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PubMed1997

Heritability of epileptic seizures in the Belgian tervueren.

Survey data were collected on the incidence of epileptic seizures in 997 Belgian tervuerens. The heritability of this disorder was estimated as 0.77 (with a 95 per cent confidence interval spanning from 0.65 to 0.88) using a Bayesian analysis in an ordered categorical threshold model. Single locus models do not appear adequate as an explanation for this inherited seizure disorder. The high heritability estimate suggests that breeders can wage a successful battle against this disorder by breeding unaffected individuals, particularly those from families with no history of seizures.

Age Factors↗

PubMed2005

The sensitivity and specificity of single manual examination tests for detection of corpora lutea in the ovaries of non-cycling cows.

OBJECTIVE: To evaluate the sensitivity and specificity of single manual examination of ovarian surface structures and of ovarian size as tests for the detection of corpora lutea in non-cycling cows DESIGN: Non cycling cows were dichotomously classified for the presence of palpable corpora lutea and for ovarian size. The performance characteristics of the palpable corpus luteum test and the ovarian size test were estimated using Bayesian analysis. Previously published information on prevalence and test performance was combined with observed data using the Gibbs Sampler to derive posterior distributions for prevalence and test parameters. RESULTS: Prior distributions for the prevalence of corpora lutea in cows not detected on heat before mating within seasonal herds were centred on 25%, and for the corpus luteum test sensitivity were centred on 70%. No prior assumptions for any other test parameter were made. From a total of 650 cows, 144 were found to have at least one corpus luteum, and 156 were found to have two small ovaries. The posterior estimate obtained for prevalence was 0.30 (95% Cl 0.22 to 0.43), for corpus luteum test sensitivity was 0.71 (95% Cl 0.49 to 0.93), and for corpus luteum test specificity was 0.98 (95% Cl 0.49 to 1.00). For the ovarian size test, the posterior estimate for size test sensitivity was 0.98 (95% Cl 0.95 to 1.00) and for size test specificity was 0.34 (95% CI 0.28 to 0.43). Sensitivity analysis indicated that corpus luteum test sensitivity ranged from 0.60 to 0.70 in most herds. CONCLUSIONS: Errors associated with pre-mating heat detection are likely to result in between 15 to 30% of cycling cows not detected in oestrous before mating, resulting in the inclusion of cycling cows within the population of non-cycling cows. This mixed population of cows is then subjected to manual examination by veterinarians in order to assign cows to treatment groups. The corpus luteum test has modest sensitivity and high specificity and the size test has high sensitivity and low specificity. Therefore the use of a single examination of the ovaries of cows not detected on heat before the mating period, in order to classify them as anovulatory anoestrous cows with or without a corpus luteum, is not sufficient to accurately classify them and thus to recommend treatment.

Animals↗

PubMed2006

Low-level otoacoustic emissions may predict susceptibility to noise-induced hearing loss.

In a longitudinal study with 338 volunteers, audiometric thresholds and otoacoustic emissions were measured before and after 6 months of noise exposure on an aircraft carrier. While the average amplitudes of the otoacoustic emissions decreased significantly, the average audiometric thresholds did not change. Furthermore, there were no significant correlations between changes in audiometric thresholds and changes in otoacoustic emissions. Changes in transient-evoked otoacoustic emissions and distortion-product otoacoustic emissions were moderately correlated. Eighteen ears acquired permanent audiometric threshold shifts. Only one-third of those ears showed significant otoacoustic emission shifts that mirrored their permanent threshold shifts. A Bayesian analysis indicated that permanent threshold shift status following a deployment was predicted by baseline low-level or absent otoacoustic emissions. The best predictor was transient-evoked otoacoustic emission amplitude in the 4-kHz half-octave frequency band, with risk increasing more than sixfold from approximately 3% to 20% as the emission amplitude decreased. It is possible that the otoacoustic emissions indicated noise-induced changes in the inner ear, undetected by audiometric tests. Otoacoustic emissions may therefore be a diagnostic predictor for noise-induced-hearing-loss risk.

