Immortal person-time in studies of cancer outcomes

Immortal person-time arises in an observational study when follow-up time is included in person-time at risk for the study outcome, even though that time precedes the last event required for entry into the study population or satisfaction of an exposure definition.1,2 Immune person-time is similar, but it pertains to outcomes other than death. If a study patient were to have incurred the outcome or been censored during immortal or immune person-time, then the patient would not have satisfied the requirements for inclusion in the study or exposure category. A study or exposure category that includes immortal or immune person-time yields a downwardly biased outcome rate and an upwardly biased survival curve. This bias occurs because the accumulated person-time exceeds person-time actually at risk. When comparing rates or survival curves among exposure categories, the net effect of immortal or immune person-time bias may be in any direction

Two-stage g-computation: Evaluating treatment and intervention impacts in observational cohorts when exposure information is partly missing

Illustrations of the g-computation algorithm to evaluate population average treatment and intervention effects have been predominantly implemented in settings with complete exposure information. Thus, worked examples of approaches to handle missing data in this causal framework are needed to facilitate wider use of these estimators. We illustrate two-stage g-computation estimators that leverage partially observed information on the full study sample and complete exposure information on a subset to estimate causal effects. In a hypothetical cohort of 1,623 human immunodeficiency virus (HIV)-positive women with 30% complete opioid prescription information, we illustrate a two-stage extrapolation g-computation estimator for the average treatment effect of shorter or longer duration opioid prescriptions; we further illustrate two-stage inverse probability weighting and imputation g-computation estimators for the average intervention effect of shortening the duration of prescriptions relative to the status quo. Two-stage g-computation estimators approximated the true risk differences for the population average treatment and intervention effects while g-computation fit to the subset of complete cases was biased. In 10,000 Monte Carlo simulations, two-stage approaches considerably reduced bias and mean squared error and improved the coverage of 95% confidence limits. Although missing data threaten validity and precision, two-stage g-computation designs offer principled approaches to handling missing information

Generalizing the per-protocol treatment effect: The case of ACTG A5095

Background Intention-to-treat comparisons of randomized trials provide asymptotically consistent estimators of the effect of treatment assignment, without regard to compliance. However, decision makers often wish to know the effect of a per-protocol comparison. Moreover, decision makers may also wish to know the effect of treatment assignment or treatment protocol in a user-specified target population other than the sample in which the trial was fielded. Here, we aimed to generalize results from the ACTG A5095 trial to the US recently HIV-diagnosed target population. Methods We first replicated the published conventional intention-to-treat estimate (2-year risk difference and hazard ratio) comparing a four-drug antiretroviral regimen to a three-drug regimen in the A5095 trial. We then estimated the intention-to-treat effect that accounted for informative dropout and the per-protocol effect that additionally accounted for protocol deviations by constructing inverse probability weights. Furthermore, we employed inverse odds of sampling weights to generalize both intention-to-treat and per-protocol effects to a target population comprising US individuals with HIV diagnosed during 2008–2014. Results Of 761 subjects in the analysis, 82 dropouts (36 in the three-drug arm and 46 in the four-drug arm) and 59 protocol deviations (25 in the three-drug arm and 34 in the four-drug arm) occurred during the first 2 years of follow-up. A total of 169 subjects incurred virologic failure or death. The 2-year risks were similar both in the trial and in the US HIV-diagnosed target population for estimates from the conventional intention-to-treat, dropout-weighted intention-to-treat, and per-protocol analyses. In the US target population, the 2-year conventional intention-to-treat risk difference (unit: %) for virologic failure or death comparing the four-drug arm to the three-drug arm was −0.4 (95% confidence interval: −6.2, 5.1), while the hazard ratio was 0.97 (95% confidence interval: 0.70, 1.34); the 2-year risk difference was −0.9 (95% confidence interval: −6.9, 5.3) for the dropout-weighted intention-to-treat comparison (hazard ratio = 0.95, 95% confidence interval: 0.68, 1.32) and −0.7 (95% confidence interval: −6.7, 5.5) for the per-protocol comparison (hazard ratio = 0.96, 95% confidence interval: 0.69, 1.34). Conclusion No benefit of four-drug antiretroviral regimen over three-drug regimen was found from the conventional intention-to-treat, dropout-weighted intention-to-treat or per-protocol estimates in the trial sample or target population

Neutral winds in the polar thermosphere as measured from dynamics explorer

Remote sensing measurements of the meridional thermospheric neutral wind using the Fabry-Perot Interferometer on Dynamics Explorer have been combined with measurements of the zonal component using the Wind and Temperature Spectrometer on the same spacecraft. The two data sets with appropriate spatial phasing and averaging determine the vector wind along the track of the polar orbiting spacecraft. A study of fifty-eight passes over the Southern (sunlit) pole has enabled the average Universal Time dependence of the wind field to be determined for essentially a single solar local time cut. The results show the presence of a "back-ground" wind field driven by solar EUV heating upon which is superposed a circulating wind field driven by high latitude momentum and energy sources.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24099/1/0000356.pd

