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[Perspectives of using the probability principles for the study of the problems of normal and pathological morphology].

On the literature available and the author's data the prospects on application of probability principles for the study of certain problems of normal and pathological morphology are discussed. Short consideration is given from the theory of probability and information with theoretical grounds for their possible application in morphology. From this standpoint some problems of morphological bases of homeostasis, adaptation, compensation and pathological processes are reviewed. Certain points of the probability theory of atherosclerotic morphogenesis and informative characteristic of malignization in stratified epithelium of laryngeal mucosa illustrate the article. General principles for further development of quantitative morphology are shortly elucidated.

Age Factors↗

Performance characteristics of rules for internal quality control: probabilities for false rejection and error detection.

When assessing the performance of an internal quality control system, it is useful to determine the probability for false rejections (pfr) and the probability for error detection (ped). These performance characteristics are estimated here by use of a computer stimulation procedure. The control rules studied include those commonly employed with Shewhart-type control charts, a cumulative sum rule, and rules applicable when a series of control measurements are treated as a single control observation. The error situations studied include an increase in random error, a systematic shift, a systematic drift, and mixtures of these. The probability for error detection is very dependent on the number of control observations and the choice of control rules. No one rule is best for detecting all errors, thus combinations of rules are desirable. Some appropriate combinations are suggested and their performance characteristics are presented.

Chemistry, Clinical↗

The effect of sampling error and measurement error and its correlation on the estimation of multi-locus fixed-bin VNTR RFLP genotype probabilities.

Bootstrapping was used to examine the effect of sampling error and measurement error and its correlation on fixed-bin genotype probabilities. Bootstrap confidence intervals (Cls) were made relative to the point estimate using the log of the inverse of the probabilities. From databases of 200-250 genotypes, sampling error alone yielded median relative 95% CIs of from one order of magnitude out of five for one locus to one out of ten for four loci. Measurement error of the test genotype fragments increased the latter to about one order of magnitude out of eight. Database measurement error and its correlation had only a slight effect on multi-locus probability uncertainty. Together, these uncertainties are several orders of magnitude greater than error due to population substructuring of a race by its major component ethnic groups.

Confidence Intervals↗

[Probability and strategy: an event-related potential study of processing syntactic anomalies].

Syntactic ambiguities requiring additional processing usually elicit positive going waveforms with onset latencies between 300 and 600 ms in the event-related potential (ERP). It is still unclear to what extent these components can be viewed either (a) as language specific in nature or (b) as members of the domain-unspecific P300 family of components. The present study investigates this question by means of probability manipulations applied to German sentences with subject-object ambiguities. Non-preferred object-subject (OS) word order requires structural revisions whereas the initially preferred subject-object (SO) word order does not. In the present experiment, the proportions of OS and SO structures were varied across experimental blocks (i.e., .25/.75 vs. .75/.25). The data of 20 participants reveal that ERP components were predominantly influenced when the subjects were explicitly informed about the actual proportions before each single block. In this case an early frontal positive component at about 400 ms and a subsequent posterior positivity were elicited by rare sentence structures irrespective of word order, suggesting that sentence processing was under strategic control. Conversely, participants that were not informed about sentence proportions showed larger positivities to the unpreferred OS sentences. Probability manipulations did not affect this pattern significantly. The data suggest that positivities evoked by syntactic ambiguities respond differently to probability manipulations than the P300 component.

Adult↗

Probability logic and probabilistic induction.

This article reviews some philosophical aspects of probability and describes how probability logic can give precise meanings to the concepts of inductive support, corroboration, refutation, and related notions, as well as provide a foundation for logically sound statistical inference. Probability logic also provides a basis for recognizing prior distributions as an integral component of statistical analysis, rather than the current misleading practice of pretending that statistics applied to observational data are objective. This basis is important, because the use of realistic priors in a statistical analysis can yield more stringent tests of hypotheses and more accurate estimates than conventional procedures.

Epidemiologic Studies↗

[Accumulated probability of hypertension in diabetes and of diabetes in hypertension].

