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Diagnostic accuracy of noninvasive fetal Rh genotyping from maternal blood--a meta-analysis.

OBJECTIVE: The purpose of this study was to determine the reported diagnostic accuracy, the validity, and the current limitations of fetal Rh genotyping from peripheral maternal blood based on the existing English-written publications. STUDY DESIGN: A search of the English literature describing fetal RhD determination from maternal blood was conducted. From each study, we determined the number of samples tested, fetal RhD genotype, the source of the fetal DNA (maternal plasma, serum, or fetal cells), gestational age, and confirmation of fetal Rh type. The presence of alloimmunization and exclusions of tested samples were noted. For the meta-analysis we calculated composite estimates using 2 random effects models, weighted GLM and Bayesian. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: We identified 37 English-written publications that included 44 protocols reporting noninvasive Rh genotyping using fetal DNA obtained from maternal blood on a total of 3261 samples. A total of 183 (183/3261, 5.6%) samples were excluded from the meta-analysis. The overall diagnostic accuracy after exclusions was 94.8%. The gestational ages ranged between 8 and 42 weeks gestation. Maternal serum and plasma were found to be the best source for accurate diagnosis of fetal RhD type in 394/410 (96.1%) and 2293/2377 (96.5%), respectively. There were 719/783 (91.8%) alloimmunized patients that were correctly diagnosed. There were 16 studies that reported 100% diagnostic accuracy in their fetal RhD genotyping. CONCLUSION: The diagnostic accuracy of noninvasive fetal Rh determination using maternal peripheral blood is 94.8%. Its use can be applicable to Rh prophylaxis and to the management of Rh alloimmunized pregnancies. Improvements of the technique and further study of structure and rearrangements of the RhD gene may improve accuracy of testing and enable large-scale, risk-free fetal RhD genotyping using maternal blood.

DNA↗

Decision support of inspired oxygen selection based on Bayesian learning of pulmonary gas exchange parameters.

OBJECTIVE: To investigate if the real-time Bayesian learning of physiological model parameters can be used to support and improve the selection of inspired oxygen fraction. METHODS AND MATERIAL: Supporting the selection of inspired oxygen fraction relies on predictions of arterial oxygen saturation. The efficacy of using these predictions to select inspired oxygen was tested retrospectively in a system for estimating gas exchange parameters of the lung (Automatic Lung Parameter Estimator, ALPE). For the predictions to offer effective decision support they need to be accurate and above all safe. These qualities were tested with data from 16 post-operative cardiac patients, using two different tests. The aim of the first test was to assess retrospectively if the predictions could have supported clinical decisions. The second test sought to establish if the predictions could support improving the efficiency of inspired oxygen selection during an ALPE oxygen titration. RESULTS: The predictions were found to be reasonably accurate, and most importantly safe in both of the tests. CONCLUSION: The method described can be used to support the selection of inspired oxygen fraction, and it has the potential to improve the efficiency of inspired oxygen selection during an oxygen titration.

Bayes Theorem↗

Relationship of P300 single-trial responses with reaction time and preceding stimulus sequence.

Variation of single-trial P300 responses was studied both in relation to reaction times and to the preceding stimulus sequence in an auditory oddball paradigm. Single-trial responses were estimated with the Subspace regularization method that is based on Bayesian estimation and linear modeling. The results of the single-trial method were compared to those of averaging. Both methods showed that the latency of the P300 was shorter and its amplitude larger for faster than slower reaction times. The P300 latency was shorter for target tones that were preceded by a large number of standard tones compared to those preceded by a small number of standard tones. The P300 amplitude was statistically significantly affected by the stimulus sequence only when analyzed with conventional averaging. In-depth analysis of standard deviations showed that the variability of the P300 single-trial latencies could explain the differences between the two methods. Specifically, the regression analysis showed that the latency correlated negatively with the number of preceding standard tones and positively with the reaction time, whereas the P300 amplitude correlated positively with the number of the preceding standard stimuli and negatively with the reaction time. The analysis of the single-trial responses gives information about the behavior of the P300 component that is lost with conventional averaging. The method used in this study is independent of subjective decision making and can be used to model changes in the dynamical behavior of the P300 component objectively.

