Whole-genome sequencing (WGS) information has played a crucial role in the SARS-CoV-2 (COVID-19) pandemic by providing evidence about variants to inform public health policy. The purpose of this study was to assess the representativeness of sequenced cases compared with all COVID-19 cases in England, between March 2020 and August 2021, by demographic and socio-economic characteristics, to evaluate the representativeness and utility of these data in epidemiological analyses. To achieve this, polymerase chain reaction (PCR)-confirmed COVID-19 cases were extracted from the national laboratory system and linked with WGS data. During the study period, over 10% of COVID-19 cases in England had WGS data available for epidemiological analysis. With sequencing capacity increasing throughout the period, sequencing representativeness compared to all reported COVID-19 cases increased over time, allowing for valuable epidemiological analyses using demographic and socio-economic characteristics, particularly during periods with emerging novel SARS-CoV-2 variants. This study demonstrates the comprehensiveness of England’s sequencing throughout the COVID-19 pandemic, rapidly detecting variants of concern, and enabling representative epidemiological analyses to inform policy.

Worldwide, cardiovascular disease (CVD) is the number 1 cause of mortality and is associated with insulin resistance (IR). Emerging biomarkers such as FGF21 and adiponectin are associated with cardiometabolic risk. Low carbohydrate, high fat (LCHF) diets have been reported to reduce cardiometabolic risk markers; however, few studies have compared a LCHF diet vs. a high carbohydrate (HC), lower fat diet under ad libitum conditions on adiponectin and FGF21. The purpose of this study was to investigate the effects of an ad libitum LCHF vs. HC diet on IR, FGF21 and adiponectin in 16 healthy adults. Ethical approval: Liverpool John Moores University Research Ethics Committee (16/ELS/029); registered with ClinicalTrials.gov (Ref. NCT03257085). Participants were randomly assigned to a HC diet (n = 8, the UK Eatwell guidelines; ≥ 50% of energy from carbohydrates) or a LCHF diet (n = 8, consume < 50 g/day of carbohydrates). All provided plasma samples at 0, 4 and 8 weeks. FGF21 (R&D Systems) was analysed via ELISA and adiponectin, insulin and glucose were analysed via immunoassay technology (Randox Evidence Investigator™ Metabolic Syndrome Arrays I & II). Mann Whitney, Friedmans, Wilcoxon tests and 2×3 ANOVA (IBM SPSS 25®) were undertaken to investigate significant differences between and within groups. The homeostatic model assessment (HOMA) was used to calculate IR. FGF21 significantly (P = 0.04) decreased (Mdn, IQR:148.16, 78.51–282.02 to 99.4, 39.87–132.29 pg/ml) after 4 weeks and significantly (P = 0.02) increased (Mdn, IQR:167.38, 80.82–232.89 pg/ml) by 8 weeks vs. baseline with LCHF. No significant differences (P > 0.05) were observed between groups. Adiponectin was significantly (P = 0.03) different at week 4 only between groups. Adiponectin increased after 4 weeks (Mdn, IQR:13.44, 9.12–25.47 to 16.64, 11.96–21.51 ng/ml) but was only significantly (P = 0.03) different by 8 weeks vs. baseline in the HC group (Mdn, IQR:16, 10.8–27.43 ng/ml). Adiponectin remained unchanged (P = 0.96) in the LCHF group. HOMA significantly decreased with both diets after 8 weeks only (mean ± SD, LCHF: 2.9 ± 1.3 to 1.8 ± 0.8, HC: 2.5 ± 0.6 to 1.9 ± 0.6, P = 0.008) but was not significantly (P = 0.60) different between groups. These preliminary data reveal that while both diets improved insulin sensitivity, they may do so by different mechanisms. Future studies are warranted to investigate further, how a LCHF vs. HC diet affects FGF21 and adiponectin, and the subsequent regulation of IR. Furthermore, studies that extend these findings by determining the impact of LCHF vs. HC on peripheral metabolism to determine potential nutrition-mediated mechanisms of metabolic adaptation are warranted.

