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1.

Background

The aims of this study were to investigate whether the preoperative hematologic markers, the neutrophil-lymphocyte ratio (NLR) or the platelet-lymphocyte ratio (PLR) were prognostic indicators and to develop a novel risk stratification model in pN0 non-small-cell lung cancer (NSCLC).

Methods

We performed a retrospective analysis of 400 consecutive pN0 NSCLC patients. Prognostic values were evaluated by Cox proportional hazard model analyses and patients were stratified according to relative risks for patients’ survival.

Results

During the follow-up, 117 patients had cancer recurrence, and 86 patients died. In univariate analysis, age, gender, smoke status and tumor size as well as WBC, NEU, LYM, PLR and NLR were significantly associated with patients’ prognosis. In multivariate analysis, age, tumor size and NLR were independent predictors for patients’ overall survival (P = 0.024, 0.001, and 0.002 respectively). PLR didn’t associated with patients’ survival in multivariate analysis. Patients were stratified into 3 risk groups and the differences among the groups were significant according to disease free survival and overall survival (P = 0.000 and 0.000 respectively).

Conclusions

We confirmed that NLR other than PLR was an independent prognostic factor. Combination of NLR, age and tumor size could stratify pN0 NSCLC patients into 3 risk groups and enabled us to develop a novel risk stratification model.  相似文献   

2.

Background

Genomic selection can be implemented by a multi-step procedure, which requires a response variable and a statistical method. For pure-bred pigs, it was hypothesised that deregressed estimated breeding values (EBV) with the parent average removed as the response variable generate higher reliabilities of genomic breeding values than EBV, and that the normal, thick-tailed and mixture-distribution models yield similar reliabilities.

Methods

Reliabilities of genomic breeding values were estimated with EBV and deregressed EBV as response variables and under the three statistical methods, genomic BLUP, Bayesian Lasso and MIXTURE. The methods were examined by splitting data into a reference data set of 1375 genotyped animals that were performance tested before October 2008, and 536 genotyped validation animals that were performance tested after October 2008. The traits examined were daily gain and feed conversion ratio.

Results

Using deregressed EBV as the response variable yielded 18 to 39% higher reliabilities of the genomic breeding values than using EBV as the response variable. For daily gain, the increase in reliability due to deregression was significant and approximately 35%, whereas for feed conversion ratio it ranged between 18 and 39% and was significant only when MIXTURE was used. Genomic BLUP, Bayesian Lasso and MIXTURE had similar reliabilities.

Conclusions

Deregressed EBV is the preferred response variable, whereas the choice of statistical method is less critical for pure-bred pigs. The increase of 18 to 39% in reliability is worthwhile, since the reliabilities of the genomic breeding values directly affect the returns from genomic selection.  相似文献   

3.

Purpose

To describe women’s condom use and assess predictors of consistent condom use and dual method use in the 6 months after the initiation of oral contraception (OC).

Methods

We conducted a planned secondary cohort analysis among women less than 25 years of age initiating oral contraceptives at public family planning clinics in Atlanta, Dallas and New York City, USA, as part of a randomized trial. These clinics provide care to predominantly African American or Hispanic women of low socioeconomic status. Participants completed interviews at enrollment and at 6 months after OC start. We used multivariate logistic regression to assess factors associated with consistent condom and dual method use at 6 months.

Results

1281 participants met the inclusion criteria for this analysis. At enrollment prior to OC start, 28% were consistent condom users. In the six months after initiation of oral contraception, only 14% always used a condom and 4% always used dual methods. In multivariate analysis, receiving basic advice to always use a condom after OC initiation from a provider during the baseline clinic consultation was associated with a 50% increase in the odds of using condoms consistently. Only 28% of participants were given this condom use advice.

Conclusions

This study documents a decline in women’s condom consistent use subsequent to initiation of the oral contraceptive and suggests that opportunities for positive intervention around condom use among women starting hormonal methods are being missed. Basic condom use advice, which is neither time consuming nor resource dependent, was associated with increased consistent use and should be immediately implemented in all family planning services.  相似文献   

4.

