Red hot frogs:Identifying the Australian frogs most at risk of extinction

More than a third of the world’s amphibian species are listed as Threatened or Extinct, with a recent assessment identifying 45 Australian frogs (18.4% of the currently recognised species) as ‘Threatened’ based on IUCN criteria. We applied structured expert elicitation to 26 frogs assessed as Critically Endangered and Endangered to estimate their probability of extinction by 2040. We also investigated whether participant experience (measured as a self-assigned categorical score, i.e. ‘expert’ or ‘non-expert’) influenced the estimates. Collation and analysis of participant opinion indicated that eight species are at high risk (>50% chance) of becoming extinct by 2040, with the disease chytridiomycosis identified as the primary threat. A further five species are at moderate–high risk (30–50% chance), primarily due to climate change. Fourteen of the 26 frog species are endemic to Queensland, with many species restricted to small geographic ranges that are susceptible to stochastic events (e.g. a severe heatwave or a large bushfire). Experts were more likely to rate extinction probability higher for poorly known species (those with <10 experts), while non-experts were more likely to rate extinction probability higher for better-known species. However, scores converged following discussion, indicating that there was greater consensus in the estimates of extinction probability. Increased resourcing and management intervention are urgently needed to avert future extinctions of Australia’s frogs. Key priorities include developing and supporting captive management and establishing or extending in-situ population refuges to alleviate the impacts of disease and climate change

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of Provider Experience on Clinician-Performed Ultrasonography for Hydronephrosis in Patients With Suspected Renal Colic

Study objectiveHydronephrosis is readily visible on ultrasonography and is a strong predictor of ureteral stones, but ultrasonography is a user-dependent technology and the test characteristics of clinician-performed ultrasonography for hydronephrosis are incompletely characterized, as is the effect of ultrasound fellowship training on predictive accuracy. We seek to determine the test characteristics of ultrasonography for detecting hydronephrosis when performed by clinicians with a wide range of experience under conditions of direct patient care.MethodsThis was a prospective study of patients presenting to an academic medical center emergency department with suspected renal colic. Before computed tomography (CT) results, an emergency clinician performed bedside ultrasonography, recording the presence and degree of hydronephrosis. CT data were abstracted from the dictated radiology report by an investigator blinded to the bedside ultrasonographic results. Test characteristics of bedside ultrasonography for hydronephrosis were calculated with the CT scan as the reference standard, with test characteristics compared by clinician experience stratified into 4 levels: attending physicians with emergency ultrasound fellowship training, attending physicians without emergency ultrasound fellowship training, ultrasound experienced non-attending physician clinicians (at least 2 weeks of ultrasound training), and ultrasound inexperienced non-attending physician clinicians (physician assistants, nurse practitioners, off-service rotators, and first-year emergency medicine residents with fewer than 2 weeks of ultrasound training).ResultsThere were 670 interpretable bedside ultrasonographic tests performed by 144 unique clinicians, 80.9% of which were performed by clinicians directly involved in the care of the patient. On CT, 47.5% of all subjects had hydronephrosis and 47.0% had a ureteral stone. Among all clinicians, ultrasonography had a sensitivity of 72.6% (95% confidence interval [CI] 65.4% to 78.9%), specificity of 73.3% (95% CI 66.1% to 79.4%), positive likelihood ratio of 2.72 (95% CI 2.25 to 3.27), and negative likelihood ratio of 0.37 (95% CI 0.31 to 0.44) for hydronephrosis, using hydronephrosis on CT as the criterion standard. Among attending physicians with fellowship training, ultrasonography had sensitivity of 92.7% (95% CI 83.8% to 96.9%), positive likelihood ratio of 4.97 (95% CI 2.90 to 8.51), and negative likelihood ratio of 0.08 (95% CI 0.03 to 0.23).ConclusionOverall, ultrasonography performed by emergency clinicians was moderately sensitive and specific for detection of hydronephrosis as seen on CT in patients with suspected renal colic. However, presence or absence of hydronephrosis as determined by emergency physicians with fellowship training in ultrasonography yielded more definitive test results. For clinicians without fellowship training, there was no significant difference between groups in the predictive accuracy of the application according to experience level