Resilience of temperate peatland vegetation communities to wildfire depends upon burn severity and pre-fire species composition.

Peatland ecosystems are of global conservation and environmental importance storing globally significant amounts of ancient carbon, regulating regional temperatures and hydrological regimes, and supporting unique biodiversity. Livestock grazing, land-use change, drainage, nutrient and acid deposition, and wildfire threaten the composition and function of many peatlands including those in the uplands of the United Kingdom. Presently, little is known about either the short- or long-term effects of wildfires within these systems in the UK. Our study aimed to evaluate how plant communities respond to wildfires across a range of vegetation communities, soil types, and burn severities. We evaluated wildfire burn severity using the ground-based Composite Burn Index adapted for treeless peatlands. Using paired burned-unburned plots, we quantified differences in the abundance of plant families and functional groups, vegetation diversity, and community composition. Multivariate differences in composition between burned and unburned areas were used as an index of community resilience to fire. Plots in heathland communities with shallow organic soils burned at the highest severities and had the greatest reductions in plant diversity and richness. There were significant declines in plot-scale species richness and diversity with increasing burn severity. Graminoids were resilient to fire whilst Ericaceae tended to increase with higher severity. Bryophyte composition was substantially altered-pleurocarpous species declined and acrocarpous species increased with greater burn severity. Community resilience was related to ground layer burn severity with higher burn severity driving greater changes in communities. Wildfire effects on temperate peatlands are a function of fire weather and site environmental and ecological characteristics. Management policy should ensure that the risk of severe wildfires is mitigated to protect ecosystem function and biodiversity. This will require system-specific fire management prescriptions across the gradient of peatland soil and vegetation types.

Measurement of the ν_{e}-Nucleus Charged-Current Double-Differential Cross Section at ⟨E_{ν}⟩=2.4 GeV Using NOvA.

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×10^{20} protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q^{2} (squared four-momentum transfer) and energy, in the range 1 GeV≤E_{ν}<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q^{2}.

Combinatorial assembly and design of enzymes.

The design of structurally diverse enzymes is constrained by long-range interactions that are necessary for accurate folding. We introduce an atomistic and machine learning strategy for the combinatorial assembly and design of enzymes (CADENZ) to design fragments that combine with one another to generate diverse, low-energy structures with stable catalytic constellations. We applied CADENZ to endoxylanases and used activity-based protein profiling to recover thousands of structurally diverse enzymes. Functional designs exhibit high active-site preorganization and more stable and compact packing outside the active site. Implementing these lessons into CADENZ led to a 10-fold improved hit rate and more than 10,000 recovered enzymes. This design-test-learn loop can be applied, in principle, to any modular protein family, yielding huge diversity and general lessons on protein design principles.

Why is William Sharp's name forgotten when his novel method for treating fractures of the Ankle is still used today?

In 1837 Guillaume von Dupuytren (1777-1835) wrote that the innovative method of reducing an ankle fracture by relaxing the calf muscles was due to both William Sharp (1729-1810) and Percivall Pott (1714-1788). While history records the many surgical achievements of Percivall Pott, little is known of William Sharp's contribution. He is probably best known as one of a remarkable family portrayed by Johan Zoffany (1733-1810) and exhibited at the Royal Academy in 1781. We review William Sharp's career and contribution as a surgeon to the treatment of fracture/dislocations of the ankle and ask why his concept is not better known today.

Early Pseudomonas aeruginosa predicts poorer pulmonary function in preschool children with cystic fibrosis.

BACKGROUND: We previously reported relatively normal pulmonary function (2 years of age) and computed tomography (CT, 1 year of age) in cystic fibrosis (CF) newborn screened (NBS) infants. We now report follow up of these children to preschool age. METHODS: 67 NBS children with CF and 41 healthy controls underwent pulmonary function tests in infancy (∼3 months, 1 year and 2 years) and at preschool (3-6 years). Broncho-alveolar lavage (BAL) and CT were undertaken in those with CF at 1 year. Primary outcomes at preschool were lung clearance index (LCI) and forced expired volume (FEV0.75). Risk factors for lung function impairment were identified by regression modelling, emphasising factors that could be identified or measured in the first 2 years of life. RESULTS: At preschool age children with CF had poorer lung function than controls, mean(95% CI) difference in LCI z-score: 1.47(0.96;1.97) and FEV0.75 z-score -0.54(-0.98; -0.10). Isolation of Pseudomonas aeruginosa before 6 months was a highly significant predictor of raised (abnormal) preschool LCI, associated with a mean (95%CI) increase of 1.69(0.43, 2.95) z-scores, compared to those with no Pseudomonas aeruginosa during the first 2 years of life. Including 2 year LCI and 1 year CT data in the predictive model increased the r2 from 13% to 61%. CONCLUSIONS: Lung function deteriorates after 2 years in NBS children with CF. Isolation of Pseudomonas aeruginosa before 6 months and minor abnormalities of infant lung function tests and CT in infancy are associated with higher preschool LCI.

