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PubMed2000

Research evaluation and diagnosis of probable Alzheimer's disease over the last two decades: I.

OBJECTIVE: To describe the experience of a research clinic diagnosing AD during the last two decades, with special emphasis on patients who meet the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable AD, their patterns of clinical presentation, and neuropathologic outcomes. BACKGROUND: Probable AD has a heterogeneous clinical presentation, and can occur in the context of complicating factors. There are few reports, and none with this large of a sample, about the pattern of presentation, the nature of comorbidities, and the sensitivity and specificity of diagnosis. RESULTS: The AD Research Center of Pittsburgh examined 1139 patients with probable AD between April 1983 and February 2000. Of these 1139 probable AD patients, 29 (2.5%) had slow progression, 27 (2%) had rapid progression, 70 (6%) had an atypical presentation, and 85 (7%) had coexistent cerebrovascular disease. Confluent periventricular white matter lesions were found in 348 (30.5%) patients with probable AD. The overall sensitivity for the diagnosis of AD was 97% and the specificity 80%. However, the accuracy for the diagnosis of AD varied over the years: from 1983 to 1989, the sensitivity was 94% and specificity 52%, and from 1990 to 2000, the sensitivity was 98% and specificity 88%. CONCLUSION: Although the diagnosis of probable AD has been used to indicate the presence of a homogeneous clinical entity, these patients can vary in presentation, onset, or clinical course. This finding is of particular importance for the understanding of the pathophysiologic basis of the disease, and for the better identification of responders to dementia treatments. Although the sensitivity for the diagnosis of AD remained above 90% over the last two decades, the specificity increased, reflecting progressive improvement in the diagnosis of other dementing disorders.

Aged↗

PubMed2003

Detection and false-alarm probabilities for laser radars that use Geiger-mode detectors.

For a direct-detection laser radar that uses a Geiger-mode detector, theory shows that the single-pulse detection probability is reduced by a factor exp(-K), where K is the mean number of primary electrons created by noise in the interval t between detector turn-on and arrival of laser photons reflected from the target. The corresponding false-alarm probability is at least 1 - exp(-K). For fixed-rate noise, one can improve the detection and false-alarm probabilities by reducing t. Moreover, when background-light noise is significant and dominates dark-current noise and when the laser signal is of the order of ten photoelectrons or more, the probabilities can be improved by reducing the amount of light falling on the detector, even if the laser signal is reduced by the same factor as the background light is. Additional analytical calculations show that identifying coincidences in data from as few as three pulses canreduce the false-alarm probability by orders of magnitude and, for some conditions, can also improve the detection probability.

Journal Article↗

PubMed1998

Effects of signal probability on individual differences in vigilance.

Decrements in the proportion of signals detected over time on task and large individual differences in performance are typical findings in studies of vigilance. This study investigates the effects of signal probability on individual differences in vigilance performance. Participants monitored stimulus events on computer displays over 2-h periods at three signal probability levels (.01, .04, & .12). Results were analyzed between groups, within groups, and within subjects. Detection decrements were found to be inversely related to signal probability levels across groups. High signal probabilities generated consistent within-group and within-subject performance, whereas low probabilities generated both lower performance and larger within-subject variance. This relationship between signal probability and within-group and within-subject variance has not been previously demonstrated. Future investigations should focus on the sources of both between-subjects and within-subject variation in vigilance performance in order to identify optimal interventions. Actual or potential applications include designing work to minimize vigilance decrement and maximize human performance under conditions that require sustained attention.

Analysis of Variance↗

PubMed2006

Tympanometric findings and the probability of middle-ear effusion in 3686 infants and young children.

OBJECTIVE: We examined relationships between tympanometric findings and the presence or absence of middle-ear effusion in a population-based sample of children under the age of 3 years. METHODS: In a study of children's development in relation to early-life otitis media, we enrolled 6350 infants soon after birth and evaluated them regularly for the presence of middle-ear effusion. In 3686 of the children, we compared tympanometric findings with otoscopic diagnoses. We categorized tympanograms according to varying combinations of tympanometric peak height, peak pressure, and width, and calculated for each resulting category the percentage of the associated ears diagnosed as having effusion. Using these findings we developed algorithms for estimating the probability of middle-ear effusion associated with tympanograms of any configuration. RESULTS: For tympanograms generally, the lower their height and the greater their width, the greater was the probability of associated middle-ear effusion; the probability also was greater when peak pressure was negative rather than positive. Among children > or = 6 months of age, effusion was diagnosed in only 2.7% of ears with tympanometric height > or = 0.6 mL, but in 80.2% of ears with flat tympanograms. Relationships among younger infants were similar but less consistent. In both age groups, the tympanographic configurations most commonly encountered were associated with either a relatively low probability (<30%) or a relatively high probability (>70%) of the presence of middle-ear effusion. The receiver operating characteristic curve we generated using the algorithm we developed for children > or = 6 months of age gave an area under the curve of 0.84. The algorithm performed equally well when applied to a separate group of children, suggesting that it is generalizable to other unselected populations. CONCLUSIONS: The present report offers two alternative methods for estimating the probability of middle-ear effusion in children aged 6 through 35 months, given any combination of tympanometric values.

