A retrospective cohort study of differential attainment, COVID and chaos: taking the difference out of a terrible trinity

Background: This study aimed to evaluate core surgical training (CST) differential attainment related to coronavirus disease 2019 (COVID-19), gender and ethnicity. The hypothesis was that COVID-19 adversely influenced CST outcomes. Methods: A retrospective cohort study of 271 anonymised CST records was undertaken at a UK Statutory Education Body. Primary effect measures were Annual Review of Competency Progression Outcome (ARCPO), Membership of the Royal College of Surgeons (MRCS) examination pass and Higher Surgical Training National Training Number (NTN) appointment. Data were collected prospectively at ARCP and analysed with non-parametric statistical methods in SPSS. Results: CSTs numbering 138 completed training pre-COVID and 133 peri-COVID. ARCPO 1, 2 and 6 were 71.9% pre-COVID versus 74.4% peri-COVID (P = 0.844). MRCS pass rates were 69.6% pre-COVID versus 71.1% peri-COVID (P = 0.968), but NTN appointment rates diminished (pre-COVID 47.4% vs. peri-COVID 36.9%, P = 0.324); none of the above varied by gender or ethnicity. Multivariable analyses by three models revealed: ARCPO was associated with gender [m:f 1:0.87, odds ratio (OR) 0.53, P = 0.043] and CST theme (Plastics vs. General OR 16.82, P = 0.007); MRCS pass with theme (Plastics vs. General OR 8.97, P = 0.004); NTN with the Improving Surgical Training run-through programme (OR 5.00, P < 0.001). Programme retention improved peri-COVID (OR 0.20, P = 0.014) with pan University Hospital rotations performing better than Mixed or District General-only rotations (OR 6.63, P = 0.018). Conclusion: Differential attainment profiles varied 17-fold, yet COVID-19 did not influence ARCPO or MRCS pass rates. NTN appointment fell by one-fifth peri-COVID, but overall training outcome metrics remained robust despite the existential threat

The Woody Guthrie Centennial Bibliography

This bibliography updates two extensive works designed to include comprehensively all significant works by and about Woody Guthrie. Richard A. Reuss published A Woody Guthrie Bibliography, 1912–1967 in 1968 and Jeffrey N. Gatten\u27s article “Woody Guthrie: A Bibliographic Update, 1968–1986” appeared in 1988. With this current article, researchers need only utilize these three bibliographies to identify all English-language items of relevance related to, or written by, Guthrie

Modulating mitophagy in mitochondrial disease

Mitochondrial diseases may result from mutations in the maternally-inherited mitochondrial DNA (mtDNA) or from mutations in nuclear genes encoding mitochondrial proteins. Their bi-genomic nature makes mitochondrial diseases a very heterogeneous group of disorders that can present at any age and can affect any type of tissue. The autophagic-lysosomal degradation pathway plays an important role in clearing dysfunctional and redundant mitochondria through a specific quality control mechanism termed mitophagy. Mitochondria could be targeted for autophagic degradation for a variety of reasons including basal turnover for recycling, starvation induced degradation, and degradation due to damage. While the core autophagic machinery is highly conserved and common to most pathways, the signaling pathways leading to the selective degradation of damaged mitochondria are still not completely understood. Type 1 mitophagy due to nutrient starvation is dependent on PI3K (phosphoinositide 3-kinase) for autophagosome formation but independent of mitophagy proteins, PINK1 (PTEN-induced putative kinase 1) and Parkin. Whereas type 2 mitophagy that occurs due to damage is dependent on PINK1 and Parkin but does not require PI3K. Autophagy and mitophagy play an important role in human disease and hence could serve as therapeutic targets for the treatment of mitochondrial as well as neurodegenerative disorders. Therefore, we reviewed drugs that are known modulators of autophagy (AICAR and metformin) and may effect this by activating the AMP-activated protein kinase signaling pathways. Furthermore, we reviewed data available on supplements, such as Coenzyme Q and the quinone idebenone, that we assert rescue increased mitophagy in mitochondrial disease by benefiting mitochondrial function

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The comparative role of key environmental factors in determining savanna productivity and carbon fluxes: a review, with special reference to northern Australia

Terrestrial ecosystems are highly responsive to their local environments and, as such, the rate of carbon uptake both in shorter and longer timescales and different spatial scales depends on local environmental drivers. For savannas, the key environmental drivers controlling vegetation productivity are water and nutrient availability, vapour pressure deficit (VPD), solar radiation and fire. Changes in these environmental factors can modify the carbon balance of these ecosystems. Therefore, understanding the environmental drivers responsible for the patterns (temporal and spatial) and processes (photosynthesis and respiration) has become a central goal in terrestrial carbon cycle studies. Here we have reviewed the various environmental controls on the spatial and temporal patterns on savanna carbon fluxes in northern Australia. Such studies are critical in predicting the impacts of future climate change on savanna productivity and carbon storage