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PubMed1996

Prognostic models for the probability of achieving an ongoing pregnancy after in-vitro fertilization and the importance of testing their predictive value.

The aim of this study was to create reliable models to predict the probability of achieving an ongoing pregnancy during in-vitro fertilization (IVF) treatment: model A, at the start of the first treatment, model B at the time of embryo transfer, and model C, during the second treatment at the end of the first IVF treatment. Prognostic models were created using data from the University Hospital Nijmegen (n = 757) and applied to the data from the Catharina Hospital Eindhoven (n = 432), The Netherlands, to test their predictive performance. The predictions of model B (made at time of embryo transfer) were fairly good (c = 0.672 in the test population). For instance, 93% of the patients who had a predicted probability of achieving an ongoing pregnancy of < 10% did not achieve an ongoing pregnancy. However, the predictions of the other two models (A and C) for Eindhoven were less reliable. The predictive value of model C was fairly high in Nijmegen (c = 0.673). Its poor performance in the test population may be explained partly by differences in effectiveness of the ovulation stimulation protocols and the decision about when to discontinue the cycle. Thus, before using prognostic models at an IVF centre, their reliability at that specific centre should be tested.

Evaluation Studies as Topic↗

PubMedDate not supplied

At how many histocompatibility loci do congenic mouse strains differ? Probability estimates and some implications.

An expression is derived for the probability that a congenic strain and its inbred partner will differ by multiple linked histocompatibility genes when the number of incompatibilities between the original donor and background strains is known and the number of backcrosses to produce the strain is specified. This probability is shown to be rather large for typical values of the pertinent variables. Potential complications in data interpretation arising from unsuspected multiple incompatibilities between a congenic pair are discussed in relation to antigenic strength, H-locus polymorphism tissue distribution of H antigens, and certain types of experiments in which the cell-mediated lympholysis assay is used.

Animals↗

PubMed1997

Protein distance constraints predicted by neural networks and probability density functions.

We predict interatomic Calpha distances by two independent data driven methods. The first method uses statistically derived probability distributions of the pairwise distance between two amino acids, whilst the latter method consists of a neural network prediction approach equipped with windows taking the context of the two residues into account. These two methods are used to predict whether distances in independent test sets were above or below given thresholds. We investigate which distance thresholds produce the most information-rich constraints and, in turn, the optimal performance of the two methods. The predictions are based on a data set derived using a new threshold which defines when sequence similarity implies structural similarity. We show that distances in proteins are predicted more accurately by neural networks than by probability density functions. We show that the accuracy of the predictions can be further increased by using sequence profiles. A threading method based on the predicted distances is presented. A homepage with software, predictions and data related to this paper is available at http://www.cbs.dtu.dk/services/CPHmodels/.

Amino Acids↗

PubMed1997

An analysis of the predictive probability of the in vitro contracture test for determining susceptibility to malignant hyperthermia.

An objective estimate of the likelihood of correct designation of malignant hyperthermia (MH) susceptibility from in vitro contracture test (IVCT) results is essential if genetic linkage studies of MH are to be more informative. The aim of this study was to generate and test statistical models that could be used to predict the probability of susceptibility of an individual to MH from the results of their IVCTs. Logistic regression of the IVCT results of an index group of 50 patients (age range 9-73 years; MH susceptible [MHS], n = 13; MH normal [MHN], n = 32; MH equivocal [MHE], n = 5) who were either at low risk of MH or were proband cases were used to generate models to predict probability of MH susceptibility. Models incorporated data from individual contracture tests or from combinations of tests (static halothane, dynamic halothane, caffeine, ryanodine) performed according to the protocols of the European Malignant Hyperthermia Group. Of the individual contracture tests, the ryanodine test was most closely correlated with MH status. Discriminatory ability of the models was assessed using receiver operating characteristic (ROC) curves. Inclusion of predictor variables from the ryanodine, caffeine, and dynamic halothane tests improved upon the discriminatory ability of the models incorporating variables from individuals tests and was considered to be the best model. The reproducibility of this model was confirmed using an ROC curve constructed using data from 47 patients (age range 10-62 years; MHS, n = 15; MHN, n = 28; MHE, n = 4) who were classified in a way similar to the index group. A further group of 153 patients (age range 9-74 years; MHS, n = 44; MHN, n = 92; MHE, n = 17) who were consecutively tested relatives of susceptible individuals was used to assess the generalizability of the best model. The model met the criteria for a useful discriminatory model with this group of patients, 125 of whom (including 9 MHE patients) could be designated as positive or negative for MH with a likelihood of more than 95%. The logistic regression models provide objective likelihoods for the MH phenotype that could be usefully incorporated into genetic linkage studies of the condition.

