Simple Estimators of the Intensity of Seasonal Occurrence

Background: Edwards's method is a widely used approach for fitting a sine curve to a time-series of monthly frequencies. From this fitted curve, estimates of the seasonal intensity of occurrence (i.e., peak-to-low ratio of the fitted curve) can be generated. Methods: We discuss various approaches to the estimation of seasonal intensity assuming Edwards's periodic model, including maximum likelihood estimation (MLE), least squares, weighted least squares, and a new closed-form estimator based on a second-order moment statistic and non-transformed data. Through an extensive Monte Carlo simulation study, we compare the finite sample performance characteristics of the estimators discussed in this paper. Finally, all estimators and confidence interval procedures discussed are compared in a re-analysis of data on the seasonality of monocytic leukemia. Results: We find that Edwards's estimator is substantially biased, particularly for small numbers of events and very large or small amounts of seasonality. For the common setting of rare events and moderate seasonality, the new estimator proposed in this paper yields less finite sample bias and better mean squared error than either the MLE or weighted least squares. For large studies and strong seasonality, MLE or weighted least squares appears to be the optimal analytic method among those considered. Conclusion: Edwards's estimator of the seasonal relative risk can exhibit substantial finite sample bias. The alternative estimators considered in this paper should be preferred

A Semiparametric Model Selection Criterion with Applications to the Marginal Structural Model

Estimators for the parameter of interest in semiparametric models often depend on a guessed model for the nuisance parameter. The choice of the model for the nuisance parameter can affect both the finite sample bias and efficiency of the resulting estimator of the parameter of interest. In this paper we propose a finite sample criterion based on cross validation that can be used to select a nuisance parameter model from a list of candidate models. We show that expected value of this criterion is minimized by the nuisance parameter model that yields the estimator of the parameter of interest with the smallest mean-squared error relative to the expected value of an initial consistent reference estimator. In a simulation study, we examine the performance of this criterion for selecting a model for a treatment mechanism in a marginal structural model (MSM) of point treatment data. For situations where all possible models cannot be evaluated, we outline a forward/backward model selection algorithm based on the cross validation criterion proposed in this paper and show how it can be used to select models for multiple nuisance parameters. We evaluate the performance of this algorithm in a simulation study of the one-step estimator of the parameter of interest in a MSM where models for both a treatment mechanism and a conditional expectation of the response need to be selected. Finally, we apply the forward model selection algorithm to a MSM analysis of the relationship between boiled water use and gastrointestinal illness in HIV positive men

Upending a Global Debate: An Empirical Analysis of the U.S. Supreme Court’s Use of Transnational Law to Interpret Domestic Doctrine,

Over the last ten years, judges, scholars, and policymakers have argued — quite vehemently at times — about whether U.S. courts should use transnational sources of law to interpret domestic legal doctrine. All eyes in this debate focus on the U.S. Supreme Court and its use, misuse, and alleged use of transnational law. And almost all the debates are normative. Some scholars and judges argue the Court is correct to use transnational law. Others believe to do so is constitutional apostacy. Still, the controversy seems to have generated more heat than light. Among the clamor can be found little empirical work on the conditions under which Supreme Court Justices actually use transnational law. Is it in fact the case that only liberal Justices employ transnational law — or do conservatives as well? In addition, there is little work on which countries Justices cite when they do use transnational law. Do they cherry pick whichever country works best in the given case, or is there a lower bound of plausibility when selecting countries to examine and cite? The authors provide the most systematic empirical exploration of the Court’s use of transnational law to date. Their results challenge conventional wisdom and prove to upend the existing debates over transnational law. The data show that Justices are more likely to reference transnational law when they exercise judicial review and when they overturn precedent, which likely explains much of the controversy around the practice. Importantly, the data show, further, that all Justices cite transnational law. Liberals cite transnational law when they render liberal decisions, and conservatives cite transnational law when they render conservative decisions. Liberals and conservatives alike employ such law because they are both ideologically conscious, strategic judicial actors who seek to support their decisions with as much persuasive material as possible. Finally, the results suggest that Justices cite countries with regard to their political and legal characteristics. They cite what the public would consider to be among the most legitimate countries across the globe. In other words, on the whole, Justices seem to borrow from countries most like the U.S. Whether these results are good or bad is unclear; what is clear, however, is that the normative debate over using transnational law must take a turn and address the authors’ findings

On-label and off-label use of high-dose influenza vaccine in the United States, 2010–2012

