Modeling left-truncated and right-censored survival data with longitudinal covariates

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.Comment: Published in at http://dx.doi.org/10.1214/12-AOS996 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Worldwide genetic variation of the IGHV and TRBV immune receptor gene families in humans.

The immunoglobulin heavy variable (IGHV) and T cell beta variable (TRBV) loci are among the most complex and variable regions in the human genome. Generated through a process of gene duplication/deletion and diversification, these loci can vary extensively between individuals in copy number and contain genes that are highly similar, making their analysis technically challenging. Here, we present a comprehensive study of the functional gene segments in the IGHV and TRBV loci, quantifying their copy number and single-nucleotide variation in a globally diverse sample of 109 (IGHV) and 286 (TRBV) humans from over a 100 populations. We find that the IGHV and TRBV gene families exhibit starkly different patterns of variation. In addition to providing insight into the different evolutionary paths of the IGHV and TRBV loci, our results are also important to the adaptive immune repertoire sequencing community, where the lack of frequencies of common alleles and copy number variants is hampering existing analytical pipelines

Inverse regression for longitudinal data

Sliced inverse regression (Duan and Li [Ann. Statist. 19 (1991) 505-530], Li [J. Amer. Statist. Assoc. 86 (1991) 316-342]) is an appealing dimension reduction method for regression models with multivariate covariates. It has been extended by Ferr\'{e} and Yao [Statistics 37 (2003) 475-488, Statist. Sinica 15 (2005) 665-683] and Hsing and Ren [Ann. Statist. 37 (2009) 726-755] to functional covariates where the whole trajectories of random functional covariates are completely observed. The focus of this paper is to develop sliced inverse regression for intermittently and sparsely measured longitudinal covariates. We develop asymptotic theory for the new procedure and show, under some regularity conditions, that the estimated directions attain the optimal rate of convergence. Simulation studies and data analysis are also provided to demonstrate the performance of our method.Comment: Published in at http://dx.doi.org/10.1214/13-AOS1193 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org). With Correction

Childhood, children and family lives in China

In this chapter we bring into focus those aspects of family lives in China that are concerned with children’s family relationships, and the ways in which such issues are part and parcel of the broader institutionalisation of childhood. We draw on theoretical frameworks in the sociology of childhood and childhood studies (e.g., Prout, 2004; Qvortrup, 2000; Smith and Greene, 2014). Since these theoretical perspectives have developed predominantly in Anglophone literature, some researchers have considered their relevance to, and utility for, China and Chinese childhoods (Goh, 2011; Miao, 2013; Wang YY, 2011, 2014a, 2014b; Zheng, 2012a, 2012b; Ribbens McCarthy et al., 2017). In engaging with existing theories, and applying them to, Chinese children’s family lives, we seek to go beyond any tendency to just ‘add in the missing children’ to existing discussions (Kesby et al., 2006: 186), and give consideration to a variety of cultural and local contexts that characterise China and illuminate why it is necessary to decentre universalist thinking (Jullien, 2008/2014

Computational Tools for Immune Repertoire Characterization and Primer Set Design

The enormous decrease in the cost of genomic sequencing over the past two decades has enabled researchers to revisit previously unaddressable questions in sequence analysis. However, this boom of genomic information has introduced new sets of problems that often demand computationally efficient methods. In this work, we describe computational tools for two such settings involving large-scale genomic data: 1) estimating copy number and allelic variation in two highly complex gene families, and 2) selective sequencing of a target genome in a complex DNA sample.We first describe a method that takes short reads from high-throughput sequencing and characterizes both copy number and allelic variation in the IGHV and TRBV loci. These two loci can vary extensively between individuals in copy number and contain genes that are highly similar, making their analysis technically challenging. Additionally, we have conducted the first study of a globally diverse sample of hundreds of individuals in these two loci from over a hundred populations. In addition to providing insight into the different evolutionary paths of the IGHV and TRBV loci, our results are also important to the adaptive immune repertoire sequencing community, where the lack of frequencies of common alleles and copy number variants is hampering existing analytical pipelines.In our second problem setting, we describe SOAPswga, an optimized and parallelized pipeline for primer design in the context of selective amplification. Unlike previous heuristic-based methods, SOAPswga uses machine learning methods to evaluate both individual primers and primer sets. Additionally, rather than brute force search for primer sets, such as in predecessor methods, SOAPswga uses branch-and-bound principles to pursue only the most promising sets. These optimizations, including the parallelization of each step, allow for a huge decrease in runtime from the order of weeks to minutes. We also discuss the results of our pipeline applied to the selective amplification of Mycobacterium tuberculosis in a sample of human blood. Lastly, we expand on the importance of this work, and in general, its potential usefulness to any setting consisting of targeted sequencing

Trade Policy and Economic Integration in a Cournot Duopoly Model

This paper investigates the policy and welfare implications of forming an economic region in the context of a Cournot duopoly model. Some theoretical results are obtained. First, the economic region lowers the external tariff (against non-partner countries) less than its pre-integration level when a sufficiently large subsidy on the imports from the partner is carried out. Second, economic integration reduces the non-partner country’s welfare. Third, although the region still gains from integration even under some partial trade liberalisation regimes, complete trade liberalisation within the region leads to higher regional welfare. Finally, trade liberalisation within the region improves the welfare of the world as a whole.Trade Policy, Economic Integration

Assessment of selected soil parameters in a long-term Western Canadian organic field experiment

A long-term field study was used to compare soil nitrogen and phosphorous status, and soil aggregate stability in organic and conventional cropping systems. Two rotations were tested: a grain only and a grain-alfalfa hay rotation. The organic systems had a lower nitrate leaching potential than the same rotations under conventional management. After 13 years, one organic system (the grain-alfalfa; no manure return) is suffering serious soil P depletion. However, the grain only and the grain-alfalfa with manure return to land systems had soil P levels similar to the prairie grass control treatment and showed no signs of P deficiency. Despite having lower levels of organic carbon, the organic soils had higher levels of wet aggregate stability than conventionally managed soils

Learnings from Data Integration for Augmented Language Models

One of the limitations of large language models is that they do not have access to up-to-date, proprietary or personal data. As a result, there are multiple efforts to extend language models with techniques for accessing external data. In that sense, LLMs share the vision of data integration systems whose goal is to provide seamless access to a large collection of heterogeneous data sources. While the details and the techniques of LLMs differ greatly from those of data integration, this paper shows that some of the lessons learned from research on data integration can elucidate the research path we are conducting today on language models