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At least 145 records · Page 8Linked to original sources
PubMed1998

Locus of frequency-dependent depression identified with multiple-probability fluctuation analysis at rat climbing fibre-Purkinje cell synapses.

1. EPSCs were recorded under whole-cell voltage clamp at room temperature from Purkinje cells in slices of cerebellum from 12- to 14-day-old rats. EPSCs from individual climbing fibre (CF) inputs were identified on the basis of their large size, paired-pulse depression and all-or-none appearance in response to a graded stimulus. 2. Synaptic transmission was investigated over a wide range of experimentally imposed release probabilities by analysing fluctuations in the peak of the EPSC. Release probability was manipulated by altering the extracellular [Ca2+] and [Mg2+]. Quantal parameters were estimated from plots of coefficient of variation (CV) or variance against mean conductance by fitting a multinomial model that incorporated both spatial variation in quantal size and non-uniform release probability. This 'multiple-probability fluctuation' (MPF) analysis gave an estimate of 510 +/- 50 for the number of functional release sites (N) and a quantal size (q) of 0.5 +/- 0.03 nS (n = 6). 3. Control experiments, and simulations examining the effects of non-uniform release probability, indicate that MPF analysis provides a reliable estimate of quantal parameters. Direct measurement of quantal amplitudes in the presence of 5 mM Sr2+, which gave asynchronous release, yielded distributions with a mean quantal size of 0.55 +/- 0.01 nS and a CV of 0.37 +/- 0.01 (n = 4). Similar estimates of q were obtained in 2 mM Ca2+ when release probability was lowered with the calcium channel blocker Cd2+. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1 microM) reduced both the evoked current and the quantal size (estimated with MPF analysis) to a similar degree, but did not affect the estimate of N. 4. We used MPF analysis to identify those quantal parameters that change during frequency-dependent depression at climbing fibre-Purkinje cell synaptic connections. At low stimulation frequencies, the mean release probability (pr) was unusually high (0.90 +/- 0.03 at 0.033 Hz, n = 5), but as the frequency of stimulation was increased, pr fell dramatically (0.02 +/- 0.01 at 10 Hz, n = 4) with no apparent change in either q or N. This indicates that the observed 50-fold depression in EPSC amplitude is presynaptic in origin. 5. Presynaptic frequency-dependent depression was investigated with double-pulse and multiple-pulse protocols. EPSC recovery, following simultaneous release at practically all sites, was slow, being well fitted by the sum of two exponential functions (time constants of 0.35 +/- 0.09 and 3.2 +/- 0.4 s, n = 5). EPSC recovery following sustained stimulation was even slower. We propose that presynaptic depression at CF synapses reflects a slow recovery of release probability following release of each quantum of transmitter. 6. The large number of functional release sites, relatively large quantal size, and unusual dynamics of transmitter release at the CF synapse appear specialized to ensure highly reliable olivocerebellar transmission at low frequencies but to limit transmission at higher frequencies.

Animals↗
PubMed1994

Comparison of probability of stroke between the Copenhagen City Heart Study and the Framingham Study.

