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"Taylor, Jeremy"
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Whittaker coefficients of geometric Eisenstein series
Geometric Langlands predicts an isomorphism between Whittaker coefficients of Eisenstein series and functions on the moduli space of
$\\check {N}$
-local systems. We prove this formula by interpreting Whittaker coefficients of Eisenstein series as factorization homology and then invoking Beilinson and Drinfeld’s formula for chiral homology of a chiral enveloping algebra.
Journal Article
Minecraft : heart of cobblestone
Farmer Cobb likes to keep his crops as neat as possible, but when neighbors eat his produce and villagers plant potatoes in his field he decides to get away from everyone and build a tall tower.
BOOK
Joint latent class models for longitudinal and time-to-event data: A review
Most statistical developments in the joint modelling area have focused on the shared random-effect models that include characteristics of the longitudinal marker as predictors in the model for the time-to-event. A less well-known approach is the joint latent class model which consists in assuming that a latent class structure entirely captures the correlation between the longitudinal marker trajectory and the risk of the event. Owing to its flexibility in modelling the dependency between the longitudinal marker and the event time, as well as its ability to include covariates, the joint latent class model may be particularly suited for prediction problems. This article aims at giving an overview of joint latent class modelling, especially in the prediction context. The authors introduce the model, discuss estimation and goodness-of-fit, and compare it with the shared random-effect model. Then, dynamic predictive tools derived from joint latent class models, as well as measures to evaluate their dynamic predictive accuracy, are presented. A detailed illustration of the methods is given in the context of the prediction of prostate cancer recurrence after radiation therapy based on repeated measures of Prostate Specific Antigen.
Journal Article
Zoom! : Architektur und Stadt im Bild = Picturing architecture and the city
Zoom! zeigt Fotografien und Videoarbeiten von siebzehn internationalen Kèunstlern, die sich mit der Beziehung und Abhèangigkeit von Architektur und gesellschaftlichem wie wirtschaftlichem Wandel beschèaftigen. In ihren Arbeiten konzentrieren sie sich nicht auf eine Reprèasentation von Bauten, sondern auf eine Annèaherung an Stadtstrukturen und deren Verèanderungsprozesse sowie auf individuelle Lebensrèaume. Im Nebeneinander der Aufnahmen aus verschiedenen Lèandern und Kontinenten -- von Italien bis Nigeria und China -- werden Brèuche und Gemeinsamkeiten sichtbar.\"--Provided by publisher.
Book
Development and Characterization of a High Density SNP Genotyping Assay for Cattle
The success of genome-wide association (GWA) studies for the detection of sequence variation affecting complex traits in human has spurred interest in the use of large-scale high-density single nucleotide polymorphism (SNP) genotyping for the identification of quantitative trait loci (QTL) and for marker-assisted selection in model and agricultural species. A cost-effective and efficient approach for the development of a custom genotyping assay interrogating 54,001 SNP loci to support GWA applications in cattle is described. A novel algorithm for achieving a compressed inter-marker interval distribution proved remarkably successful, with median interval of 37 kb and maximum predicted gap of <350 kb. The assay was tested on a panel of 576 animals from 21 cattle breeds and six outgroup species and revealed that from 39,765 to 46,492 SNP are polymorphic within individual breeds (average minor allele frequency (MAF) ranging from 0.24 to 0.27). The assay also identified 79 putative copy number variants in cattle. Utility for GWA was demonstrated by localizing known variation for coat color and the presence/absence of horns to their correct genomic locations. The combination of SNP selection and the novel spacing algorithm allows an efficient approach for the development of high-density genotyping platforms in species having full or even moderate quality draft sequence. Aspects of the approach can be exploited in species which lack an available genome sequence. The BovineSNP50 assay described here is commercially available from Illumina and provides a robust platform for mapping disease genes and QTL in cattle.
Journal Article
Criteria for the use of omics-based predictors in clinical trials
A checklist of criteria to determine the readiness of high-throughput ‘omics’-based tests for guiding patient therapy in clinical trials is discussed; the checklist, developed by the US National Cancer Institute in collaboration with additional scientists with relevant expertise, provides a framework to evaluate the strength of evidence for a test and outlines practical issues to consider before using the test in a clinical setting, with an aim to avoid premature advancement of omics-based tests in clinical trials.
Guidelines for clinical use of omics data
The potential of high-throughput 'omics' in clinical medicine is immense, with oncology leading the way in adopting these technologies. Working with researchers and clinicians from across the spectrum of these disciplines, the US National Cancer Institute (NCI) has developed a checklist of criteria that can be used to determine the readiness of omics-based tests for guiding patient care in clinical trials. Published in this Perspective feature, the checklist focuses on best practice in specimen preparation, assays, mathematical modelling, clinical trial design, ethics and more. It will be used to evaluate proposals for NCI-sponsored clinical trials in which omics tests guide therapy.
