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Hamilton, Leah, Mathieu Despard, Stephen Roll, Dylan Bellisle, Christian Hall e Allison Wright. "Does Frequency or Amount Matter? An Exploratory Analysis the Perceptions of Four Universal Basic Income Proposals". Social Sciences 12, n.º 3 (27 de fevereiro de 2023): 133. http://dx.doi.org/10.3390/socsci12030133.
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Advocates for a Universal Basic Income (UBI) argue that it would provide citizens with a basic foundation for financial security, boost the economy, alleviate poverty, encourage entrepreneurship, reduce crime, and insulate the employment sector against job losses due to automation. Still, the idea lags in popularity in the United States compared to existing cash policies such as the annual Earned Income Tax Credit and one-time COVID-19 relief packages. We hypothesize that this disparity is related to predicted uses of a UBI in comparison to annual or lump sum cash programs. In this survey of 836 Americans, we explore whether predicted behavioral responses to four randomly assigned hypothetical cash transfer scenarios vary across the domains of amount and frequency. Respondents are more likely to associate monthly payments with work disincentives and lump-sum transfers with debt repayment. Implications for UBI advocates include the need to continue educating the public on the empirical associations between UBI, employment, and expenditures.
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Ethridge, Glacia, Angel Riddick Dowden e Michael Brooks. "The Impact of Disability and Type of Crime on Employment Outcomes of African American and Latino Offenders". Journal of Applied Rehabilitation Counseling 48, n.º 4 (1 de dezembro de 2017): 46–53. http://dx.doi.org/10.1891/0047-2220.48.4.46.
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Individuals with criminal histories who struggle to gain employment may choose to turn to illegal activity or seek state and federal program assistance to support themselves and their families. African Americans and Hispanic/Latinos with disabilities and criminal histories experience barriers (i.e., disability, criminal history, and race/ethnicity) that often prevent them from obtaining or maintaining competitive integrated employment. The purpose of this article was to examine the extant literature pertinent to disability and criminal history as employment obstacles among African American and Hispanic/Latino ex-offenders. As the foundation, the article categorizes employment outcomes for these target population by disability and criminal history, discusses how state vocational rehabilitation agencies can develop a criminal history service delivery model to improve employment outcomes, presents implications for improving employment outcomes, and explores future research.
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Holm, Emily, Audrey Umbreit, Kelsey Mews e Garrett E. Schramm. "Novel Use of Text-Bot Automation for Residency Recruitment". INNOVATIONS in pharmacy 12, n.º 3 (20 de julho de 2021): 11. http://dx.doi.org/10.24926/iip.v12i3.4029.
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Purpose. To describe the employment of an automated text messaging text-bot during the 2019 American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting Residency Showcase and its impact on the number of applications received for the postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) pharmacy residency programs at a medium-sized community hospital. Methods. Visitors at the residency showcase booth were asked to text a code word to a program number. The text-bot collected the visitor’s contact information and program of interest (PGY1 or PGY2). A series of automated messages were sent to all visitors following the showcase and up until the residency application deadline. Results. 71% (20/28) of visitors to the program’s showcase booth registered with the text-bot and of these, 65% (13/20) submitted applications to the residency program in phase I of the match. Both the PGY1 and PGY2 programs saw an increase in the amount of applications received compared to previous year. Conclusion. A text messaging text-bot may be a useful residency recruitment tool.
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de Aragão Aleksandravicius, Gabriel, Ana Clara Loureiro Cruz, Carolina Niklaus Moreira da Rocha Rodrigues, Gabriela Lemos Lúcidi Pinhão, Pedro Henrique Goes Afonso, Rodrigo Coura Torres e José Manoel Seixas. "Enhancing data consistency in ATLAS and CERN HR databases through automated synchronization". EPJ Web of Conferences 295 (2024): 05004. http://dx.doi.org/10.1051/epjconf/202429505004.
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As the largest particle physics laboratory in the world, it is no surprise that CERN has a vast network of thousands of collaborators spread globally. Among CERN’s experiments, ATLAS stands out with over 6,000 active members and 300 associate institutes. This extensive community must go through the standard registering and maintenance procedures within CERN’s human resources database, called Foundation. Simultaneously, the Glance system, among other specific functions, also aims to fulfill the same objectives within the context of different CERN experiments, such as ATLAS, LHCb and ALICE. It achieves that by having its own database. Since members need to exist in the two databases, a lot of data was being duplicated. Manual updates by the ATLAS secretariat became necessary to maintain consistency over members and institutes data, such as names, employment information and authorship status. Today, the Glance system undergoes a transformative process to redefine its relationship with Foundation. The goal is to eliminate duplication of data by establishing a single source of truth. At the same time, the automation of a series of internal processes will be made to ensure synchronization between the two databases at all times, thus removing the need for manual intervention from the ATLAS secretariat. This requires some restructuring to Glance’s database, updates to the code and overall implementation of new tools that facilitate seamless communication with Foundation.
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Kaufman, Bruce E., e Gregor Gall. "Advancing Industrial Relations Theory: An Analytical Synthesis of British-American and Pluralist-Radical Ideas". Articles 70, n.º 3 (5 de outubro de 2015): 407–31. http://dx.doi.org/10.7202/1033404ar.
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SummaryProminent writers in industrial relations (IR) have concluded the field is in significant decline, partly because of a failed theory base. The theory problem is deepened because other writers conclude developing a theory foundation for industrial relations is neither possible nor desirable. We believe advancing IR theory is both needed and possible, and take up the challenge in this paper.A long-standing problem in theorizing industrial relations has been the lack of agreement on the field’s core analytical construct. However, in the last two decades writers have increasingly agreed the field is centred on the employment relationship. Another long-standing problem is that writers have theorized industrial relations using different theoretical frames of reference, including pluralist and radical-Marxist; different disciplinary perspectives, such as economics, sociology, history, and politics; and from different national traditions, such as British, French, and American.In this paper, we seek to advance IR theory and better integrate paradigms and national traditions. We do this by developing an analytical explanation for four core features of the employment relationship—generation of an economic surplus, cooperation-conflict dialectic, indeterminate nature of the employment contract, and asymmetric authority and power in the firm—using an integrative mix of ideas and concepts from the pluralist and radical-Marxist streams presented in a multi-part diagram constructed with marginalist tools from conventional economics. The diagram includes central IR system components, such as labour market, hierarchical firm, macro-economy, and nation state government. The model is used to explain the four features of the employment relationship and derive implications for IR theory and practice. Examples include the diagrammatic representation of the size and distribution of the economic surplus, a new analytical representation of labour exploitation, identification of labour supply conditions that encourage, respectively, cooperation versus conflict, and demonstration of how inequality of bargaining power in labour markets contributes to macroeconomic stagnation and unemployment.
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Smith, Damariyé L. "Kemetic Principles in African American Public Address: An Interrogation of the Rhetoric of Joseph C. Price and the Kemetic Tradition". Journal of Black Studies 51, n.º 5 (17 de junho de 2020): 458–80. http://dx.doi.org/10.1177/0021934720925743.
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The purpose of this essay is to promote the utilization of Kemetic principles in approaching African American public address. Although there have been recent studies on African American public address, the employment of the Kemetic philosophy is limited. Using the four overarching ethical principles of Kemetic rhetorical tradition as outlined by Karenga, this essay interrogates Joseph C. Price’s 1890 speech at the National Education Association national convention. A Kemetic analysis of Price’s speech reveals that African American public address endorses the dignity and rights of the human person, the well-being of family and community, the integrity and value of the environment, and the reciprocal solidarity and cooperation for the mutual benefit of humanity. This suggests that a Kemetic understanding of African American public address can (a) civically benefit the broader community because of its ethical foundation, (b) facilitate the recognition of contemporary ethical appeals in any given discourse, and (c) serve as an impetus for collective advancement toward a social justice–oriented world.
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Hart, D. G. "The Troubled Soul of the Academy: American Learning and the Problem of Religious Studies". Religion and American Culture: A Journal of Interpretation 2, n.º 1 (1992): 49–77. http://dx.doi.org/10.1525/rac.1992.2.1.03a00030.
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The decade of the 1960's was important for American scholars who studied religion. Prospects for employment brightened considerably as public and private universities and Colleges created undergraduate and graduate programs in religious studies. Becoming more self-conscious about their academic identity, professors who staffed these programs founded the American Academy of Religion in 1964, an organization designed to promote scholarship and publication in religion. One index to the growing prominence of religious studies was the survey of humanistic scholarship commissioned by Princeton University's Council on the Humanities and funded by the Ford Foundation. Of the thirteen volumes in this series, two were devoted to the field of religion: Clyde A. Holbrook's Religion, A Humanistic Field (1963), and Religion (1965), a summary of the various fields in religious studies, edited by Paul Ramsey.
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Sundar, Vidya, e Debra L. Brucker. "Personal and Organizational Determinants of Job Satisfaction for Workers With Disabilities". Rehabilitation Counseling Bulletin 62, n.º 3 (26 de abril de 2018): 170–79. http://dx.doi.org/10.1177/0034355218770272.
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Although persons with disabilities are underrepresented in the workforce, a substantial portion of adults with disabilities does work. Job satisfaction, an important predictor of productivity, job tenure, and absenteeism, may be influenced by a unique set of personal and organizational factors for persons with disabilities. Using data from the 2015 Kessler Foundation National Employment and Disability Survey (KFNEDS), we examine personal and organizational predictors of job satisfaction for American workers with disabilities. Findings from the study suggest that educational attainment, perceived pay disparities, and supervisor attitudes are associated with job satisfaction for workers with disabilities. Coworker attitudes were not associated with job satisfaction for this population.
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Kim, Jae-Hee. "TRANSINDIVIDUALITY AND POST-LABOR BASED ON SIMONDON AND STIEGLER". Kriterion: Revista de Filosofia 60, n.º 143 (agosto de 2019): 319–38. http://dx.doi.org/10.1590/0100-512x2019n14305jhk.
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ABSTRACT This article aims to elucidate a philosophical foundation of a post-labor paradigm through the transindividual technical-psychic-collective culture based on Gilbert Simondon and Bernard Stiegler. Simondon predicts that the problem of the alienation of labor due to mechanical industrialization can be overcome through the spread of post-industrial technical culture based on both technical mentality and information technology (IT). In contrast, Stiegler claims that, along with information networks, hyper-industrialization rather than post-industrialization has arrived and that, in order to recover human values in a machine empire devoid of caring, the strengthening of the ability for non-automation based on automaticity is necessary. However, Simondon’s technical culture beyond labor implies a posthumanistic vision in that it assumes the capacity of technology to mediate between the preindividual and the transindividual beyond technical instrumentalism, which is anthropocentric, and opens up transductive relationships among humans and non-humans. I will argue that Stiegler’s urgent proposal that seeks to save human life from the control of a techno-capital system, such as the reinvention of work transcending employment, must be concretized within the Simondonian posthumanistic project.
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Kostyunina, G. M. "North American Integration after 20 Years". MGIMO Review of International Relations, n.º 2(41) (28 de abril de 2015): 152–62. http://dx.doi.org/10.24833/2071-8160-2015-2-41-152-162.
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Formation of the North American Free Trade Area (NAFTA) among the three countries - the U.S., Canada and Mexico is the most striking example of successful development of integration processes in the Western Hemisphere. This year NAFTA marks the 20th anniversary of its foundation (1994). NAFTA covers trade in goods, services and movement of capital, intellectual property rights, environmental cooperation and labor cooperation. Its main advantages for member countries related to the dynamic growth of regional trade and investments, promoting the growth of industrial production (capital-intensive and high-tech industries in the U.S. and Canada, and labor-intensive industries in Mexico), increase the investment attractiveness of the economies of member countries and the promotion of employment. But there are costs, both general and specific to the individual member countries. Common costs are primarily asymmetrical level of economic interdependence, where mutual economic relations are the most developed between the U.S. and Canada, the U.S. and Mexico, and the least developed between Mexico and Canada due to historical conditions. Other costs are the differentiation in the levels of economic development, in volumes of overall GDP and per capita, population and size of the territory. But despite the costs, integration processes are successfully developed and repeatedly raised the issue of deepening economic integration between the U.S., Canada and Mexico. So, in 2000, there was put forward the concept of creating the North American community as an economic and security community by 2010, and in 2005 proposed the idea of a common currency called the Amero. But these proposals did not come true. On the agenda - the possibility of signing a new, more expanded NAFTA+, and even in the last year - the possibility to form a customs union under NAFTA.
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Ranjan, Nikhil. "Enhancing Voting Security and Efficiency". Journal of Computers, Mechanical and Management 2, n.º 3 (31 de agosto de 2023): 9–15. http://dx.doi.org/10.57159/gadl.jcmm.2.3.23065.
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This study explores developing and implementing a novel Electronic Voting Machine (EVM) system integrated with biometric identifiers to enhance voting security and efficiency significantly. Traditionally, voting processes relied on paper ballots, a system fraught with several challenges, including over-voting, the loss or misplacement of ballot papers, environmental harm due to paper consumption, and a lengthy result compilation process. An advanced EVM system is proposed to address these issues, leveraging unique biometric identifiers - facial recognition and fingerprints - for voter authentication and secure vote recording. Our EVM system effectively improves the security against bogus voting and vote repetition, which have been significant concerns in previous voting systems. This robust approach to voter authentication minimizes the likelihood of voting fraud, thus contributing to a more reliable and secure voting process. However, the transition to this advanced EVM system is challenging. The study identifies keyimplications, including the impact on employment due to automation, potential inaccuracies and biases associated with biometric technologies, and vital privacy concerns surrounding using sensitive biometric data. Despite these challenges, the proposed system provides a substantial foundation for future enhancements. Opportunities for further development include the integration of additional biometric identifiers like iris recognition, refining the accuracy of current biometric technologies, and strengthening data privacy measures.
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Poole, Janet L., Susan L. Murphy, Erin R. Foster, Alix G. Sleight, Toni Van Denend, Arash Asher, Kristine Carandang et al. "Fatigue as an Understudied Barrier to Participation in Life Roles". OTJR: Occupational Therapy Journal of Research 43, n.º 4 (24 de junho de 2023): 583–91. http://dx.doi.org/10.1177/15394492231180833.
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Fatigue is one of the most burdensome and disabling symptoms in numerous acute and chronic conditions and is associated with reduced participation in all aspects of daily life, for example, parenting, employment, and socialization. Historically, occupational practitioners played key roles in fatigue management by creating and implementing interventions. The American Occupational Therapy Foundation convened a Planning Grant Collective workshop with the goal to develop collaborative research ideas and proposals to advance the understanding and management of fatigue. Participants from occupational therapy and other disciplines, with expertise with fatigue or who were conducting research on fatigue, participated in a 3-day virtual workshop. Four main topics emerged: implementation science, treatment taxonomy, trial design and comparative effectiveness, and phenotyping. This white paper describes the proceedings, summarizes the discussions, and outlines recommendations from the PGC workshop on fatigue.
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Moore, Jay A., Andrew M. Evens, Justin Newberg, Eric A. Severson, Jennifer Mills, Jordan Carter, Rahul Matnani, Jo-Anne Vergilio, Sally E. Trabucco e Shridar Ganesan. "Genomic Ancestry in B Cell Lymphoid Malignancies". Blood 136, Supplement 1 (5 de novembro de 2020): 5–6. http://dx.doi.org/10.1182/blood-2020-137533.
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Introduction: B cell lymphoma/leukemias (BCL) are a diverse set of malignancies. The genomic landscape of many BCL subtypes have been described. However, genomic ancestry has rarely been investigated. We applied SNP-based genomic ancestry prediction to comprehensive genomic profiling (CGP) data to identify significant enrichment of ancestry by subtype. We also explored enrichment of genomic alterations (GAs) by ancestry. Methods: During routine clinical care, 2834 unique patient (pt) samples of BCLs underwent CGP for 406 DNA genes and 265 RNA genes to detect all classes of GAs on the FoundationOne® Heme platform. This dataset was enriched for relapsed/refractory pts as they are more likely to have genomic testing as part of clinical care (referral bias). Each pt was assigned an ancestry of American (AMR), African (AFR), East Asian (EAS), European (EUR), or South Asian (SAS) using a SNP-based machine learning methodology (J. Newberg et al., AACR 2019). AMR was defined using a mix of Hispanic and Latin American populations. Enrichment analyses were performed using Fisher's exact test with FDR correction. Results: We compared the ancestry composition of each BCL subtype to the overall ancestry composition of the rest of the sample set (Fig 1A). Pts of AFR ancestry were overrepresented in plasmablastic lymphoma (PBL) (OR=7.2, P<0.05); EAS pts were overrepresented in Burkitt lymphoma (BL) (OR=4.99, P<0.05); and AMR pts were overrepresented in acute B-cell lymphoblastic leukemia/lymphoma (B-ALL) (OR=3.2, P<0.001). AMR SNPs have been associated with increased risk of B-ALL and worse prognosis (PMID: 21297632). We also investigated GAs enriched in specific ancestries. B-ALL AMR pts were enriched for GAs in IL7R, IGH, CRLF2, JAK2, and IKZF1 compared to other ancestries in B-ALL (Fig 1B). These genes were associated with the high-risk Philadelphia chromosome-like ALL (Ph-like ALL) molecular subtype of B-ALL (PMID: 30181314). We found 33% of all B-ALL contained GAs consistent with Ph-like ALL (PMID: 30181314). While we noted enrichment of AMR pts in the overall B-ALL cohort, we identified additional enrichment in the Ph-like B-ALL cohort with 47% of Ph-like B-ALL pts being of AMR ancestry (OR=1.85, p<0.001). AMR pts accounted for almost half the Ph-ALL pts in this cohort; however, even in B-ALL pts without Ph-like genomic features, 32% were of AMR ancestry suggesting this enrichment is not simply due to increased CGP testing in Ph-ALL. In diffuse large B cell lymphoma (DLBCL), we found pts to be primarily of EUR ancestry, however we identified ancestry bias in GAs (Fig 1C). CD79B alterations were enriched in DLBCL pts of SAS ancestry, although not significant after FDR correction, consistent with previous reports of increased Activate B-Cell (ABC) cell of origin (COO) subtype and BTK signaling in pts from South East Asia (PMID: 31189540). CDKN2A, also frequently altered in ABC COO subtype, trended towards enrichment in EAS ancestry. CUX1, a tumor suppressor involved in PI3K signaling, was strongly enriched in AFR pts in both DLBCL and B-ALL. One CUX1 insertion variant (G870_G871insSGG) was particularly common in AFR pts with BCL (7/9 AFR, 2/9 AMR), which has been reported previously in Myelodysplastic syndromes (PMID: 24030381). CUX1 alterations have been reported to be associated with increased PI3K signaling suggesting in part PI3K inhibitor trials should proactively include pts of AFR ancestry (PMID: 24316979). Finally, EZH2 alterations were slightly enriched in AMR DLBCL pts, but showed no ancestry bias in follicular lymphoma (FL) pts, of interest given the recent EZH2 inhibitor approval in FL. Conclusions: This study described multiple important genomic differences in BCL using genomic ancestry rather than patient-reported descriptive variables. Enrichment of AMR ancestry was observed in B-ALL overall, and in Ph-like B-ALL. In addition, enrichment of CUX1 alterations was observed in both DLBCL and B-ALL of AFR ancestry. While precision medicine holds the promise to advance cancer care, many acknowledge the potential to unintentionally deepen existing health disparities (PMID: 31112478). Further analysis of ancestry informative markers in BCL, including enrichment of ancestry markers in specific cancer subtypes and ancestry-associated enrichment of specific GAs, may lead to insights into cancer biology and contribute to ongoing cancer health disparities research. Disclosures Moore: Foundation Medicine, Inc: Current Employment; Roche Holdings: Current equity holder in publicly-traded company. Evens:Abbvie: Consultancy, Honoraria; Mylteni: Consultancy, Honoraria; Research To Practice: Honoraria, Speakers Bureau; MorphoSys: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Newberg:Roche Holdings: Current equity holder in publicly-traded company; Foundation Medicine, Inc: Current Employment. Severson:Foundation Medicine, Inc: Current Employment; Roche Holdings: Current equity holder in publicly-traded company. Mills:Foundation Medicine, Inc: Current Employment; Abbvie: Current equity holder in publicly-traded company; Roche Holdings: Current equity holder in publicly-traded company; Abbott: Current equity holder in publicly-traded company; Merck: Current equity holder in publicly-traded company. Vergilio:Roche Holdings: Current equity holder in publicly-traded company; Foundation Medicine, Inc: Current Employment. Trabucco:F. Hoffmann-La Roche, Bristol-Myers Squibb Co., BioNTech: Current equity holder in publicly-traded company; Patent pending with Foundation Medicine and Genentech: Patents & Royalties: Patent pending; Foundation Medicine, Inc.: Current Employment; Bristol-Myers Squibb Co: Current equity holder in publicly-traded company; BioNTech: Current equity holder in publicly-traded company; Loxo Oncology: Divested equity in a private or publicly-traded company in the past 24 months. Ganesan:M2GEN: Research Funding; Foundation Medicine, Inc: Consultancy; Inspirata: Consultancy; Merck: Consultancy, Current Employment, Current equity holder in publicly-traded company; Silagene: Consultancy; Foghorn Therapeutics: Consultancy; Roche: Consultancy; Novartis: Consultancy.