High-dose inactivated, influenza vaccine was licensed by the FDA in December 2009 for adults aged 65 y and older. The ACIP did not issue or state a preference for a specific vaccine in the elderly population. The extent of its on-label and off-label use is unknown. Using the MarketScan Commercial Claims and Encounters and the Medicare Supplemental database, we identified individuals who received the high-dose influenza vaccine or the standard, seasonal trivalent influenza vaccine between January 1, 2010 and December 31, 2012. For people aged ≥65 y, we used multivariable regression to assess the association between patient and provider level variables and high-dose influenza vaccine versus standard influenza vaccine. We characterized all off-label high-dose vaccine administered to people younger than 65 y of age, and investigated whether sicker patients were targeted for off-label use by examining the association between various comorbid conditions and receipt of the high-dose vaccine among adults aged 18–64. Among patients aged ≥65 y who received an influenza vaccine, 18.4% received the high-dose vaccine. Uptake was minimal in 2010, but 25% and 32% of influenza shots were the high-dose formulation in 2011 and 2012, respectively. Almost 27,000 seniors received a second high-dose vaccine with a median of 368 d (IQR: 350–387 days) between doses. Older age, family practice physicians, and having PPO insurance were positively associated with receiving high-dose vaccine. There were 36,624 off-label high-dose vaccines administered. Half of the patients receiving off-label doses were aged 50–64. Adults aged 18–64 y receiving high-dose vaccine were more likely to have chronic comorbidities than people receiving standard influenza vaccine; however, there was not one specific illness that seemed to be targeted by physicians. In the first 3 y since licensure, use of the high-dose vaccine among seniors has been limited. The safety of this vaccine should be monitored closely among 2 groups of people - seniors receiving repeat doses and people <65

The Madison plasma dynamo experiment: a facility for studying laboratory plasma astrophysics

The Madison plasma dynamo experiment (MPDX) is a novel, versatile, basic plasma research device designed to investigate flow driven magnetohydrodynamic (MHD) instabilities and other high-$\beta$ phenomena with astrophysically relevant parameters. A 3 m diameter vacuum vessel is lined with 36 rings of alternately oriented 4000 G samarium cobalt magnets which create an axisymmetric multicusp that contains $\sim$14 m$^{3}$ of nearly magnetic field free plasma that is well confined and highly ionized $(>50\%)$. At present, 8 lanthanum hexaboride (LaB$_6$) cathodes and 10 molybdenum anodes are inserted into the vessel and biased up to 500 V, drawing 40 A each cathode, ionizing a low pressure Ar or He fill gas and heating it. Up to 100 kW of electron cyclotron heating (ECH) power is planned for additional electron heating. The LaB$_6$ cathodes are positioned in the magnetized edge to drive toroidal rotation through ${\bf J}\times{\bf B}$ torques that propagate into the unmagnetized core plasma. Dynamo studies on MPDX require a high magnetic Reynolds number $Rm > 1000$, and an adjustable fluid Reynolds number $10< Re <1000$, in the regime where the kinetic energy of the flow exceeds the magnetic energy ($M_A^2=($v$/$v$_A)^2 > 1$). Initial results from MPDX are presented along with a 0-dimensional power and particle balance model to predict the viscosity and resistivity to achieve dynamo action.Comment: 14 pages, 13 figure

Effects of aggregation of drug and diagnostic codes on the performance of the high-dimensional propensity score algorithm: an empirical example

BACKGROUND: The High-Dimensional Propensity Score (hd-PS) algorithm can select and adjust for baseline confounders of treatment-outcome associations in pharmacoepidemiologic studies that use healthcare claims data. How hd-PS performance is affected by aggregating medications or medical diagnoses has not been assessed. METHODS: We evaluated the effects of aggregating medications or diagnoses on hd-PS performance in an empirical example using resampled cohorts with small sample size, rare outcome incidence, or low exposure prevalence. In a cohort study comparing the risk of upper gastrointestinal complications in celecoxib or traditional NSAIDs (diclofenac, ibuprofen) initiators with rheumatoid arthritis and osteoarthritis, we (1) aggregated medications and International Classification of Diseases-9 (ICD-9) diagnoses into hierarchies of the Anatomical Therapeutic Chemical classification (ATC) and the Clinical Classification Software (CCS), respectively, and (2) sampled the full cohort using techniques validated by simulations to create 9,600 samples to compare 16 aggregation scenarios across 50% and 20% samples with varying outcome incidence and exposure prevalence. We applied hd-PS to estimate relative risks (RR) using 5 dimensions, predefined confounders, ≤ 500 hd-PS covariates, and propensity score deciles. For each scenario, we calculated: (1) the geometric mean RR; (2) the difference between the scenario mean ln(RR) and the ln(RR) from published randomized controlled trials (RCT); and (3) the proportional difference in the degree of estimated confounding between that scenario and the base scenario (no aggregation). RESULTS: Compared with the base scenario, aggregations of medications into ATC level 4 alone or in combination with aggregation of diagnoses into CCS level 1 improved the hd-PS confounding adjustment in most scenarios, reducing residual confounding compared with the RCT findings by up to 19%. CONCLUSIONS: Aggregation of codes using hierarchical coding systems may improve the performance of the hd-PS to control for confounders. The balance of advantages and disadvantages of aggregation is likely to vary across research settings

