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PubMed1995

Assessing horizontal transfer of nifHDK genes in eubacteria: nucleotide sequence of nifK from Frankia strain HFPCcI3.

The structural genes for nitrogenase, nifK, nifD, and nifH, are crucial for nitrogen fixation. Previous phylogenetic analysis of the amino acid sequence of nifH suggested that this gene had been horizontally transferred from a proteobacterium to the gram-positive/cyanobacterial clade, although the confounding effects of paralogous comparisons made interpretation of the data difficult. An additional test of nif gene horizontal transfer using nifD was made, but the NifD phylogeny lacked resolution. Here nif gene phylogeny is addressed with a phylogenetic analysis of a third and longer nif gene, nifK. As part of the study, the nifK gene of the key taxon Frankia was sequenced. Parsimony and some distance analyses of the nifK amino acid sequences provide support for vertical descent of nifK, but other distance trees provide support for the lateral transfer of the gene. Bootstrap support was found for both hypotheses in all trees; the nifK data do not definitively favor one or the other hypothesis. A parsimony analysis of NifH provides support for horizontal transfer in accord with previous reports, although bootstrap analysis also shows some support for vertical descent of the orthologous nifH genes. A wider sampling of taxa and more sophisticated methods of phylogenetic inference are needed to understand the evolution of nif genes. The nif genes may also be powerful phylogenetic tools. If nifK evolved by vertical descent, it provides strong evidence that the cyanobacteria and proteobacteria are sister groups to the exclusion of the firmicutes, whereas 16S rRNA sequences are unable to resolve the relationships of these three major eubacterial lineages.

Amino Acid Sequence↗

PubMed1991

Molecular phylogeny of plethodonine salamanders and hylid frogs: statistical analysis of protein comparisons.

The bootstrapping method of determining confidence in the topology of phylogenetic trees has been applied to electrophoretic protein data for two groups of amphibians: salamanders of two North American genera (Aneides and Plethodon) of the tribe Plethodontini and Holarctic hylid frogs. Some current methods of phylogenetic reconstruction for electrophoretic protein data have been evaluated by comparing the trees obtained from molecular data sets with available morphological data. Molecular data on the phylogenetic relationships of Aneides and Plethodon, data obtained from electrophoretic and immunological studies, indicate that Aneides probably was derived from western Plethodon subsequent to the separation of eastern and western Plethodon. Thus Plethodon very likely is a paraphyletic genus. The extremely low rate of morphological evolution in Plethodon compared with that in Aneides causes difficulty in indicating their evolutionary relationships taxonomically because there are no synapomorphic morphological characters that define either eastern or western Plethodon, whereas there are several for the genus Aneides. Thus molecular data alone probably indicate the evolutionary relationships of the species in these genera. Highton and Larson's (1979) arrangement of species of Plethodon into eight species groups is supported. The topologies of the unweighted pair-group method using arithmetic means (UPGMA) and distance Wagner trees were compared with independent morphological and molecular data on the relationships of the 28 plethodonine species. It was found that UPGMA trees indicate relationships that are more in agreement with other information than are those provided by distance Wagner trees. The use of the bootstrap technique indicates that the topologies of UPGMA trees are better supported statistically than are the topologies of distance Wagner trees. Moreover, different addition criteria produce a variety of distance Wagner trees with different topologies, each with several groupings that are not supported statistically. It is concluded that considerable caution should be used in interpreting the topology of distance Wagner trees. Very similar results were obtained with a second data set on 30 taxa of Holarctic hylid frogs. Trees obtained by the neighbor-joining method are more in agreement with UPGMA phenograms and other data, so this method of phylogenetic reconstruction may be useful to systematists not willing to assume constant rates of evolution.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed2006

A comparison of statistical methods for estimation of less than detectable ionising radiation exposures.

