Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Forecasting electron cyclotron current drive stabilization of neoclassical tearing modes in ITER

The ITER baseline design relies on ECCD to stabilize confinementdegrading disruptive NTMs [1]. However, the EC power required will take a toll on the fusion gain Q. The MDC-8 group (in existence since 2005) has the goal to provide a range of data to benchmark the Rutherford tearing stability equation for NTM evolution, allowing predictions for ITER ECCD requirements to be validated. Experimental contributors have included ASDEX UPGRADE, DIII-D, EAST, FTU, HL-2A, JT-60U, KSTAR, TEXTOR and TCV. While any m/n tearing mode island can reduce confinement, the m=2, n=1 mode at q=2 is particularly damaging. This mode is at a relatively large minor radius in the low q95∼3 safety factor of ITER and thus close to the resistive wall; with the relatively low rotation in ITER (large inertia, small torque), an uncontrolled mode will rapidly lock at low tearing mode amplitude with subsequent disruption [2]. While progress is being made in modeling of the stability space and control [3] and experiments are promising, implementation still needs to be successfully demonstrated experimentally. The ITPA consensus is that ITER's 24 1-MW gyrotrons will provide more than sufficient EC power from the upper launch mirrors to drive narrow (but not too narrow) ECCD at q=2 for stabilization, with good alignment. Broadening of the ECCD, by edge turbulence for example, is a concern that would demand more EC power but also make alignment easier. Pre-emption at lower CW power or active stabilization by early mode onset detection and higher peak (possibly lower average) pulsed power are issues still under continuing investigation. Most EC-NTM experimental studies so far are at relatively high q95 with smaller radius at q=2 and thus higher Te for better current drive efficiency, higher rotation and weaker wall coupling. DIII-D, for example, is now well poised to pursue ECCD NTM stabilization at both low q95 and at low rotation in the 2017 campaign. The MDC-8 as a whole is proceeding to narrow the experimental focus for a comparison of observations from different devices. This will establish the physics basis for successful stabilization in ITER

Error Field Correction in DIII-D Ohmic Plasmas With Either Handedness

Error field correction results in DIII-D plasmas are presented in various configurations. In both left-handed and right-handed plasma configurations, where the intrinsic error fields become different due to the opposite helical twist (handedness) of the magnetic field, the optimal error correction currents and the toroidal phases of internal(I)-coils are empirically established. Applications of the Ideal Perturbed Equilibrium Code to these results demonstrate that the field component to be minimized is not the resonant component of the external field, but the total field including ideal plasma responses. Consistency between experiment and theory has been greatly improved along with the understanding of ideal plasma responses, but non-ideal plasma responses still need to be understood to achieve the reliable predictability in tokamak error field correction

Using high-resolution LiDAR-derived canopy structure and topography to characterise hibernaculum locations of the hazel dormouse

The hazel dormouse is predominantly an arboreal species that moves down to the ground to hibernate in the autumn in temperate parts of its distributional ranges at locations not yet well understood. The main objective of this study is to test whether environmental characteristics surrounding hazel dormouse hibernacula can be identified using high-resolution remote sensing and data collected in situ. To achieve this, remotely sensed variables, including canopy height and cover, topographic slope, sky view, solar radiation and cold air drainage, were modelled around 83 dormouse hibernacula in England (n = 62) and the Netherlands (n = 21), and environmental characteristics that may be favoured by pre-hibernating dormice were identified. Data on leaf litter depth, temperature, canopy cover and distance to the nearest tree were collected in situ and analysed at hibernaculum locations in England. The findings indicated that remotely sensed data were effective in identifying attributes surrounding the locations of dormouse hibernacula and when compared to in situ information, provided more conclusive results. This study suggests that remotely sensed topographic slope, canopy height and sky view have an influence on hazel dormice choosing suitable locations to hibernate; whilst in situ data suggested that average daily mean temperature at the hibernaculum may also have an effect. Remote sensing proved capable of identifying localised environmental characteristics in the wider landscape that may be important for hibernating dormice. This study proposes that this method can provide a novel progression from habitat modelling to conservation management for the hazel dormouse, as well as other species using habitats where topography and vegetation structure influence fine-resolution favourability.</p