Adolescent↗

PubMed2007

Evolutionary relationships of "Candidatus Riesia spp.," endosymbiotic enterobacteriaceae living within hematophagous primate lice.

The primary endosymbiotic bacteria from three species of parasitic primate lice were characterized molecularly. We have confirmed the characterization of the primary endosymbiont (P-endosymbiont) of the human head/body louse Pediculus humanus and provide new characterizations of the P-endosymbionts from Pediculus schaeffi from chimpanzees and Pthirus pubis, the pubic louse of humans. The endosymbionts show an average percent sequence divergence of 11 to 15% from the most closely related known bacterium "Candidatus Arsenophonus insecticola." We propose that two additional species be added to the genus "Candidatus Riesia." The new species proposed within "Candidatus Riesia" have sequence divergences of 3.4% and 10 to 12% based on uncorrected pairwise differences. Our Bayesian analysis shows that the branching pattern for the primary endosymbionts was the same as that for their louse hosts, suggesting a long coevolutionary history between primate lice and their primary endosymbionts. We used a calibration of 5.6 million years to date the divergence between endosymbionts from human and chimpanzee lice and estimated an evolutionary rate of nucleotide substitution of 0.67% per million years, which is 15 to 30 times faster than previous estimates calculated for Buchnera, the primary endosymbiont in aphids. Given the evidence for cospeciation with primate lice and the evidence for fast evolutionary rates, this lineage of endosymbiotic bacteria can be evaluated as a fast-evolving marker of both louse and primate evolutionary histories.

Animals↗

PubMed1972

Computer-aided diagnosis: description of an adaptable system, and operational experience with 2,034 cases.

This paper describes a system of computer-aided diagnosis using an English Electric KDF9 computer linked to a terminal in a busy clinical department. Data from a series of patients were recorded, coded, and entered into the computer, which then performed a Bayesian analysis and displayed diagnostic probabilities in an adaptable format. Experience in this setting suggests that computer diagnosis may be a valuable aid to the clinician.

Abdomen↗

PubMed1996

The statistical basis of public policy: a paradigm shift is overdue.

The recent controversy over the increased risk of venous thrombosis with third generation oral contraceptives illustrates the public policy dilemma that can be created by relying on conventional statistical tests and estimates: case-control studies showed a significant increase in risk and forced a decision either to warn or not to warn. Conventional statistical tests are an improper basis for such decisions because they dichotomise results according to whether they are or are not significant and do not allow decision makers to take explicit account of additional evidence--for example, of biological plausibility or of biases in the studies. A Bayesian approach overcomes both these problems. A Bayesian analysis starts with a "prior" probability distribution for the value of interest (for example, a true relative risk)--based on previous knowledge--and adds the new evidence (via a model) to produce a "posterior" probability distribution. Because different experts will have different prior beliefs sensitivity analyses are important to assess the effects on the posterior distributions of these differences. Sensitivity analyses should also examine the effects of different assumptions about biases and about the model which links the data with the value of interest. One advantage of this method is that it allows such assumptions to be handled openly and explicitly. Data presented as a series of posterior probability distributions would be a much better guide to policy, reflecting the reality that degrees of belief are often continuous, not dichotomous, and often vary from one person to another in the face of inconclusive evidence.

Attitude to Health↗

PubMed2006

Comparison of paediatric major incident primary triage tools.

