genome. There exists no "equivalent" number of independently segregating loci for this distribution.

Genetics, Population↗

PubMed2002

Investigating the probability of sign inconsistency in the regression coefficients of markers flanking quantitative trait loci.

Estimates of the locations and effects of quantitative trait loci (QTL) can be obtained by regressing phenotype on marker genotype. Under certain basic conditions, the signs of regression coefficients flanking QTL must be the same. There is no guarantee, however, that the signs of the regression coefficient estimates will be the same. We use sign inconsistency to describe the situation in which there is disagreement between the signs of the estimated regression coefficients flanking QTL. The presence of sign inconsistency can undermine the effectiveness of QTL mapping strategies that presume intervals whose markers have regression coefficient estimates of differing sign to be devoid of QTL. This article investigates the likelihood of sign inconsistency under various conditions. We derive an analytic expression for the approximate probability of sign inconsistency in the single-QTL case. We also examine sign inconsistency probabilities when multiple QTL are present through simulation. We have discovered that the probability of sign inconsistency can be unacceptably high, even when the conditions for QTL detection are otherwise quite favorable.

Computer Simulation↗

PubMed2002

Multivariate Markov chain analysis of the probability of pregnancy in infertile couples undergoing assisted reproduction.

BACKGROUND: Estimating the probability of pregnancy leading to delivery and the influence of clinical factors on that probability is of fundamental importance in the treatment counselling of infertile couples. A variety of statistical techniques have been used to analyse fertility data, many borrowed from survival analysis. METHODS AND RESULTS: We propose an alternative method of analysis which is based on a discrete time Markov chain approach, with states 'pregnancy (leading to a delivery)', 'not pregnant', and 'censored' and in which the transition probabilities are dependent both on the clinical characteristics of the patient and the treatment given. CONCLUSIONS: We believe that the method of analysis presented here may be preferable to standard analyses in that it better reflects the clinical situation, it is a truly discrete time analysis applied to a discrete time situation, it explicitly models the censoring process (a process which in itself provides information of interest to the physician) and can be readily extended to a variety of clinical situations.

Age Factors↗

PubMed2005

Are endogenous LH levels during ovarian stimulation for IVF using GnRH analogues associated with the probability of ongoing pregnancy? A systematic review.

The aim of this systematic review was to evaluate, among women with normal ovulation or World Health Organization (WHO) II oligoanovulation who undergo ovarian stimulation for IVF using GnRH analogues, whether endogenous LH levels predict the likelihood of ongoing pregnancy beyond 12 weeks. A literature search identified six studies that answered the research question, among which two were prospective studies (one in GnRH agonist and one in GnRH antagonist cycles). None of the retrospective studies suggest that low endogenous LH levels are associated with a significantly decreased probability of ongoing pregnancy beyond 12 weeks in such patients. In the two prospective studies high endogenous LH levels during down-regulation were associated with a decreased probability of ongoing pregnancy beyond 12 weeks. Until further prospective studies modify the existing evidence summarized here, an adverse effect of low endogenous LH levels on the probability of ongoing pregnancy beyond 12 weeks is not a sensible rationale for LH supplementation during ovarian stimulation for IVF using GnRH analogues.

Female↗

PubMed1996

Re-evaluation of the probabilities for productive arrangements on the kappa and lambda loci.

V-J arrangements at Ig light chain (IgL) genes occur in resting small pre-B cells. In the absence of cell division, the probability of production kappa and lambda rearrangements is proportional to the output of kappa+ B and lambda+ B cells in bone marrow. The kinetics and probability of productive kappa or lambda rearrangements was assessed in three groups of mice carrying two (wild-type), one or no intact Igkappa gene, and the following conclusion are drawn. Kappa and lambda rearrangements occur independently at different kinetics, and rearrangements are initiated at a time when kappa rearrangements are stopping. The probability of productive kappa and lambda rearrangements per chromosome is calculated to be approximately 60 and approximately 20% respectively. Thus, a kappa gene can attempt rearrangements up to three times per chromosome during B cell development. These findings explain that the observed ratio of kappa+ B/lambda+ B cell production in wild-type mice is 95/5.