OBJECTIVE: To determine the cumulative probability of hypertension in type 2 diabetic patients, and of diabetes in patients with essential arterial hypertension. METHODS: A 15-years follow-up study of 308 subjects, 156 with type 2 diabetes and 152 with arterial hypertension. Time zero (T0) was the date in which the diabetes or the hypertension were established. The time in years from T0 up to diagnosis of hypertension in diabetics or diabetes in hypertensives was determined. The cumulative probability was calculated with the method of Kaplan and Meier. RESULTS: The incidence of hypertension in the diabetics was 4.36 patient-year, and that of diabetes in hypertensives of 1.23 patient-year (p = < 0.00001; Cl95% 4.8-14.7). After the first 5 years, 40% of the diabetics had hypertension and 12% of the hypertensives developed diabetes; at 15-years follow-up, these figures were 71% and 21% respectively (p < 0.001). CONCLUSIONS: The probability of essential arterial hypertension in type 2 diabetes was significantly higher than the incidence of diabetes in hypertensive subjects. In both instances, the risk was greater for men than for women.

Adult↗

Detection of optic disc changes with Glaucoma-Scope probability maps.

PURPOSE: To test whether a statistical method using a probability map could detect true changes in optic disc topography. METHODS: The average of three Glaucoma-Scope images (Ophthalmic Imaging Systems were used for analysis at each of two sessions. A Glaucoma-Scope probability map was constructed for each eye using statistical methods. The proportion of topographic locations with p values less than 0.05 on a modified two-sample t test (p-proportion) and the difference in the mean position of the disc (MPD) from two imaging sessions were calculated. Two pairs of stereoscopic disc photographs for 43 eyes with longitudinal follow-up were evaluated for change by four experienced glaucoma specialists masked to patient clinical information. Clinical change was considered to have occurred when the assessments of at least three of the four specialists were agreed on. The cutoff values for p-proportion and change in MPD that provided 95% specificity were calculated using a separate sample of 69 subjects who had serial images taken at two separate sessions on the same day, and thus showed no clinical change in the optic disc. RESULTS: The cutoff values of 95% specificity for the p-proportion and the change in MPD were 18% and 25.1 microns, respectively. Of 43 eyes with longitudinal follow-up, 14 showed definite clinical change. Sensitivity of the p-proportion and change in MPD for detecting this change was 100% and 85.7%, respectively. For all 43 patients with longitudinal follow-up, the percent change in intraocular pressure (IOP) correlated strongly with both the p-proportion and the change in MPD. CONCLUSION: Using data obtained with the Glaucoma-Scope, a statistical method based on probability mapping can be used to detect true changes in disc topography. The p-proportion was more sensitive than change in MPD in detecting clinical change in the study eyes. This statistical methodology may also be applicable for interpretation of data obtained with other optic disc analyzers.

Adult↗

Optimizing the prediction of perioperative mortality in vascular surgery by using a customized probability model.

BACKGROUND: Accurately assessing the probability of perioperative mortality can be useful in preoperative risk assessment and management. This study aimed to revise and customize the revised cardiac risk (Lee) index to estimate the probability of perioperative all-cause mortality in patients undergoing noncardiac vascular surgery. METHODS: We studied 2310 patients (mean age, 67.8 +/- 11.3 years; 1747 males) who underwent acute or elective major noncardiac vascular surgery between January 1, 1991, and December 31, 2000, at the Erasmus Medical Center, Rotterdam, the Netherlands. A total of 1537 patients were assigned for model development, in which the associations between predictor variables and mortality occurring within 30 days after surgery were identified to modify the Lee index, which was then evaluated in a validation cohort of 773 patients. RESULTS: The perioperative mortality rates were similar in the development (n = 103 [6.7%]) and validation (n = 50 [6.5%]) populations. The customized risk-prediction model for perioperative mortality identified type of vascular surgery, ischemic heart disease, congestive heart failure, previous stroke, hypertension, renal dysfunction, and chronic pulmonary disease as being associated with increased risk, whereas beta-blocker and statin use were associated with a lower risk of mortality. The performance of the customized index had excellent discriminative ability in both derivation and validation populations (concordance statistic, 0.88 and 0.85, respectively). CONCLUSIONS: The customized index provides more detailed information than the Lee index about the type of vascular procedure, clinical risk factors, and concomitant medication use. The customized probability model can be a useful tool to estimate the risk of perioperative all-cause mortality and facilitate subsequent treatment strategies.