BACKGROUND AND PURPOSE: We wished to test the validity of a stroke probability point system from the Framingham Study for a sample of the population of Copenhagen, Denmark. In the Framingham cohort, the regression model of Cox established the effect on stroke of the following factors: age, systolic blood pressure, the use of antihypertensive therapy, diabetes mellitus, cigarette smoking, prior cardiovascular disease, atrial fibrillation, and left ventricular hypertrophy. Derived from this model, stroke probabilities were computed for each sex based on a point system. The authors claimed that a physician can use this system for individual stroke prediction. METHODS: The Copenhagen City Heart Study is a prospective survey of 19,698 women and men aged 20 years or older invited to two cardiovascular examinations at 5-year intervals. The baseline examination included 3015 men and 3501 women aged 55 to 84 years; 474 stroke events occurred during 10 years of follow-up. In both cohorts initial cases of stroke and transient ischemic attack recorded during 10 years of follow-up were used. We used the statistical model from the Framingham Study to establish a corresponding stroke probability point system using data from the Copenhagen City Heart Study population. We then compared the effects of the relevant risk factors, their combinations, and the corresponding stroke probabilities. We also assessed stroke events during 10 years of follow-up in several subgroups of the Copenhagen population with different combinations of risk factors. RESULTS: For the Copenhagen City Heart Study population some of the risk factors (diabetes mellitus, cigarette smoking, atrial fibrillation, and left ventricular hypertrophy) had regression coefficients different from those of the Framingham Study population. Consequently, the probability of stroke for persons presenting these risk factors and their combinations varied between the two studies. For some other risk factors (age, blood pressure, and cardiovascular disease), no major differences were found. The recorded frequency of stroke events in subgroups of the Copenhagen population was compatible with the estimated probability intervals of stroke from the Copenhagen City Heart Study and with those from the Framingham Study, but these intervals were very large. CONCLUSIONS: The majority of risk factors for stroke identified by the Framingham Study also had a significant effect in the Copenhagen City Heart Study population. The differences found could be due partly to different definitions of these factors used by the two studies. Although estimated stroke probabilities based on point systems from the Copenhagen City Heart Study and the Framingham Study were similar, the points scored in the two systems did not always correspond to the same combination of risk factors. Such systems can be used for estimating stroke probability in a given population, provided that the statistical confidence limits are known and the definitions of risk factors are compatible. However, because of the large statistical uncertainty, a prognostic index should not be applied for individual prediction unless it is used as an indicator of high relative risk associated with the simultaneous presence of several risk factors.

Adult↗
PubMedDate not supplied

An evaluation of clinicians' subjective prior probability estimates.

The degree of consensus and the accuracy of subjective prior probability estimates made by 104 clinicians were examined. The clinicians' estimates were compared with objective prior probabilities obtained from published sources and actual patient outcomes. Each clinician made seven estimates based upon written case summaries abstracted from patient records. Consensus was measured by calculating estimate ranges and standard deviations. The clinicians' estimates varied widely: the smallest range was 80 (2%-82%); four of the seven probability ranges were greater than 90. The average standard deviation was 19.5. Using these prior probabilities and Bayes' theorem, widely varying posttest probabilities would result after many common diagnostic tests. Accuracy was measured using the Brier score, which ranges from 0 to 1; a score of 0 indicates perfect accuracy. The clinicians' Brier scores ranged from 0.05 to 0.57. The objectively determined probabilities achieved a Brier score of 0.11, better than that of 96% of the clinicians. Clinical experience did not consistently affect estimate accuracy or consensus. The clinicians' subjective estimates were inaccurate measures of the prior probability of disease. There was little consensus regarding disease likelihood among the clinicians. Objective prior probabilities were more accurate and less variable.

Decision Making↗
PubMed1993

Stratification of patients according to prior cardiopulmonary disease and probability assessment based on the number of mismatched segmental equivalent perfusion defects. Approaches to strengthen the diagnostic value of ventilation/perfusion lung scans in acute pulmonary embolism.

A categorical diagnosis of "high probability" or "intermediate probability" encompasses a spectrum of diagnostic probabilities of pulmonary embolism (PE) that is not communicated to the referring physician. The diagnostic value of ventilation/perfusion lung scans, in the present investigation, was strengthened by use of a table to determine the likelihood of PE in individual patients on the basis of the observed number of mismatched segmental equivalent perfusion defects. In addition, we tested the hypothesis that stratification of patients according to the presence or absence of prior cardiopulmonary disease may enhance the ventilation/perfusion scan assessment of the probability of PE among both of these clinical categories of patients. Data were derived from the collaborative study of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). Ventilation/perfusion lung scans were evaluated in 378 patients with acute PE and 672 patients in whom suspected PE was excluded. Among patients with no prior cardiopulmonary disease, > or = 1.0 mismatched segmental equivalents was indicative of PE in 102 of 118 (86 percent) vs 113 of 155 (73 percent) among patients with prior cardiopulmonary disease (p < 0.02). Among patients with prior cardiopulmonary disease, > or = 2 mismatched segmental equivalents were required to indicate > or = 80 percent probability of PE. Stratification on the basis of the presence or absence of prior cardiopulmonary disease, therefore, enhanced the ability of ventilation/perfusion scan readers to assign an accurate positive predictive value and specificity to individual patients based on the observed number of mismatched segmental equivalent defects. Among patients with no prior cardiopulmonary disease, fewer mismatched segmental equivalent defects were required to indicate a high probability of PE than were required by PIOPED criteria. The findings from some of these patients, by PIOPED criteria, would have indicated intermediate probability. Some indeterminate probability readings, therefore, will be eliminated among patients stratified with no prior cardiopulmonary disease.

