Effect of time to diagnostic testing for breast, cervical, and colorectal cancer screening abnormalities on screening efficacy: A modeling study

Background: Patients who receive an abnormal cancer screening result require follow-up for diagnostic testing, but the time to follow-up varies across patients and practices. Methods: We used a simulation study to estimate the change in lifetime screening benefits when time to follow-up for breast, cervical, and colorectal cancers was increased. Estimates were based on four independently developed microsimulation models that each simulated the life course of adults eligible for breast (women ages 50–74 years), cervical (women ages 21–65 years), or colorectal (adults ages 50–75 years) cancer screening. We assumed screening based on biennial mammography for breast cancer, triennial Papanicolaou testing for cervical cancer, and annual fecal immunochemical testing for colorectal cancer. For each cancer type, we simulated diagnostic testing immediately and at 3, 6, and 12 months after an abnormal screening exam. Results: We found declines in screening benefit with longer times to diagnostic testing, particularly for breast cancer screening. Compared to immediate diagnostic testing, testing at 3 months resulted in reduced screening benefit, with fewer undiscounted life years gained per 1,000 screened (breast: 17.3%, cervical: 0.8%, colorectal: 2.0% and 2.7%, from two colorectal cancer models), fewer cancers prevented (cervical: 1.4% fewer, colorectal: 0.5% and 1.7% fewer, respectively), and, for breast and colorectal cancer, a less favorable stage distribution. Conclusions: Longer times to diagnostic testing after an abnormal screening test can decrease screening effectiveness, but the impact varies substantially by cancer type. Impact: Understanding the impact of time to diagnostic testing on screening effectiveness can help inform quality improvement efforts. Cancer Epidemiol Biomarkers Prev; 27(2); 158–64. 2017 AACR

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

On the progenitor of binary neutron star merger GW170817

On 2017 August 17 the merger of two compact objects with masses consistent with two neutron stars was discovered through gravitational-wave (GW170817), gamma-ray (GRB 170817A), and optical (SSS17a/AT 2017gfo) observations. The optical source was associated with the early-type galaxy NGC 4993 at a distance of just ∼40 Mpc, consistent with the gravitational-wave measurement, and the merger was localized to be at a projected distance of ∼2 kpc away from the galaxy's center. We use this minimal set of facts and the mass posteriors of the two neutron stars to derive the first constraints on the progenitor of GW170817 at the time of the second supernova (SN). We generate simulated progenitor populations and follow the three-dimensional kinematic evolution from binary neutron star (BNS) birth to the merger time, accounting for pre-SN galactic motion, for considerably different input distributions of the progenitor mass, pre-SN semimajor axis, and SN-kick velocity. Though not considerably tight, we find these constraints to be comparable to those for Galactic BNS progenitors. The derived constraints are very strongly influenced by the requirement of keeping the binary bound after the second SN and having the merger occur relatively close to the center of the galaxy. These constraints are insensitive to the galaxy's star formation history, provided the stellar populations are older than 1 Gyr

Race/Ethnicity and Adoption of a Population Health Management Approach to Colorectal Cancer Screening in a Community-Based Healthcare System

