Rapid prototyping Lab-on-Chip devices for the future: A numerical optimisation of bulk optical parameters in microfluidic systems

Nuclear reactor process control is typically monitored for pure β-emitting radionuclides via manual sampling followed by laboratory analysis, leading to delays in data availability and response times. The development of an in situ microfluidic Lab on Chip (LoC) system with integrated detection capable of measuring pure β-emitting radionuclides presents a promising solution, enabling a reduction in occupational exposure and cost of monitoring whilst providing improved temporal resolution through near real-time data acquisition. However, testing prototypes with radioactive sources is time-consuming, requires specialist facilities/equipment, generates contaminated waste, and cannot rapidly evaluate a wide range of designs or configurations. Despite this, modelling multiple design parameters and testing their impact on detection with non-radioactive substitutes has yet to be adopted as best practice. The measurement of pure β emitters in aqueous media relies on the efficient transport of photons generated by the Cherenkov effect or liquid scintillators to the detector. Here we explore the role of numerical modelling to assess the impact of optical cell geometry and design on photon transmission and detection through the microfluidic system, facilitating improved designs to realise better efficiency of integrated detectors and overall platform design. Our results demonstrate that theoretical modelling and an experimental evaluation using non-radiogenic chemiluminescence are viable for system testing design parameters and their impact on photon transport. These approaches enable reduced material consumption and requirement for specialist facilities for handling radioactive materials during the prototyping process. This method establishes proof of concept and the first step towards numerical modelling approaches for the design optimisation of microfluidic LoC systems with integrated detectors for the measurement of pure β emitting radionuclides via scintillation-based detection

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

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

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

Evidence for the Preservation of Technogenic Tritiated Organic Compounds in an Estuarine Sedimentary Environment

The macrotidal Severn Estuary (southwestern UK) has received a broad range of industrial discharges since the beginning of the Industrial Revolution. A more recent anthropogenic input to the estuary has been technogenic tritium (specifically organically bound tritium, OBT). This was derived from a specialized industrial laboratory producing custom radiolabeled compounds for life science research and diagnostic testing from 1980 until 2008. While it was generally acknowledged that the radiological impact of the tritium discharges into the Estuary was small, public concern motivated the company and regulatory agencies to commission several research studies from 1998 to 2005 to better understand their environmental impact. This study examined OBT interaction with estuarine sediment by acquiring a broad range of geochemical and sedimentological data from a suite of sediment cores collected from the northern side of the Estuary. Two important observations are that the OBT compounds are strongly bound to the clay/silt fraction of sediment and that the down-core OBT profiles in intertidal and subtidal sediments are broadly similar to the discharge record. Geochemical and chronometric methods (Cu, Pb and Zn elemental profiles, 210Pb, 137Cs) provide important corroboration of the OBT record. A key additional piece of evidence that firmly authenticated the established chronology was the discovery of a previously unreported sedimentary marker layer that was generated by a major storm surge that occurred on December 13, 1981. Although this study has provided clear evidence of systematic accumulation of OBT in sedimentary sinks of the region, an estimation of its depositional inventory shows it represents only a small fraction of the total discharge. This modest retention in the principal sedimentary sinks of the Severn Estuary system reflects the particular dynamics of this highly macrotidal sediment starved estuary

The requirement for proper storage of nuclear and related decommissioning samples to safeguard accuracy of tritium data

Large volumes of potentially tritium-contaminated waste materials are generated during nuclear decommissioning that require accurate characterisation prior to final waste sentencing. The practice of initially determining a radionuclide waste fingerprint for materials from an operational area is often used to save time and money but tritium cannot be included because of its tendency to be chemically mobile. This mobility demands a specific measurement for tritium and also poses a challenge in terms of sampling, storage and reliable analysis. This study shows that the extent of any tritium redistribution during storage will depend on its form or speciation and the physical conditions of storage. Any weakly or moderately bound tritium (e.g. adsorbed water, waters of hydration or crystallisation) may be variably lost at temperatures over the range 100–300 °C whereas for more strongly bound tritium (e.g. chemically bound or held in mineral lattices) the liberation temperature can be delayed up to 800 °C. For tritium that is weakly held the emanation behaviour at different temperatures becomes particularly important. The degree of 3H loss and cross-contamination that can arise after sampling and before analysis can be reduced by appropriate storage. Storing samples in vapour tight containers at the point of sampling, the use of triple enclosures, segregating high activity samples and using a freezer all lead to good analytical practice

Low microbial respiration of leucine at ambient oceanic concentration in the mixed layer of the central Atlantic Ocean

Bacterioplankton are the primary consumers of dissolved organic matter in the ocean, thus the quantification of bacterioplankton production (BP) is essential to our understanding of carbon cycling in the largest ecosystems on Earth. We compared BP, measured as the rate of 14C-leucine or 3H-leucine uptake at close to saturating concentration (20 nmol L−1), with ambient uptake measured from dilution bioassays. We hypothesized that saturation with leucine would lead to its respiration as a carbon source, thereby not truly representing ambient BP. Seawater was collected from the photic zone throughout the Atlantic Ocean. Respiration as a proportion of total consumption (uptake + respiration) of close to ambient (0.4 nmol L−1) and close to saturating (20 nmol L−1) 14C-leucine concentrations were compared. Saturating 3H-leucine additions overestimated ambient leucine uptake at low rates (200% ± 100% ambient) and underestimated uptake at high rates (90% + 20% ambient). The proportion of total leucine uptake that was respired was threefold higher for 20 nmol L−1 14C-leucine additions than 0.4 nmol L−1 14C-leucine additions (15% ± 8% and 5% ± 4%, respectively). Consequently, microbial efficiency of leucine assimilation—an indicator of bacterioplankton growth efficiency—was significantly higher and more stable at close to ambient 14C-leucine additions than at saturating concentrations (95% ± 4% and 85% ± 8%, respectively). Thus, saturation of oligotrophic open Atlantic Ocean bacterioplankton with leucine, or other molecules indicative of microbial metabolism, leads to the measurement of a response to a nutrient addition, rather than an ambient measurement