'Core' values safe at BGS

In answer to Culshaw and Lee’s criticism of BGS policy (Geoscientist 21.10 p11), we invite readers to review our fouryear strategy (links on website) which is unchanged since publication in spring 2009. It highlights the change from ‘systematic’ to ‘responsive’ survey. BGS will complete this by the end of the strategy period, while at the same time ensuring that the 2D UK survey is refreshed and, where necessary, newly surveyed. The strategy also introduces a strong focus on remapping the UK shelf

Introduction

Global energy security throughout the next century will continue to depend significantly on fossil fuel and nuclear whilst unlocking the potential of renewable as well as unconventional sources. The UK government’s industrial strategy highlights the importance of continuing support for the oil and gas and nuclear sectors

Spatial Morphometric Analysis Using Shape-Changing Rigid-Body Chains

Morphometry is the quantitative comparison of shapes, primarily curves. As an alternate to classical methods of spatial morphometry, this work investigates a kinematic synthesis methodology for designing a spatial chain of rigid-bodies to match arbitrary spatial curves. The goal is to find a single set of spatial bodies that can be moved to approximately align with any given set of spatial curves. Previous rigid-body shape-change morphometry work focused on mechanisms composed of rigid planar links connected by prismatic and revolute joints to approximate planar curves. Open space curves are the current focus of the research. The primary advantage of this method is its capacity to describe the difference in space curves with a limited number of parameters.https://ecommons.udayton.edu/stander_posters/2395/thumbnail.jp

Feasibility of a new ‘balanced binocular viewing’ treatment for unilateral amblyopia in children aged 3–8 years (BALANCE): results of a phase 2a randomised controlled feasibility trial

Objectives: This study aimed to evaluate the safety of dichoptic balanced binocular viewing (BBV) for amblyopia in children, plus feasibility, adherence, acceptability, trial methodology and clinical measures of visual function. Design: We carried out an observer-masked parallel-group phase 2a feasibility randomised controlled trial. Setting: Two study sites, a secondary/tertiary and a community site. Participants: We enrolled 32 children aged 3–8 years with unilateral amblyopia who had completed optical adaptation where indicated. 20 children attended the 16-week exit visit (retention 63%). Interventions: Children were randomised to BBV (movies customised to interocular acuity difference at baseline) for 1 hour a day (active intervention) or standard management as per parental choice (part-time occlusion or atropine blurring, control). All interventions were used at home, daily for 16 weeks. Primary outcome measure: ‘VacMan suppression test’ of interocular balance at 16 weeks from randomisation. Secondary outcome measures: feasibility outcomes (recruitment and retention ratios, adherence with the allocated intervention); safety outcomes at other time points (changes in prevalence of diplopia, manifest strabismus, suppression/interocular balance on a range of tests); efficacy outcomes (clinical measures of visual function, such as best-corrected visual acuity, BCVA). Outcome measures were identical to those planned in the protocol. Results: Primary outcome: At baseline, values for the interocular balance point were higher (indicating greater suppression of the amblyopic eye) in the occlusion group than in the BBV group. These values shifted downwards on average for the occlusion group, significantly decreasing from baseline to week 16 (t8=4.49, p=0.002). Balance values did not change between baseline and week 16 for the BBV group (t9=−0.82, p=0.435). At 16 weeks, there was no statistical difference in interocular balance/suppression change over time between the two arms. The difference at follow-up between the arms, adjusted for baseline, was −0.02 (95% CI −0.28 to 0.23, p=0.87). Feasibility: We prescreened 144 records of potentially eligible children. Between 28 October 2019 and 31 July 2021, including an interruption due to the COVID-19 pandemic, 32 children were screened and randomised (recruitment rate 22%), 16 to BBV and 16 to standard treatment. 20 children attended the 16-week exit visit (retention 63%). Mean adherence with BBV as proportion of viewing time prescribed was 56.1% (SD36) at 8 and 57.9% (SD 30.2) at 16 weeks. Mean adherence with prescribed occlusion time was 90.1% (SD 19.7) at 8 and 59.2% (SD 24.8) at 16 weeks. Secondary safety/efficacy outcomes: One child in the BBV arm reported transient double vision, which resolved; two reported headaches, which led to withdrawal. BCVA improved from mean 0.47 (SD0.18) logMAR at randomisation to 0.26 (0.14) with standard treatment, and from 0.55 (0.28) to 0.32 (0.26) with BBV. Outcomes at 16 weeks did not differ between treatments. Participant experience: Families were generally positive about BBV, but families found both patching and BBV difficult to integrate into family routines. Conclusions: Recruitment rates indicate that a future phase 3 trial will require multiple sites or a longer enrolment period. Retention and adherence rates were lower than anticipated, which will influence future study designs. Dichoptic treatment may be equal to occlusion treatment in safety and efficacy; headaches may lead to discontinuation. Integration into family routines may constitute a barrier to implementation. Trial registration number NCT03754153