Acoustic Impedance Tests↗

PubMed2004

A Monte Carlo approach for estimation of haplotype probabilities in half-sib families.

The objective of this work was to propose an algorithm (HAPROB) to estimate haplotype probabilities for genotyped members of half-sib families for which parents lacked genotypic information. The algorithm had 2 basic steps. First, a Monte Carlo-based approach was used to estimate haplotype probabilities for sires conditional upon offspring genotypes and population allelic frequencies, and then offspring-haplotype probabilities were estimated conditional upon sire probabilities and population frequencies. The 2 steps were alternated iteratively until estimates of population frequencies were essentially unchanged. Simulation was used to evaluate effects of the number of Monte Carlo cycles on the accuracy of the reconstructed haplotypes. Fifty thousand cycles was found to be sufficient for the haplotype configurations considered. Accuracy of the algorithm was compared with that obtained by the public domain SIMWALK2 software. Predictions of the most likely haplotype configurations are produced by SIM-WALK2, but no estimates of probability are given. The accuracy of the current approach was comparable to that obtained from SIMWALK2. The proportions of times that haplotypes were reconstructed correctly were 87.0 and 92.4% (sires and offspring) for HAPROB vs. 87.5 and 91.5% for SIMWALK2. Effects of family size on accuracy of reconstruction were examined. Accuracy of reconstruction was only about 4% for sires with 2 offspring, but accuracy among the offspring themselves was 65%. Accuracy increased quickly as family size increased and reached 100% for sires with 30 offspring. Maximum accuracy for offspring was about 96%. Estimates of haplotype probabilities produced can be used in regression analyses to estimate effects of haplotypes on quantitative phenotypes.

Algorithms↗

PubMed2005

[Outcome of patients with suspected pulmonary thromboembolism and low probability ventilation/perfusion lung scan who receive no long-term anticoagulation].

OBJECTIVE: To know in our area the security of no long-term anticoagulation in patients with suspected pulmonary thromboembolism (PTE) and a low probability ventilation/perfusion (V/Q) lung scan. MATERIAL AND METHODS: Retrospective review of a series of consecutive outpatients with suspected PTE and a low probability V/Q lung scan, according to the modified PIOPED criteria, who receive no long-term anticoagulation. RESULTS: Among 38 patients with a low probability V/Q lung scan, 31 (81.6%) did not receive long-term anticoagulation. The median age was 69.1 years (range 26-88 years), and 19 (61.3%) were female. The clinical probability of PTE was moderate in 27 patients (87.1%). Twenty-two patients (71%) had a venous lower extremities echography-doppler negative for deep vein thrombosis (DVT). The median follow-up was 6.3 months (range 3-12 months). There was one case (3.2%; 95% confidence interval, 0.1-16.7%) with demonstrated PTE and DVT, and there was no death. CONCLUSION: No long-term anticoagulation in outpatients with a moderate clinical probability of PTE, a low probability V/Q lung scan and a venous lower extremities echography-doppler negative for DVT may be secure in our area.

Adult↗

PubMed2000

Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group.

Recent studies have suggested that both the subjective judgement of a physician and standardized clinical models can be helpful in the estimation of the probability of the disease in patients with suspected pulmonary embolism (PE). We performed a multi-center study in consecutive in- and outpatients with suspected PE to compare the potential diagnostic utility of these methods. Of the 517 study patients, 160 (31%) were classified as having PE. Of these patients, 14% had a low probability as estimated by the treating physician, while 25 to 36% were categorized as having a low clinical probability with the use of two previously described clinical models. The objectively confirmed prevalence of PE in these three low probability categories was 19%, 28% and 28%, respectively. The three methods yielded comparable predictive values for PE in the other probability categories. We conclude that a physician's clinical judgement alone and two standardized clinical models, although comparable, perform disappointingly in categorizing the pre-test probability in patients with suspected PE.

