Assessing periparturient ewe characteristics and nemabiome composition to guide targeted selective treatment for sustainable gastrointestinal nematodes control in sheep.

Gastrointestinal nematodes (GINs) are a significant threat to the sustainability of global sheep production. Periparturient ewes play a key role in GIN epidemiology, with increased GIN faecal egg counts (FECs) in these ewes resulting in heavy pasture contamination that facilitates parasitic gastroenteritis in immunologically naïve lambs later during the grazing period. Traditionally, blanket anthelmintic treatment would suppress GIN egg outputs in these ewes and subsequent pasture contamination. However, farmers are now advised to implement targeted selective treatment (TST) to reduce anthelmintic use and subsequent anthelmintic resistance development, yet, there is currently limited evidence to determine optimal TST strategies in ewes. In this study, the characteristics of 226 ewes on seven Welsh farms were assessed postlambing to identify factors associated with their individual strongyle FECs using negative binomial mixed model analysis. Nemabiome analysis was conducted on 34 ewes across two study farms using the Oxford Nanopore MinIon platform with an aim of identifying factors associated with variations in ewe nemabiome composition within flocks. The best-fitted model of ewe FEC incorporated ewe body condition score, dag score, breed, and an interaction effect between ewe age and litter size as fixed factors. The addition of a mean FEC value for ewes of a specific litter size on each farm further improved model fit and reduced between-farm variance in the model. Nemabiome analysis revealed significant variation in within flock nemabiome diversity on individual farms, with significantly reduced nemabiome diversity recorded in ewes exhibiting dags and in twin-bearing ewes on respective farms, whilst T. circumcincta was present as a significantly higher proportion of the nemabiome in Suffolk ewes and twin bearing ewes (P < 0.05) in respective flocks. Our data demonstrate that commonly recorded ewe characteristics can be exploited to predict individual periparturient ewe FEC and subsequently may be used as a guide for TST strategies on sheep farms once specific TST thresholds are identified to deliver the optimal balance between minimal pasture contamination and maximal GIN refugia. This study is the first to utilise Oxford Nanopore MinIon sequencing to evaluate the nemabiome of sheep, and to molecularly assess the nemabiome of individual ruminants within a flock/herd, with results indicating that significant within flock variations in nemabiome composition which may have implications for TST and flock management strategies.

Dissecting the causal polymorphism of the Lr67res multipathogen resistance gene.

Partial resistance to multiple biotrophic fungal pathogens in wheat (Triticum aestivum L.) is conferred by a variant of the Lr67 gene, which encodes a hexose-proton symporter. Two mutations (G144R, V387L) differentiate the resistant and susceptible protein variants (Lr67res and Lr67sus). Lr67res lacks sugar transport capability and was associated with anion transporter-like properties when expressed in Xenopus laevis oocytes. Here, we extended this functional characterization to include yeast and in planta studies. The Lr67res allele, but not Lr67sus, induced sensitivity to ions in yeast (including NaCl, LiCl, KI), which is consistent with our previous observations that Lr67res expression in oocytes induces novel ion fluxes. We demonstrate that another naturally occurring single amino acid variant in wheat, containing only the Lr67G144R mutation, confers rust resistance. Transgenic barley plants expressing the orthologous HvSTP13 gene carrying the G144R and V387L mutations were also more resistant to Puccinia hordei infection. NaCl treatment of pot-grown adult wheat plants with the Lr67res allele induced leaf tip necrosis and partial leaf rust resistance. An Lr67res-like function can be introduced into orthologous plant hexose transporters via single amino acid mutation, highlighting the strong possibility of generating disease resistance in other crops, especially with gene editing.

An evaluation of AI generated literature reviews in musculoskeletal radiology.