Alleles↗

PubMed2004

Dietary variety increases the probability of nutrient adequacy among adults.

Despite guidance to consume a variety of foods, the role of dietary variety in ensuring nutrient adequacy is unclear. The aim of this study was to determine whether a commodity-based measure of dietary variety was associated with the probability of nutrient adequacy after adjusting for energy and food group intakes. Subjects were 4969 men and 4800 women >/= 19 y old who participated in the Continuing Survey of Food Intakes for Individuals 1994-1996. Using 24-h recall data, the mean probability of adequacy across 15 nutrients was calculated using the Dietary Reference Intakes. Dietary variety was defined using a commodity-based method similar to that used for the Healthy Eating Index (HEI). Associations were examined in gender-specific multivariate regression models. Energy intake was a strong predictor of the mean probability of adequacy in models controlled for age, BMI, education level, and ethnicity (model R(2) = 0.60 and 0.54 for men and women, respectively). Adding the number of servings from each of the 5 Food Guide Pyramid (FGP) groups to the models significantly improved the model fit (R(2) = 0.69 and 0.66 for men and women). Adding dietary variety again significantly improved the model fit for both men and women (R(2) = 0.73 and 0.70, respectively). Variety counts within the dairy and grain groups were most strongly associated with improved nutrient adequacy. Dietary variety as defined by the HEI contributes an additional component of dietary quality that is not captured by FGP servings or energy intake.

Adult↗

PubMed2004

Assessing the probability that a positive report is false: an approach for molecular epidemiology studies.

Too many reports of associations between genetic variants and common cancer sites and other complex diseases are false positives. A major reason for this unfortunate situation is the strategy of declaring statistical significance based on a P value alone, particularly, any P value below.05. The false positive report probability (FPRP), the probability of no true association between a genetic variant and disease given a statistically significant finding, depends not only on the observed P value but also on both the prior probability that the association between the genetic variant and the disease is real and the statistical power of the test. In this commentary, we show how to assess the FPRP and how to use it to decide whether a finding is deserving of attention or "noteworthy." We show how this approach can lead to improvements in the design, analysis, and interpretation of molecular epidemiology studies. Our proposal can help investigators, editors, and readers of research articles to protect themselves from overinterpreting statistically significant findings that are not likely to signify a true association. An FPRP-based criterion for deciding whether to call a finding noteworthy formalizes the process already used informally by investigators--that is, tempering enthusiasm for remarkable study findings with considerations of plausibility.

Analysis of Variance↗

PubMed1995

The probability of pregnancy after embryo transfer is affected by the age of the patient, cause of infertility, number of embryos transferred and the average morphology score, as revealed by multiple logistic regression analysis.

Because the process of conception is affected by many variables, a multiple logistic regression analysis was performed to assess (i) the impact and relative weight of both patient and embryo variables and (ii) their possible effects on the probability of a vital pregnancy after embryo transfer. A statistical model was constructed predicting the probability of pregnancy after embryo transfer. The variables that contributed significantly to the predictive value of the model were the age of the patient, the cause of infertility, the number of embryos transferred and the average morphology score of the transferred embryos. Embryo variables appeared to have a significant but modest value in predicting the probability of pregnancy after embryo transfer. Other variables, such as the thickness of the endometrium, were found to have no prognostic value. Moreover, we found that their effect could be explained by the variables already included in the model.

Adult↗

PubMed2003

Improvement in prediction of solvent accessibility by probability profiles.

The capability of predicting folding and conformation of a protein from its primary structure is probably one of the main goals of modern biology. An accurate prediction of solvent accessibility is an intermediate step along this way. A new method for predicting solvent accessibility from single sequence and multiple alignment data is described. The method is based on probability profiles calculated on an amino acid sequence centred on the residue whose accessibility has to be predicted. A profile is constructed for each exposure category considered so as to calculate the probability of a sequence being generated by the different profiles. Prediction accuracy was tested on a variety of protein sets with two- and three-state models. Different thresholds were used according to those adopted by the authors proposing the data sets. The prediction accuracy is significantly improved over existing methods.