Aged↗

Multiple sclerosis-from probable to definite diagnosis: a 7-year prospective study.

OBJECTIVES: To investigate the rate of progression from probable to clinically definite multiple sclerosis (MS) and to define patients who had rapidly (within 1 year) progressed to a definite diagnosis. DESIGN: A 7-year prospective study. PATIENTS: A group of 163 patients experiencing their first episode of neurologic symptoms suggestive of MS. All patients had brain magnetic resonance imaging that demonstrated at least 3 demyelinating lesions at onset. RESULTS: Within the follow-up period (mean, 42 months; range, 13-84 months), 136 patients (83.4%) had an additional relapse and were thus defined as having clinically definite MS, whereas 27 patients (16.6%) were defined as having clinically probable MS. Most of the 136 patients with clinically definite MS (57.6%, 94 patients) experienced the additional relapse within 1 year. Demographic and clinical parameters at presentation were analyzed to identify variables predictive of rapid progression (within 1 year) to clinical definite MS. Motor involvement at onset was the only clinical parameter associated with rapid progression to a definite diagnosis. Survival curves demonstrated that polysymptomatic involvement and higher Extended Disability Status Scale score at presentation correlated with rapid progression to definite diagnosis. CONCLUSION: Most patients with a diagnosis of probable MS and positive brain magnetic resonance imaging will progress rapidly to clinically definite MS.

Adolescent↗

Hydrogen-bond disruption probability in proteins by a modified self-consistent harmonic approach.

Modified self-consistent harmonic approach was employed to calculate the probability for the disruption of each individual hydrogen bonds (H bonds) in x-ray crystal structure of several proteins. The computed probability for 82% of intraprotein and water-protein H bonds studied were found to be roughly consistent with estimated free energies from protein engineering and hydrogen exchange experiments. Hydrogen bonds have been proposed as part of a stereochemical code for protein folding. Proteins fold into unique three-dimensional structures; therefore those bonds involved in the folding code are expected to be stable. We have applied this method to tens of hydrogen bonds in a protein assumed to be involved in the folding code of a protein. 58% of these H bonds were found to have a lower disruption probability (-1.8 kcal/mol). Our results showed that modified self-consistent harmonic approach might be explored as a method supplement to existing methods in analysis of hydrogen bonds in proteins.

Algorithms↗

Genetic refinement and physical mapping of a 2.3 Mb probable disease region associated with a bipolar affective disorder susceptibility locus on chromosome 4q35.

A susceptibility locus for bipolar affective disorder has been mapped to chromosome 4q35 in a large multigenerational pedigree. We have expanded this analysis to include 55 pedigrees (674 individuals, 214 affecteds). The evidence for linkage to 4q35 was strengthened in this larger cohort, with a maximum two-point LOD score of 3.2 for marker D4S1652. Several other markers in the region gave LOD scores greater than 1.5. Non-parametric analysis provided additional support for linkage to the 4q35 region. To further refine this region, haplotype analysis was carried out in 16 of the 55 pedigrees that showed evidence of linkage. As there is no evidence for an ancestral haplotype, nor a one-to-one correspondence between the disease and putative disease haplotype, we undertook an analysis based on pedigree-specific, identical-by-descent allele-sharing in order to define a probable disease region. This analysis indicated that the percentage sharing of alleles, identical-by-descent, in affecteds of all linked pedigrees increases from 60% at the centromeric markers to 75% for markers at the telomere. Maximal allele sharing occurred between markers D4S3051 and 4qTEL13 with this 24 cM region defining a probable disease region. We have constructed a physical map of the 4q35 interval consisting of a YAC contig and BAC clones. Based on this map the probable disease region between D4S3051 and 4qTEL13 corresponds to only 2.3 Mb. This region is very gene poor with only three known genes indicated from the YAC/BAC map. The small number of genes will facilitate systematic screening for variations associated with bipolar disorder.

