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

The performance of prototype Vacuum Phototriodes in the first full sized Supercrystal array for the ECAL Endcaps

The performance of prototype Vacuum Phototriodes is presented from the first full sized Supercrystal array for the CMS ECAL Endcaps. The array was exposed to high energy electrons in H4 and tested in magnetic fields of up to 3 T in H2, in the CERN North area, in July and August 1999. The mean VPT electron yield, normalised to a naked crystal light yield of 8 photoelectrons into an HPMT, was found to be 25 electrons/ MeV at 3 T for devices from Research Institute Electron, 35 electrons/MeV for devices from Hamamatsu and 18/23 electrons/MeV from Electron Tubes

Resolution of a Prototype Lead Tungstate Crystal Matrix with Vacuum Phototriode Readout for the CMS Endcap Electromagnetic Calorimeter

Data obtained in June 1998 from a 3x3 array of PbWO4 in the H4 testbeam indicate that an energy resolution better than 0.5% at 100GeV can be obtained from a matrix of PbWO4 endcap crystals with vacuum phototriode readout. These data are the first obtained for ECAL endcap shaped crystals and used crystals 220mm long with 24.7x24.7mm^2 front face. Tests with a full sized super-crystal, a 5x5 array of fullsized crystals ( 28.6x28.6mm^2 front face), will be performed in summer 1999

Two-quadrant high-volume sub-Tenon's anaesthesia for vitrectomy:a randomised controlled trial

Background: Total volume using a standard single inferonasal injection for sub-Tenon's anaesthesia is limited by an increase in intraocular pressure (IOP) and commonly requires the operating surgeon to top-up the block intraoperatively. This study compares the efficacy and safety of a two-quadrant technique that allows the use of a higher volume of local anaesthetic. Methods: 54 patients undergoing vitrectomy were randomised into two groups. The control group (n=27) received a standard 5 ml single inferonasal sub-Tenon injection of a 50:50 mixture of 2% lidocaine and 0.5% bupivacaine with 150 IU hyaluronidase. The study group (n=27) received a 5 ml inferonasal and 5 ml superotemporal injection of the same mixture (10 ml total). The primary outcome measure was the number of intraoperative top-ups required. Secondary outcome measures were intraoperative and postoperative pain scores, IOP, block onset time, ocular akinesia, eyelid akinesia and chemosis. Results: 24 patients required a top-up in the control group. No patients required a top-up in the study group (p<0.001). IOP measurements were similar in both groups. Block onset was shorter, eyelid akinesia was improved and pain scores were also reduced in the study group intraoperatively and at 0-2 h, 4-6 h, 10-14 h and 20-24 h postoperatively. Conclusions: Two-quadrant sub-Tenon's anaesthesia using 10 ml of a 50:50 mixture of 2% lidocaine and 0.5% bupivacaine with 150 IU hyaluronidase seems to be more effective than a single-quadrant technique at reducing intraoperative and postoperative pain during vitrectomy

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

BACKGROUND: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. METHODS: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18-55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. FINDINGS: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). INTERPRETATION: ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme. FUNDING: UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen

The effect of urban ground covers on arthropods: An experiment.

Changes to the ground layer in urban areas are extensive, but the effects on arthropod fauna are poorly understood. We undertook a manipulative experiment to examine the response of arthropods to small-scale variation in ground covers commonly found in urban parks and gardens in Australia. The ground covers tested were bare ground, leaf litter, woodchips and grass, with plot sizes of 3.6 m2. Epigeic arthropods were sampled with pitfall traps and Tullgren funnels over 12 months following establishment of the treatments. All epigeic arthropods were sorted to order and the ants (Hymenoptera: Formicidae), beetles (Coleoptera), millipedes (Diplopoda) and slaters (Isopoda: Oniscidea) were examined at lower taxonomic levels. Diverse arthropods rapidly colonised previously cleared plots in all four treatments and were most abundant in grass plots. The diversity of ants and beetles was significantly different in different ground covers and tended to be most diverse in grass plots. Despite the treatments providing very different microclimates, the fauna studied did not show strong selection for a particular cover type overall. The abundance of grass cover in the surrounding area may have led to the grass plots having the greatest abundance of arthropods. These results have important implications for developing effective small-scale conservation efforts for arthropods in anthropogenically modified landscapes, especially for species with poor dispersal abilities.This research was conducted while B.N. was a recipient of an Australian Postgraduate Award and a Holsworth Wildlife Research Grant. Additional funding and support were provided by the Baker Foundation