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Grapevine water status exhibits substantial variability even within a single vineyard. Understanding how edaphic, topographic, and climatic conditions impact grapevine water status heterogeneity at the field scale, in non-irrigated vineyards, is essential for winemakers as it significantly influences wine quality. This study aimed to quantify the spatial distribution of grapevine leaf water potential (Ψleaf) within vineyards and to assess the influence of soil property heterogeneity, topography, and climatic conditions on intra-field variability in two non-irrigated vineyards during two viticultural seasons. By combining multilinear vegetation indices from very-high-spatial-resolution multispectral, thermal, and lidar imageries collected with uncrewed aerial systems (UASs), we efficiently and robustly captured the spatial distribution of Ψleaf across both vineyards on different dates. Our results demonstrated that in non-irrigated vineyards, the spatial distribution of Ψleaf was mainly governed by the within-vineyard soil hydraulic conductivity heterogeneity (R2 up to 0.81) and was particularly marked when the evaporative demand and the soil water deficit increased, since the range of Ψleaf was greater, up to 0.73 MPa, in these conditions. However, topographic attributes (elevation and slope) were less related to grapevine Ψleaf variability. These findings show that the soil property within-field spatial distribution and climatic conditions are the primary factors governing Ψleaf heterogeneity observed in non-irrigated vineyards, and their effects are concomitant.

The collection of this dataset of published archaeobotanical data from the Indus Civilisation (c.3200–1500BC) was carried out by the author as part of her doctoral work, and has continued up to October 2017. The dataset represents a systematic collation of all primary published macrobotanical data, regardless of their designation as ‘crop’, ‘fully domesticated’ or ‘wild/weedy’ species. The dataset comprises 63 sites and 339 ‘taxa’ (including less confidently identified elements such as ‘charred seed’). Data is presented as presence/absence due to different sampling, quantification and data presentation practices. Funding statement: This paper developed out of research conducted while the author was a PhD student working as part of the 'Land, Water and Settlement' project, which has been investigating human–environment relations in northwest India. It presents material gathered for a literature review that formed part of the author’s PhD dissertation, and expanded upon during her first post-doctoral position as Trevelyan research fellow at Selwyn College, University of Cambridge. The PhD research was funded by the Arts and Humanities Research Council (AHRC), United Kingdom (Grant No. 1080510), and this paper has been written up while she has been a Post-doctoral Research Associate at the Joukowsky Institute for Archaeology and the Ancient World, Brown University, and published while she is a post doctoral fellow at the Department of Anthropology, University of Pennsylvania. The 'Land, Water and Settlement' project ran from 2007 to 2014 and was primarily funded by a Standard Award from the UK India Education Research Initiative United Kingdom (UKIERI) under the title ‘From the collapse of Harappan urbanism to the rise of the great Early Historic cities: Investigating the cultural and geographical transformation of northwest India between 2000 and 300 BC’. Smaller grants were also awarded by the British Academy’s Stein Arnold Fund, United Kingdom, the Isaac Newton Trust, the McDonald Institute for Archaeological Research, United Kingdom, and the Natural Environment Research Council (NERC), United Kingdom.

This study presents the first genome and transcriptome analyses for Fusarium oxysporum f. sp. lactucae (Fola) which causes Fusarium wilt disease of lettuce. Long-read genome sequencing of three race 1 (Fola1) and three race 4 (Fola4) isolates revealed key differences in putative effector complement between races and with other F. oxysporum ff. spp. following mimp-based bioinformatic analyses. Notably, homologues of Secreted in Xylem (SIX) genes, also present in many other F. oxysporum ff. spp, were identified in Fola, with both SIX9 and SIX14 (multiple copies with sequence variants) present in both Fola1 and Fola4. All Fola4 isolates also contained an additional single copy of SIX8. RNAseq of lettuce following infection with Fola1 and Fola4 isolates identified highly expressed effectors, some of which were homologues of those reported in other F. oxysporum ff. spp. including several in F. oxysporum f. sp. apii. Although SIX8, SIX9 and SIX14 were all highly expressed in Fola4, of the two SIX genes present in Fola1, only SIX9 was expressed as further analysis revealed that SIX14 gene copies were disrupted by insertion of a transposable element. Two variants of Fola4 were also identified based on different genome and effector-based analyses. This included two different SIX8 sequence variants which were divergently transcribed from a shared promoter with either PSE1 or PSL1 respectively. In addition, there was evidence of two independent instances of HCT in the different Fola4 variants. The involvement of helitrons in Fola genome rearrangement and gene expression is discussed.

