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Background The COVID-19 pandemic has led to more than 760,000 deaths worldwide (correct as of 16th August 2020). Studies suggest a hyperinflammatory response is a major cause of disease severity and death. Identitfying COVID-19 patients with hyperinflammation may identify subgroups who could benefit from targeted immunomodulatory treatments. Analysis of cytokine levels at the point of diagnosis of SARS-CoV-2 infection can identify patients at risk of deterioration. Methods We used a multiplex cytokine assay to measure serum IL-6, IL-8, TNF, IL-1β, GM-CSF, IL-10, IL-33 and IFN-γ in 100 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton (UK). Demographic, clinical and outcome data were collected for analysis. Results Age > 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). IL-6, IL-8, TNF, IL-1β and IL-33 were significantly associated with adverse outcome. Clinical parameters were predictive of poor outcome (AUROC 0.71), addition of a combined cytokine panel significantly improved the predictability (AUROC 0.85). In those ≤70 years, IL-33 and TNF were predictive of poor outcome (AUROC 0.83 and 0.84), addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs 0.77). Conclusions A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. Monthly or as-needed (PRN) dosing strategies of intravitreal ranibizumab have been established as efficacious treatment options for neovascular AMD. More recently, the ‘treat-and-extend’ dosing regimen (TREX) is being adopted in clinical practice as it represents a patient-centric and economical option, reducing treatment burden by extending injection intervals when possible. However, the efficacy of TREX using ranibizumab monotherapy remains to be defined. Therefore, we performed a systematic review to assess the current evidence for TREX using ranibizumab by searching MEDLINE, Embase and PubMed. Of the 1733 articles identified, nine TREX studies were included in our analysis ( n =748 eyes). Average patient age was 79.25 (range: 77.34–82.00; SD: 7.27). Baseline BCVA ranged from 48.5–68.9 ETDRS letters. BCVA improvement was 8.92 letters at 1 year (range: 6.5–11.5; SD: 7.54), as a weighted mean accounting for numbers of study eyes. The weighted mean number of injections at one year was 8.60 (range: 7.3–12.0; SD: 1.73). Previously, the landmark ANCHOR and MARINA trials reported gains of 11.3 and 7.2 letters, respectively, using monthly ranibizumab. Chin-Yee et al reported a gain of 3.5 ETDRS letters with 5.3 (S.D. 0.66) PRN ranibizumab injections as weighted means at 1 year in their recent systematic review. Our analysis suggests that TREX delivers visual outcomes superior to PRN and approaches similar efficacy to monthly injections. Further RCTs are needed to fully evaluate the efficacy and economy of TREX in the long-term.

Synopsis As the discovery of cryptic species has increased in frequency, there has been an interest in whether geometric morphometric data can detect fine-scale patterns of variation that can be used to morphologically diagnose such species. We used a combination of geometric morphometric data and an ensemble of five supervised machine learning methods (MLMs) to investigate whether plastron shape can differentiate two putative cryptic turtle species, Actinemys marmorata and Actinemys pallida. Actinemys has been the focus of considerable research due to its biogeographic distribution and conservation status. Despite this work, reliable morphological diagnoses for its two species are still lacking. We validated our approach on two datasets, one consisting of eight morphologically disparate emydid species, the other consisting of two subspecies of Trachemys (T. scripta scripta, T. scripta elegans). The validation tests returned near-perfect classification rates, demonstrating that plastron shape is an effective means for distinguishing taxonomic groups of emydids via MLMs. In contrast, the same methods did not return high classification rates for a set of alternative phylogeographic and morphological binning schemes in Actinemys. All classification hypotheses performed poorly relative to the validation datasets and no single hypothesis was unequivocally supported for Actinemys. Two hypotheses had machine learning performance that was marginally better than our remaining hypotheses. In both cases, those hypotheses favored a two-species split between A. marmorata and A. pallida specimens, lending tentative morphological support to the hypothesis of two Actinemys species. However, the machine learning results also underscore that Actinemys as a whole has lower levels of plastral variation than other turtles within Emydidae, but the reason for this morphological conservatism is unclear.

Cuora yunnanensis is an extinct turtle known from 12 specimens collected from Yunnan, China, before 1908. We used ancient DNA methods to sequence 1723 base pairs of mitochondrial DNA from a museum specimen of C. yunnanensis. Unlike some rare 'species' recently described from the pet trade, C. yunnanensis represents a lineage that is distinct from other known turtles. Besides C. yunnanensis, two other valid species (C. mccordi, C. zhoui) are unknown in the wild but are supposedly from Yunnan. Intensive field surveys for surviving wild populations of these critically endangered species are urgently needed.