Background

The recent advent of high-throughput SNP genotyping technologies has opened new avenues of research for population genetics. In particular, a growing interest in the identification of footprints of selection, based on genome scans for adaptive differentiation, has emerged.

Methodology/Principal Findings

The purpose of this study is to develop an efficient model-based approach to perform Bayesian exploratory analyses for adaptive differentiation in very large SNP data sets. The basic idea is to start with a very simple model for neutral loci that is easy to implement under a Bayesian framework and to identify selected loci as outliers via Posterior Predictive P-values (PPP-values). Applications of this strategy are considered using two different statistical models. The first one was initially interpreted in the context of populations evolving respectively under pure genetic drift from a common ancestral population while the second one relies on populations under migration-drift equilibrium. Robustness and power of the two resulting Bayesian model-based approaches to detect SNP under selection are further evaluated through extensive simulations. An application to a cattle data set is also provided.

Conclusions/Significance

The procedure described turns out to be much faster than former Bayesian approaches and also reasonably efficient especially to detect loci under positive selection.  相似文献   

5.

Background

In a given population the age pattern of mortality is an important determinant of total number of deaths, age structure, and through effects on age structure, the number of births and thereby growth. Good mortality models exist for most populations except those experiencing generalized HIV epidemics and some developing country populations. The large number of deaths concentrated at very young and adult ages in HIV-affected populations produce a unique ‘humped’ age pattern of mortality that is not reproduced by any existing mortality models. Both burden of disease reporting and population projection methods require age-specific mortality rates to estimate numbers of deaths and produce plausible age structures. For countries with generalized HIV epidemics these estimates should take into account the future trajectory of HIV prevalence and its effects on age-specific mortality. In this paper we present a parsimonious model of age-specific mortality for countries with generalized HIV/AIDS epidemics.

Methods and Findings

The model represents a vector of age-specific mortality rates as the weighted sum of three independent age-varying components. We derive the age-varying components from a Singular Value Decomposition of the matrix of age-specific mortality rate schedules. The weights are modeled as a function of HIV prevalence and one of three possible sets of inputs: life expectancy at birth, a measure of child mortality, or child mortality with a measure of adult mortality. We calibrate the model with 320 five-year life tables for each sex from the World Population Prospects 2010 revision that come from the 40 countries of the world that have and are experiencing a generalized HIV epidemic. Cross validation shows that the model is able to outperform several existing model life table systems.

Conclusions

We present a flexible, parsimonious model of age-specific mortality for countries with generalized HIV epidemics. Combined with the outputs of existing epidemiological and demographic models, this model makes it possible to project future age-specific mortality profiles and number of deaths for countries with generalized HIV epidemics.  相似文献   

6.

Introduction

With the renewed drive towards malaria elimination, there is a need for improved surveillance tools. While time series analysis is an important tool for surveillance, prediction and for measuring interventions’ impact, approximations by commonly used Gaussian methods are prone to inaccuracies when case counts are low. Therefore, statistical methods appropriate for count data are required, especially during “consolidation” and “pre-elimination” phases.

Methods

Generalized autoregressive moving average (GARMA) models were extended to generalized seasonal autoregressive integrated moving average (GSARIMA) models for parsimonious observation-driven modelling of non Gaussian, non stationary and/or seasonal time series of count data. The models were applied to monthly malaria case time series in a district in Sri Lanka, where malaria has decreased dramatically in recent years.

Results

The malaria series showed long-term changes in the mean, unstable variance and seasonality. After fitting negative-binomial Bayesian models, both a GSARIMA and a GARIMA deterministic seasonality model were selected based on different criteria. Posterior predictive distributions indicated that negative-binomial models provided better predictions than Gaussian models, especially when counts were low. The G(S)ARIMA models were able to capture the autocorrelation in the series.

Conclusions

G(S)ARIMA models may be particularly useful in the drive towards malaria elimination, since episode count series are often seasonal and non-stationary, especially when control is increased. Although building and fitting GSARIMA models is laborious, they may provide more realistic prediction distributions than do Gaussian methods and may be more suitable when counts are low.  相似文献   

7.
8.