IntroductionDelivering surfactant via thin catheters (minimal-invasive surfactant therapy (MIST); less invasive surfactant administration (LISA)) has become a common procedure. However, the effect of tracheal obstruction caused by catheters of different sizes on tracheal resistance in extremely low gestational age newborns (ELGANs) is unknown.MethodsTo investigate the effect of catheters size 3.5, 5 and 6 French on airway resistance in ELGANs of 23–28 weeks gestational age during LISA, we performed calculations based on Hagen-Poiseuille's law and compared these with a clinically and physically more accurate method: computational fluid dynamics (CFD) simulations of respiratory airflow, performed in 3D virtual airway models derived from MRI.ResultsThe presence of the above catheters decreased the cross-sectional area of the infants' tracheal entrance (the cricoid ring) by 13–53%. Hagen-Poiseuille's law predicted an increase in resistance by 1.5–4.5 times and 1.3–2.6 times in ELGANs born at 23 and 28 weeks, respectively. However, CFD simulations demonstrated an even higher increase in resistance of 3.4–85.1 and 1.1–3.5 times, respectively. The higher calculated resistances were due to the extremely narrow remaining lumen at the glottis and cricoid with the catheter inserted, resulting in a stronger glottal jet and turbulent airflow, which was not predicted by Hagen-Poiseuille.ConclusionCatheter thickness can greatly increase tracheal resistance during LISA-procedures in ELGANs. Based on these models, it is recommended to use the thinnest catheter possible during LISA in ELGANs to avoid unnecessary increases in airway resistance in infants already experiencing dyspnea due to respiratory distress syndrome.

Abstract Decongestion reduces blood flow in the nasal turbinates, enlarging the airway lumen. Although the enlarged airspace reduces the trans-nasal inspiratory pressure drop, symptoms of nasal obstruction may relate to nasal cavity air-conditioning. Thus, it is necessary to quantify the efficiency of nasal cavity conditioning of the inhaled air. This study quantifies both overall and regional nasal air-conditioning in a cohort of 10 healthy subjects using computational fluid dynamics simulations before and after nasal decongestion. The 3D virtual geometry model was segmented from magnetic resonance images (MRI). Each subject was under two MRI acquisitions before and after the decongestion condition. The effects of decongestion on nasal cavity air conditioning efficiency were modelled at two inspiratory flowrates: 15 and 30 L min−1 to represent restful and light exercise conditions. Results show inhaled air was both heated and humidified up to 90% of alveolar conditions at the posterior septum. The air-conditioning efficiency of the nasal cavity remained nearly constant between nostril and posterior septum but dropped significantly after posterior septum. In summary, nasal cavity decongestion not only reduces inhaled air added heat by 23% and added moisture content by 19%, but also reduces the air-conditioning efficiency by 35% on average.

Abstract Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species’ population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate ‘intactness scores’: the remaining proportion of an ‘intact’ reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region’s major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems.

Abstract Current myocardial infarction treatments focus on improving hemodynamics rather than addressing the problem of lost myocardium impairing left ventricular function. Epicardial infarct repair with a bioactive patch placed on the ischemic area is an emerging approach to promote endogenous myocardial repair. We report the use of a second-generation CorMatrix-extracellular matrix (ECM) patch as an adjunct to surgical revascularization in treating a young patient with diffuse, multivessel coronary artery disease unamenable to PCI and a large anterior myocardial infarction. The progressive myocardial scar shrinkage and increase in left ventricular ejection fraction from 10 to 51% are generally not observed with surgical revascularization therapy alone, suggesting this new patch has adjunctive potential to current revascularization therapy.