OBJECTIVES: To determine the sensitivity and specificity of paediatric major incident triage scores. The Paediatric Triage Tape (PTT), Careflight, Simple Triage and Rapid Treatment (START), and JumpSTART systems were tested. METHODS: In total, 3461 children presenting to a South African emergency department with trauma were scored using the four different methods. The sensitivity and specificity of the four scores was calculated against the Injury Severity Score (ISS), New ISS (NISS), and a modification of the Garner criteria (a measure of need for urgent clinical intervention). We also performed a Bayesian analysis of the scores against three different types of major incident. RESULTS: None of the tools showed high sensitivity and specificity. Overall, the Careflight score had the best performance in terms of sensitivity and specificity. The performance of the PTT was very similar. In contrast, the JumpSTART and START scores had very low sensitivities, which meant that they failed to identify patients with serious injury, and would have missed the majority of seriously injured casualties in the models of major incidents. CONCLUSION: The Careflight or PTT methods of triage should be used in paediatric major incidents in preference to the jumpSTART or START methods.

Algorithms↗

PubMed1985

Detection of high risk coronary artery disease by thallium imaging.

One hundred and three patients who underwent coronary arteriography were studied by thallium imaging and the results analysed by Bayesian principles to assess the usefulness of semiquantitative stress thallium imaging for predicting the presence or absence of multivessel coronary disease. Significant disease was found in 80 patients, of whom 77 had abnormal thallium scans (sensitivity 96%). Thallium images were normal in 15 of 23 patients with no significant disease (specificity 65%). Multiple thallium segmental defects were found to be 90% sensitive and 65% specific for multivessel coronary artery disease and were present in 80% of patients with left main stem disease and in 93% of patients with triple vessel disease. A single thallium defect or normal scan excluded multivessel, left main, and triple vessel disease with 81%, 94%, and 91% predictive accuracy respectively. By Bayesian analysis the predictive accuracy for excluding multivessel disease was greater than 90% in patients with a pretest probability of multivessel disease of less than or equal to 40%. Coronary arteriography to exclude multivessel disease is therefore unnecessary in a high proportion of patients with known or suspected coronary artery disease.

Adult↗

PubMed2005

Incidence of sports and recreation related injuries resulting in hospitalization in Wisconsin in 2000.

OBJECTIVE: To describe the incidence and patterns of sports and recreation related injuries resulting in inpatient hospitalization in Wisconsin. Although much sports and recreation related injury research has focused on the emergency department setting, little is known about the scope or characteristics of more severe sports injuries resulting in hospitalization. SETTING: The Wisconsin Bureau of Health Information (BHI) maintains hospital inpatient discharge data through a statewide mandatory reporting system. The database contains demographic and health information on all patients hospitalized in acute care non-federal hospitals in Wisconsin. METHODS: The authors developed a classification scheme based on the International Classification of Diseases External cause of injury code (E code) to identify hospitalizations for sports and recreation related injuries from the BHI data files (2000). Due to the uncertainty within E codes in specifying sports and recreation related injuries, the authors used Bayesian analysis to model the incidence of these types of injuries. RESULTS: There were 1714 (95% credible interval 1499 to 2022) sports and recreation-related injury hospitalizations in Wisconsin in 2000 (32.0 per 100,000 population). The most common mechanisms of injury were being struck by/against an object in sports (6.4 per 100,000 population) and pedal cycle riding (6.2 per 100,000). Ten to 19 year olds had the highest rate of sports and recreation related injury hospitalization (65.3 per 100,000 population), and males overall had a rate four times higher than females. CONCLUSIONS: Over 1700 sports and recreation related injuries occurred in Wisconsin in 2000 that were treated during an inpatient hospitalization. Sports and recreation activities result in a substantial number of serious, as well as minor injuries. Prevention efforts aimed at reducing injuries while continuing to promote participation in physical activity for all ages are critical.

Adolescent↗

PubMed1977

Alpha1-fetoprotein in the diagnosis of hepatoma: statistical and cost benefit aspects.

