Distinguished Chair Research Articles

Two-Sided Cultural Fit: The Differing Behavioral Consequences of Cultural Congruence Based on Values Versus Perceptions

How do people establish and maintain cultural fit with an organization? Prior research has offered two perspectives that have heretofore been conceptually disconnected. One focuses on personal values, whereas another emphasizes perceptions of the cultural code. We develop a theoretical account that integrates these approaches by linking them to distinct mechanisms and behavioral consequences of cultural fit. We propose that value congruence—the match between one’s values and those that prevail in an organization—relates to the mechanism of group attachment and shapes behavior when one periodically steps back from day-to-day interactions, assesses one’s identification with an organization, and determines whether to stay or voluntarily depart. In contrast, we argue that perceptual congruence—the degree to which one implicitly understands an organization’s prevailing values and norms—relates to the mechanism of interpersonal coordination and influences behavior when one engages in routine peer interactions. Accordingly, we theorize that these two forms of cultural fit relate to distinct behaviors, voluntary exit and linguistic conformity with peers, respectively. Drawing on email and survey data from a midsized technology firm, we find support for our theory and discuss the implications of our findings for research on person-culture fit, dual-process models of culture and cognition, and the pairing of surveys with digital trace data. Funding: This work was supported by the Berkeley Culture Center, the Cortese Distinguished Chair in Management, the Grether Chair of Business Administration and Public Policy.

Kimberly Prather wins Esselen Award

The 36th Gustavus John Esselen Award for Chemistry in the Public Interest has been awarded to Kimberly A. Prather , distinguished chair in atmospheric chemistry at the Scripps Institution of Oceanography, University of California San Diego. The Esselen Award recognizes chemists whose scientific and technical achievements have contributed to the public good and enhanced the public’s perception of chemistry. Prather is being honored for her use of mass spectrometry to characterize individual aerosols in the atmosphere. Her discoveries have clarified the impact of aerosols on climate, air pollution, water quality, and disease transmission. Most recently, in media interviews and briefings with public health and other leaders, Prather has spotlighted the importance of acknowledging aerosol transmission to reduce the spread of COVID-19. Prather will receive her award during a ceremony at Harvard University on April 14, after which she will deliver a public lecture titled “Tiny Critters, Huge Impacts: How Microbes