Background: Few interventions are documented to meet person-centred needs of older people with serious multimorbidity in low- and middle-income countries where access to palliative care is limited. Most of the care in these settings is delivered by primary care health workers. Aim: This study reports the development and acceptability testing of a communication skills training and mentorship intervention for primary health care workers in Malawi. Setting: This study was conducted at Mangochi District Hospital in the south-eastern region of Malawi. Methods: Twelve primary health care workers (four clinical officers and eight nurses) working in the primary care clinics received the intervention. The intervention was designed using modified nominal group technique, informed by stakeholder interviews and a theory of change workshop. Acceptability is reported from thematic analysis of a focus group discussion with primary health care workers who received the intervention using NVivo version 14. Results: Older persons with serious multi-morbidity and their caregivers identified a need for enhanced communication with their healthcare providers. This helped to inform the development of a communication training skills and mentorship intervention package based on the local best practice six-step Ask-Ask-Tell-Ask-Ask-Plan framework. Primary health care workers reported that the intervention supported person-centred communication and improved the quality of holistic assessments, although space, workload and availability of medication limited the implementation of person-centred communication. Conclusion: The Ask-Ask-Tell-Ask-Ask-Plan framework, supported person-centered communication and improved the quality of holistic assessment. Contribution: This intervention offers an affordable, local model for integrating person-centered palliative care in resource-limited primary healthcare settings.

Abstract Infective endocarditis caused by Mycobacterium abscessus is an uncommon event that, when it does occur, usually requires surgical valve replacement. The pulmonary valve is the least common heart valve involved in infective endocarditis. We present a rare case of isolated pulmonary valve endocarditis with Mycobacterium abscessus in a patient with recurrent sternal infections following repeated coronary artery bypass.

Key Clinical Message Despite emphasis for emergent surgical treatment of Stanford type A aortic dissections, pregnant patients that are clinically stable may safely receive a staged approach instead, with delivery followed by delayed dissection repair.

Red raspberry (Rubus idaeus L.) is an economically valuable soft-fruit species with a relatively small (~300 Mb) but highly heterozygous diploid (2n = 2x = 14) genome. Chromosome-scale genome sequences are a vital tool in unravelling the genetic complexity controlling traits of interest in crop plants such as red raspberry, as well as for functional genomics, evolutionary studies, and pan-genomics diversity studies. In this study, we developed genome sequences of a primocane fruiting variety ('Autumn Bliss') and a floricane variety ('Malling Jewel'). The use of long-read Oxford Nanopore Technologies sequencing data yielded long read lengths that permitted well resolved genome sequences for the two cultivars to be assembled. The de novo assemblies of 'Malling Jewel' and 'Autumn Bliss' contained 79 and 136 contigs respectively, and 263.0 Mb of the 'Autumn Bliss' and 265.5 Mb of the 'Malling Jewel' assembly could be anchored unambiguously to a previously published red raspberry genome sequence of the cultivar 'Anitra'. Single copy ortholog analysis (BUSCO) revealed high levels of completeness in both genomes sequenced, with 97.4% of sequences identified in 'Autumn Bliss' and 97.7% in 'Malling Jewel'. The density of repetitive sequence contained in the 'Autumn Bliss' and 'Malling Jewel' assemblies was significantly higher than in the previously published assembly and centromeric and telomeric regions were identified in both assemblies. A total of 42,823 protein coding regions were identified in the 'Autumn Bliss' assembly, whilst 43,027 were identified in the 'Malling Jewel' assembly. These chromosome-scale genome sequences represent an excellent genomics resource for red raspberry, particularly around the highly repetitive centromeric and telomeric regions of the genome that are less complete in the previously published 'Anitra' genome sequence.