Methods were developed to estimate the ionising radiation dose below the detection level (DL) of personal monitoring devices for a case-control study of protracted radiation exposure and lung cancer. Exposure data were grouped by dosemeter type and monitoring period. Each group contained dosimetry data that were interval-censored from limitations in measurement precision and included left-censoring of observations below detection. The grouped data were fit to a three parameter hybrid-lognormal distribution by maximum likelihood estimation. Using the fitted distribution, bootstrap samples were either simulated by Monte Carlo or constructed by sampling with replacement. The resulting bootstrap sample distributions were then used to predict the missing dose values and the associated uncertainty in the estimate. Among study subjects, 1357 workers were monitored with film dosimetry. Among the 39,263 dose observations 20,416 were recorded as zero dose, indicating 52% left-censoring. The statistical methods estimated 0.31 person-Sv below the DL or approximately 1% of the total collective dose for this study population.

Case-Control Studies↗

PubMed2000

Phylogenetic relationships of agaric fungi based on nuclear large subunit ribosomal DNA sequences.

Phylogenetic relationships of mushrooms and their relatives within the order Agaricales were addressed by using nuclear large subunit ribosomal DNA sequences. Approximately 900 bases of the 5' end of the nucleus-encoded large subunit RNA gene were sequenced for 154 selected taxa representing most families within the Agaricales. Several phylogenetic methods were used, including weighted and equally weighted parsimony (MP), maximum likelihood (ML), and distance methods (NJ). The starting tree for branch swapping in the ML analyses was the tree with the highest ML score among previously produced MP and NJ trees. A high degree of consensus was observed between phylogenetic estimates obtained through MP and ML. NJ trees differed according to the distance model that was used; however, all NJ trees still supported most of the same terminal groupings as the MP and ML trees did. NJ trees were always significantly suboptimal when evaluated against the best MP and ML trees, by both parsimony and likelihood tests. Our analyses suggest that weighted MP and ML provide the best estimates of Agaricales phylogeny. Similar support was observed between bootstrapping and jackknifing methods for evaluation of tree robustness. Phylogenetic analyses revealed many groups of agaricoid fungi that are supported by moderate to high bootstrap or jackknife values or are consistent with morphology-based classification schemes. Analyses also support separate placement of the boletes and russules, which are basal to the main core group of gilled mushrooms (the Agaricineae of Singer). Examples of monophyletic groups include the families Amanitaceae, Coprinaceae (excluding Coprinus comatus and subfamily Panaeolideae), Agaricaceae (excluding the Cystodermateae), and Strophariaceae pro parte (Stropharia, Pholiota, and Hypholoma); the mycorrhizal species of Tricholoma (including Leucopaxillus, also mycorrhizal); Mycena and Resinomycena; Termitomyces, Podabrella, and Lyophyllum; and Pleurotus with Hohenbuehelia. Several groups revealed by these data to be nonmonophyletic include the families Tricholomataceae, Cortinariaceae, and Hygrophoraceae and the genera Clitocybe, Omphalina, and Marasmius. This study provides a framework for future systematics studies in the Agaricales and suggestions for analyzing large molecular data sets.

Agaricales↗

PubMed1996

Confidence intervals for measures of interaction.

Interaction, defined as departure of disease rates from an additive model, can be measured by the relative excess risk due to interaction, or the attributable proportion due to interaction. Point estimates can be obtained using multiple logistic regression. Using simulated case-control data, we compare several confidence interval estimation techniques for these measures. These include a symmetrical interval based on the delta method estimate of the variance, and three types of bootstrap confidence intervals. One such bootstrap method has coverage closest to the nominal level and is the most evenly balanced with respect to the direction in which intervals miss the true value. The estimation methods are applied to data from an actual case-control study, and the results are interpreted in light of the simulation study.

Case-Control Studies↗

PubMed2003

Clinically relevant interpretation of genotype for resistance to abacavir.