Harvard Hospital Names Chair in Nadelson’s Honor

Back to table of contents Previous article Next article APA & MeetingsFull AccessHarvard Hospital Names Chair in Nadelson’s HonorKatie O'ConnorKatie O'ConnorSearch for more papers by this authorPublished Online:29 Nov 2022https://doi.org/10.1176/appi.pn.2022.12.12.5AbstractBrigham and Women’s Hospital established the Carol C. Nadelson, M.D., Distinguished Chair in Psychiatry in honor of APA’s first woman president. Hemioni Amonoo, M.D., M.P.P., was appointed the chair’s inaugural incumbent.For past APA President Carol Nadelson, M.D., it all began in Brooklyn, N.Y. As a little girl, she announced to her parents that she wanted to be a doctor. She was told, “But girls don’t do that.”While completing her training at Beth Israel Medical Center, Carol Nadelson, M.D., and her peers opened the first daycare center for women faculty, as well as a rape crisis center.Yet now, Harvard Medical School’s Brigham and Women’s Hospital has established the Carol C. Nadelson, M.D., Distinguished Chair in Psychiatry as an enduring tribute to the profound impact Nadelson has had on generations of patients, trainees, women clinicians, and colleagues, said Robert Higgins, M.D., M.S.H.A., president of Brigham and Women’s Hospital and executive vice president at Mass General Brigham. Higgins spoke at an event last June to honor Nadelson and the chair’s inaugural incumbent, Hermioni Amonoo, M.D., M.P.P.“This is an enormous honor and quite a surprise to me,” Nadelson told Psychiatric News. She was APA’s first woman president, serving in that position for the 1985-1986 term. She was also the first editor in chief of APA Publishing (Psychiatric News https://psychnews.psychiatryonline.org/doi/10.1176/appi.pn.2019.8a20).Nationally, 41, or 35%, of the 116 chairs of psychiatry departments were women in 2021, the year for which the most recent data are available, according to the Association of American Medical Colleges. That percentage is higher than the national average of women who are department chairs in the clinical sciences, which is 24%. Comparatively, 22% of the chairs were women in internal medicine departments, 43% were women in pediatric departments, and 1% were women in surgery departments.The experience for women in medicine has changed drastically since Nadelson completed her training. During her speech at the June event, she shared how, as the only woman in her pre-med program, she was not taken seriously and was harassed and mercilessly teased. She experienced the same treatment in medical school, where there were, at most, only two women in each of her classes. “The landscape for women at that point was not promising,” Nadelson said during her speech, noting that the changes for women that were taking place in the rest of culture and society were not evident in medical education.She completed her training at Beth Israel Medical Center in Boston, where the chair of psychiatry was a woman. “That was incredibly reassuring, and it gave the women a chance to live in a community that was open,” Nadelson said.In 1998, Nadelson was asked to develop the Office for Women’s Careers at Brigham and Women’s Hospital. Upon taking that position, she met with every department chair and division chief to review their women faculty and learn why they were not getting promoted. She helped the women faculty write the papers and get into the positions necessary to advance their careers, helping to develop a fellowship program that offered support for women who were also juggling other responsibilities, like taking care of their children.Eventually, Nadelson would return to teaching and mentoring residents. During the June event, David A. Silbersweig, M.D., noted that Nadelson is still involved in supporting her mentees and their projects. “Carol is a pioneer in the true sense of the word in psychiatry and for women in medicine,” said Silbersweig, who is chair of the Department of Psychiatry and Institute for the Neurosciences at Brigham and Women’s and Faulkner hospitals.During her remarks, Amonoo called Nadelson “an illustrious woman, pacesetter, and a true role model.”“We all have so much to learn from you,” she continued, speaking to Nadelson. “Being named the inaugural incumbent of this chair that bears your name is such an honor.” ■“Recording of the celebration of the creation of the Carol C. Nadelson, M.D., Distinguished Chair in Psychiatry” ISSUES NewArchived

Abstract 3975: Clonal emergence of resistance to methotrexate in osteosarcoma barcoded PDX cells

Abstract Introduction: Osteosarcoma is known to have significant intratumoral heterogeneity. In order to elucidate the clonal emergence of resistance to targeted and cytotoxic chemotherapy in osteosarcoma we have worked on barcoding our cell lines derived from patient derived xenograft (PDX) models. Methods: The cell lines were derived from the PDX models by disaggregation and serial culture using STR to confirm the identity of each of the derived cell lines. The cell lines were barcoded using a lentiviral vector to transduce cells with a unique DNA transcript that was incorporated into the tumor cell genome. Two different cytoxicity assays, the Alamar Blu Cytotoxicity test in combination with the Incucyte® Cytotxicity Assay protocol, were used to evaluate the resistance of the PDX cells to the drug Methotrexate (MTX) that is largely used in the treatment of this disease. Further evaluation of the clonality of the resistant cells will be performed by sequencing the barcodes which will be complemented by functional assays of MTX transport, metabolism and target inhibition. Results: The PDX derived cell lines (n=10) were exposed to serial concentrations of MTX with different exposure durations obtaining the IC50 (range 0.23-376 uM) and IC95 (range 0.8- 4500 uM) for each PDX cell line. Subsequently every PDX cell line previously tested was exposed to the IC95 of MTX, in the same conditions used before, in order to obtain clones resistant to MTX. Numerous clones (72 clones from 10 cell lines) have been obtained. For each clone DNA and RNA has been extracted in order to perform sequencing of the DNA barcoded to determine if the genomic signature of the resistant clones is present in a subpopulation at the onset of treatment and if resistance arises from Darwinian selection or from stochastic alterations during and potentially related to treatment lead to emergence of a new resistant phenotype. RNA sequencing (RNA-Seq) will suggest the pathway alterations that may be associated with the emergence of resistance. Functional assays of MTX resistance will further define the basis of the resistance that emerged. Conclusion: Barcoded PDX derived osteosarcoma cell lines have been created with resistant clones obtained after MTX treatment. Sequencing of barcodes, RNA-Seq profiling and functional assays will yield critical information on the clonality and mechanisms of resistance which will be presented. This work was supported by SAA, Inc., The Foster Foundation and the Barbara Epstein Foundation. Richard Gorlick receives support as the H. Grant Taylor, M.D., W.W. Sutow, M.D. and Margaret P. Sullivan, M.D. Distinguished Chair. Citation Format: Giuseppe Longo, Sylvester Jusu, Zhongting Zhang, Zhaohui Xu, Wendong Zhang, Michael Roth, Rui Yang, Douglas Harrison, Jonathan Gill, Richard Gorlick. Clonal emergence of resistance to methotrexate in osteosarcoma barcoded PDX cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3975.

