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2.
Int J Cancer ; 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31037736

RESUMO

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.

3.
Hum Genet ; 138(4): 307-326, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30820706

RESUMO

Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10- 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10- 4, replication P = 6.7 × 10- 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Frequência do Gene , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
4.
Am J Hum Genet ; 102(5): 904-919, 2018 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-29727690

RESUMO

Genome-wide association studies (GWASs) have successfully identified thousands of genetic variants for many complex diseases; however, these variants explain only a small fraction of the heritability. Recently, genetic association studies that leverage external transcriptome data have received much attention and shown promise for discovering novel variants. One such approach, PrediXcan, is to use predicted gene expression through genetic regulation. However, there are limitations in this approach. The predicted gene expression may be biased, resulting from regularized regression applied to moderately sample-sized reference studies. Further, some variants can individually influence disease risk through alternative functional mechanisms besides expression. Thus, testing only the association of predicted gene expression as proposed in PrediXcan will potentially lose power. To tackle these challenges, we consider a unified mixed effects model that formulates the association of intermediate phenotypes such as imputed gene expression through fixed effects, while allowing residual effects of individual variants to be random. We consider a set-based score testing framework, MiST (mixed effects score test), and propose two data-driven combination approaches to jointly test for the fixed and random effects. We establish the asymptotic distributions, which enable rapid calculation of p values for genome-wide analyses, and provide p values for fixed and random effects separately to enhance interpretability over GWASs. Extensive simulations demonstrate that our approaches are more powerful than existing ones. We apply our approach to a large-scale GWAS of colorectal cancer and identify two genes, POU5F1B and ATF1, which would have otherwise been missed by PrediXcan, after adjusting for all known loci.

5.
Biometrics ; 73(2): 551-561, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28295175

RESUMO

Functional data arise frequently in biomedical studies, where it is often of interest to investigate the association between functional predictors and a scalar response variable. While functional linear models (FLM) are widely used to address these questions, hypothesis testing for the functional association in the FLM framework remains challenging. A popular approach to testing the functional effects is through dimension reduction by functional principal component (PC) analysis. However, its power performance depends on the choice of the number of PCs, and is not systematically studied. In this article, we first investigate the power performance of the Wald-type test with varying thresholds in selecting the number of PCs for the functional covariates, and show that the power is sensitive to the choice of thresholds. To circumvent the issue, we propose a new method of ordering and selecting principal components to construct test statistics. The proposed method takes into account both the association with the response and the variation along each eigenfunction. We establish its theoretical properties and assess the finite sample properties through simulations. Our simulation results show that the proposed test is more robust against the choice of threshold while being as powerful as, and often more powerful than, the existing method. We then apply the proposed method to the cerebral white matter tracts data obtained from a diffusion tensor imaging tractography study.


Assuntos
Modelos Lineares , Imagem de Tensor de Difusão , Análise de Componente Principal
6.
Biostatistics ; 18(1): 119-131, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27474101

RESUMO

The development of next-generation sequencing technologies has allowed researchers to study comprehensively the contribution of genetic variation particularly rare variants to complex diseases. To date many sequencing analyses of rare variants have focused on marginal genetic effects and have not explored the potential role environmental factors play in modifying genetic risk. Analysis of gene-environment interaction (GxE) for rare variants poses considerable challenges because of variant rarity and paucity of subjects who carry the variants while being exposed. To tackle this challenge, we propose a hierarchical model to jointly assess the GxE effects of a set of rare variants for example, in a gene or regulatory region, leveraging the information across the variants. Under this model, GxE is modeled by two components. The first component incorporates variant functional information as weights to calculate the weighted burden of variant alleles across variants, and then assess their GxE interaction with the environmental factor. Since this information is a priori known, this component is fixed effects in the model. The second component involves residual GxE effects that have not been accounted for by the fixed effects. In this component, the residual GxE effects are postulated to follow an unspecified distribution with mean 0 and variance [Formula: see text] We develop a novel testing procedure by deriving two independent score statistics for the fixed effects and the variance component separately. We propose two data-adaptive combination approaches for combining these two score statistics and establish the asymptotic distributions. An extensive simulation study shows that the proposed approaches maintain the correct type I error and the power is comparable to or better than existing methods under a wide range of scenarios. Finally we illustrate the proposed methods by a exome-wide GxE analysis with NSAIDs use in colorectal cancer.