Adolescent↗

PubMed1997

Attention and probability effects in the human occipital cortex: an optical imaging study.

A new imaging technique (event-related optical signal, EROS) reveals the time course of neural activity in selected cortical areas of normal human subjects. This technique was used to study the event-related activity in striate and extrastriate occipital areas in an experiment in which spatial selective attention and stimulus probability were manipulated. The results show that attention effects are evident in the initial response in extrastriate cortex (latency < 100 ms), but not in striate cortex, confirming previous modeling effects. They also show that the initial response in striate cortex is modulated by stimulus probability, suggesting the occurrence of pre-attentive memory phenomena in primary visual cortex.

Adult↗

PubMed1985

Probability of survival as a prognostic and severity of illness score in critically ill surgical patients.

A new quantitative method for measuring the prognosis and severity of illness in terms of probability of survival was developed from 224 studies in an index population of 220 critically ill surgical patients. Patients were selected preoperatively to eliminate pre-existing cardiac disease, cirrhosis, nutritional debility, shock or sepsis, in order to evaluate the physiologic relationships of surgical trauma to outcome free of confounding associated medical disorders. The empirically derived numeric severity index was calculated from the probability of survival for each of 28 hemodynamic and oxygen transport variables at each time period after surgery. The score correctly indicated patient outcome in 96% of the index population and 94% of an independent, prospective population. The survivors' score consistently predicted survival within 21.6 +/- 4.4 (SEM) h after the end of surgery. The severity score of those who died consistently predicted nonsurvival within 37 +/- 11 (SEM) h after the end of surgery. We conclude that the score provides a useful, objective, physiologic measure of the severity of illness and prognosis.

Biological Transport↗

PubMed1992

Exact calculation of probabilities of false positives and false negatives for low background counting.

The purpose of this paper is to demonstrate the derivation and use of exact formulas, and their algorithms, for calculating the probabilities alpha of Type I errors, and beta of Type II errors, for low blank total counts (Poisson-distributed). The calculations are carried out to examine the alpha and beta probabilities at low blank levels of the decision level (DL) and minimum detectable amount (MDA) formulations as adopted in the Health Physics Society Standard, "Performance Criteria for Radiobioassay." These formulations are consistent with those published by L.A. Currie, which have received wide acceptance in defining lower limits of detection (LLD). Although Currie's formulation was derived assuming a normal distribution in net counts, the behavior of the distribution of net counts at low count levels, which is a distribution of the difference between two Poisson variates, is such that the MDA formulation in the standard could be considered acceptable for the purpose of providing one simple formulation of MDA. The derivations in this note can also be useful in other problems involving differences in Poisson variates, such as those in certain population studies.

Background Radiation↗

PubMed2000

Probability of metabolic tissue recovery after thrombolytic treatment of experimental stroke: a magnetic resonance spectroscopic imaging study in rat brain.

The effect of thrombolytic therapy on metabolic changes was studied in rats submitted to thromboembolic stroke. Reperfusion was initiated at three different time points, 1.5, 3, and 4.5 hours after embolism (n = 3 each), by injection of recombinant tissue-type plasminogen activator (rt-PA). Recovery was observed during 5 hours of reperfusion using perfusion-weighted images and a two-dimensional 1H magnetic resonance spectroscopic imaging (MRSI) technique. Temporal evolution of the cerebral metabolites lactate and N-acetyl-aspartate (NAA) was determined. To analyze the chances of metabolic tissue recovery, the outcome of treatment, defined by a reversal of lactate concentration, was compared with the lactate intensity before treatment. In untreated animals (n = 4), clot embolism resulted in a drop of perfusion signal intensity in the occluded hemisphere followed by an increase of lactate concentration and a decrease of NAA that persisted throughout the observation period. Thrombolysis partially restored blood flow, but the mean lactate concentration decreased only slightly after successful lysis in animals treated 1.5 hours after embolism. If treatment was initiated later, no decline of lactate level was observed. Five hours after initiation of thrombolysis, the average tissue lactate amounted to 95 +/- 6, 111 +/- 17, and 139 +/- 60% of the early ischemic value (40 minutes after embolization) if treatment began 1.5, 3, and 4.5 hours after embolism, respectively. The NAA level declined slightly but never showed a recovery after rt-PA treatment. In individual pixels, the probability of metabolic tissue recovery clearly declined with increasing lactate concentration before thrombolysis. Interestingly, this probability was independent of treatment delay, but the number of pixels with low lactate declined with increasing ischemia time. Potential clinical applications of MRSI include monitoring of therapeutic intervention as well as support for prognosis of outcome after rt-PA treatment.