Adult↗

A Bayesian approach to evaluating net clinical benefit allowed for parameter uncertainty.

BACKGROUND AND OBJECTIVE: Although randomized controlled trials (RCTs) are conducted to establish whether novel interventions work on average in the patient population, there is a growing desire to move to a more individualized approach to evaluation. The potential benefits and harms of a treatment policy may differ between individuals. If these benefits and harms are not evaluated distinctly, and in a quantitative framework, transparency can be lost in the decision-making process. METHODS: Glasziou and Irwig have outlined the concept of net clinical treatment benefit for identifying the patients for whom the potential benefits of treatment outweigh the possible side effects. This study revisits the decision whether to use warfarin to treat atrial fibrillation. In this analysis, RCT and various sorts of observational data are synthesized. RESULTS: This reanalysis brings into question the conclusions of the original analysis on who would benefit from warfarin; however, caution is advised, due to limitations in the quality of life data available. CONCLUSION: A fully realized Bayesian implementation of the model is presented. This provides a framework for including uncertainty related to the estimation of all model parameters, and permits both direct probability statements and credible intervals for specific patient groups to be expressed.

Anticoagulants↗

The use of Markov chain Monte Carlo for analysis of correlated binary data: patterns of somatic cells in milk and the risk of clinical mastitis in dairy cows.

Two analytical approaches were used to investigate the relationship between somatic cell concentrations in monthly quarter milk samples and subsequent, naturally occurring clinical mastitis in three dairy herds. Firstly, cows with clinical mastitis were selected and a conventional matched analysis was used to compare affected and unaffected quarters of the same cow. The second analysis included all cows, and in order to overcome potential bias associated with the correlation structure, a hierarchical Bayesian generalised linear mixed model was specified. A Markov chain Monte Carlo (MCMC) approach, that is Gibbs sampling, was used to estimate parameters. The results of both the matched analysis and the hierarchical modelling suggested that quarters with a somatic cell count (SCC) in the range 41,000-100,000 cells/ml had a lower risk of clinical mastitis during the next month than quarters <41,000 cell/ml. Quarters with an SCC >200,000 cells/ml were at the greatest risk of clinical mastitis in the next month. There was a reduced risk of clinical mastitis between 1 and 2 months later in quarters with an SCC of 81,000-150,000 cells/ml compared with quarters below this level. The hierarchical modelling analysis identified a further reduced risk of clinical mastitis between 2 and 3 months later in quarters with an SCC 61,000-150,000 cells/ml, compared to other quarters. We conclude that low concentrations of somatic cells in milk are associated with increased risk of clinical mastitis, and that high concentrations are indicative of pre-existing immunological mobilisation against infection. The variation in risk between quarters of affected cows suggests that local quarter immunological events, rather than solely whole cow factors, have an important influence on the risk of clinical mastitis. MCMC proved a useful tool for estimating parameters in a hierarchical Bernoulli model. Model construction and an approach to assessing goodness of model fit are described.

Animals↗

Aligned 18S for Zoraptera (Insecta): phylogenetic position and molecular evolution.

The order Zoraptera (angel insects) is one of the least known insect groups, containing only 32 extant species. The phylogenetic position of Zoraptera is poorly understood, but it is generally thought to be closely related to either Paraneoptera (hemipteroid orders: booklice, lice, thrips, and bugs), Dictyoptera (blattoid orders: cockroaches, termites, and mantis), or Embioptera (web spinners). We inferred the phylogenetic position of Zoraptera by analyzing nuclear 18S rDNA sequences, which we aligned according to a secondary structure model. Maximum likelihood and Bayesian analyses both supported a close relationship between Zoraptera and Dictyoptera with relatively high posterior probability. The 18S sequences of Zoraptera exhibited several unusual properties: (1) a dramatically increased substitution rate, which resulted in very long branches; (2) long insertions at helix E23; and (3) modifications of secondary structures at helices 12 and 18.

Animals↗

A hierarchical Bayesian meta-analysis of randomised clinical trials of drug-eluting stents.

