Effects of a parent training using telehealth: Equity and access to early intervention for rural families

Children living in geographically rural areas may have limited access to early, intensive evidence-based interventions suggesting children residing in these areas are less likely to experience positive outcomes than their urban-dwelling peers.  Telehealth offers an option to rural families seeking early intervention by using communication technologies where providers are able to consult and deliver services in real-time over geographical distances. To our knowledge, no other study has examined the implementation of P-ESDM in rural natural environments within the framework of the state’s early intervention program. Using a multiple baseline design across participants, the current study investigated the effects of the parent-Early Start Denver Model implemented within a rural northeastern state’s existing IDEA Part C early intervention program.  Parents demonstrated increased fidelity to intervention strategies and reported satisfaction with the program’s ease of implementation and observed child gains.  Statistically significant pre-to post- change in children’s ASD symptomatology were reported for the domains of communication, social reciprocity and repetitive and restricted behaviors.  Support for parent-mediated interventions, the importance of fidelity of implementation for sustainability of intervention strategies, and the need to explore telehealth as a viable service delivery option to improve developmental trajectories for toddlers with autism are discussed

Personalized ctDNA micro-panels can monitor and predict clinical outcomes for patients with triple-negative breast cancer

Circulating tumor DNA (ctDNA) in peripheral blood has been used to predict prognosis and therapeutic response for triple-negative breast cancer (TNBC) patients. However, previous approaches typically use large comprehensive panels of genes commonly mutated across all breast cancers. Given the reduction in sequencing costs and decreased turnaround times associated with panel generation, the objective of this study was to assess the use of custom micro-panels for tracking disease and predicting clinical outcomes for patients with TNBC. Paired tumor-normal samples from patients with TNBC were obtained at diagnosis (T0) and whole exome sequencing (WES) was performed to identify somatic variants associated with individual tumors. Custom micro-panels of 4-6 variants were created for each individual enrolled in the study. Peripheral blood was obtained at baseline, during Cycle 1 Day 3, at time of surgery, and in 3-6 month intervals after surgery to assess variant allele fraction (VAF) at different timepoints during disease course. The VAF was compared to clinical outcomes to evaluate the ability of custom micro-panels to predict pathological response, disease-free intervals, and patient relapse. A cohort of 50 individuals were evaluated for up to 48 months post-diagnosis of TNBC. In total, there were 33 patients who did not achieve pathological complete response (pCR) and seven patients developed clinical relapse. For all patients who developed clinical relapse and had peripheral blood obtained ≤ 6 months prior to relapse (n = 4), the custom ctDNA micro-panels identified molecular relapse at an average of 4.3 months prior to clinical relapse. The custom ctDNA panel results were moderately associated with pCR such that during disease monitoring, only 11% of patients with pCR had a molecular relapse, whereas 47% of patients without pCR had a molecular relapse (Chi-Square; p-value = 0.10). In this study, we show that a custom micro-panel of 4-6 markers can be effectively used to predict outcomes and monitor remission for patients with TNBC. These custom micro-panels show high sensitivity for detecting molecular relapse in advance of clinical relapse. The use of these panels could improve patient outcomes through early detection of relapse with preemptive intervention prior to symptom onset

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

The NANOGrav 11-Year Data Set: Arecibo Observatory Polarimetry And Pulse Microcomponents

We present the polarization pulse profiles for 28 pulsars observed with the Arecibo Observatory by the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) timing project at 2.1 GHz, 1.4 GHz, and 430 MHz. These profiles represent some of the most sensitive polarimetric millisecond pulsar profiles to date, revealing the existence of microcomponents (that is, pulse components with peak intensities much lower than the total pulse peak intensity). Although microcomponents have been detected in some pulsars previously, we present microcomponents for PSRs B1937+21, J1713+0747, and J2234+0944 for the first time. These microcomponents can have an impact on pulsar timing, geometry, and flux density determination. We present rotation measures for all 28 pulsars, determined independently at different observation frequencies and epochs, and find the Galactic magnetic fields derived from these rotation measures to be consistent with current models. These polarization profiles were made using measurement equation template matching, which allows us to generate the polarimetric response of the Arecibo Observatory on an epoch-by-epoch basis. We use this method to describe its time variability, and find that the polarimetric responses of the Arecibo Observatory's 1.4 and 2.1 GHz receivers vary significantly with time.Comment: 41 pages, 20 figure