PURPOSE: The use of artificial intelligence (AI) tools to aid in summarizing information in medicine and research has recently garnered a huge amount of interest. While tools such as ChatGPT produce convincing and naturally sounding output, the answers are sometimes incorrect. Some of these drawbacks, it is hoped, can be avoided by using programmes trained for a more specific scope. In this study we compared the performance of a new AI tool (the-literature.com) to the latest version OpenAI's ChatGPT (GPT-4) in summarizing topics that the authors have significantly contributed to. METHODS: The AI tools were asked to produce a literature review on 7 topics. These were selected based on the research topics that the authors were intimately familiar with and have contributed to through their own publications. The output produced by the AI tools were graded on a 1-5 Likert scale for accuracy, comprehensiveness, and relevance by two fellowship trained consultant radiologists. RESULTS: The-literature.com produced 3 excellent summaries, 3 very poor summaries not relevant to the prompt, and one summary, which was relevant but did not include all relevant papers. All of the summaries produced by GPT-4 were relevant, but fewer relevant papers were identified. The average Likert rating was for the-literature was 2.88 and 3.86 for GPT-4. There was good agreement between the ratings of both radiologists (ICC = 0.883). CONCLUSION: Summaries produced by AI in its current state require careful human validation. GPT-4 on average provides higher quality summaries. Neither tool can reliably identify all relevant publications.

The Parallel Pandemic: A Systematic Review on the Effects of the COVID-19 Pandemic on OCD among Children and Adolescents.

The COVID-19 pandemic and the accompanying social changes severely impacted mental health globally. Children and adolescents may have been vulnerable to adverse mental health outcomes, especially obsessive-compulsive disorder (OCD), due to their underdeveloped resilience and coping skills stemming from their progressing physical and psychological development. Few studies have explored the parallels between the pandemic and OCD trends in this population. This systematic review aims to identify the impacts of COVID-19 on OCD among children and adolescents. Using the PRISMA guidelines, a systematic search of eight databases for studies that assessed OCD outcomes independently or as part of other psychiatric diagnoses during the COVID-19 pandemic was conducted. The search was limited to studies on humans and those written in English and published between January 2020 and May 2023. We identified 788 articles, out of which 71 were selected for a full-text review. Twenty-two papers were synthesized from 10 countries for the final analysis. We found that 77% of our studies suggested that the COVID-19 pandemic had a negative impact on OCD among children and adolescents. We also found a complex interplay of individual, household, and socio-structural factors associated with the aggravation of OCD. Conversely, a few studies revealed that the pandemic strengthened relationships and resilience. The findings of this study emphasize the need for mental health screening and support for this population, especially during pandemic periods.

Registry-derived stage (RD-Stage) for capturing cancer stage at diagnosis for endometrial cancer.

BACKGROUND: Capture of cancer stage at diagnosis is important yet poorly reported by health services to population-based cancer registries. In this paper we describe current completeness of stage information for endometrial cancer available in Australian cancer registries; and develop and validate a set of rules to enable cancer registry medical coders to calculate stage using data available to them (registry-derived stage or 'RD-Stage'). METHODOLOGY: Rules for deriving RD-stage (Endometrial carcinoma) were developed using the American Joint Commission on Cancer (AJCC) TNM (tumour, nodes, metastasis) Staging System (8th Edition). An expert working group comprising cancer specialists responsible for delivering cancer care, epidemiologists and medical coders reviewed and endorsed the rules. Baseline completeness of data fields required to calculate RD-Stage, and calculation of the proportion of cases for whom an RD stage could be assigned, was assessed across each Australian jurisdiction. RD-Stage (Endometrial cancer) was calculated by Victorian Cancer Registry (VCR) medical coders and compared with clinical stage recorded by the patient's treating clinician and captured in the National Gynae-Oncology Registry (NGOR). RESULTS: The necessary data completeness level for calculating RD-Stage (Endometrial carcinoma) across various Australian jurisdictions varied from 0 to 89%. Three jurisdictions captured degree of spread of cancer, rendering RD-Stage unable to be calculated. RD-Stage (Endometrial carcinoma) could not be derived for 64/485 (13%) cases and was not captured for 44/485 (9%) cases in NGOR. At stage category level (I, II, III, IV), there was concordance between RD-Stage and NGOR captured stage in 393/410 (96%) of cases (95.8%, Kendall's coefficient = 0.95). CONCLUSION: A lack of consistency in data captured by, and data sources reporting to, population-based cancer registries meant that it was not possible to provide national endometrial carcinoma stage data at diagnosis. In a sample of Victorian cases, where surgical pathology was available, there was very good concordance between RD-Stage (Endometrial carcinoma) and clinician-recorded stage data available from NGOR. RD-Stage offers promise in capturing endometrial cancer stage at diagnosis for population epidemiological purposes when it is not provided by health services, but requires more extensive validation.