Evaluating the performance characteristics of five lateral flow assays for the detection of the SARS-CoV-2 nucleocapsid antigen.

In response to the COVID-19 pandemic, lateral flow assays (LFAs) for the detection of SARS-CoV-2 antigen have been proposed as a complementary option to the more costly and time consuming reverse-transcriptase polymerase chain reaction (RT-PCR). We assessed five commercially available SARS-CoV-2 antigen detecting LFAs (ASSUT EUROPE (Rome, Italy), Besthree (Taizhou, China), Encode (Zhuhai, China), Fortress (Antrim UK), and Hughes Medical (Buckinghamshire, UK), using samples collected from hospitalised individuals with COVID-19 and compared these results against established RT-PCR assays with the aim of estimating test performance characteristics. We performed a diagnostic accuracy study of the five LFAs on 110 inpatients with confirmed COVID-19 and 75 COVID-19 negative control participants. Assay evaluation was performed using a modified version of each manufacturer's protocol allowing for parallel testing of a single sample on multiple assays. Additional variables were studied including infection acquisition, oxygenation requirements at time of swabbing, and patient outcomes. The 110 patients were 48% (53) female, with mean age 67 years (range 26-100 years), and 77% (85) cases were community onset SARS-CoV-2. Across the five assays, sensitivity ranged from 64 (95% CI 53-73) to 76% (95% CI 65-85); Fortress performed best with sensitivity of 76% (95% CI 65-85). Specificity was high across all assays with 4/5 LFAs achieving 100%. LFA sensitivity was not dependant on RT-PCR cycle thresholds. SARS-CoV-2 antigen detecting LFAs may complement RT-PCR testing to facilitate early diagnosis and provide community testing strategies for identification of patients with COVID-19, however we find suboptimal test performance characteristics across a range of commercially available manufacturers, below WHO and MHRA pre-set sensitivity performance thresholds. With such variation in sensitivity between LFAs and PCR testing and between assay brands, we advise caution in the deployment of LFAs outside of environments with clinical oversight.

Disposable FFP2 and Type IIR Medical-Grade Face Masks: An Exhaustive Analysis into the Leaching of Micro- and Nanoparticles and Chemical Pollutants Linked to the COVID-19 Pandemic.

The COVID-19 pandemic has increased the worldwide production and use of disposable plastic face masks (DPFMs). The release of micro- and nanopollutants into the environment is one of the impacts derived from regulated and unregulated disposal of DPFMs. This study focuses on the emission of pollutants from medical-grade DPFMs when submerged in deionized water, simulating regulated and unregulated disposal of these masks. Three brands of FFP2 and three brands of Type IIR medical masks, produced in various countries (UK, EU, and non-EU), were investigated. Field emission gun scanning electron microscopy (FEG-SEM) was used to obtain high-resolution images of the micro- and nanoparticles, and 0.02 µm pore size inorganic membranes were used to retain and subsequently analyze smaller particle size nanoparticles (>20 nm) released from the DPFMs. Particles and fibers in the micro- and nanoscale were found in all six DPFM brands. SEM with energy-dispersive spectroscopy analysis revealed the presence of particles containing different heavy metals like lead, mercury, and arsenic. Inductively coupled plasma mass spectrometry analysis confirmed the leaching of trace heavy metals to water (antimony up to 2.41 µg/L and copper up to 4.68 µg/L). Liquid chromatography-mass spectrometry analysis identified polar organic species related to plastic additives and contaminants such as polyamide-66 monomers and oligomers.

Impact of coronavirus disease 2019 on head and neck urgent suspected cancer referral pathways in rural Wales.