Timing and predictors of severe rotavirus gastroenteritis among unvaccinated infants in low- and middle-income countries

Delays in rotavirus vaccine schedule could improve performance in low- and middle-income countries (LMICs). However, delaying the first dose could be detrimental if infants experience severe rotavirus gastroenteritis (RVGE) early in life. Our objective was to describe the timing and predictors of severe RVGE in unvaccinated children in LMICs. We analysed the placebo arms from two clinical trials (cohort 1: NCT00241644; cohort 2: NCT00362648). We estimated the rate, cumulative incidence (per 1000 infants) and age distribution of severe RVGE episodes. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between baseline factors and severe RVGE. Cumulative incidence at 6 months of age was 23/1000 (95% CI 15-30) in cohort 1 and 6/1000 (95% CI 3-8) in cohort 2. Early antibiotic use (compared with no use) was associated with 2.03 (95% CI 1.18-3.48) and 1.41 (95% CI 0.80-2.51) times the rate of severe RVGE in cohorts 1 and 2, respectively. The cumulative incidence of severe RVGE was low at 6 months of age, suggesting that a 4-week delay in the vaccination schedule may not result in a large number of severe RVGE episodes prior to vaccine receipt. Copyright © Cambridge University Press 2018

Approaches to Selecting "Time Zero" in External Control Arms with Multiple Potential Entry Points: A Simulation Study of 8 Approaches

Background: When including data from an external control arm to estimate comparative effectiveness, there is a methodological choice of when to set “time zero,” the point at which a patient would be eligible/enrolled in a contemporary study. Where patients receive multiple lines of eligible therapy and thus alternative points could be selected, this issue is complex. Methods: A simulation study was conducted in which patients received multiple prior lines of therapy before entering either cohort. The results from the control and intervention data sets are compared using 8 methods for selecting time zero. The base-case comparison was set up to be biased against the intervention (which is generally received later), with methods compared in their ability to estimate the true intervention effectiveness. We further investigate the impact of key study attributes (such as sample size) and degree of overlap in time-varying covariates (such as prior lines of therapy) on study results. Results: Of the 8 methods, 5 (all lines, random line, systematically selecting groups based on mean absolute error, root mean square error, or propensity scores) showed good performance in accounting for differences between the line at which patients were included. The first eligible line can be statistically inefficient in some situations. All lines (with censoring) cannot be used for survival outcomes. The last eligible line cannot be recommended. Conclusions: Multiple methods are available for selecting the most appropriate time zero from an external control arm. Based on the simulation, we demonstrate that some methods frequently perform poorly, with several viable methods remaining. In selecting between the viable methods, analysts should consider the context of their analysis and justify the approach selected. There are multiple methods available from which an analyst may select “time zero” in an external control cohort. This simulation study demonstrates that some methods perform poorly but most are viable options, depending on context and the degree of overlap in time zero across cohorts. Careful thought and clear justification should be used when selecting the strategy for a study

The Wisconsin Plasma Astrophysics Laboratory

The Wisconsin Plasma Astrophysics Laboratory (WiPAL) is a flexible user facility designed to study a range of astrophysically relevant plasma processes as well as novel geometries that mimic astrophysical systems. A multi-cusp magnetic bucket constructed from strong samarium cobalt permanent magnets now confines a 10 m$^3$, fully ionized, magnetic-field free plasma in a spherical geometry. Plasma parameters of $T_{e}\approx5$ to $20$ eV and $n_{e}\approx10^{11}$ to $5\times10^{12}$ cm$^{-3}$ provide an ideal testbed for a range of astrophysical experiments including self-exciting dynamos, collisionless magnetic reconnection, jet stability, stellar winds, and more. This article describes the capabilities of WiPAL along with several experiments, in both operating and planning stages, that illustrate the range of possibilities for future users.Comment: 21 pages, 12 figures, 2 table