Abstract Nasal decongestant reduces blood flow to the nasal turbinates, reducing tissue volume and increasing nasal airway patency. This study maps the changes in nasal anatomy and measures how these changes affect nasal resistance, flow partitioning between superior and inferior cavity, flow patterns and wall shear stress. High-resolution MRI was applied to capture nasal anatomy in 10 healthy subjects before and after application of a topical decongestant. Computational fluid dynamics simulated nasal airflow at steady inspiratory flow rates of 15 L.min $$^{-1}$$ - 1 and 30 L.min $$^{-1}$$ - 1 . The results show decongestion mainly increases the cross-sectional area in the turbinate region and SAVR is reduced (median approximately 40 $$\%$$ % reduction) in middle and lower parts of the cavity. Decongestion reduces nasal resistance by 50 $$\%$$ % on average, while in the posterior cavity, nasal resistance decreases by a median factor of approximately 3 after decongestion. We also find decongestant regularises nasal airflow and alters the partitioning of flow, significantly decreasing flow through the superior portions of the nasal cavity. By comparing nasal anatomies and airflow in their normal state with that when pharmacologically decongested, this study provides data for a broad range of anatomy and airflow conditions, which may help characterize the extent of nasal variability.

BackgroundEquitable cancer survivorship care for gay and bisexual male (GBM) prostate cancer survivors should be responsive to their sexual health needs. Rates of sexually transmitted infections (STIs) are higher among GBM compared to heterosexual men across the lifespan. In addition, evidence suggests that GBM will use a variety of strategies to cope with sexual dysfunction that may increase risk for STIs. The purpose of this study was to determine the prevalence of STIs following prostate cancer treatment among GBM and identify risk factors.MethodsIn 2019, 401 GBM previously treated for prostate cancer were recruited into the Restore-2 Study. They completed a baseline online questionnaire with items assessing STIs diagnosed since being treated for prostate cancer. Any STI diagnoses was regressed on demographic, clinical, and relationship related variables using binary logistic regression.ResultsForty-five participants (11.4%) were diagnosed with an STI during or following their prostate cancer treatment. The mostly commonly diagnosed STI was syphilis (4.3%), followed by gonorrhoea (2.8%), and chlamydia (2.5%). Four participants were infected with HIV following their prostate cancer treatment. Independent risk factors for STI diagnosis included time since prostate cancer diagnosis (aOR = 1.18; 95% CI: 1.10-1.26), nonmonogamous sexual relationship (aOR = 11.23; 95% CI: 2.11-59.73), better sexual function (aOR = 1.02; 95% CI: 1.01-1.04), penile injection treatment (aOR = 3.28; 95% CI: 1.48-7.29), and multiple sex partners (aOR = 5.57; 95% CI: 1.64-18.96).ConclusionsGBM prostate cancer survivors are at risk for STIs. Culturally responsive STI prevention should be incorporated into cancer survivorship plans, particularly as men are treated for and regain sexual function over time.

IntroductionProstate cancer treatment has established effects on the health-related quality of life (HRQOL) of patients. While racial/ethnic differences in HRQOL have been explored in heterosexual patients, this is the first study to examine racial/ethnic differences in a cohort of sexual minority prostate cancer survivors.MethodsWe used data from the Restore-1 study, an online cross-sectional survey of sexual and gender minority (SGM) prostate cancer survivors in North America, to explore the association between race/ethnicity and HRQOL. General mental and physical HRQOL was assessed using the Short-Form Health Survey version 2 (SF-12). The frequency and distress of prostate cancer specific symptoms was assessed using the Expanded Prostate Cancer Composite (EPIC) scale. Multivariable linear regression was used to estimate mean differences in HRQOL between sexual minority men of color and their white, non-Hispanic counterparts after adjustment for pertinent demographic and medical characteristics.ResultsAmong 190 participants, 23 (12%) self-identified as non-white and/or Hispanic. In unadjusted analysis, sexual minority men of color compared to their white counterparts reported worse HRQOL scores in the EPIC hormonal summary (73.8 vs. 81.8) and hormonal function (70.9 vs 80.5) domains. Clinically important differences between men of color and their white counterparts were seen in the EPIC bowel function (mean difference (MD): -4.5, 95% CI: -9.9, 0.8), hormonal summary (MD: -8.0, 95% CI: -15.6, -0.4), hormonal function (MD: -9.6, 95% CI: -17.6, -1.6), and hormonal bother (MD: -6.7, 95% CI: -14.4, 1.1) domains. After adjustment for covariates, clinically important differences persisted between men of color and white, non-Hispanic men on the hormonal summary (74.4 vs. 81.7), hormonal function (71.3 vs. 80.3), and hormonal bother (77.0 vs. 82.7) domains.ConclusionsThis exploratory study provides the first evidence that sexual minority men of color may have worse HRQOL outcomes compared to white, non-Hispanic sexual minority men following prostate cancer treatment.