OBJECTIVE: To develop a stepwise methodology for the development and validation of clinically relevant genotypic score for resistance to antiretroviral drugs and to apply this approach to the genotypic resistance to abacavir. METHODS: All patients having received abacavir during the Narval trial were included in this study. The impact of each nucleoside analogue resistance mutation on the virologic response to abacavir was studied in a univariate analysis. Mutations with a P value < 0.20 and those selected by abacavir were retained. According to the number of mutations three levels of resistance were defined. A multivariate analysis accounting for confonding variables assessed whether the genotypic score was an independent predictor of the response. The robustness of the score was analysed using the bootstrap resampling method. RESULTS: In the 175 patients exposed to abacavir, the strongest association between the decrease in viral load and the number of mutations was observed with a set of six mutations at codons 41, 67, 210, 215, 74 and 184 of the reverse transcriptase gene. In patients with fewer than four mutations (no evidence of resistance) the median decrease in viral load was -1.64 log(10) copies/ml while it was -0.69 log(10) and -0.19 log(10) in those with four (possible resistance) and five or six (resistance) mutations respectively. In the multivariate analysis this score was an independent predictor of the response. The bootstrap analysis showed the robustness of the score. CONCLUSIONS: We developed a new strategy for the analysis of correlation between genotype profile at baseline and virologic response.

Algorithms↗

PubMed1999

Validation procedures in radiologic diagnostic models. Neural network and logistic regression.

OBJECTIVE: To compare the performance of two predictive radiologic models, logistic regression (LR) and neural network (NN), with five different resampling methods. METHODS: One hundred sixty-seven patients with proven calvarial lesions as the only known disease were enrolled. Clinical and CT data were used for LR and NN models. Both models were developed with cross-validation, leave-one-out, and three different bootstrap algorithms. The final results of each model were compared with error rate and the area under receiver operating characteristic curves (Az). RESULTS: The NN obtained statistically higher Az values than LR with cross-validation. The remaining resampling validation methods did not reveal statistically significant differences between LR and NN rules. CONCLUSIONS: The NN classifier performs better than the one based on LR. This advantage is well detected by three-fold cross-validation but remains unnoticed when leave-one-out or bootstrap algorithms are used.

Adolescent↗

PubMed2002

Assessment of symptom exacerbations in a longitudinal study of children with Tourette's syndrome or obsessive-compulsive disorder.

OBJECTIVES: The severity of tic and obsessive-compulsive (OC) symptoms varies over time. Consequently, how do we, as clinicians, know when a change in symptom severity occurs that falls outside of the normal range of fluctuation? The goal of this study was to describe the level of symptom severity fluctuation over time and to establish an objective, prospective, and quantitative method for identifying symptom exacerbations in children with Tourette's syndrome, obsessive-compulsive disorder (OCD), or both. A second major aim was to assess whether fluctuations in tic and OC symptom severity covaried with one another. METHOD: Monthly consecutive Yale Global Tic Severity Scale and Children's Yale-Brown Obsessive Compulsive Scale scores were prospectively obtained in 64 children diagnosed with Tourette's syndrome and/or OCD for periods ranging from 3 to 39 months. Exacerbation thresholds were estimated by using state-of-the-art bootstrap methods. These thresholds were then independently evaluated by asking two expert clinicians to identify, retrospectively, clinically significant exacerbations based on a review of all available clinical and research records. RESULTS: The severity of tic and OC symptoms displayed a high degree of intrasubject variability. Exacerbation thresholds, which incorporated the change score from the previous month and the current symptom score, provided the best agreement with those of expert clinicians. When both tic and OC symptoms were present, they showed a significant degree of covariation. CONCLUSIONS: Evidence-based treatments are coming of age. The use of valid, clinician-rated severity scales will likely become a standard part of clinical practice. Bootstrapping methods may provide a quantitative and convenient way to obtain clinically valid thresholds to assess tic and OC symptom exacerbations. This method has the potential to be applied to other symptom domains where exacerbation thresholds are needed.

Adolescent↗

PubMed2006

Development and validation of a nomogram for predicting outcome of patients with vulvar cancer.