Animals↗

PubMed2000

Experts' assessment of probability and level of pesticide exposure in agricultural workers.

The occupational history of the parents of 261 infants with congenital malformations and 261 matched controls was collected. During the relevant time period before the birth of their child, 183 parents were involved in agricultural activities, 49% of them having directly applied pesticides. Two experts assessed the probability and the level of exposure to each quoted pesticide (582 observations) by using 4-point scales. Interrater agreement was estimated. Kappa-weighted values for probability and level of exposure were, respectively, kappa = 0.36 and kappa = 0.39. In the analysis of some categories of exposure (non-applicators, herbicides) very low interrater agreement was observed. In epidemiological studies, detailed assessment of pesticide exposure (product-by-product) is needed to investigate the effects of pesticides on health. But the application of experts' judgment in this area needs more research in assessing the validity of this approach.

Abnormalities, Drug-Induced↗

PubMed2003

A new "TRISS-like" probability of survival model for intubated trauma patients.

BACKGROUND: Prehospital trauma patient field intubations and paralyzations, using neuromuscular blocking agents before emergency department respiratory and neurologic assessments are made, bias assessments and outcome evaluations using probability-of-survival models, such as TRISS and A Severity Characterization of Trauma (ASCOT). We present a newly developed "TRISS-like" probability-of-survival model for intubated blunt- and penetrating-injured patient assessment. METHODS: From a population of 51397 consecutively admitted trauma patients, this study used all 5740 (11.2% of the total injured population) intubated patients with complete data from a statewide trauma registry from October 1, 1993, to September 30, 1996. Model performance was evaluated using standard calibration and discrimination measures and z and W statistics of significance. RESULTS: The new model accurately predicted survival for blunt- and penetrating-injured intubated patients and is applicable to 11 etiologic patient populations. CONCLUSION: Study findings suggest that the new TRISS-like model should be used to assess both blunt- and penetrating-injured intubated patients. Use of this new model provides an analytical method for addressing a significant limitation of both the standard TRISS and ASCOT models, which are not applicable to intubated injured patient assessment. In addition, use of this model will complement TRISS/ASCOT assessments of nonintubated trauma patients and thus permit appropriate assessments for both intubated and nonintubated injured patient study populations.

Adolescent↗

PubMed2002

The method of joint probability distribution functions applied to SIR-MIR and to SIRAS-MIRAS cases.

SIR-MIR and SIRAS-MIRAS cases are studied by application of the joint probability distribution method. The final results are conditional probability distributions of the protein phases given the structure-factor moduli of the protein and of the derivatives, and the structure factors of the heavy-atom substructures. The approach is able to treat errors arising from measurements, from the heavy-atom structure model and from the lack of isomorphism. The relations between the present approach and previous methods are described. The formulas have been implemented in a procedure that is able to automatically phase protein reflections up to protein resolution [Giacovazzo, Ladisa & Siliqi (2002). Acta Cryst. A58, 598-604].

Algorithms↗

PubMed2003

Propensities, probabilities, and the Boltzmann hypothesis.

The relative strengths of interactions involving polypeptide chains can be estimated with reasonable accuracy with statistical potentials, free-energy functions derived from the frequency of occurrence of structural arrangements of residues or atoms in collections of protein structures. Recent published work has shown that the energetics of side-chain/backbone interactions can be modeled by the phi/psi propensities of the 20 amino acids. In this report, the more commonly used phi/psi probabilities are demonstrated to fail in evaluating the free energies of protein conformations because of an overriding preference for all helical structures. Comparison of the hypothetical reactions implied by these two different statistics-propensities versus probabilities-leads to the conclusion that the Boltzmann hypothesis may only be applicable for the calculation of statistical potentials after the starting conformation has been specified. This conclusion supports a simple conjecture: The surprising success of the Boltzmann hypothesis in explaining the energetics of protein structures is a direct consequence of a real equilibrium, one extending over evolutionary time that has maintained the stability of each protein within a narrow range of values.

Amino Acid Sequence↗

PubMed2003

Sequential conditional probability ratio tests for normalized test statistic on information time.