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Santaella, Maria E., Michelle L. Witkop, Kevin Mills, Michael Recht, Donna DiMichele e Leonard A. Valentino. "National Hemophilia Foundation Enlists Diverse Patient Voices to Inform a National Research Blueprint for Inherited Bleeding Disorders". Blood 138, Supplement 1 (5 de novembro de 2021): 1904. http://dx.doi.org/10.1182/blood-2021-147857.
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Abstract Background: The inherited bleeding disorder (IBD) community has witnessed significant advances in care, yet important gaps persist, particularly in rare disorders and underserved populations. An initiative spearheaded by the National Hemophilia Foundation (NHF) and shaped by the patient community aims to accelerate progress through a national research blueprint. The blueprint is being designed to identify and guide research priorities toward those areas that most significantly impact the lives of individuals affected today and articulate clearly defined opportunities to make the greatest impact for the future. Methods: NHF has enlisted individuals with IBDs as subject matter experts (SMEs) to guide this initiative by elevating the most pressing issues affecting them today and informing expert discussions on actionable research priorities for the future. SME insights have been collected through listening sessions, a cross-community survey, and participation in multi-disciplinary working groups. The NHF State of the Science Research Summit (SOS) in September 2021 will address the input of the working groups and will also feature patient vignettes to illustrate today's unmet needs and contextualize the research priorities identified to address them. As part of this interactive Summit, SMEs from traditionally underrepresented patient populations are also being enlisted to participate in remote participation groups (RPGs) with the goal of soliciting input that further tailors the research priorities to the needs of these populations. The RPGs will be comprised of individuals with bleeding disorders or their caregivers who represent specific populations by race/ethnicity (for example, African Americans, Asian Americans, Indigenous persons, Mexican and Central American Hispanic individuals, etc.). Within each group, NHF will aim to include individuals with diverse experiences based on their IBD, barriers related to access to care, gender and sexual orientation. During each session, the moderated RPGs will participate in the live summit, discuss the expert dialogue, and share real-time perspectives and comments about how the content addresses, or not, their specific community needs. The expert SOS panel will then have the chance to address their comments. The commentary from these sessions will be included in the NHF blueprint to define the research path forward for the community. The RPGs are also expected to be reconvened in Spring 2022 to review and improve upon the opportunities identified in the blueprint. Results: NHF has enlisted broad and diverse community support to ensure the blueprint accurately represents the opportunities to create meaningful and lasting impact for individuals with IBDs. In total, 42 patients and caregivers participated in listening sessions; 125 contributed to the community survey; 15 are participating in the Summit working groups and approximately 200 are being enlisted for the remote participation groups. The themes to be addressed during the SOS reflect the input provided by the SMEs and health professionals (see Table 1). Conclusions: Actively soliciting the patient community's views is central in our process to advance research in IBDs. By enlisting the participation of historically underserved community segments, this effort aims to address some of the most persistent and pressing issues affecting the IBD community today. Specific insights from the RPG participation in the Summit will be included in the presentation. This blueprint, which will guide the U.S. research community, could help fundamentally redefine the experience of diverse populations living with these disorders. Figure 1 Figure 1. Disclosures Witkop: Teralmmune, Inc.: Consultancy. Recht: Octapharma: Consultancy; Novo Nordisk: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; uniQure: Consultancy; Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy. Valentino: Spark: Ended employment in the past 24 months.
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Blokhin, Konstantin V. "World Geopolitical Competition in the Context of the Fourth Industrial Revolution". RUDN Journal of Political Science 22, n.º 3 (15 de dezembro de 2020): 339–51. http://dx.doi.org/10.22363/2313-1438-2020-22-3-339-351.
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Article analyzes predictive estimates and concepts presented by the Western intellectual community, regarding prospects for development of new trends in the global economy, caused by the fourth industrial revolution. Author draws on a variety of sources, including reports from US think tanks, works by representatives of global financial and technocratic elite, and works by American intellectuals. Methodological basis of the study is a theory of the world system of I. Wallerstein, which allows to identify dynamic and conflicting lines of interaction between two geopolitical centers of the world - the United States and China. Based on an analysis of current trends, modern experts predict revolutionary changes in modern technologies that can decisively affect socio-political stability, not only in Western countries, but in developing countries as well. Author shows that the new technological structure is changing not only sector structure of the economy, but also has a strong impact on employment. According to American analysts, new technologies can destabilize socio-political stability in any country, especially in countries where cheap labor is a traditional tool. Robotization and automation of production can become a competitive advantage of the United States and Western countries in competition with China. Article notes that Russia is only at the very beginning of technological revolution, behind big five leading countries. Overcoming its lag in the field of AI and robotics requires adoption of comprehensive measures of economic, scientific and political nature. Ignoring realities of technological progress is fraught with increase in threats to national security.
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O’Hara, Anthony. "Institutional regimes, long wave systemic risk and great international crisis of 2008-2012". Panoeconomicus 59, n.º 1 (2012): 1–12. http://dx.doi.org/10.2298/pan1201001o.
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This paper studies the relationship between long-term growth of GDP per capita, institutional regimes of accumulation (ROA), systemic risk and the Great International Crisis of 2008-2010. The principle hypothesis behind the work is that the ROA provides a foundation for long-term growth as a type of fundamental variable, and that this growth provides a buffer against systemic risk in the sense that sustainable growth provides resources for debt provision and employment stimulation. The emergence of a viable ROA is crucial for long waves of growth which stimulate both private sector profit and public sector tax receipts which (using conventional terminology) reduce the structural deficit for both sectors. Low rates of long-term growth, therefore, provide a good indicator of the emergence of ?long wave systemic risk? (LWSR), which left such nations vulnerable to uncertainty, financial crisis and recession. The paper investigates the inability of growth for various decades to ?cover? instabilities associated with the Great Crisis, leading to high rates of LWSR, especially for European and North American nations that bore the brunt of the crisis.
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Chandler, Martin, Michael Recht, Chunla He, Thomas Moulton e Lena Charafi. "Real-World Effectiveness of Damoctocog Alfa Pegol in the Subgroup of Adolescent Hemophilia A Patients Aged 12-18 Years in the ATHNdataset". Blood 138, Supplement 1 (5 de novembro de 2021): 4241. http://dx.doi.org/10.1182/blood-2021-152345.
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Abstract Background: The ATHNdataset is a HIPAA-compliant, de-identified database, sponsored by the American Thrombosis and Hemostasis Network. Over 40,000 people with a bleeding or clotting disorder followed at United States hemophilia treatment centers (HTC) have submitted health information, including 15,747 hemophilia A patients. Aims: To evaluate the effectiveness of damoctocog alfa pegol (BAY 94-9027/Jivi®) to treat hemophilia A adolescent patients aged between 12-18 years in a real-world setting. Methods: The ATHNdataset was queried for people with hemophilia A aged ≥12 years of age treated with damoctocog alfa pegol. From this dataset adolescent patients aged between 12-18 years, treated either prophylactically or on-demand were identified. Collected data included baseline demographic data, treatment history, comorbidities and bleeding rates. The data were captured via patient chart review and entered into the database. The database was queried for patient data between January 1, 2010 and October 31, 2020. Results: At the data cutoff, 16 patients aged between 12-18 years were being treated with damoctocog alfa pegol. In this group, 13 patients (81%) had severe hemophilia A and 3 patients (19%) had mild/moderate disease. The majority of patients were male - 14/16 (87.5%) with 2/16 (12.5%) being female and the mean age of patients was 15.9 years old (median = 15.8). Of the total, 4 patients (25%) had a history of inhibitors. Patients had an average of 1.2 years of therapy with damoctocog alfa pegol and most (56%) had over 12 months of treatment. All the patients included in this analysis had documented bleeding rates in the ATHN system (Table 1). Mean total annualized bleed rate (ABR) was 0.05. Mean joint ABR and spontaneous ABR were zero. In the subgroup of patients who were on prophylaxis with damoctocog alfa pegol (n = 13), the mean total ABR, joint ABR and spontaneous ABR were zero. The proportion of patients with zero total bleeds during the entire observational period was 15/16 (94%) in the overall cohort and 13/13 (100%) in adolescent patients who were on prophylaxis. The majority of patients who were on prophylaxis 9/13 (69%) were treated twice-weekly with the mean weekly dose of 77.2 IU/kg/wk. Conclusions: The data from this analysis show that damoctocog alfa pegol provides protection from bleeding events in adolescent patients aged 12-18 years in the real-world setting. Mean ABR was low in this patient population, with 94% of patients experiencing zero bleeds. This data should be interpreted with caution due to limitations in real-world studies. Figure 1 Figure 1. Disclosures Recht: American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy. He: ATHN: Ended employment in the past 24 months. Moulton: Bayer: Current Employment. Charafi: Bayer: Current Employment.
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Borzova, Alla Yu, Olga V. Volosyuk e Nino D. Nikolashvili. "Spanish Humanitarian Policy in Latin America: Peculiarities and Priorities". Vestnik RUDN. International Relations 22, n.º 3 (15 de dezembro de 2022): 586–99. http://dx.doi.org/10.22363/2313-0660-2022-22-3-586-599.
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The article deals with the establishment and formation of the humanitarian policy of Spain, the evolution of the concept of “Hispanidad” in relation to Latin America, when Spain, along with the expansion of investment and economic cooperation, was building up educational, scientific, cultural interaction based on a common historical past, and intended positioning itself as a “bridge” between the EU and this region. The authors apply the theory of constructivism, based on the position that “historical and cultural paradigms,” norms and beliefs, and not only economic power influences the rapprochement of states. The chronological order makes possible to trace the evolution of the features and priorities of the country’s humanitarian policy, starting from the second half of the 2010s, when it was reduced to the dominance of the educational and scientific factor in Spanish public diplomacy towards Latin America. The Spanish state has achieved significant results in improving the system of higher education, making it attractive to foreign students. The activities of public and private structures (Ministry of Foreign Affairs, AECID, Carolina Foundation, Casa America) are focused not only at creating a positive image of Spain (the Program “Spain Global”), but also at forming a common Ibero-American scientific and educational space. In the Ibero-American Community of Nations (ICN), which unites countries on the basis of language and culture, an important place is given to youth problems related to the availability of quality education and employment, as well as issues of digitalization, economic modernization, renewable energy. Within the framework of the ICN, the Tordesillas Group, the Association of Ibero-American Universities, the La Rabida Group, etc., are intended to implement the 2021 Goals in the field of education. The use of professional research networks, the introduction of new skills and competencies for students and teachers, the creation of the Ibero-American Institute for Education and Productivity (IIEYP), focusing on the relationship between education and economic growth, became a real basis for strengthening a common Ibero-American educational and scientific space as a main priority in the actual humanitarian policy of Spain.
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Messenger, Heather, Chunla He, Michael Recht e Roshni Kulkarni. "A Cross-Sectional Study of the American Thrombosis and Hemostasis Network Dataset for Outcomes of Dental Extractions in People with Hemophilia". Blood 138, Supplement 1 (5 de novembro de 2021): 346. http://dx.doi.org/10.1182/blood-2021-148498.
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Abstract BACKGROUND: Dental extraction (DE) is one of the most common procedures in people with hemophilia A or hemophilia B (PWH-A, PWH-B), yet little is known about impact of the type of hemophilia, hemostatic therapies, and bleeding outcomes. To date, there is no standard protocol for how to treat PWH undergoing DE. Similar overall bleeding rates occur with pre- and postoperative factor replacement (FRP) therapy and single dose preoperative FRP (11.9% and 11.4%, respectively) (DE. Bajkin et al. Haemophilia 2020). METHODS: We analyzed the American Thrombosis and Hemostasis Network dataset (ATHNdataset) to assess trends in prophylactic factor use and its impact on bleeding outcomes following dental extraction in PWH-A and PWH-B ≥2 years of age. A DE bleeding episode was defined as any oral or mouth bleeding occurring during or within one week following a DE procedure. Treated bleeds were defined as any oral or mouth bleeds treated with hemostatic medications during or within one week post-DE. Hospitalization and emergency department (ED) visit events were defined as any that occurred during or one day after a DE. Data on sociodemographic, clinical characteristics, and outcomes were collected prospectively between 2013 and 2019 at annual clinical visits to 134 ATHN-affiliated sites. Categorical variables were summarized using frequency and percentage. Logistic regression was used to evaluate associations between DE and sociodemographic and clinical variables. Simple logistic regression models were applied to identify factors potentially associated with dental bleeding episodes among PWH. RESULTS: Sociodemographic and clinical characteristics revealed that of the 19,048 PWH in the ATHNdataset, 1,157 subjects underwent 1,301 episodes of DE; a majority (74.9%) were diagnosed hemophilia A and 94.4% were male. The odds of a DE were approximately 148% higher among male PWH compared to female PWH (OR: 2.48; 95%CI: 1.93-3.20). PWH with severe disease were less likely to undertake DE than those with mild hemophilia (OR: 0.83; 95%CI: 0.72-0.95). Compared to PWH-B, PWH-A tended to have DEs at a younger age (<30 years). The chance of a DE did not differ by race, hemophilia type, and currently having or having a history of inhibitor. No significant associations were found between dental extraction, education or employment among PWH ages >18 years. Dental extraction clinical outcomes and related treatments indicated approximately 34% of PWH used prophylaxis versus on-demand therapy (18%) 292for dental/mouth bleeding. Approximately 5% of PWH who underwent DE reported oral/mouth bleeds within one week of the procedure. Of those bleeding episodes, 28.0% of hemophilia A patients and 12.5% of hemophilia B patients reported two or more oral/mouth bleeds during, and one-week post-DE. Rates of hospitalizations and ED visits were 7.4% and 1.3% respectively for PWH-A and 8.8% and 0.9% respectively for PWH-B. Among oral/mouth bleeds related to dental extraction, 34.0% and 50.0% patients with hemophilia A and B respectively received hemostatic therapies such as DDAVP, factor concentrates, or antifibrinolytics. Factors associated with DE bleeding were as follows: Dental extractions performed with prophylactic regimen were found to experience insignificantly fewer dental bleeding episodes (P>0.05). Similarly, no statistically significant difference in bleeding rate after DE was found in those using extended half-life factor (EHL) compared to standard half-life products (SHL). Prophylaxis was more prevalent among PWH-A compared to PWH-B (37.3% vs. 25.2% respectively). SHL products were more commonly used than EHL products for on-demand therapy (8.3% vs. 0.5% respectively) as well as prophylaxis (19.8% vs. 8.1%). PWH who have ever developed an inhibitor significantly increased the odds of dental bleeding (OR:2.09, 95%CI: 1.21-3.63). However, no significant relationship was found between inhibitor and DE bleedings among PWH who have been exposed to emicizumab (P=0.168). DISCUSSION: This is the largest study of DE outcomes in PWH. DE tends to be performed more in those with mild hemophilia and at an earlier age. The use of hemostatic therapies and factor prophylaxis is associated with insignificantly less bleeding. The ATHNdataset allowed studies of outcomes in a large cohort of PWH. This project was part of the ATHN CARE Award. Disclosures He: ATHN: Ended employment in the past 24 months. Recht: Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment. Kulkarni: Bayer: Consultancy, Research Funding; CSL Behring: Consultancy; Genentech/Roche: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Catalyst Bioscience: Research Funding; Foundation for Women and Girls with Blood Disorders: Membership on an entity's Board of Directors or advisory committees.
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Wu, Yongyi. "An Analysis of the Attitudes and Behaviors of American Society towards Segregation after the Abolition of Slavery". Lecture Notes in Education Psychology and Public Media 4, n.º 1 (17 de maio de 2023): 574–78. http://dx.doi.org/10.54254/2753-7048/4/2022216.
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African Americans are often associated with weakness in the United States. They not only have a difficult life, but they also face discrimination and hatred as a result of their insecure employment. But, in reality, African Americans have faced a lot of pushback and struggle since the end of the nineteenth century, and they continue to do so to this day. Since the promulgation and implementation of the National Declaration of Human Rights, more than 170 states have launched varying degrees of anti-black movements: the United States Constitution states that all citizens have equal civil rights, and the federal government shall not deprive citizens of their liberties in any way. This paper focuses on the reasons for American societys perspective on this problem, as well as the related conduct throughout the segregation period. From a social standpoint, a complete and in-depth investigation and study of African Americans can assist in improving understanding, raise consciousness, and promote societal harmony and growth. This study investigates a wide range of American societys perspectives and behaviors on the topic of black segregation through a literature review and collects relevant materials to create a theoretical foundation for this paper. According to the findings of the study, under the segregation period, the majority of white people were treated unfairly because of the concept of white supremacy, while the majority of African Americans who opposed apartheid were for the same rights. At the same time, the minorities were white students and members of racial organizations who opposed it because they advocated equality. There are relevant pieces of literature about other groups and persons of other races other than African Americans who opposed the unequal treatment of African Americans throughout the segregation period. This component may be the subject of future investigation.
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Dos Santos, Marcos Leonardo Ferreira, e Isabel Lausanne Fontgalland. "Analysis of the Polluter-Pays Principle in the Itapessoca River Estuary, Goiana – Pernambuco". Revista de Gestão Social e Ambiental 17, n.º 1 (8 de fevereiro de 2023): e03175. http://dx.doi.org/10.24857/rgsa.v17n1-022.
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Brazil has the largest mangrove areas in the American continent, constituting an important economic resource used by coastal populations in the tropics due to its great diversity, carbon richness and functionality.
Objective: To present the critical areas of mangroves and the degradation of the geo-economic mosaic.
Theoretical framework: the Pigou-Coase principle was focused in order to understand the restoration structure in mangrove areas, through the polluter-pays principle, focusing on the mangrove conditions in the estuary of the Itapessoca river, Goiana-PE, Brazil, which suffers a high process of environmental decharacterization.
Method: Case study based on the reference of R. Yin, with the employment of bibliometrics’ tools (WoS) and mapping mosaic using QGis and SIRGAS software.
Results and Conclusions: In the Itapessoca region it can be observed that there is no rigor of use of risk or preserved area, since the principles are the foundation of the rules the legislation is not comprehensive, and there is presence of predatory treatment.
Research Impact: Case studies constitute an important type of research as it anchors what is most impactful to local reality vis a vis theoretical platform.
Originality: The PPP model applied to the mangrove of Itapessoca-Pernambuco-Brazil.
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Witkop, Michelle L., Michael Recht, Donna DiMichele, Kevin Mills, Leonard A. Valentino e Maria E. Santaella. "National Hemophilia Foundation Convenes Diverse Community Voices to Define an Actionable National Research Blueprint for Inherited Bleeding Disorders". Blood 138, Supplement 1 (5 de novembro de 2021): 4952. http://dx.doi.org/10.1182/blood-2021-149518.
