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"Tipton, Sara M"
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English Language and the Medical Profession: Instructing and Assessing the Communication Skills of International Physicians
\"English Language and the Medical Profession: Instructing and Assessing the Communication Skills of International Physicians
eBook
Past and future global transformation of terrestrial ecosystems under climate change
Impacts of global climate change on terrestrial ecosystems are imperfectly constrained by ecosystem models and direct observations. Pervasive ecosystem transformations occurred in response to warming and associated climatic changes during the last glacial-to-interglacial transition, which was comparable in magnitude to warming projected for the next century under high-emission scenarios. We reviewed 594 published paleoecological records to examine compositional and structural changes in terrestrial vegetation since the last glacial period and to project the magnitudes of ecosystem transformations under alternative future emission scenarios. Our results indicate that terrestrial ecosystems are highly sensitive to temperature change and suggest that, without major reductions in greenhouse gas emissions to the atmosphere, terrestrial ecosystems worldwide are at risk of major transformation, with accompanying disruption of ecosystem services and impacts on biodiversity.
Journal Article
Safety and Immune Responses Following Anti-PD-1 Monoclonal Antibody Infusions in Healthy Persons With Human Immunodeficiency Virus on Antiretroviral Therapy
Abstract
Background
T cells in people with human immunodeficiency virus (HIV) demonstrate an exhausted phenotype, and HIV-specific CD4+ T cells expressing programmed cell death 1 (PD-1) are enriched for latent HIV, making antibody to PD-1 a potential strategy to target the latent reservoir.
Methods
This was a phase 1/2, randomized (4:1), double-blind, placebo-controlled study in adults with suppressed HIV on antiretroviral therapy with CD4+ counts ≥350 cells/μL who received 2 infusions of cemiplimab versus placebo. The primary outcome was safety, defined as any grade 3 or higher adverse event (AE) or any immune-related AE (irAE). Changes in HIV-1–specific polyfunctional CD4+ and CD8+ T-cell responses were evaluated.
Results
Five men were enrolled (median CD4+ count, 911 cells/μL; median age, 51 years); 2 received 1 dose of cemiplimab, 2 received 2 doses, and 1 received placebo. One participant had a probable irAE (thyroiditis, grade 2); another had a possible irAE (hepatitis, grade 3), both after a single low-dose (0.3 mg/kg) infusion. The Safety Monitoring Committee recommended no further enrollment or infusions. All 4 cemiplimab recipients were followed for 48 weeks. No other cemiplimab-related serious AEs, irAEs, or grade 3 or higher AEs occurred. One 2-dose recipient of cemiplimab had a 6.2-fold increase in polyfunctional, Gag-specific CD8+ T-cell frequency with supportive increases in plasma HIV RNA and decreases in total HIV DNA.
Conclusions
One of 4 participants exhibited increased HIV-1-specific T-cell responses and transiently increased HIV-1 expression following 2 cemiplimab infusions. The occurrence of irAEs after a single, low dose may limit translating the promising therapeutic results of cemiplimab for cancer to immunotherapeutic and latency reversal strategies for HIV.
Clinical Trials Registration. NCT03787095.
One of 4 participants administered anti-PD-1 antibody exhibited increased HIV-1–specific T-cell responses and transiently increased HIV-1 expression. Significant immune-related adverse events after a single, low dose of anti-PD-1 antibody may limit translating the benefits of anti-PD-1 therapies from cancer to HIV.
Journal Article
Randomized Clinical Trial to Assess the Impact of the Broadly Neutralizing HIV-1 Monoclonal Antibody VRC01 on HIV-1 Persistence in Individuals on Effective ART
Broadly neutralizing monoclonal antibodies (bnMAbs) may promote clearance of HIV-1-expressing cells through antibody-dependent cell-mediated cytotoxicity. We evaluated the effect of the CD4-binding site bnMAb, VRC01, on measures of HIV-1 persistence in chronically infected individuals.
A5342 was a phase 1, randomized, double-blind, placebo-controlled, parallel-arm study. Participants on effective antiretroviral therapy (ART) were randomized to receive 2 infusions of VRC01 (40 mg/kg) at entry and week 3, and 2 infusions of placebo (saline) at weeks 6 and 9; or 2 infusions of placebo at entry and week 3, and 2 infusions of VRC01 at weeks 6 and 9.
Infusion of VRC01 was safe and well tolerated. The median fold-change in the cell-associated HIV-1 RNA/DNA ratio from baseline to week 6 was 1.12 and 0.83 for the VRC01 and placebo arms, respectively, with no significant difference between arms (
= .16). There were no significant differences in the proportions with residual plasma viremia ≥1 copies/mL or in phorbol 12-myristate 13-acetate/ionomycin-induced virus production from CD4
T cells between arms (both
> .05).
In individuals with chronic HIV-1 infection on ART, VRC01 infusions were safe and well tolerated but did not affect plasma viremia, cellular HIV-1 RNA/DNA levels, or stimulated virus production from CD4
T cells.
NCT02411539.
Journal Article
Do Product Warnings Increase Safe Behavior? A Meta-Analysis
In a meta-analysis of warnings literature, the authors examine empirical studies containing no-warning control groups to address the question of whether the presence of on-product warnings increases the safe behavior of product users. The major findings of the study are that (1) warnings increase safe behavior and (2) this increase is found for both nonstudent and student subjects.
Journal Article