OBJECTIVE: To assess the impact of the coronavirus disease 2019 pandemic on head and neck urgent suspected cancer referral pathways in rural areas of Wales. METHOD: A retrospective audit was conducted of 2234 head and neck urgent suspected cancer referrals received from January 2019 to November 2020. RESULTS: The referrals dropped by 35 per cent in 2020 compared to the same period in 2019. The time from general practitioner referral to the first ENT appointment improved during the pandemic (8.0 vs 10.0 days; p < 0.001). Of referrals, 92.1 per cent were seen within a 14-day period in 2020, compared with 79.6 per cent in 2019 (p < 0.001). There were no differences between 2020 and 2019 in terms of: the (confirmed cancer) conversion rate (10.6 per cent vs 9.7 per cent; p = 0.60), general practitioner referral to multidisciplinary team discussion time (35.5 vs 41.5 days; p = 0.40) or general practitioner referral to initiation of treatment time (68.0 vs 78.0 days; p = 0.16). CONCLUSION: Whilst coronavirus disease 2019 reduced the number of overall head and neck urgent suspected cancer referrals, the pathways were generally unchanged, if not slightly improved, in rural Wales.

Search for Active-Sterile Antineutrino Mixing Using Neutral-Current Interactions with the NOvA Experiment.

This Letter reports results from the first long-baseline search for sterile antineutrinos mixing in an accelerator-based antineutrino-dominated beam. The rate of neutral-current interactions in the two NOvA detectors, at distances of 1 and 810 km from the beam source, is analyzed using an exposure of 12.51×10^{20} protons-on-target from the NuMI beam at Fermilab running in antineutrino mode. A total of 121 of neutral-current candidates are observed at the far detector, compared to a prediction of 122±11(stat.)±15(syst.) assuming mixing only between three active flavors. No evidence for ν[over ¯]_{µ}→ν[over ¯]_{s} oscillation is observed. Interpreting this result within a 3+1 model, constraints are placed on the mixing angles θ_{24}<25° and θ_{34}<32° at the 90% C.L. for 0.05 eV^{2}≤Δm_{41}^{2}≤0.5 eV^{2}, the range of mass splittings that produces no significant oscillations at the near detector. These are the first 3+1 confidence limits set using long-baseline accelerator antineutrinos.

A prospective observational study of preoperative natriuretic peptide testing in adult non-cardiac surgical patients in hospitals in Western Cape Province, South Africa.

BACKGROUND: International guidelines recommend risk stratification to identify high-risk non-cardiac surgical patients. It is also recommended that all patients aged ≥45 years with significant cardiovascular disease should have preoperative natriuretic peptide (NP) testing. Abnormal preoperative B-type NPs have a strong association with postoperative cardiac complications. In South African hospitals, it is not known how many patients with significant cardiovascular disease scheduled for intermediate- to high-risk surgery will have raised NPs. OBJECTIVES: To determine the prevalence of abnormal (raised) NPs in non-cardiac surgical patients with cardiac clinical risk factors. A secondary objective was to develop a model to identify surgical patients who may benefit from preoperative NP screening. METHODS: The inclusion criteria were patients aged ≥45 years presenting for elective, non-obstetric, intermediate- to high-risk non-cardiac surgery with at least one of the following cardiovascular risk factors: a history of ischaemic heart disease or peripheral vascular disease (coronary equivalent); a history of stroke or transient ischaemic attack; a history of congestive cardiac failure; diabetes mellitus currently on an oral hypoglycaemic agent or insulin; and serum creatinine level >175 µmol/L (>2.0 mg/dL). Blood samples for N-terminal-prohormone B-type NP (NT-proBNP) were collected before induction of anaesthesia. The preoperative prognostic threshold for abnormal (raised) NT-proBNP was ≥300 pg/mL. A generalised linear mixed model was used to determine the association between the risk factors and an abnormal NT-proBNP level. RESULTS: Of 172 patients, 63 (37%) had an elevated preoperative NT-proBNP level. The comorbidities independently associated with elevated preoperative NT-proBNP were coronary artery disease or peripheral vascular disease, congestive cardiac failure, and a creatinine level >175 µmol/L CONCLUSIONS: We strongly recommend that non-cardiac surgical patients aged ≥45 years undergoing intermediate- or high-risk noncardiac surgery with a history of coronary artery disease/peripheral vascular disease, congestive cardiac failure or elevated creatinine have preoperative NP testing as part of risk stratification.