Algorithms↗

PubMed2000

Performance of the Mortality Probability Models in assessing severity of illness during the first week in the intensive care unit.

OBJECTIVE: To extend the Mortality Probability Models (MPM) II severity system to time periods between 4 and 7 days after admission to the intensive care unit (ICU). DESIGN: Prospective inception cohort. SETTING: Fifteen adult medical and surgical ICUs in Spain. PATIENTS: A total of 1,441 patients aged > or =18 yrs consecutively admitted from April 1, 1995 through July 31, 1995. INTERVENTIONS: Prospective data collection during the stay of the patient in the ICU. Data collected included demographic information, length-of-stay and vital status at both ICU and hospital discharge, as well as all variables necessary for computing the MPM II system at admission and during the first 7 days of stay in the ICU MEASUREMENTS AND MAIN RESULTS: Calibration and discrimination of the four existing MPM II models (MPM0, MPM24, MPM48, and MPM72) were assessed in the study database. The MPM II system overestimated the mortality of patients with probabilities of death > or =0.4. The MPM24 model was customized. Models for time periods between 48 hrs and 7 days (MPM48 to MPMd7) were obtained using the same strategy that was used to develop the original MPM48 and the MPM72 models. The variable coefficients of the MPM24 model were kept fixed and the constant terms of the MPM48 to MPMd7 models were estimated by logistic regression. The constant term stabilized after the fourth day of admission and it was similar to the constant term of the MPM72 model. The customized MPM72 performed very well for days 4 to 7 after admission to the ICU. CONCLUSIONS: If the patient's condition stays the same day after day, the probability of dying in the hospital increases until 72 hrs, and then stabilizes. A severity measure that performs well at 72 hrs can be a useful tool for measuring severity at later time periods.

Critical Care↗

PubMed1988

The impact of the probability of causation on the radiation protection program.

Although the probability of causation approach is the only scientific basis on which a given cancer can be judged to be causally related to a given exposure, the impact of this concept on the radiation safety program could be counter-productive. As health physicists, the practices and the concepts we employ have been developed to protect the worker. Effective dose equivalent and committed dose equivalent are protective concepts but useless for probability of causation analysis. Perhaps extensive records will be the only way that good radiation protection and probability of causation analysis can coexist.

Humans↗

PubMed2002

The probability of finding a localized area with elevated contamination by using a mobile detector.

This paper examines the probability that a localized area with elevated contamination can be found by using a mobile detector. In the case studied, the area of elevated contamination has an elliptical shape and the detector has a circular field of view. The probability of finding the contaminated area is a function of factors related to both the contaminated area and the detector. The paper examines the dependence of the probability on a number of these factors. The results presented are applicable to any characteristic that can be detected with a scanning system that provides complete coverage of an area. They can be used as the basis for designs or evaluations that involve determining whether localized areas of contamination are present in an area of interest.

Environmental Monitoring↗

PubMed1997

Probability model of hospital death for severe trauma patients based on the Simplified Acute Physiology Score I: development and validation. Archivio Diagnostico.

