Representing the Arctic in global surface temperature time series of recent climate change

The Arctic is an important region in the study of climate change, but monitoring surface temperatures in this region is challenging, particularly in areas covered by sea ice. Here in situ, satellite and reanalysis data were utilised to investigate whether global warming over recent decades could be better estimated by changing the way the Arctic is treated in calculating global mean temperature. The degree of difference arising from using five different techniques, based on existing temperature anomaly dataset techniques, to estimate Arctic SAT anomalies over land and sea ice were investigated using reanalysis data as a testbed. Techniques which interpolated anomalies were found to result in smaller errors than non-interpolating techniques. Kriging techniques provided the smallest errors in anomaly estimates. Similar accuracies were found for anomalies estimated from in situ meteorological station SAT records using a kriging technique. Whether additional data sources, which are not currently utilised in temperature anomaly datasets, would improve estimates of Arctic surface air temperature anomalies was investigated within the reanalysis testbed and using in situ data. For the reanalysis study, the additional input anomalies were reanalysis data sampled at certain supplementary data source locations over Arctic land and sea ice areas. For the in situ data study, the additional input anomalies over sea ice were surface temperature anomalies derived from the Advanced Very High Resolution Radiometer satellite instruments. The use of additional data sources, particularly those located in the Arctic Ocean over sea ice or on islands in sparsely observed regions, can lead to substantial improvements in the accuracy of estimated anomalies. Decreases in Root Mean Square Error can be up to 0.2K for Arctic-average anomalies and more than 1K for spatially resolved anomalies. Further improvements in accuracy may be accomplished through the use of other data sources

An investigation into the impact of using various techniques to estimate Arctic surface air temperature anomalies

Time series of global and regional mean Surface Air Temperature (SAT) anomalies are a common metric used to estimate recent climate change. Various techniques can be used to create these time series from meteorological station data. The degree of difference arising from using five different techniques, based on existing temperature anomaly dataset techniques, to estimate Arctic SAT anomalies over land and sea ice were investigated using reanalysis data as a testbed. Techniques which interpolated anomalies were found to result in smaller errors than non-interpolating techniques relative to the reanalysis reference. Kriging techniques provided the smallest errors in estimates of Arctic anomalies and Simple Kriging was often the best kriging method in this study, especially over sea ice. A linear interpolation technique had, on average, Root Mean Square Errors (RMSEs) up to 0.55 K larger than the two kriging techniques tested. Non-interpolating techniques provided the least representative anomaly estimates. Nonetheless, they serve as useful checks for confirming whether estimates from interpolating techniques are reasonable. The interaction of meteorological station coverage with estimation techniques between 1850 and 2011 was simulated using an ensemble dataset comprising repeated individual years (1979-2011). All techniques were found to have larger RMSEs for earlier station coverages. This supports calls for increased data sharing and data rescue, especially in sparsely observed regions such as the Arctic

Control-focused, nonlinear and time-varying modelling of dielectric elastomer actuators with frequency response analysis

Current models of dielectric elastomer actuators (DEAs) are mostly constrained to first principal descriptions that are not well suited to the application of control design due to their computational complexity. In this work we describe an integrated framework for the identification of control focused, data driven and time-varying DEA models that allow advanced analysis of nonlinear system dynamics in the frequency-domain. Experimentally generated input–output data (voltage-displacement) was used to identify control-focused, nonlinear and time-varying dynamic models of a set of film-type DEAs. The model description used was the nonlinear autoregressive with exogenous input structure. Frequency response analysis of the DEA dynamics was performed using generalized frequency response functions, providing insight and a comparison into the time-varying dynamics across a set of DEA actuators. The results demonstrated that models identified within the presented framework provide a compact and accurate description of the system dynamics. The frequency response analysis revealed variation in the time-varying dynamic behaviour of DEAs fabricated to the same specifications. These results suggest that the modelling and analysis framework presented here is a potentially useful tool for future work in guiding DEA actuator design and fabrication for application domains such as soft robotics

The roles of encoding and retrieval processes in associative and categorical memory illusions

Four experiments investigated the origin of associative and categorical memory illusions by comparing the effects of study and test associations on Deese/Roediger-McDermott (DRM) and categorized lists. Experiments 1 and 2 found that levels of false recognition with both list types were increased by manipulations that facilitated the generation of associates at study (blocked presentation of study lists and explicit instructions to generate associates of studied items). Experiments 3 and 4 showed that manipulations designed to increase test associations (test-induced priming and part-set cuing) did not increase levels of false memory with either list type. These findings indicate that false memories produced by both DRM and categorized lists are influenced by associations activated at study but not by associations activated at test

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Valuing the bowling alley: Contestations over the preservation of spaces of everyday urban multiculture in London

This paper builds on ‘the convivial, everyday turn’ (Neal et al, 2013) by approaching the workings of complex urban spaces of multiculture as entangled with processes of urban change that are infused with judgments and contestations about what is of value. This paper explores the competing value claims made for a leisure space, a London bowling alley, used by a diverse group of people (in terms of dis/ability, ethnicity, gender, class and age) that has been threatened with demolition. The paper examines how arguments about diversity and inclusivity are deployed in these debates and how official discourses are resisted through the mobilisation of other articulations of social value. The paper argues that the combination of the hollowing out of the concept of diversity and the political and economic context results in a paradox whereby multiculturalism is celebrated as an atmosphere and generator of capital while existing physical spaces of everyday urban multiculture are at best unprotected and at worst not recognised, devalued and demolished

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 (anti-spike 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. FUNDING: UK Vaccine Task Force and National Institute for Health Research

Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: three month analyses of the COV-BOOST trial

OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters. METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. RESULTS: Among the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAd, schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10085) following ChAd/ChAd/BNT). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentration at D84 following BNT/BNT initial doses were higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses

SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits.

Hexanucleotide repeat expansions in the C9ORF72 gene are the commonest known genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Expression of repeat transcripts and dipeptide repeat proteins trigger multiple mechanisms of neurotoxicity. How repeat transcripts get exported from the nucleus is unknown. Here, we show that depletion of the nuclear export adaptor SRSF1 prevents neurodegeneration and locomotor deficits in a Drosophila model of C9ORF72-related disease. This intervention suppresses cell death of patient-derived motor neuron and astrocytic-mediated neurotoxicity in co-culture assays. We further demonstrate that either depleting SRSF1 or preventing its interaction with NXF1 specifically inhibits the nuclear export of pathological C9ORF72 transcripts, the production of dipeptide-repeat proteins and alleviates neurotoxicity in Drosophila, patient-derived neurons and neuronal cell models. Taken together, we show that repeat RNA-sequestration of SRSF1 triggers the NXF1-dependent nuclear export of C9ORF72 transcripts retaining expanded hexanucleotide repeats and reveal a novel promising therapeutic target for neuroprotection.MRC, ERC, FP