Effectiveness of a short video-based educational intervention on factors related to clinical trial participation in adolescents and young adults: a pre-test/post-test design

Abstract Background Poor clinical trial enrollment continues to be pervasive and is especially problematic among young adults and youth, and among minorities. Efforts to address barriers to enrollment have been predominantly focused on adult diseased populations. Because older adults may already have established attitudes, it is imperative to identify strategies that target adolescents and young adults. The purpose of this study was to test the effectiveness of an educational video on factors related to clinical trial participation among a healthy adolescent and young adult population. Methods Participants completed a 49-item pre-test, viewed a 10-min video, and completed a 45-item post-test to assess changes in attitudes, knowledge, self-efficacy, receptivity to, and intention to participate (primary outcome) in clinical trials. Descriptive statistics, paired samples t-tests, and Wilcoxon signed-rank tests were conducted. Results The final analyses included 935 participants. The mean age was 20.7 years, with almost 70% aged 18 to 20 years. The majority were female (73%), non-Hispanic (92.2%), white (70%), or African American (20%). Participants indicated a higher intention to participate in a clinical trial (p < 0.0001) and receptivity to hearing more about a clinical trial (p < 0.0001) after seeing the video. Intention to participate (definitely yes and probably yes) increased by an absolute 18% (95% confidence interval 15–22%). There were significant improvements in attitudes, knowledge, and self-efficacy scores for all participants (p < 0.0001). Conclusions The results of this study showed strong evidence for the effectiveness of a brief intervention on factors related to participation in clinical trials. This supports the use of a brief intervention, in a traditional educational setting, to impact the immediate attitudes, knowledge, self-efficacy, and intention to participate in clinical trial research among diverse, healthy adolescents and young adults.https://deepblue.lib.umich.edu/bitstream/2027.42/146769/1/13063_2018_Article_3097.pd

C-terminal phosphorylation of NaV1.5 impairs FGF13-dependent regulation of channel inactivation

International audienceVoltage-gated Na(+) (NaV) channels are key regulators of myocardial excitability, and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent alterations in NaV1.5 channel inactivation are emerging as a critical determinant of arrhythmias in heart failure. However, the global native phosphorylation pattern of NaV1.5 subunits associated with these arrhythmogenic disorders and the associated channel regulatory defects remain unknown. Here, we undertook phosphoproteomic analyses to identify and quantify in situ the phosphorylation sites in the NaV1.5 proteins purified from adult WT and failing CaMKIIδc-overexpressing (CaMKIIδc-Tg) mouse ventricles. Of 19 native NaV1.5 phosphorylation sites identified, two C-terminal phosphoserines at positions 1938 and 1989 showed increased phosphorylation in the CaMKIIδc-Tg compared with the WT ventricles. We then tested the hypothesis that phosphorylation at these two sites impairs fibroblast growth factor 13 (FGF13)-dependent regulation of NaV1.5 channel inactivation. Whole-cell voltage-clamp analyses in HEK293 cells demonstrated that FGF13 increases NaV1.5 channel availability and decreases late Na(+) current, two effects that were abrogated with NaV1.5 mutants mimicking phosphorylation at both sites. Additional co-immunoprecipitation experiments revealed that FGF13 potentiates the binding of calmodulin to NaV1.5 and that phosphomimetic mutations at both sites decrease the interaction of FGF13 and, consequently, of calmodulin with NaV1.5. Together, we have identified two novel native phosphorylation sites in the C terminus of NaV1.5 that impair FGF13-dependent regulation of channel inactivation and may contribute to CaMKIIδc-dependent arrhythmogenic disorders in failing hearts

Evolving a puncture black hole with fixed mesh refinement

We present an algorithm for treating mesh refinement interfaces in numerical relativity. We detail the behavior of the solution near such interfaces located in the strong field regions of dynamical black hole spacetimes, with particular attention to the convergence properties of the simulations. In our applications of this technique to the evolution of puncture initial data with vanishing shift, we demonstrate that it is possible to simultaneously maintain second order convergence near the puncture and extend the outer boundary beyond 100M, thereby approaching the asymptotically flat region in which boundary condition problems are less difficult and wave extraction is meaningful.Comment: 18 pages, 12 figures. Minor changes, final PRD versio

Speaking out about gender imbalance in invited speakers improves diversity.