Rapid, non-invasive, in vivo measurement of tissue mechanical properties using gravitational loading and a nonlinear virtual fields method.

Measuring the mechanical properties of soft tissues in vivo is important in biomechanics and for diagnosis and staging of diseases, but challenging because it is difficult to control the boundary conditions. We present a novel, non-invasive method for measuring tissue properties using gravitational loading. MRI images of an organ in different positions are registered to measure tissue displacements due to gravitational forces in different positions. Considering equilibrium between stresses and gravity, we established a nonlinear virtual fields method to identify the tissue properties. The method was applied to the human brain as a proof of concept, using an Ogden model. Sensitivity analysis showed that the bulk modulus could be identified accurately while the shear modulus was identified with greater uncertainty; the strains were too small to identify the strain stiffening exponent. The measured properties agreed well with published in vitro data. The technique offers very promising perspectives, allowing the non-invasive measurement of otherwise inaccessible tissues and providing new information such as the bulk modulus under static loading, which has never previously been measured in vivo.

A positively tuned voltage indicator for extended electrical recordings in the brain.

Genetically encoded voltage indicators (GEVIs) enable optical recording of electrical signals in the brain, providing subthreshold sensitivity and temporal resolution not possible with calcium indicators. However, one- and two-photon voltage imaging over prolonged periods with the same GEVI has not yet been demonstrated. Here, we report engineering of ASAP family GEVIs to enhance photostability by inversion of the fluorescence-voltage relationship. Two of the resulting GEVIs, ASAP4b and ASAP4e, respond to 100-mV depolarizations with ≥180% fluorescence increases, compared with the 50% fluorescence decrease of the parental ASAP3. With standard microscopy equipment, ASAP4e enables single-trial detection of spikes in mice over the course of minutes. Unlike GEVIs previously used for one-photon voltage recordings, ASAP4b and ASAP4e also perform well under two-photon illumination. By imaging voltage and calcium simultaneously, we show that ASAP4b and ASAP4e can identify place cells and detect voltage spikes with better temporal resolution than commonly used calcium indicators. Thus, ASAP4b and ASAP4e extend the capabilities of voltage imaging to standard one- and two-photon microscopes while improving the duration of voltage recordings.

Impulsivity and Treatment Outcomes in Individuals with Cocaine Use Disorder: Examining the Gap between Interest and Adherence.

Background: Impulsivity is implicated in the development and maintenance of Cocaine Use Disorder (CUD). Less work has examined impulsivity's role on interest in initiating treatment, treatment adherence, or treatment response. No pharmacotherapies are approved for CUD, so efforts to understand and bolster the effects of psychotherapy are important in guiding and refining treatment. The present study examined the impact of impulsivity on interest in treatment, treatment initiation, treatment adherence, and treatment outcomes in individuals with CUD. Methods: Following the completion of a larger study on impulsivity and CUD participants were offered 14 sessions of (12 weeks) Cognitive Behavioral Relapse Prevention (CBT-RP). Before starting treatment, participants completed seven self-report and four behavioral measures of impulsivity. Sixty-eight healthy adults (36% female) with CUD (aged 49.4 ± 7.9) expressed an interest in treatment. Results: Greater scores on several self-report measures of impulsivity, and fewer difficulties with delayed gratification were associated with increased interest in treatment in both males and females. 55 participants attended at least 1 treatment session, while 13 participants did attend a single session. Individuals who attended at least one treatment session scored lower on measures of lack of perseverance and procrastination. Still, measures of impulsivity did not reliably predict session attendance nor the frequency of cocaine-positive urine samples throughout treatment. Males attended nearly twice as many treatment sessions as females despite nonsignificant associations between impulsivity in males and the number of sessions attended. Conclusions: Greater impulsivity in individuals with CUD was associated with expressing an interest in treatment, but not treatment adherence or response.