Background

The theory of genomic selection is based on the prediction of the effects of quantitative trait loci (QTL) in linkage disequilibrium (LD) with markers. However, there is increasing evidence that genomic selection also relies on "relationships" between individuals to accurately predict genetic values. Therefore, a better understanding of what genomic selection actually predicts is relevant so that appropriate methods of analysis are used in genomic evaluations.

Methods

Simulation was used to compare the performance of estimates of breeding values based on pedigree relationships (Best Linear Unbiased Prediction, BLUP), genomic relationships (gBLUP), and based on a Bayesian variable selection model (Bayes B) to estimate breeding values under a range of different underlying models of genetic variation. The effects of different marker densities and varying animal relationships were also examined.

Results

This study shows that genomic selection methods can predict a proportion of the additive genetic value when genetic variation is controlled by common quantitative trait loci (QTL model), rare loci (rare variant model), all loci (infinitesimal model) and a random association (a polygenic model). The Bayes B method was able to estimate breeding values more accurately than gBLUP under the QTL and rare variant models, for the alternative marker densities and reference populations. The Bayes B and gBLUP methods had similar accuracies under the infinitesimal model.

Conclusions

Our results suggest that Bayes B is superior to gBLUP to estimate breeding values from genomic data. The underlying model of genetic variation greatly affects the predictive ability of genomic selection methods, and the superiority of Bayes B over gBLUP is highly dependent on the presence of large QTL effects. The use of SNP sequence data will outperform the less dense marker panels. However, the size and distribution of QTL effects and the size of reference populations still greatly influence the effectiveness of using sequence data for genomic prediction.  相似文献   

9.

Background

Classification and regression tree (CART) models are tree-based exploratory data analysis methods which have been shown to be very useful in identifying and estimating complex hierarchical relationships in ecological and medical contexts. In this paper, a Bayesian CART model is described and applied to the problem of modelling the cryptosporidiosis infection in Queensland, Australia.

Methodology/Principal Findings

We compared the results of a Bayesian CART model with those obtained using a Bayesian spatial conditional autoregressive (CAR) model. Overall, the analyses indicated that the nature and magnitude of the effect estimates were similar for the two methods in this study, but the CART model more easily accommodated higher order interaction effects.

Conclusions/Significance

A Bayesian CART model for identification and estimation of the spatial distribution of disease risk is useful in monitoring and assessment of infectious diseases prevention and control.  相似文献   

10.

Background

Graduate entry medicine raises new questions about the suitability of students with different backgrounds. We examine this, and the broader issue of effectiveness of selection and assessment procedures.

Methods

The data included background characteristics, academic record, interview score and performance in pre-clinical modular assessment for two years intake of graduate entry medical students. Exploratory factor analysis is a powerful method for reducing a large number of measures to a smaller group of underlying factors. It was used here to identify patterns within and between the selection and performance data.

Principal Findings

Basic background characteristics were of little importance in predicting exam success. However, easily interpreted components were detected within variables comprising the ‘selection’ and ‘assessment’ criteria. Three selection components were identified (‘Academic’, ‘GAMSAT’, ‘Interview’) and four assessment components (‘General Exam’, ‘Oncology’, ‘OSCE’, ‘Family Case Study’). There was a striking lack of relationships between most selection and performance factors. Only ‘General Exam’ and ‘Academic’ showed a correlation (Pearson''s r = 0.55, p<0.001).

Conclusions

This study raises questions about methods of student selection and their effectiveness in predicting performance and assessing suitability for a medical career. Admissions tests and most exams only confirmed previous academic achievement, while interview scores were not correlated with any consequent assessment.  相似文献   

11.

Introduction

HIV stigma is a contributing factor to poor patient outcomes. Although HIV stigma has been documented, its impact on patient well-being in the southern US is not well understood.

Methods

Thirty-two adults participated in cognitive interviews after completing the Berger HIV or the Van Rie stigma scale. Participant responses were probed to ensure the scales accurately measured stigma and to assess the impact stigma had on behavior.

Results

Three main themes emerged regarding HIV stigma: (1) negative attitudes, fear of contagion, and misperceptions about transmission; (2) acts of discrimination by families, friends, health care providers, and within the workplace; and (3) participants’ use of self-isolation as a coping mechanism. Overwhelming reluctance to disclose a person’s HIV status made identifying enacted stigma with a quantitative scale difficult.

