Publications by authors named "C Frank Bennett"

2,443 Publications

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Comparison and impact of COVID-19 for patients with cancer: a survival analysis of fatality rate controlling for age, sex and cancer type.

BMJ Health Care Inform 2021 May;28(1)

Department of Biomedical Informatics, The University of Utah School of Medicine, Salt Lake City, Utah, USA

Objectives: Prior research has reported an increased risk of fatality for patients with cancer, but most studies investigated the risk by comparing cancer to non-cancer patients among COVID-19 infections, where cancer might have contributed to the increased risk. This study is to understand COVID-19's imposed HR of fatality while controlling for covariates, such as age, sex, metastasis status and cancer type.

Methods: We conducted survival analyses of 4606 cancer patients with COVID-19 test results from 16 March to 11 October 2020 in UK Biobank and estimated the overall HR of fatality with and without COVID-19 infection. We also examined the HRs of 13 specific cancer types with at least 100 patients using a stratified analysis.

Results: COVID-19 resulted in an overall HR of 7.76 (95% CI 5.78 to 10.40, p<10) by following 4606 patients with cancer for 21 days after the tests. The HR varied among cancer type, with over a 10-fold increase in fatality rate (false discovery rate ≤0.02) for melanoma, haematological malignancies, uterine cancer and kidney cancer. Although COVID-19 imposed a higher risk for localised versus distant metastasis cancers, those of distant metastases yielded higher overall fatality rates due to their multiplicative effects.

Discussion: The results confirmed prior reports for the increased risk of fatality for patients with COVID-19 plus hematological malignancies and demonstrated similar findings of COVID-19 on melanoma, uterine, and kidney cancers.

Conclusion: The results highlight the heightened risk that COVID-19 imposes on localised and haematological cancer patients and the necessity to vaccinate uninfected patients with cancer promptly, particularly for the cancer types most influenced by COVID-19. Results also suggest the importance of timely care for patients with localised cancer, whether they are infected by COVID-19 or not.
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http://dx.doi.org/10.1136/bmjhci-2021-100341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117441PMC
May 2021

Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant.

N Engl J Med 2021 May 5. Epub 2021 May 5.

From Novavax, Gaithersburg, MD (V.S., L. Fries, S.C.-C., M.Z., C.B., G.A., E.F., J.S.P., A.R., S.N., I.C., G.M.G., F.D.); and the South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences (S.B., V.B., A.L.K., A.O.-J., A.T., S.A.M.), Wits Reproductive Health and HIV Institute (L. Fairlie, G.B.), University of the Witwatersrand, and Soweto Clinical Trials Centre (Q.B., A.E.B.), Johannesburg, Josha Research Centre, Bloemfontein (Z.H., J.J.L., S.F.), the Paediatric Infectious Diseases Unit (M.A., R.M.), the Respiratory and Critical Care Unit (U.L., N.L.), the Department of Obstetrics and Gynaecology (D.M.), Centre for the AIDS Programme of Research in South Africa (S.H.), and Kwazulu-Natal Research Innovation and Sequencing Platform (T.O.), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, the Setshaba Research Centre, Tshwane (M.S.L.M., A.P., K.A.), the Limpopo Clinical Research Initiative, Rustenburg (L. Fouche, P.-L.V.), the Madibeng Centre for Research, Department of Family Medicine, School of Health, University of Pretoria (C.L.), and the Aurum Institute (C.G.), Pretoria, the South African TB Vaccine Initiative (M.T., N.S., A.L.) and the Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine, and UCT Lung Institute (K.D., A.E.), University of Cape Town, and the Health Systems Research Unit and the HIV Prevention Research Unit, South African Medical Research Council (N.S., A.G.), Cape Town, Mzansi Ethical Research Centre, Middelburg (G.K., F.G.P.), and Peermed Clinical Trial Centre, Kempton Park (N.C.-G.) - all in South Africa.

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1-2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission.

Methods: In this phase 2a-b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)-negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 μg of recombinant spike protein with 50 μg of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection.

Results: Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV-positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, -0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups.