A rational comparison of different serum concentrations of alpha1-fetoprotein (S-AFP) in the diagnosis of hepatoma must be made. We took data on the sensitivity and specificity of different diagnostic S-AFP concentrations from the literature and evaluated them statistically and by Bayesian analysis. In our patients (hepatoma prevalence 0.028) a sensitive diagnostic concentration (30-50 ng/ml) will misdiagnose hepatoma so often that a positive test will indicate hepatoma in only 10% of cases. A positive test at a specific diagnostic concentration (500 ng/ml) indicates hepatoma in 100% of cases and is preferable in terms of cost benefit. Although the lower concentration will diagnose a larger proportion of patients with hepatoma (74% compared with 59%) the 'costs' of excluding false positives are considerable (A$2545 per extra case with 2.5% of patients suffering significant morbidity). In western societies, where the prevalence of hepatoma is low, a higher, less sensitive but more specific diagnostic S-AFP concentration is appropriate.

Carcinoma, Hepatocellular↗

PubMed2006

Alpha-1-antitrypsin deficiency: optimal therapeutic regimen based on population pharmacokinetics.

BACKGROUND: Exogenous doses of 60 mg/kg alpha(1)-antitrypsin (AAT) every 7 days are recommended in patients with severe AAT deficiency. However, long term administration of weekly doses is not well accepted by patients. Using pharmacokinetic simulations, we evaluated whether steady state minimum concentrations of total AAT can be maintained above the threshold of 0.5 g/l with longer intervals between doses. METHODS: Several sets of exogenous AAT versus time simulations were studied using a non-linear mixed effect approach with dosage regimens every 7, 14, 21, and 28 days. For each regimen the mean exogenous AAT trough concentrations and 5/95th percentiles were determined. The results obtained were applied to estimate the individual optimal dose at 7, 14, and 21 days in six patients using Bayesian analysis. RESULTS: The simulations showed that a dose of 50 mg/kg AAT every 7 days was sufficient to obtain nadir concentrations. Doses of 120 and 100 mg/kg every 14 days were also adequate, but 180 mg/kg given every 21 days required total AAT monitoring to avoid underdosage. Longer intervals were inappropriate. Dosage individualisation confirmed that AAT infusions given every 14 days maintained the nadir level of 0.5 g/l without a significant dose increase compared with current practice. When the time span between doses was fixed at 21 days, a mean relative AAT dose enhancement of 91% and 13%, respectively, was required to achieve sustained total AAT concentrations above the target level for 100% and 85% of the interval between doses. CONCLUSIONS: It is feasible to extend the interval between doses of AAT to 14 or 21 days to achieve adequate trough total AAT concentrations. This study might be used as a starting point for clinical evaluation of the regimens described.

Aged↗

PubMedDate not supplied

Solitary pulmonary nodules: Part II. Evaluation of the indeterminate nodule.

Various strategies may be used to evaluate indeterminate solitary pulmonary nodules. Growth rate assessment is an important and cost-effective step in the evaluation of these nodules. Clinical features (eg, patient age, history of prior malignancy, presenting symptoms, smoking history) can be useful in suggesting the diagnosis and aiding in management planning. Bayesian analysis allows more precise determination of the probability of malignancy (pCa). Decision analysis models suggest that the most cost-effective management strategy depends on the pCa for a given nodule. At contrast material-enhanced computed tomography, nodular enhancement of less than 15 HU is strongly predictive of a benign lesion, whereas enhancement of more than 20 HU typically indicates malignancy. At 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography, lesions with low FDG uptake are typically benign, whereas those with increased FDG uptake are typically malignant. Results of transthoracic needle aspiration biopsy influence management in approximately 50% of cases and, in indeterminate lesions with a pCa between 0.05 and 0.6, is the best initial diagnostic procedure. It is optimally used in peripheral nodules and has been reported to establish a benign diagnosis in up to 91% of cases. Although there is no one correct management approach, the ability to distinguish benign from malignant solitary pulmonary lesions has improved with the use of these strategies.

Bayes Theorem↗

PubMedDate not supplied

Solitary pulmonary nodules: Part I. Morphologic evaluation for differentiation of benign and malignant lesions.

