8,522 research outputs found

    MyPathway human epidermal growth factor receptor 2 basket study: Pertuzumab + trastuzumab treatment of a tissue-agnostic cohort of patients with human epidermal growth factor receptor 2-altered advanced solid tumors.

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    Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The MyPathway multiple-basket study (ClinicalTrials.gov identifier: NCT02091141) is evaluating targeted therapies in nonindicated tumors with relevant molecular alterations. We assessed pertuzumab + trastuzumab in a tissue-agnostic cohort of adult patients with human epidermal growth factor receptor 2 (HER2)-amplified and/or -overexpressed and/or -mutated solid tumors. The primary end point was objective response rate (ORR); secondary end points included survival and safety. At data cutoff (March 2022), 346 patients with HER2 amplification and/or overexpression with/without HER2 mutations (n = 263), or HER2 mutations alone (n = 83) had been treated. Patients with HER2 amplification and/or overexpression had an ORR of 25.9% (68/263, 95% CI, 20.7 to 31.6), including five complete responses (urothelial [n = 2], salivary gland [n = 2], and colon [n = 1] cancers). Activity was higher in those with wild-type (ORR, 28.1%) versus mutated KRAS (ORR, 7.1%). Among patients with HER2 amplification, ORR was numerically higher in patients with immunohistochemistry (IHC) 3+ (41.0%; 32/78) or 2+ (21.9%; 7/32), versus 1+ (8.3%; 1/12) or no expression (0%; 0/20). In patients with HER2 mutations alone, ORR was 6.0% (5/83, 95% CI, 2.0 to 13.5). Pertuzumab + trastuzumab showed activity in various HER2-amplified and/or -overexpressed tumors with wild-type KRAS, with the range of activity dependent on tumor type, but had limited activity in the context of KRAS mutations, HER2 mutations alone, or 0-1+ HER2 expression

    Spleen tyrosine kinase/FMS-like tyrosine kinase-3 inhibition in relapsed/refractory B-cell lymphoma, including diffuse large B-cell lymphoma: updated data with mivavotinib (TAK-659/CB-659)

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    Non-Hodgkin’s lymphoma; SYK inhibitor; Relapsed/refractoryLinfoma no Hodgkin; Inhibidor de SYK; Recidivante/refractarioLimfoma no Hodgkin; Inhibidor de SYK; Recaiguda/refractĂ riaWe report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib, presenting data for the overall cohort of lymphoma patients, and the subgroup of patients with diffuse large B-cell lymphoma (DLBCL; including an expanded cohort not included in the initial report). Patients with relapsed/refractory lymphoma for which no standard treatment was available received mivavotinib 60–120 mg once daily in 28-day cycles until disease progression/unacceptable toxicity. A total of 124 patients with lymphoma, including 89 with DLBCL, were enrolled. Overall response rates (ORR) in response-evaluable patients were 45% (43/95) and 38% (26/69), respectively. Median duration of response was 28.1 months overall and not reached in DLBCL responders. In subgroups with DLBCL of germinal center B-cell (GCB) and non-GCB origin, ORR was 28% (11/40) and 58% (7/12), respectively. Median progression free survival was 2.0 and 1.6 months in the lymphoma and DLBCL cohorts, respectively. Grade ≄3 treatment-emergent adverse events occurred in 96% of all lymphoma patients, many of which were limited to asymptomatic laboratory abnormalities; the most common were increased amylase (29%), neutropenia (27%), and hypophosphatemia (26%). These findings support SYK as a potential therapeutic target for the treatment of patients with B-cell lymphomas, including DLBCL.This study was funded by Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA

    Uncrewed surface vehicles network in support to EOOS: the EuroSea project

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    A wide range of platforms and systems constitute the current Global Ocean Observing System (GOOS) including satellites, research vessels, floats, underwater gliders, fixed-point observatories, sea level stations, high frequency radar and uncrewed surface vehicles. The European Ocean Observing System (EOOS) is designed to align and integrate Europe’s ocean observing capacity, promote a systematic and collaborative approach to collecting information on the state and variability of our seas, and underpin sustainable management of the marine environment and its resources. EOOS attempts to link the currently disparate observing system components and promote novel technology and infrastructure development, standardization, open access to data, and capacity building. Within the framework of EOOS is the EU-funded EuroSea project, with the overall goal to consolidate an integrated interdisciplinary ocean-observing-system to deliver essential information for the wellbeing, blue growth and sustainable management of the ocean, based on the implementation and coordination of the different observing networks above-mentioned, being the Uncrewed Surface Vehicles (USV) technology one of the novelties in terms of network initiative attempting to engage existing and forthcoming actors from public and private sectors, to consolidate an international USV network under common standard operational procedures and regulatory framework in support to EOOS strategy.Peer Reviewe