BackgroundThere is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation.Methods and findingsWith the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes. We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for ≤315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [p < 0.001] and 1.74, 1.61 to 1.88 versus influenza controls [p < 0.001]). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants.ConclusionsIn this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.

Gold nanoparticles (GNPs) have immense potential in biomedicine, but understanding their interactions with serum proteins is crucial as it could change their biological profile due to the formation of a protein corona, which could then affect their ultimate biodistribution in the body. Grafting GNPs with polyethylene glycol (PEG) is a widely used practice in research in order to decrease opsonization of the particles by serum proteins and to decrease particle uptake by the mononuclear phagocyte system. We investigated the impact of PEGylation on the formation of protein coronae and the subsequent uptake by macrophages and MDA-MB-231 cancer cells. Furthermore, we investigated the in vivo biodistribution in xenograft tumor-bearing mice using a library of 4 and 10 nm GNPs conjugated with a gadolinium chelate as MRI contrast agent, cancer-targeting aptamer AS1411 (or CRO control oligonucleotide), and with or without PEG molecules of different molecular weight (Mw: 1, 2, and 5 kDa). In vitro results showed that PEG failed to decrease the adsorption of proteins; moreover, the cellular uptake by macrophage cells was contingent on the different configurations of the aptamers and the length of the PEG chain. In vivo biodistribution studies showed that PEG increased the uptake by tumor cells for some GNPs, albeit it did not decrease the uptake of GNPs by macrophage-rich organs.

Objectives COVIDTrach is a UK multicentre prospective cohort study project that aims to evaluate the outcomes of tracheostomy in patients with COVID-19 receiving mechanical ventilation and record the incidence of SARS-CoV-2 infection among healthcare workers involved in the procedure.Design Data on patient demographic, clinical history and outcomes were entered prospectively and updated over time via an online database (REDCap). Clinical variables were compared with outcomes, with logistic regression used to develop a model for mortality. Participants recorded whether any operators tested positive for SARS-CoV-2 within 2 weeks of the procedure.Setting UK National Health Service departments involved in treating patients with COVID-19 receiving mechanical ventilation.Participants The cohort comprised 1605 tracheostomy cases from 126 UK hospitals collected between 6 April and 26 August 2020.Main outcome measures Mortality following tracheostomy, successful wean from mechanical ventilation and length of time from tracheostomy to wean, discharge from hospital, complications from tracheostomy, reported SARS-CoV-2 infection among operators.Results The median time from intubation to tracheostomy was 15 days (IQR 11, 21). 285 (18%) patients died following the procedure. 1229 (93%) of the survivors had been successfully weaned from mechanical ventilation at censoring and 1049 (81%) had been discharged from hospital. Age, inspired oxygen concentration, positive end-expiratory pressure setting, fever, number of days of ventilation before tracheostomy, C reactive protein and the use of anticoagulation and inotropic support independently predicted mortality. Six reports were received of operators testing positive for SARS-CoV-2 within 2 weeks of the procedure.Conclusions Tracheostomy appears to be safe in mechanically ventilated patients with COVID-19 and to operators performing the procedure and we identified clinical parameters that are predictive of mortality.Trial registration number The study is registered with ClinicalTrials.Gov (NCT04572438).

