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PubMed1989

A dynamic model for the structure of acyl carrier protein in solution.

The determination of solution structures of proteins using two-dimensional NMR data is commonly based on the assumption that the structure can be represented by a single rigid conformer. We present here a procedure whereby this assumption can be relaxed and illustrate its application to acyl carrier protein from Escherichia coli, a small negatively charged protein with no internal disulfide bonds. The methodology rests on a model having two distinct conformers in dynamic equilibrium. Use of this two-state model results in a dramatic improvement in fit to cross-relaxation-derived distance constraints and a substantial lowering of molecular mechanics energies for individual conformers of acyl carrier protein. The two-state model retains the three-helix motif previously identified on the basis of a one-state structure, but substantial motion of loop regions and the C-terminal peptide, as well as partial disruption of the second helix, is suggested to occur. Support for the existence of these motions can be found in amide exchange rate and spin relaxation time data.

Acyl Carrier Protein↗

PubMed2005

Spatial registration of multichannel multi-subject fNIRS data to MNI space without MRI.

The registration of functional brain data to the common brain space offers great advantages for inter-modal data integration and sharing. However, this is difficult to achieve in functional near-infrared spectroscopy (fNIRS) because fNIRS data are primary obtained from the head surface and lack structural information of the measured brain. Therefore, in our previous articles, we presented a method for probabilistic registration of fNIRS data to the standard Montreal Neurological Institute (MNI) template through international 10-20 system without using the subject's magnetic resonance image (MRI). In the current study, we demonstrate our method with a new statistical model to facilitate group studies and provide information on different components of variability. We adopt an analysis similar to the single-factor one-way classification analysis of variance based on random effects model to examine the variability involved in our improvised method of probabilistic registration of fNIRS data. We tested this method by registering head surface data of twelve subjects to seventeen reference MRI data sets and found that the standard deviation in probabilistic registration thus performed for given head surface points is approximately within the range of 4.7 to 7.0 mm. This means that, if the spatial registration error is within an acceptable tolerance limit, it is possible to perform multi-subject fNIRS analysis to make inference at the population level and to provide information on positional variability in the population, even when subjects' MRIs are not available. In essence, the current method enables the multi-subject fNIRS data to be presented in the MNI space with clear description of associated positional variability. Such data presentation on a common platform, will not only strengthen the validity of the population analysis of fNIRS studies, but will also facilitate both intra- and inter-modal data sharing among the neuroimaging community.

Adult↗

PubMed1999

Inherited genetic predisposition in breast cancer. A population-based perspective.

Two classes of inherited susceptibility genes may be considered in the etiology of breast and other common cancers. First, genes have been identified that confer a high degree of breast cancer (BC) risk, usually associated with hereditary syndromes, but disease-associated germline variants in these genes are relatively rare in the general population. These include BRCA1, BRCA2, and TP53. The proportion of BC in the general population that can be explained by these genes is relatively small. Second, variant genotypes at other loci may confer a relatively smaller degree of cancer risk, but they are carried by a larger proportion of the general population. As a result, the proportion of BC that could be explained by these genes may be relatively large. To understand the genetic basis for BCs in the general population, both of these classes of genes may need to be considered. This paper presents an overview of genes thought to be involved in BC susceptibility. Genes that confer a high degree of risk are more likely to result in hereditary patterns of cancer that are amenable to identification by genetic epidemiologic methods using pedigree data. More common (e.g., nonhereditary) forms of BC may be optimally analyzed by molecular epidemiologic studies using case-case, case-control, or cohort designs. The use of an appropriate study design is crucial to the identification of genes with relatively small effects on BC risk. To understand the inherited factors that explain BC in the general population, consideration should be given to genes with different allele frequencies and magnitudes of effect, using appropriate analytical approaches. By understanding the complex interactions of these genes with one another and with exposures, improved risk assessment and potential for targeted cancer prevention strategies may be possible.

Breast Neoplasms↗

PubMed2006

A general approach for two-stage analysis of multilevel clustered non-Gaussian data.