Phase 2a randomised controlled feasibility trial of a new ‘balanced binocular viewing’ treatment for unilateral amblyopia in children age 3–8 years : trial protocol

Introduction Treatments for amblyopia, the most common vision deficit in children, often have suboptimal results. Occlusion/atropine blurring are fraught with poor adherence, regression and recurrence. These interventions target only the amblyopic eye, failing to address imbalances of cortical input from the two eyes (‘suppression’). Dichoptic treatments manipulate binocular visual experience to rebalance input. Poor adherence in early trials of dichoptic therapies inspired our development of balanced binocular viewing (BBV), using movies as child-friendly viewable content. Small observational studies indicate good adherence and efficacy. A feasibility trial is needed to further test safety and gather information to design a full trial. Methods/analysis We will carry out an observer-masked parallel-group phase 2a feasibility randomised controlled trial at two sites, randomising 44 children aged 3–8 years with unilateral amblyopia to either BBV or standard occlusion/atropine blurring, with 1:1 allocation ratio. We will assess visual function at baseline, 8 and 16 weeks. The primary outcome is intervention safety at 16 weeks, measured as change in interocular suppression, considered to precede the onset of potential diplopia. Secondary outcomes include safety at other time points, eligibility, recruitment/retention rates, adherence, clinical outcomes. We will summarise baseline characteristics for each group and assess the treatment effect using analysis of covariance. We will compare continuous clinical secondary endpoints between arms using linear mixed effect models, and report feasibility endpoints using descriptive statistics. Ethics/dissemination This trial has been approved by the London-Brighton & Sussex Research Ethics Committee (18/LO/1204), National Health Service Health Research Authority and Medicines and Healthcare products Regulatory Agency. A lay advisory group will be involved with advising on and disseminating the results to non-professional audiences, including on websites of funder/participating institutions and inputting on healthcare professional audience children would like us to reach. Reporting to clinicians and scientists will be via internal and external meetings/conferences and peer-reviewed journals

Lead isotopes as tracers of crude oil migration within deep crustal fluid systems

Although Pb, U, and Th may be fractionated between crude oil and formation waters, Pb isotopes are not. This unique property makes Pb isotopes a particularly useful marker of hydrocarbon generation and migration. Here we show that Pb isotopes offer a new vision of long-range (secondary) oil migration relevant to the formation of oil fields. North Sea oils are largely generated from Jurassic black shales, yet their Pb isotopes are mixtures of Cenozoic to Proterozoic end-members. The same observation is made for crude oils from the Paris Basin, the Barents Sea, Libya, Kuwait, Kazakhstan, and Australia. Bulk Pb in crude oil therefore, for the most part, is foreign to its source rock(s). Our high-precision Pb isotope data on 195 crude oils worldwide, the first such data set in the published literature, and 17 Northern European black shales indicate that deep-seated Pb components originating beneath the source rocks are ubiquitous in crude oil. This implies that oil fields are embedded in basinal convective systems of hydrous fluids heated from below. Plumes of hot fluids rise from the lower thermal boundary layer, which Pb isotopes require douse the basement, into the core of the porous-flow convective cell where they dissolve the newly formed hydrocarbons sequestered in the source rocks. The fluids finally unload unmixed formation waters and crude oil at the base of the upper (conductive) boundary layer where they can be trapped in favorable sites. Based on these new insights we argue that Pb isotopes in crude oil constitute a good tracer of oil migration