Glioblastoma brain tumors represent an aggressive form of gliomas that is hallmarked by being extremely invasive and aggressive due to intra and inter-tumoral heterogeneity. This complex tumor microenvironment makes even the newer advancements in glioblastoma treatment less effective long term. In developing newer treatment technologies against glioblastoma, one should tailor the treatment to the tumor microenvironment, thus allowing for a more robust and sustained anti-glioblastoma effect. Here, we present a novel gold nanoparticle therapy explicitly designed for bioactivity against glioblastoma representing U87MG cell lines. We employ standard conjugation techniques to create oligonucleotide-coated gold nanoparticles exhibiting strong anti-glioblastoma behavior and optimize their design to maximize bioactivity against glioblastoma. Resulting nanotherapies are therapy specific and show upwards of 75% inhibition in metabolic and proliferative activity with stark effects on cellular morphology. Ultimately, these gold nanotherapies are a good base for designing more multi-targeted approaches to fighting against glioblastoma.

Background: Mortality from COVID-19 shows a strong relationship with age and pre-existing medical conditions, as does mortality from other causes. We aimed to investigate how specific factors are differentially associated with COVID-19 mortality as compared to mortality from causes other than COVID-19. Methods: Working on behalf of NHS England, we carried out a cohort study within the OpenSAFELY platform. Primary care data from England were linked to national death registrations. We included all adults (aged ≥18 years) in the database on 1st February 2020 and with >1 year of continuous prior registration; the cut-off date for deaths was 9th November 2020. Associations between individual-level characteristics and COVID-19 and non-COVID deaths, classified according to the presence of a COVID-19 code as the underlying cause of death on the death certificate, were estimated by fitting age- and sex-adjusted logistic models for these two outcomes. Findings: 17,456,515 individuals were included. 17,063 died from COVID-19 and 134,316 from other causes. Most factors associated with COVID-19 death were similarly associated with non-COVID death, but the magnitudes of association differed. Older age was more strongly associated with COVID-19 death than non-COVID death (e.g. ORs 40.7 [95% CI 37.7-43.8] and 29.6 [28.9-30.3] respectively for ≥80 vs 50-59 years), as was male sex, deprivation, obesity, and some comorbidities. Smoking, history of cancer and chronic liver disease had stronger associations with non-COVID than COVID-19 death. All non-white ethnic groups had higher odds than white of COVID-19 death (OR for Black: 2.20 [1.96-2.47], South Asian: 2.33 [2.16-2.52]), but lower odds than white of non-COVID death (Black: 0.88 [0.83-0.94], South Asian: 0.78 [0.75-0.81]). Interpretation: Similar associations of most individual-level factors with COVID-19 and non-COVID death suggest that COVID-19 largely multiplies existing risks faced by patients, with some notable exceptions. Identifying the unique factors contributing to the excess COVID-19 mortality risk among non-white groups is a priority to inform efforts to reduce deaths from COVID-19. Funding: Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.

Fusarium oxysporum is a soilborne fungal plant pathogen responsible for causing disease in many economically important crops with “special forms” (formae speciales) adapted to infect specific plant hosts. F. oxysporum f. sp. pisi (FOP) is the causal agent of Fusarium wilt disease of pea. It has been reported in every country where peas are grown commercially. Disease is generally controlled using resistant cultivars possessing single major gene resistance and therefore there is a constant risk of breakdown. The main aim of this work was to characterise F. oxysporum isolates collected from diseased peas in the United Kingdom as well as FOP isolates obtained from other researchers representing different races through sequencing of a housekeeping gene and the presence of Secreted In Xylem (SIX) genes, which have previously been associated with pathogenicity in other F. oxysporum f. spp. F. oxysporum isolates from diseased United Kingdom pea plants possessed none or just one or two known SIX genes with no consistent pattern of presence/absence, leading to the conclusion that they were foot-rot causing isolates rather than FOP. In contrast, FOP isolates had different complements of SIX genes with all those identified as race 1 containing SIX1, SIX6, SIX7, SIX9, SIX10, SIX11, SIX12, and SIX14. FOP isolates that were identified as belonging to race 2 through testing on differential pea cultivars, contained either SIX1, SIX6, SIX9, SIX13, SIX14 or SIX1, SIX6, SIX13. Significant upregulation of SIX genes was also observed in planta over the early stages of infection by different FOP races in pea roots. Race specific SIX gene profiling may therefore provide potential targets for molecular identification of FOP races but further research is needed to determine whether variation in complement of SIX genes in FOP race 2 isolates results in differences in virulence across a broader set of pea differential cultivars.