BACKGROUND: Drug-eluting stents (DES) are associated with lower restenosis rates than bare-metal stents (BMS), but the benefits and safety of the new devices have not been systematically quantified across different trials. We undertook a meta-analysis of randomised trials comparing BMS and stents eluting sirolimus or paclitaxel. METHODS: A systematic literature search aimed to identify all randomised clinical trials with 6-12 months of clinical follow-up. Results were pooled by a hierarchical Bayesian random-effects model with prespecified stratification for drug and the presence of carrier polymer. The primary outcomes examined were rates of death, myocardial infarction, target-lesion revascularisation, major adverse cardiac events (death, myocardial infarction, and target-vessel revascularisation), and angiographic restenosis. FINDINGS: We identified 11 eligible trials involving 5103 patients. The pooled mortality rates were low for both DES and BMS with no evidence of any difference between them (odds ratio 1.11 [95% credible interval 0.61-2.06]). Pooled rates of myocardial infarction showed no between-group difference (0.92 [0.65-1.25]). The rate of major adverse cardiac events was 7.8% with DES and 16.4% with BMS (0.42 [0.32-0.53]), and the angiographic restenosis rates were also lower for DES (8.9% vs 29.3%; 0.18 [0.06-0.40]). The pooled rates of major adverse cardiac events for each DES type and the respective BMS were: for sirolimus, 6.8% versus 21.0% (0.28 [0.17-0.41]); for polymer-based paclitaxel 8.7% versus 16.7% (0.47 [0.25-0.71]); and for non-polymer-based paclitaxel 7.7% versus 9.5% (0.64 [0.42-1.00]). We did not observe higher rates of edge restenosis, stent thrombosis, or late incomplete stent apposition with DES, although the credible intervals were wide. INTERPRETATION: Sirolimus-eluting and polymeric paclitaxel-eluting stents are effective at decreasing rates of angiographic restenosis and major adverse cardiac events compared with BMS. However, there is no evidence that they affect mortality or myocardial-infarction rates. They also appear to be safe in the short to medium term, although definitive conclusions are not possible. Larger studies with longer follow-up are needed to define better the role of these new devices.

Angioplasty, Balloon, Coronary↗

Phylogeny of shorebirds, gulls, and alcids (Aves: Charadrii) from the cytochrome-b gene: parsimony, Bayesian inference, minimum evolution, and quartet puzzling.

Charadrii (shorebirds, gulls, and alcids) have exceptional diversity in ecological, behavioral, and life-history traits. A phylogenetic framework is necessary to fully understand the relationships among these traits. Despite several attempts to resolve the phylogeny of the Charadrii, none have comprehensively utilized molecular sequence data. Complete and partial cytochrome-b gene sequences for 86 Charadrii and five Falconides species (as outgroup taxa) were obtained from GenBank and aligned. We analyzed the resulting matrices using parsimony, Bayesian inference, minimum evolution, and quartet puzzling methods. Posterior probabilities, decay indices, and bootstrapping provide strong support for four major lineages consisting of gulls, alcids, plovers, and sandpipers, respectively. The broad structure of the trees differ significantly from all previous hypotheses of Charadrii phylogeny in placing the plovers at the base of the tree below the sandpipers in a pectinate sequence towards a large clade of gulls and alcids. The parsimony, Bayesian, and minimum evolution models provide strong evidence for this phylogenetic hypothesis. This is further corroborated by non-tree based measures of support and conflict (Lento plots). The quartet puzzling trees are poorly resolved and inconclusive.

Animals↗

Declining threshold for hypoxia in the Gulf of Mexico.