“Demons of the Biocentric Worldview”: A Queer Conversation with Susan Stryker

Susan Stryker is professor emerita of gender and women's studies. Since retiring from UofA, she has been Presidential Fellow and Visiting Professor of Gender, Women's, and Sexuality Studies at Yale University (2019-2020) and Barbara Lee Distinguished Chair in Women's Leadership, Mills College (2020-2022). She continues to serve as executive editor of TSQ: Transgender Studies Quarterly, and as co-editor of the Duke University Press book series ASTERISK: gender, trans-, and all that comes after. She is the author of Transgender History: The Roots of Today's Revolution (2008, 2017), co-editor of the two-volume Transgender Studies Reader (2006, 2013) and The Transgender Studies Reader Remix (2022), as well as co-director of the Emmy-winning documentary film Screaming Queens: The Riot at Compton's Cafeteria (2005). She is currently working to complete her book manuscript, Changing Gender: A Trans History of North America from Colonization to the Present (under contract to Farrar Straus Giroux), and developing a variety of film and television projects.

Nitration of CCL2 disrupts the tumor-protective function of CCL2 in bladder cancer

Abstract The chemokine CCL2 (C-C motif ligand 2) is best known for its ability to induce trafficking of immune cells by binding its primary receptor, CCR2. The recruitment of immunosuppressive monocytes by CCL2 promotes cancer in several tumor types. Surprisingly, we previously found an unanticipated protective role for CCL2 signaling in bladder cancer (BC). To determine if CCL2’s effect to suppress bladder tumor growth is dependent on T cells, we examined the effects of α-CCL2 antibody in wild-type versus T cell-deficient mice. The protective effect of CCL2 was lost in T cell-deficient mice and on T cell depletion in wild-type mice. Mixed bone marrow chimera experiments also showed that CCR2+ T cells were preferentially recruited by CCL2 to the bladder compared with CCR2− T cells suggesting that the protective effect of CCL2 in BC is through CCR2+ T cells. Most studies researching chemokines, including CCL2, in cancer assume the chemokine to be completely active and do not consider their different modified states which may be one of the critical reasons behind the failure of chemokines in clinical trials. We show for the first time that bladder tumors induce post-translational nitration of CCL2 and block T cell recruitment to the bladder which is restored by exogenous recombinant (r) CCL2 treatment. However, the chemical nitration of rCCL2 abolished this therapeutic efficacy of rCCL2 and was associated with decreased bladder T cell infiltration and more monocytes infiltration in BC. Our study analyzed the role of nitrated CCL2 in BC which explained certain paradoxes between CCL2 levels and patient outcomes in cancer. We also developed a novel BC treatment strategy using rCCL2 which should lead to effective combinations with existing BC immunotherapies. Supported by (1) the Mays Family Cancer Center at University of Texas Health San Antonio (P30 CA054174), (2) the Roger L. And Laura D. Zeller Charitable Foundation Chair in Urologic Cancer, (3) the Glenda and Gary Woods Distinguished Chair in GU Oncology, (4) the Max & Minnie Tomerlin Voelcker Fund, (5) CDMRP CA170270/P1P2, (6) Bladder Cancer Advocacy Network (BCAN), (7) Research Training Award (RP170345) from the Cancer Prevention & Research Institute of Texas (8) MSTP Program (NIH T32GM113896)