In this article, we propose a two-stage approach to modeling multilevel clustered non-Gaussian data with sufficiently large numbers of continuous measures per cluster. Such data are common in biological and medical studies utilizing monitoring or image-processing equipment. We consider a general class of hierarchical models that generalizes the model in the global two-stage (GTS) method for nonlinear mixed effects models by using any square-root-n-consistent and asymptotically normal estimators from stage 1 as pseudodata in the stage 2 model, and by extending the stage 2 model to accommodate random effects from multiple levels of clustering. The second-stage model is a standard linear mixed effects model with normal random effects, but the cluster-specific distributions, conditional on random effects, can be non-Gaussian. This methodology provides a flexible framework for modeling not only a location parameter but also other characteristics of conditional distributions that may be of specific interest. For estimation of the population parameters, we propose a conditional restricted maximum likelihood (CREML) approach and establish the asymptotic properties of the CREML estimators. The proposed general approach is illustrated using quartiles as cluster-specific parameters estimated in the first stage, and applied to the data example from a collagen fibril development study. We demonstrate using simulations that in samples with small numbers of independent clusters, the CREML estimators may perform better than conditional maximum likelihood estimators, which are a direct extension of the estimators from the GTS method.

Animals↗

PubMed2006

Hypothesis testing and Bayesian estimation using a sigmoid Emax model applied to sparse dose-response designs.

Application of a sigmoid Emax model is described for the assessment of dose-response with designs containing a small number of doses (typically, three to six). The expanded model is a common Emax model with a power (Hill) parameter applied to dose and the ED50 parameter. The model will be evaluated following a strategy proposed by Bretz et al. (2005). The sigmoid Emax model is used to create several contrasts that have high power to detect an increasing trend from placebo. Alpha level for the hypothesis of no dose-response is controlled using multiple comparison methods applied to the p-values obtained from the contrasts. Subsequent to establishing drug activity, Bayesian methods are used to estimate the dose-response curve from the sparse dosing design. Bayesian estimation applied to the sigmoid model represents uncertainty in model selection that is missed when a single simpler model is selected from a collection of non-nested models. The goal is to base model selection on substantive knowledge and broad experience with dose-response relationships rather than criteria selected to ensure convergence of estimators. Bayesian estimation also addresses deficiencies in confidence intervals and tests derived from asymptotic-based maximum likelihood estimation when some parameters are poorly determined, which is typical for data from common dose-response designs.

Algorithms↗

PubMed1996

The stability of estrogen and progesterone receptors in patients receiving preoperative chemotherapy for locally advanced breast carcinoma.

The determination of estrogen (ER) and progesterone receptor (PR) content is routine in the management of carcinoma of the breast. Such data are commonly used to predict responses to endocrine therapy. Preoperative chemotherapy is often utilized in the treatment of patients with locally advanced carcinoma of the breast. However, little attention has been focused upon the effect of preoperative chemotherapy on hormonal receptor expression in that setting. The purpose of this study is to evaluate the effect of preoperative chemotherapy on ER and PR expression in patients with locally advanced breast carcinoma. Patients with T3 or T4 adenocarcinoma of the breast from Charity Hospital in New Orleans were studied. Levels of ER and PR were determined from tissue blocks obtained at diagnostic biopsy, as well as after the preoperative chemotherapy. The receptor levels were determined using immunohistochemistry and quantified using image analysis. We evaluated 21 locally advanced cancer patients who received at least three cycles of standard chemotherpay regimens. Of these patients, 11 achieved a partial response, with 3 achieving a complete response after preoperative chemotherapy. A total of 33 per cent of patients had a significant change in hormonal receptor content after preoperative chemotherapy. ER changed in 17%, PR in 22%, and both ER and PR in 6%. These data show that ER and/or PR expression changed in 33% of patients studied. Further, ER and PR status does not appear to predict or correlate with response to chemotherapy. This suggests that determination of ER and PR may best be performed from definitive resection specimens in patients who receive preoperative chemotherapy.

Adenocarcinoma↗

PubMed2005

Development and validation of a dental pain-screening questionnaire.