The northwestern Gulf of Mexico shelf has been nicknamed "The Dead Zone" due to annual summertime (May-September) bottom-water hypoxia (dissolved oxygen < or =2 mg L(-1)) that can be extensive (>20 000 km2) and last for several months. Hypoxia has been attributed to eutrophication caused by increasing nitrogen loads, although directly linking hypoxia to nitrogen is difficult. While the areal extent of hypoxia has been shown to increase with Mississippi River flow, it is unclear whether this increase results from enhanced vertical water-column stratification or from eutrophication caused by river-borne nutrients. Disentangling the relative contributions of eutrophication versus stratification has important management consequences. Our analysis indicates that the top:bottom salinity difference is an important predictor of hypoxia, exhibiting a threshold, where the probability of hypoxia increases rapidly, at approximately 4.1 ppt. Using a Bayesian change-point model, we show that this stratification threshold decreased from 1982 to 2002, indicating the degree of stratification needed to induce hypoxia has gone down. Although this declining threshold does not link hypoxia and nitrogen, it does implicate a long-term factor transcending yearly flow-induced stratification differences. Concurrently, we show that surface temperature increased, while surface dissolved oxygen decreased, suggesting that factors in addition to nitrogen may be influencing the incidence of hypoxia in the bottom water.

Atlantic Ocean↗

The effects of interaction between familial and reproductive factors on breast cancer risk: a combined analysis of seven case-control studies.

In this paper, a combined analysis was performed to study the interaction between familial risk and reproductive life factors. In particular, the interaction between familial risk and breast cell mitotic activity (BCMA), as assessed by duration of ovarian activity, was investigated because of the potential importance of mitotic activity on genetically susceptible cells. The present analysis included 3152 cases and 4404 controls in seven case-control studies from four countries. The interaction effect was estimated in each study separately, then combined using two different methods: a multivariate weighted average and a Bayesian random-effects model. The main effects of reproductive life factors on the risk of breast cancer were in agreement with the previous findings. In particular, an increased duration of BCMA before the first childbirth and over life was found to increase the risk of breast cancer (P < 0.001). Slightly increasing but non-significant, familial risks were observed with increasing number of children (P = 0.17), increasing age at first childbirth (P > 0.2) and increasing duration of BCMA (P > 0.2). There was no modification in familial risk with age at menarche and no clear pattern with menopause characteristics. A weak influence of reproductive and menstrual factors on the familial risk emerged from the present study.

Adult↗

Biased biological functions of horizontally transferred genes in prokaryotic genomes.

Horizontal gene transfer is one of the main mechanisms contributing to microbial genome diversification. To clarify the overall picture of interspecific gene flow among prokaryotes, we developed a new method for detecting horizontally transferred genes and their possible donors by Bayesian inference with training models for nucleotide composition. Our method gives the average posterior probability (horizontal transfer index) for each gene sequence, with a low horizontal transfer index indicating recent horizontal transfer. We found that 14% of open reading frames in 116 prokaryotic complete genomes were subjected to recent horizontal transfer. Based on this data set, we quantitatively determined that the biological functions of horizontally transferred genes, except mobile element genes, are biased to three categories: cell surface, DNA binding and pathogenicity-related functions. Thus, the transferability of genes seems to depend heavily on their functions.

Algorithms↗

Single-point phenytoin dosage predictions in Singapore Chinese.

Phenytoin dosing is often difficult in a clinical situation because of the non-linear nature of phenytoin metabolism at therapeutic plasma concentrations. This study was performed to examine retrospectively five pharmacokinetic methods of adjusting phenytoin dosage based on a single steady-state plasma phenytoin concentration-dose pair in 66 epileptic Chinese children and adults. The methods compared included four fixed-parameter(s) methods (1 = the fixed Km (Michaelis-Menten constant) method; 2 = the fixed Vm (maximum rate of elimination) method; 3 = the fixed Vmax/Km method; 4 = the fixed S (slope of logarithmic growth model) method) and a Bayesian feedback method (method 5). Measures of bias or accuracy (mean error, percentage dose) and precision (root mean squared error, percentage dose) were 20.1/88.0, -1.85/21.5, 2.14/21.9, -1.07/21.1 and -1.98/22.2, respectively. Method 1 was significantly inferior to methods 2-5 with respect to accuracy and precision. The correlation between the predicted and observed doses was higher with methods 2-5 (r = 0.862, 0.855, 0.866 and 0.841, respectively) when compared to method 1 (r = 0.539). All methods had a sizeable number of poor predictions (range: 21.2% for method 4 to 37.9% for method 1), i.e. predictions with an error of greater than 20% of the dose. With respect to the frequency of poor versus good predictions, comparisons of all methods showed no significant differences.