Assuntos
Interação Gene-Ambiente , Modelos Genéticos , Modelos Estatísticos , Análise de Sequência de DNA/estatística & dados numéricos , Humanos
7.
PLoS One ; 11(7): e0158468, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27383645

RESUMO

Despite the importance of trauma in healthspan and lifespan in humans as well as in non-human species, with one important exception the literature in both gerontology and ecology contains virtually no experimental demographic studies concerned with trauma in any species. We used dietary manipulation [full diet (F) versus sugar-only (S)] to produce four levels of frailty in 55-day old tephritid fruit flies (Anastrepha ludens) that were then subject to the trauma of cage transfer stress (n = 900/sex in each of the 4 treatments). The key results included the following: (1) there is a trauma effect caused by the transfer that depends on previous diet before transfer, new diet after transfer and gender of the fly; (2) males are more vulnerable than females; (3) if initial diet was F, flies are relatively immune against the trauma, and the subsequent diet (F or S) does not matter; (4) however if initial diet was S, then the effect of the trauma depends largely on the diet after the transfer; (5) flies transferred from S to F diets do very well in terms of remaining longevity (i.e. greatest remaining longevity), while flies transferred from S to S diet do poorly (i.e. shortest remaining longevity). We discuss both the strengths and weaknesses of this study and implications of the results.


Assuntos
Dieta , Longevidade/fisiologia , Estresse Fisiológico , Tephritidae/fisiologia , Algoritmos , Animais , Comportamento Animal , Restrição Calórica , Feminino , Fertilidade/fisiologia , Masculino , Modelos de Riscos Proporcionais , Fatores Sexuais
8.
Ann Stat ; 44(3): 1298-1331, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29527068

RESUMO

In this paper, we investigate frailty models for clustered survival data that are subject to both left- and right-censoring, termed "doubly-censored data". This model extends current survival literature by broadening the application of frailty models from right-censoring to a more complicated situation with additional left censoring. Our approach is motivated by a recent Hepatitis B study where the sample consists of families. We adopt a likelihood approach that aims at the nonparametric maximum likelihood estimators (NPMLE). A new algorithm is proposed, which not only works well for clustered data but also improve over existing algorithm for independent and doubly-censored data, a special case when the frailty variable is a constant equal to one. This special case is well known to be a computational challenge due to the left censoring feature of the data. The new algorithm not only resolves this challenge but also accommodate the additional frailty variable effectively. Asymptotic properties of the NPMLE are established along with semi-parametric efficiency of the NPMLE for the finite-dimensional parameters. The consistency of Bootstrap estimators for the standard errors of the NPMLE is also discussed. We conducted some simulations to illustrate the numerical performance and robustness of the proposed algorithm, which is also applied to the Hepatitis B data.

9.
J Agric Food Chem ; 63(46): 10200-8, 2015 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-26574624

RESUMO

The colloidal complexes composed of grape seed proanthocyanidin (GSP) and gelatin (GLT), as natural antioxidants to improve stability and inhibit lipid oxidation in menhaden fish oil emulsions, were evaluated. The interactions between GSP and GLT, and the chemical structures of GSP/GLT self-assembled colloidal complexes, were characterized by isothermal titration calorimetry (ITC), circular dichroism (CD), and Fourier transform infrared spectroscopic (FTIR) studies. Fish oil was emulsified with GLT to obtain an oil-in-water (o/w) emulsion. After formation of the emulsion, GLT was fixed by GSP to obtain the GSP/GLT colloidal complexes stabilized fish oil emulsion. Menhaden oil emulsified by GSP/GLT(0.4 wt %) colloidal complexes yielded an emulsion with smaller particles and higher emulsion stability as compared to its GLT emulsified counterpart. The GSP/GLT colloidal complexes inhibited the lipid oxidation in fish oil emulsions more effectively than free GLT because the emulsified fish oil was surrounded by the antioxidant GSP/GLT colloidal complexes. The digestion rate of the fish oil emulsified with the GSP/GLT colloidal complexes was reduced as compared to that emulsified with free GLT. The extent of free fatty acids released from the GSP/GLT complexes stabilized fish oil emulsions was 63.3% under simulated digestion condition, indicating that the fish oil emulsion was considerably hydrolyzed with lipase.