Apolipoproteins (apo) regulate lipoprotein characteristics and lipid metabolism. ApoC-III is a regulator of triglyceride-rich lipoprotein (TRL) metabolism and apolipoproteins are important biomarkers for cardiovascular disease (CVD) risk prediction. A low carbohydrate high fat (LCHF) diet improves cardiometabolic risk, especially via reduction of TRL. However, few studies have compared a LCHF vs. a high carbohydrate (HC), lower fat diet under ad libitum conditions on apoC-III levels. The objectives of this investigation were to measure the effect of a LCHF vs. a HC diet on apoC-III, apoA1, apoB and apoB/apoA1 in 16 healthy Caucasian adults aged 19–64. Ethical approval: Liverpool John Moores University Research Ethics Committee (16/ELS/029); registered with ClinicalTrials.gov (Ref. NCT03257085). Participants randomly assigned to a HC diet (UK Eatwell guidelines; ≥ 50% of energy from carbohydrates) (n = 8), or a LCHF diet (consume < 50 g/day of carbohydrates) (n = 8) provided plasma samples at 0, 4 and 8 weeks. ApoA1 and apoB were analysed by an automated chemistry analyser (Daytona, Randox Laboratories Ltd, UK). ApoC-III was analysed via ELISA (Thermo Fisher Ltd, USA). Factorial 2×3 ANOVA and ANCOVA (IBM SPSS 25®) were undertaken to investigate significant differences and to control for variables influenced by baseline measures and visceral adipose tissue (VAT). Results show 0, 4, and 8 weeks respectively: ApoC-III (LCHF: 19.12 ± 9.14, 16.05 ± 7.95, 15.11 ± 3.17 mg/dl; HC: 22.13 ± 8.38, 28.22 ± 13.85, 22.22 ± 7.7 mg/dl) showed no significant (P = 0.319) change. No significant (P = 0.23) change was also observed in ApoB (LCHF: 107.25 ± 20.35, 111.38 ± 24.81, 111.43 ± 19.93 mg/dl; HC: 94.38 ± 20.79, 105.00 ± 20.13, 99.00 ± 29.09 mg/dl). Similarly apoA1 (LCHF: 158.71 ± 14.27, 166.50 ± 23.09, 173.00 ± 29.42 mg/dl; HC: 164.71 ± 30.25, 172.50 ± 29.44, 174.00 ± 32.83 mg/dl) showed no significant change (P = 0.76). This resulted in a relatively unchanged apoB/A1 throughout the study in both diets (P = 0.30). No significant (P > 0.05) differences were found after 4 weeks or between groups also. ANCOVA revealed a trend (P = 0.06) in apoC-III for a difference between groups (LCHF: Δ-6.6 mg/dl vs. HC: Δ1.2 mg/dl) after 8 weeks but no significant (P > 0.05) changes in other apolipoproteins were detected. These preliminary data reveal that a LCHF diet does not improve the apolipoprotein profile; however, when accounting for other metabolic risk factors (i.e. VAT) there was a trend towards lowering apoC-III levels (P = 0.06). Modulation of apoC-III may lead to improved lipid metabolism, but higher-powered studies are warranted before any improvement on CVD risk can be inferred.

We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from $z = 0.35$ to 3; and a deep, high-redshift HI IM survey over 100 deg2 from $z = 3$ to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to $z \sim 3$ with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to $z = 6$ . These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.