OBJECTIVE: To construct and validate a nomogram to predict relapse-free survival of patients treated for vulvar cancer. METHODS: Data from 244 patients treated for vulvar cancer at a single institution (Creteil, France) were used as a training set to develop and calibrate a nomogram for predicting relapse-free survival and local relapse-free survival. We used bootstrap resampling for the internal validation and we tested the nomogram on an independent validation set of patients (Torino, Italy) for the external validation. RESULTS: The nomograms were based on a Cox proportional hazards regression model. Covariates for the relapse-free survival model included age, T stage, number of metastatic nodes, bilateral lymph node involvement, omission of the lymphadenectomy, margin status, lymphovascular space invasion, and depth of invasion. The concordance indices were 0.85 and 0.83 in the training set before and after bootstrapping, respectively, and 0.83 in the validation set. The predictions of our nomogram discriminated better than did the International Federation of Gynecology and Obstetrics stage (0.83 compared with 0.78, P = .01). The calibration of our nomogram was good. In the validation set, 2-year and 5-year relapse-free survival were well predicted with less than 5% difference between the predicted and observed survivals for each quartile. A nomogram for predicting local relapse was also developed. CONCLUSION: We have developed nomograms for predicting distant and local relapse of vulvar cancer at 2 and 5 years and validated them both internally and externally. These nomograms will be freely available on the International Society for the Study of Vulvovaginal Disease Web site. LEVEL OF EVIDENCE: III.

Adult↗

PubMed2004

Oral decontamination is cost-saving in the prevention of ventilator-associated pneumonia in intensive care units.

OBJECTIVE: Although the development of ventilator-associated pneumonia (VAP) is assumed to increase costs of intensive care unit stay, it is unknown whether prevention of VAP by means of oropharyngeal decontamination is cost-effective. Because of wide ranges of individual patient costs, crude cost comparisons did not show significant cost reductions. DESIGN: Based on actual cost data of 181 individual patients included in a former randomized clinical trial, cost-effectiveness of prevention of VAP was determined using a decision model and univariate sensitivity analyses, and bootstrapping was used to assess the impact of variability in the various outcomes. DATA SOURCE: Published data on prevention of VAP by oropharyngeal decontamination, which resulted in a relative risk for VAP of 0.45, with a baseline rate of VAP of 29% among control patients. The mean costs of the intervention were 351 dollars per patient (32 dollars per patient per day). All other costs were derived from the hospital administrative database for all individual patients. RESULTS OF BASE-CASE ANALYSIS: Prevention of VAP led to mean total costs of 16,119 dollars and 18,268 dollars for patients without preventive measures administered. Thus, costs were saved and instances of VAP were prevented. Similar results were observed in terms of overall survival. RESULTS OF SENSITIVITY ANALYSIS: Prevention of VAP remains cost-saving if the relative risk for VAP because of intervention is <0.923, the costs of the intervention are less than 2,500 dollars, and the prevalence of VAP without intervention is >4%. Bootstrapping confirmed that, with about 80% certainty, oropharyngeal decontamination results in prevention of VAP and simultaneously saves costs. In terms of a survival benefit, the results are less evident; the results indicate that with only about 60% certainty can we confirm that oropharyngeal decontamination would result in a survival benefit and simultaneously save costs. CONCLUSIONS: This study provides strong evidence that prevention of VAP by means of oropharyngeal decontamination is cost-effective.

Antibiotic Prophylaxis↗

PubMed2006

Population pharmacokinetics of allopurinol in full-term neonates with perinatal asphyxia.

