8 research outputs found
Predicting ambulatory energy expenditure in lower limb amputees using multi-sensor methods
PurposeTo assess the validity of a derived algorithm, combining tri-axial accelerometry and heart rate (HR) data, compared to a research-grade multi-sensor physical activity device, for the estimation of ambulatory physical activity energy expenditure (PAEE) in individuals with traumatic lower-limb amputation.MethodsTwenty-eight participants [unilateral (n = 9), bilateral (n = 10) with lower-limb amputations, and non-injured controls (n = 9)] completed eight activities; rest, ambulating at 5 progressive treadmill velocities (0.48, 0.67, 0.89, 1.12, 1.34m.s-1) and 2 gradients (3 and 5%) at 0.89m.s-1. During each task, expired gases were collected for the determination of and subsequent calculation of PAEE. An Actigraph GT3X+ accelerometer was worn on the hip of the shortest residual limb and, a HR monitor and an Actiheart (AHR) device were worn on the chest. Multiple linear regressions were employed to derive population-specific PAEE estimated algorithms using Actigraph GT3X+ outputs and HR signals (GT3X+HR). Mean bias±95% Limits of Agreement (LoA) and error statistics were calculated between criterion PAEE (indirect calorimetry) and PAEE predicted using GT3X+HR and AHR.ResultsBoth measurement approaches used to predict PAEE were significantly related (Pr = 0.92, bilateral; r = 0.93, and control; r = 0.91, and AHR; unilateral; r = 0.86, bilateral; r = 0.81, and control; r = 0.67). Mean±SD percent error across all activities were 18±14%, 15±12% and 15±14% for the GT3X+HR and 45±20%, 39±23% and 34±28% in the AHR model, for unilateral, bilateral and control groups, respectively.ConclusionsStatistically derived algorithms (GT3X+HR) provide a more valid estimate of PAEE in individuals with traumatic lower-limb amputation, compared to a proprietary group calibration algorithm (AHR). Outputs from AHR displayed considerable random error when tested in a laboratory setting in individuals with lower-limb amputation.</div
Diversity of methyl halide-degrading microorganisms in oceanic and coastal waters
Methyl halides have a significant impact on atmospheric chemistry, particularly in the degradation of stratospheric ozone. Bacteria are known to contribute to the degradation of methyl halides in the oceans and marine bacteria capable of using methyl bromide and methyl chloride as sole carbon and energy source have been isolated. A genetic marker for microbial degradation of methyl bromide ( cmuA ) was used to examine the distribution and diversity of these organisms in the marine environment. Three novel marine clades of cmuA were identified in unamended seawater and in marine enrichment cultures degrading methyl halides. Two of these cmuA clades are not represented in extant bacteria, demonstrating the utility of this molecular marker in identifying uncultivated marine methyl halide-degrading bacteria. The detection of populations of marine bacteria containing cmuA genes suggests that marine bacteria employing the CmuA enzyme contribute to methyl halide cycling in the ocean
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
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 ”g in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 ”g 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 51·6â77·5) 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 203·3â214·8). 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 030â27 162), which increased to 37 460 ELU/mL (31 996â43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41â1·78). 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 996â30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826â64 452), with a geometric mean fold change of 2·19 (1·90â2·52). 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 10·37â14·32) and 15·90 (12·92â19·58) 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 3·24â16·54] in the BNT162b2 group and 6·22 [3·90â9·92] 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
Sustainable, Equitable and Decent Job Creation in South Africa: The Crucial Role of the Local Developmental Statee
Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial
Background:
Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (OxfordâAstraZeneca; hereafter referred to as ChAd) or BNT162b2 (PfizerâBioNtech, hearafter referred to as BNT).
Methods:
COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY) control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130.
Findings:
Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44â61) in the younger age group and 76 years (73â78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41â59) in the younger age group and 78 years (75â82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5â2·3) in the half VLA group to 32·3 (24·8â42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7â1·6) for ChAd to 3·6 (2·4â5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0â1·5) in the half VLA group to 11·5 (9·4â14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7â1·6) for half VLA to 4·7 (3·1â7·1) for m1273. The results were similar between those aged 30â69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30â69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273.
Interpretation:
All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination.
Funding:
UK Vaccine Taskforce and National Institute for Health Research