Feasibility of a new ‘balanced binocular viewing’ treatment for unilateral amblyopia in children aged 3–8 years (BALANCE):results of a phase 2a randomised controlled feasibility trial

Objectives This study aimed to evaluate the safety of dichoptic balanced binocular viewing (BBV) for amblyopia in children, plus feasibility, adherence, acceptability, trial methodology and clinical measures of visual function. Design We carried out an observer-masked parallel-group phase 2a feasibility randomised controlled trial. Setting Two study sites, a secondary/tertiary and a community site. Participants We enrolled 32 children aged 3–8 years with unilateral amblyopia who had completed optical adaptation where indicated. 20 children attended the 16-week exit visit (retention 63%). Interventions Children were randomised to BBV (movies customised to interocular acuity difference at baseline) for 1 hour a day (active intervention) or standard management as per parental choice (part-time occlusion or atropine blurring, control). All interventions were used at home, daily for 16 weeks. Primary outcome measure ‘VacMan suppression test’ of interocular balance at 16 weeks from randomisation. Secondary outcome measures: feasibility outcomes (recruitment and retention ratios, adherence with the allocated intervention); safety outcomes at other time points (changes in prevalence of diplopia, manifest strabismus, suppression/interocular balance on a range of tests); efficacy outcomes (clinical measures of visual function, such as best-corrected visual acuity, BCVA). Outcome measures were identical to those planned in the protocol. Results Primary outcome: At baseline, values for the interocular balance point were higher (indicating greater suppression of the amblyopic eye) in the occlusion group than in the BBV group. These values shifted downwards on average for the occlusion group, significantly decreasing from baseline to week 16 (t8=4.49, p=0.002). Balance values did not change between baseline and week 16 for the BBV group (t9=−0.82, p=0.435). At 16 weeks, there was no statistical difference in interocular balance/suppression change over time between the two arms. The difference at follow-up between the arms, adjusted for baseline, was −0.02 (95% CI −0.28 to 0.23, p=0.87). Feasibility: We prescreened 144 records of potentially eligible children. Between 28 October 2019 and 31 July 2021, including an interruption due to the COVID-19 pandemic, 32 children were screened and randomised (recruitment rate 22%), 16 to BBV and 16 to standard treatment. 20 children attended the 16-week exit visit (retention 63%). Mean adherence with BBV as proportion of viewing time prescribed was 56.1% (SD36) at 8 and 57.9% (SD 30.2) at 16 weeks. Mean adherence with prescribed occlusion time was 90.1% (SD 19.7) at 8 and 59.2% (SD 24.8) at 16 weeks. Secondary safety/efficacy outcomes One child in the BBV arm reported transient double vision, which resolved; two reported headaches, which led to withdrawal. BCVA improved from mean 0.47 (SD0.18) logMAR at randomisation to 0.26 (0.14) with standard treatment, and from 0.55 (0.28) to 0.32 (0.26) with BBV. Outcomes at 16 weeks did not differ between treatments. Participant experience Families were generally positive about BBV, but families found both patching and BBV difficult to integrate into family routines. Conclusions Recruitment rates indicate that a future phase 3 trial will require multiple sites or a longer enrolment period. Retention and adherence rates were lower than anticipated, which will influence future study designs. Dichoptic treatment may be equal to occlusion treatment in safety and efficacy; headaches may lead to discontinuation. Integration into family routines may constitute a barrier to implementation

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination