Estimation of Conditional Power for Cluster-Randomized Trials with Interval-Censored Endpoints

Cluster-randomized trials (CRTs) of infectious disease preventions often yield correlated, interval-censored data: dependencies may exist between observations from the same cluster, and event occurrence may be assessed only at intermittent clinic visits. This data structure must be accounted for when conducting interim monitoring and futility assessment for CRTs. In this article, we propose a flexible framework for conditional power estimation when outcomes are correlated and interval-censored. Under the assumption that the survival times follow a shared frailty model, we first characterize the correspondence between the marginal and cluster-conditional survival functions, and then use this relationship to semiparametrically estimate the cluster-specific survival distributions from the available interim data. We incorporate assumptions about changes to the event process over the remainder of the trial---as well as estimates of the dependency among observations in the same cluster---to extend these survival curves through the end of the study. Based on these projected survival functions we generate correlated interval-censored observations, and then calculate the conditional power as the proportion of times (across multiple full-data generation steps) that the null hypothesis of no treatment effect is rejected. We evaluate the performance of the proposed method through extensive simulation studies, and illustrate its use on a large cluster-randomized HIV prevention trial

Evolution of the Corticotropin-releasing Hormone Signaling System and Its Role in Stress-induced Phenotypic Plasticity

Developing animals respond in variation in their habitats by altering their rules of development and/or their morphologies (i.e., they exhibit phenotypic plasticity). In vertebrates, one mechanism by which plasticity is expressed is through activation of the neuroendocrine system, which transduces environmental information into a physiological response. Recent findings of ours with amphibians and of others with mammals show that the primary vertebrate stress neuropeptide, corticotropin-releasing hormone (CRH), is essential for adaptive developmental responses to environmental stress. For instance, CRH-dependent mechanisms cause accelerated metamorphosis in response to pond-drying in some amphibian species, and intrauterine fetal stress syndromes in humans precipitate preterm birth. CRH may be a phylogenetically ancient developmental signaling molecule that allows developing organisms to escape deleterious changes in their larval/fetal habitat. The response to CRH is mediated by at least two different receptor subtypes and may also be modulated by a secreted binding protein.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73287/1/j.1749-6632.1999.tb07877.x.pd

Fourteenth annual report of the Power Affiliates Program.

Includes bibliographical references

Eighteenth annual report of the Power Affiliates Program.

Includes bibliographical references

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Optimization of negative central shear discharges in shaped cross sections

Magnetohydrodynamic (MHD) stability analyses of Negative Central Shear (NCS) equilibria have revealed a new understanding of the limiting MHD instabilities in NCS experiments. Ideal stability calculations show a synergistic effect between cross section shape and pressure profile optimization; strong shaping and broader pressure independently lead to moderately higher {Beta} limits, but broadening of the pressure profile in a strongly dee-shaped cross- section leads to a dramatic increase in the ideal {Beta} limit. Localized resistive interchange (RI) modes can be unstable in the negative shear region and are most restrictive for peaked pressure profiles. Resistive global modes can also be destabilized significantly below the ideal P limit. Experiments largely confirm the general trends, and diagnostic measurements and numerical stability calculations are found to be in good qualitative agreement. Observed disruptions in NCS discharges with L-mode edge and strongly peaked pressure, appear to be initiated by interactions between the RI, and the global ideal and resistive modes

Patient navigation across the cancer care continuum: An overview of systematic reviews and emerging literature

OnlinePublPatient navigation is a strategy for overcoming barriers to reduce disparities and to improve access and outcomes. The aim of this umbrella review was to identify, critically appraise, synthesize, and present the best available evidence to inform policy and planning regarding patient navigation across the cancer continuum. Systematic reviews examining navigation in cancer care were identified in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Cumulative Index of Nursing and Allied Health (CINAHL), Epistemonikos, and Prospective Register of Systematic Reviews (PROSPERO) databases and in the gray literature from January 1, 2012, to April 19, 2022. Data were screened, extracted, and appraised independently by two authors. The JBI Critical Appraisal Checklist for Systematic Review and Research Syntheses was used for quality appraisal. Emerging literature up to May 25, 2022, was also explored to capture primary research published beyond the coverage of included systematic reviews. Of the 2062 unique records identified, 61 systematic reviews were included. Fifty‐four reviews were quantitative or mixed‐methods reviews, reporting on the effectiveness of cancer patient navigation, including 12 reviews reporting costs or cost‐effectiveness outcomes. Seven qualitative reviews explored navigation needs, barriers, and experiences. In addition, 53 primary studies published since 2021 were included. Patient navigation is effective in improving participation in cancer screening and reducing the time from screening to diagnosis and from diagnosis to treatment initiation. Emerging evidence suggests that patient navigation improves quality of life and patient satisfaction with care in the survivorship phase and reduces hospital readmission in the active treatment and survivorship care phases. Palliative care data were extremely limited. Economic evaluations from the United States suggest the potential cost‐effectiveness of navigation in screening programs.Raymond J. Chan, Vivienne E. Milch, Fiona Crawford, Williams, Ria Joseph, Jolyn Johal, Narayanee Dick, Matthew P. Wallen, Julie Ratcliffe, Anupriya Agarwal, Larissa Nekhlyudov, Matthew Tieu, Manaf Al, Momani, Scott Turnbull, Rahul Sathiaraj, Dorothy Keefe, Nicolas H. Har

Characterization of anticoagulant heparinoids by immunoprofiling

Heparinoids are used in the clinic as anticoagulants. A specific pentasaccharide in heparinoids activates antithrombin III, resulting in inactivation of factor Xa and–when additional saccharides are present–inactivation of factor IIa. Structural and functional analysis of the heterogeneous heparinoids generally requires advanced equipment, is time consuming, and needs (extensive) sample preparation. In this study, a novel and fast method for the characterization of heparinoids is introduced based on reactivity with nine unique anti-heparin antibodies. Eight heparinoids were biochemically analyzed by electrophoresis and their reactivity with domain-specific anti-heparin antibodies was established by ELISA. Each heparinoid displayed a distinct immunoprofile matching its structural characteristics. The immunoprofile could also be linked to biological characteristics, such as the anti-Xa/anti-IIa ratio, which was reflected by reactivity of the heparinoids with antibodies HS4C3 (indicative for 3-O-sulfates) and HS4E4 (indicative for domains allowing anti-factor IIa activity). In addition, the immunoprofile could be indicative for heparinoid-induced side-effects, such as heparin-induced thrombocytopenia, as illustrated by reactivity with antibody NS4F5, which defines a very high sulfated domain. In conclusion, immunoprofiling provides a novel, fast, and simple methodology for the characterization of heparinoids, and allows high-throughput screening of (new) heparinoids for defined structural and biological characteristics

Measurement of the CP-Violating Asymmetry Amplitude sin2β\beta

We present results on time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 million Y(4S) --> B Bbar decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B0 or B0bar from its decay products. The amplitude of the CP-violating asymmetry, which in the Standard Model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta = 0.741 +/- 0.067 (stat) +/- 0.033 (syst) and |lambda| = 0.948 +/- 0.051 (stat) +/- 0.017 (syst). The magnitude of lambda is consistent with unity, in agreement with the Standard Model expectation of no direct CP violation in these modes