Discussion

Fear of discrimination resulted in participants isolating themselves from friends or experiences to avoid disclosure. Participant unwillingness to disclose their HIV status to friends and family could lead to an underestimation of enacted HIV stigma in quantitative scales.  相似文献   

12.

Introduction

Interferon regulatory factor 1 (IRF1) is induced by HIV early in the infection process and serves two functions: transactivation of the HIV-1 genome and thus replication, and eliciting antiviral innate immune responses. We previously described three IRF1 polymorphisms that correlate with reduced IRF1 expression and reduced HIV susceptibility.

Objective

To determine whether IRF1 polymorphisms previously associated with reduced HIV susceptibility play a role in HIV pathogenesis and disease progression in HIV-infected ART-naïve individuals.

Methods

IRF1 genotyping for polymorphisms (619, MS and 6516) was performed by PCR in 847 HIV positive participants from a sex worker cohort in Nairobi, Kenya. Rates of CD4+ T cell decline and viral loads (VL) were analyzed using linear mixed models.

Results

Three polymorphisms in the IRF1, located at 619, microsatellite region and 6516 of the gene, previously associated with decreased susceptibility to HIV infection show no effect on disease progression, either measured by HIV-1 RNA levels or the slopes of CD4 decline before treatment initiation.

Conclusion

Whereas these three polymorphisms in the IRF1 gene protect against HIV-1 acquisition, they appear to exert no discernable effects once infection is established.  相似文献   

13.

Background

In quantitative trait mapping and genomic prediction, Bayesian variable selection methods have gained popularity in conjunction with the increase in marker data and computational resources. Whereas shrinkage-inducing methods are common tools in genomic prediction, rigorous decision making in mapping studies using such models is not well established and the robustness of posterior results is subject to misspecified assumptions because of weak biological prior evidence.

Methods

Here, we evaluate the impact of prior specifications in a shrinkage-based Bayesian variable selection method which is based on a mixture of uniform priors applied to genetic marker effects that we presented in a previous study. Unlike most other shrinkage approaches, the use of a mixture of uniform priors provides a coherent framework for inference based on Bayes factors. To evaluate the robustness of genetic association under varying prior specifications, Bayes factors are compared as signals of positive marker association, whereas genomic estimated breeding values are considered for genomic selection. The impact of specific prior specifications is reduced by calculation of combined estimates from multiple specifications. A Gibbs sampler is used to perform Markov chain Monte Carlo estimation (MCMC) and a generalized expectation-maximization algorithm as a faster alternative for maximum a posteriori point estimation. The performance of the method is evaluated by using two publicly available data examples: the simulated QTLMAS XII data set and a real data set from a population of pigs.

Results

Combined estimates of Bayes factors were very successful in identifying quantitative trait loci, and the ranking of Bayes factors was fairly stable among markers with positive signals of association under varying prior assumptions, but their magnitudes varied considerably. Genomic estimated breeding values using the mixture of uniform priors compared well to other approaches for both data sets and loss of accuracy with the generalized expectation-maximization algorithm was small as compared to that with MCMC.

Conclusions

Since no error-free method to specify priors is available for complex biological phenomena, exploring a wide variety of prior specifications and combining results provides some solution to this problem. For this purpose, the mixture of uniform priors approach is especially suitable, because it comprises a wide and flexible family of distributions and computationally intensive estimation can be carried out in a reasonable amount of time.  相似文献   

14.

Background

Genomic selection has become an important tool in the genetic improvement of animals and plants. The objective of this study was to investigate the impacts of breeding value estimation method, reference population structure, and trait genetic architecture, on long-term response to genomic selection without updating marker effects.

Methods

Three methods were used to estimate genomic breeding values: a BLUP method with relationships estimated from genome-wide markers (GBLUP), a Bayesian method, and a partial least squares regression method (PLSR). A shallow (individuals from one generation) or deep reference population (individuals from five generations) was used with each method. The effects of the different selection approaches were compared under four different genetic architectures for the trait under selection. Selection was based on one of the three genomic breeding values, on pedigree BLUP breeding values, or performed at random. Selection continued for ten generations.

