Potential for diagnosis of infectious disease from the 100,000 Genomes Project Metagenomic Dataset: Recommendations for reporting results

The identification of microbiological infection is usually a diagnostic investigation, a complex process that is firstly initiated by clinical suspicion. With the emergence of high-throughput sequencing (HTS) technologies, metagenomic analysis has unveiled the power to identify microbial DNA/RNA from a diverse range of clinical samples (1). Metagenomic analysis of whole human genomes at the clinical/research interface bypasses the steps of clinical scrutiny and targeted testing and has the potential to generate unexpected findings relating to infectious and sometimes transmissible disease. There is no doubt that microbial findings that may have a significant impact on a patient’s treatment and their close contacts should be reported to those with clinical responsibility for the sample-donating patient. There are no clear recommendations on how such findings that are incidental, or outside the original investigation, should be handled. Here we aim to provide an informed protocol for the management of incidental microbial findings as part of the 100,000 Genomes Projectwhich may have broader application in this emerging field. As with any other clinical information, we aim to prioritise the reporting of data that are most likely to be of benefit to the patient and their close contacts. We also set out to minimize risks, costs and potential anxiety associated with the reporting of results that are unlikely to be of clinical significance. Our recommendations aim to support the practice of microbial metagenomics by providing a simplified pathway that can be applied to reporting the identification of potential pathogens from metagenomic datasets. Given that the ambition for UK sequenced human genomes over the next 5 years has been set to reach 5 million and the field of metagenomics is rapidly evolving, the guidance will be regularly reviewed and will likely adapt over time as experience develops

Reply to: Revisiting life history and morphological proxies for early mammaliaform metabolic rates

Non peer reviewe

Reptile-like physiology in Early Jurassic stem-mammals

Despite considerable advances in knowledge of the anatomy, ecology and evolution of early mammals, far less is known about their physiology. Evidence is contradictory concerning the timing and fossil groups in which mammalian endothermy arose. To determine the state of metabolic evolution in two of the earliest stem-mammals, the Early Jurassic Morganucodon and Kuehneotherium, we use separate proxies for basal and maximum metabolic rate. Here we report, using synchrotron X-ray tomographic imaging of incremental tooth cementum, that they had maximum lifespans considerably longer than comparably sized living mammals, but similar to those of reptiles, and so they likely had reptilian-level basal metabolic rates. Measurements of femoral nutrient foramina show Morganucodon had blood flow rates intermediate between living mammals and reptiles, suggesting maximum metabolic rates increased evolutionarily before basal metabolic rates. Stem mammals lacked the elevated endothermic metabolism of living mammals, highlighting the mosaic nature of mammalian physiological evolution. Modern mammals are endothermic, but it has not been clear when this type of metabolism evolved. Here, Newham et al. analyse tooth and bone structure in Early Jurassic stem-mammal fossils to estimate lifespan and blood flow rates, which inform about basal and maximum metabolic rates, respectively, and show these stem-mammals had metabolic rates closer to modern ectothermic reptiles than to endothermic mammals.Peer reviewe

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Australian Core Skills Framework (ACSF)

The Australian Core Skills Framework (ACSF) provides a rich, detailed picture of real life performance in the five core skills of: Learning, Reading, Writing, Oral Communication and Numeracy. These skills are essential for individuals to participate effectively in our society. They are inextricably interwoven into all parts of our lives, being directly or indirectly linked to the physical, social and economic wellbeing of individuals, workplace productivity and safety, community interaction and capacity, and ultimately to Australia’s economic and community wellbeing. The ACSF reflects contemporary use of English in Australia. The ACSF has been developed to facilitate a consistent national approach to the identification and development of the core skills in diverse personal, community, work, and education and training contexts. It offers: shared concepts and language for identifying, describing and discussing core skills; and a systematic approach to benchmarking, monitoring and reporting on core skills performance

Palaeontology of primitive wombats

Wombats (Vombatidae, Marsupialia) are fossorial marsupials that are most closely related to koalas amongst living marsupials. The cheek teeth of wombats are unique amongst Australian marsupials in being hypselodont (the condition where the teeth continue to grow throughout life and the formation of roots is suppressed). Hypselodonty is an adaptation to high degrees of tooth wear. The fossil record of vombatids is largely restricted to Pliocene to recent deposits and is largely represented by isolated teeth. Six genera are currently recognised from these deposits, all of which have hypselodont teeth. To date, a single isolated vombatid tooth has been described from pre-Pliocene deposits of South Australia and is the only example of a vombatid cheek tooth that possesses roots.Seventy specimens, representing five species of vombatid, have been recovered from Oligo-Miocene deposits in the Riversleigh World Heritage Site in northwestern Queensland and are described here. Among these are four new species and one new genus. A new species of Warendja from Riversleigh is described. It represents the oldest known hypselodont vombatid. This species is compared with additional specimens of the Pleistocene species of Warendja (W wakefieldi). Three species of Rhizophascolonus and a new monotypic genus are also described. Phylogenetic analysis of these taxa indicates that Rhizophascolonus may represent a sister taxon to the other vombatids. These specimens comprise almost all known examples of Oligo-Miocene vombatids. Most of the specimens are isolated teeth and are highly variable in size and morphology. Cusp detail is clearly preserved on many, allowing for omparison with the cusp morphology on juvenile cheek teeth of the common wombat (Vombatus ursinus).All of the taxa found in the deposits at Riversleigh share a number of characters such as marked differences in enamel thickness and height around the cheek teeth. It is argued here that these shared characters are indicative of high amounts of tooth wear and/or occlusal stresses acting on the trailing edge enamel. Combined with evidence of scratch-digging adaptations of the forelimbs it is suggestive of a rhizophagous niche for at least some of these early vombatids

Supplementary material 1 from: Ahl LI, Bellucci L, Brewer P, Gagnier P-Y, Haston EM, Livermore L, De Smedt S, Hardy HM, Enghoff H (2023) Digitisation of natural history collections: criteria for prioritisation. Research Ideas and Outcomes 9: e114548. https://doi.org/10.3897/rio.9.e114548

ICEDIG and GBIF repor

Supplementary material 4 from: Ahl LI, Bellucci L, Brewer P, Gagnier P-Y, Haston EM, Livermore L, De Smedt S, Hardy HM, Enghoff H (2023) Digitisation of natural history collections: criteria for prioritisation. Research Ideas and Outcomes 9: e114548. https://doi.org/10.3897/rio.9.e114548

Survey 2, Multiple-choice questionnair

Supplementary material 3 from: Ahl LI, Bellucci L, Brewer P, Gagnier P-Y, Haston EM, Livermore L, De Smedt S, Hardy HM, Enghoff H (2023) Digitisation of natural history collections: criteria for prioritisation. Research Ideas and Outcomes 9: e114548. https://doi.org/10.3897/rio.9.e114548

Additional literature searche

Supplementary material 2 from: Ahl LI, Bellucci L, Brewer P, Gagnier P-Y, Haston EM, Livermore L, De Smedt S, Hardy HM, Enghoff H (2023) Digitisation of natural history collections: criteria for prioritisation. Research Ideas and Outcomes 9: e114548. https://doi.org/10.3897/rio.9.e114548

ApMS1.3 Corpus of previous studies on prioritisation of digitisation compile