Dental pain, estimated to affect 12-40% of community-dwelling adults, is a symptom of a wide range of clinical conditions. A population screening instrument is needed to study their prevalence. This project aimed to develop a questionnaire for classifying a sample of dental pain patients into three groups of common dental pain conditions, i.e. Group 1 (Acute periapical periodontitis and Irreversible pulpitis), Group 2 (Reversible pulpitis and Dentine hypersensitivity) and Group 3 (Pericoronitis). Initial items were generated through a literature review, individual unstructured patient interviews and consultation with experts. Items generated were administered to a sample of dental pain patients for self-completion. Responses were subjected to a series of factor and discriminant analyses to identify questions capable of differentiating the sample into three groups, originally categorized by clinical diagnosis, with high classification rates. The selected items were administered to a further sample of dental pain patients to test for its sensitivity and specificity in classifying the sample into three groups against the gold standard of clinical diagnosis. The final 16-item Dental Pain Questionnaire (DePaQ) was capable of correctly classifying 89.7% of dental pain cases initially categorized by clinical diagnoses. The sensitivity of the questionnaire was 0.80-Group z1, 0.85-Group 2 and 0.59-Group 3. Specificity was 0.83-Group A1, 0.89-Group A2 and 0.90-Group 3. The DePaQ, which can easily be administered by non-clinical personnel, may be used to collect epidemiological data on common dental pain conditions, assess dental needs for a specified population, and triage of patients seeking treatment for dental pain.

Adolescent↗

PubMed1999

Quantitative nuclear cystography does not predict outcome in patients with primary vesicoureteral reflux.

PURPOSE: Quantitative nuclear cystography has been advocated as a tool for determining the prognosis in children with primary vesicoureteral reflux. We reviewed our data on this technique to assess its usefulness for predicting the outcome in this population. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients with primary reflux in whom findings were positive on at least 2 nuclear cystograms at our institution between 1992 and 1997. Patients followed at least 3 years were stratified according to outcome. Unfavorable prognostic criteria included bladder volume at reflux onset 60% or less of total bladder capacity and calculated volume of reflux 2% or greater of bladder capacity. RESULTS: Of the 107 patients in our study 63 were followed for 3 years or longer, and reflux resolved in 17, was repaired in 24 and persisted in 22. Mean patient age at latest followup, duration of followup and number of cystograms did not significantly differ among groups. Intermittent reflux in 33% of the patients followed 3 years or longer was not associated with outcome or detrusor instability. Bladder and reflux volume varied and was nonpredictive in individuals. CONCLUSIONS: Quantitative nuclear cystography did not predict the outcome in patients followed for primary vesicoureteral reflux at a single institution for 3 years or longer. Intermittent reflux was common. These data suggest that nuclear cystography cannot be used to assess reliably the prognosis in individuals. Strong consideration should be given to using negative findings on 2 cystograms to confirm reflux resolution in patients at high risk.

Adolescent↗

PubMedDate not supplied

Descriptive study of the clinical and nutritional profile and follow-up of premature babies in a Kangaroo Mother Care Program.

OBJECTIVE: To describe the profile of premature newborns participating in the Kangaroo Mother Care Program and the data from follow-up, and to verify possible correlations between these descriptive data. METHODS: A descriptive study of 70 children, 5-34 months old, born between April 1999 and 2002, with gestational age of 32.5 weeks, birth weight 1,560 g, participating in the Kangaroo Mother Care Program (modified for Brazil) for at least 3 days. They were discharged from Kangaroo Mother Care weighing around 3,000 g and followed-up to 1 year. RESULTS: Birth weight, gestational age and Apgar scores were determinants of better clinical, nutritional and motor outcomes as well as for enrollment on the Kangaroo Mother Care Program. During the second phase of the program 8.6% of the children were readmitted due to apnea. Exclusive breastfeeding started at a mean postconceptual age of 35.3 weeks and mean age postpartum of 18.6 days. By hospital discharge, children were at a mean age of 29 days, mean weight of 1,734 g and 85.7% were on exclusive breastfeeding. Predominant breastfeeding up to 6 months of age was observed in 60.3%. We initially identified motor disorders in 42.8% decreasing to 14.3% in the final review of records, including cerebral palsy (6.9%) and retarded motor development (6.9%). CONCLUSIONS: Enrollment on the Kangaroo Mother Care Program, in common with data on breastfeeding and clinical outcomes were determined by gestational age and birth weight and were influenced by clinical conditions of each preterm infant. Kangaroo Mother Care proved itself a good breastfeeding instrument, but its role as an intervention for motor development must be better investigated.