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Abstract Background: An ambitious initiative underway in the inherited bleeding disorder (IBD) community aims to create a national research blueprint that can help accelerate research progress and address important gaps in care, particularly within rare disorders and underserved populations. Led by the National Hemophilia Foundation (NHF), the effort is defined by input from across the community, including research leaders, patient subject matter experts (SMEs), caregivers, allied health professionals and specialists, and industry. Two foundational principles of the blueprint are that a) it must deliver on key issues that most significantly impact the lives of those affected by an IBD, and b) the priorities defined are relevant and actionable in order to provoke real and lasting changes in the care paradigm. Methods: To ensure the blueprint accurately reflects the most pressing needs from across the community, NHF has enlisted the support of diverse segments of the population throughout the process. Listening: NHF coordinated a comprehensive, community-wide listening exercise, including focus groups, virtual listening sessions, and consumer and professional surveys, to collect insights that have shaped and guided the blueprint development. Engagement: Representatives from across the IBD community have been enlisted to participate in the development process through enrollment in one of six interdisciplinary working groups (WGs), each focusing on broad themes raised during the listening exercises. (Table 1) In total, 164 individuals are participating in the WGs, including chapter representatives, allied healthcare providers, researchers, federal partners and other IBD organizations. Each WG also features experts outside the IBD community who can introduce innovations from other fields. Finally, each WG includes the participation of subject matter experts (SMEs), individuals affected by bleeding disorders who provide personal perspectives on the value and potential impact of the proposed research priorities. NHF is actively supporting these groups with regular engagement, guidance, and recommendations while encouraging robust dialogue to distill critical priority research areas. To ensure the blueprint is well defined and actionable, NHF has devised a rigorous development and refinement process. Feasibility Assessment: Together with expert advisers, NHF has defined a set of feasibility criteria to help the WGs address potential opportunities based on three key areas: (see Figures 1 and 2) Feasibility assesses the difficulty in answering the proposed question, including required expertise, infrastructure, and resources.Impact estimates the change we can foster through the priority.And risk considers the challenges of the research question, such as the risk/benefit ratio for novel strategies and any ethical considerations. Each research priority or model is scored based on these areas, and the combined evaluation will determine how they are included and prioritized in the blueprint. Summit: Upon completion of the WG assessments, NHF will bring the community together for a State of the Science (SOS) Research Summit, September 12-15, 2021, during which each WG will summarize their recommendations for live, interactive discussion. During each session, panels will discuss the recommendations and collect feedback from community participants, as well as from remote participation groups comprised of representatives from underserved segments of the population. Results: The discussions from the working groups and Research Summit will be consolidated into a series of manuscripts and published as a community-driven national research blueprint in mid-2022. The voices of individuals affected by IBDs have been the central driver in this process, from the listening activities and WGs to the planned SOS, and the community will continue to champion the efforts defined in the blueprint. Conclusions: This initiative represents an opportunity to catalyze impactful change in the treatment of IBDs. To ensure its success, NHF has methodically enlisted broad community involvement and driven a rigorous prioritization process in order to identify specific and actionable topics that will help guide research plans for the IBD community. Our hope is that this blueprint will help shepherd advances in care that could fundamentally redefine the experience of living with these disorders. Figure 1 Figure 1. Disclosures Witkop: Teralmmune, Inc.: Consultancy. Recht: Sanofi: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Genentech: Consultancy; Hema Biologics: Consultancy; CSL Behring: Consultancy; Takeda: Consultancy; uniQure: Consultancy; Catalyst Biosciences: Consultancy; Pfizer: Consultancy; Kedrion: Consultancy. Valentino: Spark: Ended employment in the past 24 months.
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Forsberg Jr., Clyde. "Esotericism and the “Coded Word” in Mormonism". International Journal for the Study of New Religions 2, n.º 1 (14 de agosto de 2011): 29–54. http://dx.doi.org/10.1558/ijsnr.v2i1.29.
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In the history of American popular religion, the Latter-day Saints, or Mormons, have undergone a series of paradigmatic shifts in order to join the Christian mainstream, abandoning such controversial core doctrines and institutions as polygamy and the political kingdom of God. Mormon historians have played an important role in this metamorphosis, employing a version (if not perversion) of the Church-Sect Dichotomy to change the past in order to control the future, arguing, in effect, that founder Joseph Smith Jr’s erstwhile magical beliefs and practices gave way to a more “mature” and bible-based self-understanding which is then said to best describe the religion that he founded in 1830. However, an “esoteric approach” as Faivre and Hanegraaff understand the term has much to offer the study of Mormonism as an old, new religion and the basis for a more even methodological playing field and new interpretation of Mormonism as equally magical (Masonic) and biblical (Evangelical) despite appearances. This article will focus on early Mormonism’s fascination with and employment of ciphers, or “the coded word,” essential to such foundation texts as the Book of Mormon and “Book of Abraham,” as well as the somewhat contradictory, albeit colonial understanding of African character and destiny in these two hermetic works of divine inspiration and social commentary in the Latter-day Saint canonical tradition.
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Rendo, Pablo, Mary-Kate Barrette-Grischow, Lynne Smith, JM Korth-Bradley, Robert Charnigo e Frank E. Shafer. "Evaluation of Two Secondary Prophylaxis Regimens of Recombinant Factor IX(r-IX) in Moderately Severe to Severe( FIX ≤2%) Hemophilia B Patients". Blood 120, n.º 21 (16 de novembro de 2012): 4628. http://dx.doi.org/10.1182/blood.v120.21.4628.4628.
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Abstract Abstract 4628 Background: Hemophilia B is an X-linked coagulation disorder characterized by a deficiency in factor IX (FIX), which results in spontaneous or trauma-induced bleeding primarily in joints, muscles, and soft tissues. Prevention and treatment of bleeding episodes in patients with hemophilia B is based upon replacing deficient FIX, either prophylactically or on an on-demand basis, with plasma-derived or recombinant FIX products. Prophylaxis therapy (ie, long-term, regular treatment) with FIX products is endorsed by the World Health Organization, World Federation of Hemophilia, and National Hemophilia Foundation as a primary therapeutic option for individuals with severe hemophilia B. Still, the use of prophylaxis is underutilized, as shown in data from North American and European hemophilia centers, where only 21% to 55% of individuals with hemophilia B were identified as receiving prophylactic FIX therapy (Rocca A et al. Blood Transfus 2011;9:60; Aznar JA et al. Haemophilia 2011;17:542; Biss TT et al. Haemophilia 2008;14:923). Factors implicated for this phenomenon include difficulty in venous access (particularly with primary prophylaxis in children), as well as overall adherence and willingness to commit to a highly demanding treatment schedule (Valentino LA. Haemophilia 2004;10:147; Collins PW et al. Haemophilia 2011;17:2; Santagostino E. Haemophilia 2010;16:13). The potential benefits of utilizing a once-weekly prophylactic regimen versus a more frequent dosing regimen include increased convenience for patients and their caregivers owing to fewer infusions and less preparation and infusion time, and the preservation of venous access. Objective: This study aimed to compare the safety and efficacy results for 2 prophylaxis regimens of nonacog alfa in moderately severe and severe hemophilia B patients. Methods: This multicenter, open-label crossover study enrolled 50 patients with moderately severe or severe (FIX C ≤ 2%) hemophilia B. Patients were treated on demand for 16 weeks, and 47 were subsequently randomized to 1 of 2 prophylactic regimens (nonacog alfa 100 IU/kg once weekly or 50 IU/kg biweekly) for 16 weeks. Following the initial prophylactic regimen, patients underwent an 8-week washout period of on-demand (OD) therapy then were crossed over to receive the other prophylactic regimen. The primary end point was the annualized number of bleeding episodes, expressed as the annualized bleeding rate (ABR). The results of this study were previously reported (Valentino LA, et al, 2011 ISTH abstract 1293). Results: Comparisons between once-weekly and twice-weekly prophylaxis regimens are given in Tables 1 and 2 and in Figure. No thrombosis, inhibitor, or allergic reactions were reported. Survival curve analysis comparing 100 IU once weekly to 50 IU twice weekly using the Kaplan-Meier technique showed no significant difference in the timing or extent of either type of treatment failure (p=0.14 for joint, p=0.61 for soft tissue/muscle by the Chi-squared [log-rank] analysis). Conclusions: Once-weekly prophylaxis with nonacog alfa 100 IU/kg is a safe and effective alternative to twice-weekly prophylaxis at 50 IU/kg. Once-weekly dosing may present a reasonable option for patients with severe hemophilia B, offering more convenience to patients and their caregivers compared with more frequent prophylactic dosing regimens. Disclosures: Rendo: Pfizer Inc.: Employment. Barrette-Grischow:Pfizer Inc.: Employment. Smith:Pfizer Inc.: Employment. Korth-Bradley:Pfizer Inc.: Employment. Charnigo:Pfizer Inc.: Employment. Shafer:Pfizer Inc.: Employment.
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Price, Mark, Arliene Ravelo, Elisa Weiss, Peggy Ann Torney, Victor Gonzalez, Maria Sae-Hau, Carol Mansfield et al. "What Are Patients' Preferences and Satisfaction Regarding Modes of Administration for the Treatment of Chronic Lymphocytic Leukemia (CLL), Diffuse Large B-Cell Lymphoma (DLBCL), and Follicular Lymphoma (FL)?" Blood 132, Supplement 1 (29 de novembro de 2018): 5897. http://dx.doi.org/10.1182/blood-2018-99-115327.
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Abstract OBJECTIVES: In recent years, there has been an increase in the number of treatments with different administration modes for patients with CLL, DLBCL, and FL, providing patients with options that were previously unavailable. However, there is a dearth of quantitative evidence for how patients make decisions when choosing treatments and on patients' opinions regarding the burden of disease, treatment, and satisfaction with processes involved in treatment. We developed a survey to understand patient experiences, preferences, and factors that contribute to decision making. This study aims to quantify patient-reported information via standard survey items with categorical Likert options that measure aspects of satisfaction with patients' most recent treatment. Additionally, patient preferences for various modes of treatment administration will be measured through direct assessment. METHODS: To design the survey, a rigorous approach consisting of consultation with medical experts, patient advocacy organizations, and research team members was undertaken. Additionally, concept elicitation and cognitive pretesting with patients yielded important attributes to measure, including satisfaction with and preference for various aspects of treatment, treatment schedule and burden, travel time, work productivity and caregiver impact. A particular focus was given to the impact of disease and treatment on health-related quality of life. Specific topics in this category included impact on energy levels, sleep, concentration, emotional health, personal relationships, anxiety and uncertainty, and optimism about future health status. RESULTS: The draft survey questionnaire was developed and pretested in semistructured interviews with patients (n = 14). Four patients with CLL, 5 patients with DLBCL, and 6 patients with FL were interviewed. Eight patients were male and 6 were female, and mean patient age was 59 (range: 33-74). Interview results suggested that patients experience a significant time burden related to the treatment of their disease. All survey items (including those addressing preferences for treatments based on duration and level of satisfaction with various time and resource dependent treatment characteristics) were refined during the interviews. The final survey is currently being administered online to patients who are associated with The Leukemia & Lymphoma Society and The Lymphoma Research Foundation. We anticipate surveying 500 patients, with results ready for the 2018 American Society of Hematology Annual Meeting. CONCLUSIONS: Evaluations of patient satisfaction, preferences, and priorities are increasingly important as patients are enabled to take more active roles in decision-making for their treatment pathways. Our present study will yield necessary data on important treatment attributes among patients with CLL, DLBCL, and FL. A large-scale evaluation of patient satisfaction and preferences can be used for education of the clinical and broader medical community in a landscape that includes several new therapies. Disclosures Price: Genentech: Consultancy. Ravelo:Genentech: Employment. Weiss:Genentech: Research Funding. Torney:Genentech: Research Funding. Gonzalez:Genentech: Research Funding. Sae-Hau:Genentech: Research Funding. Mansfield:Takeda Pharmaceuticals International Co: Consultancy; Genentech: Consultancy. Comenencia-Ortiz:Genentech: Employment. Cunanan:Genentech: Consultancy. Masaquel:Roche: Equity Ownership; Genentech: Employment, Equity Ownership. Dawson:Genentech: Employment.
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Berthon, Charles. "eu-alc Cooperation Efforts to Achieve Millennium Development Goal 3: “Promote Gender Equality and Empower Women”". InterNaciones, n.º 14 (2 de maio de 2018): 39–57. http://dx.doi.org/10.32870/in.v0i14.7078.
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Gender inequality as well as violence against women is a major problem in Latin America and the Caribbean. It is manifested in issues such as gender violence, lower political participation by women, employment and wage inequality, female illiteracy and the difficulty women have gaining access to full sexual and reproductive health. The Latin American continent has achieved progress towards gender equality and women’s empowerment under the Millennium Development Goals, including equal access to primary education between girls and boys. However women and girls continue to suffer high rates of discrimination and violence in most Latin American countries.In this specific region of the world, mentalities of both civil and political actors of the society, need to fully process the fact that gender equality is not only a fundamental human right, but a necessary foundation for a peaceful, prosperous and sustainable society. Women’s economic empowerment is defined as a transformational process, in which women gain increased access to and power over economic assets and economic decisions. Through programs like Eurosocial and alfa III financed by the European Commission, the European Union has been seeking to increase its cooperation with Latin America in this domain. Some projects like Equality, carried out within the framework of these programs, directly or indirectly aimed at providing women and girls with equal access to education, health care, decent work, and representation in political and economic decision-making processes.Achieving these goals would certainly contribute to develop more sustainable economies and benefit societies and the population on its whole, as it partially did already. Nevertheless it has been made clear over the years, with a low financial aid dedicated to the problem, that this aspect of the cooperation was not the very first priority of the European Union in Latin America. As for today, 17 years after setting the millennium goals, one thing is sure: there is yet a lot to be done to promote gender equality and women empowerment in Latin America.
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Kucukal, Erdem, Aaron Wolfe, Ryan Kocevar, Lalitha V. Nayak, Samuel Sowemimo-Coker, John Zak, Laurel Omert e Umut A. Gurkan. "Hypoxic Storage of Red Blood Cells: Assessment of Adhesion Properties Using a Standardized Endothelium-on-a-Chip Microfluidic Platform". Blood 138, Supplement 1 (5 de novembro de 2021): 1072. http://dx.doi.org/10.1182/blood-2021-151270.
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Abstract Background: Blood transfusions are routine medical procedures in which stored blood or blood products (i.e., red blood cells, RBCs) are given to the patient to prevent adverse health outcomes due to acute or chronic anemia. The current regulations require RBCs to be stored at 4 ºC not more than 42 days before a transfusion. However, RBCs undergo extensive rheological changes during storage and may contribute to complications associated with transfusion. Hemanext has recently introduced an innovative storage system to ameliorate such storage lesions, in which RBCs are stored in a hypoxic environment, and thus they are exposed to much lower oxidative stress during storage. In this study, we report the changes in adhesion properties of stored RBCs to human endothelial cells following a 42-day storage in normoxia vs hypoxia, using a standardized endothelialized microfluidic platform: Endothelium-on-a-chip. Methods: Two units of 1-day old blood type O positive leukocyte reduced RBCs in additive solution were pooled and divided into equal aliquots (300mL each) A and B. Unit A was stored under conventional normoxic storage condition at 4°C for 42 days. Unit B was deoxygenated so that the percent oxygen saturation of the hemoglobin was less than 20%. The deoxygenated RBCs were stored in an oxygen impermeable storage bag for 42 days at 4°C. Adhesion levels were tested at the beginning (baseline, Week 1) and the end of the storage period (Week 6). To conduct the adhesion experiments, human umbilical vein endothelial cells (HUVECs) were first cultured within microfluidic channels under flow for at least 48 hours. Next, the HUVECs were treated with 40 µM heme for 4 hours at 37 ºC [1]. RBCs were centrifuged to remove the storage buffer and resuspended in basal cell culture medium (EGM, Lonza, Morristown, USA) supplemented with 10 mM HEPES at a hematocrit of 40%. A 15 µl of RBC solution was then injected over heme-activated HUVECs at a shear stress of 1 dyne/cm 2 followed by a 10-minute rinse with fresh basal culture medium to remove non-adherent RBCs. At the end of the experiment, adherent erythrocytes were manually quantified. Control experiments were conducted with non-activated HUVECs. Results: We found that RBCs that were stored under conventional normoxic condition displayed higher adhesion to heme-activated HUVECs than hypoxic condition as illustrated in Figure 1A and 1B. The baseline adhesion levels (Week 1) to non-activated HUVECs (control) were negligible (Fig. 1C, normoxia: 13±6; hypoxia: 18±10, p>0.05) while both cell populations had considerable adhesion levels to heme-activated HUVECs at baseline (Fig. 1C, normoxia: 372±59; hypoxia: 335±37). Following a 6-week storage, adhesion of RBCs stored in normoxia to heme-activated HUVECs was higher compared to those stored in hypoxic conditions while the p-value was not significant, which was likely due to the limited sample size (Fig. 1C, 1782±519 vs 594±55, p=0.08, N=3). These results suggest that storage-mediated RBC adhesion to heme-activated HUVECs may be ameliorated by the novel hypoxic-storage condition. Discussion: This study showed a decrease in the adhesion of hypoxic RBCs to heme-activated HUVECs when compared to conventionally stored RBCs for transfusion. This result suggests that hypoxic RBCs may reduce the risk of developing vaso-occlusion (VOC) after RBC transfusion in patients such as in sickle cell disease where adhesion to heme-activated HUVECs has been implicated in the pathogenesis of VOC [1]. Acknowledgements: This work was funded by Hemanext. The authors would like to thank the Ohio Third Frontier Technology Validation and Start-up Fund (TVSF) and National Science Foundation Phase-I Small Business Technology Transfer (STTR) award, which supported this work in part. Stored RBCs were donated by Hemanext. Reference: 1. Kucukal, E., et al., American Journal of Hematology, 2018. 93(8): p.1050-1060 Figure 1 Figure 1. Disclosures Kucukal: BioChip Labs: Current Employment, Patents & Royalties. Kocevar: BioChip Labs: Current Employment. Nayak: BioChip Labs: Current Employment. Sowemimo-Coker: Hemanext: Current Employment. Zak: BioChip Labs: Current Employment, Current holder of stock options in a privately-held company; XaTek: Current Employment, Current holder of stock options in a privately-held company; TecTraum Inc: Current Employment, Current holder of stock options in a privately-held company. Omert: Hemanext: Current Employment. Gurkan: Biochip Labs: Patents & Royalties; Hemex Health, Inc.: Current Employment, Patents & Royalties; Dx Now Inc.: Patents & Royalties; Xatek Inc.: Patents & Royalties.
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Bertsch, Thomas, Wilhelm Behringer, Sabine Blaschke, Richard Body, Simon Davidson, Anna Rieger, Daniel Horner et al. "Diagnostic Accuracy of the Tina-Quant D-Dimer Gen.2 Assay with Age-Adjusted Cut-Off Ranges for Evaluation of Patients with Suspected Deep Vein Thrombosis or Pulmonary Embolism". Blood 136, Supplement 1 (5 de novembro de 2020): 14–15. http://dx.doi.org/10.1182/blood-2020-139235.
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Introduction: Fibrin degradation products, D-Dimer and X-oligomers, are biomarkers for activation of coagulation. D-Dimer testing is recommended as an additional diagnostic tool for proximal deep vein thrombosis (DVT) and pulmonary embolism (PE), in conjunction with clinical presentation and pre-test probability (Lim, et al. Blood Adv. 2018). D-Dimer levels naturally increase in patients over the age of 50 years, which reduces the specificity of D-Dimer levels as a diagnostic aid for proximal DVT and PE in older patients. We conducted a study to assess the diagnostic accuracy of the Tina-quant® D-Dimer Gen.2 (D-DI2; Roche Diagnostics) assay in patients with a low or intermediate pretest probability for proximal DVT or PE (Bertsch, et al. ISTH 2020; abstract PB0600). An exploratory objective of the study was to evaluate the diagnostic accuracy of the D-DI2 assay in the total study population after applying an age-adjusted cut-off value for patients aged >50 years. Methods: This prospective, observational, multi-center study was conducted between July 2017 and August 2019. Samples were collected at six European hospitals or specialist referral centers, or purchased from a commercial vendor (BioPartners Inc.). The 3.2% citrated plasma samples were analyzed at a central site using the D-DI2 assay on the cobas t 711 analyzer (Roche Diagnostics). Eligible patients were aged ≥18 years, presenting with symptoms suggestive of proximal DVT and/or PE, and with a low or intermediate pretest probability of DVT or PE by Wells score. Main exclusion criteria included DVT and/or PE symptoms for >7 days or a previous diagnosis of DVT and/or PE. DVT and/or PE were diagnosed according to local imaging protocols and standard-of-care procedures, in line with current clinical guidelines. Patients were followed-up for ≥90 days after hospital discharge to verify the clinical diagnosis and record any adverse events. In the primary analysis, a D-DI2 assay cut-off value of 0.5 μg fibrinogen equivalent units (FEU)/mL was applied across all patients, regardless of age. For the purpose of this exploratory analysis, age-adjusted cut-off values were calculated by multiplying age by 0.01 μg FEU/mL for patients aged >50 years. Results: In total, 2516 patients were included in the analysis (1741 DVT cohort; 775 PE cohort); of these, 1538 patients were aged >50 years (996 DVT cohort; 542 PE cohort) and the D-DI2 assay cut-off values for these patients were age-adjusted accordingly. The parameters for diagnostic accuracy for both the DVT and PE cohorts, unadjusted and age-adjusted values, are provided in the Table. Both negative predictive value (NPV) and sensitivity remained high after adjustment for age across both cohorts; however, there were slight decreases compared with the unadjusted values. Positive predictive value (PPV) was increased in both cohorts after age adjustment when compared with the unadjusted values. A reduction in false positives were reported for both the DVT (27%) and PE (26%) cohorts when adjusted for age compared with the unadjusted values. After age-adjustment, the number of false negatives in the total study population increased slightly in the DVT cohort (from zero to one case) and in the PE cohort (from one to five cases). Overall, specificity was increased when the results were adjusted for age. Conclusions: In our study population, when used in conjunction with a low or intermediate pretest probability for DVT and/or PE according to Wells criteria, the D-DI2 assay identifies patients at very low risk for proximal DVT and PE. Adjustment of the cut-off value for age resulted in a slight decrease in NPV, though still below the diagnostic threshold. The benefit of a reduction in false positives observed after age adjustment has the potential to prevent further unnecessary diagnostic procedures for patients. Disclosures Bertsch: Nuremberg General Hospital/Paracelsus Medical University: Current Employment. Blaschke:BMBF: Research Funding; Innovationsfonds: Research Funding; DGINA: Membership on an entity's Board of Directors or advisory committees. Body:University of Manchester: Current Employment; Beckman Coulter: Consultancy; LumiraDx: Consultancy; Roche Diagnostics: Consultancy; Siemens Healthineers: Consultancy; Abbott Point of Care: Consultancy; Abbott Point of Care: Research Funding; Roche Diagnostics: Research Funding; American Association of Clinical Chemistry (sponsored session from Roche, Abbott, ET Healthcare, Ortho, Siemens, Beckman): Speakers Bureau; LumiraDx advisory committee: Membership on an entity's Board of Directors or advisory committees; Creavo (chair of Trial Steering Committee): Membership on an entity's Board of Directors or advisory committees. Davidson:Roche Diagnostics International: Current Employment. Rieger:Roche Diagnostics GmbH: Current Employment. Horner:Salford Royal NHS Foundation Trust: Current Employment. Sonner:Roche Diagnostics GmbH: Consultancy; TRIGA-S Scientific Solutions: Current Employment. Sun:Roche Diagnostics GmbH: Current Employment. Turnes:ICON Clinical Research UK Ltd: Current Employment. Hoffman:Roche Diagnostics GmbH, Germany: Current Employment.