The solitary pulmonary nodule is a common radiologic abnormality that is often detected incidentally. Although most solitary pulmonary nodules have benign causes, many represent stage I lung cancers and must be distinguished from benign nodules in an expeditious and cost-effective manner. Evaluation of specific morphologic features of a solitary pulmonary nodule with conventional imaging techniques can help differentiate benign from malignant nodules and obviate further costly assessment. Small size and smooth, well-defined margins are suggestive of but not diagnostic for benignity. Lobulated contour as well as an irregular or spiculated margin with distortion of adjacent vessels are typically associated with malignancy. There is considerable overlap in the internal characteristics (eg, attenuation, cavitation, wall thickness) of benign and malignant nodules. The presence of intranodular fat is a reliable indicator of a hamartoma. The presence and pattern of calcification can also help differentiate benign from malignant nodules. Computed tomography (CT) (particularly thin-section CT) is 10-20 times more sensitive than standard radiography and allows objective, quantitative assessment of calcification. Initial evaluation often results in nonspecific findings, in which case nodules are classified as indeterminate and require further evaluation to exclude malignancy. Growth rate assessment, Bayesian analysis, contrast material-enhanced CT, positron emission tomography, and transthoracic needle aspiration biopsy can be useful in this regard.

Biopsy, Needle↗

PubMed2005

Differential gene expression in pulmonary artery endothelial cells exposed to sickle cell plasma.

Clinical variability in sickle cell disease (SCD) suggests a role for extra-erythrocytic factors in the pathogenesis of vasoocclusion. We hypothesized that endothelial cell (EC) dysfunction, one possible modifier of disease variability, results from induction of phenotypic changes by circulating factors. Accordingly, we analyzed gene expression in cultured human pulmonary artery ECs (HPAEC) exposed to plasma from 1) sickle acute chest syndrome (ACS) patients, 2) SCD patients at steady state, 3) normal volunteers, and 4) serum-free media, using whole genome microarrays (U133A-B GeneChip, Affymetrix). Data were analyzed by Bayesian analysis of differential gene expression (BADGE). Differential expression was defined by the probability of >1.5 fold change in signal intensity greater than 0.999 and a predicted score of 70-100, measured by cross-validation. Compared with normal plasma, plasma from SCD patients (steady state) resulted in differential expression of 50 genes in HPAEC. Of these genes, molecules involved in cholesterol biosynthesis and lipid transport, the cellular stress response, and extracellular matrix proteins were most prominent. Another 58 genes were differentially expressed in HPAEC exposed to plasma from ACS patients. The pattern of altered gene expression suggests that plasma from SCD patients induces an EC phenotype which is anti-apoptotic and favors cholesterol biosynthesis. An altered EC phenotype elicited by SCD plasma may contribute to the pathogenesis of sickle vasoocclusion.

Anemia, Sickle Cell↗

PubMed2004

Are ATM mutations 7271T-->G and IVS10-6T-->G really high-risk breast cancer-susceptibility alleles?

Two mutations of the ATM gene were recently suggested to confer breast cancer risks similar to mutations of BRCA1 or BRCA2. Here, we set out to confirm these findings in 961 families with non-BRCA1/BRCA2 breast cancer from diverse geographical regions. We did not detect the ATM 7271T-->G mutation in any family. The ATM IVS10-6T-->G mutation was detected in eight families, which was similar to its frequency among population-matched control individuals (pooled Mantel-Haenszel odds ratio = 1.60; 95% confidence interval = 0.48 to 5.35; P = 0.44). Bayesian analysis of linkage in the ATM IVS10-6T-->G-positive families showed an overall posterior probability of causality for this mutation of 0.008. We conclude that the ATM IVS10-6T-->G mutation does not confer a significantly elevated breast cancer risk and that ATM 7271T-->G is a rare event in familial breast cancer.

Alleles↗

PubMed2003

Chronic nephropathies: individual risk for progression to end-stage renal failure as predicted by an integrated probabilistic model.