Adolescent↗

Cluster analysis of gene expression dynamics.

This article presents a Bayesian method for model-based clustering of gene expression dynamics. The method represents gene-expression dynamics as autoregressive equations and uses an agglomerative procedure to search for the most probable set of clusters given the available data. The main contributions of this approach are the ability to take into account the dynamic nature of gene expression time series during clustering and a principled way to identify the number of distinct clusters. As the number of possible clustering models grows exponentially with the number of observed time series, we have devised a distance-based heuristic search procedure able to render the search process feasible. In this way, the method retains the important visualization capability of traditional distance-based clustering and acquires an independent, principled measure to decide when two series are different enough to belong to different clusters. The reliance of this method on an explicit statistical representation of gene expression dynamics makes it possible to use standard statistical techniques to assess the goodness of fit of the resulting model and validate the underlying assumptions. A set of gene-expression time series, collected to study the response of human fibroblasts to serum, is used to identify the properties of the method.

Bayes Theorem↗

Comparative effects of pharmacological interventions in the prophylactic treatment of tension-type headache: systematic review and network meta-analysis.

BACKGROUND: Tension-type headache (TTH) is the most common neurological disorder. The comparative effect of pharmacological interventions for TTH prophylaxis remains unclear. We aimed to assess the comparative effects of pharmacological interventions in the prophylactic treatment of TTH. METHODS: Ovid Medline, Embase, and Cochrane were searched from inception to 12 December, 2025. Randomized controlled trials (RCTs) of medications compared to placebo or another medication for preventing TTH were included. The primary outcome was headache days per month. A Bayesian random-effect model was employed as the primary analysis of chronic TTH. RESULTS: Thirty-five RCTs were included, 33 (88.6%) RCTs involved chronic TTH patients, and 24 RCTs provided available data for meta-analysis. Amitriptyline 100&#x2009;mg presented more reduction of monthly headache days than placebo at 4&#x2009;and 8&#x2009;weeks (4&#x2009;weeks: MD -6.59, 95% CrI -11.22 to -0.64; 8&#x2009;weeks: MD -6.14, 95% CrI -10.27 to -0.87). BTX-A 100&#x2009;U can reduce monthly headache days (MD -3.79, 95% CrI -7.16 to -0.33). Amitriptyline 100&#x2009;mg was the highest-ranked treatment for monthly headache days at 4 (SUCRA 0.85), 8 (SUCRA 0.85), and 24 (SUCRA 0.87) weeks; 12&#x2009;weeks was lidocaine 25&#x2009;ml (SUCRA 0.75). Amitriptyline 100&#x2009;mg and BTX-A 500&#x2009;U showed a higher adverse event rate than placebo. CONCLUSION: Amitriptyline 100&#x2009;mg and BTX-A 100&#x2009;U may be options to reduce monthly headache days in patients with chronic TTH. Given the low to very low certainty of evidence, high risk of bias, and high heterogeneity, more studies are needed. TRIAL REGISTRATION: PROSPERO (CRD42025639586).

Humans↗

Longitudinal profiling of health care units based on continuous and discrete patient outcomes.

Monitoring health care quality involves combining continuous and discrete outcomes measured on subjects across health care units over time. This article describes a Bayesian approach to jointly modeling multilevel multidimensional continuous and discrete outcomes with serial dependence. The overall goal is to characterize trajectories of traits of each unit. Underlying normal regression models for each outcome are used and dependence among different outcomes is induced through latent variables. Serial dependence is accommodated through modeling the pairwise correlations of the latent variables. Methods are illustrated to assess trends in quality of health care units using continuous and discrete outcomes from a sample of adult veterans discharged from 1 of 22 Veterans Integrated Service Networks with a psychiatric diagnosis between 1993 and 1998.

Bayes Theorem↗

Predicting the cumulative risk of false-positive mammograms.