Demographic Trends in US HIV Diagnoses, 2008–2017: Data Movies

In this editorial, we introduce the data movie as a tool for investigating and communicating changing patterns of disease using the example of HIV in the United States. The Centers for Disease Control and Prevention currently tracks all new HIV diagnoses through the National HIV Surveillance System. Understanding what these data tell us is critical to the goal of ending the HIV epidemic in the United States.1 However, summarizing trends across multiple population characteristics simultaneously—for example, exploring how the age distribution of new diagnoses varies by geographic region and how that relationship has changed over time—can be difficult. Because data movies allow us to visualize complex relationships more easily than large tables or paneled figures, they can help us take full advantage of our increasingly rich national surveillance data

Five-Year Mortality for Adults Entering Human Immunodeficiency Virus Care Under Universal Early Treatment Compared With the General US Population

Background: Mortality among adults with human immunodeficiency virus (HIV) remains elevated over those in the US general population, even in the years after entry into HIV care. We explore whether the elevation in 5-year mortality would have persisted if all adults with HIV had initiated antiretroviral therapy within 3 months of entering care. Methods: Among 82 766 adults entering HIV care at North American AIDS Cohort Collaboration clinical sites in the United States, we computed mortality over 5 years since entry into HIV care under observed treatment patterns. We then used inverse probability weights to estimate mortality under universal early treatment. To compare mortality with those for similar individuals in the general population, we used National Center for Health Statistics data to construct a cohort representing the subset of the US population matched to study participants on key characteristics. Results: For the entire study period (1999-2017), the 5-year mortality among adults with HIV was 7.9% (95% confidence interval [CI]: 7.6%-8.2%) higher than expected based on the US general population. Under universal early treatment, the elevation in mortality for people with HIV would have been 7.2% (95% CI: 5.8%-8.6%). In the most recent calendar period examined (2011-2017), the elevation in mortality for people with HIV was 2.6% (95% CI: 2.0%-3.3%) under observed treatment patterns and 2.1% (.0%-4.2%) under universal early treatment. Conclusions: Expanding early treatment may modestly reduce, but not eliminate, the elevation in mortality for people with HIV

Proximity effect at superconducting Sn-Bi2Se3 interface

We have investigated the conductance spectra of Sn-Bi2Se3 interface junctions down to 250 mK and in different magnetic fields. A number of conductance anomalies were observed below the superconducting transition temperature of Sn, including a small gap different from that of Sn, and a zero-bias conductance peak growing up at lower temperatures. We discussed the possible origins of the smaller gap and the zero-bias conductance peak. These phenomena support that a proximity-effect-induced chiral superconducting phase is formed at the interface between the superconducting Sn and the strong spin-orbit coupling material Bi2Se3.Comment: 7 pages, 8 figure

Heavy Quarks and Heavy Quarkonia as Tests of Thermalization

We present here a brief summary of new results on heavy quarks and heavy quarkonia from the PHENIX experiment as presented at the "Quark Gluon Plasma Thermalization" Workshop in Vienna, Austria in August 2005, directly following the International Quark Matter Conference in Hungary.Comment: 8 pages, 5 figures, Quark Gluon Plasma Thermalization Workshop (Vienna August 2005) Proceeding

Centrality Dependence of the High p_T Charged Hadron Suppression in Au+Au collisions at sqrt(s_NN) = 130 GeV

PHENIX has measured the centrality dependence of charged hadron p_T spectra from central Au+Au collisions at sqrt(s_NN)=130 GeV. The truncated mean p_T decreases with centrality for p_T > 2 GeV/c, indicating an apparent reduction of the contribution from hard scattering to high p_T hadron production. For central collisions the yield at high p_T is shown to be suppressed compared to binary nucleon-nucleon collision scaling of p+p data. This suppression is monotonically increasing with centrality, but most of the change occurs below 30% centrality, i.e. for collisions with less than about 140 participating nucleons. The observed p_T and centrality dependence is consistent with the particle production predicted by models including hard scattering and subsequent energy loss of the scattered partons in the dense matter created in the collisions.Comment: 7 pages text, LaTeX, 6 figures, 2 tables, 307 authors, resubmitted to Phys. Lett. B. Revised to address referee concerns. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm

Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV

The invariant differential cross section for inclusive electron production in p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4 <= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the inclusive electron spectrum from semileptonic decays of hadrons carrying heavy flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via three independent methods. The resulting electron spectrum from heavy flavor decays is compared to recent leading and next-to-leading order perturbative QCD calculations. The total cross section of charm quark-antiquark pair production is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm