Flexible semiparametric joint modeling: an application to estimate individual lung function decline and risk of pulmonary exacerbations in cystic fibrosis.

BACKGROUND: Epidemiologic surveillance of lung function is key to clinical care of individuals with cystic fibrosis, but lung function decline is nonlinear and often impacted by acute respiratory events known as pulmonary exacerbations. Statistical models are needed to simultaneously estimate lung function decline while providing risk estimates for the onset of pulmonary exacerbations, in order to identify relevant predictors of declining lung function and understand how these associations could be used to predict the onset of pulmonary exacerbations. METHODS: Using longitudinal lung function (FEV1) measurements and time-to-event data on pulmonary exacerbations from individuals in the United States Cystic Fibrosis Registry, we implemented a flexible semiparametric joint model consisting of a mixed-effects submodel with regression splines to fit repeated FEV1 measurements and a time-to-event submodel for possibly censored data on pulmonary exacerbations. We contrasted this approach with methods currently used in epidemiological studies and highlight clinical implications. RESULTS: The semiparametric joint model had the best fit of all models examined based on deviance information criterion. Higher starting FEV1 implied more rapid lung function decline in both separate and joint models; however, individualized risk estimates for pulmonary exacerbation differed depending upon model type. Based on shared parameter estimates from the joint model, which accounts for the nonlinear FEV1 trajectory, patients with more positive rates of change were less likely to experience a pulmonary exacerbation (HR per one standard deviation increase in FEV1 rate of change = 0.566, 95% CI 0.516-0.619), and having higher absolute FEV1 also corresponded to lower risk of having a pulmonary exacerbation (HR per one standard deviation increase in FEV1 = 0.856, 95% CI 0.781-0.937). At the population level, both submodels indicated significant effects of birth cohort, socioeconomic status and respiratory infections on FEV1 decline, as well as significant effects of gender, socioeconomic status and birth cohort on pulmonary exacerbation risk. CONCLUSIONS: Through a flexible joint-modeling approach, we provide a means to simultaneously estimate lung function trajectories and the risk of pulmonary exacerbations for individual patients; we demonstrate how this approach offers additional insights into the clinical course of cystic fibrosis that were not possible using conventional approaches

The Threads of Texas: A story of enduring identity in a changing state

The Threads of Texas is a research project launched by More in Common to understand change in Texas: the divergent views toward change that are pulling Texans apart, and the shared identity and dreams for the future that can bring Texans together.Texas is continuously in a state of change — economically, politically, demographically. As Texas grapples with major changes, how do Texans across age, race, and political parties hold onto what they perceive as "truly Texan?" How does Texas replicate its DNA to maintain its sense of identity as new people, new ideas, and new industries make their homes in the state? These questions have become more urgent as the COVID-19 pandemic and the 2021 winter storm challenge the Texas social and economic landscape.These are the questions that inspired More in Common to launch a landmark study of the state of Texas. In 2020 and 2021, we heard from over 4000 Texans from across the state, including experts in Texan culture and leaders of Texas industries. We capture the striking and ultimately hopeful attitudes of Texans: We find that although Texans on far ends of the ideological spectrum feel exhausted by political divisions, most Texans say that the ties that bind us are stronger than what divides us. They believe in a changing Texas where everyone feels they belong

Platinum deposition on functionalised graphene for corrosion resistant oxygen reduction electrodes

Graphene-related materials are promising supports for electrocatalysts due to their stability and high surface area. Their innate surface chemistries can be controlled and tuned via functionalisation to improve the stability of both the carbon support and the metal catalyst. Functionalised graphenes were prepared using either aryl diazonium functionalisation or non-destructive chemical reduction, to provide groups adapted for platinum deposition. XPS and TGA-MS measurements confirmed the presence of polyethyleneglycol and sulfur-containing functional groups, and provided consistent values for the extent of the reactions. The deposited platinum nanoparticles obtained were consistently around 2 nm via reductive chemistry and around 4 nm via the diazonium route. Although these graphene-supported electrocatalysts provided a lower electrochemical surface area (ECSA), functionalised samples showed enhanced specific activity compared to a commercial platinum/carbon black system. Accelerated stress testing (AST) showed improved durability for the functionalised graphenes compared to the non-functionalised materials, attributed to edge passivation and catalyst particle anchoring

Quantitative Analysis of Culture Using Millions of Digitized Books

We constructed a corpus of digitized texts containing about 4% of all books ever printed. Analysis of this corpus enables us to investigate cultural trends quantitatively. We survey the vast terrain of ‘culturomics,’ focusing on linguistic and cultural phenomena that were reflected in the English language between 1800 and 2000. We show how this approach can provide insights about fields as diverse as lexicography, the evolution of grammar, collective memory, the adoption of technology, the pursuit of fame, censorship, and historical epidemiology. Culturomics extends the boundaries of rigorous quantitative inquiry to a wide array of new phenomena spanning the social sciences and the humanities.MathematicsPsycholog

Non-invasive diagnostic tests for Helicobacter pylori infection

BACKGROUND: Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES: To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS: We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA: We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as13C or14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS: We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS: In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions

A Metadata Action Language

The data management problem comprises data processing and data tracking. Data processing is the creation of new data based on existing data sources. Data tracking consists of storing metadata descriptions of available data. This paper addresses the data management problem by casting it as an AI planning problem. Actions are data-processing commands, plans are dataflow programs and goals are metadata descriptions of desired data products. Data manipulation is simply plan generation and execution, and a key component of data tracking is inferring the effects of an observed plan. We introduce a new action language for data management domains, called ADILM. We discuss the connection between data processing and information integration and show how a language for the latter must be modified to support the former. The paper also discusses information gathering within a data-processing framework, and show how ADILM metadata expressions are a generalization of Local Completeness

Bandwidth Enabled Flight Operations: Examining the Possibilities

The Bandwidth Enabled Flight Operations project is a research effort at the NASA Ames Research Center to investigate the use of satellite communications to improve aviation safety and capacity. This project is a follow on to the AeroSAPIENT Project, which demonstrated methods for transmitting high bandwidth data in various configurations. For this research, we set a goal to nominally use only 10 percent of the available bandwidth demonstrated by AeroSAPIENT or projected by near-term technology advances. This paper describes the results of our research, including available satellite bandwidth, commercial and research efforts to provide these services, and some of the limiting factors inherent with this communications medium. It also describes our investigation into the needs of the stakeholders (Airlines, Pilots, Cabin Crews, ATC, Maintenance, etc). The paper also describes our development of low-cost networked flight deck and airline operations center simulations that were used to demonstrate two application areas: Providing real time weather information to the commercial flight deck, and enhanced crew monitoring and control for airline operations centers