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Lin, Yi, Thomas Martin, Adam D. Cohen, Andrzej Jakubowiak, Jagoda Jasielec, Saad Z. Usmani, Deepu Madduri et al. "Cytokine Release Syndrome in Patients with Relapsed/Refractory Multiple Myeloma Treated with Ciltacabtagene Autoleucel in the Phase 1b/2 CARTITUDE-1 Study". Blood 136, Supplement 1 (5 de novembro de 2020): 45–46. http://dx.doi.org/10.1182/blood-2020-136360.
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Background: The phase 1b/2 CARTITUDE-1 study (NCT03548207) is evaluating ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells), a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed/refractory (R/R) multiple myeloma (MM). Cytokine release syndrome (CRS), a known side effect of CAR-T therapy, can be mild to life-threatening and requires careful monitoring and management. Here, we analyzed CRS and cytokine profiles in CARTITUDE-1. Methods: Eligible patients (aged ≥18 years) had a diagnosis of MM per International Myeloma Working Group criteria, measurable disease, Eastern Cooperative Oncology Group performance status ≤1, received ≥3 prior regimens or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and received an anti-CD38 antibody. Bridging therapy was permitted after apheresis. At 5-7 days prior to cilta-cel infusion, lymphodepletion was performed with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 days. Cilta-cel was administered as a single infusion at a target dose of 0.75×106 (range: 0.5-1.0×106) CAR+ viable T cells/kg. CRS was graded using Lee et al (Blood 2014) in the phase 1b portion and American Society for Transplantation and Cellular Therapy (ASTCT) in the phase 2 portion. In this combined analysis, Lee et al criteria were mapped to ASTCT criteria for patients in the phase 1b portion. Serum samples for cytokine profiling were collected prior to lymphodepletion, prior to cilta-cel infusion and 2 hours post-infusion on Day 1, at regular time points until Day 100, and if CRS was suspected or reported. Results: A total of 97 patients with R/R MM were treated with cilta-cel; median follow-up for this analysis was 8.8 months (range: 1.5-20.4). CRS was reported in 92 (94.8%) patients. A total of 48 (49.5%) patients had grade 1 CRS, 38 (39.2%) had grade 2, 4 (4.1%) had grade 3, and 1 had grade 5 (1.0%); maximum toxicity grade according to the ASTCT consensus grading system could not be derived for 1 patient with CRS in the phase 1b portion. Median time to CRS onset from cilta-cel infusion was 7.0 days (range: 1-12). Median duration of CRS was 4.0 days (range: 1-27, excluding n=1 with 97 days). Supportive measures to treat CRS or CRS symptoms were administered to 87 (89.7%) patients, most commonly tocilizumab (69.1%), acetaminophen (68.0%), corticosteroids (20.6%), and anakinra (18.6%). CRS resolved in 91 (98.9%) patients; the patient with grade 5 CRS/hemophagocytic lymphohistiocytosis died on Day 99 subsequent to sequelae of grade 4 CRS. Across all patients, levels of interleukin (IL)-6, IL-10, and interferon-γ peaked at Days 7-14 post-cilta-cel infusion. Conclusions: CRS after cilta-cel treatment was low grade and manageable in most patients with R/R MM. The low rate of grade ≥3 CRS, median time to CRS onset of 7.0 days, and median duration of 4.0 days suggests outpatient dosing of cilta-cel may be feasible; this approach is being explored in the phase 2 CARTITUDE-2 study (NCT04133636). Disclosures Lin: Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company: Consultancy, Research Funding; Vineti: Consultancy; Takeda: Research Funding; Merck: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding. Martin:Janssen: Research Funding; AMGEN: Research Funding; Sanofi: Research Funding; Seattle Genetics: Research Funding; GSK: Consultancy. Cohen:Novartis: Other: Patents/Intellectual property licensed, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees. Jakubowiak:AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive, Juno: Consultancy, Honoraria. Usmani:Celgene: Other; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Research Funding; GSK: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Array Biopharma: Research Funding; Merck: Consultancy, Research Funding; Abbvie: Consultancy; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Incyte: Research Funding. Madduri:AbbVie: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Foundation Medicine: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau. Stewart:Janssen, BMS, Sanofi-Aventis, GSK: Honoraria; Tempus, Inc., Genomics England LLC: Membership on an entity's Board of Directors or advisory committees. Singh:Janssen: Current Employment. Zudaire:Janssen: Current Employment. Yeh:Janssen: Current Employment. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Geng:Legend Biotech USA Inc.: Current Employment. Wu:Legend Biotech USA Inc.: Current Employment. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Wang:Legend Biotech USA Inc.: Current Employment. Berdeja:CRISPR Therapeutics: Consultancy, Research Funding; EMD Sorono: Research Funding; Teva: Research Funding; Servier: Consultancy; Vivolux: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Karyopharm: Consultancy; Kesios: Research Funding; Kite Pharma: Consultancy; Legend: Consultancy; Genentech, Inc.: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Cellularity: Research Funding; Constellation: Research Funding; Glenmark: Research Funding; CURIS: Research Funding; Bioclinica: Consultancy; Amgen: Consultancy, Research Funding; Bluebird: Research Funding; Poseida: Research Funding; Acetylon: Research Funding; Prothena: Consultancy; Lilly: Research Funding. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy.
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Trompetter, Linda, Arthur Breese, James Calderone, Grace S. Fisher, Rodrigo Gereda, Mari King, Richard Kramer et al. "Focus Group Study of Diverse Local Populations and Their Health Care Experiences in Northeastern Pennsylvania". Californian Journal of Health Promotion 3, n.º 3 (1 de setembro de 2005): 73–126. http://dx.doi.org/10.32398/cjhp.v3i3.650.
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This investigation was conducted through the support of the College Misericordia Diversity Institute and a grant from the Blue Ribbon Foundation of Blue Cross of Northeastern Pennsylvania. Focus group participants were 49 adults from seven minority populations residing in northeastern Pennsylvania’s Luzerne and Lackawanna counties. Data was collected by 11 focus group leaders who were members of a Blue Ribbon Grant Core Committee at College Misericordia in 2004. The seven populations studied were African Americans, Arabic Muslims, Asian-Chinese and Korean, Gay and Lesbian, Hispanic, Jewish, and Asian Indian. A 30-question survey was used to collect data during one to two hour focus group interviews. Through content analysis, six problematic issues faced by many of the participants were identified. All of the findings were validated by a review process. The six issues faced by the 7 groups were: 1) Economics, Education, and Employment Influence Life for Newcomers, 2) Customs and Traditions Sometimes Sacrificed- The Influence of American Culture, 3) Socialization Often Limited to Same Population Group, 4) Mixed Acceptance Level from Area Natives, 5) Bilingual Challenges Impede Optimal Inclusion, 6) Health Care Access Problems. The aforementioned cross-groups study is explored in this report. The study also yielded seven other reports (one for each diverse population) which provide a description of that particular focus group’s perspective on topics such as religion, food, family, customs, and health care (see Appendices A, B, C, D, E, F, and G). Findings of this study are being disseminated in a local effort to educate health care professionals. Future research will be needed to determine if progress is being made in fulfilling the health care needs of all diverse populations living in Luzerne and Lackawanna County, as well as other parts of northeastern Pennsylvania.
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Manco-Johnson, Marilyn, Hans-Joerg Hertfelder, Theodosia A. Kalfa, Emmett H. Broxson, Lisa Bomgaars, Amy D. Shapiro, Dyck-Jones Jacqueline et al. "Treatment of Patients with Severe Congenital Protein C Deficiency in a Registry Study of Protein C Concentrate (Human)". Blood 128, n.º 22 (2 de dezembro de 2016): 2605. http://dx.doi.org/10.1182/blood.v128.22.2605.2605.
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Abstract The objective of this non-interventional, international registry was to collect and assess safety and outcomes of all treatment with protein C concentrate for patients with protein C deficiency in Europe and the United States. Here we report the results from 25 patients with severe congenital protein C deficiency (SCPCD). Any patient who received treatment with protein C concentrate was eligible for the study; there were no exclusion criteria. There were no predefined visits, laboratory tests and/or procedures, or interventions at enrollment or during the study. Management of patients was at the discretion of the investigator. Clinical data collected during the treatment course of these patients are reported here. Twenty-five patients with congenital protein C deficiency from 10 US study sites and 10 study sites in the EU were enrolled into the study. The median age at study entry was 11.12 years (range: 1.3- 43.7 years). No patient was <1 month old, 2 (8.0%) patients were 1 month to <2 years old, 12 (48.0%) patients were 2 to <12 years old, 3 (12%) patients were 12 to <18 and 8 (32%) patients were ≥18 years old. The median duration of study participation was 39.7 months (range: 0.9 to 59.9 months). Thirteen (52%) patients were male and 12 (48%) were female. The initial clinical presentation that led to the diagnosis of SCPCD occurred prior to enrollment into the study (years in some cases). The initial presentations included primarily thromboembolic events (18 [52.9%]) or purpura fulminans (16 [47.1%]). During the study there were 259 treatment regimens with protein C concentrate, including 113 (43.6%) for acute episodes, 29 (11.2%) for short term replacement for surgical procedures, and 117 (45.2%) for long term prophylaxis. There were large variations in protein C treatments prescribed. The most common dose and frequency in patients treated for acute episodes was 60 IU/kg administered once a day. Protein C concentrate was administered at enrollment either intravenously or subcutaneously (SQ). During the study, 217/259 (83.8%) treatment regimens of protein C concentrate were administered intravenously and 42 (16.2%) were administered SQ. Nine patients received SQ infusions prophylactically and three of these 9 patients also used SQ infusions for treatment of an acute episode. Of 25 acute episodes in 7 patients treated with protein C concentrate, 22 (88.0%) resulted in recovery, 2 (8.0%) showed improvement and 1 (4.0%) was unchanged; there was no instance of worsening of an acute episode. Protein C concentrate was effective in prevention of coagulopathy and thrombosis in 23 (100%) short-term replacement treatments for surgery/invasive procedures performed in 13 patients with SCPCD. The median protein C activity level increased from 2.5% (range: 0.0 to 40.0%) at diagnosis (unaugmented) to 41.0% (range: 1.0% to 264.0%) following protein C concentrate infusion. One patient (4.0%) with congenital heart disease died of congestive heart failure, assessed as not related to protein C concentrate. Of 111 AEs in 22 patients, 83 AEs in 17 patients occurred during treatment with protein C concentrate. Of these 83 AEs, only 3 were considered related to protein C concentrate: a single patient had 2 SAEs (abdominal pain and pain in extremity) and 1 nonserious AE (purpura fulminans) that were considered by the investigator to be possibly related to administration of protein C concentrate. The results of this registry provide additional evidence for the use of protein C concentrate as an effective and safe short-term replacement therapy for surgery/invasive procedures and for acute episodes in patients with congenital protein C deficiency. No new safety concerns were identified. Disclosures Manco-Johnson: Bayer: Honoraria, Research Funding; Baxter/Baxalta/Shire: Honoraria; Biogen: Honoraria; NovoNordisk: Honoraria; CSL Behring: Honoraria. Hertfelder:Bayer Healthcare: Consultancy, Honoraria, Other: Support of Congress, Educational and Scientific Meeting Participations; Baxter/Baxalta/Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of Congress Participation; Pfizer: Consultancy, Honoraria, Other: Support of Congress, Educational and Scientific Meeting Participations; Daiichi-Sankyo Germany: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of Congress Participations; NovoNordisc: Other: Support of Congress Participations; Sanofi Aventis: Honoraria, Other: Educational meeting Participations, Speakers Bureau; Octapharma Germany: Other: Support of Congress Participations. Kalfa:Baxter/Baxalta/Shire: Research Funding. Bomgaars:Boeringer Ingleheim: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Membership on DSMB. Shapiro:National Hemophilia Foundation: Membership on an entity's Board of Directors or advisory committees; OPKO: Other: Clinical research protocols; Octopharma: Other: Clinical research protocols; PTC Therapeutics: Other: Clinical research protocols; Bayer healthcare Pharmaceuticals: Other: International network on pediatric hemophilia; Baxter/Baxalta/Shire: Membership on an entity's Board of Directors or advisory committees, Other: Clinical research protocols; Genentech: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Other: Clinical research protocols; Daiichi Sankyo: Other: Clinical research protocols; Biogen: Membership on an entity's Board of Directors or advisory committees, Other: Clinical research protocols; Novo Nordisk Hemophilia Foundation: Membership on an entity's Board of Directors or advisory committees; Kedrion Biopharma: Consultancy; ProMetic Life Sciences: Consultancy; American Thrombosis and Hemostasis Network: Other: Medical Director; Selexys: Other: Clinical research protocols; Novartis: Other: Clinical research protocols; CSL Behring: Other: Clinical research protocols. Jacqueline:Baxalta US Inc., now part of Shire: Employment, Equity Ownership. Ehrle:Baxter/Baxalta/Shire: Employment, Equity Ownership. Finnerty:Baxalta/Baxter: Employment. Gelmont:Baxter/Baxalta/Shire: Employment, Equity Ownership. Yel:Baxter/Baxalta/Shire: Employment, Equity Ownership. Loghman-Adham:Baxter/Baxalta/Shire: Employment, Equity Ownership.
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Popiński, Krzysztof. "Wroclaw Electronic Works: Wrocławskie Zakłady Elektroniczne „Elwro” 1959–2000". Studia Historiae Oeconomicae 39, n.º 1 (1 de dezembro de 2021): 125–44. http://dx.doi.org/10.2478/sho-2021-0005.
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Abstract Based on the research potential of the Wrocław higher education center and its achievements in mathematics and automation, Wrocławskie Zakłady Elektroniczne “Elwro” was launched in the capital of Lower Silesia, in the late 1950s. Starting with the production of relatively simple electrotechnical devices, the company transformed in just a few years into a manufacturer of digital machines of its own design, “Odra”. They have found wide application in science, administration, communication and industry − both in Poland and abroad, mainly in the Comecon member states. The 1970s were the period of the peak development of WZE “Elwro”, in which apart from devices of its own design, computers belonging to the so-called Uniform System of Digital Electronic Machines of Comecon countries, were also being produced. The effects of the economic crisis of the 1980s abruptly reduced the orders for computers produced in “Elwro”, and their development and production was slowed down by problems with obtaining materials that were scarce in the country and foreign currency for foreign purchases. The technological distance between the “Elwro” offer and the equipment manufactured in the leading countries of the West was growing. After the start of the system transformation in the country, the management of “Elwro” attempted to carry out radical organizational transformations and grant the company the status of a joint-stock company. However, they were held back for too long by both the lack of government support and the concerns of the works council. Meanwhile, deteriorating economic results forced the management of “Elwro” to reduce employment and sell more and more assets. Ultimately, in 1993, the plants were transformed into a sole-shareholder company of the State Treasury, and then sold to the German concern “Siemens”. For the new owner, the only thing that mattered was the access to the Polish telecommunications market obtained in this way. He did not use the still existing human resources and production potential of “Elwro” and, shortly after the purchase, practically liquidated the company. In 2000, its remains were sold to the American telecommunications company “Teletec Holding”, which changed the name of the company to “Teletec Polska” S.A.
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Kucukal, Erdem, Aaron Wolfe, Ryan Kocevar, Lalitha V. Nayak, Andreas Bruederle, John Zak e Umut A. Gurkan. "Assessment of the Effect of Crizanlizumab on Red Blood Cell Adhesion to Endothelial Cells Using a Standardized Endothelium-on-a-Chip Microfluidic Platform". Blood 138, Supplement 1 (5 de novembro de 2021): 2021. http://dx.doi.org/10.1182/blood-2021-151695.
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Abstract Background: Chronic upregulation of P-selectin (P-sel) on blood cells and the endothelium leads to abnormal red blood cell (RBC) adhesion to endothelial cells, significantly contributing to vaso-occlusive crises (VOCs), which are a major cause of morbidity and mortality in patients with sickle cell disease (SCD). Crizanlizumab (criz, a.k.a. SEG101) is a humanized anti-P-sel monoclonal antibody and has recently been approved by the Food and Drug Administration to reduce the frequency of VOCs in SCD patients. Here, we report in vitro assessment of the effect of criz on patient-specific RBC adhesion to heme-activated human endothelial cells using a standardized endothelialized microfluidic platform, the Endothelium-on-a-chip. Methods: Whole blood samples were collected from 13 subjects with SCD (13 HbSS and 1 HbSC) in EDTA vacutainers. RBCs were isolated via centrifugation from whole blood and then resuspended in basal cell culture medium (EBM, Lonza, Morristown, USA) at a hematocrit of 20% buffered with 10 mM of HEPES. Human umbilical vein endothelial cells (HUVECs) were obtained from Lonza and cultured within the microfluidic channels at 15 dyne/cm 2 for at least 48 hours prior to experiments. For long-term activation, HUVECs were treated with 40 µM heme for 4 hours +/- 100 µg/ml criz for 1 hour followed by injection of blood samples through the microfluidic channels. For short-term activation, blood samples were supplemented with 40 µM heme +/- 100 µg/ml criz and injected through the microfluidic channels for 15 minutes. Thereafter, non-adherent RBCs were rinsed via either only heme-containing EGM or heme- and criz-containing EGM, and the remaining RBCs were quantified based on published methods [1]. Student's t-test was used to calculate statistical significance. Results: We found that 4-hour heme activation of HUVECs resulted in significantly elevated RBC adhesion compared to baseline although adhesion levels were heterogenous among the patient population (Fig. 1A, 1671±522 vs 17±4, p<0.05). Treatment of 4-hour heme-activated HUVECs with criz did not significantly decrease RBC adhesion (Fig. 1A, 1170±413 vs 1671±522, p>0.05), while we observed lower RBC adhesion to criz treated HUVECs for certain subjects (Fig. 1B). By contrast, criz treatment significantly reduced the number of adherent RBCs to 15-min heme-activated HUVECs (Fig. 1C, 135±40 vs 1513±617, p<0.05). Next, we assessed whether criz would disrupt already established adhesive interactions between RBCs and 15-min heme-activated HUVECs. To do so, we first allowed RBCs to adhere to heme-activated HUVECs (for 15-min) and then rinsed the microchannels (at 10 μl/min) via either a heme- or both heme- and criz-containing solution (for 15 min). We then quantified the number of adherent RBCs at min=0 and min=15. While only 10% of the adherent RBCs remained in the microchannels following a 15-minute wash with criz, this ratio was 60% without criz (Fig. 1E). Discussion: Our results show that the magnitude of inhibition of RBC adhesion to HUVECs with criz correlated with the duration of heme-activation (4 hours vs 15 minutes). This is likely due to variable levels of different adhesion molecules on acute or chronically activated HUVECs. For instance, it has been shown that P-selectin is rapidly translocated to the cell surface following heme activation [1], but its concentration on cell surface significantly decays with time. Previous experiments have shown that sickle RBCs can adhere to cell adhesion molecules such as ICAM-1 [2], which mechanistically may play a role in the case of a chronically activated endothelium. We are currently exploring whether criz would also reduce RBC adhesion to acutely activated endothelial cells that are under chronic stress. These preliminary results suggest that the Endothelium-on-a-chip, as partner in novel therapeutic studies, could help monitoring dynamics of targeted therapies in SCD patients during drug development and in clinical trials. Acknowledgements: This work was funded by Novartis. The authors would like to thank the Ohio Third Frontier Technology Validation and Start-up Fund (TVSF) and National Science Foundation Phase-I Small Business Technology Transfer (STTR) award, which supported this work in part. Crizanlizumab was donated by Novartis. References: 1. Kucukal, E., et al., American Journal of Hematology, 2018. 93(8): p.1050-60 2. Kucukal, E., et al., Blood Advances, 2020. 4(15):3688-98 Figure 1 Figure 1. Disclosures Kucukal: BioChip Labs: Current Employment, Patents & Royalties. Kocevar: BioChip Labs: Current Employment. Nayak: BioChip Labs: Current Employment. Bruederle: Novartis Pharma AG: Current Employment. Zak: XaTek: Current Employment, Current holder of stock options in a privately-held company; BioChip Labs: Current Employment, Current holder of stock options in a privately-held company; TecTraum Inc: Current Employment, Current holder of stock options in a privately-held company. Gurkan: Dx Now Inc.: Patents & Royalties; Hemex Health, Inc.: Current Employment, Patents & Royalties; Biochip Labs: Patents & Royalties; Xatek Inc.: Patents & Royalties.