Bayesian Solar Wind Modeling with Pulsar Timing Arrays

Using Bayesian analyses we study the solar electron density with the NANOGrav 11-year pulsar timing array (PTA) dataset. Our model of the solar wind is incorporated into a global fit starting from pulse times-of-arrival. We introduce new tools developed for this global fit, including analytic expressions for solar electron column densities and open source models for the solar wind that port into existing PTA software. We perform an ab initio recovery of various solar wind model parameters. We then demonstrate the richness of information about the solar electron density, $n_E$, that can be gleaned from PTA data, including higher order corrections to the simple $1/r^2$ model associated with a free-streaming wind (which are informative probes of coronal acceleration physics), quarterly binned measurements of $n_E$ and a continuous time-varying model for $n_E$ spanning approximately one solar cycle period. Finally, we discuss the importance of our model for chromatic noise mitigation in gravitational-wave analyses of pulsar timing data and the potential of developing synergies between sophisticated PTA solar electron density models and those developed by the solar physics community.Comment: 22 pages, 7 figures, Submitted to Ap

The NANOGrav 12.5-Year Data Set: Polarimetry and Faraday Rotation Measures from Observations of Millisecond Pulsars with the Green Bank Telescope

In this work, we present polarization profiles for 23 millisecond pulsars observed at 820 MHz and 1500 MHz with the Green Bank Telescope as part of the NANOGrav pulsar timing array. We calibrate the data using Mueller matrix solutions calculated from observations of PSRs B1929+10 and J1022+1001. We discuss the polarization profiles, which can be used to constrain pulsar emission geometry, and present both the first published radio polarization profiles for nine pulsars and the discovery of very low intensity average profile components ("microcomponents") in four pulsars. Using the Faraday rotation measures, we measure for each pulsar and use it to calculate the Galactic magnetic field parallel to the line of sight for different lines of sight through the interstellar medium. We fit for linear and sinusoidal trends in time in the dispersion measure and Galactic magnetic field and detect magnetic field variations with a period of one year in some pulsars, but overall find that the variations in these parameters are more consistent with a stochastic origin.Comment: 35 pages, 21 figures. Accepted to Ap

The NANOGrav 12.5-Year Data Set: Dispersion Measure Mis-Estimation with Varying Bandwidths

Noise characterization for pulsar-timing applications accounts for interstellar dispersion by assuming a known frequency-dependence of the delay it introduces in the times of arrival (TOAs). However, calculations of this delay suffer from mis-estimations due to other chromatic effects in the observations. The precision in modeling dispersion is dependent on the observed bandwidth. In this work, we calculate the offsets in infinite-frequency TOAs due to mis-estimations in the modeling of dispersion when using varying bandwidths at the Green Bank Telescope. We use a set of broadband observations of PSR J1643-1224, a pulsar with an excess of chromatic noise in its timing residuals. We artificially restricted these observations to a narrowband frequency range, then used both data sets to calculate residuals with a timing model that does not include short-scale dispersion variations. By fitting the resulting residuals to a dispersion model, and comparing the ensuing fitted parameters, we quantify the dispersion mis-estimations. Moreover, by calculating the autocovariance function of the parameters we obtained a characteristic timescale over which the dispersion mis-estimations are correlated. For PSR J1643-1224, which has one of the highest dispersion measures (DM) in the NANOGrav pulsar timing array, we find that the infinite-frequency TOAs suffer from a systematic offset of ~22 microseconds due to DM mis-estimations, with correlations over ~1 month. For lower-DM pulsars, the offset is ~7 microseconds. This error quantification can be used to provide more robust noise modeling in NANOGrav's data, thereby increasing sensitivity and improving parameter estimation in gravitational wave searches.Comment: 15 pages, 7 figure

The NANOGrav 12.5-Year Data Set:Dispersion Measure Misestimations with Varying Bandwidths