Contributors

REBECCA ANDERSEN teaches US History and Public History at Utah State University. She received a PhD in history from Arizona State University. Her work centers on twentieth-century Mormon environmental and urban history and has been published in the Utah Historical Quarterly. Andersen's recent book chapter, “‘For the Strength of the Hills’: Casting a Concrete Zion” appeared in The Earth Will Appear as the Garden of Eden: Essays in Mormon Environmental History (2019).SARA DANT is Brady Presidential Distinguished Professor and Chair of History at Weber State University. Her work focuses on environmental politics in the United States, with a particular emphasis on the creation and development of consensus and bipartisanism. She is the author of Losing Eden: An Environmental History of the American West, an advisor and interviewee for Ken Burns's forthcoming documentary film The American Buffalo, the author of several prize-winning articles on western environmental politics, the co-author of the two-volume Encyclopedia of American National Parks, and the author of chapters for three books on Utah.WILLIAM T. PARRY is Professor Emeritus of Geology and Geophysics at the University of Utah. He taught geological subjects at Texas Tech University and the University of Utah and has worked for oil and mining companies. Parry's latest book is Utah's Nineteenth-Century Stone Quarries (2020). His wife Gayle is the great-granddaughter of William S. Godbe and the granddaughter of Anthony H. Godbe.LAURIE J. BRYANT spent her childhood in what were then the wilds of southern California—hills and deserts, bays and beaches—and she chose a career that allowed her to work in those places, paleontology. After earning a Bachelor's degree in geology at Occidental College, she went to the South Dakota School of Mines to study with the famous R. W. Wilson, and then to the University of California, Berkeley. Bryant's two sons grew up as she did, in the outdoors. After a series of consulting jobs, she became one of the first Regional Paleontologists for the Bureau of Land Management, first in Wyoming and then in Utah. Thanks to the influence of Thomas Carter and W. Randall Dixon, Utah's history and architecture captured Bryant's interest after she retired and have held it ever since.MICHAEL W. HOMER is a Salt Lake City trial lawyer who has written books and articles concerning Utah and Mormon history. He is the past chair of the Utah Board of State History, a fellow of the Utah State Historical Society, chair of the J. Willard Marriott Library Advisory Board, a member of the Baker Street Irregulars and the Sherlock Holmes Society of London, and a past president of the Alta Club. He serves as the Honorary Italian Consul in Utah and was recently recognized by the President of the Italian Republic as a Cavaliere dell'Ordine della Stella D'Italia (Knight of the Order of the Star of Italy).

Contributors

Contributors

Preface

In order to accelerate the development of advanced manufacturing, promote in-depth integration of the Internet, big data, artificial intelligence and the real economy, and foster new growth areas and new drivers in such areas as high-end and medium consumption, innovation-driven development, green and low-carbon development, sharing economy, modern supply chain and human capital services. Computer Academy of Guangdong, Association of Computing Education in Chinese Universities, and Zhuhai Ton-Bridge Medical Technology together with AEIC Academic Exchange Information Center, hosted the 2021 Guangdong-Hong Kong-Macao Greater Bay Area Artificial Intelligence and Big Data Forum (AIBDF 2021) in Zhuhai, China during September 24 to 26, 2021.This conference focused on artificial intelligence, big data and medical and big health AI science, aimed to provide a platform for experts and scholars, engineers and researchers to share scientific research results and cutting-edge technologies, understand academic development trends, broaden research ideas, strengthen academic research and discussion, and promote cooperation in the industrialization of academic achievements.About 300 participants from academic, high-education institutes and other organizations took part in the conference. The conference model was divided into two sessions, including oral presentations and keynote speeches. In the first part, some scholars, whose submissions were selected as the excellent papers, were given 15 minutes to perform their oral presentations one by one. Then in the second part, keynote speakers were each allocated 30-45 minutes to hold their speeches. We were very honored to have Prof. Guoqiang Han, from South China University of Technology as our Conference Chairman.In the keynote presentation part, we invited 16 professors as our keynote speakers. The first keynote speaker, Prof. Junlong Chen, Distinguished Chair Professor, Doctoral Supervisor, Dean of School of Computer Science and Engineering, from South University of Technology. The others keynote speakers as follow: Prof. Guoliang Chen, Parallel algorithms, high performance computing experts; Prof. Anhui Liang, the director of the interdisciplinary research center of optical fiber communication and bio-optics, Shandong University of Science and Technology; Prof. Weijia Jia, from International College of Beijing Normal University-Hong Kong Baptist University; Prof. Zhengtian Fang, from La Trobe University in Australia; Prof. Yutong Lu, from Sun Yat-sen University; Prof. Young Liang, from Macau University of Science and Technology; Prof. Nong Xiao, from Sun Yat-sen University; Prof. Xiaofeng Zhu, from University of Electronic Science and Technology of China; Prof. Jianxin Wang, from Central South University; Prof. Xuan Wang, from Harbin Institute of Technology institute; Prof. Guoqiang Zhong, a member of ACM, IEEE, IAPR and China computer society; Prof. Bing Shi, a member of IEEE, ACM and CCF; Assoc. Prof. Chunjiang Duanmu, from Zhejiang Normal University; Prof. Yang Yue, from Nankai University; Prof. Na Li, from Xi’dian University.The proceedings present a selection of high-quality papers submitted to the conference by researchers from universities, research institutes, and industry. All papers were subjected to peer-review by conference committee members and international reviewers. The papers were selected based on their quality and their relevance to the conference. The proceedings present recent advances in the fields of Direction of Big data, Direction of Artificial Intelligence, Direction of Medical and health care and others related research.I would like to express special gratitude to members of the conference committee and organizers of the conference. I would also like to thank the reviewers for their valuable time and advice which helped in improving the quality of the papers selected for presentation at the conference and for publication in the proceedings. Finally, I want to thank the authors, the members of the organizing committee, the reviewers, the chairpersons, sponsors, and all other conference participants for their support of AIBDF 2021.The Committee of AIBDF 2021List of Committee member are available in this pdf.