Assuntos
Coloides/farmacologia , Digestão/efeitos dos fármacos , Emulsões/metabolismo , Óleos de Peixe/metabolismo , Gelatina/farmacologia , Extrato de Sementes de Uva/farmacologia , Proantocianidinas/farmacologia , Antioxidantes , Coloides/química , Estabilidade de Medicamentos , Ácidos Graxos/metabolismo , Óleos de Peixe/química , Gelatina/química , Extrato de Sementes de Uva/química , Hidrólise , Lipase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Proantocianidinas/química
10.
Intensive Care Med ; 41(10): 1791-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26183489

RESUMO

PURPOSE: Conventional echocardiography may not detect subtle cardiac dysfunction of septic patients. Two-dimensional left ventricular (LV) global peak systolic longitudinal strain (GLS) can detect early cardiac dysfunction. We sought to determine the prognostic value of GLS for septic shock patients admitted to intensive care units (ICUs). METHODS: We prospectively included 111 ICU patients with septic shock. A full medical history was recorded for each patient, and LV systolic function, including GLS, was measured. Our endpoints were ICU and hospital mortality. RESULTS: The ICU and hospital mortalities were 31.5% (n = 35) and 35.1% (n = 39), respectively. There was no significant difference in LV ejection fraction of the non-survivors and the survivors; however, upon ICU admission, the non-survivors exhibited GLSs that were less negative than those of the survivors, which indicated worse LV systolic function. GLS of -13% presented the best sensitivity and specificity in the prediction of mortality (area under the curve 0.79). The patients with GLS ≥ -13% exhibited higher ICU and hospital mortality rates (hazard ratio 4.34, p < 0.001 and hazard ratio 4.21, p < 0.001, respectively). Cox regression analyses revealed that higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores and less negative GLSs were independent predictors of ICU and hospital mortalities. GLS was found to add prognostic information to the APACHE II score. CONCLUSIONS: These findings suggest that combining GLS and the APACHE II score has additive value in the prediction of ICU and hospital mortalities and that GLS may help in early identification of high-risk septic shock patients in ICU.


Assuntos
Cuidados Críticos/métodos , Choque Séptico/mortalidade , Choque Séptico/fisiopatologia , Sobreviventes/estatística & dados numéricos , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Ecocardiografia Tridimensional , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiografia , Fatores de Risco , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagem
11.
Biomed Res Int ; 2014: 217290, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24895553

RESUMO

Using a speckle-tracking echocardiography (STE), we recently demonstrated that a left ventricular (LV) global longitudinal strain (GLS) ≥ -15% and the serum cardiac troponin T (cTnT) concentration are associated with mortality in stable hemodialysis patients with preserved LV ejection fraction (LVEF). In this study, we explored the relationship between cTnT and echocardiographic parameters and evaluated whether the prognostic value provided by cTnT is independent of a GLS ≥ -15% and vice versa. Eighty-eight stable hemodialysis patients with preserved LVEF were followed for 31 months. STE studies and measurements of cTnT were performed at baseline. CTnT concentration had a modest correlation with GLS (rs = 0.44; P < 0.001) but had a weak or nonsignificant correlation with other echocardiographic parameters. Adjusting for clinical parameters, hazard ratios for each increase of 0.01 ng/mL in cTnT, and a GLS ≥ -15% on mortality were 1.13 (P = 0.009) and 3.09 (P = 0.03) without significant interaction between cTnT and GLS ≥ -15%. In addition, an increased cTnT concentration, a GLS ≥ -15%, or their combination showed significant additional predictive value for mortality when included in models consisting of clinical parameters. Therefore, both cTnT and a GLS ≥ -15% are independent predictors of mortality and are useful for risk stratification.