Bipolar Disorder↗

The probability distribution of side-chain conformations in [Leu] and [Met]enkephalin determines the potency and selectivity to mu and delta opiate receptors.

The structure of enkephalin, a small neuropeptide with five amino acids, has been simulated on computers using molecular dynamics. Such simulations exhibit a few stable conformations, which also have been identified experimentally. The simulations provide the possibility to perform cluster analysis in the space defined by potentially pharmacophoric measures such as dihedral angles, side-chain orientation, etc. By analyzing the statistics of the resulting clusters, the probability distribution of the side-chain conformations may be determined. These probabilities allow us to predict the selectivity of [Leu]enkephalin and [Met]enkephalin to the known mu- and delta-type opiate receptors to which they bind as agonists. Other plausible consequences of these probability distributions are discussed in relation to the way in which they may influence the dynamics of the synapse.

Enkephalin, Leucine↗

Breast cancer incidence, penetrance and survival in probable carriers of BRCA1 gene mutation in families linked to BRCA1 on chromosome 17q12-21.

Eight breast cancer pedigrees with a high probability of containing individuals with the BRCA1 gene mutation (odds 79.2-99.9 per cent) were identified through genetic linkage analysis using probes located within q12-22 on the long arm of chromosome 17. Some 102 female relatives were successfully typed with one or both of adjacent markers D17S588 and D17S579, and 41 were probable non-BRCA1 mutation carriers. Of the remaining 61 women classified as probable BRCA1 carriers, breast cancer was diagnosed in 35. As expected from epidemiological segregation analysis studies, 13 of these had bilateral disease. Approximately two-thirds of women unaffected by malignancy and alive at the time of observation were non-BRCA1 carriers. Lifetime disease penetrance of the BRCA1 gene was 88 per cent and this plateau was reached earlier (by age 65 years) than that estimated in segregation analysis. The survival curve of patients with breast cancer was less steep in BRCA1 gene carriers than that in the general population; 5-, 10- and 20-year survival rates unadjusted for non-cancer deaths were 83, 63 and 41 per cent respectively. The 5-year survival rate was significantly higher in BRCA1 carriers than that in an age-matched Scottish population (P < 0.05).

Adult↗

Long-term survival probabilities for childhood rhabdomyosarcoma. A population-based evaluation.

BACKGROUND: Evidence from clinical trials has documented improvements in event-free survival from childhood rhabdomyosarcoma (RMS) since the 1970s; however, the survival experience of children enrolled on cancer clinical trials may not reflect the full range of patients treated in community settings. The current study evaluated 5-year survival and 10-year conditional survival for RMS from U.S. population-based cancer registry data. METHODS: Public-use data from the Surveillance, Epidemiology, and End Results (SEER) program were used in life table and Cox regression analyses to evaluate RMS survival by patient age at diagnosis, gender, tumor histology, tumor site and stage, and major treatment eras among 848 children who were age < 20 years at the time of diagnosis, were a resident of 1 of 9 geographic reporting regions, and were diagnosed between 1973 and 2000. RESULTS: The 5-year survival probabilities were found to be highest for younger-age children (ages 1-4 years: 77%), patients with localized disease (83%), those whose tumors had an embryonal histology (67%), and patients with orbital (86%) and genitourinary (80%) tumor sites. Poor prognosis was associated with diagnosis during infancy (47%) and adolescence (48%); metastatic disease at the time of presentation (31%); alveolar histology (49%); and tumors of the extremities (50%), retroperitoneum (52%), and trunk (52%). Conditional 10-year survival probabilities among those who survived > or = 5 years were 85% or higher. The probability of survival by stage at the time of diagnosis increased with each successive treatment era, suggesting a stage shift phenomenon over time. CONCLUSIONS: Large variations in 5-year survival were evident depending on patient age and tumor characteristics. However, children who survived the first 5 years after diagnosis were found to have an excellent long-term prognosis. The patterns in RMS survival noted from the current population-based evaluation did not appear to differ substantially from those previously reported by major clinical trials.

