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"Coplan, Scott"
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Frequent and unpredictable changes in COVID-19 policies and restrictions reduce the accuracy of model forecasts
Between June and August 2020, an agent-based model was used to project rates of COVID-19 infection incidence and cases diagnosed as positive from 15 September to 31 October 2020 for 72 geographic settings. Five scenarios were modelled: a baseline scenario where no future changes were made to existing restrictions, and four scenarios representing small or moderate changes in restrictions at two intervals. Post hoc, upper and lower bounds for number of diagnosed Covid-19 cases were compared with actual data collected during the prediction window. A regression analysis with 17 covariates was performed to determine correlates of accurate projections. It was found that the actual data fell within the lower and upper bounds in 27 settings and out of bounds in 45 settings. The only statistically significant predictor of actual data within the predicted bounds was correct assumptions about future policy changes (OR 15.04; 95% CI 2.20–208.70; p = 0.016). Frequent changes in restrictions implemented by governments, which the modelling team was not always able to predict, in part explains why the majority of model projections were inaccurate compared with actual outcomes and supports revision of projections when policies are changed as well as the importance of modelling teams collaborating with policy experts.
Journal Article
A Monoclonal Antibody Recognizing Human Cancers with Amplification/Overexpression of the Human Epidermal Growth Factor Receptor
Epidermal growth factor receptor (EGFR) has attracted considerable attention as a target for cancer therapy. Wild-type (wt)EGFR is amplified/overexpressed in a number of tumor types, and several mutant forms of the coding gene have been found, with Δ EGFR, a deletion mutation lacking exons 2-7 of the external domain, being the most common and particularly associated with glioblastoma. We generated monoclonal antibodies (mAbs) against NR6Δ EGFR(mouse fibroblast line NR6 transfected with Δ EGFR). mAb 806 with selective reactivity for NR6Δ EGFRin mixed hemadsorption assays, fluorescence-activated cell sorting, Western blot, and immunohistochemistry was analyzed in detail and compared with mAbs 528 (anti-wtEGFR) and DH8.3 (anti-Δ EGFR). In xenograft tumors and molecularly pretyped glioblastomas, the reactivity pattern was as follows: 528 reactive with amplified and nonamplified wtEGFR; DH8.3 reactive with Δ EGFR; and 806 reactive with amplified/overexpressed wtEGFR (with or without Δ EGFR). In normal tissues, 528 but not DH8.3 or 806 was widely reactive with many organs, e.g., liver expressing high EGFR levels. In glioblastoma and non-CNS tumor panels, 806 was reactive with a high proportion of glioblastomas and a substantial number of epithelial cancers of lung and of head and neck. DH8.3 reactivity was restricted to Δ EGFR-positive glioblastoma. Thus, 806 represents a category of mAbs that recognizes tumors with EGFR amplification/overexpression but not normal tissues or tumors with normal EGFR levels. Our study also indicates that Δ EGFR is restricted to glioblastoma, in contrast to other reports that this mutation is found in tumors outside the brain.
Journal Article
Cross-Reactivity of Anti–HIV-1 T Cell Immune Responses among the Major HIV-1 Clades in HIV-1–Positive Individuals from 4 Continents
BackgroundThe genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti–HIV-1 T cell responses to the infecting HIV-1 clade relative to other major circulating clades MethodsCellular immune responses to HIV-1 clades A, B, and C were compared by standardized interferon-γ enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV-1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV-1 ResultsCellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade reactivity of cellular immune responses to HIV-1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89–1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62–0.73]). The difference in cross-clade reactivity to Nef and Gag proteins was significant (P<.0001) ConclusionsCross-clade reactivity of cellular immune responses can be substantial but varies by viral protein
Journal Article
Impact of Indinavir on the Quality of Life in Patients with Advanced HIV Infection Treated with Zidovudine and Lamivudine
Objective. In AIDS Clinical Trial Group (ACTG) study 320, triple-combination antiretroviral therapy including indinavir significantly slowed progression to acquired immunodeficiency syndrome or death, compared with treatment with dual nucleoside reverse-transcriptase inhibitors (NRTIs) alone, in zidovudine-experienced patients with advanced human immunodeficiency virus (HIV) infection. We examined the impact of indinavir on quality of life in participants from this study.
Journal Article