Assuntos
Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Miocárdio/metabolismo , Diálise Renal/mortalidade , Volume Sistólico , Troponina T/metabolismo , Idoso , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Modelos de Riscos Proporcionais , Curva ROC , Análise de Regressão , Estatísticas não Paramétricas , Ultrassonografia
12.
PLoS One ; 9(3): e89457, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24599060

RESUMO

BACKGROUND: High circulating interleukin (IL)-18 level predicts a higher hospitalization rate among dialysis patients, possibly through cardiovascular mechanisms; however, whether higher IL-18 level is associated with mortality in dialysis patients is less clear. In addition, its impacts on left ventricular (LV) function are also unknown. We conducted a cohort study to examine the impacts of IL-18 level on LV function and prognosis among clinically stable hemodialysis patients. METHODS: Clinically stable patients undergoing maintenance hemodialysis (≥ 3 months) were prospectively enrolled from December 2008 to January 2009, and were followed up for 31 months. The enrolled patients (41% male, 66.4 ± 10.9 years of age) received 2-dimensional echocardiography and myocardial deformation (strain) analysis, including LV peak systolic longitudinal strain (GLS) and circumferential strain (CS). Laboratory measurements were also performed. Cox regression analysis was used to investigate prognostic factors. RESULTS: Seventy-five patients were stratified into 2 groups by the median value of IL-18 (654.2 pg/ml). Between these 2 groups, there was no significant difference in baseline characteristics including LV ejection fraction. The high IL-18 group had a worse LV systolic function as demonstrated by reduced GLS and CS. Seventeen patients (22.7%) died during the follow-up period. Multivariate Cox regression analysis showed that low serum albumin, the presence of hypertension, high serum IL-18, and less negative GLS (>-15%) were independently associated with all-cause mortality. No significant interaction between IL-18 and less negative GLS was noted in the final Cox model. CONCLUSION: Hemodialysis patients with high IL-18 levels tend to have worse LV systolic function and higher mortality rate. However, elevated serum IL-18 level is predictive of poor prognosis among stable hemodialysis patients, independently of LV dysfunction. This suggests an additional value of IL-18 to echocardiographic study in predicting all-cause mortality, and IL-18 may be helpful in early risk stratification of hemodialysis patients.


Assuntos
Hipertrofia Ventricular Esquerda/sangue , Interleucina-18/sangue , Falência Renal Crônica/sangue , Disfunção Ventricular Esquerda/sangue , Idoso , Feminino , Hospitalização , Humanos , Hipertrofia Ventricular Esquerda/mortalidade , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Curva ROC , Diálise Renal , Disfunção Ventricular Esquerda/mortalidade , Função Ventricular Esquerda
13.
Clin J Am Soc Nephrol ; 8(9): 1564-74, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23704303

RESUMO

BACKGROUND AND OBJECTIVES: Little is known about the optimal echocardiographic parameters for risk stratification in stable dialysis patients with preserved left ventricular ejection fraction (LVEF) (ejection fraction ≥ 50%). Left ventricular (LV) global peak systolic longitudinal strain (GLS) is the ratio of the maximal change in myocardial longitudinal length in systole to the original length and reliably and accurately assesses LV function. During systole, LV myocardium in the longitudinal direction shortens and GLS is represented by a negative value. The more negative value of GLS, the better the LV function is. This study hypothesized that subtle abnormalities of GLS are associated with an adverse prognosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This prospective study collected clinical and echocardiographic data (including GLS) from 88 stable hemodialysis patients (mean age 67.0 ± 11.2 years; 35% men) with preserved LVEF. These patients were enrolled from December 2008 to January 2009 and were followed-up for 25.6 ± 9.9 months. The primary outcome was all-cause mortality. Multivariate Cox regression analysis was used to investigate risk factors for mortality. RESULTS: The mortality group (n=24) had lower albumin levels, less negative GLS, and higher prevalence of coronary artery disease and diabetes mellitus than the survival group. Using a GLS cutoff value of -15%, the less negative GLS group (GLS ≥-15%) had a higher mortality rate. Cox regression analyses revealed that lower albumin level (hazard ratio, 0.16; 95% confidence interval, 0.05 to 0.53; P=0.003) and less negative GLS (hazard ratio, 3.57; 95% confidence interval, 1.41 to 9.04; P=0.01) were independent predictors of all-cause mortality. Furthermore, less negative GLS was associated with a higher cardiovascular death rate. CONCLUSIONS: Less negative GLS is predictive of poor prognosis among stable hemodialysis patients with preserved LVEF.


