The MASSIVE Survey. VI. The spatial sistribution and kinematics of warm ionized gas in the most massive local early-type galaxies

We present the first systematic investigation of the existence, spatial distribution, and kinematics of warm ionized gas as traced by the [O ii] 3727 Å emission line in 74 of the most massive galaxies in the local universe. All of our galaxies have deep integral-field spectroscopy from the volume- and magnitude-limited MASSIVE survey of early-type galaxies with stellar mass $\mathrm{log}({M}_{* }/{M}_{\odot })\gt 11.5$ (M K < −25.3 mag) and distance D < 108 Mpc. Of the 74 galaxies in our sample, we detect warm ionized gas in 28, which yields a global detection fraction of 38 ± 6% down to a typical [O ii] equivalent width limit of 2 Å. MASSIVE fast rotators are more likely to have gas than MASSIVE slow rotators with detection fractions of 80 ± 10% and 28 ± 6%, respectively. The spatial extents span a wide range of radii (0.6–18.2 kpc; 0.1–4R e ), and the gas morphologies are diverse, with 17/28 ≈ 61 ± 9% being centrally concentrated, 8/28 ≈ 29 ± 9% exhibiting clear rotation out to several kiloparsecs, and 3/28 ≈ 11 ± 6% being extended but patchy. Three out of four fast rotators show kinematic alignment between the stars and gas, whereas the two slow rotators with robust kinematic measurements available exhibit kinematic misalignment. Our inferred warm ionized gas masses are roughly ~105 M ⊙. The emission line ratios and radial equivalent width profiles are generally consistent with excitation of the gas by the old underlying stellar population. We explore different gas origin scenarios for MASSIVE galaxies and find that a variety of physical processes are likely at play, including internal gas recycling, cooling out of the hot gaseous halo, and gas acquired via mergers

A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19:Accord-2

BACKGROUND: Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95).METHODS: ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay.RESULTS: Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels.CONCLUSIONS: Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.</p

The Grizzly, October 1, 1991

Whittaker Relates Gulf Experience • Sorority Pledging Underway • U.S.E.A.C. Conference a Success • Ursinus Students Feel the Excitement of Habitat • College Tutorial Project Thrives • U.C. Welcomes New Instructors • Leadershop 1991 • U.S.G.A. Finds a Home • A Plea for Help • GN\u27R: Illusion ... of Good Music • State Museum Exhibits Berman Sculptures • Jane Ira Bloom Jazzes It Up • Sky Sands Strikes Ursinus • Aerobics Attack • The Tempting Temple • Field Hockey Faces Tough Times • Bears Terrorized by Western Maryland • Lady Bears Finish 4th • Bears Tee Off • Runners Get Recognition • Soccer Splits Two • Cross Country Cruises to 3rd Place • Gift to Give • Alcohol Policy Enforcement Tightens • Intellect Over Image • Wismer Whine • Healing the Wounds of the Gulf War • The Search For the Chemical Promisehttps://digitalcommons.ursinus.edu/grizzlynews/1278/thumbnail.jp

Abstracts from the NIHR INVOLVE Conference 2017

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Assembly of π-Conjugated Helical Peptides into a Porous and Evolvable Protein-like Lattice

The evolution of proteins from simpler, self-assembled peptides provides a powerful blueprint for the design of complex synthetic mate-rials. Previously, peptide–metal frameworks using short sequences (≤ 3 residues) have shown great promise as proteomimetic materials that exhibit sophisticated capabilities. However, their evolution has been hindered due to few mutable residues and restricted choice of side-chains that are compatible with metal ions. Herein, we developed a non-covalent strategy using π-stacking to assemble much longer peptides into crystalline frameworks that tolerate even previously incompatible acidic and basic functionalities, and allow an unprecedent-ed level of pore mutations. Single-crystal X-ray structures are provided for all mutants to guide and validate rational design. These materi-als exhibit hallmark protein behaviors such as guest-selective induced-fit and assembly of multi-metallic units. Significantly, we demon-strate facile evolution of the framework to substantially increase affinity towards a complex organic molecule

Infrastructure and operating processes of PIONEER, the HDR-UK Data Hub in Acute Care and the workings of the Data Trust Committee: a protocol paper.

INTRODUCTION Health Data Research UK designated seven UK-based Hubs to facilitate health data use for research. PIONEER is the Hub in Acute Care. PIONEER delivered workshops where patients/public citizens agreed key principles to guide access to unconsented, anonymised, routinely collected health data. These were used to inform the protocol. METHODS This paper describes the PIONEER infrastructure and data access processes. PIONEER is a research database and analytical environment that links routinely collected health data across community, ambulance and hospital healthcare providers. PIONEER aims ultimately to improve patient health and care, by making health data discoverable and accessible for research by National Health Service, academic and commercial organisations. The PIONEER protocol incorporates principles identified in the public/patient workshops. This includes all data access requests being reviewed by the Data Trust Committee, a group of public citizens who advise on whether requests should be supported prior to licensed access. ETHICS AND DISSEMINATION East Midlands-Derby REC (20/EM/0158): Confidentiality Advisory Group (20/CAG/0084). www.PIONEERdatahub.co.uk

Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies

Translating the genetic and epigenetic heterogeneity underlying human cancers into therapeutic strategies is an ongoing challenge. Large-scale sequencing efforts have uncovered a spectrum of mutations in many hematologic malignancies, including acute myeloid leukemia (AML), suggesting that combinations of agents will be required to treat these diseases effectively. Combinatorial approaches will also be critical for combating the emergence of genetically heterogeneous subclones, rescue signals in the microenvironment, and tumor-intrinsic feedback pathways that all contribute to disease relapse. To identify novel and effective drug combinations, we performed ex vivo sensitivity profiling of 122 primary patient samples from a variety of hematologic malignancies against a panel of 48 drug combinations. The combinations were designed as drug pairs that target nonoverlapping biological pathways and comprise drugs from different classes, preferably with Food and Drug Administration approval. A combination ratio (CR) was derived for each drug pair, and CRs were evaluated with respect to diagnostic categories as well as against genetic, cytogenetic, and cellular phenotypes of specimens from the two largest disease categories: AML and chronic lymphocytic leukemia (CLL). Nearly all tested combinations involving a BCL2 inhibitor showed additional benefit in patients with myeloid malignancies, whereas select combinations involving PI3K, CSF1R, or bromodomain inhibitors showed preferential benefit in lymphoid malignancies. Expanded analyses of patients with AML and CLL revealed specific patterns of ex vivo drug combination efficacy that were associated with select genetic, cytogenetic, and phenotypic disease subsets, warranting further evaluation. These findings highlight the heuristic value of an integrated functional genomic approach to the identification of novel treatment strategies for hematologic malignancies

A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2

Background: increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95).Methods: ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay.Results: efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels.Conclusions: overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.</p