O5‐08‐01: Trends In Racial And Ethnic Differences In Dementia Prevalence Rates And Disease Awareness

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153266/1/alzjjalz2019064876.pd

Racial and Ethnic Differences in Knowledge About One’s Dementia Status

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156478/1/jgs16442.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156478/3/jgs16442_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156478/2/jgs16442-sup-0001-supinfo.pd

Regulation of Hepatic Triacylglycerol Metabolism by CGI-58 Does Not Require ATGL Co-activation

SummaryAdipose triglyceride lipase (ATGL) and comparative gene identification 58 (CGI-58) are critical regulators of triacylglycerol (TAG) turnover. CGI-58 is thought to regulate TAG mobilization by stimulating the enzymatic activity of ATGL. However, it is not known whether this coactivation function of CGI-58 occurs in vivo. Moreover, the phenotype of human CGI-58 mutations suggests ATGL-independent functions. Through direct comparison of mice with single or double deficiency of CGI-58 and ATGL, we show here that CGI-58 knockdown causes hepatic steatosis in both the presence and absence of ATGL. CGI-58 also regulates hepatic diacylglycerol (DAG) and inflammation in an ATGL-independent manner. Interestingly, ATGL deficiency, but not CGI-58 deficiency, results in suppression of the hepatic and adipose de novo lipogenic program. Collectively, these findings show that CGI-58 regulates hepatic neutral lipid storage and inflammation in the genetic absence of ATGL, demonstrating that mechanisms driving TAG lipolysis in hepatocytes differ significantly from those in adipocytes

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma

Background: Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells. Methods: In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival. Results: A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported. Conclusions: Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.). Copyright © 2021 Massachusetts Medical Society

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

PHANGS-ML: Dissecting Multiphase Gas and Dust in Nearby Galaxies Using Machine Learning

The PHANGS survey uses Atacama Large Millimeter/submillimeter Array, Hubble Space Telescope, Very Large Telescope, and JWST to obtain an unprecedented high-resolution view of nearby galaxies, covering millions of spatially independent regions. The high dimensionality of such a diverse multiwavelength data set makes it challenging to identify new trends, particularly when they connect observables from different wavelengths. Here, we use unsupervised machine-learning algorithms to mine this information-rich data set to identify novel patterns. We focus on three of the PHANGS-JWST galaxies, for which we extract properties pertaining to their stellar populations; warm ionized and cold molecular gas; and polycyclic aromatic hydrocarbons (PAHs), as measured over 150 pc scale regions. We show that we can divide the regions into groups with distinct multiphase gas and PAH properties. In the process, we identify previously unknown galaxy-wide correlations between PAH band and optical line ratios and use our identified groups to interpret them. The correlations we measure can be naturally explained in a scenario where the PAHs and the ionized gas are exposed to different parts of the same radiation field that varies spatially across the galaxies. This scenario has several implications for nearby galaxies: (i) The uniform PAH ionized fraction on 150 pc scales suggests significant self-regulation in the interstellar medium, (ii) the PAH 11.3/7.7 μm band ratio may be used to constrain the shape of the non-ionizing far-ultraviolet to optical part of the radiation field, and (iii) the varying radiation field affects line ratios that are commonly used as PAH size diagnostics. Neglecting this effect leads to incorrect or biased PAH sizes

PHANGS-ML: dissecting multiphase gas and dust in nearby galaxies using machine learning

The PHANGS survey uses ALMA, HST, VLT, and JWST to obtain an unprecedented high-resolution view of nearby galaxies, covering millions of spatially independent regions. The high dimensionality of such a diverse multi-wavelength dataset makes it challenging to identify new trends, particularly when they connect observables from different wavelengths. Here we use unsupervised machine learning algorithms to mine this information-rich dataset to identify novel patterns. We focus on three of the PHANGS-JWST galaxies, for which we extract properties pertaining to their stellar populations; warm ionized and cold molecular gas; and Polycyclic Aromatic Hydrocarbons (PAHs), as measured over 150 pc-scale regions. We show that we can divide the regions into groups with distinct multiphase gas and PAH properties. In the process, we identify previously-unknown galaxy-wide correlations between PAH band and optical line ratios and use our identified groups to interpret them. The correlations we measure can be naturally explained in a scenario where the PAHs and the ionized gas are exposed to different parts of the same radiation field that varies spatially across the galaxies. This scenario has several implications for nearby galaxies: (i) The uniform PAH ionized fraction on 150 pc scales suggests significant self-regulation in the ISM, (ii) the PAH 11.3/7.7 \mic~ band ratio may be used to constrain the shape of the non-ionizing far-ultraviolet to optical part of the radiation field, and (iii) the varying radiation field affects line ratios that are commonly used as PAH size diagnostics. Neglecting this effect leads to incorrect or biased PAH sizes.Comment: Main results in figures 6 and 12. Submitted to ApJ, and comments are welcome

Evaluating knowledge to support climate action: A framework for sustained assessment. report of an independent advisory committee on applied climate assessment.