Adult↗

PubMed2000

Disparity in neurotransmitter release probability among competing inputs during neuromuscular synapse elimination.

Competition among the several motor axons transiently innervating neonatal muscle fibers results in an increasing disparity in the quantal content and synaptic territory of each competitor, culminating in the permanent loss of all but one axon from neuromuscular junctions. We asked whether differences in the probability of neurotransmitter release also contribute to the increasing disparity in quantal content among competing inputs, and when in the process of competition changes in release probability become apparent. To address these questions, intracellular recordings were made from dually innervated neonatal mouse soleus muscle fibers, and quantal content and paired-pulse facilitation were evaluated for each input. At short interpulse intervals, paired-pulse facilitation was significantly higher for the weaker input with the smaller quantal content than the stronger input with the larger quantal content. Because neurotransmitter release probability across all release sites is inversely related to the extent of facilitation observed after paired-pulse stimulation, this result suggests that release probability is lower for weak compared with strong inputs innervating the same junction. A disparity in the probability of neurotransmitter release thus contributes to the disparity in quantal content that occurs during synaptic competition. Together, this work suggests that an input incapable of sustaining a high release probability may be at a competitive disadvantage for synaptic maintenance.

Animals↗

PubMed2005

[Suicide probability: an assessment terms of reasons for living, hopelessness and loneliness].

PURPOSE: The purpose of the current study is to specify the reasons that hold people clinging to life; to investigate their suicide probability, and to describe the relationship of these variables with other variables such as hopelessness and loneliness, taking age, education and other socioeconomic variables into consideration. METHOD: The subjects were 683, randomly chosen adolescents and adults between the ages of 15-65, residing in Ankara and Izmir. The assessment instruments were Reasons for Living Inventory, Suicide Probability Scale, UCLA Loneliness Scale, and Beck Hopelessness Scale. The data were analyzed using the SPSS for Windows 10.00. RESULTS: The analyses revealed that the group aged between 15-25 years reported fewer reasons for living, higher suicide probability, more hopelessness and loneliness, compared to older ages. Moreover, women reported more reasons for living, along with less loneliness and hopelessness. The regression analyses pointed out that age, education level, hopelessness, loneliness and reasons for living are predictive variables for suicide probability. CONCLUSION: As it was previously reported the current study also revealed that age is an important variable to be taken into consideration when suicide probability is being determined. In addition, was also found to be an important variable, at least for this Country. In parallel with the results of the studies in the relevant literature, reasons for living, hopelessness, and loneliness were found to be significant predictors of suicide probability.

Adolescent↗

PubMed2005

Specific features of the contact history of probable cases of severe acute respiratory syndrome.

OBJECTIVE: To describe the specific features of the contact history of probable cases of severe acute respiratory syndrome (SARS) in Beijing. METHODS: Data of SARS cases notified from the Beijing Municipal Center for Disease Control and Prevention (BCDC) and supplemented by other channels were collected. All the data were analyzed by descriptive epidemiology. RESULTS: (1) The number of probable cases with contact history was significantly higher than the excluded cases. (2) The proportion of probable cases with contact history descended with epidemic development, but this situation did not occur in health care workers (HCWs). (3) The fatality rate of probable cases with contact history was significantly higher than the cases without contact history (OR = 1.489). (4) The proportion of probable cases with contact history was 85.86% among health care workers, which was significantly higher than that of non-health care workers (85.86% v.s. 56.44%, OR=4.69). CONCLUSIONS: (1) The susceptible persons with contact history may not get infected, and the contact history is just a sufficient condition of infecting SARS; (2) There are 3 conceivable reasons for the descending trend of the proportion in probable cases with contact history; (3) The contact history is one of the risk factors of the death of SARS cases; (4) The risk of contacting with SARS among health care workers is approximately 5 times higher than that of non-HCWs.

China↗

PubMed2005

[The diagnosis of definitive or probable tuberculosis and latent tuberculosis infection in children with suspected tuberculosis].