Cross-sector storage and modeling needed for deep decarbonization

Noah Kittner is an assistant professor in energy in the Department of Environmental Sciences and Engineering, Gillings School of Global Public Health and in the Environment, Ecology, and Energy Program at the University of North Carolina at Chapel Hill. His research examines the role of energy storage in the transition to low-carbon energy systems and deep decarbonization. Sergio Castellanos is an assistant professor in the Department of Civil, Architectural and Environmental Engineering at the University of Texas at Austin, where he leads the Rapid, Equitable & Sustainable Energy Transitions (RESET) Lab focusing on equitable pathways for decarbonized energy systems. Patricia Hidalgo-Gonzalez is an assistant professor in the Jacobs School of Engineering and an affiliate member in the Center for Energy Research at the University of California, San Diego. She is the director of the Renewable Energy and Advanced Mathematics Laboratory. She is one of the academic co-leads of the IEEE Power & Energy Society Task Force "Data-Driven Controls for Distributed Systems." Her research focuses on high penetration of renewable energy using optimization, control theory, and machine learning with safety guarantees. Daniel M Kammen is the James and Katherine Lau Distinguished Chair in Sustainability, and Chair of the Energy and Resources Group, Professor in the Goldman School of Public Policy, and Professor of Nuclear Engineering at the University of California, Berkeley. He has served as Chief Technical Specialist for Renewable Energy and Energy Efficiency at the World Bank, and Science Envoy in the US Department of State. His work is focused on the science and policy of decarbonization at scales from homes to villages to large utility-scale systems. He has been a Coordinating Lead Author for the IPCC since 1999. Sarah Kurtz is a Professor at the University of California Merced. She spent more than 30 years at the National Renewable Energy Laboratory studying multi-junction III-V solar cells, reliability of photovoltaic modules and systems, and other solar-related projects. She is now leading a study of the value of long-duration storage, funded by the California Energy Commission.

Steven McKnight wins Welch Award

Steven L. McKnight, Distinguished Chair in Basic Biomedical Research at the University of Texas Southwestern Medical Center, is the winner of the 2020 Robert A. Welch Award in Chemistry. The $500,000 prize recognizes basic chemical research that benefits humankind. McKnight will also receive a gold medallion. “Steve McKnight has done creative and breakthrough science for decades,” Peter B. Dervan, chair of the Welch Foundation Scientific Advisory Board, says in a statement. “Throughout his 45-year career, he has used molecular, biochemical and biophysical methods to study regulatory pathways. These findings provided the initial conceptual framework for understanding how combinatorial models of DNA regulatory proteins generate the complex patterns of gene expression required for growth and development.” According to the award citation, McKnight is being honored “for his original contributions that identified the regulatory regions of eukaryotic genes, gene specific transcription factors, and the role of low complexity sequences in proteins that

Steven McKnight wins Welch Award

Steven L. McKnight, Distinguished Chair in Basic Biomedical Research at the University of Texas Southwestern Medical Center, is the winner of the 2020 Robert A. Welch Award in Chemistry. The $500,0...