Acute Disease↗
PubMed2003

The modulation of simple reaction time by the spatial probability of a visual stimulus.

Simple reaction time (SRT) in response to visual stimuli can be influenced by many stimulus features. The speed and accuracy with which observers respond to a visual stimulus may be improved by prior knowledge about the stimulus location, which can be obtained by manipulating the spatial probability of the stimulus. However, when higher spatial probability is achieved by holding constant the stimulus location throughout successive trials, the resulting improvement in performance can also be due to local sensory facilitation caused by the recurrent spatial location of a visual target (position priming). The main objective of the present investigation was to quantitatively evaluate the modulation of SRT by the spatial probability structure of a visual stimulus. In two experiments the volunteers had to respond as quickly as possible to the visual target presented on a computer screen by pressing an optic key with the index finger of the dominant hand. Experiment 1 (N = 14) investigated how SRT changed as a function of both the different levels of spatial probability and the subject's explicit knowledge about the precise probability structure of visual stimulation. We found a gradual decrease in SRT with increasing spatial probability of a visual target regardless of the observer's previous knowledge concerning the spatial probability of the stimulus. Error rates, below 2%, were independent of the spatial probability structure of the visual stimulus, suggesting the absence of a speed-accuracy trade-off. Experiment 2 (N = 12) examined whether changes in SRT in response to a spatially recurrent visual target might be accounted for simply by sensory and temporally local facilitation. The findings indicated that the decrease in SRT brought about by a spatially recurrent target was associated with its spatial predictability, and could not be accounted for solely in terms of sensory priming.

Analysis of Variance↗
PubMed1985

Effects of stimulus probability and visual similarity on stimulus encoding.

Visual similarity, stimulus probability, and stimulus contrast were manipulated in two memory-scanning experiments to determine how stimulus probability affects encoding. Two hypotheses were tested: The first, a featural facilitation hypothesis, localizes the effect of stimulus probability on feature extraction; the second claims that stimulus probability has its effect on stimulus recognition. In both experiments, visual similarity was found to slow encoding, particularly under low-contrast conditions. This effect was larger for low probability stimuli than for high probability stimuli and increased as the difference in probability between two visually similar stimuli increased. These results are inconsistent with the featural facilitation hypothesis, but can be explained in terms of differential priming of internal recognition responses for members of the stimulus set, such that more probable members are more easily recognized.

Form Perception↗
PubMed2000

Protein fold recognition by total alignment probability.

We present a protein fold-recognition method that uses a comprehensive statistical interpretation of structural Hidden Markov Models (HMMs). The structure/fold recognition is done by summing the probabilities of all sequence-to-structure alignments. The optimal alignment can be defined as the most probable, but suboptimal alignments may have comparable probabilities. These suboptimal alignments can be interpreted as optimal alignments to the "other" structures from the ensemble or optimal alignments under minor fluctuations in the scoring function. Summing probabilities for all alignments gives a complete estimate of sequence-model compatibility. In the case of HMMs that produce a sequence, this reflects the fact that due to our indifference to exactly how the HMM produced the sequence, we should sum over all possibilities. We have built a set of structural HMMs for 188 protein structures and have compared two methods for identifying the structure compatible with a sequence: by the optimal alignment probability and by the total probability. Fold recognition by total probability was 40% more accurate than fold recognition by the optimal alignment probability. Proteins 2000;40:451-462.