Computational fluid dynamics (CFD) simulations of respiratory airflow have the potential to change the clinical assessment of regional airway function in health and disease, in pulmonary medicine and otolaryngology. For example, in diseases where multiple sites of airway obstruction occur, such as obstructive sleep apnea (OSA), CFD simulations can identify which sites of obstruction contribute most to airway resistance and may therefore be candidate sites for airway surgery. The main barrier to clinical uptake of respiratory CFD to date has been the difficulty in validating CFD results against a clinical gold standard. Invasive instrumentation of the upper airway to measure respiratory airflow velocity or pressure can disrupt the airflow and alter the subject's natural breathing patterns. Therefore, in this study, we instead propose phase contrast (PC) velocimetry magnetic resonance imaging (MRI) of inhaled hyperpolarized 129Xe gas as a non-invasive reference to which airflow velocities calculated via CFD can be compared. To that end, we performed subject-specific CFD simulations in airway models derived from 1H MRI, and using respiratory flowrate measurements acquired synchronously with MRI. Airflow velocity vectors calculated by CFD simulations were then qualitatively and quantitatively compared to velocity maps derived from PC velocimetry MRI of inhaled hyperpolarized 129Xe gas. The results show both techniques produce similar spatial distributions of high velocity regions in the anterior-posterior and foot-head directions, indicating good qualitative agreement. Statistically significant correlations and low Bland-Altman bias between the local velocity values produced by the two techniques indicates quantitative agreement. This preliminary in vivo comparison of respiratory airway CFD and PC MRI of hyperpolarized 129Xe gas demonstrates the feasibility of PC MRI as a technique to validate respiratory CFD and forms the basis for further comprehensive validation studies. This study is therefore a first step in the pathway towards clinical adoption of respiratory CFD.

The oomycete Phytophthora fragariae is a highly destructive pathogen of cultivated strawberry (Fragaria × ananassa), causing the root rotting disease, “red core”. The host-pathogen interaction has a well described gene-for-gene resistance relationship, but to date neither candidate avirulence nor resistance genes have been identified. We sequenced a set of American, Canadian, and United Kingdom isolates of known race type, along with three representatives of the closely related pathogen of the raspberry (Rubus idaeus), P. rubi, and found a clear population structure, with a high degree of nucleotide divergence seen between some race types and abundant private variation associated with race types 4 and 5. In contrast, between isolates defined as United Kingdom races 1, 2, and 3 (UK1-2-3) there was no evidence of gene loss or gain; or the presence of insertions/deletions (INDELs) or Single Nucleotide Polymorphisms (SNPs) within or in proximity to putative pathogenicity genes could be found associated with race variation. Transcriptomic analysis of representative UK1-2-3 isolates revealed abundant expression variation in key effector family genes associated with pathogen race; however, further long read sequencing did not reveal any long range polymorphisms to be associated with avirulence to race UK2 or UK3 resistance, suggesting either control in trans or other stable forms of epigenetic modification modulating gene expression. This work reveals the combined power of population resequencing to uncover race structure in pathosystems and in planta transcriptomic analysis to identify candidate avirulence genes. This work has implications for the identification of putative avirulence genes in the absence of associated expression data and points toward the need for detailed molecular characterisation of mechanisms of effector regulation and silencing in oomycete plant pathogens.