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Demmer, Irina, Susanne Huschens, Dietrich Potthoff, Jörg Tomeczkowski, Christian Englisch, Pushpike Thilakarathne, Joris Diels, Shaji K. Kumar, Brian GM Durie e Lewin Eisele. "Indirect Comparison Using Individual Patient Level Data Comparing Efficacy and Safety of a Daratumumab Monotherapy Vs. EU Approved Comparator Therapies in Patients with Multiple Myeloma". Blood 132, Supplement 1 (29 de novembro de 2018): 3541. http://dx.doi.org/10.1182/blood-2018-99-116884.
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Abstract Introduction. Efficacy and safety of daratumumab monotherapy (DARA mono) in relapsed/refractory multiple myeloma (rrMM) has been shown in the single-arm phase I/II trial GEN501 and the single-arm phase II trial SIRIUS (1, 2). Since then, several indirect treatment comparisons of DARA mono versus comparator therapies have been published showing consistent results with an overall survival benefit for DARA mono (3, 4, 5, 6). This analysis compares efficacy and for the first time also safety of DARA mono data versus an international historic control group, adjusting for differences in patient populations based on individual patient level data (IPD). Methods. IPD from the SIRIUS trial and from the International Myeloma Foundation (IMF)-cohort (7), a retrospective, multicenter cohort, were compared using a multivariate Cox proportional hazards model, on the endpoints of efficacy (overall survival (OS)) and safety (discontinuation due to adverse events (DISCONAE)). The IMF-cohort included patients with rrMM who received at least three prior lines of therapy, were refractory to both an immunomodulator (IMiD) and a proteasome inhibitor (PI), and were exposed to an alkylating agent. An inclusion criterion for the historic control group in this analysis was treatment with EU approved regimens. Baseline covariates adjusted for in the regression model included age, gender, prior lines of therapy, albumin, beta-2 microglobulin, prior exposure to pomalidomide and carfilzomib, and PI/IMiD refractory status. Several sensitivity analyses were run, including multiple imputation of missing values. Results. Data from 106 patients treated with DARA mono (16 mg/kg) were available from SIRIUS; 258 patients from the IMF chart review fulfilled the inclusion criteria; most frequent treatment regimens contained pomalidomide plus dexamethasone (PomDex) (n=172), bortezomib (n=31), carfilzomib (n=21), cyclophosphamide (n=14) and lenalidomide (n=9). The adjusted HR for OS was 0.41 [0.25, 0.69], p<0.001, and 0.23 [0.05, 1.00], p=0.050 for DISCONAE, in favor of daratumumab. Results were consistent across a range of sensitivity analyses and were similar when restricting the comparison to DARA vs. PomDex, with HR=0.35 [0.19, 0.64], p<0.001 for OS and 0.20 [0.03, 1.54], p=0.123 for DISCONAE. Conclusions. This comparison using real-world data of rrMM patients suggests improved efficacy and safety for DARA mono compared to approved therapy regimens used in clinical practice, including PomDex. References. Lokhorst, H. M., Plesner, T., Laubach, J. P., Nahi, H., Gimsing, P., Hansson, M., et al. Targeting CD38 With Daratumumab Monotherapy in Multiple Myeloma. The New England Journal of Medicine. 2015. Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, et al. Daratumumab Monotherapy in Patients with Treatment-Refractory Multiple Myeloma (SIRIUS): An Open-Label, Randomised, Phase 2 Trial. The Lancet. 2016. Usmani S, Ahmadi T, Ng Y, Lam A, Desai A, Potluri R, Mehra M. Analysis of Real-World Data on Overall Survival in Multiple Myeloma Patients With ≥3 Prior Lines of Therapy Including a Proteasome Inhibitor (PI) and an Immunomodulatory Drug (IMiD), or Double Refractory to a PI and an IMiD. The Oncologist. 2016. Van Sanden S, Ito T, Diels J, Vogel M, Belch A, Oriol A. Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison. The Oncologist. 2017. Usmani SZ, Diels J, Ito T, Mehra M, Khan I, Lam A. Daratumumab monotherapy compared with real-world historical control data in heavily pretreated patients with highly refractory multiple myeloma: An adjusted treatment comparison. American Journal of Heamtology. 2017. Jelínek T, Maisnar V, Pour L, Špička I, Minařík J, Gregora E, et al. Adjusted comparison of daratumumab monotherapy versus real-world historical control data from the Czech Republic in heavily pretreated and highly refractory multiple myeloma patients. Current Medical Research an Opinion. 2017. Kumar SK, Dimopoulos MA, Kastritis E, Terpos E, Nahi H, Goldschmidt H, et al. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia. 2017. Disclosures Demmer: Janssen: Employment. Huschens:Janssen: Employment. Potthoff:Janssen: Employment. Tomeczkowski:Janssen: Employment. Englisch:Janssen: Employment. Thilakarathne:Janssen: Employment. Diels:Janssen: Employment. Kumar:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Durie:Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Janssen: Consultancy. Eisele:Janssen: Employment.
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Manojlovic, Zarko, Austin Christofferson, Christophe Legendre, Gill Spreyer, Seungchan Kim, Winnie Liang, George Mulligan et al. "In-Depth Molecular Profiling of Multiple Myeloma in African Americans". Blood 126, n.º 23 (3 de dezembro de 2015): 2973. http://dx.doi.org/10.1182/blood.v126.23.2973.2973.
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Abstract Introduction: Multiple Myeloma (MM) is a complex malignancy of plasma cells well-described hyperdyploidy, and immunoglobulin gene rearrangements. To promote rapid advances in the field, Multiple Myeloma Research Foundation (MMRF) initiative is an intensive and comprehensive longitudinal study (CoMMpass) designed to create a rich discovery ecosystem to through in-depth clinical and molecular profiling to understand the molecular perturbations of the disease in the context of therapy. The large study population empowered us to stratify mutational landscapes among different ethnicities to influence on broader disparities in tumor dynamics. Methods: Clinical data, tumor/normal sample collection, and mutational landscape analysis described in this abstract are derived from MMRF CoMMpass IA7 release that is composed of self-identified 93 African American (AA) and 377 European American (EA). The post-processing and primary analysis was done on baseline samples only. Whole exome sequencing was analyzed for the detection of somatic events. Secondary analysis was performed using MutSigCV (Mutation Significance) algorithm and GISTIC (The Genomic Identification of Significant Targets in Cancer) to determine the significance of coding mutations and copy number events. Results: Our preliminary comparison analysis of CoMMpass IA7 data demonstrated that overall there was no statistical difference (p=0.5973) in nonsilent mutation burden between the two stratified groups, AA (μ=63.9 mutations/patient) vs EA (μ=73.7 mutations/patient). However, we have observed several notable differences. The most notable population difference (p<0.0001) was TP53 mutation occurrence, which was more common in EA 5.6% (21/377) compared AA 2.1% (2/93). Furthermore, MutSig analysis also revealed a novel candidate PTCHD3 (p = 7.07E-06, q = 3.33E-02) with 6% occurrence in AA compared to only 0.04% in EA. Furthermore, we looked at mutation occurrence difference of at least 5 fold between the two stratified populations. We have identified several additional genes that have higher mutation frequencies in tumors from AA patients including: ANKRD26, BCL7A, BRWD3. Interestingly, majority is implicated in epigenetic regulatory mechanisms. Moreover, despite the complex karyotype in MM translocations, our analysis demonstrated a lower frequency of 14q32 translocations in tumors from AA patients (10%) compared to tumors from EA patients (37%). These data would independently validate our previously reported differences in 14q32 breakpoints between these two populations. Conclusion: Data from this comprehensive diverse multi-institutional longitudinal study has afforded us the opportunity to study population differences among MM patients in an unprecedented way. Taking advantage of high quality, high-resolution whole exome and whole-genome data has allowed us to identify potential differences in the genomic and molecular landscape of MM from AA and EA patients. These data may help us further understand the incidence and outcomes among patients from these populations. As CoMMpass continues to mature these datasets will be retested that may result in some of these preliminary reported events to either level off, or increase in power. Disclosures Mulligan: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Lonial:Janssen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Onyx: Consultancy, Research Funding. Keats:Translational Genomic Research Institute: Employment.
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Kastein, Benjamin. "People Make the Difference". Rubber Chemistry and Technology 63, n.º 5 (1 de novembro de 1990): 81–95. http://dx.doi.org/10.5254/1.3538291.
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Abstract The Las Vegas meeting of the Rubber Division, ACS, provided attendees the opportunity to hear the interview of Mr. Arnold H. Smith, by Mr. Herbert A. Endres, recorded April 7, 1966. Mr. Smith, as Secretary-Treasurer of the Division from 1919 to 1928, and as Chairman in 1929, was the person most responsible for laying the foundation which supported the growth of the Division to its present status. The India Rubber Section was sanctioned by the American Chemical Society on December 30, 1909. The 28 chemists from the rubber industry who were the organizing members, had the objective of meeting together to solve mutual problems. The major problem for everyone in 1909 was the variable quality of the 36 varieties of wild rubber from the jungles of Central and South America and Africa. Para rubber from the Hevea Brasiliensis tree was considered to be the best type available, but there were at least 13 variations, identified by source of the Para rubber. Charles C. Goodrich, as first chairman of the India Rubber Section, moved immediately to resolve the problem and appointed a committee, chaired by Dr. Charles Knight of Buchtel College, to develop standard methods of testing and evaluation. The committee diligently addressed the subject and reported to the Section at each meeting for 10 years, but progress was slow. Members attending had been instructed by their superiors, “Listen—but don't talk!” Not a very satisfactory format for conducting a meeting. Several key individuals helping to organize the India Rubber Section were W. C. Geer, Chief Chemist at the B. F. Goodrich Co. and George Oenslager, of the Diamond Rubber Co. Geer invented the air oven used to accelerate heat aging of rubber samples, and Oenslager is famous for discovering the effect on vulcanization of organic accelerators in 1906 and for the use of carbon blacks in treads in 1911. Although the sharing of technical information was tantalizing slow during the early years, the American Chemical Society, at their meeting in Buffalo, April 7, 1919, approved the formation of the Division of Rubber Chemistry. John B. Tuttle, first chairman of the Division in 1919, with Arnold H. Smith as secretary-treasurer, determined to bring to the members technical information less restricted in content, and from their neutral position of employment at the National Bureau of Standards, thought results could be obtained.
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Malec, Lynn M., Nikki Hirsh, Carrie O'Neill, Crystal Watson e Michael Recht. "ATHN Transcends: A Natural History Cohort Study of the Safety, Effectiveness and Practice of Treatment in People with Non-Neoplastic Hematologic Disorders". Blood 138, Supplement 1 (5 de novembro de 2021): 4242. http://dx.doi.org/10.1182/blood-2021-148209.
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Abstract Background: Clinical researchers affiliated with the American Thrombosis and Hemostasis Network (ATHN) conduct multi-institutional, observational cohort studies assessing the safety and effectiveness of various interventions for people affected by bleeding and clotting disorders. In parallel with the growth of ATHN's clinical studies, the number of new therapies for all congenital and acquired hematologic conditions, not just those for bleeding and clotting disorders, is increasing. Some of the recently FDA-approved therapies for congenital and acquired hematologic conditions have yet to demonstrate long-term safety and effectiveness. In addition, results from well-controlled, pivotal studies often cannot be replicated once a therapy has been approved for general use. With this explosion of potential new therapies on the horizon, it is imperative that clinicians and clinical researchers in the field of non-neoplastic hematology have a uniform, secure, unbiased, and enduring method to collect long-term safety and efficacy data. The overarching objective of ATHN Transcends (NCT04398628) is to characterize the safety, effectiveness, and practice of treatments for all people with congenital and acquired hematologic disorders in the United States. Study Design and Methods: ATHN Transcends is a longitudinal, natural history, observational cohort study being conducted at approximately 150 ATHN-affiliated sites (ATHN Affiliate Network). Participants will be followed for a minimum of 15 years. Specific data will be collected for participants enrolled in cohort-specific arms. Each participant will be assigned in a single cohort: Hemophilia, Von Willebrand Disease, Congenital Platelet Disorder, Rare Bleeding Disorders, Bleeding Not Otherwise Specified, Thrombosis/Thrombophilia, or Non-Neoplastic Hematologic Conditions (see Figure 1). Inclusion criteria include: any age, any congenital or acquired non-neoplastic hematologic disorder, having a bleeding phenotype with an unknown diagnosis, or having a connective tissue disorder with a bleeding tendency. Exclusion criteria include not qualifying for a cohort and the unwillingness or inability to give informed consent or assent. Data will be collected at baseline, every three months, annually and at study exit (Figure 2). Participant biologic samples will be collected at enrollment and yearly thereafter. Safety endpoints mirror those collected by the European Haemophilia Safety Surveillance and include allergic and other acute events, treatment-emergent side effects of therapy, transfusion-transmitted infections, inhibitor development, thrombosis and cardiovascular events, malignancies, neurologic events, and deaths. Adverse events of special interest including thrombotic microangiopathies, anti-drug antibodies, unanticipated bleeding, and hospitalizations will be collected. A panel of patient-reported outcomes (Table 1) will be collected at baseline and annually. Descriptive statistics will be calculated to analyze the primary and secondary outcomes. If there are questions involving multiple cohorts, given there is adequate power to make comparisons between cohorts, for a discrete outcome, we will report estimated difference in percentage between cohorts as well as the 95% confidence interval (CI) of such a difference. If the outcome measurement is a continuous variable, we will report the mean difference and its associated 95% CI. Discussion: The key advantages of an independent study conducted by the ATHN Affiliate Network include the ability to observe participants on a variety of treatment regimens regardless of regimen dosing, frequency, or time of initiation; the ability to observe participants on recently FDA-approved therapies as well as continued monitoring of well-established therapies; the ability to enrich the ATHNdataset; and the ability to be the initial cohort study involving potentially all ATHN-affiliated sites to provide the infrastructure for all congenital and acquired hematologic disorders-related sub-studies in cooperation with other funders, including federal, foundation, academic and industry sources. ATHN Transcends received central institutional review board approval in April 2020. The protocol is currently being rolled out throughout the ATHN Affiliate Network. Figure 1 Figure 1. Disclosures Malec: HEMA Biologics: Consultancy; Genentech: Consultancy; Sanofi: Consultancy, Research Funding; Pfizer: Consultancy; CSL Behring: Consultancy; Takeda: Consultancy. Recht: uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy; Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment.
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Madduri, Deepu, Jesus G. Berdeja, Saad Z. Usmani, Andrzej Jakubowiak, Mounzer Agha, Adam D. Cohen, A. Keith Stewart et al. "CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel, a B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy, in Relapsed/Refractory Multiple Myeloma". Blood 136, Supplement 1 (5 de novembro de 2020): 22–25. http://dx.doi.org/10.1182/blood-2020-136307.
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Background: Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells) is a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity. In the phase 1 LEGEND-2 study in China, LCAR-B38M yielded deep, durable responses with a manageable safety profile in patients (pts) with relapsed/refractory multiple myeloma (R/R MM). The phase 1b/2 CARTITUDE-1 study (NCT03548207) is further evaluating cilta-cel in this pt population in the US. We present updated data from the phase 1b portion along with initial phase 2 data. Methods: Eligible pts (aged ≥18 y) were diagnosed with MM per International Myeloma Working Group (IMWG) criteria and had measurable disease, Eastern Cooperative Oncology Group performance status ≤1, received ≥3 prior regimens or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and received an anti-CD38 antibody. After apheresis, bridging therapy was permitted. Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 d were used for lymphodepletion. A single infusion of cilta-cel at a target dose of 0.75×106 (range 0.5-1.0×106) CAR+ viable T cells/kg was administered 5-7 d after start of lymphodepletion. The primary objective of the phase 1b portion was to characterize cilta-cel safety and establish the recommended phase 2 dose; the primary objective of the phase 2 portion was to evaluate cilta-cel efficacy. Response was assessed per IMWG criteria and minimal residual disease (MRD) by next-generation sequencing. Adverse events (AEs) were graded using CTCAE v5.0. In the phase 1b portion, cytokine release syndrome (CRS) was graded by Lee et al (Blood 2014) and neurotoxicity by CTCAE v5.0; in the phase 2 portion, CRS and neurotoxicity were graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria. In this combined analysis, Lee et al and CTCAE v5.0 were mapped to ASTCT criteria for CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), respectively. Results: As of the May 20, 2020 clinical cutoff, 97 pts (58.8% male; median age 61.0 y [range 43-78]) with R/R MM received cilta-cel (29 in phase 1b; 68 in phase 2). Median follow-up duration was 8.8 mo (range 1.5-20.4). Pts had received a median of 6 prior lines of therapy (range 3-18); 83.5% were penta-exposed, 87.6% were triple-refractory, 41.2% were penta-refractory, and 97.9% were refractory to last line of therapy. Overall response rate per independent review committee (primary endpoint) was 94.8% (95% CI 88.4-98.3), with a stringent complete response rate of 55.7% (95% CI 45.2-65.8), very good partial response rate of 32.0% (95% CI 22.9-42.2), and partial response rate of 7.2% (95% CI 3.0-14.3). All pts achieved a reduction in M-protein. Median time to first response was 1.0 mo (range 0.9-5.8; 80.4% ≤1.0 mo), and median time to complete response or better was 1.8 mo (range 0.9-12.5; 74.1% ≤3.0 mo); responses deepened over time (Figure). Median duration of response was not reached (NR). Of 52 MRD-evaluable pts, 94.2% were MRD-negative at 10-5. The 6-mo progression-free survival (PFS) and overall survival (OS) rates (95% CI) were 87.4% (78.9-92.7) and 93.8% (86.7-97.2), respectively; median PFS and OS were NR. Ten deaths occurred during the study; 8 were due to AEs (both related and unrelated; CRS/hemophagocytic lymphohistiocytosis, neurotoxicity, respiratory failure, sepsis, septic shock, pneumonia, lung abscess, and acute myelogenous leukemia [n=1 each]), and 2 due to progressive disease. AEs reported in >70% of pts were CRS (94.8%; grade [gr] 3/4 4.1%), neutropenia (90.7%; gr 3/4 90.7%), anemia (81.4%; gr 3/4 68.0%), and thrombocytopenia (79.4%; gr 3/4 59.8%). Median time to CRS onset was 7.0 d (range 1-12) and median duration 4.0 d (range 1-27, excluding n=1 with 97 d). CAR-T cell-related neurotoxicity was reported in 20.6% of pts (gr 3/4 10.3%). Cilta-cel CAR+ T cells showed maximum peripheral expansion at 14 d (range 9-43). Among pts with 6 mo' individual follow-up, 67% had cilta-cel CAR+ T cells below the level of quantification (2 cells/µL) in peripheral blood. Conclusions: Preliminary phase 1b/2 data from CARTITUDE-1 indicate a single low-dose infusion of cilta-cel leads to early, deep, and durable responses in heavily pretreated pts with MM with a safety profile consistent with LEGEND-2. Further investigation of cilta-cel in other MM populations is underway. Disclosures Madduri: Celgene: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Foundation Medicine: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau. Berdeja:Teva: Research Funding; Bluebird: Research Funding; Bioclinica: Consultancy; Celgene: Consultancy, Research Funding; EMD Sorono: Research Funding; Kite Pharma: Consultancy; Prothena: Consultancy; Cellularity: Research Funding; Karyopharm: Consultancy; Servier: Consultancy; Legend: Consultancy; Poseida: Research Funding; Lilly: Research Funding; Acetylon: Research Funding; CURIS: Research Funding; Janssen: Consultancy, Research Funding; Genentech, Inc.: Research Funding; Glenmark: Research Funding; Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Constellation: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Vivolux: Research Funding; Abbvie: Research Funding; Amgen: Consultancy, Research Funding; Kesios: Research Funding; Novartis: Research Funding. Usmani:Celgene: Other; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; GSK: Consultancy, Research Funding; Pharmacyclics: Research Funding; Merck: Consultancy, Research Funding; Abbvie: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Incyte: Research Funding; Array Biopharma: Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding. Jakubowiak:Adaptive, Juno: Consultancy, Honoraria; AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cohen:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Other: Patents/Intellectual property licensed, Research Funding. Stewart:Janssen, BMS, Sanofi-Aventis, GSK: Honoraria; Tempus, Inc., Genomics England LLC: Membership on an entity's Board of Directors or advisory committees. Hari:Amgen: Consultancy; BMS: Consultancy; GSK: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Incyte Corporation: Consultancy. Htut:City of Hope Medical Center: Current Employment. Munshi:OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy; Janssen: Consultancy; Adaptive: Consultancy; Legend: Consultancy; Amgen: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; AbbVie: Consultancy; C4: Current equity holder in private company. Deol:Novartis: Consultancy; Kite, a Gilead Company: Consultancy. Lesokhin:BMS: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Janssen: Research Funding; Juno: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; GenMab: Consultancy, Honoraria. Singh:Janssen: Current Employment. Zudaire:Janssen: Current Employment. Yeh:Janssen: Current Employment. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Zhuang:Janssen: Current Employment. Infante:Janssen: Current Employment. Geng:Legend Biotech USA Inc.: Current Employment. Wu:Legend Biotech USA Inc.: Current Employment. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Rizvi:Legend Biotech USA Inc.: Current Employment. Fan:Legend Biotech USA Inc.: Current Employment. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. Lin:Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Merck: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Vineti: Consultancy; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees. Martin:AMGEN: Research Funding; Seattle Genetics: Research Funding; Janssen: Research Funding; GSK: Consultancy; Sanofi: Research Funding.
