Effect of a Russian-backbone live-attenuated influenza vaccine with an updated pandemic H1N1 strain on shedding and immunogenicity among children in The Gambia : an open-label, observational, phase 4 study

Background The efficacy and effectiveness of the pandemic H1N1 (pH1N1) component in live attenuated influenza vaccine (LAIV) is poor. The reasons for this paucity are unclear but could be due to impaired replicative fitness of pH1N1 A/California/07/2009-like (Cal09) strains. We assessed whether an updated pH1N1 strain in the Russian-backbone trivalent LAIV resulted in greater shedding and immunogenicity compared with LAIV with Cal09. Methods We did an open-label, prospective, observational, phase 4 study in Sukuta, a periurban area in The Gambia. We enrolled children aged 24–59 months who were clinically well. Children received one dose of the WHO prequalified Russian-backbone trivalent LAIV containing either A/17/California/2009/38 (Cal09) or A/17/New York/15/5364 (NY15) based on their year of enrolment. Primary outcomes were the percentage of children with LAIV strain shedding at day 2 and day 7, haemagglutinin inhibition seroconversion, and an increase in influenza haemagglutinin-specific IgA and T-cell responses at day 21 after LAIV. This study is nested within a randomised controlled trial investigating LAIV–microbiome interactions (NCT02972957). Findings Between Feb 8, 2017, and April 12, 2017, 118 children were enrolled and received one dose of the Cal09 LAIV from 2016–17. Between Jan 15, 2018, and March 28, 2018, a separate cohort of 135 children were enrolled and received one dose of the NY15 LAIV from 2017–18, of whom 126 children completed the study. Cal09 showed impaired pH1N1 nasopharyngeal shedding (16 of 118 children [14%, 95% CI 8·0–21·1] with shedding at day 2 after administration of LAIV) compared with H3N2 (54 of 118 [46%, 36·6–55·2]; p<0·0001) and influenza B (95 of 118 [81%, 72·2–87·2]; p<0·0001), along with suboptimal serum antibody (seroconversion in six of 118 [5%, 1·9–10·7]) and T-cell responses (CD4+ interferon γ-positive and/or CD4+ interleukin 2-positive responses in 45 of 111 [41%, 31·3–50·3]). After the switch to NY15, a significant increase in pH1N1 shedding was seen (80 of 126 children [63%, 95% CI 54·4–71·9]; p<0·0001 compared with Cal09), along with improvements in seroconversion (24 of 126 [19%, 13·2–26·8]; p=0·011) and influenza-specific CD4+ T-cell responses (73 of 111 [66%, 60·0–75·6; p=0·00028]). The improvement in pH1N1 seroconversion with NY15 was even greater in children who were seronegative at baseline (24 of 64 children [38%, 95% CI 26·7–49·8] vs six of 79 children with Cal09 [8%, 2·8–15·8]; p<0·0001). Persistent shedding to day 7 was independently associated with both seroconversion (odds ratio 12·69, 95% CI 4·1–43·6; p<0·0001) and CD4+ T-cell responses (odds ratio 7·83, 95% CI 2·99–23·5; p<0·0001) by multivariable logistic regression. Interpretation The pH1N1 component switch that took place between 2016 and 2018 might have overcome the poor efficacy and effectiveness reported with previous LAIV formulations. LAIV effectiveness against pH1N1 should, therefore, improve in upcoming influenza seasons. Our data highlight the importance of assessing replicative fitness, in addition to antigenicity, when selecting annual LAIV components

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available

Information and digital literacies; a review of concepts

A detailed literature reviewing, analysing the multiple and confusing concepts around the ideas of information literacy and digital literacy at the start of the millennium. The article was well-received, and is my most highly-cited work, with over 1100 citations

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research