Background: Screening outreach programs using population health management principles offer services uniformly to all eligible persons, but racial/ethnic colorectal cancer (CRC) screening patterns in such programs are not well known. Objective: To examine the association between race/ethnicity and the receipt of CRC screening and timely follow-up of positive results before and after implementation of a screening program. Design: Retrospective cohort study of screen-eligible individuals at the Kaiser Permanente Northern California community-based integrated healthcare delivery system (2004–2013). Subjects: A total of 868,934 screen-eligible individuals 51–74 years of age at cohort entry, which included 662,872 persons in the period before program implementation (2004–2006), 654,633 during the first 3 years after implementation (2007–2009), and 665,268 in the period from 4 to 7 years (2010–2013) after program implementation. Intervention: A comprehensive system-wide long-term effort to increase CRC that included leadership alignment, goal-setting, and quality assurance through a PHM approach, using mailed fecal immunochemical testing (FIT) along with offering screening at office visits. Main Measures: Differences over time and by race/ethnicity in up-to-date CRC screening (overall and by test type) and timely follow-up of a positive screen. Race/ethnicity categories included non-Hispanic white, non-Hispanic black, Hispanic/Latino, Asian/Pacific Islander, Native American, and multiple races. Key Results: From 2004 to 2013, age/sex-adjusted CRC screening rates increased in all groups, including 35.2 to 81.1 % among whites and 35.6 to 78.0 % among blacks. Screening rates among Hispanics (33.1 to 78.3 %) and Native Americans (29.4 to 74.5 %) remained lower than those for whites both before and after program implementation. Blacks, who had slightly higher rates before program implementation (adjusted rate ratio [RR] = 1.04, 99 % CI: 1.02–1.05), had lower rates after program implementation (RR for period from 4 to 7 years = 0.97, 99 % CI: 0.96–0.97). There were also substantial improvements in timely follow-up of positive screening results. Conclusions: In this screening program using core PHM principles, CRC screening increased markedly in all racial/ethnic groups, but disparities persisted for some groups and developed in others, which correlated with levels of adoption of mailed FIT

Correction: The complex genetics of gait speed: Genome-wide metaanalysis approach [Aging, (Albany NY), 9, 1, (2017), (209-246)]doi 10.18632/aging.101151

Applying HaploReg v4.1 analysis to the 536 variants resulted in 9 categories (Supplementary Table 8): miscRNA (1 variant); snoRNA (2 variants); microRNA (4 variants); snRNA (9 variants); pseudogenes (14 variants); sequencing in progress (43 variants); LINC RNA (86 variants); and 372 variants within protein coding genes. In addition, some variants annotate to the same gene resulting in a total of 139 genes (protein-coding or non-coding). Of those genes, 6 are exceptionally long, containing over a million base-pairs, the longest of which is PTPRT coded by 1117219bp. The shortest genes are the ones coding for micro (MIR3143) or small nuclear (U7) RNAs at 63bp each. There is only partial information regarding the chromatin state of each variant. However, from the information gathered in the analysis we observed 14 transcription start sites and 245 enhancers (Supplementary Table 8)

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of

Multi-messenger Observations of a Binary Neutron Star Merger

International audienceOn 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of $\sim 1.7\,{\rm{s}}$ with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg(2) at a luminosity distance of ${40}_{-8}^{+8}$ Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 $\,{M}_{\odot }$. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at $\sim 40\,{\rm{Mpc}}$) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position $\sim 9$ and $\sim 16$ days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Estimating the contribution of dynamical ejecta in the kilonova associated with GW170817

The source of the gravitational-wave (GW) signal GW170817, very likely a binary neutron star merger, was also observed electromagnetically, providing the first multi-messenger observations of this type. The two-week-long electromagnetic (EM) counterpart had a signature indicative of an r-process-induced optical transient known as a kilonova. This Letter examines how the mass of the dynamical ejecta can be estimated without a direct electromagnetic observation of the kilonova, using GW measurements and a phenomenological model calibrated to numerical simulations of mergers with dynamical ejecta. Specifically, we apply the model to the binary masses inferred from the GW measurements, and use the resulting mass of the dynamical ejecta to estimate its contribution (without the effects of wind ejecta) to the corresponding kilonova light curves from various models. The distributions of dynamical ejecta mass range between Mej = 10 -³ - 10-² M⊙ for various equations of state, assuming that the neutron stars are rotating slowly. In addition, we use our estimates of the dynamical ejecta mass and the neutron star merger rates inferred from GW170817 to constrain the contribution of events like this to the r-process element abundance in the Galaxy when ejecta mass from post-merger winds is neglected. We find that if 10% of the matter dynamically ejected from binary neutron star (BNS) mergers is converted to r-process elements, GW170817-like BNS mergers could fully account for the amount of r-process material observed in the Milky Way