Sequential conditional probability ratio tests (SCPRTs) provide monitoring procedures with a unique property that a decision reached at early stopping is unlikely to be reversed should the trial continue to the planned end (Xiong, X., 1995, Journal of the American Statistical Association 90, 1463-1473; Tan, M., Xiong, X., and Kutner, M. H., 1998, Biometrics 54, 682-95). It actually provides a probability statement of a conclusion reversal, should the proposed interim analysis plan be used. To broaden its scope of applications, in this article we develop the SCPRT in terms of Brownian motion, which is applicable to most clinical trials with various endpoints. In addition, we utilize the unique structure of the SCPRT to derive a class of adaptive sequential tests that retain the significance level and power in the presence of a nuisance parameter. We illustrate the proposed methods with examples in clinical trials.

Biometry↗

PubMed2001

Augmented inverse probability weighted estimator for Cox missing covariate regression.

This article investigates an augmented inverse selection probability weighted estimator for Cox regression parameter estimation when covariate variables are incomplete. This estimator extends the Horvitz and Thompson (1952, Journal of the American Statistical Association 47, 663-685) weighted estimator. This estimator is doubly robust because it is consistent as long as either the selection probability model or the joint distribution of covariates is correctly specified. The augmentation term of the estimating equation depends on the baseline cumulative hazard and on a conditional distribution that can be implemented by using an EM-type algorithm. This method is compared with some previously proposed estimators via simulation studies. The method is applied to a real example.

Analysis of Variance↗

PubMed2002

Robust inference for event probabilities with non-Markov event data.

Multistate event data, in which a single subject is at risk for multiple events, is common in biomedical applications. This article considers nonparametric estimation of the vector of probabilities of state membership at time t. Estimators, derived under the Markov assumption, have been shown (Datta and Satten, 2001, Statistics and Probability Letters 55, 403-411) to be consistent for data that is non-Markov. Inference, however, must take into account possibly non-Markov transitions when constructing confidence bands for event curves. We develop robust confidence bands for these curves, evaluate them via simulation, and illustrate the method on two datasets.

AIDS-Related Opportunistic Infections↗

PubMed2005

Bayesian inferences on predictors of conception probabilities.

Reproductive scientists and couples attempting pregnancy are interested in identifying predictors of the day-specific probabilities of conception in relation to the timing of a single intercourse act. Because most menstrual cycles have multiple days of intercourse, the occurrence of conception represents the aggregation across Bernoulli trials for each intercourse day. Because of this data structure and dependency among the multiple cycles from a woman, implementing analyses has proven challenging. This article proposes a Bayesian approach based on a generalization of the Barrett and Marshall model to incorporate a woman-specific frailty and day-specific covariates. The model results in a simple closed form expression for the marginal probability of conception, and has an auxiliary variables formulation that facilitates efficient posterior computation. Although motivated by fecundability studies, the approach can be used for efficient variable selection and model averaging in general applications with categorical or discrete event time data.

Adult↗

PubMed1990

The combined effect of incubation temperature, pH and sorbic acid on the probability of growth of non-proteolytic, type B Clostridium botulinum.

It has been reported that non-proteolytic strains of Clostridium botulinum will grow at 3.3 degrees C, and they are therefore of concern in relation to certain chilled foods. The effects of combinations of inhibitory factors may be used to reduce the risk of growth of these bacteria in foods. The combined effect of pH values between 4.8 and 7.0, temperatures between 6 degrees and 30 degrees C, and sorbic acid concentrations up to 2270 mg/l on the probability of growth from a single spore of non-proteolytic, type B strains in a culture medium has been determined. A mathematical model has been developed that enables the effect of varying combinations of these factors on the probability of growth of non-proteolytic, type B Cl. botulinum to be predicted.

Clostridium botulinum↗

PubMed1995

Achieving equal probability of selection under various random sampling strategies.

The underlying objective of epidemiological investigations is to extrapolate results from a sample to the relevant population. The simplest way of achieving this is to adopt a sampling strategy in which each individual in the population has the same chance of being selected--that is, to employ an 'equal probability of selection method' (epsem). The easiest ways of achieving this are to use simple random sampling or stratified random sampling with a constant sampling fraction. These strategies are often impracticable, however, particularly in large investigations covering a wide geographical area where resource implications dictate a more complex approach such as multi-stage or cluster sampling. Following detailed definitions and appropriate illustrations of these terms, the main purpose of this paper is to provide a working guide of how to achieve epsem using these various random sampling techniques. In brief, for multi-stage sampling with the rare feature of equal-sized first stage units, epsem is achieved by applying the above simple or stratified approaches to the first stage units. Even in the more realistic scenario of unequal first stage units, the same options apply provided that a fixed proportion of second stage units are to be selected (cluster sampling is in fact just one example of this, with 100% sampling of second stage units). If on the other hand a fixed number of second stage units are to be selected then for epsem the first stage units should be selected with each one having a probability proportionate to its size.

Data Collection↗