Using integrative taxonomy to distinguish cryptic halfbeak species and interpret distribution patterns, fisheries landings, and speciation

Context. Species classification disputes can be resolved using integrative taxonomy, which involves the use of both phenotypic and genetic information to determine species boundaries. Aims. Our aim was to clarify species boundaries of two commercially important cryptic species of halfbeak (Hemiramphidae), whose distributions overlap in south-eastern Australia, and assist fisheries management. Methods. We applied an integrative taxonomic approach to clarify species boundaries and assist fisheries management. Key results. Mitochondrial DNA and morphological data exhibited significant differences between the two species. The low level of mitochondrial DNA divergence, coupled with the lack of difference in the nuclear DNA, suggests that these species diverged relatively recently (c. 500 000 years ago) when compared with other species within the Hyporhamphus genus (>2.4 million years ago). Genetic differences between the species were accompanied by differences in modal gill raker counts, mean upper- jaw and preorbital length, and otolith shape. Conclusions. On the basis of these genetic and morphological differences, as well as the lack of morphological intergradation between species along the overlapping boundaries of their geographical distributions, we propose that Hyporhamphus australis and Hyporhamphus melanochir remain valid species. Implications. This study has illustrated the need for an integrative taxonomic approach when assessing species boundaries and has provided a methodological framework for studying other cryptic fish species in a management context

COVID-19 in children: analysis of the first pandemic peak in England.

OBJECTIVES: To assess disease trends, testing practices, community surveillance, case-fatality and excess deaths in children as compared with adults during the first pandemic peak in England. SETTING: England. PARTICIPANTS: Children with COVID-19 between January and May 2020. MAIN OUTCOME MEASURES: Trends in confirmed COVID-19 cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity rates in children compared with adults; community prevalence of SARS-CoV-2 in children with acute respiratory infection (ARI) compared with adults, case-fatality rate in children with confirmed COVID-19 and excess childhood deaths compared with the previous 5 years. RESULTS: Children represented 1.1% (1,408/129,704) of SARS-CoV-2 positive cases between 16 January 2020 and 3 May 2020. In total, 540 305 people were tested for SARS-COV-2 and 129,704 (24.0%) were positive. In children aged <16 years, 35,200 tests were performed and 1408 (4.0%) were positive for SARS-CoV-2, compared to 19.1%-34.9% adults. Childhood cases increased from mid-March and peaked on 11 April before declining. Among 2,961 individuals presenting with ARI in primary care, 351 were children and 10 (2.8%) were positive compared with 9.3%-45.5% in adults. Eight children died and four (case-fatality rate, 0.3%; 95% CI 0.07% to 0.7%) were due to COVID-19. We found no evidence of excess mortality in children. CONCLUSIONS: Children accounted for a very small proportion of confirmed cases despite the large numbers of children tested. SARS-CoV-2 positivity was low even in children with ARI. Our findings provide further evidence against the role of children in infection and transmission of SARS-CoV-2

Spatial profiling of gastric cancer patient-matched primary and locoregional metastases reveals principles of tumour dissemination.

OBJECTIVE: Endoscopic mucosal biopsies of primary gastric cancers (GCs) are used to guide diagnosis, biomarker testing and treatment. Spatial intratumoural heterogeneity (ITH) may influence biopsy-derived information. We aimed to study ITH of primary GCs and matched lymph node metastasis (LNmet). DESIGN: GC resection samples were annotated to identify primary tumour superficial (PTsup), primary tumour deep (PTdeep) and LNmet subregions. For each subregion, we determined (1) transcriptomic profiles (NanoString 'PanCancer Progression Panel', 770 genes); (2) next-generation sequencing (NGS, 225 gastrointestinal cancer-related genes); (3) DNA copy number profiles by multiplex ligation-dependent probe amplification (MLPA, 16 genes); and (4) histomorphological phenotypes. RESULTS: NanoString profiling of 64 GCs revealed no differences between PTsup1 and PTsup2, while 43% of genes were differentially expressed between PTsup versus PTdeep and 38% in PTsup versus LNmet. Only 16% of genes were differently expressed between PTdeep and LNmet. Several genes with therapeutic potential (eg IGF1, PIK3CD and TGFB1) were overexpressed in LNmet and PTdeep compared with PTsup. NGS data revealed orthogonal support of NanoString results with 40% mutations present in PTdeep and/or LNmet, but not in PTsup. Conversely, only 6% of mutations were present in PTsup and were absent in PTdeep and LNmet. MLPA demonstrated significant ITH between subregions and progressive genomic changes from PTsup to PTdeep/LNmet. CONCLUSION: In GC, regional lymph node metastases are likely to originate from deeper subregions of the primary tumour. Future clinical trials of novel targeted therapies must consider assessment of deeper subregions of the primary tumour and/or metastases as several therapeutically relevant genes are only mutated, overexpressed or amplified in these regions

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Fusion Learning Colloquium 2022 - Proceedings

This is the proceedings of the 2022 Fusion Learning Colloquium held at Bournemouth University in the UK