    Resilience as a potential modifier of racial inequities in preterm birth

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    PURPOSE: In the United States, preterm birth is 55% more common among Black compared to White individuals and psychosocial stressors may contribute. Resilience is associated with improved health outcomes outside of pregnancy. However, whether resilience modifies preterm birth inequity is unknown. We hypothesized that high resilience would reduce inequities in preterm birth risk. METHODS: This study analyzes data from 535 pregnancies among Black (n=101, 19%) and White (n=434, 81%) participants from the Spontaneous Prematurity and Epigenetics of the Cervix prospective cohort. Participants completed the Connor-Davidson Resilience Scale. We calculated risk ratios (RR) for preterm birth among Black compared to White participants, stratified by resilience tertiles, to test for effect measure modification. RESULTS: Among those in the lowest resilience tertile, there were 6 (20.7%) preterm births among Black and 7 (4.9%) among White participants (RR: 4.26; 95% confidence interval (CI): 1.53, 11.81). Among those in the highest resilience tertile, there were 8 (18.2%) preterm births among Black and 14 (9.5%) among White participants (RR: 1.92; 95% CI: 0.87, 4.24. Adjusting for education and income, the Black:White RR was 2.00 (95% CI 0.47, 8.64) in the lowest tertile, and 3.49 (95% CI 1.52, 8.01) in the highest tertile. CONCLUSIONS: Black-White preterm birth inequity did not differ among resilience strata and remained significant in the highest tertile. Our findings suggest that high resilience is inadequate to overcome Black:White racial inequity in preterm birth

    Examining the Impact of Stress and Fear of COVID-19 on Transit Travel

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    The COVID-19 pandemic initially caused a significant decrease in travel. Whereas highway travel rebounded quickly, transit use has not fully returned and may not fully return in the short or medium term. This report discusses the results from a survey of travelers\u27 stated use of transit before, during, and after the pandemic, focusing on identifying factors associated with the change in transit use, including stress and fear of COVID-19. The study included data collection in three experiment phases. In the first phase of data collection, the survey was distributed via several online platforms while the data for the second phase of the experiment was collected at Texas A&M’s Human Behavior Laboratory (HBL). The third phase included a virtual reality (VR) experiment conducted at the University of Puerto Rico at Mayagüez that included skin conductance response measurements along with the survey questionnaire. The research found there may be as many as 35% to 45% of respondents who will not use transit as much in the future due to COVID-19. This higher range occurs if both the responses “Extremely” and “Very” are considered indicators of future travel decisions for survey questions asking the importance or likeliness of COVID-19 factors. However, if we consider only those respondents who indicated “Extremely Important,” “Extremely Likely,” and “Extremely Uncomfortable,” then a lower range of 15% to 25% of respondents will not use transit as much in the future. When examining Texas A&M students only, the percentage who may use less transit due to COVID-19 is likely smaller than 15%, but greater than 0%. Therefore, in addition to telecommuting and mode shifts caused by the pandemic, transit agencies must overcome the stresses and fears that commuters have related to COVID-19 for ridership to return to pre-pandemic levels

    IRAS 00450+7401 and the mid-infrared fade/burst cycle of R Coronae Borealis-type stars

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    We present optical and infrared imaging and spectroscopy of the R Coronae Borealis-type (R Cor Bor) star IRAS 00450+7401. Optical spectra further confirm its classification as a cool R Cor Bor system, having a hydrogen-deficient carbon star spectral sub-class of HdC5 or later. Mid-infrared spectroscopy reveals the typical ~8 um ``hump'' seen in other R Cor Bor stars and no other features. A modern-epoch spectral energy distribution shows bright emission from hot dust having Tdust>600 K. Historical infrared data reveal generally cooler dust color temperatures combined with long-term fading trends, but provide no discernible correlation between flux level and temperature. Investigating the most mid-infrared variable R Cor Bor stars found in IRAS, AKARI, and WISE data reveals similar fading trends, bursts that can show a factor of up to 10 change in flux density between epochs, and blackbody-fit dust color temperatures that span 400-1300 K. While some R Cor Bor stars such as IRAS 00450+7401 appear to undergo fade/burst cycles in the mid-infrared, significant gaps in temporal coverage prevent conclusively identifying any preferred timescale for their mid-infrared variability and circumstellar dust temperature changes.Comment: AJ accepted, 15 pages, 6 figures, 5 tables, and an appendi

    Nurse Like Me Mentorship Program: A DNP Approach to Elevating Health Equity

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    The nursing profession is facing a growing shortage. Although diversity in the nursing profession is improving, unacceptable gaps remain. In addition, post-pandemic study findings show that younger nurses are at a higher risk for leaving the nursing profession, increasing the threats of shortage and diversity beyond what was previously predicted. Nurse shortages and diversity gaps impact our community's health and health equity. The Nurse Like Me (NLM) mentorship project sought to mitigate nurse shortage and improve nurse diversity through the mentoring of diverse high school students interested in nursing by diverse college nursing students with similar interests and or demographics. The project took place over eight weeks between September 2021 and November 2021. During those eight weeks, high school students from a local public school were paired with college nursing students from a NC Historically Black College/University (HBCU) for nurse mentoring. The mentee/mentor pairs met biweekly for a total of four meetings. During the meetings mentors provided general education on the nursing profession, discussed college nursing programs, reviewed nursing service scholarships, and answered mentee questions about nursing. At the end of the eight weeks, the high school mentees showed a significant increase in their interest in college nursing programs, increased awareness of nursing service scholarships, and were satisfied with the program. Feedback from the mentees and mentors all revealed a positive experience with the NLM project. The goals of the project aligned with the goals of Kannapolis City Schools' 2020-2025 Strategic Plan, the North Carolina State Board of Education's 2025 Statewide Strategic Plan, the North Carolina Institute of Medicine's Healthy North Carolina 2030, and the American Association of Colleges of Nursing's Enhancing Diversity in the Nursing Workforce fact sheet

    4D Flow cardiovascular magnetic resonance consensus statement: 2023 update

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    Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 ‘4D Flow CMR Consensus Statement’. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards.ISSN:1097-6647ISSN:1532-429
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