Algorithms↗
PubMed2003

Probably benign lesions at breast magnetic resonance imaging: preliminary experience in high-risk women.

BACKGROUND: The purpose of the current study was to determine the frequency of 'probably benign' interpretations at breast magnetic resonance (MR) imaging screening of high-risk women and the frequency of subsequent malignancy in these women. METHODS: The authors performed a retrospective review of the records of 367 asymptomatic women with normal mammograms who had a high risk of developing breast cancer and whose first breast MR imaging screening examinations occurred during a 2-year period. The number of "probably benign" interpretations was determined, and follow-up data were obtained. RESULTS: A "probably benign" interpretation was given to 89 (24%) of 367 women. Follow-up MR imaging was performed for 70 (79%) of 89 women, with a median follow-up time of 11 months (range, 1-24 months). Twenty women subsequently underwent biopsy at a median of 9 months (range, 1-18 months) after MR imaging, due to progression on follow-up MR imaging (n=14) or for other reasons (n=6). Malignancies were found in 9 women, constituting 45% of the 20 women who underwent biopsy and 10% of the 89 women with probably benign lesions. In 6 of the 9 women who developed malignant disease (7% of the 89 women in the study), the malignancy was detected by follow-up MR imaging of an area that previously was interpreted as probably benign. Tumor histology was ductal carcinoma in situ (DCIS) in five patients and infiltrating ductal carcinoma in four. CONCLUSIONS: A "probably benign" interpretation was given to 24% of high-risk women at their first breast MR imaging screening examination. In 7-10% of women with "probably benign" interpretations, malignant disease subsequently developed in an area initially judged to be probably benign; of these malignancies, more than half were DCIS, and more than half were detected by MR imaging only.

Adult↗
PubMed2003

Assessment of clinical utility of 18F-FDG PET in patients with head and neck cancer: a probability analysis.

The purpose of this study was to calculate disease probabilities based on data of patients with head and neck cancer in the register of our institution and to perform a systematic review of the available data on the accuracy of PET in the primary assessment and follow-up of patients with head and neck cancer. The pre-test probability of head and neck cancer among patients in our institutional data registry was assessed. Then the published literature was selected and appraised according to a standard protocol of systematic reviews. Two reviewers independently selected and extracted data on study characteristics, quality and accuracy. Accuracy data were used to form 2 x 2 contingency tables and were pooled to produce summary receiver operating characteristic (ROC) curves and summary likelihood ratios for positive and negative testing. Finally post-test probabilities were calculated on the basis of the pre-test probabilities of this patient group. All patients had cytologically or histologically proven cancer. The prevalence of additional lymph node metastases on PET in staging examinations was 19.6% (11/56), and that of locoregional recurrence on restaging PET was 28.6% (12/42). In the primary assessment of patients, PET had positive and negative likelihood ratios of 3.9 (2.56-5.93) and 0.24 (0.14-0.41), respectively. Disease probabilities were therefore 49.4% for a positive test result and 5.7% for a negative test result. In the assessment of recurrence these values were 3.96 (2.8-5.6) and 0.16 (0.1-0.25), resulting in probabilities of 49.7% and 3.8%. PET evaluation for involvement of lymph nodes had positive and negative likelihood ratios of 17.26 (10.9-27.3) and 0.19 (0.13-0.27) for primary assessment and 11.0 (2.93-41.24) and 0.14 (0.01-1.88) for detection of recurrence. The probabilities were 81.2% and 4.5% for primary assessment and 73.3% and 3.4% for assessment of recurrence. It is concluded that in this clinical setting the main advantage of PET is the ability to reliably rule out the presence of disease in both staging and restaging. Further research is required to derive probabilities for individual patients from sequential testing as applied in the diagnostic work-up of patients with head and neck cancer.

Adult↗
PubMed1996

Determination of channel open probabilities from multichannel data.