BACKGROUND: The cumulative risk of a false-positive mammogram can be substantial. We studied which variables affect the chance of a false-positive mammogram and estimated cumulative risks over nine sequential mammograms. METHODS: We used medical records of 2227 randomly selected women who were 40-69 years of age on July 1, 1983, and had at least one screening mammogram. We used a Bayesian discrete hazard regression model developed for this study to test the effect of patient and radiologic variables on a first false-positive screening and to calculate cumulative risks of a false-positive mammogram. RESULTS: Of 9747 screening mammograms, 6. 5% were false-positive; 23.8% of women experienced at least one false-positive result. After nine mammograms, the risk of a false-positive mammogram was 43.1% (95% confidence interval [CI] = 36.6%-53.6%). Risk ratios decreased with increasing age and increased with number of breast biopsies, family history of breast cancer, estrogen use, time between screenings, no comparison with previous mammograms, and the radiologist's tendency to call mammograms abnormal. For a woman with highest-risk variables, the estimated risk for a false-positive mammogram at the first and by the ninth mammogram was 98.1% (95% CI = 69.3%-100%) and 100% (95% CI = 99.9%-100%), respectively. A woman with lowest-risk variables had estimated risks of 0.7% (95% CI = 0.2%-1.9%) and 4.6% (95% CI = 1. 1%-12.5%), respectively. CONCLUSIONS: The cumulative risk of a false-positive mammogram over time varies substantially, depending on a woman's own risk profile and on several factors related to radiologic screening. By the ninth mammogram, the risk can be as low as 5% for women with low-risk variables and as high as 100% for women with multiple high-risk factors.

Adult↗

The platypus is in its place: nuclear genes and indels confirm the sister group relation of monotremes and Therians.

Morphological data supports monotremes as the sister group of Theria (extant marsupials + eutherians), but phylogenetic analyses of 12 mitochondrial protein-coding genes have strongly supported the grouping of monotremes with marsupials: the Marsupionta hypothesis. Various nuclear genes tend to support Theria, but a comprehensive study of long concatenated sequences and broad taxon sampling is lacking. We therefore determined sequences from six nuclear genes and obtained additional sequences from the databases to create two large and independent nuclear data sets. One (data set I) emphasized taxon sampling and comprised five genes, with a concatenated length of 2,793 bp, from 21 species (two monotremes, six marsupials, nine placentals, and four outgroups). The other (data set II) emphasized gene sampling and comprised eight genes and three proteins, with a concatenated length of 10,773 bp or 3,669 amino acids, from five taxa (a monotreme, a marsupial, a rodent, human, and chicken). Both data sets were analyzed by parsimony, minimum evolution, maximum likelihood, and Bayesian methods using various models and data partitions. Data set I gave bootstrap support values for Theria between 55% and 100%, while support for Marsupionta was at most 12.3%. Taking base compositional bias into account generally increased the support for Theria. Data set II exclusively supported Theria, with the highest possible values and significantly rejected Marsupionta. Independent phylogenetic evidence in support of Theria was obtained from two single amino acid deletions and one insertion, while no supporting insertions and deletions were found for Marsupionta. On the basis of our data sets, the time of divergence between Monotremata and Theria was estimated at 231-217 MYA and between Marsupialia and Eutheria at 193-186 MYA. The morphological evidence for a basal position of Monotremata, well separated from Theria, is thus fully supported by the available molecular data from nuclear genes.

Amino Acid Sequence↗

Bayesian evaluation of the modified zinc test and the acid phosphatase spot test for forensic semen investigation.

The modified zinc test is evaluated as a screening instrument in forensic semen identification using the classical acid phosphatase test as a "gold standard" reference. Both tests were applied to vaginal swabs taken from women (n = 456) at varying time periods after sexual intercourse and the corresponding sensitivity and specificity were calculated for both tests separately and for their parallel and serial combination strategies, with the microscopical visualization of sperm as end criterion. The results were submitted to Bayesian calculations and a model was obtained, giving the posterior probabilities of finding or not finding sperm in a microscopical preparate for any possible prior probability. For the largest part of the theoretical sperm prevalence range, negative predictions were more informative than positive ones. With the prior probability of finding spermatozoa set at P = 0.5 (Bayes' postulate of neutral prior probability), the model was applied to a set of 192 pieces of evidentiary material from alleged sexual assaults.

Acid Phosphatase↗