Adult↗

PubMed1994

Partial purification of murine tumor-associated peptide epitopes common to histologically distinct tumors, melanoma and sarcoma, that are presented by H-2Kb molecules and recognized by CD8+ tumor-infiltrating lymphocytes.

The B16/BL6 melanoma is a relatively nonimmunogenic tumor expressing low levels of MHC class I molecules. BL6 clones expressing transfected H-2Kb class I molecules were, by contrast, highly immunogenic in immunocompetent mice. Tumor-infiltrating lymphocytes (TILs) generated from the H-2Kb+ BL6 lesions (Thy 1.2+, CD8+, CD4-) efficiently lysed H-2Kb+ melanoma (CL8-1 and 2Kb38) and the H-2Kb+ nonrelated 3-methylcholanthrene (MCA)-105 sarcoma, but not the H-2Kb- parental melanoma BL6-8. This strongly suggests that CL8-1, 2Kb38, and MCA-105 express identical or cross-reactive T cell epitopes recognized by CL8-1 TILs in the context of the H-2Kb class I allele. To identify the T cell epitopes, peptides were acid-eluted from various cells, and fractionated by HPLC. Five HPLC fractions (F1mel-F5mel) of 70 tested contained peptides derived from H-2Kb+ CL8-1 melanoma (but not H-2Kb- melanomas) that were capable of conferring susceptibility to CL8-1 TIL lysis on H-2b-expressing target cells (EL4, C1R.Kb), but not on H-2d-expressing P815 target cells. CL8-1 TILs failed to recognize peptides derived from H-2Kb+ nonmelanoma targets such as EL4 or normal B6 splenocytes. Interestingly, CL8-1 TILs appeared to recognize peptide species contained in two HPLC fractions derived from the MCA-105 sarcoma (F1sar and F5sar). Conversely, TILs derived from MCA-105 lesions recognized MCA-105 and CL8-1 tumor cells, as well as F5mel and F5sar peptides presented by EL4 targets. These data support common murine tumor-associated peptide epitopes presented by H-2Kb and recognized by CD8+ CTLs derived from histologically distinct tumors, melanoma and sarcoma.

Animals↗

PubMed1984

Measuring the reliability of clinical data: the case for using three observers.

Misclassification of clinical data occurs commonly, because of measurement or judgmental errors, or because of bias in the observational method. The sensitivity and specificity of a given observer (or method) may sometimes be estimated by comparison with an independent "definitive" diagnosis; this is not routinely practical, however, if the "definitive" method involves additional risk or cost. A second possibility is to compare two independent, fallible observers, using an index of agreement such as the kappa statistic; the misclassification probabilities are not then estimable, and the agreement indices have the disadvantage of being dependent on the population prevalence. In contrast, if three or more independent observers are used, their reliability may be assessed by the direct estimation of sensitivity and specificity. An example is given of a series of patients who were independently evaluated by three radiologists.

Data Collection↗

PubMed2001

Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer.

UNLABELLED: Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US 6395 per additional life-year gained (LYG) in Spain (1995/96 values) to $US 44,690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US 13,135 (year of costs not reported) to $US 25,131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US 50,000 for new therapies and compare well with incremental costs reported for other oncological and life-saving therapies. Patient preferences and quality of life are important issues due to the short survival of patients with advanced ovarian cancer. Two cost-utility studies reported similar incremental cost-utility ratios (ICURs). In the study based on US costs, the ICUR of paclitaxel/cisplatin treatment was US $18,200 per additional quality-adjusted life-year (QALY) [1995 drug costs]. In a Canadian study the ICUR ranged from 11,600 Canadian dollars ($Can) to $Can 24,200 (1996 costs) per additional progression-free QALY depending on the choice of second-line treatment. CONCLUSIONS: Paclitaxel used in combination with cisplatin offers survival and utility gains versus cyclophosphamide plus cisplatin, when used as first-line treatment in patients with stage III or IV ovarian cancer. The incremental cost for these gains is within the accepted range for healthcare interventions. However, pharmacoeconomic analyses of paclitaxel plus carboplatin--a combination widely accepted for use in women with advanced ovarian cancer and with clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and tolerability profile--are currently lacking. Nevertheless, results of available pharmacoeconomic data support the clinical use of paclitaxel/platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced ovarian cancer.