BACKGROUND/AIMS: To predict risk of end-stage renal disease (ESRD) in individual patients with chronic nephropathy. METHODS: Sequential use of univariate analyses and Cox regression to identify risk factors, artificial neural network to quantify their relative importance and Bayesian analysis to address uncertainty of relationships and incorporate ESRD prevalence information in 344 patients with chronic nephropathy enrolled in the Ramipril Efficacy In Nephropathy study. RESULTS: Serum creatinine (SC), 24-hour urinary protein excretion (UPE) and calcium-phosphorus (Ca*P) product were, in this order, the strongest time-adjusted ESRD predictors. Individual risk of ESRD ranged from near zero when SC and UPE were <1.66 mg/dl and <3 g/24 h, to 69% when SC, UPE and Ca*P were > or =2.41 mg/dl, > or =3 g/24 h and > or =32.64 mg2/dl2, respectively. Receiver operating characteristic curves showed that within lowest, middle and highest tertiles of basal SC (0.90-1.65, 1.66-2.40 and 2.41-6.30 mg/dl, respectively) the model accurately predicted ESRD (AUC = 0.80, 0.72 and 0.65; p = 0.0003, 0.0001 and 0.0022, respectively), quality of life or treatment costs. CONCLUSION: Integrated use of regression analysis and probabilistic models allows computation of individual risk of progression to ESRD and related utilities. This may help in optimizing care and costs in nephrology and other medical areas and designing trials in high-risk patients.

Analysis of Variance↗

PubMed2006

Color and genomic ancestry in Brazilians: a study with forensic microsatellites.

The population of Brazil, formed by extensive admixture between Amerindians, Europeans and Africans, is one of the most variable in the world. We have recently published a study that used ancestry-informative markers to conclude that in Brazil, at an individual level, color, as determined by physical evaluation, was a poor predictor of genomic ancestry, estimated by molecular markers. To corroborate these findings we undertook the present investigation based on data from 12 commercially available forensic microsatellites that were utilized to estimate the personal genomic origin for each of 752 individuals from the city of São Paulo, belonging to different Brazilian color categories (275 Whites, 192 Intermediates and 285 Blacks). The genotypes permitted the calculation of a personal likelihood-ratio estimator of African or European ancestry. Although the 12 marker set proved capable of discriminating between European and African individuals, we observed very significant overlaps among the three color categories of Brazilians. This was confirmed quantitatively using a Bayesian analysis of population structure that did not demonstrate significant genetic differentiation between the three color groups. These results corroborate and validate our previous conclusions using ancestry-informative markers that in Brazil at the individual level there is significant dissociation of color and genomic ancestry.

Black People↗

PubMed1984

Embolic potential of left ventricular thrombi detected by two-dimensional echocardiography.

We sought to determine whether an association existed between the echocardiographic appearance of left ventricular thrombi and systemic embolization. We reviewed the clinical and echocardiographic characteristics of 60 patients who underwent diagnostic two-dimensional echocardiography for left ventricular thrombi. Sixteen of these 60 patients (27%) had evidence of systemic embolization. Multiple echocardiographic characteristics of left ventricular thrombi were analyzed, including mobility, shape, heterogeneity, echo density, layering, central echo lucency, presence within an aneurysm, and association with low-density swirling echoes. Incidence of embolization was significantly higher in patients with thrombi that were mobile or protruded into the left ventricular cavity (p less than .002 and p less than .05, respectively). Bayesian analysis indicated that the pretest likelihood for embolization was 27% and increased in the presence of mobility, central echo lucency, and protrusion to 60%, 50%, and 40%, respectively. A stepwise regression indicated that mobility was the first and protrusion the second most helpful echocardiographic characteristic in identifying patients with embolic phenomena. Clinical features were of less help in identifying the risk for embolization of patients with left ventricular thrombi. Nine of 31 patients (29%) with recent myocardial infarction (less than 3 weeks) has emboli in contrast to five of 26 patients (19%) with remote myocardial infarction (greater than 3 weeks) (p = NS). The three patients without infarction had congestive cardiomyopathy and two had emboli.

Echocardiography↗