Omissions of qualified women scientists from major meeting programs continue to occur despite a surge in articles indicating persistent gender-discriminatory practices in hiring and promotion, and calls for gender balance in conference organizing committees

Familial Amyotrophic Lateral Sclerosis-associated Mutations Decrease the Thermal Stability of Distinctly Metallated Species of Human Copper/Zinc Superoxide Dismutase

We report the thermal stability of wild type (WT) and 14 different variants of human copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis (FALS). Multiple endothermic unfolding transitions were observed by differential scanning calorimetry for partially metallated SOD1 enzymes isolated from a baculovirus system. We correlated the metal ion contents of SOD1 variants with the occurrence of distinct melting transitions. Altered thermal stability upon reduction of copper with dithionite identified transitions resulting from the unfolding of copper-containing SOD1 species. We demonstrated that copper or zinc binding to a subset of “WT-like” FALS mutants (A4V, L38V, G41S, G72S, D76Y, D90A, G93A, and E133Δ) conferred a similar degree of incremental stabilization as did metal ion binding to WT SOD1. However, these mutants were all destabilized by ∼1–6 °C compared with the corresponding WT SOD1 species. Most of the “metal binding region” FALS mutants (H46R, G85R, D124V, D125H, and S134N) exhibited transitions that probably resulted from unfolding of metal-free species at ∼4–12 °C below the observed melting of the least stable WT species. We conclude that decreased conformational stability shared by all of these mutant SOD1s may contribute to SOD1 toxicity in FALS

Using a Differential Emission Measure and Density Measurements in an Active Region Core to Test a Steady Heating Model

The frequency of heating events in the corona is an important constraint on the coronal heating mechanisms. Observations indicate that the intensities and velocities measured in active region cores are effectively steady, suggesting that heating events occur rapidly enough to keep high temperature active region loops close to equilibrium. In this paper, we couple observations of Active Region 10955 made with XRT and EIS on \textit{Hinode} to test a simple steady heating model. First we calculate the differential emission measure of the apex region of the loops in the active region core. We find the DEM to be broad and peaked around 3\,MK. We then determine the densities in the corresponding footpoint regions. Using potential field extrapolations to approximate the loop lengths and the density-sensitive line ratios to infer the magnitude of the heating, we build a steady heating model for the active region core and find that we can match the general properties of the observed DEM for the temperature range of 6.3 $<$ Log T $<$ 6.7. This model, for the first time, accounts for the base pressure, loop length, and distribution of apex temperatures of the core loops. We find that the density-sensitive spectral line intensities and the bulk of the hot emission in the active region core are consistent with steady heating. We also find, however, that the steady heating model cannot address the emission observed at lower temperatures. This emission may be due to foreground or background structures, or may indicate that the heating in the core is more complicated. Different heating scenarios must be tested to determine if they have the same level of agreement.Comment: 16 pages, 9 figures, accepted to Ap

The Chandra XBootes Survey - III: Optical and Near-IR Counterparts

The XBootes Survey is a 5-ks Chandra survey of the Bootes Field of the NOAO Deep Wide-Field Survey (NDWFS). This survey is unique in that it is the largest (9.3 deg^2), contiguous region imaged in X-ray with complementary deep optical and near-IR observations. We present a catalog of the optical counterparts to the 3,213 X-ray point sources detected in the XBootes survey. Using a Bayesian identification scheme, we successfully identified optical counterparts for 98% of the X-ray point sources. The optical colors suggest that the optically detected galaxies are a combination of z<1 massive early-type galaxies and bluer star-forming galaxies whose optical AGN emission is faint or obscured, whereas the majority of the optically detected point sources are likely quasars over a large redshift range. Our large area, X-ray bright, optically deep survey enables us to select a large sub-sample of sources (773) with high X-ray to optical flux ratios (f_x/f_o>10). These objects are likely high redshift and/or dust obscured AGN. These sources have generally harder X-ray spectra than sources with 0.1<f_x/f_o<10. Of the 73 X-ray sources with no optical counterpart in the NDWFS catalog, 47 are truly optically blank down to R~25.5 (the average 50% completeness limit of the NDWFS R-band catalogs). These sources are also likely to be high redshift and/or dust obscured AGN.Comment: 19 pages, 13 figures, ApJ accepted. Catalog can be found at: http://www.noao.edu/noao/noaodeep or ftp://archive.noao.edu/pub/catalogs/xbootes