Expression of the wheat multipathogen resistance hexose transporter Lr67res is associated with anion fluxes.

Many disease resistance genes in wheat (Triticum aestivum L.) confer strong resistance to specific pathogen races or strains, and only a small number of genes confer multipathogen resistance. The Leaf rust resistance 67 (Lr67) gene fits into the latter category as it confers partial resistance to multiple biotrophic fungal pathogens in wheat and encodes a Sugar Transport Protein 13 (STP13) family hexose-proton symporter variant. Two mutations (G144R, V387L) in the resistant variant, Lr67res, differentiate it from the susceptible Lr67sus variant. The molecular function of the Lr67res protein is not understood, and this study aimed to broaden our knowledge on this topic. Biophysical analysis of the wheat Lr67sus and Lr67res protein variants was performed using Xenopus laevis oocytes as a heterologous expression system. Oocytes injected with Lr67sus displayed properties typically associated with proton-coupled sugar transport proteins-glucose-dependent inward currents, a Km of 110 ± 10 µM glucose, and a substrate selectivity permitting the transport of pentoses and hexoses. By contrast, Lr67res induced much larger sugar-independent inward currents in oocytes, implicating an alternative function. Since Lr67res is a mutated hexose-proton symporter, the possibility of protons underlying these currents was investigated but rejected. Instead, currents in Lr67res oocytes appeared to be dominated by anions. This conclusion was supported by electrophysiology and 36Cl- uptake studies and the similarities with oocytes expressing the known chloride channel from Torpedo marmorata, TmClC-0. This study provides insights into the function of an important disease resistance gene in wheat, which can be used to determine how this gene variant underpins disease resistance in planta.

The Skagit County choir COVID-19 outbreak - have we got it wrong?

OBJECTIVES: Over time, papers or reports may come to be taken for granted as evidence for some phenomenon. Researchers cite them without critically re-examining findings in the light of subsequent work. This can give rise to misleading or erroneous results and conclusions. We explore whether this has occurred in the widely reported outbreak of SARS-CoV-2 at a rehearsal of the Skagit Valley Chorale in March 2020, where it was assumed, and subsequently asserted uncritically, that the outbreak was due to a single infected person. STUDY DESIGN: Review of original report and subsequent modelling and interpretations. METHODS: We reviewed and analysed original outbreak data in relation to published data on incubation period, subsequent modelling drawing on the data, and interpretations of transmission characteristics of this incident. RESULTS: We show it is vanishingly unlikely that this was a single point source outbreak as has been widely claimed and on which modelling has been based. CONCLUSION: An unexamined assumption has led to erroneous policy conclusions about the risks of singing, and indoor spaces more generally, and the benefits of increased levels of ventilation. Although never publicly identified, one individual bears the moral burden of knowing what health outcomes have been attributed to their actions. We call for these claims to be re-examined and for greater ethical responsibility in the assumption of a point source in outbreak investigations.

Child, parent, and family mental health and functioning in Australia during COVID-19: comparison to pre-pandemic data.

The COVID-19 pandemic presents significant risks to population mental health. Despite evidence of detrimental effects for adults, there has been limited examination of the impact of COVID-19 on parents and children specifically. We aim to examine patterns of parent and child (0-18 years) mental health, parent substance use, couple conflict, parenting practices, and family functioning during COVID-19, compared to pre-pandemic data, and to identify families most at risk of poor outcomes according to pre-existing demographic and individual factors, and COVID-19 stressors. Participants were Australian mothers (81%) and fathers aged 18 years and over who were parents of a child 0-18 years (N = 2365). Parents completed an online self-report survey during 'stage three' COVID-19 restrictions in April 2020. Data were compared to pre-pandemic data from four Australian population-based cohorts. Compared to pre-pandemic estimates, during the pandemic period parents reported higher rates of parent depression, anxiety, and stress (Cohen's d = 0.26-0.81, all p < 0.001), higher parenting irritability (d = 0.17-0.46, all p < 0.001), lower family positive expressiveness (d = - 0.18, p < 0.001), and higher alcohol consumption (22% vs 12% drinking four or more days per week, p < 0.001). In multivariable analyses, we consistently found that younger parent age, increased financial deprivation, pre-existing parent and child physical and mental health conditions, COVID-19 psychological and environmental stressors, and housing dissatisfaction were associated with worse parent and child functioning and more strained family relationships. Our data suggest wide-ranging, detrimental family impacts associated with the COVID-19 pandemic; and support policy actions to assist families with financial supports, leave entitlements, and social housing.