Optimising equity of access: how should we allocate slots to the most competitive trials in Cystic Fibrosis (CF)?

BACKGROUND: Trial participation can allow people with CF early access to CFTR modulator therapies, with high potential for clinical benefit. Therefore, the number of people wishing to participate can substantially exceed the number of slots available. We aimed to understand how the CF community thinks slots to competitive trials should be allocated across the UK and whether this should be driven by clinical need, patients' engagement/adherence or be random. For the latter, we explored site-level versus registry-based, national randomisation processes. METHODS: We developed an online survey, recruiting UK-based stakeholders through social media, newsletters and personal contacts. Closed questions were analysed for frequencies and percentages of responses. Free-text questions were analysed using thematic analysis. RESULTS: We received 203 eligible responses. Overall, 75% of stakeholders favoured allocation of slots to individual sites based on patient population size, although pharma favoured allocation based on previous metrics. Currently, few centres have defined strategies for allocating slots locally. At face-value, stakeholders believe all eligible participants should have an equal chance of getting a slot. However, further questioning reveals preference for prioritisation strategies, primarily perceived treatment adherence, although healthcare professionals were less likely to favour this strategy than other stakeholder groups. The majority of stakeholders would prefer to allocate slots and participate in trials locally but 80% said if necessary, they would engage in a system of national allocation. CONCLUSIONS: Fair allocation to highly competitive trials does not appear to have a universally acceptable solution. Therefore, transparency and empathy remain critical to negotiate this uncertain territory.

Restoration of gallery forest patches improves recruitment of motacú palms (Attalea princeps) while diversifying and increasing wildlife populations.

Globally, forest-savanna mosaic landscapes are of significant conservation importance but have been widely impacted by human land-use. We studied how restoration, through cessation of long-term cattle grazing impacts (i) forest regeneration; (ii) forest understory structure and composition; and (iii) populations and diversity of large mammals and nocturnal birds, within naturally patchy gallery forests in the Beni Savannas of Bolivia. Comparing grazed and restored sites, we assessed the abundance and composition of tree functional types at different life stages (seedlings, saplings and adults), with focus on the region's key palm species Attalea princeps (motacú). Additionally, we surveyed habitat structure and composition in the shrub and ground-layer, and monitored occurrence and encounter rates of large mammals and nocturnal birds along dusk and evening transects. We found evidence of lower recruitment of motacú palms on the grazed site and lower potential for natural motacú regeneration. Principal Components Analysis revealed forests on grazed sites had simpler, more open shrub-layers and altered ground-layer structure and composition including increased bare ground. Mammal species richness was greater on the restored site, and there were more declining, globally threatened and site-unique species. Species richness was similar for nocturnal birds within forests on both the grazed and restored site, but nearly all species tended to be encountered more frequently on the restored site. Our results suggest cattle negatively impact forest regeneration and alter the structure and composition of the shrub and ground layer with potential consequences for the diversity and abundance of wildlife. Our study represents one of only a handful completed in the Beni region of Bolivia to date. The Beni is currently under pressure from widespread, largely unregulated cattle ranching. Our results thus provide vital evidence to support development of restoration and conservation policy, and its integration with rangeland management in this threatened and critically understudied region.

Asthma and high-intensity interval training have no effect on clustered cardiometabolic risk or arterial stiffness in adolescents.

PURPOSE: Cardiometabolic risk, including arterial stiffness, is increasing in youth. Those with asthma are suggested to be particularly at risk of cardiovascular disease. Efficient and effective strategies are required to prevent the atherosclerotic process in youth. The purpose of this study was to investigate the effect of 6 months high-intensity interval training (HIIT) on cardiometabolic risk in youth with and without asthma. METHODS: 65 adolescents (31 mild asthma; 34 non-asthma) were recruited, 32 (16 asthma) of whom were randomly allocated to receive HIIT three times per week for 6 months. At baseline, mid-intervention, post-intervention and at a 3-month follow-up, anthropometric, metabolic and vascular determinants of cardiometabolic risk were assessed. Following principal component analysis (PCA), linear mixed models were used to assess the influence of asthma, HIIT and their interaction. RESULTS: Seven factors were identified which explained 88% of the common variance shared among the parameters. Those with asthma demonstrated lower arterial stiffness factor scores mid-intervention (P = 0.047) and lower cholesterol factor scores post-intervention (P = 0.022) but there was no effect of the intervention, or interaction effects, on any PCA-identified factor, at any time-point. HIIT was associated with a lower low-density lipoprotein and diastolic blood pressure at mid-intervention. DISCUSSION: Neither arterial stiffness nor clustered cardiometabolic risk are influenced by HIIT in adolescents with or without asthma, despite important changes in blood lipid and pressure profiles. Blood pressure, augmentation and pulse wave velocity should be considered physiologically distinct constructs and as potential markers of cardiovascular health.

