Regression with imputed covariates: a generalized missing indicator approach

International audienceA common problem in applied regression analysis is that covariate values may be missing for some observations but imputed values may be available. This situation generates a trade-off between bias and precision: the complete cases are often disarmingly few, but replacing the missing observations with the imputed values to gain precision may lead to bias. In this paper we formalize this trade-off by showing that one can augment the regression model with a set of auxiliary variables so as to obtain, under weak assumptions about the imputations, the same unbiased estimator of the parameters of interest as complete-case analysis. Given this augmented model, the bias-precision trade-off may then be tackled by either model reduction procedures or model averaging methods. We illustrate our approach by considering the problem of estimating the relation between income and the body mass index (BMI) using survey data affected by item non-response, where the missing values on the main covariates are filled in by imputations

p53 mutations in L3-loop zinc-binding domain, DNA-ploidy, and S phase fraction are independent prognostic indicators in colorectal cancer: A prospective study with a five-year follow-up

p53 gene alterations are among the most common events observed in colorectal cancer, and are accompanied frequently by DNA aneuploidy and high proliferative activity. The prognostic significance of such mutations remains controversial. We prospectively evaluated the prognostic significance of p53 mutations, DNA-ploidy, and S phase fraction (SPF) in a consecutive series of 160 colorectal cancer patients (median follow-up 71 months). Tumor DNA was screened for p53 mutations by PCR/single-strand conformational polymorphism/sequencing. DNA-ploidy and SPF were assessed by DNA flow cytometry. p53 mutations were detected in 68 of 160 (42.5%) cases. In 56% (38 of 68) of these, p53 mutations were found in conserved areas of the gene and in 44% (30 of 68 cases) outside the conserved regions. Eighteen of the 68 cases (26%) had mutations in the L3 loop, 11 of 68 (16%) in the L1 loop-sheet-\u3b1 helix motif, and 39 of 68 (58%) outside L3 and loop-sheet-\u3b1 helix. Seventy-five percent of the cases (120 of 160) showed DNA aneuploidy, whereas 18% of these (22 of 120) were multiclonal. The major independent predictors for both disease relapse and death were advanced Dukes' stage, p53 mutations affecting L3 loop, DNA-aneuploid tumors, and high SPF (>18.5%). Our results show that mutations in L3 functional domain, more than any mutations, are important biological indicators to predict the outcome of patients indicating that these mutations have biological relevance in terms of colorectal cancer disease course

Obstetric near-miss cases among women admitted to intensive care units in Italy

Objective. Maternal near-miss defines a narrow category of morbidity encompassing potentially life-threatening episodes. The purpose of this study was to detect near-miss instances among women admitted to intensive care units or coronary units, analyze associated causes, and compute absolute and specific maternal morbidity rates in six Italian regions. Design. Observational retrospective study. Setting. Six Italian regions representing 49% of all resident Italian women aged 15-49 years. Population. The study population included all pregnant women aged 15-49 years admitted to intensive care units or coronary care units in the participating regions. Cases were defined as women aged 15-49 years resident in the participating regions, with one or more hospitalizations in intensive care for pregnancy or any pregnancy outcome between 2004 and 2005. Methods. Cases were identified through the Hospital Discharge Database. Enrolled cases were diagnosed according to the 9th International Classification of Diseases. Main outcome measure. Maternal near-miss rate (number of women experiencing an admission to intensive care units/all women with live or stillborn babies). Results. A total of 1259 near-miss cases were identified and the total maternal near-miss rate was 2.0/1000 deliveries. Seventy percent of the women were admitted to intensive care units or coronary units after a cesarean section. The leading associated risk factors were obstetric hemorrhage/disseminated intravascular coagulation (40%) and hypertensive disorders of pregnancy (29%). Conclusions. Monitoring of near-miss morbidity in conjunction with mortality surveillance could help to identify effective preventive measures for potentially life-threatening episodes

Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND:Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques

Bringing the benefits of David to Goliath: special economic zones and institutional improvement

The theory behind special economic zones (SEZs) focuses on their role in overcoming broader policy failings in a country. This paper hypothesizes that the ability of smaller countries to reform more quickly provides a theoretical ‘missing link’ as to how SEZs can assist reform, developing the idea of SEZs as a ‘small country in a large country’. Using a new database, the paper tests this proposition by examining if SEZs have actually been able to spur on institutional improvement in large countries. Results show that SEZs do influence the institutional development of a country, contingent upon prevailing institutional trends

Inequality of opportunity in the land of opportunities : 1968-2001

We measure inequality of opportunity for earnings acquisition in the U.S. between 1968 and 2001. Following recent theories of social justice, earnings determinants are divided into two parts: Circumstances, which are characteristics outside individual control and effort representing factors impacting earnings but under individuals’ responsibility. Equality of opportunity requires that inequality of circumstances must be corrected while differences of effort must remain unaltered. Circumstances are represented by parental education and occupation, ethnic origin, place of birth and age. Effort is modeled with schooling choices and labour supply decisions. Using the PSID from 1968 to 2001, we provide two alternative assessments of inequality of opportunity using counterfactual distributions. The statistical framework is semi-parametric and builds on duration models. Finally, we conclude that inequality of opportunity represents between 20 and 43% of earnings inequality, but decreases all over the period reaching around 18% in 2001