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Pipe, Steven W., Francesca Ferrante, Muriel Reis, Sara Wiegmann, Claudia Lange, Manuela Braun e Lisa A. Michaels. "First-in-Human Gene Therapy Study of AAVhu37 Capsid Vector Technology in Severe Hemophilia A - BAY 2599023 has Broad Patient Eligibility and Stable and Sustained Long-Term Expression of FVIII". Blood 136, Supplement 1 (5 de novembro de 2020): 44–45. http://dx.doi.org/10.1182/blood-2020-139803.
Texto completo da fonteResumo:
Background Gene therapy for hemophilia A has the potential to reduce the treatment burden for patients and their care providers by eliminating the need for regular factor VIII (FVIII) prophylaxis through long-term expression of endogenous FVIII at levels sufficient to provide bleed protection. Host immunity to the capsid serotype limits patients' eligibility and may impact the balance between vector dose and clinical outcome. BAY 2599023 (AAVhu37FVIII) is the first clinical-stage adeno-associated virus (AAV) gene therapy vector based on the AAVhu37 serotype. BAY 2599023 is a non-replicating AAV vector and contains a single-stranded DNA genome encoding a B-domain-deleted FVIII, under the control of a liver-specific promoter/enhancer combination optimized for transgenic expression. The AAVhu37 capsid is a member of the hepatotropic clade E family, and was selected based on preclinical studies demonstrating efficient liver-directed FVIII gene transfer, favorable biodistribution and durable FVIII expression. However, pre-existing humoral immunity against AAV capsids may limit patient eligibility. Here, we evaluate the seroprevalence and titer levels of pre-existing neutralizing antibodies (Nabs) against AAVhu37, and additional AAV capsids, using cell-based transduction inhibition assays. We also report current, preliminary, long-term safety and FVIII activity following a single intravenous infusion of BAY 2599023, in a phase 1/2 open-label, first-in-human, dose-finding study (NCT03588299). Methods Seroprevalence and titer distribution of Nabs against AAVhu37, AAV5 and AAV8 have been assessed in serum samples derived from 100 US patients with hemophilia A (African American and Caucasian male donors, 19-61 years). For AAVhu37, the clinical trial Nab assay was utilized to determine Nab titer levels according to cellular transduction inhibition. Additionally, we developed and fully validated Nab assays for AAV5 and AAV8. The ongoing BAY 2599023 phase 1/2 dose-finding study included male patients aged ≥18 years with severe hemophilia A, each receiving a single intravenous infusion of BAY 2599023. Patients were enrolled sequentially into three dose cohorts (0.5 × 1013 GC/kg, 1.0 × 1013 GC/kg and 2.0 × 1013 GC/kg), each comprising two patients. Patients had no history of FVIII inhibitors, no detectable neutralizing immunity against the AAVhu37 capsid above a Nab titer of 1:5, and ≥150 exposure days to FVIII products. Primary endpoints were adverse events (AEs), serious AEs (SAEs) and AEs/SAEs of special interest (S/AESIs). The secondary endpoint was change in FVIII activity from baseline. Informed patient consent and ethics committee approval were obtained. Results In the seroprevalence study, the lowest pre-existing Nab prevalence was found for AAVhu37, with a low maximum observed titer of 1:26. Based on our results, 86% of patients would be eligible for AAVhu37-based treatment (Table 1). To date, patients in the first (0.5 × 1013 GC/kg) and second cohort (1.0 × 1013 GC/kg) have completed ≥52 weeks of observation; patients in cohort 3 (2.0 × 1013 GC/kg) have at least 33 weeks of observation. Regardless of the level achieved and the assay used, 5 out of 6 of patients show sustained FVIII levels (all ≥5%) over time and up to 16 months. Patients in cohorts 2 and 3 have all been off prophylaxis since ~6 weeks after gene transfer. No spontaneous bleeds were reported after achieving protective FVIII levels (>15 IU/dL) and discontinuation of prophylaxis in the third cohort. No SAEs have been reported to date. Mild-to-moderate elevation in alanine aminotransferase/aspartate aminotransferase were recorded for one patient in the second cohort and both patients in the third cohort. All were treated with corticosteroids (one resolved, two in resolution). The latest follow-up data for up to 22 months will be presented. Conclusions BAY 2599023 has a broad patient eligibility due to low seroprevalence and low titers of pre-existing Nabs against AAVhu37 compared with other AAVs. BAY 2599023 has a good safety profile, with the potential to achieve endogenous expression of FVIII at therapeutic levels over an extended period. Successful proof-of-concept has been achieved, with measurable and sustained expression of endogenous FVIII. Disclosures Pipe: Apcintex, Bayer, BioMarin, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., Sangamo Therapeutics, Sanofi, Takeda, Spark Therapeutics, uniQure: Consultancy; Siemens: Research Funding; Medical and Scientific Advisory Council to the National Hemophilia Foundation; Medical Advisory Board to World Federation of Hemophilia: Membership on an entity's Board of Directors or advisory committees. Ferrante:Bayer: Current Employment. Reis:Bayer: Current Employment. Wiegmann:Bayer: Current Employment. Lange:Bayer: Current Employment, Current equity holder in private company. Braun:Bayer: Current Employment, Current equity holder in private company. Michaels:Bayer: Current Employment.
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Croft, Paul J. "Assessing “The Excitement of Meteorology!” for Young Scholars". Bulletin of the American Meteorological Society 80, n.º 5 (1 de maio de 1999): 879–92. http://dx.doi.org/10.1175/1520-0477-80.5.879.
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The National Science Foundation Young Scholar Program “The Excitement of Meteorology!” successfully brought the atmospheric and related sciences to high school students in Mississippi. The four-week summer program was administered through the Jackson State University Meteorology Program in the Department of Physics, Atmospheric Sciences, and General Science and was supported by the Mississippi Science Partnership program office. This commuter program provided an opportunity to learn, study, and research the field of meteorology. Through instructional sessions, laboratories, field trips, and peer contact participants were exposed to the concepts of atmospheric motion, the development of storms, and the practical application of meteorology during a one-month period. The program was intended to help students make their own career decisions and to foster their interest in the sciences and meteorology. The goals and objectives of the program were to develop basic science skills; make participants aware of the interdisciplinary nature of meteorology; provide participants with the opportunity to see and hear the meteorologist as a researcher, teacher, and communicator; provide the information and incentive necessary for participants to choose a career in meteorology or the sciences; make participants aware of the various employment opportunities in the field; and show the moral and ethical responsibilities and importance of atmospheric science to society. Thirty sophomore and junior high school student participants (22 females and 8 males, nearly all of whom were African–American) completed the program. All were tested on their meteorological knowledge and skills gained during the program and questioned about their field and lecture experiences. They also “graded” the effectiveness of all speakers, presentations, videotapes, and laboratory sessions. Through surveys it was found that the participants' desire to pursue a science career and to go to college were increased by the program. They also indicated that the program objectives had been met and that the program had met their expectations. They were particularly pleased with the opportunity to work in a college setting and with professional scientists.
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Lust, John A., Saad Z. Usmani, Mehdi Hamadani, Charles Barranco, Martha Q. Lacy, Angela Dispenzieri, Morie A. Gertz et al. "Phase 1b/2a Open-Label, Multiple-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of SNS01-T Administered by Intravenous Infusion in Patients with Relapsed or Refractory Multiple Myeloma." Blood 120, n.º 21 (16 de novembro de 2012): 2973. http://dx.doi.org/10.1182/blood.v120.21.2973.2973.
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Abstract Abstract 2973 Eukaryotic translation initiation Factor 5A (eIF5A) has been implicated in the regulation of apoptosis and is the only known protein to be modified by hypusination. Hypusinated eIF5A is the predominant form of eIF5A in cancer cells. However, in its unhypusinated form, eIF5A is pro-apoptotic. SNS01-T, designed to treat B-cell cancers, consists of two active components: a plasmid DNA expressing eIF5AK50R (human eIF5A containing a lysine to arginine substitution at position 50) which remains pro-apoptotic because it cannot be hypusinated, and an siRNA against an untranslated region of native eIF5A mRNA. When these two components are combined with linear polyethyleneimine (PEI), the nucleic acids are condensed into nanoparticles for protection from degradation in the blood and enhanced delivery to tissues. The eIF5AK50R transgene is under the control of the B29 promoter and enhancer, which restricts expression to B cells. The mode of action of SNS01-T is to use an eIF5A-specific siRNA to deplete the pool of hypusinated eIF5A in myeloma cells while simultaneously adding pro-apoptotic eIF5AK50R. In vitro cell studies and in vivo xenograft studies have demonstrated the efficacy of this approach. Eligible patients are enrolled sequentially into four cohorts of increasingly higher doses. Each cohort will receive SNS01-T by intravenous infusion twice weekly for 6 consecutive weeks and then be observed every 4 weeks during a 24-week follow-up period. Eligible patients must have been diagnosed with multiple myeloma according to IMWG criteria, have measurable disease, have relapsed disease after two or more prior treatment regimens, have a life expectancy of at least 3 months, and not be eligible to receive any other standard therapy known to extend life expectancy. The primary objective is to evaluate the safety and tolerability of multiple ascending doses of SNS01-T. Secondary objectives include pharmacokinetics, immunogenicity studies, proinflammatory cytokine quantitation, and therapeutic efficacy. The required number of 3 patients completed the dosing schedule in Cohort 1 from a total of 6 patients enrolled. Two of three patients had not progressed on treatment, based on standard response criteria including the monoclonal protein, and were considered stable at week 3 and week 6 the end of the dosing regimen. Three patients were withdrawn from the study by their physicians due to disease progression before completing treatment. One of the responding patients has continued to have stable disease at week 10, a month after the end of treatment with SNS01-T. The first group of patients received 0.0125 mg/kg, approximately 1 mg per patient by intravenous infusion. The planned dose levels for the second, third and fourth groups are 0.05, 0.2 and 0.375 mg/kg, respectively. The results to date of this first in man clinical trial indicate that SNS01-T was safely administered without dose-limiting toxicities in the first group of multiple myeloma patients. The MTD has not yet been reached. (Clinical Trials.gov Identifier: NCT01435720.) Disclosures: Hamadani: Celgene Corp: Speakers Bureau; American Cancer Society 116837-IRG-09–061–01: Research Funding; ASBMT & Millennium New Investigator Award: Research Funding; Conquer Cancer Foundation of ASCO: Research Funding. Barranco:Senesco Technologies: Employment. Thompson:Senesco Technologies Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Taylor:Senesco Technologies Inc.: stock options Other. Dondero:Senesco Technologies Inc.: Employment.
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Pemmaraju, Naveen, Andrew A. Lane, Kendra L. Sweet, Anthony S. Stein, Sumithira Vasu, William Blum, David A. Rizzieri et al. "Results of Pivotal Phase 2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)". Blood 132, Supplement 1 (29 de novembro de 2018): 765. http://dx.doi.org/10.1182/blood-2018-99-118966.
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Abstract Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive hematologic malignancy with a historical overall survival (OS) of ~8-14 months from diagnosis and no approved therapies or standard of care. Tagraxofusp (Elzonris™; SL-401) is a novel targeted therapy directed to the interleukin-3 receptor-α (CD123), a target expressed on BPDCN and other malignancies. Tagraxofusp was granted Breakthrough Therapy Designation for the treatment of patients with BPDCN, and a rolling Biologics License Application (BLA) submission to the U.S. Food and Drug Administration (FDA) was completed in June 2018. Detailed results from the pivotal trial of tagraxofusp in BPDCN will be presented. Methods: This pivotal Phase 2 clinical trial is a multicenter, open label, non-randomized, single-arm trial designed to determine safety and efficacy of tagraxofusp in patients with BPDCN. In Stage 1 (lead-in), first line (1L) and relapsed/refractory (r/r) patients with BPDCN received tagraxofusp as a daily IV infusion at 7, 9, or 12 mcg/kg/day on days 1-5 of a 21-day cycle. Patients with BPDCN enrolled in subsequent stages received tagraxofusp at the dose determined in Stage 1 (12 mcg/kg). Stage 2 (expansion) enrolled 1L and r/r patients, and Stage 3 (pivotal, confirmatory) enrolled only 1L patients. Results: 45 patients with BPDCN (Stages 1 and 2, n=32; Stage 3, n=13) were enrolled at 7 sites in the US, including 32 (71%) patients as 1L. Median age was 70 years (range, 22-84); 82% male. Median follow-up for all 1L patients treated at 12 mcg/kg (n=29) was 13.8 months (range 0.2-37.4+). The most common treatment-related adverse events (TRAEs) at 12 mcg/kg in 148 patients treated in four clinical trials with tagraxofusp were transaminitis (44%), hypoalbuminemia (44%), and thrombocytopenia (26%). Capillary leak syndrome (CLS), all grades, occurred in 17% of patients across all indications at 12 mcg/kg; 0.7% (1/148) and 1.6% (3/182) of cases resulted in death across all indications at 12 mcg/kg and all doses, respectively. The Stage 3 pivotal cohort met its primary endpoint with a 54% (7/13) rate of CR+CRc (95% CI: 25.1, 80.8). Across Stages 1, 2 and 3, in 1L patients dosed at 12 mcg/kg (n=29), ORR was 90% (26/29) with a 72% (21/29) rate of CR+CRc+CRi (ORR=overall response rate; CR=complete response; CRc=clinical CR: absence of gross disease with minimal residual skin abnormality; CRi=CR with incomplete hematologic recovery). 45% (13/29) of first-line patients treated with 12 mcg/kg were bridged to stem cell transplant (SCT) (10 allo+3 auto). In r/r patients, ORR was 69% (9/13) with a 38% (5/13) rate of CR+CRc+CRi. Additional patient follow-up will be provided. Conclusions: The pivotal trial of tagraxofusp was the largest prospectively designed, multi-center trial specifically dedicated to patients with BPDCN. This study has met its primary endpoint, and also demonstrated high response rates that were generally achieved early in the course of treatment and maintained over multiple cycles of therapy. Safety profile demonstrated most common toxicities of transaminitis, hypoalbuminemia, and thrombocytopenia; occurrence of CLS was the most serious TRAE, which was overall manageable in this population. Patients with BPDCN are being enrolled in an additional cohort, Stage 4, to ensure ongoing access. Tagraxofusp is also being evaluated in other trials including in patients with chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF). Disclosures Pemmaraju: celgene: Consultancy, Honoraria; SagerStrong Foundation: Research Funding; stemline: Consultancy, Honoraria, Research Funding; cellectis: Research Funding; novartis: Research Funding; abbvie: Research Funding; samus: Research Funding; daiichi sankyo: Research Funding; plexxikon: Research Funding; Affymetrix: Research Funding. Lane:N-of-one: Consultancy; Stemline Therapeutics: Research Funding. Sweet:Agios: Consultancy; Jazz: Speakers Bureau; BMS: Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Astellas: Consultancy; Celgene: Honoraria, Speakers Bureau; Jazz: Speakers Bureau; Astellas: Consultancy; BMS: Honoraria; Phizer: Consultancy; Agios: Consultancy; Celgene: Honoraria, Speakers Bureau; Phizer: Consultancy. Stein:Amgen Inc.: Speakers Bureau; Celgene: Speakers Bureau. Vasu:Boehringer Ingelheim Inc: Membership on an entity's Board of Directors or advisory committees. Blum:Tolero: Research Funding; Forma: Research Funding; Astellas: Consultancy; Xencor: Research Funding; Boehringer Ingelheim: Research Funding; Pfizer: Consultancy. Rizzieri:Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Arog: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wang:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Novartis: Speakers Bureau; Novartis: Speakers Bureau; Jazz: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Duvic:Guidepoint Global: Consultancy; Eisai: Research Funding; Allos: Research Funding; Clinical Care Options: Consultancy; Array Biopharma: Consultancy, Honoraria; Spatz Foundation: Research Funding; Defined Health: Consultancy; Medivir AB: Membership on an entity's Board of Directors or advisory committees; MiRagen Therapeutics: Consultancy; MEDACorp: Consultancy; Taiwan Liposome Company LTD: Consultancy; Medscape: Other: Speaker/Preceptor; Concert Pharmaceuticals, Inc.: Consultancy; Kyowa Hakko Kirin, Co: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Huya Bioscience Int'l: Consultancy; Shape: Research Funding; Kiniksa Pharmaceuticals: Consultancy; Soligenix, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Forty Seven, Inc.: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cell Medica Inc.: Consultancy, Honoraria; Dr. Reddy's Laboratories (A.K.A. Promius Pharma): Consultancy; Huron Consulting Group: Consultancy; Aclaris Therapeutics Int'l Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; UT MD Anderson Cancer Center: Employment; The Lynx Group: Consultancy; Evidera, Inc.: Consultancy; Mallinckrddt Pharmaceuticals (formerly Therakos): Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; American Council on Extracorporeal Photopheresis (ACE): Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tetralogics: Research Funding; Precision Oncology, LLC: Membership on an entity's Board of Directors or advisory committees; Oncoceuticals: Research Funding; Jonathan Wood & Associates: Other: Speaker; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Rhizen Pharma: Research Funding. Spence:Stemline Therapeutics: Consultancy. Shemesh:Stemline Therapeutics: Employment, Equity Ownership. Brooks:Stemline Therapeutics: Employment, Equity Ownership. Bergstein:Stemline Therapeutics: Employment, Equity Ownership. Chen:Stemline Therapeutics: Employment, Equity Ownership. Dunn:Stemline Therapeutics: Employment, Equity Ownership. McDonald:Stemline Therapeutics: Employment, Equity Ownership. Sloan:Stemline Therapeutics: Consultancy. Konopleva:Stemline Therapeutics: Research Funding.