Results

Differences in long-term selection response were small. For a genetic architecture with a very small number of three to four quantitative trait loci (QTL), the Bayesian method achieved a response that was 0.05 to 0.1 genetic standard deviation higher than other methods in generation 10. For genetic architectures with approximately 30 to 300 QTL, PLSR (shallow reference) or GBLUP (deep reference) had an average advantage of 0.2 genetic standard deviation over the Bayesian method in generation 10. GBLUP resulted in 0.6% and 0.9% less inbreeding than PLSR and BM and on average a one third smaller reduction of genetic variance. Responses in early generations were greater with the shallow reference population while long-term response was not affected by reference population structure.

Conclusions

The ranking of estimation methods was different with than without selection. Under selection, applying GBLUP led to lower inbreeding and a smaller reduction of genetic variance while a similar response to selection was achieved. The reference population structure had a limited effect on long-term accuracy and response. Use of a shallow reference population, most closely related to the selection candidates, gave early benefits while in later generations, when marker effects were not updated, the estimation of marker effects based on a deeper reference population did not pay off.  相似文献   

15.

Purpose

Improve the ability to infer sex behaviors more accurately using network data.

Methods

A hybrid network analytic approach was utilized to integrate: (1) the plurality of reports from others tied to individual(s) of interest; and (2) structural features of the network generated from those ties. Network data was generated from digitally extracted cell-phone contact lists of a purposeful sample of 241 high-risk men in India. These data were integrated with interview responses to describe the corresponding individuals in the contact lists and the ties between them. HIV serostatus was collected for each respondent and served as an internal validation of the model’s predictions of sex behavior.

Results

We found that network-based model predictions of sex behavior and self-reported sex behavior had limited correlation (54% agreement). Additionally, when respondent sex behaviors were re-classified to network model predictions from self-reported data, there was a 30.7% decrease in HIV seroprevalence among groups of men with lower risk behavior, which is consistent with HIV transmission biology.

Conclusion

Combining the relative completeness and objectivity of digital network data with the substantive details of classical interview and HIV biomarker data permitted new analyses and insights into the accuracy of self-reported sex behavior.  相似文献   

16.

Background

Imperfect diagnostic testing reduces the power to detect significant predictors in classical cross-sectional studies. Assuming that the misclassification in diagnosis is random this can be dealt with by increasing the sample size of a study. However, the effects of imperfect tests in longitudinal data analyses are not as straightforward to anticipate, especially if the outcome of the test influences behaviour. The aim of this paper is to investigate the impact of imperfect test sensitivity on the determination of predictor variables in a longitudinal study.

Methodology/Principal Findings

To deal with imperfect test sensitivity affecting the response variable, we transformed the observed response variable into a set of possible temporal patterns of true disease status, whose prior probability was a function of the test sensitivity. We fitted a Bayesian discrete time survival model using an MCMC algorithm that treats the true response patterns as unknown parameters in the model. We applied our approach to epidemiological data of bovine tuberculosis outbreaks in England and investigated the effect of reduced test sensitivity in the determination of risk factors for the disease. We found that reduced test sensitivity led to changes to the collection of risk factors associated with the probability of an outbreak that were chosen in the ‘best’ model and to an increase in the uncertainty surrounding the parameter estimates for a model with a fixed set of risk factors that were associated with the response variable.

Conclusions/Significance

We propose a novel algorithm to fit discrete survival models for longitudinal data where values of the response variable are uncertain. When analysing longitudinal data, uncertainty surrounding the response variable will affect the significance of the predictors and should therefore be accounted for either at the design stage by increasing the sample size or at the post analysis stage by conducting appropriate sensitivity analyses.  相似文献   

17.
18.

Objective

The evaluation of HIV treatment programs is generally based on an estimation of survival among patients receiving antiretroviral treatment (ART). In large HIV programs, loss to follow-up (LFU) rates remain high despite active patient tracing, which is likely to bias survival estimates and survival regression analyses.

