Impact of Sauropod Dinosaurs on Lagoonal Substrates in the Broome Sandstone (Lower Cretaceous), Western Australia

Existing knowledge of the tracks left by sauropod dinosaurs (loosely ‘brontosaurs’) is essentially two-dimensional, derived mainly from footprints exposed on bedding planes, but examples in the Broome Sandstone (Early Cretaceous) of Western Australia provide a complementary three-dimensional picture showing the extent to which walking sauropods could deform the ground beneath their feet. The patterns of deformation created by sauropods traversing thinly-stratified lagoonal deposits of the Broome Sandstone are unprecedented in their extent and structural complexity. The stacks of transmitted reliefs (underprints or ghost prints) beneath individual footfalls are nested into a hierarchy of deeper and more inclusive basins and troughs which eventually attain the size of minor tectonic features. Ultimately the sauropod track-makers deformed the substrate to such an extent that they remodelled the topography of the landscape they inhabited. Such patterns of substrate deformation are revealed by investigating fragmentary and eroded footprints, not by the conventional search for pristine footprints on intact bedding planes. For that reason it is not known whether similar patterns of substrate deformation might occur at sauropod track-sites elsewhere in the world

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

An outbreak of norovirus genogroup II associated with New South Wales oysters

Introduction: Currently available antigen tests for norovirus (NoV) have excellent specificity but negative results do not always rule out infection. Real-time reverse transcription polymerase chain reaction (RT-PCR) is a useful method for detecting and genotyping NoV in humans and oysters. An outbreak of NoV associated with oyster consumption in northern New South Wales confirmed the value of real-time RT-PCR where immunochromatography (ICT) tests were negative. Methods: Eight cases of gastrointestinal illness in northern NSW, clinically suggestive of NoV infection, were associated with consumption of oysters. A joint environmental investigation was conducted by the New South Wales Food Authority and local council. One human sample was collected and tested for NoV using ICT and real-time RT-PCR. Oyster samples were tested for NoV utilising real-time RT-PCR. Results: The patient with a stool sample had NoV genogroup II (GII) confirmed by real-time RT-PCR after testing negative by ICT. Illness in all cases was consistent with NoV with median incubation and duration of 36 and 50.5 hours respectively. All cases consumed oysters that were harvested from the same area. Three oyster samples from the harvest area were also positive for NoV GII. A nearby leaking sewer line was identified as the likely source of the contamination with hydrological studies confirming its potential to contaminate implicated oyster leases. Conclusion: This investigation confirmed the value of real-time RT-PCR testing of human specimens where ICT tests are negative and clinical illness is suggestive of NoV infection. NoV real-time RT-PCR and epidemiological evidence effectively linked human infection with oyster contamination to motivate a thorough environmental investigation and appropriate action to mitigate further public health risk

Land-Use Modelling in New Zealand: Current Practice and Future Needs

New Zealand faces the challenge of using our land in ways that are not only resilient to future pressures and sustain our rural communities but also enhance our natural environment. For the public and private sectors to make robust land-use decisions under uncertainty, high-quality modelling tools and data are essential. The drivers of land-use decisions are complex and models provide a structured methodology for investigating these. While New Zealand is fortunate to have a range of different modelling tools, these have historically been used in a sporadic and ad hoc way, and underlying datasets are deficient in some areas. As the foundation for more strategic development of New Zealand’s modelling capability, this paper profiles the main land-sector and farm- and production-related models and datasets currently applied in New Zealand. It also explores priority policy areas where modelling is needed, such as achieving emission reduction targets; managing freshwater, biodiversity and soil quality; and understanding the distributional impacts of policy options as well as climate change. New Zealand’s modelling capability could be strengthened by collecting and sharing land-use data more effectively; building understanding of underlying relationships informed by primary research; creating more collaborative and transparent processes for applying common datasets, scenarios and assumptions, and conducting peer review; and conducting more integrated modelling across environmental issues. These improvements will require strategic policies and processes for refining model development, providing increased, predictable and sustained funding for modelling activity and underlying data collection and primary research, and strengthening networks across modellers inside and outside of government

Wake up call: Response from authors [eLetter]

We are pleased that our article has stimulated debate. This was our intention. We are disappointed that some correspondents dismiss our argument by attacking a stereotype of who they think we are or a caricature of what they think we might have said, rather than addressing what we actually did say. Such correspondents have missed, or ignored, the point of the article – namely, to ask whether the de-medicalisation that has taken place over recent years in British psychiatry is bad for the health of patients and the specialty. We believe this is a question that is worth taking seriously. It is clear from the substantial eletter correspondence and other feedback that many psychiatrists share our concerns and wish for constructive debate. This primary concern with the decline in medical standards of care and the deliberate politicization of debates about service delivery does not imply that we cannot (a) embrace the importance of the full range of biological, psychological and social interventions for psychiatric illness and (b) value our non-psychiatric fellow professionals, and their integral contributions to mental health care. We also believe to be self-evident that services should be informed by the experiences of patients, their relatives and carers and that multidisciplinary team work is crucial for optimal management of psychiatric illness. We are not terribly interested in what is past. We are much more interested to look ahead. Of the wide range of views expressed by respondents, we believe the voice of trainees and those contemplating a career in psychiatry should carry particular weight and we should like to hear more from them. They are the future of British psychiatry

Biodiversity inventories in high gear: DNA barcoding facilitates a rapid biotic survey of a temperate nature reserve

International audienc

Coordinated Vascular Endothelial Growth Factor Expression and Signaling During Skeletal Myogenic Differentiation

Angiogenesis is largely controlled by hypoxia-driven transcriptional up-regulation and secretion of vascular endothelial growth factor (VEGF) and its binding to the endothelial cell tyrosine receptor kinases, VEGFR1 and VEGFR2. Recent expression analysis suggests that VEGF is expressed in a cell-specific manner in normoxic adult tissue; however, the transcriptional regulation and role of VEGF in these tissues remains fundamentally unknown. In this report we demonstrate that VEGF is coordinately up-regulated during terminal skeletal muscle differentiation. We reveal that this regulation is mediated in part by MyoD homo- and hetero-dimeric transcriptional mechanisms. Serial deletions of the VEGF promoter elucidated a region containing three tandem CANNTG consensus MyoD sites serving as essential sites of direct interaction for MyoD-mediated up-regulation of VEGF transcription. VEGF-null embryonic stem (ES) cells exhibited reduced myogenic differentiation compared with wild-type ES cells, suggesting that VEGF may serve a role in skeletal muscle differentiation. We demonstrate that VEGFR1 and VEGFR2 are expressed at low levels in myogenic precursor cells and are robustly activated upon VEGF stimulation and that their expression is coordinately regulated during skeletal muscle differentiation. VEGF stimulation of differentiating C2C12 cells promoted myotube hypertrophy and increased myogenic differentiation, whereas addition of sFlt1, a VEGF inhibitor, resulted in myotube hypotrophy and inhibited myogenic differentiation. We further provide evidence indicating VEGF-mediated myogenic marker expression, mitogenic activity, migration, and prosurvival functions may contribute to increased myogenesis. These data suggest a novel mechanism whereby VEGF is coordinately regulated as part of the myogenic differentiation program and serves an autocrine function regulating skeletal myogenesis