Conclusions: The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT04533399.).
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http://dx.doi.org/10.1056/NEJMoa2103055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091623PMC
May 2021

Observation of microstructure evolution during inertia friction welding using in-situ synchrotron X-ray diffraction.

J Synchrotron Radiat 2021 May 19;28(Pt 3):790-803. Epub 2021 Mar 19.

Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE, United Kingdom.

The widespread use and development of inertia friction welding is currently restricted by an incomplete understanding of the deformation mechanisms and microstructure evolution during the process. Understanding phase transformations and lattice strains during inertia friction welding is essential for the development of robust numerical models capable of determining optimized process parameters and reducing the requirement for costly experimental trials. A unique compact rig has been designed and used in-situ with a high-speed synchrotron X-ray diffraction instrument to investigate the microstructure evolution during inertia friction welding of a high-carbon steel (BS1407). At the contact interface, the transformation from ferrite to austenite was captured in great detail, allowing for analysis of the phase fractions during the process. Measurement of the thermal response of the weld reveals that the transformation to austenite occurs 230 °C below the equilibrium start temperature of 725 °C. It is concluded that the localization of large strains around the contact interface produced as the specimens deform assists this non-equilibrium phase transformation.
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http://dx.doi.org/10.1107/S1600577521001569DOI Listing
May 2021

Overcoming bacteriophage insensitivity in Staphylococcus aureus using clindamycin and azithromycinat sub-inhibitory concentrations.

Allergy 2021 Apr 30. Epub 2021 Apr 30.

Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville South, Australia.

Staphylococcus aureus is a pathogen of major concern in both acute infections as well as chronic conditions such as chronic rhinosinusitis (CRS). Bacteriophage (phage) therapy has been considered in Western countries as early as the 1920s and has recently regained interest for its potential to treat infections caused by antibiotic resistant strains including Methicillin Resistant Staphylococcus aureus (MRSA). However, bacteria can adapt and become resistant to phages. The ability to overcome phage resistance is considered critically important for phage therapy applications. Here we show that sub-inhibitory concentrations of Protein Synthesis Inhibitor (PSI) antibiotics clindamycin, erythromycin and azithromycin could sensitise phage-resistantS. aureus strains to phages in vitro and in vivo. All 3 antibiotics showed synergy when combined with multiple lytic phages against 9 S. aureus clinicalisolates in planktonic growth and 2 strains forming biofilms. The combination of clindamycin and phages was safe and could eradicate S. aureussinonasal biofilms in a murine model of sinusitis. This data supports the potential use of phage-PSI antibiotic combination therapies in particular for difficult to treat infections with phage-resistantS. aureus and MRSA strains.
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http://dx.doi.org/10.1111/all.14883DOI Listing
April 2021

Parallel Training of Analog Neural Network Using Electrochemical Random-Access Memory.

Front Neurosci 2021 8;15:636127. Epub 2021 Apr 8.

Sandia National Laboratories, Livermore, CA, United States.

In-memory computing based on non-volatile resistive memory can significantly improve the energy efficiency of artificial neural networks. However, accurate training has been challenging due to the nonlinear and stochastic switching of the resistive memory elements. One promising analog memory is the electrochemical random-access memory (ECRAM), also known as the redox transistor. Its low write currents and linear switching properties across hundreds of analog states enable accurate and massively parallel updates of a full crossbar array, which yield rapid and energy-efficient training. While simulations predict that ECRAM based neural networks achieve high training accuracy at significantly higher energy efficiency than digital implementations, these predictions have not been experimentally achieved. In this work, we train a 3 × 3 array of ECRAM devices that learns to discriminate several elementary logic gates (AND, OR, NAND). We record the evolution of the network's synaptic weights during parallel (on-line) training, with outer product updates. Due to linear and reproducible device switching characteristics, our crossbar simulations not only accurately simulate the epochs to convergence, but also quantitatively capture the evolution of weights in individual devices. The implementation of the first parallel training together with strong agreement with simulation results provides a significant advance toward developing ECRAM into larger crossbar arrays for artificial neural network accelerators, which could enable orders of magnitude improvements in energy efficiency of deep neural networks.
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http://dx.doi.org/10.3389/fnins.2021.636127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060477PMC
April 2021