Gabapentin increases the abuse liability of alcohol alone and in combination with oxycodone in participants with co-occurring opioid and alcohol use disorder.

BACKGROUND: People who have co-occurring Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) carry a higher risk of adverse outcomes, including drug overdose. Early clinical and preclinical studies suggested that gabapentin may be effective in treating both disorders. The present study was designed to assess the effects of gabapentin on the subjective and physiological effects of oxycodone (OXY) and alcohol (ALC), alone and in combination. METHODS: During an 8-week, inpatient, within-subject, randomized, double-blind, placebo-controlled crossover study, non-treatment seeking participants (N = 13; 12 M/1F; 44.1 ± 3 years of age) with OUD and AUD were maintained on oral morphine (120 mg daily). Under gabapentin (1800 mg/day) and placebo (0 mg/day) maintenance, participants completed nine separate test sessions (three sessions per week) during which they received an oral solution containing 0, 15, or 30 mg/70 kg OXY in combination with 0, 0.5, or 0.75 g/kg ALC. During test sessions, subjective effects and physiological responses were assessed repeatedly on 100-mm visual analog scales (VAS). The primary outcome variable was the VAS rating of drug liking after receiving the drug challenge. RESULTS: Alcohol alone (but not oxycodone alone) produced dose-related increases in several positive subjective responses, including drug liking. Gabapentin significantly increased drug liking when given in combination with ALC and OXY + ALC (p < 0.05). Gabapentin did not clinically compromise respiration or other vital functions. CONCLUSIONS: Gabapentin may increase the abuse liability of ALC and OXY + ALC in those with co-occurring OUD and AUD.

MRI safety, imaging artefacts, and grid distortion evaluated for FFP3 respiratory masks worn throughout the COVID-19 pandemic.

AIM: To determine which filtering face piece (FFP3) respirators worn throughout the COVID-19 pandemic are safe for magnetic resonance imaging (MRI). MATERIALS AND METHODS: Three clinical MRI sequences were performed to assess imaging artefacts, grid distortion, and local heating for eight commercially available FFP3 respirators. All examinations were performed at Cardiff University Brain Research Imaging Centre using a 3 T Siemens Magnetom Prisma with a 64-channel head and neck coil. Each FFP3 mask was positioned on a custom-developed three-dimensional (3D) head phantom for testing. RESULTS: Five of the eight FFP3 masks contained ferromagnetic components and were regarded as "MRI unsafe". One mask was considered "MRI conditional" and only two masks were deemed "MRI safe" for both MRI staff and patients. Temperature strips positioned at the nasal bridge of the phantom did not exhibit local heating. A maximum grid distortion of 5 mm was seen in the anterior portion of the head of the ferromagnetic FFP3 masks. CONCLUSION: This study has demonstrated the importance of assessing respiratory FFP3 masks for use in and around MRI machines. Future research involving FFP3 masks can be conducted safely by following the procedures laid out in this study.

Haplotype variants of Sr46 in Aegilops tauschii, the diploid D genome progenitor of wheat.