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Escobar, Miguel A., Amy Dunn, Doris Quon, Ben Trzaskoma, Lucy Lee, Richard H. Ko e Shannon L. Carpenter. "A Phase IV, Multicenter, Open-Label Study of Emicizumab Prophylaxis in Persons with Hemophilia a with or without FVIII Inhibitors Undergoing Minor Surgical Procedures". Blood 136, Supplement 1 (5 de novembro de 2020): 30–31. http://dx.doi.org/10.1182/blood-2020-134906.
Texto completo da fonteResumo:
Introduction: Emicizumab is a subcutaneously administered, bispecific, humanized monoclonal antibody that bridges factor (F)IXa and FX to restore the function of missing activated FVIII in persons with hemophilia A (PwHA). This study (NCT03361137) was designed to evaluate the safety and efficacy of emicizumab prophylaxis in PwHA with or without FVIII inhibitors undergoing minor surgical procedures without additional prophylaxis with bypassing agents (BPAs; for patients with FVIII inhibitors) or FVIII (for patients without FVIII inhibitors). Methods: This Phase IV, multicenter, single-arm, open-label study enrolled PwHA of any age, with or without FVIII inhibitors, who were scheduled to undergo minor surgical procedures. Patients were required to have received a minimum of four loading doses of emicizumab (3mg/kg once weekly for 4 weeks) prior to surgical procedure; subsequent maintenance doses of emicizumab were 1.5mg/kg once weekly, 3mg/kg every 2 weeks, or 6mg/kg every 4 weeks. Patients were required to be adherent to emicizumab prophylaxis. Treatment with emicizumab was scheduled to continue for at least 1 month after surgery. No other prophylactic treatment with coagulation factor was permitted. Outcome measures included incidence of excessive bleeding intra-operatively and until discharge from surgery, use of BPAs or FVIII to control bleeding (intra- and post-operatively), incidence of adverse events (AEs), and the percentage of patients with complications requiring hospitalization or return to surgery. Excessive bleeding was defined as a rating of fair to poor on the hemostatic rating scale and translates to an intra- and/or post-operative blood loss of ≥25% over expectation for a patient without hemophilia prior to discharge from surgery. Patients were followed for 28 days following discharge from surgery. Results: Between June 28, 2018 and March 13, 2020, 14 PwHA undergoing minor surgeries were enrolled (with FVIII inhibitors n=11; without FVIII inhibitors n=3); one PwHA with FVIII inhibitors enrolled but did not have surgery and discontinued prematurely, therefore the surgery analysis population comprised 13 patients (with FVIII inhibitors n=10; without FVIII inhibitors n=3). The majority (78.6%) of those enrolled were <18 years of age and all surgeries were either central venous access device (CVAD) removal (n=11) or dental procedures (n=2; Table 1). Of the 10 patients with FVIII inhibitors, one CVAD removal led to excessive bleeding during surgery with a need for BPA therapy, two patients undergoing CVAD removal received BPA therapy during surgery but had no reported excessive bleeding, three (two CVAD removals, one dental extraction) had post-operative bleeding that required use of a BPA (Table 2). Seven patients with FVIII inhibitors had zero bleeds after discharge from surgery. None of the three PwHA without FVIII inhibitors had excessive bleeding necessitating FVIII treatment during surgery or until discharge; two CVAD removals resulted in zero bleeds post-operatively and one dental extraction led to a post-operative bleed that did not require treatment. No serious AEs, thromboembolic events (TEs), thrombotic microangiopathies (TMAs) or deaths were reported during the study. Overall, 10 AEs occurred in five patients with FVIII inhibitors (headache n=3, limb injury, procedural pain, pyrexia, constipation, device occlusion, adhesiolysis, and hematoma, all n=1); no AEs were reported in patients without FVIII inhibitors. There were no AEs leading to dose modification, interruption or withdrawal of treatment, and no patient in either group had surgical complications requiring hospitalization or a return to surgery. The study was terminated early due to low enrollment and the limited variety of surgery types. Conclusions: In this study of mostly pediatric PwHA with and without FVIII inhibitors receiving emicizumab prophylaxis, minor surgeries were safely performed. The majority of surgeries were performed without additional prophylactic coagulation factor, however the small sample size should be considered here. There were no serious AEs, TEs, TMAs, or deaths. These findings are consistent with results from previous studies of patients undergoing minor surgery while receiving emicizumab prophylaxis. Disclosures Escobar: National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Dunn:Genentech, Inc.: Consultancy; Nationwide Children's Hospital: Current Employment; World Federation of Hemophilia USA: Membership on an entity's Board of Directors or advisory committees; Medscape: Honoraria; Spire: Honoraria; ATHN: Research Funding; Takeda: Research Funding; BioMarin: Research Funding; uniQure: Consultancy. Quon:Octapharma: Honoraria; Bayer: Honoraria; Biomarin: Honoraria, Speakers Bureau; Bioverativ/Sanofi: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Shire/Takeda: Speakers Bureau; Orthopaedic Institute for Children: Current Employment. Trzaskoma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Lee:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Ko:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Carpenter:Novo Nordisk: Honoraria; Genentech, Inc.: Honoraria; American Thrombosis and Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Research Funding; Shire: Research Funding; Hemostasis & Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; American Academy of Pediatrics: Other: PREP Heme/Onc editorial board; Kedrion: Honoraria.
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Bronté-Hall, Lanetta, Matthew Parkin, Courtney Green, Elsa Tchouambou, Lynn Huynh, Charu Puri-Sharma, Rose Chang, Anjulika Chawla, James Signorovitch e Gershwin Theophilus Blyden. "Real-World Clinical Burden of Sickle Cell Disease in the US Community-Practice Setting: A Single-Center Experience from the Foundation for Sickle Cell Disease Research". Blood 134, Supplement_1 (13 de novembro de 2019): 5856. http://dx.doi.org/10.1182/blood-2019-128700.
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Background Sickle cell disease (SCD) is a progressively debilitating monogenic disease characterized by unpredictable, acute, life-threatening episodes and chronic complications such as hemolytic anemia and end-organ damage. It presents with a range of severity resulting in significant morbidity, poor quality of life, and early mortality. Real-world data on treatments and clinical outcomes for patients (pts) with SCD are limited, particularly in the community clinical care setting. The objectives of this retrospective real-world study were to characterize clinical manifestations and management of pts with SCD treated at the Foundation for Sickle Cell Disease Research (FSCDR). Methods A retrospective longitudinal analysis of an electronic health records (EHR) database from the FSCDR, which captured laboratory testing, treatments, and records on outpatient, emergency, and inpatient visits, was conducted. All unique pts with SCD assigned a medical record number in the EHR (N=172) were considered. Data from external records were manually entered into the EHR to supplement the EHR database. To address limitations of a real-world database, medical records for all pts included were manually reviewed and validation was performed on 10% of the sample. Pt demographics, clinical characteristics, hydroxyurea (HU) treatment (as captured by prescriptions and usage notes), administration of red blood cell transfusions, vaso-occlusive crisis (VOC) events and acute chest syndrome (ACS) (based on physician assessment) were described. Annual VOC rates were summarized by dividing the number of events by the total follow-up duration in years. Results In total, 122 pts with SCD were included. Twenty-three pts were excluded as they were not actively seeking care and/or had no relevant clinical data from 01/01/15-07/19/19. Data for 27 pts <22 years of age were unavailable at time of analysis (results of this cohort will be included in the presentation). Among all pts, 76 (62.3%) were female and 118 (96.7%) were Black or African American. The mean age at time of analysis was 39.1 (standard deviation [SD] 12.3) years with 9 (7.4%) 22-24 year-olds, 67 (54.9%) 25-40 year-olds, 35 (28.7%) 41-55 year-olds, and 11 (9.0%) ≥ 56 year-olds. The most common genotypes were HbSS (77.0%) and HbSC (17.2%). Over a mean follow-up period of 2.9 (interquartile range: 2.0, 4.4) years, 27 (22.1%) pts were treated with HU and 66 (54.1%) pts received transfusions, of which 1 (1.5%) pt chronically received episodic transfusions (i.e., continuous monthly transfusions for ≥ 6 months). The mean total hemoglobin (Hb) was 8.3 (SD 1.7) for HbSS pts and 10.9 (SD 1.5) for HbSC pts. Among pts who never received HU or transfusions during follow-up, mean Hb was 9.4 (SD 1.7) for HbSS pts and 11.4 (SD 1.6) for HbSC pts. Among pts who ever received HU or transfusions, mean Hb was 7.7 (SD 1.3) for HbSS pts and 10.3 (SD 1.1) for HbSC pts. Eleven (9.0%) pts had ≥ 1 ACS whereas 97 (79.5%) pts had ≥ 1 VOC event. ACS and VOC events occurred mostly in pts 25-55 years of age (ACS: 9 [81.8%] pts aged 25-40 years and 2 [18.2%] pts aged 41-55 years; VOC: 54 [55.7%] pts aged 25-40 years and 29 [29.9%] pts aged 41-55 years). Annual rates of VOC are described in Figure 1. Conclusions This is one of the first studies to describe clinical characteristics and management of pts with SCD in a community practice setting. Higher Hb levels among pts who never vs ever received HU or transfusions during follow-up may be a reflection of who were selected for treatment and additional studies to take into account timing of treatment and Hb assessments and confounding factors need to be conducted. The study found high VOC rates particularly among pts aged ≤ 40 years. Lower VOC rates among older pts do not necessarily indicate less severe disease. One potential reason for lower VOC rates among older pts with SCD is that cumulative exposure to ischemia-related tissue injury and resulting end organ damage may decrease VOC-related pain over time. Further investigation to elucidate the rate of VOC decline observed in older pts is needed, including looking at underlying health and end organ damage. While limitations are inherent in real-world studies, these findings underlie the ability to and importance of studying SCD management and clinical outcomes in community care settings. This study highlights the clinical burden of SCD and possibly higher than expected unmet need in this community setting. Disclosures Bronté-Hall: bluebird bio: Research Funding. Huynh:bluebird bio: Research Funding. Puri-Sharma:bluebird bio: Employment. Chang:bluebird bio: Research Funding. Chawla:bluebird bio: Employment. Signorovitch:bluebird bio: Research Funding.
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Chrisentery-Singleton, Tammuella, W. Allan Alexander, Ahmad Al-Sabbagh, Daniel Bonzo, Michael U. Callaghan, Miguel A. Escobar, Adam Giermasz et al. "Athn 16: Safety of Coagulation Factor VIIa (recombinant)-Jncw for the Treatment of Bleeding Events in Patients with Congenital Hemophilia a or B with Inhibitors with or without Prophylactic Treatment". Blood 138, Supplement 1 (5 de novembro de 2021): 3201. http://dx.doi.org/10.1182/blood-2021-146247.
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Abstract Background: A new recombinant activated factor VII, eptacog beta (SEVENFACT®, rFVIIa-jncw) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of bleeding events (BEs) in individuals >12 years of age with hemophilia A or B (HAB) with inhibitors. In the eptacog beta phase III trial (Wang, Haemophilia, 2017), 87% of BEs were successfully treated using two different dosing regimens within 12 hours of bleeding onset. In two studies looking at the safety of eptacog beta Ducore, Haemophilia, 2017), a total of 11 treatment-emergent adverse events (TEAEs) were reported in 42 participants, all mild and transitory. To date, no studies designed to assess safety of treatment of breakthrough BEs in people on emicizumab with eptacog beta have been performed. Objective: To evaluate the safety of eptacog beta when used to treat BEs in participants with HAB with inhibitors with or without prophylactic treatment. Methods: ATHN 16 (NCT04647227) is a phase IV, United States-centric multi-center, open-label safety study enrolling participants with HAB with inhibitors aged 12 to 65 years, inclusive, who are either on long-term prophylactic treatment (e.g., emicizumab) at risk of experiencing a breakthrough BE or who are not on prophylactic treatment who may need to control a BE. Exclusion criteria include any bleeding disorder in addition to HAB, a known hypersensitivity to eptacog beta or rabbit proteins, or the inability to provide informed consent. The maximum study duration for any participant in the study is up to 2 years from the time of enrollment. We plan to enroll between 28 to 55 participants with the goal of collecting data on 100 BEs. Safety of eptacog beta will be evaluated based on events included in the European Haemophilia Safety Surveillance (EUHASS) protocol, including allergic or other acute events, treatment-emergent side effects, transfusion-transmitted infections, inhibitor development, thrombosis, cardiovascular events, malignancies, neurological events, and death. After signed informed consent is obtained, demographics, bleeding disorder history, inhibitor history, baseline medical and surgical history for the 6-month period before the baseline visit will be captured. Each participant will receive nine 75 µg/kg doses of eptacog beta supplied by the study funder. Eptacog beta will be administered at the time of a BE by the participant or by study staff; the dose and duration of treatment will be determined at the discretion of the treating physician. BE details such as timing, any treatments associated with the BE (including eptacog beta), and timing of resolution of the BE will be collected as well as surgical procedures and all AEs and serious AEs. Results: At the time of abstract submission, ATHN 16, having received central IRB approval, is being rolled out across the United States Hemophilia Treatment Center Network. There are a total of 20 sites where the protocol will be conductedalex. We plan to report participant demographics, BE details, as well as all safety data meeting the EUHASS endpoints. In addition, we will report any pregnancies as AEs of special interest. All serious AEs will also be reported. The ATHN 16 Safety Analysis Set is defined as all participants who received at least a single dose of eptacog beta. Baseline characteristics will be summarized using descriptive statistics for continuous variables, and frequencies and percentages for categorical variables. The number and percentage of participants with treatment-emergent AEs (TEAEs), serious AEs (SAEs), serious TEAEs, and treatment-related TEAEs (i.e., adverse drug reactions) will be presented for all participants. The number and percentage of participants with TEAEs and/or allergic and anaphylactic reactions will be presented for all participants. There are no pre-specified efficacy endpoints. Conclusions: ATHN 16 will explore the safety of eptacog beta as therapy for BEs in participants with HAB complicated by inhibitors with or without concurrent prophylactic treatment. As the first interventional study sponsored by ATHN, ATHN 16 represents a crucial step forward in ATHN's clinical research capabilities. Disclosures Chrisentery-Singleton: CSL Behring: Consultancy, Speakers Bureau; Roche/Genentech: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; HEMA Biologics: Consultancy, Honoraria; Novo Nordisk: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Pfizer: Consultancy; Sanofi: Consultancy; Spark: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Kedrion: Consultancy; Biomarin: Speakers Bureau; Global Blood Therapeutics: Speakers Bureau; Bayer: Honoraria; BPL Plasma: Honoraria. Alexander: HEMA Biologics: Consultancy, Ended employment in the past 24 months; Johnson & Johnson: Current equity holder in publicly-traded company; Pfizer: Current equity holder in publicly-traded company; Roche/Genentech: Current equity holder in publicly-traded company. Al-Sabbagh: LFB: Current Employment. Bonzo: LFB: Current Employment. Callaghan: Kedrion: Consultancy; Biomarin: Consultancy; Spark: Consultancy; uniQure: Consultancy; Global Blood Therapeutics: Consultancy, Speakers Bureau; Pfizer: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Speakers Bureau; Roche/Genentech: Consultancy, Speakers Bureau; Alnylum: Current equity holder in publicly-traded company; Hema Biologics: Consultancy; Forma: Consultancy; Chesei: Consultancy; Agios Pharmaceuticals: Current Employment. Giermasz: Bayer: Consultancy; ATHN: Consultancy; NovoNordisk: Consultancy; UniQure: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Bioverativ/Sanofi: Consultancy, Research Funding, Speakers Bureau; Sangamo Therapeutics,: Research Funding; Pfizer: Consultancy; Genentech/Roche: Consultancy, Research Funding, Speakers Bureau; BioMarin: Consultancy, Research Funding. Journeycake: LFB: Honoraria; HEMA Biologics: Honoraria. Nasr: HEMA Biologics: Consultancy. Quon: Orthopaedic Institute for Children: Current Employment. Recht: uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; American Thrombosis and Hemostasis Network: Current Employment; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy; Oregon Health & Science University: Current Employment.
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Gaiti, Federico, Allegra Hawkins, Paulina Chamely, Ariel Swett, Xiaoguang Dai, Lloyd Kluegel, Celine Chen et al. "Single-Cell Multi-Omics Defines the Cell-Type Specific Impact of SF3B1 Splicing Factor Mutations on Hematopoietic Differentiation in Human Clonal Hematopoiesis and Myelodysplastic Syndromes". Blood 138, Supplement 1 (5 de novembro de 2021): 145. http://dx.doi.org/10.1182/blood-2021-147529.
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Abstract Splicing factor mutations are recurrent genetic alterations in blood disorders, highlighting the importance of alternative splicing regulation in hematopoiesis. Specifically, mutations in splicing factor 3B subunit 1 (SF3B1) are implicated in the pathogenesis of myelodysplastic syndromes (MDS) and linked to a high-risk of leukemic transformation in clonal hematopoiesis (CH). SF3B1 mutations are associated with aberrant RNA splicing, leading to increased cryptic 3' splice site (ss) usage and MDS with ring sideroblasts phenotype. The study of mutant SF3B1-driven splicing aberrations in humans has been hampered by the inability to distinguish mutant and wildtype single cells in patient samples and the inadequate coverage of short-read sequencing over splice junctions. To overcome these limitations, we developed GoT-Splice by integrating Genotyping of Transcriptomes (GoT; Nam et al. 2019) with Nanopore long-read single-cell transcriptome profiling and CITE-seq (Fig. A). This allowed for the simultaneous single-cell profiling of protein and gene expression, somatic mutation status, and alternative splicing. Our method selectively enriched full-length sequencing reads with the accurate structure, enabling the capture of higher number of junctions per cell and greater coverage uniformity vs. short-read sequencing (10x Genomics; Fig. B, C). We applied GoT-Splice to CD34+ bone marrow progenitor cells from MDS (n = 15,436 cells across 3 patients; VAF: [0.38-0.4]) to study how SF3B1 mutations corrupt human hematopoiesis (Fig. D). High-resolution mapping of SF3B1 mutvs. SF3B1 wt hematopoietic progenitors revealed an increasing fitness advantage of SF3B1 mut cells towards the megakaryocytic-erythroid lineage, resulting in an expansion of SF3B1 muterythroid progenitor (EP) cells (Fig. E, F). Accordingly, SF3B1 mutEP cells displayed higher protein expression of erythroid lineage markers, CD71 and CD36, vs. SF3B1 wt cells (Fig. G). In these SF3B1 mutEP cells, we identified up-regulation of genes involved in regulation of cell cycle and checkpoint controls (e.g., CCNE1, TP53), and mRNA translation (eIFs gene family; Fig. H). Next, while SF3B1 mut cells showed the expected increase of cryptic 3' splicing vs. SF3B1 wt cells (Fig. I), they exhibited distinct cryptic 3' ss usage as a function of hematopoietic progenitor cell identity, displaying stage-specific aberrant splicing during erythroid maturation (Fig. J). In less differentiated EP cells, we observed mis-splicing of genes involved in iron homeostasis, such as the hypoxia-inducible factor HIF1A, and key regulators of erythroid cell growth, such as SEPT2. At later stages, we observed mis-splicing of BAX, a pro-apoptotic member of the Bcl-2 gene family and transcriptional target of p53, and erythroid-specific genes (e.g., PPOX). We further predicted 54% of the aberrantly spliced mRNAs to introduce premature stop codons, promoting RNA degradation through nonsense-mediated decay (NMD). In line with this notion, we observed a significant decrease in expression of NMD-inducing genes in SF3B1 mut vs . SF3B1 wtEP cells (Fig. K). Lastly, splicing factor mutations observed in CH subjects provide an opportunity to interrogate the downstream impact of SF3B1 mutations prior to development of disease. Like MDS, by applying GoT-splice to CD34+ progenitor cells from SF3B1 mut CH subjects (n = 9,007 cells across 2 subjects; VAF: [0.15-0.22]; Fig. L), we revealed increased mutant cell frequency in EP cells (Fig. M) with concomitant increased expression of genes involved in mRNA translation (Fig. N), consistent with SF3B1 mutation causing mis-splicing injury to translational machinery and ineffective erythropoiesis. Notably, CH patients already exhibited cell-type specific cryptic 3' ss usage in SF3B1 mut cells (Fig. O). In summary, we developed a novel multi-omics single-cell toolkit to examine the impact of splicing factor mutations on cellular fitness directly in human samples. With this approach, we showed that, while SF3B1 mutations arise in uncommitted HSCs, their effect on fitness increases with differentiation into committed EPs, in line with the mutant SF3B1-driven dyserythropoiesis phenotype. We revealed that SF3B1 mutations exert cell-type specific mis-splicing that leads to abnormal erythropoiesis. Finally, we demonstrated that the impact of SF3B1 mutations on EP cells begins before disease onset, as observed in CH subjects. Figure 1 Figure 1. Disclosures Dai: Oxford Nanopore Technologies: Current Employment. Beaulaurier: Oxford Nanopore Technologies: Current Employment. Drong: Oxford Nanopore Technologies: Current Employment. Hickey: Oxford Nanopore Technologies: Current Employment. Juul: Oxford Nanopore Technologies: Current Employment. Wiseman: Astex: Research Funding; Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Takeda: Consultancy; StemLine: Consultancy. Harrington: Oxford Nanopore Technologies: Current Employment. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy. Abdel-Wahab: H3B Biomedicine: Consultancy, Research Funding; Foundation Medicine Inc: Consultancy; Merck: Consultancy; Prelude Therapeutics: Consultancy; LOXO Oncology: Consultancy, Research Funding; Lilly: Consultancy; AIChemy: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Envisagenics Inc.: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees.