Pulmonary tuberculosis (Tbc) continues to be an important cause of morbidity in children in our country and in the world. There are diagnostic difficulties in the evaluation of the patients with suspected Tbc. In our study of 118 cases, the signs or symptoms suggestive of pulmonary Tbc have a microbiologically confirmed ratio of 26% within the cases having a positive tuberculin test result or having a contact with an adult that had Tbc. Thirty-one (26%) patients were diagnosed with definite Tbc, 48 (41%) patients with probable Tbc and 28 (24%) patients with latent Tbc infection. The tuberculin test was positive in 22 (71%) patients with definite Tbc and in 29 (60%) patients with probable Tbc. A history of a contact with an adult having Tbc has been observed in 18 (58%) patients in definite Tbc case group, in 23 (48%) patients in probable Tbc case group and in 13 (46%) patients in latent Tbc infection case group. No significant difference has been observed between patients with definite or probable pulmonary Tbc according to the average age, sex, tuberculin test positivity and history of Tbc contact. The most common clinical symptoms that has been observed in both groups were cough, fever and weight loss and the most common radiological finding that has been found in both groups was persistent infiltration. Definite or probable Tbc cases were treated for a period of 6 months with 3 anti-Tbc drugs. There were no patients who had failed to response to the treatment. These results showed that, the diagnostic criteria used for probable pulmonary Tbc are also useful in detecting the patients who should be treated with anti-Tbc drugs.

Adolescent↗

PubMed1989

Intuitive reasoning about probability: theoretical and experimental analyses of the "problem of three prisoners".

Among various Bayesian problems of probability, the "problem of three prisoners" (Lindley, 1971; Mosteller, 1965) is an especially good example which illustrates the drastic discrepancy between intuitive reasoning and mathematical formal reasoning about probability. In particular, it raises intriguing questions concerning the mathematical and cognitive relevance of factors such as prior probabilities and the context in which certain information is given. In the current paper, we report a new version of the problem which turned out to be even more counterintuitive. This new version was also designed so that different inferential schemes would lead to separate estimates of posterior probability. The data obtained from questionnaires and theoretical analyses of the original and modified problems suggest that: (1) The psychological processes of intuitive reasoning are qualitatively different from mathematical reasoning. (2) The tendency to neglect prior probabilities (Tversky & Kahneman, 1974, 1982) is not always the critical factor for illusory judgments. (3) Intuitive judgments can be categorized by several, distinctive propositional beliefs from which the judgments are apparently derived. We call these prototypical, crude beliefs "subjective theorems," and discuss their nature and roles in the current paper.

Adult↗

PubMedDate not supplied

Pregnancy probabilities during use of the Creighton Model Fertility Care System.

OBJECTIVE: To evaluate pregnancy probabilities during use of the Creighton Model Fertility Care System (CrMS). DESIGN: Couples who began use of the CrMS were entered into this observational cohort study. Follow-up included detailed reviews of use of the CrMS. Pregnancy probabilities were calculated with both net and gross life-table analysis through 18 months. SETTING: A natural family planning service delivery program based at an urban hospital in Houston, Tex. SUBJECTS: A group of 701 couples who received instruction in the CrMS were entered into the study. Most couples (93%) were engaged or married. Most women were white (83%), between the ages of 20 and 34 years (88%), and college graduates (58%). MAIN OUTCOME MEASURE: Pregnancies were classified based on a detailed evaluation involving the pregnant woman (usually with her partner). RESULTS: At 12 months, the following net pregnancy probabilities were found per 100 couples: method-related pregnancies, 0.14; pregnancies caused by user and/or teacher error, 2.72; pregnancies caused by achieving-related behavior (genital contact during a time known to be fertile), 12.84; unresolved pregnancies, 1.43; and total pregnancies, 17.12. Pregnancy probabilities were similar when stratified by the following reproductive categories: uncomplicated regular cycles, long cycles, discontinuing oral contraceptives, breastfeeding, and other. CONCLUSIONS: Pregnancy probabilities of the CrMS compare favorably with those of other methods of family planning. Most pregnancies result from genital contact during a known fertile time. Women need not have regular cycles to use the CrMS successfully.

Adolescent↗

PubMed2001

Probability binning comparison: a metric for quantitating univariate distribution differences.

BACKGROUND: Comparing distributions of data is an important goal in many applications. For example, determining whether two samples (e.g., a control and test sample) are statistically significantly different is useful to detect a response, or to provide feedback regarding instrument stability by detecting when collected data varies significantly over time. METHODS: We apply a variant of the chi-squared statistic to comparing univariate distributions. In this variant, a control distribution is divided such that an equal number of events fall into each of the divisions, or bins. This approach is thereby a mini-max algorithm, in that it minimizes the maximum expected variance for the control distribution. The control-derived bins are then applied to test sample distributions, and a normalized chi-squared value is computed. We term this algorithm Probability Binning. RESULTS: Using a Monte-Carlo simulation, we determined the distribution of chi-squared values obtained by comparing sets of events derived from the same distribution. Based on this distribution, we derive a conversion of any given chi-squared value into a metric that is analogous to a t-score, i.e., it can be used to estimate the probability that a test distribution is different from a control distribution. We demonstrate that this metric scales with the difference between two distributions, and can be used to rank samples according to similarity to a control. Finally, we demonstrate the applicability of this metric to ranking immunophenotyping distributions to suggest that it indeed can be used to objectively determine the relative distance of distributions compared to a single control. CONCLUSION: Probability Binning, as shown here, provides a useful metric for determining the probability that two or more flow cytometric data distributions are different. This metric can also be used to rank distributions to identify which are most similar or dissimilar. In addition, the algorithm can be used to quantitate contamination of even highly-overlapping populations. Finally, as demonstrated in an accompanying paper, Probability Binning can be used to gate on events that represent significantly different subsets from a control sample. Published 2001 Wiley-Liss, Inc.