BACKGROUND: We evaluated whether or not the Simplified Acute Physiology Score (SAPS) I is a suitable audit system for trauma patients admitted to general intensive care units (ICUs). A probability model for SAPS I was retrospectively assessed on trauma patients admitted to general ICUs from 1990 to 1992. Because it was determined that SAPS did not fit the data well, we developed a customized probability model of SAPS I for trauma patients and validated it prospectively on an independent data set (patients admitted to general ICU in 1993-1994). Measures of calibration (goodness of fit) and discrimination (receiver operating characteristic curve) were adopted to assess the performance of the model. METHODS: A multicenter study was performed involving general ICUs in northern Italy that participated in a project of standardized data collection. This project is known in Italy under the acronym of ARCHIDIA (Diagnostic Archive). All patients consecutively admitted to the ICU were registered in the data base from January 1, 1990, to December 31, 1994 (16,767 patients). For the SAPS analysis, we considered only patients who fulfilled the following criteria: older than 17 years, length of stay longer than 24 hours, and SAPS I correctly computed. Inclusion criteria resulted in 12,156 patients analyzed; there were 1,936 patients with trauma. RESULTS: Trauma patients represented more than 15% of all patients admitted to ICUs during the period considered. Compared with the general population, they were younger (41.2 vs. 56.7 years), stayed in ICUs for longer periods (12.4 vs. 9.5 days), and had a lower hospital mortality rate (17.8 vs. 28.7%). Because the original probability model did not perform well among patients with trauma, a new model was developed and prospectively validated only for trauma patients (customization). Measures of calibration and discrimination showed a good performance both in the developmental (goodness of fit: chi2 = 8.47; p = 0.38; area under the curve = 0.94 +/- 0.01) and in the validation (goodness of fit: chi2 = 12.75; p = 0.12; area under the curve = 0.85 +/- 0.01) data sets. CONCLUSION: Customization of SAPS I for trauma patients has shown good calibration and high discriminatory power in Italian ICUs and when applied to an independent data base. The advantage of customization would be the collection of the same set of variables for all patients admitted to ICUs against the use of specific scoring systems.

Adult↗

PubMed2003

Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer.

PURPOSE: We retrospectively reviewed the clinical followup for a large series of men with clinically localized prostate cancer who underwent radical retropubic prostatectomy to identify clinical and/or pathological indicators of biochemical (prostate specific antigen [PSA]) recurrence. We then used those indicators to develop multivariate models for determination of recurrence probability following radical retropubic prostatectomy. MATERIALS AND METHODS: From 1982 to 1999, 2,091 consecutive men underwent radical retropubic prostatectomy and pelvic lymphadenectomy for clinically localized adenocarcinoma of the prostate (clinical stage T1c or T2 disease with Gleason score 5 or greater). Actuarial analysis was performed comparing freedom from biochemical recurrence after radical retropubic prostatectomy (PSA 0.2 ng./ml. or greater.) using the Kaplan-Meier method. Event time distributions for the time to recurrence were compared using the log rank statistic or the Cox proportional hazards regression model. The first model was developed using preoperative variables only and the second model using all available variables. Observed and predicted recurrence-free survival curves for different models were compared to select a model for calculation of predicted recurrence-free probabilities and confidence intervals. RESULTS: With a median followup of 5.9 years (range 1 to 17) 360 men (17%) had biochemical recurrence. Overall actuarial 5, 10 and 15-year biochemical recurrence-free survival rates were 84%, 72% and 61%, respectively. The relative risk of biochemical recurrence following surgery decreased with time, even after adjusted for other perioperative parameters. Variables identified for the preoperative model were biopsy Gleason score, clinical TNM stage and PSA. Variables identified for the postoperative model were prostatectomy Gleason score, PSA and pathological organ confinement status. Nomograms were generated and corrected for the decreasing relative risk of biochemical recurrence over time. CONCLUSIONS: Using 3 preoperative or postoperative parameters, these nomograms can easily be used to determine the 3, 5, 7 and 10-year biochemical recurrence-free survival probabilities among men who undergo radical retropubic prostatectomy for clinically localized prostate cancer in the modern era.

Adenocarcinoma↗

PubMedDate not supplied

Propranolol for disruptive behaviors in nursing home residents with probable or possible Alzheimer disease: a placebo-controlled study.