International Response to COVID-19

Articles| August 2020 International Response to COVID-19 Audrée A. Bendo, MD, MS, FASA Audrée A. Bendo, MD, MS, FASA Audrée A. Bendo, MD, MS, FASA Distinguished Service Professor and Chair, Department of Anesthesiology, SUNY Downstate Health Sciences University, Brooklyn, New York. Search for other works by this author on: This Site PubMed Google Scholar ASA Monitor August 2020, Vol. 84, 39–40. https://doi.org/10.1097/01.M99.0000695220.96372.53 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Search Site Citation Audrée A. Bendo; International Response to COVID-19. ASA Monitor 2020; 84:39–40 doi: https://doi.org/10.1097/01.M99.0000695220.96372.53 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll PublicationsASA Monitor Search Advanced Search Topics: covid-19 As the COVID-19 pandemic unfolded this past winter, anesthesiologists have worked at the front lines, demonstrating their leadership role in clinical care and COVID-19 research. National anesthesiology societies worldwide have supported their members through information, clinical resources, and learning opportunities. For this annual article, ASA decided to highlight the actions of some of our international anesthesia society partners by asking them to tell us how they have been supporting their members during the pandemic. We thank them for their contributions and efforts to improve global health care during the COVID-19 pandemic. Dr. Luis Antonio Diego - Director of COVID-19 Committee Dr. Augusto Takaschima - Vice-President of SBA Dr. Rogean Nunes - President of SBA In response to COVID-19, the SBA established a task force to develop statements and guidelines for Portuguese- speaking health workers. These files, along with webinars, FAQs, and an online chat (with voluntary physicians), can be found... You do not currently have access to this content.

254-LB: Characterization of Ghrelin Receptor Expression in Mouse Islets Reveals Pancreatic Polypeptide Cells as a Key Ghrelin Target

Objective: While expression of the ghrelin receptor, GHSR (growth hormone secretagogue receptor), by pancreatic islets has been investigated, data regarding the specific islet cell types that express GHSR are inconsistent and incomplete. For instance, transcriptomic studies indicate marked GHSR expression by somatostatin (SST)-secreting delta cells vs. little to no GHSR expression by alpha cells and beta cells, which contrasts studies suggesting direct actions of ghrelin on GHSRs expressed by alpha cells and beta cells. Also, to our knowledge, GHSR expression by pancreatic polypeptide (PP) cells has not previously been directly investigated. The aims of this study were to determine GHSR expression within the four principal islet endocrine cell types and the effects of ghrelin on circulating PP. Methods: Ghsr-IRES-Cre mice, which express Cre recombinase directed by the GHSR promoter, crossed to Cre-dependent ROSA26-YFP reporter mice were used to histologically identify GHSR expression in islets. Double and triple labeling for YFP-immunoreactivity (IR) with insulin-IR, glucagon-IR, SST-IR, and/or PP-IR was performed to determine GHSR co-expression with islet hormones. Pharmacological manipulations were used to examine in vivo effects of acyl-ghrelin on plasma PP. Results: Eighty-five % of YFP-IR cells expressed PP-IR, 50% expressed SST-IR, and none expressed insulin-IR or glucagon-IR. GHSR antagonist raised plasma PP in overnight-fasted C57BL/6N mice. However, acyl-ghrelin administration had no effect on plasma PP in C57BL/6N mice. Conclusions: These results suggest that within mouse pancreatic islets, GHSR expression occurs most abundantly in PP cells and that pharmacologic blockade of ghrelin action raises plasma PP. Disclosure D. Gupta: None. B.K. Mani: None. K. Shankar: None. S. Osborne-Lawrence: None. N. Metzger: None. J.M. Zigman: Stock/Shareholder; Self; Medtronic. Funding Diana and Richard C. Strauss Professorship in Biomedical Research; Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine; Kent and Jodi Foster Distinguished Chair in Endocrinology; University of Texas Southwestern Medical Center (to J.M.Z.)