In newborn infants, allopurinol is being tested as a free radical scavenger to prevent brain damage caused by reperfusion and oxygenation after perinatal hypoxia and ischemia (birth asphyxia). To develop rational dosing schemes for future studies, knowledge of the pharmacokinetics in this patient group is essential. In the present study, a population pharmacokinetic model was designed and validated for allopurinol in this specific patient group. One-compartment and 2-compartment models were fitted to plasma concentration time data of 24 newborns entered in 2 clinical trials using nonlinear mixed effects modeling. A bootstrap procedure was performed to check the robustness of the model. The data were best described using a 1-compartment model with linear elimination. Estimated pharmacokinetic parameters were volume of the central compartment (V, 0.79 L/kg) and total body clearance (CL, 0.078 L/h/kg), with 42% and 60% interindividual variability, respectively. The median values for these parameters of 1000 bootstrap replicates were very similar (95% confidence intervals were 0.67 to 0.96 and 0.054 to 0.10 for V and CL, respectively), indicating the robustness of the model. A population pharmacokinetic model has been designed and validated which adequately describes the data of 2 clinical studies in critically ill newborn infants. The model will be used to design dosing strategies for future evaluation of the benefits of allopurinol in these patients.

Allopurinol↗

PubMed2006

Application of routine monitoring data for determination of the population pharmacokinetics and enteral bioavailability of phenytoin in neonates and infants with seizures.

This study investigated the population pharmacokinetics and the enteral bioavailability of phenytoin (PTN) in neonates and infants with seizures. Data from 83 patients were obtained retrospectively from medical records. A 1-compartment model was fitted to the log-transformed concentration data using NONMEM. Between-subject variability and interoccasion variability were modelled exponentially together with a log transform, both-sides exponential residual unexplained variance model. Covariates in nested models were screened for significance. Model robustness was assessed by bootstrapping with replacement (n = 500) from the study data. The parameters of the final pharmacokinetic model were clearance (L/h) = 0.826.[weight (WT, kg) / 70].[1 + 0.0692.(postnatal age (d) - 11)]; volume of distribution (L) = 74.2.[WT (kg) / 70]; absolute enteral bioavailability = 0.76; absorption rate constant (h) = 0.167. The between-subject variability for clearance and volume of distribution was 74.2% and 65.6%, respectively. The interoccasion variability for clearance was 54.4%. The unexplained variability was 51.1%. Final model parameter values deviated from median bootstrap estimates by less than 9%. Phenytoin disposition in neonates and infants can be described satisfactorily by linear pharmacokinetics. The values of allometrically scaled clearance and volume were similar to adult values, suggesting no major kinetic differences between adults and infants on the basis of size alone. Postnatal age independently influenced clearance. Switching from enteral to intravenous routes may require a dosage adjustment. The results of this study provide a basis for more rational prescribing of phenytoin in infants and neonates.

Administration, Intranasal↗

PubMed2005

Nomograms including nuclear matrix protein 22 for prediction of disease recurrence and progression in patients with Ta, T1 or CIS transitional cell carcinoma of the bladder.

PURPOSE: We developed and validated nomograms that accurately predict disease recurrence and progression in patients with Ta, T1, or CIS transitional cell carcinoma (TCC) of the bladder using a large international cohort. METHODS: Univariate and multivariate logistic regression models targeted histologically confirmed disease recurrence, and focused on 2,542 patients with bladder TCC from 10 participating centers. Variables consisted of pre-cystoscopy voided urine Nuclear Matrix Protein 22 (NMP22) assay, urine cytology, age and gender. Resulting nomograms were internally validated with bootstrapping. Nomogram performance was explored graphically with Loess smoothing plots. RESULTS: Overall 957 patients had recurrent TCC. Tumor grade and stage was available for 898 patients, including 24% grade I, 43% grade II, and 33% grade III; 45% stage Ta, 32% T1 and/or CIS, and 23% T2 or greater. Bootstrap corrected predictive accuracy for any TCC recurrence was 0.842; grade III Ta/T1 or CIS was 0.869; and T2 or higher stage TCC of any grade was 0.858. Virtually perfect performance characteristics were observed for the nomograms predicting any TCC recurrence or grade III Ta/T1 or CIS. The nomogram predicting T2 or higher stage TCC overestimated the observed probability for predicted values greater than 45%. CONCLUSIONS: We developed and internally validated nomograms that incorporate urinary NMP22, cytology, age and gender to predict with high accuracy the probability of disease recurrence and progression in patients with Ta, T1, and/or CIS bladder TCC. These nomograms could provide a means for individualizing followup in patients with Ta, T1, CIS bladder TCC.

