An Exploratory Study of the Likelihood of Adopting Genetic Counseling and Testing for Lynch Syndrome-related Colorectal Cancer Among Primary Care Physicians in Florida

Genetic counseling and testing for inherited cancer syndromes have the potential to save lives and may be an avenue for addressing health care disparities among African Americans newly diagnosed with colorectal cancer (CRC); and their close relatives. African Americans are more likely to be diagnosed with CRC at younger ages (under age 50 years), and diagnosed at later stages when cancer is more aggressive and difficult to treat, which are factors associated with hereditary cancers such as Lynch syndrome-related CRC. Considering the benefits of genetic testing for hereditary cancer syndromes - risk stratification, preventive surveillance, targeted treatment, and subsequent reduction in morbidity and mortality among patients by up to 60% - it appears that genetic testing may have a role in prevention, early intervention and reduction of CRC disparities in African Americans. Primary care physicians (PCPs), often the access point to the healthcare system, were anticipated to be at the forefront of genetic counseling and testing. However, a growing body of literature indicates that PCPs see genetic testing as the role of a specialist. This quantitative survey research study, based on the constructs of the Diffusion of Innovation Theory (Rogers, 2003), explored the factors which influence the likelihood of adoption of genetic counseling and testing for Lynch syndrome-related colorectal cancer among PCPs in Florida

Measurement of the Free-Floating Planet Mass Function with Simultaneous Euclid and WFIRST Microlensing Parallax Observations

Free-floating planets are the remnants of violent dynamical rearrangements of planetary systems. It is possible that even our own solar system ejected a large planet early in its evolution. WFIRST will have the ability to detect free-floating planets over a wide range of masses, but it will not be able to directly measure their masses. Microlensing parallax observations can be used to measure the masses of isolated objects, including free-floating planets, by observing their microlensing events from two locations. The intra-L2 separation between WFIRST and Euclid is large enough to enable microlensing parallax measurements, especially given the exquisite photometric precision that both spacecraft are capable of over wide fields. In this white paper we describe how a modest investment of observing time could yield hundreds of parallax measurements for WFIRST's bound and free-floating planets. We also describe how a short observing campaign of precursor observations by Euclid can improve WFIRST's bound planet and host star mass measurements.Comment: Astro2020 White Pape

Exploring the Association of Physician Characteristics to Patient Requests for Genetic Testing

Background: Cancer genomic testing improves health outcomes for individuals at risk, drives cost-efficiency, and facilitates healthcare equity; however, little is known about how physician demographic and practice characteristics influence patient requests for genetic testing. Purpose: To explore whether (and to what extent) physician demographic and practice characteristics are associated with patient requests for cancer genetic testing. Methods: A cross-sectional quantitative design survey was distributed to 1240 primary care physicians registered with the state health department who had active licenses and main practices in Florida. Primary care physicians were defined as those who practice family medicine, internal medicine, obstetrics, and gynecology. The survey tool was developed from a search of the literature and two previously validated surveys. It was administered using a modified Dillmanstrategy. The study sample size was 317 physicians, with an 85% response rate based upon a targeted sample of 372. Statistical calculations were performed using SPSS version 27 and STATA release 17.Results: Logistic regression model found significant associations between patient requests and physicians\u27 race and professional practice size. Physicians identified as White were 1.840 times as likely to have patient requests for genetic testing (p=.036) than physicians whose race was other than White. Physicians whose professional practices were solo or small groups were 2.39 times as likely to have patient requests (p=.001) than physicians affiliated with larger practices. Discussion: Patient requests may be leveraged by physicians, other healthcare providers, and public health professionals; patient requests present a significant opportunity for increasing genetic testing and thus promoting better health outcomes for patients with Lynch syndrome-related colorectal cancer

Overview of the Alberta Kidney Disease Network

<p>Abstract</p> <p>Background</p> <p>The Alberta Kidney Disease Network is a collaborative nephrology research organization based on a central repository of laboratory and administrative data from the Canadian province of Alberta.</p> <p>Description</p> <p>The laboratory data within the Alberta Kidney Disease Network can be used to define patient populations, such as individuals with chronic kidney disease (using serum creatinine measurements to estimate kidney function) or anemia (using hemoglobin measurements). The administrative data within the Alberta Kidney Disease Network can also be used to define cohorts with common medical conditions such as hypertension and diabetes. Linkage of data sources permits assessment of socio-demographic information, clinical variables including comorbidity, as well as ascertainment of relevant outcomes such as health service encounters and events, the occurrence of new specified clinical outcomes and mortality.</p> <p>Conclusion</p> <p>The unique ability to combine laboratory and administrative data for a large geographically defined population provides a rich data source not only for research purposes but for policy development and to guide the delivery of health care. This research model based on computerized laboratory data could serve as a prototype for the study of other chronic conditions.</p

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

White Paper: Exoplanetary Microlensing from the Ground in the 2020s

Microlensing can access planet populations that no other method can probe: cold wide-orbit planets beyond the snow line, planets in both the Galactic bulge and disk, and free floating planets (FFPs). The demographics of each population will provide unique constraints on planet formation. Over the past 5 years, U.S. microlensing campaigns with Spitzer and UKIRT have provided a powerful complement to international ground-based microlensing surveys, with major breakthroughs in parallax measurements and probing new regions of the Galaxy. The scientific vitality of these projects has also promoted the development of the U.S. microlensing community. In the 2020s, the U.S. can continue to play a major role in ground-based microlensing by leveraging U.S. assets to complement ongoing ground-based international surveys. LSST and UKIRT microlensing surveys would probe vast regions of the Galaxy, where planets form under drastically different conditions. Moreover, while ground-based surveys will measure the planet mass-ratio function beyond the snow line, adaptive optics (AO) observations with ELTs would turn all of these mass ratios into masses and also distinguish between very wide-orbit planets and genuine FFPs. To the extent possible, cooperation of U.S. scientists with international surveys should also be encouraged and supported