Adult↗

PubMed2005

Statistical methods for multivariate interval-censored recurrent events.

Multi-type recurrent event data arise when two or more different kinds of events may occur repeatedly over a period of observation. The scientific objectives in such settings are often to describe features of the marginal processes and to study the association between the different types of events. Interval-censored multi-type recurrent event data arise when the precise event times are unobserved, but intervals are available during which the events are known to have occurred. This type of data is common in studies of patients with advanced cancer, for example, where the events may represent the development of different types of metastatic lesions which are only detectable by conducting bone scans of the entire skeleton. In this setting it is of interest to characterize the incidence of the various types of bone lesions, to estimate the impact of treatment and other covariate effects on the development of new lesions, and to understand the relationship between the processes generating the bone lesions. We develop joint models for multi-type interval-censored recurrent events which accommodate dependencies between different types of events and enable one to examine the covariate effects via regression. However, since the marginal likelihood resulting from the multivariate random effect model is intractable, we describe a Gibbs sampling algorithm to facilitate model fitting and inference. We use generalized estimating equations for estimation and inference based on marginal models. The finite sample properties of the marginal approach are studied via simulation. The estimates of both the regression coefficients and the variance-covariance parameters are shown to have negligible bias and 95 per cent confidence intervals based on the asymptotic variance formula are shown to have excellent empirical coverage probabilities in all of the settings considered. The application of these methods to data from a trial of women with advanced breast cancer provides insight into the clinical course of bone metastases in this population.

Bayes Theorem↗

PubMed1999

Domain orientation and dynamics in multidomain proteins from residual dipolar couplings.

The data most commonly available for the determination of macromolecular structures in solution are NOE based distance estimates and spin-spin coupling constant based dihedral angle estimates. This information is, unfortunately, inherently short-range in nature. Thus, for many multidomain proteins, little information is available to accurately position weakly interacting domains with respect to each other. Recent studies of proteins aligned in dilute liquid crystalline solvents have shown the utility of measuring anisotropic spin interactions, such as residual dipolar couplings, to obtain unique long-range structural information. In this work, the latter approach is taken to explore the relative domain orientation in a two-domain fragment from the protein barley lectin. An approach based on singular value decomposition as opposed to simulated annealing is used to directly determine order tensors for each domain from residual (15)N-(1)H dipolar couplings, and the limitations of the two approaches are discussed. Comparison of the order tensor principal axis frames as separately determined for each domain indicates that the two domains are not oriented as in the crystal structure of wheat germ agglutinin, a highly homologous protein ( approximately 95% sequence identical). Furthermore, differences in the order tensor values suggest that the two domains are not statically positioned but are experiencing different reorientational dynamics and, to a large degree, may be considered to reorient independently. Data are also presented that suggest that a specific association occurs between one domain and the lipid bicelles comprising the liquid crystal solvent.

Computer Simulation↗

PubMed2004

Estimating marginal effects in accelerated failure time models for serial sojourn times among repeated events.

Recurrent event data are commonly encountered in longitudinal studies when events occur repeatedly over time for each study subject. An accelerated failure time (AFT) model on the sojourn time between recurrent events is considered in this article. This model assumes that the covariate effect and the subject-specific frailty are additive on the logarithm of sojourn time, and the covariate effect maintains the same over distinct episodes, while the distributions of the frailty and the random error in the model are unspecified. With the ordinal nature of recurrent events, two scale transformations of the sojourn times are derived to construct semiparametric methods of log-rank type for estimating the marginal covariate effects in the model. The proposed estimation approaches/inference procedures also can be extended to the bivariate events, which alternate themselves over time. Examples and comparisons are presented to illustrate the performance of the proposed methods.

Age of Onset↗

PubMedDate not supplied

Incidence and description of scooter-related injuries among children.