Point-of-care SARS-CoV-2 serological assays for enhanced case finding in a UK inpatient population.

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Case identification is currently made by real-time polymerase chain reaction (PCR) during the acute phase and largely restricted to healthcare laboratories. Serological assays are emerging but independent validation is urgently required to assess their utility. We evaluated five different point-of-care (POC) SARS-CoV-2 antibody test kits against PCR, finding concordance across the assays (n = 15). We subsequently tested 200 patients using the OrientGene COVID-19 IgG/IgM Rapid Test Cassette and find a sensitivity of 74% in the early infection period (day 5-9 post symptom onset), with 100% sensitivity not seen until day 13, demonstrating inferiority to PCR testing in the infectious period. Negative rate was 96%, but in validating the serological tests uncovered potential false-negatives from PCR testing late-presenting cases. A positive predictive value (PPV) of 37% in the general population precludes any use for general screening. Where a case definition is applied however, the PPV is substantially improved (95.4%), supporting use of serology testing in carefully targeted, high-risk populations. Larger studies in specific patient cohorts, including those with mild infection are urgently required to inform on the applicability of POC serological assays to help control the spread of SARS-CoV-2 and improve case finding of patients that may experience late complications.

In vitro characterization of the effects of chronic insulin stimulation in mouse 3T3-L1 and human SGBS adipocytes.

Hyperinsulinemia is the hallmark of the development of insulin resistance and precedes the diagnosis of type 2 diabetes. Here we evaluated the effects of prolonged exposure (≥4 days) to high insulin doses (150 nM) in vitro in two adipose cell types, mouse 3T3-L1 and human SGBS. Chronic insulin treatment significantly decreased lipid droplet size, insulin signalling and insulin-stimulated glucose uptake. 3T3-L1 displayed an increased basal glucose internalization following chronic insulin treatment, which was associated with increased GLUT1 expression. In addition, both cells showed increased basal lipolysis. In conclusion, we report the effects of prolonged hyperinsulinemia in 3T3-L1 and SGBS, highlighting similarities and discrepancies between the cell types, to be considered when using these cells to model insulin-induced insulin resistance.

Associations between caries levels and BMI measures among five-year-old children. Analysis and cross-sectional multi-variable analysis at individual child level.

OBJECTIVES: To establish the existence and directions of any associations between measures of body mass index (BMI) with caries levels using individual measures of each as derived from national surveys in England. METHODS: The BMIs of five-year-old children calculated from the 2017 National Child Measurement Programme and caries measures from the 2016-17 Public Health England (PHE) National dental epidemiology survey were securely linked at a child level. Comparison at individual level of caries levels and BMI z scores was done using multivariable regression. RESULTS: Records for 67,033 children were linked and allocated a deprivation quintile. An association between BMI Z score categories and caries levels was established. Caries prevalence was higher among overweight (24.4%) and very overweight (27.6%) children compared with those of average BMI (22.5%). Odds ratios were statistically significant at 1.08 and 1.14 for prevalence among overweight and very overweight children. Children of low BMI were found to have higher caries severity (1.2 d3mft) and extent (4.4 d3mft among those with any caries) compared to children of healthy BMI (0.7 d3mft, 3.3 d3mft) with statistically significant Incidence Rate Ratio of 1.24. Underweight children were more likely to have caries experience and more severe attack compared with children of healthy weight. Deprivation and ethnicity were confounding factors. CONCLUSIONS: There is some association between child BMI status and caries levels whereby caries prevalence among children of higher BMI is increased. The associations are over and above those of deprivation, ethnicity and water fluoridation individually, but these factors impact on the strength of the link between BMI and caries.