Algorithms↗

PubMedDate not supplied

Sample size and the probability of a successful trial.

This paper describes the distinction between the concept of statistical power and the probability of getting a successful trial. While one can choose a very high statistical power to detect a certain treatment effect, the high statistical power does not necessarily translate to a high success probability if the treatment effect to detect is based on the perceived ability of the drug candidate. The crucial factor hinges on our knowledge of the drug's ability to deliver the effect used to power the study. The paper discusses a framework to calculate the 'average success probability' and demonstrates how uncertainty about the treatment effect could affect the average success probability for a confirmatory trial. It complements an earlier work by O'Hagan et al. (Pharmaceutical Statistics 2005; 4:187-201) published in this journal. Computer codes to calculate the average success probability are included.

Algorithms↗

PubMed2001

Probabilities of encounters between objects in biological systems: meta-observer view.

Encounters between objects play a crucial role in creating specific patterns of organization in many biological systems. This paper explores a general, quantitative principle of encounter probabilities, applicable over various levels of organization, as a fundamental step toward a comprehensive theory of biological probability ranging from cells through organisms to ecological communities. Based on the cognizers-system model, a general description of encounter probabilities in a finite position space is derived as a function of the number, or density, of objects with cognitive, selectivity properties incorporated as parameters. There is a prevailing wisdom, as supposed in many scientific thoughts, that the per-unit-time number of encounters between focal and target objects is given as a linear function of the density of target objects. One result shows that this idea does not describe the real nature of encounter probabilities or rates, but only a special case or approximation of a fundamental description. The analysis also explicates conditions for ignoring the presence of non-target objects, and those for the aggregation of two or more different objects into the same type sharing the same cognitive properties in the description of the probabilities.

Animals↗

PubMed1994

Root probabilities for intraspecific gene trees under neutral coalescent theory.

The rooting of intraspecific gene or haplotype trees has proven to be difficult using the traditional techniques of rooting species trees such as outgroups. As an alternative, we apply neutral coalescent theory to the problems of determining the root of an intraspecific gene tree and the relative ages of the haplotypes. By using a recursive equation, exact root probabilities can be calculated for small cladograms and sample sizes. These exact probabilities indicate that root probabilities are not very sensitive to the parameter theta, which is four times the mutation rate times the inbreeding effective size. The exact probabilities also indicate that root probabilities are not very sensitive to the absolute numbers of each haplotype (allele) class, only their relative proportions. The exact method, unfortunately, is not feasible for implementation with larger data sets with present algorithms and computers. However, the exact results suggested a simple heuristic for determining outgroup weights; that is, finding the haplotype that is the oldest in the sample and that can serve as an outgroup for the remainder of the haplotype tree. Computer simulations revealed that these outgroup weights are strongly correlated with actual age and are much better indicators of haplotype age than is the haplotype frequency, another commonly used indicator of relative age.

Gene Frequency↗

PubMed2002

The probability of topological concordance of gene trees and species trees.

The concordance of gene trees and species trees is reconsidered in detail, allowing for samples of arbitrary size to be taken from the species. A sense of concordance for gene tree and species tree topologies is clarified, such that if the "collapsed gene tree" produced by a gene tree has the same topology as the species tree, the gene tree is said to be topologically concordant with the species tree. The term speciodendric is introduced to refer to genes whose trees are topologically concordant with species trees. For a given three-species topology, probabilities of each of the three possible collapsed gene tree topologies are given, as are probabilities of monophyletic concordance and concordance in the sense of N. Takahata (1989), Genetics 122, 957-966. Increasing the sample size is found to increase the probability of topological concordance, but a limit exists on how much the topological concordance probability can be increased. Suggested sample sizes beyond which this probability can be increased only minimally are given. The results are discussed in terms of implications for molecular studies of phylogenetics and speciation.

Biological Evolution↗