The US National Cancer Institute (NCI), in collaboration with scientists representing multiple areas of expertise relevant to ‘omics’-based test development, has developed a checklist of criteria that can be used to determine the readiness of omics-based tests for guiding patient care in clinical trials. The checklist criteria cover issues relating to specimens, assays, mathematical modelling, clinical trial design, and ethical, legal and regulatory aspects. Funding bodies and journals are encouraged to consider the checklist, which they may find useful for assessing study quality and evidence strength. The checklist will be used to evaluate proposals for NCI-sponsored clinical trials in which omics tests will be used to guide therapy.
Journal Article
Time-varying associations of patient and tumor characteristics with cancer survival: an analysis of SEER data across 14 cancer sites, 2004–2017
PurposeSurveillance, Epidemiology, and End Results (SEER) cancer registries provides information about survival duration and cause of death for cancer patients. Baseline demographic and tumor characteristics such as age, sex, race, year of diagnosis, and tumor stage can inform the expected survival time of patients, but their associations with survival may not be constant over the post-diagnosis period.MethodsUsing SEER data, we examined if there were time-varying associations of patient and tumor characteristics on survival, and we assessed how these relationships differed across 14 cancer sites. Standard Cox proportional hazards models were extended to allow for time-varying associations and incorporated into a competing-risks framework, separately modeling cancer-specific and other-cause deaths. For each cancer site and for each of the five factors, we estimated the relative hazard ratio and absolute hazard over time in the presence of competing risks.ResultsOur comprehensive consideration of patient and tumor characteristics when estimating time-varying hazards showed that the associations of age, tumor stage at diagnosis, and race/ethnicity with risk of death (cancer-specific and other-cause) change over time for many cancers; characteristics of sex and year of diagnosis exhibit some time-varying patterns as well. Stage at diagnosis had the largest associations with survival.ConclusionThese findings suggest that proportional hazards assumptions are often violated when examining patient characteristics on cancer survival post-diagnosis. We discuss several interesting results where the relative hazards are time-varying and suggest possible interpretations. Based on the time-varying associations of several important covariates on survival after cancer diagnosis using a pan-cancer approach, the likelihood of the proportional hazards assumption being met or corresponding interpretation should be considered in survival analyses, as flawed inference may have implications for cancer care and policy.
Journal Article
Transitions between cigarette, ENDS and dual use in adults in the PATH study (waves 1–4): multistate transition modelling accounting for complex survey design
IntroductionEven prior to 2018, electronic nicotine delivery systems (ENDS) began to dramatically change the landscape of tobacco products and product use patterns in the USA.MethodsUsing a Markov multistate transition model accounting for complex survey design, transition rates between never, non-current, cigarette, ENDS and dual use states were estimated for 23 253 adult participants in waves 1–4 (approximately 2013–2017) of the Population Assessment of Tobacco and Health study. We made short-term transition projections and estimated HRs for age, sex, race/ethnicity, education and income.ResultsCigarette use was persistent among adults, with 89.7% (95% CI 89.1% to 90.3%) of exclusive cigarette users and 86.1% (95% CI 84.4% to 87.9%) of dual users remaining cigarette users (either exclusive or dual) after one wave. In contrast, ENDS use was less persistent, with 72.1% (95% CI 69.6% to 74.6%) of exclusive ENDS users and 50.5% (95% CI 47.8% to 53.3%) of dual users remaining ENDS users (with or without cigarettes) after one wave. Exclusive ENDS users were more likely to start cigarette use after one wave than either never users (HR 25.2; 95% CI 20.9 to 30.5) or non-current users (HR 5.0; 95% CI 4.3 to 5.8). Dual users of ENDS and cigarettes were more likely to stop using cigarettes than exclusive cigarette users (HR 1.9; 95% CI 1.6 to 2.3). Transition rates varied among sociodemographic groups.ConclusionsMultistate transition models are an effective tool for uncovering and characterising longitudinal patterns and determinants of tobacco use from complex survey data. ENDS use among US adults was less persistent than cigarette use prior to 2018.
Journal Article
Gene expression–based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study
Studies of gene expression in lung cancer have the potential to affect patient care, but the general applicability of the derived classifiers is unclear. David Beer and his colleagues now analyze more than 400 lung tumors from subjects at six institutions using eight different classifiers and show that the combination of molecular and clinical data best predicts patient survival (
pages 812–813
).
Although prognostic gene expression signatures for survival in early-stage lung cancer have been proposed, for clinical application, it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training–testing, multi-site, blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) could be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early-stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas.
Journal Article