KEY MESSAGE: Stem rust resistance genes, SrRL5271 and Sr672.1 as well as SrCPI110651, from Aegilops tauschii, the diploid D genome progenitor of wheat, are sequence variants of Sr46 differing by 1-2 nucleotides leading to non-synonymous amino acid substitutions. The Aegilops tauschii (wheat D-genome progenitor) accessions RL 5271 and CPI110672 were identified as resistant to multiple races (including the Ug99) of the wheat stem rust pathogen Puccinia graminis f. sp. tritici (Pgt). This study was conducted to identify the stem rust resistance (Sr) gene(s) in both accessions. Genetic analysis of the resistance in RL 5271 identified a single dominant allele (SrRL5271) controlling resistance, whereas resistance segregated at two loci (SR672.1 and SR672.2) for a cross of CPI110672. Bulked segregant analysis placed SrRL5271 and Sr672.1 in a region on chromosome arm 2DS that encodes Sr46. Molecular marker screening, mapping and genomic sequence analysis demonstrated SrRL5271 and Sr672.1 are alleles of Sr46. The amino acid sequence of SrRL5271 and Sr672.1 is identical but differs from Sr46 (hereafter referred to as Sr46_h1 by following the gene nomenclature in wheat) by a single amino acid (N763K) and is thus designated Sr46_h2. Screening of a panel of Ae. tauschii accessions identified an additional allelic variant that differed from Sr46_h2 by a different amino acid (A648V) and was designated Sr46_h3. By contrast, the protein encoded by the susceptible allele of Ae. tauschii accession AL8/78 differed from these resistance proteins by 54 amino acid substitutions (94% nucleotide sequence gene identity). Cloning and complementation tests of the three resistance haplotypes confirmed their resistance to Pgt race 98-1,2,3,5,6 and partial resistance to Pgt race TTRTF in bread wheat. The three Sr46 haplotypes, with no virulent races detected yet, represent a valuable source for improving stem resistance in wheat.

Shifts in gut microbiome across five decades of repeated guppy translocations in Trinidadian streams.

An organism's gut microbiome can alter its fitness, yet we do not know how gut microbiomes change as their hosts evolve in the wild. We took advantage of a five-decade 'chronosequence' of translocated fish populations to examine associated changes in the gut microbiome. Populations of Trinidadian guppies have displayed parallel phenotypic convergence six times when moved from high predation (HP) to low predation (LP) environments. Across four drainages, we found microbiomes of fish translocated 5-6 years prior to sampling were already distinct from the microbiomes of their HP source populations. Changes in environmental conditions were most important in driving this shift, followed by phenotypic shifts in gut morphology. After 30-60 years in LP environments, microbiome composition was still distinct from native LP populations, but microbiome function was not. We found some evidence that nitrogen fixation enhanced gut nutrient absorption, but most functional shifts were not parallel across drainages. Stream-and drainage-specific signatures were present for both composition and function, despite our overall finding of consistent microbiome change across drainages. As we unravel the complexities of host-microbiome evolution in the wild, studies should consider environmental microbial colonization, host phenotypic plasticity in nature, and more realistic environmental conditions excluded from laboratory studies.

Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia.

Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children (n = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (r: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (r: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.

What can we Learn from Patients who Died from Covid-19 Following Escalation to a Respiratory High Dependency Unit for Trial of Non-Invasive Respiratory Support?

Background: Covid-19 infection is associated with significant risk of death, particularly in older, comorbid patients. Emerging evidence supports use of non-invasive respiratory support (CPAP and high-flow nasal oxygen [HFNO]) in this context, but little is known about its use in patients receiving end-of-life care. Methods: This was a retrospective study of 33 patients who died of Covid-19 on the Respiratory High Dependency Unit at the John Radcliffe Hospital, Oxford between 28/03/20 and 20/05/20. Data was sourced via retrospective review of electronic patient records and drug charts. Results: Patients dying from Covid-19 on the Respiratory HDU were comorbid with median Charlson Comorbidity Index 5 (IQR 4-6); median age 78 (IQR 72-85). Respiratory support was trialled in all but one case with CPAP being the most common form of first line respiratory support (84.8%) however, was only tolerated in 44.8% of patients. Median time to death was 10.7 days from symptom onset (IQR 7.5-14.6) and 4.9 days from hospital admission (IQR 3.1-8.3). 48.5% of patients remained on respiratory support at the time of death. Conclusions: End-of-life care for patients with Covid-19 remains a challenge. Patients tend to be frail and comorbid with a rapid disease trajectory. Non-Invasive Respiratory Support may play a key role in symptom management in select patients, however, further work is needed in order to identify patients who will most benefit from Respiratory Support and those for whom withdrawal may prevent unnecessary distress at the end of life or potential prolongation of suffering.