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Querfeld, Christiane, Theresa Pacheco, Francine M. Foss, Ahmad S. Halwani, Pierluigi Porcu, Anita G. Seto, Judy Ruckman et al. "Preliminary Results of a Phase 1 Trial Evaluating MRG-106, a Synthetic microRNA Antagonist (LNA antimiR) of microRNA-155, in Patients with CTCL". Blood 128, n.º 22 (2 de dezembro de 2016): 1829. http://dx.doi.org/10.1182/blood.v128.22.1829.1829.
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Abstract Introduction and Objectives: microRNAs are small, non-coding RNAs that regulate expression of multiple genes which impact physiological processes and cellular phenotypes. miR-155-5p is a well-described onco-miR with a strong mechanistic link to cutaneous T-cell lymphoma (CTCL). A LNA-modified oligonucleotide inhibitor of miR-155-5p, MRG-106, was selected based on its ability to de-repress canonical miR-155-5p targets in multiple mycosis fungoides (MF) cell lines in vitro. In preclinical models, MRG-106 showed significant pharmacodynamic activity without requiring additional formulation. The objective of this first-in-human study is to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of MRG-106 in patients with mycosis fungoides (MF). Methodology: This Phase 1 trial employs a dose-escalation design to evaluate both intratumoral and subcutaneous administration of MRG-106 at doses of 75 mg and up to 900 mg per injection, respectively. Patients were required to be ≥ 18 years old, have a confirmed diagnosis of MF, be clinical stage I-III with plaques or tumors, be on a stable treatment regimen or without any concomitant therapy for MF, and have no other major illness. The first 6 patients were dosed with four or five 75 mg intratumoral injections of MRG-106 over 2 weeks. In addition, 4 patients received saline injections in a second lesion on the same schedule. Skin biopsies were taken from MRG-106 and saline treated lesions for molecular, bioanalytical, and histological analyses, before the first dose and after the last dose. Results: Six patients (5M/1F, median age 61 years, 5 Caucasian/ 1 African-American) were dosed intratumorally. All tolerated the administrations well with only minimal erythema at the site of injection noted in one patient. One patient was discontinued from the trial due to rapid progression of disease, which was considered not related to the study drug. There were no clinically significant adverse events or laboratory abnormalities. To date, the first cohort of 6 patients has either completed the dosing period (5 patients) or discontinued due to progressive disease (1 patient). All patients showed a reduction in the baseline Composite Assessment of Index Lesion Severity (CAILS) score in both MRG-106-treated and saline-treated lesions. The maximal reduction was on average 55% [range: 33% to 77%] in the MRG-106 treated lesion and 39% [range:13% to 75%] in the saline treated lesions). In all the subjects that completed dosing, the MRG-106 treated lesions had a CAILS score reduction of ≥ 50% which was maintained to the end of study; in contrast, a ≥ 50% reduction was observed in only one saline treated lesion. Most patients noted a marked decrease in systemic pruritus. Histological examination of pre-treatment and post-treatment biopsies of the same lesion injected with MRG-106 from five evaluable patients revealed that one patient had a complete loss of the neoplastic infiltrate, two patients had a reduction in neoplastic cell infiltrate density and depth, one patient had fewer CD30+ large atypical cells, and one patient demonstrated no change. After the first dose, MRG-106 had a mean t1/2 in plasma of 4.4 hours, and a mean Cmaxof 1.4 µg/mL. The drug was detectable 24 hours after the last dose in the MRG-106-injected lesions that were biopsied. Gene expression analysis of the pre- and post-treatment biopsies showed transcript changes consistent with the expected mechanism of action of MRG-106. Conclusions: These promising preliminary results in this first-in-human study in 6 MF patients show that intratumoral injection of MRG-106 was well-tolerated, and demonstrated encouraging therapeutic improvements in cutaneous lesions, based on CAILS scores and histological findings. In addition, reductions in CAILS scores in other lesions as well as decreases in systemic symptoms such as pruritus were observed. Preliminary biomarker analysis indicates that MRG-106 induces transcriptional changes consistent with on-target activity and molecular proof of concept. The trial is ongoing and additional results will be presented as available. Disclosures Querfeld: Actelion: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Foss:Seattle Genetics: Consultancy, Speakers Bureau; Spectrum Pharmaceuticals: Consultancy; Eisai: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau. Halwani:Bristol-Myers Squibb: Research Funding; Abbvie: Consultancy, Research Funding; Amgen: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy, Research Funding; Genentech: Research Funding; Kyowa Hakko Kirin: Research Funding; Immune Design: Research Funding. Porcu:miRagen: Other: Investigator in a clinical trial; celgene: Other: Investigator in a clinical trial; Innate Pharma: Other: Investigator in a clinical trial; Millenium: Other: investigator in a clinical trial. Seto:miRagen: Employment. Ruckman:miRagen Therapeutics, Inc: Employment. Landry:Accera, Inc: Consultancy; miRagen: Consultancy. Jackson:miRagen: Employment. Pestano:miRagen Therapeutics: Employment. Dickinson:miRagen Therapeutics: Employment. Sanseverino:miRagen Therapeutics: Employment. Rodman:Nivalis: Employment, Equity Ownership; miRagen Therapeutics: Consultancy. Gordon:GLPI: Consultancy, Equity Ownership; IGM: Consultancy; Globavir: Consultancy; Pre-cell: Consultancy; Industrial Laboratories: Membership on an entity's Board of Directors or advisory committees; Taiho: Consultancy; Flugen: Consultancy; Bayer: Consultancy; miRagen Therapeutics: Consultancy; Clinipace: Consultancy; Caring for Colorado Foundation: Membership on an entity's Board of Directors or advisory committees; Ruesch Center for the Cure of Gastrointestinal Cancer: Membership on an entity's Board of Directors or advisory committees; Axion: Membership on an entity's Board of Directors or advisory committees; TEQ laboratories: Membership on an entity's Board of Directors or advisory committees. Marshall:miRagen Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: inventor on various patents; BiOptix: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Fluorofinder: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; AmideBio: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Colorado BioScience Association: Membership on an entity's Board of Directors or advisory committees; Atlas Venture: Consultancy.
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Slovak, Marilyn L., Yi Ning, Lei Yu, Stephen Hunger, Andrew J. Carroll, Theresa C. Brown, Lynda J. Campbell et al. "Targeted Microarray Analyses Augment the Clinical Cytogenetic Diagnosis of Acute Lymphoblastic Leukemia (ALL): Submicroscopic Genetic Events Improve Diagnosis, Contribute to Risk Stratification, and Provide Genetic Markers for Minimal Residual Disease (MRD) Testing". Blood 116, n.º 21 (19 de novembro de 2010): 2690. http://dx.doi.org/10.1182/blood.v116.21.2690.2690.
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Abstract Abstract 2690 Cytogenetic aberrations are key diagnostic and prognostic markers in ALL; however, suboptimal chromosome morphology, low lymphoblast mitotic activity in cell culture and the inability to detect subtle (≤ 5∼10 Mb) abnormalities often preclude a rapid and accurate ALL clinical cytogenetic workup. Recent genome-wide microarray studies have reported submicroscopic DNA copy number alterations (CNAs) in ALL that target key genes involved in B-cell and T-cell cellular processes (cell cycle regulation, differentiation, proliferation and survival) and alterations of these genes are rapidly being associated with clinical treatment and outcome (e.g., IKZF1, NUP214/ABL1, NUP214/SET, PTEN, PTPN2). To improve the cytogenetic diagnosis of ALL, we analyzed DNA samples from 22 newly-diagnosed, pediatric T-cell and 22 B-cell (16 newly diagnosed and 6 relapse) ALL patients (pts) using a 133K targeted oligo-based microarray. The aCGH results were compared to their cytogenetic, FISH and clinic-pathological findings. When sufficient material was available, locus-specific FISH studies were performed to confirm the submicroscopic CNAs. The 22 pediatric T-cell samples, obtained from the COG Cell Bank, showed the following karyotypes: del(6q) alone (n=10), del(6q) with one or two additional abnormalities (n=8), or normal karyotypes (n=4). The B-cell ALL karyotypes showed one to three abnormalities (n=10), ≥5 abnormalities (n=10), including hypodiploidy/hyperdiploidy/near-triploid/near tetraploidy, or normal karyotypes (n=2). Twelve B-cell ALL pts showed prognostically-significant translocations. By aCGH, CNAs were observed in all 44 cases, ranging from five to14 (median, 8) CNAs in T-cell and three to 35 (median, 10) CNAs in B-cell ALL. aCGH detected del(6q) in all 18 known T-cell pts (size range, 16.8 kb to 106 Mb) and in six B-cell pts. Submicroscopic aberrations detected in T-cell ALL included: CDKN2A (mono or bi-allelic) deletions (n=19), ranging in size from 24 kb to 6.76 Mb, including 6 focal deletions under 200 kb, a ∼77 Kb deletion in 1p33, resulting in a STIL/TAL1 fusion (n=8), other TAL1 or STIL deletions (n=3), PTEN deletions (n=6) ranging from 15 kb to 1 Mb (n=6), 49 kb biallelic GSTT1 deletions (n=4), and TLX3 rearrangements (n=2) including a case with a ABL1/NUP214 fusion and a focal biallelic PTPN2 deletion. Cryptic deletions in 4q31.3/FBXW7 and in 9q34 resulting in a SET/NUP214 fusion and duplication of MYB were observed in a single case. In B-cell ALL, recurring “cryptic” deletions were of IKZF1 (n=6), TOX (n=3), PAX5 (n= 5) CDKN2A (mono- or bi-allelic) (n=10), ETV6 (n=6), BTG1 (n=4), C20orf94 (n=3), EBF1 (n=2), TP53 (n=2), and miR650 (n=2). Single CNAs observed in B-cell ALL included: CDKN2C, LCK, BTLA, MECOM, TBL1XR1, AFF1, LEF1, HEF, RAG1, ATF7IP, JAK2, PTEN, ID4, CASC3, COMMD1, and the drug receptor gene NRCC1. Gains observed in residual or relapsed B-cell ALL were MYC, MLL, miR657, and at 13q31.3, which includes GPC5 and multiple miRNAs (latter also seen in three cases of T-cell), and PPP2R5A in a t(4;11) pt. Imbalances in TRG (7p14), TRB (7q34), and TRA/TRD (14q11.2) were noted in T-cell pts whereas IGH, IGK and/or IGL were clearly seen in B-cell pts. Three translocations, t(9;22), t(4;11) and t(12;21), were also detected by microarray using linear amplification followed by aCGH. These findings demonstrated that aCGH can improve the cytogenetic diagnosis of ALL, contribute to risk stratification, and provide genetic markers for MRD testing. Moreover, these results provide a rationale for the integration of targeted microarray technology in the clinical evaluation of ALL. Disclosures: Slovak: PerkinElmer: Employment. Hunger:bristol myers squibb: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shaffer:PerkinElmer: Employment; American College of Medical Genetics Foundation: Membership on an entity's Board of Directors or advisory committees. Ballif:PerkinElmer: Employment. Schultz:PerkinElmer: Employment.
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Journeycake, Janna, Dunlei Cheng, Tammuella Chrisentery-Singleton, Vidhi Desai, Annette von Drygalski, Carol Fedor, Nikki Hirsh et al. "Reduced Dosing Frequency Following a Switch to Rix-FP for the Treatment of Hemophilia B: Results from the Athn 2 Study". Blood 138, Supplement 1 (5 de novembro de 2021): 1039. http://dx.doi.org/10.1182/blood-2021-144617.
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Abstract Introduction: The approval of extended half-life recombinant factor IX (rFIX) replacement products has expanded the range of therapeutic options available for the treatment of hemophilia B. Compared with standard half-life FIX, these products allow for extended dosing intervals while maintaining appropriate bleed control. One such extended half-life product is rIX-FP (IDELVION; CSL Behring), a recombinant fusion protein linking rFIX with recombinant albumin, offering the possibility of dosing up to every 21 days in adults. The ATHN 2: Factor Switching Study provides information on patient outcomes following a switch from a previous FIX product to rIX-FP. Methods: ATHN 2 was a factor-switching study sponsored by the American Thrombosis and Hemostasis Network (ATHN) conducted in participants across the US hemophilia treatment center (HTC) network. This was a multi-center, longitudinal, observational study with two arms: a prospective arm following participants for up to one year after switching factor replacement product, and a retrospective arm including participants who have switched products within the 50 weeks prior to enrollment with retrospective and/or prospective assessment for up to one year. Male and female children and adults (≥2 years) with FIX clotting activity ≤5% of normal who had previously been treated with plasma-derived or recombinant FIX for at least 50 exposure days were eligible for inclusion. Treatment was administered at the discretion of the participant's hemophilia caregiver. Data was collected at study/clinic visits, or via a telephone interview conducted every three months. Baseline demographic data was collected for all participants. The prescribed dosing frequency for each participant was collected before and after the switch to rIX-FP, including dosing frequency taken from the first and last treatment records taken during the study following the switch. Participants were also asked to rank their satisfaction with rIX-FP upon the completion or early termination of the study. Results: A total of 41 participants were included in this analysis; 27 in the prospective arm and 14 in the retrospective arm. The mean (SD) age across all participants was 22.5 (17.1) years, ranging from 2 to 71 years. The median age was 18 years old and most participants had severe hemophilia B (FIX activity <1%; n=26, 63%). Prior to the switch to rIX-FP, 76% (n=31) of participants were receiving prophylaxis and 24% (n=10) received episodic treatment. The majority of participants (62%) receiving prophylaxis were treated twice a week (Table 1). Following the treatment switch, 93% of participants were initially assigned to a once-weekly or less frequent dosing regimen. This proportion remained stable over the course of the study, with 89% of participants on once-weekly or less frequent prophylaxis by the time of the last record taken. Among 23 participants with complete data on their prophylaxis dose interval before and after treatment switch, 70% of the participants were able to extend their dose frequency and maintain the extended dose frequency through the study. Thirty-seven participants responded to the satisfaction survey, with the majority (n=33, 89%) being somewhat or very satisfied with rIX-FP treatment. Conclusions: Switching to rIX-FP allowed participants to extend their prophylaxis dosing interval and a majority of participants were able to maintain the extended dose interval through the study period. In addition, a majority of participants were satisfied with rIX-FP treatment, altogether suggesting that extended half-life factor replacement with rIX-FP offers a valuable treatment option for hemophilia B. Figure 1 Figure 1. Disclosures Journeycake: HEMA Biologics: Honoraria; LFB: Honoraria. Chrisentery-Singleton: Biomarin: Speakers Bureau; Kedrion: Consultancy; Takeda: Consultancy, Speakers Bureau; Spark: Consultancy, Research Funding; Sanofi: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Hema Biologics: Consultancy; Grifols: Consultancy; Genentech: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau. Desai: CSL Behring: Current Employment. von Drygalski: Pfizer: Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hematherix, Inc: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Super FVa; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; uniQure: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Patel: CSL Behring: Current Employment. Raffini: CSL Behring: Consultancy; Genentech: Consultancy; HEMA Biologics: Consultancy; Bayer: Consultancy; XaTek: Consultancy. Recht: Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Catalyst Biosciences: Consultancy. Sidinio: Biomarin: Consultancy; Takeda: Consultancy, Research Funding; Pfizer: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Guardian Therapeutics: Consultancy; Octapharma: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; Catalyst: Consultancy. Wang: Bayer: Consultancy; Biomarin: Consultancy; CSL Behring: Consultancy; Genentech: Consultancy; Hema Biologics: Consultancy; Novo Nordisk: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; uniQure: Consultancy. Zhang: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Neufeld: Pfizer: Consultancy; Chiesi: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Octapharma: Consultancy, Research Funding; Acceleron Pharma: Consultancy; Baxter: Consultancy; Shire: Consultancy; Takeda: Consultancy; CSL: Consultancy; Biogen: Consultancy; Novo Nordisk: Consultancy; Bristol Myers-Squibb: Consultancy; ATHN: Research Funding; Celgene: Research Funding.
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Brooks, Roy. "Black Boarding Academies as a Prudential Reparation". Columbia Journal of Race and Law 13, n.º 1 (30 de maio de 2023): 790–852. http://dx.doi.org/10.52214/cjrl.v13i1.11665.
Texto completo da fonteResumo:
With billions of dollars pledged and trillions of dollars demanded to redress slavery and Jim Crow (“Black Reparations”) the question of how best to use these funds has moved into the forefront of the ongoing campaign for racial justice in our post-civil rights society. Reparatory strategies typically target the norms and structures that sustain racial disadvantage wrought by slavery and Jim Crow. The goal of such transitional reparations is to extinguish the menace of white supremacy and systemic racism across the board. Restructuring in housing, education, employment, voting, law enforcement, health care, and the environment—social transformation—is absolutely needed in the United States if the race problem is ever to be resolved. That much is clear beyond peradventure. The hard question, however, is whether Black Reparations can take us there. Are Black Reparations (or reparations in general) powerful enough to engineer social transformation, or what in this case would be “transitional racial justice”? Unfortunately, I do not believe they can. The American race problem is simply too big for reparations to fix. It would take decades of massive amounts of government spending and the sustained moral commitment of the American people to achieve transitional racial justice in this country. The inflationary impact of the requisite spending (estimated at $6.4 trillion to $59.2 trillion) would give opponents of reparations an easy target. Moreover, transitional reparations have rarely been attempted in other countries and when tried it has never succeeded to my knowledge. South Africa attempted to use reparations for social transformation. While there has been a transformation of political power, giving Black South Africans a strong voice in the government, economic power remains in the hands of White South Africans and racial discrimination in housing and education continues. Although at one time I was among scholars who had hoped Black Reparations could deliver a much-needed Third Reconstruction, I would be remiss as a passionate supporter of Black Reparations for many decades to ignore the cold facts—reparations have never successfully reconstructed a society.
But the perfect should not be the enemy of the good. While Black Reparations may not be sufficient for transitional racial justice, they can still play an important role in moving toward that goal. This Article attempts to show one way of doing so. It argues that the initial payment of Black Reparations should take the shape of an education reparation. Education can, as it has in the past with Brown v. Board of Education, provide a foundation for significant racial progress. The type of education reparation broached in this Article gives African American (or Black American) parents or guardians a unique choice for educating their children—Black Boarding Academies (BBAs). Kick started with public reparations, BBAs would begin with PK-3 low-income Black children, giving special attention to those at risk of falling into the dreadful foster care system, and would expand to accommodate other classes of Black students once financially stable with post-reparations funding. Like most public boarding schools, BBAs will have to be sustained with both public and private funds. Fortunately, there is a wide range of available sources. Historically, boarding schools have a poor reputation in educating children of color, especially Indigenous Americans. The few primary and secondary schools that board Black students have not experienced such problems. Neither have Historically Black Colleges and Universities (HBCUs) at the postsecondary education level. Following in this rich tradition, BBAs will provide a safe and nurturing environment for Black students. Pedagogically, BBAs will prepare students not just to survive but to thrive. Students will be prepared to assume positions of leadership in our society whether they go directly into the job market or matriculate at HBCUs or predominantly white institutions. One of the most effective instructional models in the country for leadership-oriented teaching can be found in elite New England Prep Schools. They have been doing this for centuries. Using a modified version of their pedagogy—one self-consciously infused with a racial sensibility—BBAs will be able to extend the pipeline to leadership, normally available to upper-income and even middle-income African American students, to low-income African American students. Indeed, the latter are the most vulnerable descendants of the enslaved.