We developed a method for determining whether channels in a multichannel patch or bilayer have the same or statistically significantly different open probabilities. We use a maximum likelihood method to fit the distribution of (unbinned) current amplitudes and to provide estimates of individual channel open probabilities, single channel currents, and standard deviations of the channel currents. These parameters are used to compare models with increasing constraints on the open probabilities including the model where all channels have different open probabilities and the model where all channels have the same open probability. A chi 2 statistic is used to identify models that are statistically less likely to predict the data. The ability of multichannel data to determine individual open probabilities is limited by two factors: the signal to noise ratio of the record and the fact that changes in amplitude distributions caused by a 0.2 difference in open probabilities are comparable in magnitude to the variations caused by random channel gating. These limitations notwithstanding, we demonstrate the utility of our approach by using it to analyze the open probabilities of 3 large conductance Ca2(+)-activated K+ channels in an artificial lipid bilayer revealing the response of one of those channels to GTP gamma S.

Ion Channels↗
PubMed2003

Definition of displacement probability and diffusion time in q-space magnetic resonance measurements that use finite-duration diffusion-encoding gradients.

In q-space diffusion NMR, the probability P(r,td) of a molecule having a displacement r in a diffusion time td is obtained under the assumption that the diffusion-encoding gradient g has an infinitesimal duration. However, this assumption may not always hold, particularly in human MRI where the diffusion-encoding gradient duration delta is typically of the same order of magnitude as the time offset Delta between encoding gradients. In this case, finite-delta effects complicate the interpretation of displacement probabilities measured in q-space MRI, and the form by which the signal intensity relates to them. By considering the displacement-specific dephasing, , of a set of spins accumulating a constant displacement vector r in the total time Delta+delta during which diffusion is encoded, the probability recovered by a finite-delta q-space experiment can be interpreted. It is shown theoretically that a data analysis using a modified q-space index q=gammadeltaetag, with gamma the gyromagnetic ratio and eta=square root (Delta-delta/3)/(Delta+delta), recovers the correct displacement probability distribution if diffusion is multi-Gaussian free diffusion. With this analysis, we show that the displacement distribution P(r,texp) is measured at the experimental diffusion-encoding time texp=Delta+delta, and not at the reduced diffusion time tr=Delta-delta/3 as is generally assumed in the NMR and MRI literature. It is also shown that, by defining a probability P(y,Delta) that a time t deltac then eta is not equal to square root (Delta-delta/3)/(Delta+delta) which implies that we can no longer obtain the correct displacement probability from the displacement distribution. In the case that /g/=18 mT/m and Delta-delta=5 ms, the parameter deltac in ms is given by "deltac=0.49a2+0.24" where a is the sphere's radius expressed in microm. Simulation of q-space restricted diffusion MRI experiments indicate that if eta=square root (Delta-delta/3)/(Delta+delta), the recovered displacement probability is always better than the Gaussian approximation, and the measured diffusion coefficient matches the diffusion coefficient at time texp=Delta+delta better than it matches the diffusion coefficient at time tr=Delta-delta/3. These results indicate that q-space MRI measurements of displacement probability distributions are theoretically possible in biological tissues using finite-duration diffusion-encoding gradients provided certain compartment size and diffusion encoding gradient duration constraints are met.

Journal Article↗
PubMed2002

Inhibition, response mode, and stimulus probability: a comparative event-related potential study.

OBJECTIVES: In the present study, effects of response mode (finger movement or counting) and stimulus probability on inhibitory processes were studied. METHODS: Electroencephalographic activity was registered in a visual go/nogo paradigm. Subjects either responded manually to go stimuli or counted silently the occurrence of each go stimulus in different conditions. In both response mode conditions, response probability was varied. RESULTS: For finger movement and counting, similar N2 and P3 go/nogo effects were found. The amplitude of the nogo N2 and nogo P3 varied as a negative function of nogo stimulus probability. The go P3 varied as a negative function of go stimulus probability. In the manual condition, however, the descending flank of the go N2 at anterior electrode sites was more negative in the 0.50go and 0.75go probability trials than in the 0.25go probability trials. CONCLUSIONS: The results of the present study confirm the hypothesis that differences between go and nogo event-related potentials are not dependent on overt movement-related potentials. It could be speculated that the probability effect on the N2 amplitude in go trials in the manual condition has to be explained in terms of a modulation of the strength of motoric preparation processes varying as a positive function of the probability of the go stimulus.