OBJECTIVE: To describe trends in scooter-related injuries among US youth and compare scooter injuries to those related to in-line skates and skateboards. DESIGN: Retrospective review of data for children 1-19 years old from the National Electronic Injury Surveillance System of the US Consumer Product Safety Commission for 1997-2002. RESULTS: There were an estimated 190,878 scooter-related injuries (95% confidence interval: 145,984-235,773) among children treated in US emergency departments; 90% were in those 15 years old or younger. There was a marked increase in scooter-related injuries in 2000, injuries peaked in 2001, and declined. In 2002, the number of scooter-related injuries was similar to in-line skates and lower than skateboard-related injuries. Scooter- and in-line skate-associated injuries primarily involved children 5-12 years old: rates of scooter-related injuries were higher than rates of in-line skate-associated injuries among those 1-9 years old. Skateboard-related injuries more often involved teens. Forearm fractures accounted for 56% of fractures related to scooters (vs 74% in-line skates and 49% skateboards, chi-square, P < .01). Five percent of children injured using scooters had a closed head injury or skull fracture, similar to in-line skates and skateboards. CONCLUSIONS: The annual number of injuries related to scooters, which peaked in 2001, is now similar to the number of injuries related to in-line skates. Injuries related to scooters primarily involve children 5-12 years old, and forearm fractures are common. These data suggest helmets should be used, and protective equipment should be developed to reduce forearm fractures.

Adolescent↗

PubMed2003

Noninvasive and invasive micropapillary (low-grade) serous carcinoma of the ovary: a clinicopathologic analysis of 135 cases.

Reports describing the behavior of micropapillary serous carcinomas (MPSCs) of the ovary have focused on those that are noninvasive. There are only very limited data on the behavior of those that are invasive. To further characterize the behavior of MPSCs, invasive versus noninvasive primary tumors were distinguished based on the presence or absence of destructive infiltrative growth. To qualify for inclusion, invasive MPSCs, like the noninvasive tumors, were required to display a micropapillary architecture and low-grade nuclei. A total of 135 cases of MPSC were identified: 96 noninvasive and 39 invasive. On follow-up, survival for 10 patients with stage I noninvasive and invasive MPSCs was 100%, and survival for women with stage II and III noninvasive and invasive MPSCs with noninvasive implants was 80%. In contrast, the 5-year and 10-year survival for patients with stage II and III noninvasive MPSCs with invasive implants was 85% and 55%, respectively. The 5-year and 10-year survival for women with invasive MPSCs and invasive implants was 55% and 45%, respectively. The median time from diagnosis to death for women with noninvasive and invasive MPSCs with invasive implants was 60 months (range 33-240 months). The indolent behavior of these low-grade carcinomas distinguishes them from conventional serous carcinomas, which are high-grade aggressive neoplasms. Five of six patients with small (<5 mm) MPSCs in whom follow-up was available presented with high stage disease. Of these five women, three are alive and well and two are alive with disease (one with invasive and one with noninvasive implants). Nearly three fourths of noninvasive MPSCs were associated with atypical proliferative serous tumors, adenofibromas, or both, and 62% of invasive MPSCs were associated with noninvasive MPSCs, atypical proliferative serous tumors, and adenofibromas, alone or in combination. In addition to the frequent mixtures of these tumor components, transitions between them were common. These data in conjunction with recent molecular genetic studies strongly suggest that MPSCs (low-grade carcinomas) arise from atypical proliferative serous tumors unlike conventional serous carcinomas (high-grade carcinomas), which appear to develop de novo. The findings provide further support for the hypothesis that there are distinct pathways of carcinogenesis for low-grade and high-grade serous carcinoma of the ovary.

Adolescent↗

PubMed2005

Bayesian analysis of hierarchical pattern-mixture models for clinical trials data with attrition and comparisons to commonly used ad-hoc and model-based approaches.

This article addresses the problem of making scientifically sound inferences from clinical trials data with attrition, when reasons of attrition seem related to the outcomes of interest. The problem is particularly difficult when the effect of a covariate is to be estimated and if the dropout mechanism appears to operate differently at different levels of the covariate. In this context, multiple imputation under a multilevel pattern-mixture model that allows random variation across dropout groups is presented. Using simulated data generated around an alcoholic hepatitis trial, we compare the performance of this model and commonly used ad-hoc and model-based approaches.

Algorithms↗