Assuntos
Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/mortalidade , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/mortalidade , Idoso , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus/epidemiologia , Ecocardiografia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Diálise Renal , Insuficiência Renal Crônica/terapia , Albumina Sérica/metabolismo , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem
14.
J Pediatr Gastroenterol Nutr ; 54(1): 97-100, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21716132

RESUMO

OBJECTIVE: The present study aimed to investigate the association between serial serum alanine aminotransferase (ALT) and spontaneous hepatitis B e antigen (HBeAg) seroconversion age in chronic hepatitis B virus (HBV)-infected children. PATIENTS AND METHODS: One hundred four HBeAg-positive chronic genotype B or C HBV-infected patients were included in this long-term prospective cohort study (mean initial age 7.20 years). Serial serum ALT levels and HBV serology markers were measured every 6 to 12 months. The 104 subjects made a total of 2525 visits during the study period, and the majority (93.6%) of visits were within a 1-year interval apart from previous visits. Cox proportional hazards model with time-dependent covariates was used in the survival analysis of HBeAg in these subjects. RESULTS: During the chronic course of HBV infection, the median remaining times to spontaneous HBeAg seroconversion were 8.35, 5.14, 4.25, 3.95, and 2.80 years after the ALT levels crossed 20, 30, 40, 60, and 150 IU/L, respectively. The incidence rate of spontaneous HBeAg seroconversion within 6 months when a subject entered the phase of ALT between 60 and 150 IU/L was 5.57 times that of the phase with ALT < 60 IU/L. The incidence rate of HBeAg seroconversion once ALT levels were above 150 IU/L was 9.87 times that of the phase of ALT < 60 IU/L. CONCLUSIONS: The ALT levels above 30 IU/L served as a cutoff of the inflammatory phase in chronic genotype B and C HBV-infected patients. Serial ALT levels in chronic HBV-infected subjects offer a predicted effect on the occurrence of spontaneous HBeAg seroconversion.


Assuntos
Alanina Transaminase/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Genótipo , Hepatite B Crônica/imunologia , Humanos , Lactente , Inflamação , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Valores de Referência
15.
Ann Stat ; 40(3): 1465-1488, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29479122

RESUMO

There is a surge in medical follow-up studies that include longitudinal covariates in the modeling of survival data. So far, the focus has been largely on right censored survival data. We consider survival data that are subject to both left truncation and right censoring. Left truncation is well known to produce biased sample. The sampling bias issue has been resolved in the literature for the case which involves baseline or time-varying covariates that are observable. The problem remains open however for the important case where longitudinal covariates are present in survival models. A joint likelihood approach has been shown in the literature to provide an effective way to overcome those difficulties for right censored data, but this approach faces substantial additional challenges in the presence of left truncation. Here we thus propose an alternative likelihood to overcome these difficulties and show that the regression coefficient in the survival component can be estimated unbiasedly and efficiently. Issues about the bias for the longitudinal component are discussed. The new approach is illustrated numerically through simulations and data from a multi-center AIDS cohort study.

16.
Entomol Exp Appl ; 140(3): 181-188, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22791908

RESUMO

Reproductive data of individual insects are extremely hard to collect under natural conditions, thus the study of research questions related to oviposition has not advanced. Patterns of oviposition are often inferred only indirectly, through monitoring of host infestation, whereas the influence of age structure and several other factors on oviposition remains unknown. Using a new approach, in this article, we live-trapped wild Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) females on the Greek island of Chios during two field seasons. For their remaining lifetime, these females were placed individually in small cages and their daily oviposition was monitored. Reproduction rates between cohorts from different collection dates were then compared. The results showed that in the different captive cohorts the average remaining lifetime and reproduction were highly variable within and between seasons. Multivariate regression analysis showed that the month of capture had a significant effect on captive life span, average daily reproduction, and patterns of egg laying. The effect of year was significant on reproduction, but not on captive life span. These differences between sampling periods probably reflect differences in the availability of hosts and other factors that vary during the season and affect age structure and reproduction. Using a non-parametric generalized additive model, we found a statistically significant correlation between the captive life span and the average daily reproduction. These findings and the experimental approach have several important implications.

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