Adolescent↗

An algorithm for computing nucleic acid base-pairing probabilities including pseudoknots.

Given a nucleic acid sequence, a recent algorithm allows the calculation of the partition function over secondary structure space including a class of physically relevant pseudoknots. Here, we present a method for computing base-pairing probabilities starting from the output of this partition function algorithm. The approach relies on the calculation of recursion probabilities that are computed by backtracking through the partition function algorithm, applying a particular transformation at each step. This transformation is applicable to any partition function algorithm that follows the same basic dynamic programming paradigm. Base-pairing probabilities are useful for analyzing the equilibrium ensemble properties of natural and engineered nucleic acids, as demonstrated for a human telomerase RNA and a synthetic DNA nanostructure.

Algorithms↗

Differentiation of cultured pre-adipose cells: a probability model.

Some cells of the established preadipose cell line, 3T3-L1, synthesize triglyceride after becoming confluent and quiescent. An analysis of the distribution of clusters of lipid-containing cells was consistent with a commitment event during exponential growth followed by clonal growth of committed cells. Experiments were designed to determine if the final clonal pattern of fat among nonfat cells could be described by a probability model. Undifferentiated cells (fibroblastic cells with no detectable accumulation of triglycerides) were plated at various cell numbers so that the total number of cell divisions to confluence could be controlled. Cells were passaged by trypsinization and replating, or trypsinization followed by passage through a narrow-bore needle before replating. Passing cells through a 22G needle seems to eliminate already committed cells from the population. We determined the percentage of fat cells and the range of clone sizes in cultures in which clone sizes depended upon the number of allowed cell divisions. Patterns of clone sizes in experimental cultures were compared to expected patterns obtained by computer simulations of several programmed and stochastic commitment models. Both the observed range of clone sizes and pattern of clones can be approximated by a simple stochastic model, suggesting that commitment to fat production in 3T3-L1 cells is a random process occurring with a fixed probability in single cells in exponential growth, followed by division of both committed and uncommitted cells. The probability of commitment was essentially constant at each cell division. The number of cells committed during each passage is just large enough to replace "terminally differentiated" lipid-containing cells that have been lost, thereby maintaining a constant percentage of fat cells in any given culture of 3T3-L1.

Adipose Tissue↗

An important role of a "probable ATP-binding component of ABC transporter" during the process of Pseudomonas aeruginosa resistance to fluoroquinolone.

In order to find new drug target to eliminate the fluoroquinolone resistance, the in vitro progress of Pseudomonas aeruginosa fluoroquinolone resistance was mimicked, and then proteomic analysis was applied to comparing different protein profiles during the resistant process. The results show that the expression of a "probable ATP-binding component of ATP binding cassette (ABC) transporter" existed in ciprofloxacin-intermediate and -resistant strains, but not in sensitive strain. In addition, the ciprofloxacin concentrations in P. aeruginosa strains, which were obtained from the progress of P. aeruginosa fluoroquinolone resistance, were determined by means of HPLC; the results show that the decrease of the intracellular concentration of drug and the expression of this new protein nearly take place simultaneously. The changes of mRNA levels of the probable ATP-binding component of ABC transporter were detected by virtue of RT-PCR and showed that this protein did not express in the sensitive strains but expressed increasingly in the intermediate and resistant strains. In order to determine the relationships between the development of antibiotic resistance and this protein further, a DNAzyme was designed to aim at the mRNA of the probable ATP-binding component of ABC transporter directly; the ciprofloxacin resistance of P. aeruginosa was partially reduced in vivo by inhibiting the expression of this protein. This DNAzyme has no effect on sensitive strain. And the comparison of drug intracellular concentrations between DNAzyme-treated strains and its control strains shows that this protein may be included in the course of active drug efflux.

ATP-Binding Cassette Transporters↗