Noise characterization for pulsar-timing applications accounts for interstellar dispersion by assuming a known frequency dependence of the delay it introduces in the times of arrival (TOAs). However, calculations of this delay suffer from misestimations due to other chromatic effects in the observations. The precision in modeling dispersion is dependent on the observed bandwidth. In this work, we calculate the offsets in infinite-frequency TOAs due to misestimations in the modeling of dispersion when using varying bandwidths at the Green Bank Telescope. We use a set of broadband observations of PSR J1643−1224, a pulsar with unusual chromatic timing behavior. We artificially restricted these observations to a narrowband frequency range, then used both the broad- and narrowband data sets to calculate residuals with a timing model that does not account for time variations in the dispersion. By fitting the resulting residuals to a dispersion model and comparing the fits, we quantify the error introduced in the timing parameters due to using a reduced frequency range. Moreover, by calculating the autocovariance function of the parameters, we obtained a characteristic timescale over which the dispersion misestimates are correlated. For PSR J1643−1224, which has one of the highest dispersion measures (DM) in the NANOGrav pulsar timing array, we find that the infinite-frequency TOAs suffer from a systematic offset of ∼22 μs due to incomplete frequency sampling, with correlations over about one month. For lower-DM pulsars, the offset is ∼7 μs. This error quantification can be used to provide more robust noise modeling in the NANOGrav data, thereby increasing the sensitivity and improving the parameter estimation in gravitational wave searches

Evaluation of an electronic warfarin nomogram for anticoagulation of hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Warfarin nomograms to guide dosing have been shown to improve control of the international normalized ratio (INR) in the general outpatient setting. However, the effectiveness of these nomograms in hemodialysis patients is unknown. We evaluated the effectiveness of anticoagulation using an electronic warfarin nomogram administered by nurses in outpatient hemodialysis patients, compared to physician directed therapy.</p> <p>Methods</p> <p>Hemodialysis patients at any of the six outpatient clinics in Calgary, Alberta, treated with warfarin anticoagulation were included. Two five-month time periods were compared: prior to and post implementation of the nomogram. The primary endpoint was adequacy of anticoagulation (proportion of INR measurements within range ± 0.5 units).</p> <p>Results</p> <p>Overall, 67 patients were included in the pre- and 55 in the post-period (with 40 patients in both periods). Using generalized linear mixed models, the adequacy of INR control was similar in both periods for all range INR levels: in detail, range INR 1.5 to 2.5 (pre 93.6% (95% CI: 88.6% - 96.5%); post 95.6% (95% CI: 89.4% - 98.3%); p = 0.95); INR 2.0 to 3.0 (pre 82.2% (95% CI: 77.9% - 85.8%); post 77.4% (95% CI: 72.0% - 82.0%); p = 0.20); and, INR 2.5 to 3.5 (pre 84.3% (95% CI: 59.4% - 95.1%); post 66.8% (95% CI: 39.9% - 86.0%); p = 0.29). The mean number of INR measurements per patient decreased significantly between the pre- (30.5, 95% CI: 27.0 - 34.0) and post- (22.3, 95% CI: 18.4 - 26.1) (p = 0.003) period. There were 3 bleeding events in each of the periods.</p> <p>Conclusions</p> <p>An electronic warfarin anticoagulation nomogram administered by nurses achieved INR control similar to that of physician directed therapy among hemodialysis patients in an outpatient setting, with a significant reduction in frequency of testing. Future controlled trials are required to confirm the efficacy of this nomogram.</p

The NANOGrav Nine-year Data Set:Observations, Arrival Time Measurements, and Analysis of 37 Millisecond Pulsars

We present high-precision timing observations spanning up to nine years for 37 millisecond pulsars monitored with the Green Bank and Arecibo radio telescopes as part of the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) project. We describe the observational and instrumental setups used to collect the data, and methodology applied for calculating pulse times of arrival; these include novel methods for measuring instrumental offsets and characterizing low signal-to-noise ratio timing results. The time of arrival data are fit to a physical timing model for each source, including terms that characterize time-variable dispersion measure and frequency-dependent pulse shape evolution. In conjunction with the timing model fit, we have performed a Bayesian analysis of a parameterized timing noise model for each source, and detect evidence for excess low-frequency, or "red," timing noise in 10 of the pulsars. For 5 of these cases this is likely due to interstellar medium propagation effects rather than intrisic spin variations. Subsequent papers in this series will present further analysis of this data set aimed at detecting or limiting the presence of nanohertz-frequency gravitational wave signals