Adult↗
PubMed2002

The effect of stimulus probability on P3 in the respiratory-related evoked potential.

The present study investigated the effect of target stimulus probability on the P3 component of the respiratory-related evoked potential (RREP). A single respiratory stimulus paradigm was employed where normal breaths served as standard stimuli and occluded breaths presented at various probability levels served as target stimuli. EEG was recorded from 29 channels in young adults in two conditions. In Condition 1, occlusions were presented at target probabilities of 0.5, 0.33, 0.25, 0.2, 0.1, and 0.05, that is, every 2nd, 3rd, 4th, 5th, 10th, and 20th breath. Order of target probability presentation varied randomly. Condition 2 used the same target probabilities, but held breathing rate constant by using a paced respiration task. Results indicated that P3 amplitude was significantly affected by stimulus probability, such that the component showed an inverse relationship with probability. This effect was similar between conditions. However, P3 amplitude reduced and latency increased when the secondary task of paced respiration was introduced. These data suggest that models developed to describe the effect of stimulus probability on the amplitude of visual and auditory P3 components are applicable to the respiratory somatosensory modality.

Adult↗
PubMed1978

Reaction time and probability on isolated terms.

The reaction-time probability effect on isolated trials was found to be asymmetrical in an experiment on 64 college students. There was a large drop in RT for a high-probability probe trial embedded in a block of low-probability trials, but a much smaller rise for a low-probability trial embedded in high-probability trials. Thus, low- but not high-probability responses seem to be influenced by characteristics of the trial block. If the basis of the probability effect were the strategic placement of the criterion for response initiation, symmetrical results should have been obtained. A motivational account which accords with the present data is that the subject is ordinarily willing to prepare but is averse to doing so in some (not entirely specified) low-probability circumstances.

Journal Article↗
PubMed2004

Probabilities of spurious connections in gene networks: application to expression time series.

MOTIVATION: The reconstruction of gene networks from gene-expression microarrays is gaining popularity as methods improve and as more data become available. The reliability of such networks could be judged by the probability that a connection between genes is spurious, resulting from chance fluctuations rather than from a true biological relationship. RESULTS: Unlike the false discovery rate and positive false discovery rate, the decisive false discovery rate (dFDR) is exactly equal to a conditional probability without assuming independence or the randomness of hypothesis truth values. This property is useful not only in the common application to the detection of differential gene expression, but also in determining the probability of a spurious connection in a reconstructed gene network. Estimators of the dFDR can estimate each of three probabilities: (1) The probability that two genes that appear to be associated with each other lack such association. (2) The probability that a time ordering observed for two associated genes is misleading. (3) The probability that a time ordering observed for two genes is misleading, either because they are not associated or because they are associated without a lag in time. The first probability applies to both static and dynamic gene networks, and the other two only apply to dynamic gene networks.

Algorithms↗
PubMed1997

Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history.