1892-P: Meal- and Glucose-Induced Suppression of Ghrelin Release Is Mediated Primarily by Ghrelin Cell-Expressed Insulin Receptors

Objective: The hormone ghrelin both regulates and is regulated by food intake and blood glucose. Yet, the mechanisms restricting ghrelin release after meals or upon glucose delivery have remained elusive. Here, we tested whether meal and glucose-associated rises in plasma insulin act via ghrelin cell-expressed insulin receptors to suppress ghrelin release. Methods: We generated ghrelin cell-selective insulin receptor-knock out (GIRKO) mice by crossing ghrelin-Cre mice with floxed-insulin receptor mice. We examined ghrelin release using hyperinsulinemic-hypoglycemic clamps, glucose tolerance tests (GTTs), a fast-refeed protocol, and gastric mucosal cell primary cultures. Results: During clamps, plasma ghrelin fell in WT control groups (by 85%) but not in GIRKO mice, leading to a 29% lower glucose infusion rate in GIRKO mice. During GTTs, plasma ghrelin was suppressed in controls (by 42%) but not in GIRKO mice. During the refeed phase of a fast-refeed protocol, plasma ghrelin fell in controls (by 49%) but not in GIRKO mice. Also, insulin suppressed ghrelin release in isolated ghrelin cells of controls (by 19%) but not of GIRKO mice. Conclusions: These data suggest that insulin, acting via ghrelin cell-expressed insulin receptors, is a key mediator of ghrelin release in response to meals, glucose administration, and insulin infusion. Further, suppressed ghrelin release resulting from direct insulin action on ghrelin cells restricts ghrelin’s capacity to protect against hypoglycemia during over-insulinization. Disclosure K. Shankar: None. S. Takemi: None. D. Gupta: None. B.K. Mani: None. S. Osborne-Lawrence: None. N. Metzger: None. E. Berglund: None. J.M. Zigman: Stock/Shareholder; Self; Medtronic. Funding National Institutes of Health (R01DK119341-01A1, R01DK103884 to J.M.Z.), (R01DK109408 to E.B.), (R01DK119341 to J.M.Z., E.B.); David and Teresa Disiere Foundation (to J.M.Z.); Diana and Richard C. Strauss Professorship in Biomedical Research; Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine; Kent and Jodi Foster Distinguished Chair in Endocrinology (to J.M.Z.); Uehara Memorial Foundation (to S.T.)

Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19

BackgroundCoronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context.MethodsUsing an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020.ResultsOf the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those ≤65 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74).ConclusionsOur study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital.)

RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

SummaryBackgroundHydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19.MethodsWe did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation).Findings96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.InterpretationWe were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.FundingWilliam Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.

An interview with Eric Olson.

Eric Olson is Professor and Chair of Molecular Biology at the University of Texas Southwestern Medical Center, USA, where he holds the Robert A. Welch Distinguished Chair in Science, the Annie and Willie Nelson Professorship in Stem Cell Research and the Pogue Distinguished Chair in Research in Cardiac Birth Defects. In 1999, he was elected to the US National Academy of Sciences and, in 2001, to the Institute of Medicine of the National Academy. He has received several awards, including the American Heart Association Research Achievement Award in 2008 and the Eugene Braunwald Academic Mentorship award in 2016. He has a lifelong interest in muscle development and disease, with a particular interest in Duchenne muscular dystrophy. In this interview, conducted at the Society for Developmental Biology's 2019 meeting in Boston, Massachusetts, USA, he discusses his experiences in academia and industry, as well as reflecting on the people and opportunities that contributed to his career.

Adi Gazdar, MD: one of the founders of the molecular pathology of cancer, a great scientist and a great man

Adi Gazdar, MD, a true giant in the field of lung cancer research, passed away aged 81 on December 29, 2018. Dr. Gazdar held the W. Ray Wallace Distinguished Chair in Molecular Pathology Research and was Professor of Pathology at the Hamon Center for Therapeutic Oncology Research and Department of Pathology at the University of Texas Southwestern Medical Center in Dallas, TX. Adi Gazdar was one of the first true “molecular pathologists” of lung cancer and help leaded the development of this area around the world through is publications, collaborations, and mentoring activities. He is survived by his wife of 49 years, Celia Gazdar.

In Memoriam: James T. Willerson, MD (1939-2020).

In Memoriam: James T. Willerson, MD (1939-2020).