A Regional Model Study of High Latitude Tropospheric Ozone and its Precursors.

The Arctic has warmed disproportionately relative to mid-latitudes over recent decades. This warming is predominantly controlled by radiative forcing from well-mixed greenhouse gases, amplified by efficient Arctic climate feedbacks. However, warming from changes in short-lived climate pollutants (SLCPs), such as tropospheric ozone, have been shown to contribute substantially to Arctic warming, whilst also degrading air quality. Arctic SLCP abundances are controlled by long-range transport from mid-latitudes, and by local sources within the Arctic. At present, high latitude emissions of SLCPs and ozone precursors (e.g nitrogen dioxide [NO2]) are poorly quantified, with a paucity of in-situ observations. Using a regional chemistry transport model, this thesis aims to improve the understanding of processes controlling tropospheric ozone abundances and distributions in areas of limited in-situ observations at high latitudes. In western Siberia there is widespread negative bias in modelled tropospheric column NO2 when compared to satellite observations from May–August. Despite the large negative bias, the spatial correlations between model and observed NO2 columns suggest that the spatial pattern of NOx sources in the region is well represented. Scaling the two largest anthropogenic sectors (energy & transport) by a factor of 2 reduces column NO2 bias (fractional mean bias =−0.66 to −0.35). The findings in this thesis suggest that western Siberian ozone is more sensitive to anthropogenic emissions, particularly from the transport sector, and the contribution from fire emissions maximises in June and is largely confined to latitudes south of 60°N. Ozone dry deposition fluxes from the model simulations show that the dominant ozone dry deposition sink in the region is to forest vegetation, averaging 8.0 Tg of ozone per month. In Fairbanks, Alaska, modelled surface ozone is overestimated during springtime, with an interplay between ozone being vertically mixed down from ozone-rich air above and subsequent ozone loss to NO (O3 + NO = NO2) dominating ozone abundances, suppressing surface ozone. This also leads to significant overestimations in surface NO2. Sensitivity studies tested modelled ozone sensitivity to Fairbanks NOx emissions and model upper boundary conditions. Results suggest that upper troposphere ozone is sensitive to a 20% reduction in initial boundary condition ozone, which brings the values in-line with observations. Whilst a doubling of NOx emissions from within Fairbanks improves the model ozone bias at the surface, but still leads to model overestimation above the boundary layer

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

An Island Drifting Apart. Why Haiti is mired in poverty while the Dominican Republic forges ahead

The 2010 earthquake in Haiti has exposed the extreme vulnerability of a society where the state and the economy simultaneously fail to deliver. The Dominican Republic has witnessed several phases of rapid economic growth since the 1870s and, from the 1970s onwards, a sustained process of political emancipation. Douglas North, John Wallis and Barry Weingast have developed a conceptual framework to explain different long-term performance characteristics of societies, which we apply to the case of Hispaniola. We argue that it captures the internal logic of the political economy of both societies but fails to account for the effect of different foreign relations