The Australian banjo frogs are a distinctive group of medium to large, terrestrial, and burrowing limnodynastid frogs known for their conspicuous, single-note advertisement calls which are often likened to the pluck of a banjo string. Preliminary analyses of mitochondrial DNA sequences had previously indicated that the present taxonomy of the group, based primarily on morphology and advertisement calls, may not best reflect the true evolutionary relationships among taxa. In this study, we use comprehensive geographic sampling and integrative analyses of mitochondrial DNA sequences, nuclear single-nucleotide polymorphisms, adult morphology, and advertisement call data to re-evaluate the systematics and taxonomy of the Northern Banjo Frog (Limnodynastes terraereginae) and allied taxa. Our study reveals the presence of three evolutionarily distinct, morphologically divergent, and narrowly allopatric lineages that replace each other in a north–south series from the tip of Cape York Peninsula to the Sydney Basin in the south. Our findings demonstrate that our understanding of the systematics and taxonomy of Australian frogs remains incomplete, even for large and apparently “well-known” species that live in densely populated areas.

The evolutionary relationships of the burrowing amphisbaenians ('worm lizards') have long been controversial for several reasons: the rarity of museum specimens available for study, highly derived morphological conditions that can confound comparative studies and difficulty in obtaining tissues for molecular phylogenetic studies because of their secretive habits in the wild. We present a phylogenetic analysis of two nuclear genes obtained from both fresh tissues and museum specimens of worm lizards. We achieved sufficient taxonomic sampling for analysis by extracting DNA from museum specimens using a modified forensics protocol. Results show the limbless Rhineuridae to be the most basal lineage, whereas the limbed Bipedidae occupy a more derived position as the sister-taxon to a Trogonophidae-Amphisbaenidae clade. This pattern of relationships indicates widespread morphological convergence within the group, including three independent incidences of limb loss. Convergence in skull shape and scalation is also prevalent. Mosaic evolution in the skull versus postcranial skeleton parallels that seen in snake evolution.

The phylogeny and systematic position of Gomphillaceae was reconstructed using a combined Bayesian analysis of nuclear LSU rDNA and mitochondrial SSU rDNA sequences. Twenty-four partial sequences of 12 taxa (11 Gomphillaceae and one Asterothyriaceae) plus two new sequences of Stictis radiata (Ostropales outgroup) were generated and aligned with the corresponding sequences retrieved from GenBank, resulting in an alignment of 82 taxa that was analyzed using a Bayesian approach with Markov chain Monte Carlo (B/MCMC) methods. Our results confirm Gomphillaceae sensu Vezda and Poelt plus Asterothyriaceae to be a monophyletic group, with an unresolved relationship between the two families. Placement of Gomphillaceae and Asterothyriaceae within Ostropales sensu Kauff and Lutzoni, as sister of Thelotremataceae, also is strongly supported. Alternative hypotheses placing Gomphillaceae in Lecanorales (Cladoniaceae), Agyriales (Baeomycetaceae) or within bitunicate Ascomycota (Arthoniomycetes, Chaetothyriomycetes, Dothideomycetes) were rejected with our dataset. After recent synonymization of Dimerella with Coenogonium (Ostropales: Coenogoniaceae), we propose the new combination Coenogonium pineti (one of our Ostropales outgroup taxa in this analysis).

The influence of water stress on johnsongrass [Sorghum halepense (L.) Pers. ♯ SORHA] physiology was evaluated in a semiarid environment. Stomatal conductance of johnsongrass responded to more negative leaf water potential and increasing leaf temperature. The sensitivity of the leaf temperature effect was dependent on the soil water content. At low soil water content, conductance was limited by low water potential, and increasing leaf temperature had little effect. Conductance of CO2 was related to net photosynthesis in a curvilinear manner, with conductance levels greater than 0.3 mol·m-2· s-1 being in excess of that necessary for maximum photosynthesis. At both high conductance levels and low levels associated with increased water stress, intercellular CO2 concentration increased, indicating nonstomatal limitations to photosynthesis. Decreased osmotic potential provided the highest correlation with the linear decline of photosynthetic rate as stress intensified. The expression of osmotic adjustment in johnsongrass is reported during grain filling. Plants in the milkdough stage of grain filling had approximately 0.3 MPa lower osmotic potential at any relative water content than those at anthesis.