Methods

We compared uncorrected survival estimates derived from routine program data with estimates obtained by applying six correction methods that use updated outcome data by a field survey targeting LFU patients in a rural HIV program in Malawi. These methods were based on double-sampling and differed according to the weights given to survival estimates in LFU and non-LFU subpopulations. We then proposed a correction of the survival regression analysis.

Results

Among 6,727 HIV-infected adults receiving ART, 9% were LFU after one year. The uncorrected survival estimates from routine data were 91% in women and 84% in men. According to increasing sophistication of the correction methods, the corrected survival estimates ranged from 89% to 85% in women and 82% to 77% in men. The estimates derived from uncorrected regression analyses were highly biased for initial tuberculosis mortality ratios (RR; 95% CI: 1.07; 0.76–1.50 vs. 2.06 to 2.28 with different correction weights), Kaposi sarcoma diagnosis (2.11; 1.61–2.76 vs. 2.64 to 3.9), and year of ART initiation (1.40; 1.17–1.66 vs. 1.29 to 1.34).

Conclusions

In HIV programs with high LFU rates, the use of correction methods based on non-exhaustive double-sampling data are necessary to minimise the bias in survival estimates and survival regressions.  相似文献   

19.
P Gao  X Zhou  ZN Wang  YX Song  LL Tong  YY Xu  ZY Yue  HM Xu 《PloS one》2012,7(7):e42015

Objective

Over the past decades, many studies have used data mining technology to predict the 5-year survival rate of colorectal cancer, but there have been few reports that compared multiple data mining algorithms to the TNM classification of malignant tumors (TNM) staging system using a dataset in which the training and testing data were from different sources. Here we compared nine data mining algorithms to the TNM staging system for colorectal survival analysis.

Methods

Two different datasets were used: 1) the National Cancer Institute''s Surveillance, Epidemiology, and End Results dataset; and 2) the dataset from a single Chinese institution. An optimization and prediction system based on nine data mining algorithms as well as two variable selection methods was implemented. The TNM staging system was based on the 7th edition of the American Joint Committee on Cancer TNM staging system.

Results

When the training and testing data were from the same sources, all algorithms had slight advantages over the TNM staging system in predictive accuracy. When the data were from different sources, only four algorithms (logistic regression, general regression neural network, Bayesian networks, and Naïve Bayes) had slight advantages over the TNM staging system. Also, there was no significant differences among all the algorithms (p>0.05).

Conclusions

The TNM staging system is simple and practical at present, and data mining methods are not accurate enough to replace the TNM staging system for colorectal cancer survival prediction. Furthermore, there were no significant differences in the predictive accuracy of all the algorithms when the data were from different sources. Building a larger dataset that includes more variables may be important for furthering predictive accuracy.  相似文献   

20.

Background

For the first time in the history of HIV, new bio-medical interventions have been shown to be effective in preventing HIV transmission. For these new HIV prevention technologies (NPTs) to have an impact on the epidemic, they must be widely used. This study uses a discrete choice experiment (DCE) to: understand the relative strength of women’s preferences for product characteristics, understand the implications for substitution away from male condoms, and inform realistic modelling of their potential impact and cost-effectiveness.

Methods

A DCE was conducted among 1017 women in urban South Africa. Women were presented with choices between potential women’s NPTs (microbicides, diaphragm, female condom) and ‘what I did last time’ (use or not use a condom) with different HIV and pregnancy prevention effectiveness’ and prices. Choice probabilities are estimated using the nested logit model and used to predict uptake.

Results

In this high HIV prevalence setting, HIV prevention effectiveness is the main driver of uptake followed by pregnancy prevention effectiveness. For example a microbicide with poor effectiveness would have niche appeal at just 11% predicted uptake, while a highly effective microbicide (95% effective against HIV and pregnancy) would have far wider appeal (56% predicted uptake). Though women who reported not using condoms were more likely to choose the NPTs, at current very high rates of male condom use in South Africa (60%), about half of microbicide uptake is projected to be among those currently not using condoms.

Conclusions

Women are very interested in NPTs, especially if highly effective in preventing HIV and pregnancy. Women in greatest need were also most likely to switch to the new products. Where products are not yet available for distribution, proxy data, such as that generated by DCEs, can bring realism to overly optimistic uptake scenarios found in many current impact models.  相似文献   

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