Adolescent↗

PubMed2003

Mapping the SF-12 to preference-based instruments: convergent validity in a low-income, minority population.

BACKGROUND: The profile-based SF-12 has a low respondent burden and is used widely in clinical settings to monitor health and evaluate programs. Deriving preference scores for the SF-12 health profile would permit its use in cost-effectiveness analyses. Previous mapping studies of SF family instruments to preference-based instruments have not examined convergent validity or performance in low-income, minority populations. OBJECTIVES: To map the SF-12 to the EuroQol (EQ-5D Index) and the Health Utilities Index Mark 3 (HUI3) in a low-income, predominantly minority sample. RESEARCH DESIGN: We used a cross-sectional survey data. SUBJECTS: We studied a convenience sample of 240 low-income, predominantly Latino and black patients attending a community health center in New York. MEASURES: We used separate regressions of the EQ-5D Index and HUI3 onto the physical (PCS-12) and mental (MCS-12) components of the SF-12 scores as measures. RESULTS: For the EQ-5D Index regression, the adjusted variance explained was 58% (bootstrap validation 95% confidence interval [CI], 46-66). For the HUI3 regression, the adjusted variance explained was 51% (bootstrap 95% CI, 39-59). The correlation coefficient between the 2 predicted measures was 0.96. The correlation of the predicted HUI3 with the EQ-5D Index (0.73) and the predicted EQ-5D Index with the HUI3 (0.70) exceeded that between the 2 original preference-based measures themselves (0.69). CONCLUSIONS: These pilot results suggest that the SF-12 could be successfully mapped to both the EQ-5D Index and HUI3, yielding preference-based scores that demonstrate convergent validity in a low-income, minority sample.

Adolescent↗

PubMed2007

Use of bioelectrical impedance analysis and anthropometry to measure fat-free mass in children and adolescents with Crohn disease.

OBJECTIVES: To investigate the precision of published prediction equations for fat-free mass (FFM) from bioimpedance measurements in children with Crohn disease using dual-energy X-ray absorptiometry (DXA) as an in vivo gold standard. METHODS: Fat-free mass of 49 white boys and girls ages 7.3 to 16.9 y suffering from Crohn disease was measured by DXA. Body weight, height and bioimpedance measurements were also collected. FFM measured by DXA (FFM(DXA)) was compared with FFM predicted by the only 5 published prediction equations available for children and adolescents. An equation was developed for predicting FFM and was validated using a bootstrap method. RESULTS: When correlating predicted FFM with FFM(DXA), Schaefer's equation showed the highest R2 (0.950), the smallest standard error of estimate (SEE) (2.05 kg) and the smallest percentage error (0.28%). Our prediction equation for estimating FFM was FFM = 0.652 Ht2/Z + 0.0385 Wt + 0.586 Age - 0.327, R2 = 0.951, SEE = 2.08, P < 0.0005, where Ht2/Z is the impedance index in cm2/ohm, Wt is body weight in kilograms, age is in years. R2 value from bootstrap method was 0.950 +/- 0.01 (95% confidence interval 0.927-0.968), indicating an acceptable validation of the derived formula. CONCLUSIONS: The formula of Schaefer is the best for predicting FFM. The present study provides a new prediction equation for estimating FFM in children with Crohn disease that may be used in clinical settings in which more sophisticated body composition measuring equipments are not available.

Absorptiometry, Photon↗

PubMed2004

Children with cancer, fever, and treatment-induced neutropenia: risk factors associated with illness requiring the administration of critical care therapies.