The deep subsurface of other planetary bodies is of special interest for robotic and human exploration. The subsurface provides access to planetary interior processes, thus yielding insights into planetary formation and evolution. On Mars, the subsurface might harbour the most habitable conditions. In the context of human exploration, the subsurface can provide refugia for habitation from extreme surface conditions. We describe the fifth Mine Analogue Research (MINAR 5) programme at 1 km depth in the Boulby Mine, UK in collaboration with Spaceward Bound NASA and the Kalam Centre, India, to test instruments and methods for the robotic and human exploration of deep environments on the Moon and Mars. The geological context in Permian evaporites provides an analogue to evaporitic materials on other planetary bodies such as Mars. A wide range of sample acquisition instruments (NASA drills, Small Planetary Impulse Tool (SPLIT) robotic hammer, universal sampling bags), analytical instruments (Raman spectroscopy, Close-Up Imager, Minion DNA sequencing technology, methane stable isotope analysis, biomolecule and metabolic life detection instruments) and environmental monitoring equipment (passive air particle sampler, particle detectors and environmental monitoring equipment) was deployed in an integrated campaign. Investigations included studying the geochemical signatures of chloride and sulphate evaporitic minerals, testing methods for life detection and planetary protection around human-tended operations, and investigations on the radiation environment of the deep subsurface. The MINAR analogue activity occurs in an active mine, showing how the development of space exploration technology can be used to contribute to addressing immediate Earth-based challenges. During the campaign, in collaboration with European Space Agency (ESA), MINAR was used for astronaut familiarization with future exploration tools and techniques. The campaign was used to develop primary and secondary school and primary to secondary transition curriculum materials on-site during the campaign which was focused on a classroom extra vehicular activity simulation.

Geochemical and related studies have been made of near-surface sediments from the River Clyde estuary and adjoining areas, extending from Glasgow to the N, and W as far as the Holy Loch on the W coast of Scotland, UK. Multibeam echosounder, sidescan sonar and shallow seismic data, taken with core information, indicate that a shallow layer of modern sediment, often less than a metre thick, rests on earlier glacial and post-glacial sediments. The offshore Quaternary history can be aligned with onshore sequences, with the recognition of buried drumlins, settlement of muds from quieter water, probably behind an ice dam, and later tidal delta deposits. The geochemistry of contaminants within the cores also indicates shallow contaminated sediments, often resting on pristine pre-industrial deposits at depths less than 1m. The distribution of different contaminants with depth in the sediment, such as Pb (and Pb isotopes), organics and radionuclides, allow chronologies of contamination from different sources to be suggested. Dating was also attempted using microfossils, radiocarbon and 210Pb, but with limited success. Some of the spatial distribution of contaminants in the surface sediments can be related to grain-size variations. Contaminants are highest, both in absolute terms and in enrichment relative to the natural background, in the urban and inner estuary and in the Holy Loch, reflecting the concentration of industrial activity.

In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.

Complex design challenges exist in designing for a dynamic and ageing world. Designing for older adults is a timely and important issue. Understanding user requirements is vital and the appropriate exchange of this knowledge is crucial in the pursuit of supportive, sustainable buildings and the longevity of built-environment design.

Capturing reflections from Built Environment Professionals (BEPs) in the UK, this paper investigates the practitioners’ viewpoint on knowledge exchange by specifically focusing on the scenario of designing for the requirements of older people. Thematic analysis of BEP conversations (n=10) and the results from a questionnaire (N=35) are presented.

Findings uncover recommendations towards the enhancement of knowledge exchange. They highlight the fundamentals of good communication, the desire for structured knowledge, the value of contextual guidance, the importance of a visual format for BEPs, and the need for forms of guidance to support client motivations.

The design process can be enabled by equipping practitioners with information about user requirements. Interestingly, it was also found that BEPs find value in direct user-engagement although further support tools for these engagements with building users was desired.

Appropriate exchange of knowledge is essential for effective ‘real-world’ design impact. These findings, built from the scenario of designing for older adults, also apply to the broader context of all guidance used by Built Environment Professionals.

We describe a PCR-based method called Amplified Methylation Polymorphism (AMP) for scanning genomes for DNA methylation changes. AMP detects tissue-specific DNA methylation signatures often representing junctions between methylated and unmethylated DNA close to intronexon junctions and/or associated with CpG islands. Identical AMP profiles are detected for healthy, young, monozygotic twins.