Reconciling qualitative storylines and quantitative descriptions: an iterative approach

Energy system transition research has been experimenting with the integration of qualitative and quantitative analysis due to the increased articulation it provides. Current approaches tend to be heavily biased by qualitative or quantitative methodologies, and more often are aimed toward a single academic discipline. This paper proposes an interdisciplinary methodology for the elaboration of energy system socio-technical scenarios, applied here to the low carbon transition of the UK. An iterative approach was used to produce quantitative descriptions of the UK's energy transition out to 2050, building on qualitative storylines or narratives that had been developed through the formal application of a transition pathways approach. The combination of the qualitative and quantitative analysis in this way subsequently formed the cornerstone of wider interdisciplinary research, helping to harmonise assumptions, and facilitating ‘whole systems’ thinking. The methodology pulls on niche expertise of contributors to map and investigate the governance and technological landscape of a system change. Initial inconsistencies were found between energy supply and demand and addressed, the treatment of gas generation, capacity factors, total installed generating capacity and installation rates of renewables employed. Knowledge gaps relating to the operation of combined heat and power, sources of waste heat and future fuel sources were also investigated. Adopting the methodological approach to integrate qualitative and quantitative analysis resulted in a far more comprehensive elaboration than previously, providing a stronger basis for wider research, and for deducing more robust insights for decision-making. It is asserted that this formal process helps build robust future scenarios not only for socio political storylines but also for the quantification of any qualitative storyline

Transition pathways for a UK low-carbon electricity system: comparing scenarios and technology implications

The United Kingdom (UK) has placed itself on a transition towards a low-carbon economy and society, through the imposition of a goal of reducing its ‘greenhouse’ gas emissions by 80% by 2050. A set of three low-carbon ‘Transition Pathways’ were developed to examine the influence of different governance arrangements on achieving a low-carbon future. They focus on the power sector, including the potential for increasing use of low-carbon electricity for heating and transport. These transition pathways were developed by starting from narrative storylines regarding different governance framings, drawing on interviews and workshops with stakeholders and analysis of historical analogies. Here the quantified pathways are compared and contrasted with the main scenarios developed in the UK Government’s 2011 Carbon Plan. This can aid an informed debate on the technical feasibility and social acceptability of realising transition pathways for decarbonising the UK energy sector by 2050. The contribution of these pathways to meeting Britain’s energy and carbon reduction goals are therefore evaluated on a ‘whole systems’ basis, including the implications of ‘upstream emissions’ arising from the ‘fuel supply chain’ ahead of power generators themselves

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529

Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Background We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.Methods We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR positivity.Findings We identified 20 candidate blood transcriptomic signatures of viral infection from 18 studies and evaluated their accuracy among 169 blood RNA samples from 96 participants over 24 weeks. Participants were recruited between March 23 and March 31, 2020. 114 samples were from 41 participants with SARS-CoV-2 infection, and 55 samples were from 55 test-negative controls. The median age of participants was 36 years (IQR 27–47) and 69 (72%) of 96 were women. Signatures had little overlap of component genes, but were mostly correlated as components of type I interferon responses. A single blood transcript for IFI27 provided the highest accuracy for discriminating between test-negative controls and test-positive individuals at the time of their first positive SARS-CoV-2 PCR result, with AUROC of 0·95 (95% CI 0·91–0·99), sensitivity 0·84 (0·70–0·93), and specificity 0·95 (0·85–0·98) at a predefined threshold (Z score >2). The transcript performed equally well in individuals with and without symptoms. Three other candidate signatures (including two to 48 transcripts) had statistically equivalent discrimination to IFI27 (AUROCs 0·91–0·95).Interpretation Our findings support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection for screening individuals at high risk of infection, such as contacts of index cases, to facilitate early case isolation and early use of antiviral treatments as they emerge

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

The effect of sward type and fertilizer rate on milk production of spring calving, grazing dairy cows

International audienceGrazed grass is considered the cheapest feed available for dairy cows in temperate regions. The objective of this study was to quantify the effect of sward type (perennial ryegrass (Lolium perenne L.; PRG)) sown with and without white clover (Trifolium repens L.; WC) and nitrogen (N) fertilizer rate (150 and 250 kg N ha-1) on milk production of grazing dairy cows. 120 cows were randomly divided to each of the four grazing treatments (PRG-only receiving either 150 or 250 kg N ha-1 and PRG-WC receiving either 150 or 250 kg N ha-1) as they calved, and swards were rotationally grazed at stocking rate of 2.75 cows ha-1. There was a significant effect of sward type on milk production (P>0.001). Over the three-year study, cows grazing the PRG-WC treatments had greater milk yield (+222 kg) and milk solids (kg fat + protein) yield (+27 kg) than cows grazing the PRG-only treatments. Nitrogen fertilizer rate did not affect milk production but did affect herbage production. This significant increase in milk production suggests the inclusion of white clover in grazing systems can be used effectively to increase milk production and reduce nitrogen use

A Retrospective Analysis of White Clover ( Trifolium repens L.) Content Fluctuation in Perennial Ryegrass ( Lolium perenne L.) Swards under 4 Years of Intensive Rotational Dairy Grazing

International audienceThe objective of this study was to examine fluctuations in white clover (Trifolium repens L.) content in perennial ryegrass (Lolium perenne L.) swards within a high nitrogen (250 kg N/ha) input grazing dairy system. The data came from a larger, overall system experiment within which all management and growing condition variables were categorised each year for the 40 paddocks that contained perennial ryegrass-white clover swards, over four growing years. Within that study, eight perennial ryegrass cultivars were examined, each sown individually with two white clover cultivars in a 50:50 mix of ‘Chieftain’ and ‘Crusader’. To determine management associations and meteorological patterns with white clover content and rate/direction of change, separate generalised linear models were used to analyse each individual management or meteorological variable. Paddocks with high white clover contents were associated with lower pre- and post-grazing sward heights, lower pasture cover over the winter period and shorter over-winter period. Perennial ryegrass cultivars with lower pre- and post-grazing height, lower pre-grazing pasture mass and pasture yield removed, all retained more white clover in their swards. Soil fertility remained a key factor that affected white clover persistence influencing the degree of responses in all treatments, particularly soil phosphorus (P) levels. Beyond this, higher white clover contents and lower rates of white clover decline were associated with paddocks that received lower rainfall, had higher soil moisture deficits and received more radiation into the base of the sward, particularly around the time of grazing