OBJECTIVES: To identify clinical and laboratory characteristics of pediatric patients with cancer, fever, and treatment-induced neutropenia, available at existing at initial presentation, that are independently associated with the development of illnesses requiring administration of critical care therapies. METHODS: We retrospectively collected historical, clinical, and laboratory data on initial presentation for all pediatric (younger than 18 years) cancer patients admitted for fever and treatment-induced neutropenia at our institution over a 5-year period. The outcome variable was the need for administration of a critical care therapy within 24 hours of admission. A multivariable analysis was performed and internally validated using bootstrap analysis. RESULTS: We identified 303 events in 143 patients, of which 36 (11.9%) received a critical care therapy. Higher temperature at presentation and capillary filling time (CFT) of >3 seconds retained significance in the multivariable analysis and were validated by the bootstrap analysis. The positive and negative predictive values of the presence of either temperature of > or =39.5 degrees C or CFT of >3 seconds were 35% and 91%, respectively. CONCLUSIONS: Pediatric patients with cancer, fever, and treatment-induced neutropenia who present with higher fever or prolonged CFT are at increased risk of developing life-threatening illnesses requiring administration of critical care therapies, independent of hematologic factors, type of cancer, or other physiologic signs of sepsis.

Adolescent↗

PubMed2026

Tertiary lymphoid structure transcriptomic signatures show limited and cohort-dependent value for predicting axillary nodal involvement in oestrogen receptor-positive luminal breast cancer.

Tertiary lymphoid structures (TLS) are associated with prognosis in solid tumours. Their value for predicting axillary nodal involvement in oestrogen receptor-positive luminal breast cancer remains uncertain. Three published TLS signatures were scored by single-sample gene set enrichment analysis in oestrogen receptor-positive luminal tumours. The Cancer Genome Atlas Breast Invasive Carcinoma cohort (TCGA-BRCA) included 632 cases, of which 379 met strict consensus. METABRIC included 1086 cases, of which 663 met strict consensus. Logistic models adjusted for age and pathological tumour stage. Strict consensus, majority vote, and continuous scores were compared. Performance assessment included bootstrapped changes in area under the receiver-operating-characteristic curve, Brier scores, calibration, and decision-curve analysis. Survival was evaluated in METABRIC and explored in TCGA-BRCA. Strict-consensus TLS status was not associated with nodal positivity in TCGA-BRCA (adjusted odds ratio: 0.95, 95% confidence interval: 0.62-1.45, P = 0.822). METABRIC was similar (odds ratio: 0.76, 95% confidence interval: 0.55-1.06, P = 0.105). Full-cohort METABRIC analyses detected small majority-vote and continuous-score associations, absent in TCGA-BRCA. Across specifications, bootstrapped changes in area under the receiver-operating-characteristic curve ranged from 0.0002 to 0.0089, with minimal Brier-score improvement and no stable decision-curve benefit. In METABRIC, the univariable overall survival association attenuated after age adjustment (hazard ratio: 1.33-1.10). TCGA-BRCA survival analyses were nonsignificant. TLS transcriptomic signals showed small, cohort-dependent associations with nodal status but no reproducible or clinically meaningful incremental predictive value. These data do not support replacing sentinel lymph node biopsy with a TLS signature in oestrogen receptor-positive luminal breast cancer.

breast cancer↗

PubMed2000

Common structure in panels of short ecological time-series.

Typically, in many studies in ecology, epidemiology, biomedicine and others, we are confronted with panels of short time-series of which we are interested in obtaining a biologically meaningful grouping. Here, we propose a bootstrap approach to test whether the regression functions or the variances of the error terms in a family of stochastic regression models are the same. Our general setting includes panels of time-series models as a special case. We rigorously justify the use of the test by investigating its asymptotic properties, both theoretically and through simulations. The latter confirm that for finite sample size, bootstrap provides a better approximation than classical asymptotic theory. We then apply the proposed tests to the mink-muskrat data across 81 trapping regions in Canada. Ecologically interpretable groupings are obtained, which serve as a necessary first step before a fuller biological and statistical analysis of the food chain interaction.

Animals↗