Author Posting. © American Meteorological Society, 2019. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Weather Climate and Society 11(3), (2019):465-487, doi: 10.1175/WCAS-D-18-0134.1.As states, cities, tribes, and private interests cope with climate damages and seek to increase preparedness and resilience, they will need to navigate myriad choices and options available to them. Making these choices in ways that identify pathways for climate action that support their development objectives will require constructive public dialogue, community participation, and flexible and ongoing access to science- and experience-based knowledge. In 2016, a Federal Advisory Committee (FAC) was convened to recommend how to conduct a sustained National Climate Assessment (NCA) to increase the relevance and usability of assessments for informing action. The FAC was disbanded in 2017, but members and additional experts reconvened to complete the report that is presented here. A key recommendation is establishing a new nonfederal “climate assessment consortium” to increase the role of state/local/tribal government and civil society in assessments. The expanded process would 1) focus on applied problems faced by practitioners, 2) organize sustained partnerships for collaborative learning across similar projects and case studies to identify effective tested practices, and 3) assess and improve knowledge-based methods for project implementation. Specific recommendations include evaluating climate models and data using user-defined metrics; improving benefit–cost assessment and supporting decision-making under uncertainty; and accelerating application of tools and methods such as citizen science, artificial intelligence, indicators, and geospatial analysis. The recommendations are the result of broad consultation and present an ambitious agenda for federal agencies, state/local/tribal jurisdictions, universities and the research sector, professional associations, nongovernmental and community-based organizations, and private-sector firms.This report would not have been possible without the support and participation of numerous organizations and individuals. We thank New York State Governor Andrew M. Cuomo for announcing in his 2018 State of the State agenda that the IAC would be reconvened. The New York State Energy Research and Development Authority (Contract ID 123416), Columbia University’s Earth Institute, and the American Meteorological Society provided essential financial support and much more, including sage advice and moral support from John O’Leary, Shara Mohtadi, Steve Cohen, Alex Halliday, Peter deMenocal, Keith Seitter, Paul Higgins, and Bill Hooke. We thank the attendees of a workshop, generously funded by the Kresge Foundation in November of 2017, that laid a foundation for the idea to establish a civil-society-based assessment consortium. During the course of preparing the report, IAC members consulted with individuals too numerous to list here—state, local, and tribal officials; researchers; experts in nongovernmental and community-based organizations; and professionals in engineering, architecture, public health, adaptation, and other areas. We are so grateful for their time and expertise. We thank the members and staff of the National Academy of Sciences, Engineering, and Medicine’s Committee to Advise the U.S. Global Change Research Program for providing individual comments on preliminary recommendations during several discussions in open sessions of their meetings. The following individuals provided detailed comments on an earlier version of this report, which greatly sharpened our thinking and recommendations: John Balbus, Tom Dietz, Phil Duffy, Baruch Fischhoff, Brenda Hoppe, Melissa Kenney, Linda Mearns, Claudia Nierenberg, Kathleen Segerson, Soroosh Sorooshian, Chris Weaver, and Brian Zuckerman. Mary Black provided insightful copy editing of several versions of the report. We also thank four anonymous reviewers for their effort and care in critiquing and improving the report. It is the dedication, thoughtful feedback, expertise, care, and commitment of all these people and more that not only made this report possible, but allow us all to continue to support smart and insightful actions in a changing climate. We are grateful as authors and as global citizens. Author contributions: RM, SA, KB, MB, AC, JD, PF, KJ, AJ, KK, JK, ML, JM, RP, TR, LS, JS, JW, and DZ were members of the IAC and shared in researching, discussing, drafting, and approving the report. BA, JF, AG, LJ, SJ, PK, RK, AM, RM, JN, WS, JS, PT, GY, and RZ contributed to specific sections of the report.2020-05-2