OBJECTIVE: Enhanced behavioral responsiveness to central nervous system (CNS) norepinephrine (NE) in Alzheimer disease (AD) may contribute to the pathophysiology of disruptive behaviors such as aggression, uncooperativeness with necessary care, irritability, and pressured pacing. We evaluated the efficacy of the beta-adrenergic antagonist propranolol for treatment-resistant disruptive behaviors and overall behavioral status in nursing home residents with probable or possible AD. METHODS: Thirty-one subjects (age 85 +/- 8 [SD]) with probable or possible AD and persistent disruptive behaviors that interfered with necessary care were randomized to propranolol (n = 17) or placebo (n = 14) in a double-blind study. Stable doses of previously prescribed psychotropics were maintained at pre-study dose during the study. Following a propranolol or placebo dose titration period of up to 9 days (per a dosing algorithm), subjects were maintained on maximum achieved dose for 6 weeks. Primary outcome measures were the Neuropsychiatric Inventory (NPI) and the Clinical Global Impression of Change (CGIC). RESULTS: Propranolol augmentation (mean achieved dose 106 +/- 38 mg/d) was significantly more effective than placebo for improving overall behavioral status on the total NPI score and CGIC. Improvement in individual NPI items within propranolol subjects was significant only for "agitation/aggression" and "anxiety," and reached borderline statistical significance favoring propranolol over placebo only for "agitation/aggression." Pressured pacing and irritability did not appear responsive to propranolol. In propranolol subjects rated "moderately improved" or "markedly improved" on the CGIC at the end of the double-blind study phase, improvement of overall behavioral status had diminished substantially after 6 months of open-label propranolol treatment. CONCLUSION: Short-term propranolol augmentation treatment appeared modestly effective and well tolerated for overall behavioral status in nursing home residents with probable or possible AD complicated by disruptive behaviors. Propranolol may be helpful specifically for aggression and uncooperativeness (the behaviors assessed by the NPI "agitation/aggressiveness" item). However, the usefulness of propranolol in this very old and frail population was limited by the high frequency of relative contraindications to beta-adrenergic antagonist treatment and diminution of initial behavioral improvements over time.

Adrenergic beta-Antagonists↗

PubMed1997

Survival probability of drug resistant mutants in malaria parasites.

This study predicts the ultimate probability of survival of a newly arisen drug resistant mutant in a population of malaria parasites, with a view to understanding what conditions favour the evolution of drug resistance. Using branching process theory and a population genetics transmission model, the probabilities of survival of one- and two-locus new mutants are calculated as functions of the degree of drug pressure, the mean and variation in transmission rate, and the degree of natural selection against the mutant. Probability of survival increases approximately linearly with drug pressure, the slope of the line increasing with mean transmission rate. Thus increased drug pressure, especially in combination with high transmission rates, strongly favours the evolution of drug resistance. These conclusions also hold for the case of multiple drug resistance where it is coded for by two unlinked loci: the greater effective recombination breakdown in high transmission areas is counteracted by greater effective selection so that the net effect of higher transmission rates is to favour the evolution of multiple drug resistance. High variability in transmission rate and natural selection against the mutants are unfavourable to mutant survival, though these are relatively weak forces.

Animals↗

PubMed2001

Adiabatic elimination and reduced probability distribution functions in spatially extended systems with a fluctuating control parameter.

We obtain the stationary probability distribution functions of the order parameter near onset for the one-dimensional real Ginzburg-Landau and Swift-Hohenberg equations with a fluctuating control parameter. A perturbative expansion in the intensity of the fluctuations leads to a hierarchy of Fokker-Planck equations for conditional probability distribution functions that relate components of the order parameter that evolve in different time scales. Successive integration leads to a Fokker-Planck equation for the slowest mode, which we solve analytically for the models studied. In all cases, the probability distribution function above onset is of the form P(A0) approximately A(delta)(0)e(-gammaA20), where A0 is the slow component of the order parameter and the values of delta and gamma depend explicitly on the intensity of the fluctuations. Knowledge of P(A0) allows the calculation of an effective bifurcation threshold and of the moments of A0 above threshold.

Journal Article↗

PubMed2002

Estimating probabilities from experimental frequencies.

Estimating the probability distribution q governing the behavior of a certain variable by sampling its value a finite number of times most typically involves an error. Successive measurements allow the construction of a histogram, or frequency count f, of each of the possible outcomes. In this work, the probability that the true distribution be q, given that the frequency count f was sampled, is studied. Such a probability may be written as a Gibbs distribution. A thermodynamic potential, which allows an easy evaluation of the mean Kullback-Leibler divergence between the true and measured distribution, is defined. For a large number of samples, the expectation value of any function of q is expanded in powers of the inverse number of samples. As an example, the moments, the entropy, and the mutual information are analyzed.

Journal Article↗