BACKGROUND: Heritable mutations of the breast cancer gene BRCA1 are rare, occurring in fewer than 1% of women in the general population, and therefore account for a small proportion of cases of breast and ovarian cancers. Nevertheless, the presence of such mutations is highly predictive of the development of these cancers. PURPOSE: We developed and applied a mathematic model for calculating the probability that a woman with a family history of breast and/or ovarian cancer carries a mutation of BRCA1. METHODS AND RESULTS: As a basis for the model, we use Mendelian genetics and apply Bayes' theorem to information on the family history of these diseases. Of importance are the exact relationships of all family members, including both affected and unaffected members, and ages at diagnosis of the affected members and current ages of the unaffected members. We used available estimates of BRCA1 mutation frequencies in the general population and age-specific incidence rates of breast and ovarian cancers in carriers and noncarriers of mutations to estimate the probability that a particular member of the family carries a mutation. This probability is based on cancer statuses of all first- and second-degree relatives. We first describe the model by considering single individuals: a woman diagnosed with breast and/or ovarian cancer and also a woman free of cancer. We next considered two artificial and two actual family histories and addressed the sensitivity of our calculations to various assumptions. Particular relationships of family members with and without cancer can have a substantial impact on the probability of carrying a susceptibility gene. Ages at diagnosis of affected family members and their types of cancer are also important. A woman with two primary cancers can have a probability of carrying a mutation in excess of 80%, even with no other information about family history. The number and relationships of unaffected members, along with their current ages or ages at death, are critical determinants of one's carrier probability. An affected woman with several cancers in her family can have a probability of carrying a mutation that ranges from close to 100% to less than 5%. CONCLUSION: Our model gives informative and specific probabilities that a particular woman carries a mutation. IMPLICATIONS: This model focuses on mutations in BRCA1 and assumes that all other breast cancer is sporadic. With the cloning of BRCA2, we now know that this assumption is incorrect. We have adjusted the model to include BRCA2, but the use of this version must await publication of penetrance data for BRCA2, including those for male breast cancer that are apparently associated with BRCA2 but not with BRCA1. The current model is, nevertheless, appropriate and useful. Of principal importance is its potential and that of improved versions for aiding women and their health care providers in assessing the need for genetic testing.

Adult↗
PubMed2001

Rapid D-dimer testing and pre-test clinical probability in the exclusion of deep venous thrombosis in symptomatic outpatients.

We assessed the performance of three rapid D-dimer tests (Auto Dimertest, VIDAS and Tinaquant) in combination with a pretest clinical probability model for deep venous thrombosis (DVT) in 106 consecutive outpatients with suspected DVT. Contrast venography or colour-coded duplex ultrasonography demonstrated the presence of DVT in 47 patients (14 distal DVT and 33 proximal DVT). First, we assessed the accuracy indices for different cut-off levels of the rapid D-dimer tests. Sensitivity was found to be 97.9-100%, negative predictive value (NPV) was 96.3-100%, and the exclusion rate was 24.5-31.1%. Next, the patients were grouped according to the pre-test clinical probability model in categories with low, moderate or high probability. In patients with a low pre-test probability, DVT would have been directly ruled out and the patients would not have undergone further investigations. In patients with a moderate probability, D-dimer testing and, in the case of a positive result, objective testing would have been performed and, in the case of a negative result, they would have been ruled out of having DVT. Patients with high probability would directly have undergone objective tests for DVT. The combination with the pre-test clinical probability model improved the exclusion rate (43.5-44.6%), whereas sensitivity (97.5-100%) and NPV (97.6-100%) remained roughly unchanged. The combination of rapid D-dimer tests with a pre-test clinical probability model may help to reduce unnecessary work-up in patients with suspected DVT.

Adolescent↗
PubMed1994

An algorithm for Monte Carlo estimation of genotype probabilities on complex pedigrees.

Exact probability and likelihood computation on complex pedigrees is often infeasible, since exact methods are too computationally intensive even with today's computing technology. A statistical tool, Markov chain Monte Carlo (MCMC), is increasingly being explored as a technique for estimating probabilities of genotypic configurations on pedigrees conditional on phenotypic data. However, this conditional probability distribution on a complex pedigree is, in general, multimodal, and multimodality is one of the major difficulties in MCMC exploration of a probability surface. In this paper, a new member of the MCMC Metropolis-Hastings class of algorithms is proposed; the heated-Metropolis algorithm. The algorithm achieves passage through low probability states to other local modes of the probability distribution, and so provides much improved estimates of probabilities of interest. The example considered is the estimation of the probabilities of carrier genotype for the founders of a complex pedigree in which a very rare lethal recessive trait is segregating.

Algorithms↗