Blue Arabia : Palaeolithic and Underwater Survey in SW Saudi Arabia and the Role of Coasts in Pleistocene Dispersal

The role of coastal regions and coastlines in the dispersal of human populations from Africa and across the globe has been highlighted by the recent polarisation between coastal and interior models. The debate has been clouded by the use of the single term ‘coastal dispersal’ to embrace what is in fact a wide spectrum of possibilities, ranging from seafaring populations who spend most of their time at sea living off marine resources, to land-based populations in coastal regions with little or no reliance on marine foods. An additional complicating factor is the fact of Pleistocene and early Holocene sea-level change, which exposed an extensive coastal region that is now submerged, and may have afforded very different conditions from the modern coastal environment. We examine these factors in the Arabian context and use the term ‘Blue’ to draw attention to the fertile coastal rim of the Arabian Peninsula, and to the now submerged offshore landscape, which is especially extensive in some regions. We further emphasise that the attractions of the coastal rim are a product of two quite different factors, ecological diversity and abundant water on land, which have created persistently ‘Green’ conditions throughout the vagaries of Pleistocene climate change in some coastal regions, especially along parts of the western Arabian escarpment, and potentially productive marine environments around its coastline, which include some of the most fertile in the world. We examine the interplay of these factors in the Southwest region of Saudi Arabia and the southern Red Sea, and summarise some of the results of recent DISPERSE field investigations, including survey for Palaeolithic sites on the mainland, and underwater survey of the continental shelf in the vicinity of the Farasan Islands. We conclude that coastlines are neither uniformly attractive nor uniformly marginal to human dispersal, that they offer diverse opportunities that were spatially and temporally variable at scales from the local to the continental, and that investigating Blue Arabia in relation to its episodically Green interior is a key factor in the fuller understanding of long-term human population dynamics within Arabia and their global implications

Investigating the Palaeolithic Landscapes and Archaeology of the Jizan and Asir Regions, Southwestern Saudi Arabia

The archaeology of the Arabian Peninsula is pivotal to understanding the timing and mode of dispersals of hominin populations from Africa, with growing evidence supporting a Southern Route across the Hanish Sill in the Southern Red Sea. Yet, despite recent key discoveries, our understanding of the hominin occupation of the peninsula remains patchy. This situation is particularly marked in coastal Southwestern Saudi Arabia, a region key in dispersal debates given its proximity to the proposed Southern Route. Identification of the routes and conditions of hominin dispersals from Africa has focussed on reconstructing broad-scale climatic and vegetation zones. Yet physical landscapes are also critical to palaeoenvironmental reconstruction at the local scale. They can moderate or amplify climatic influence, and modify the distribution of plant and animal resources. The DISPERSE project aims to develop systematic methods for reconstructing Palaeolithic landscapes at a variety of geographical scales, and their impact on patterns of human evolution and dispersal. This paper reports the preliminary results of archaeological and geomorphological survey carried out in February-March 2013 in the Jizan and Asir regions, Southwestern Saudi Arabia. Satellite imagery was used to identify areas of potential preservation and visibility of Palaeolithic sites, as well as key geomorphological features to inform landscape reconstruction. ESA, MSA and potentially later artefacts were recorded at a number of locations and geographical settings in the region. These sites are placed within the developing model of landscape evolution, and preliminary hypotheses of hominin landscape use and technological aspects are outlined. These hypotheses will be tested through future survey seasons, ultimately allowing assessment of the factors controlling human occupation and dispersal

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Parvovirus Minute Virus of Mice Induces a DNA Damage Response That Facilitates Viral Replication

Infection by DNA viruses can elicit DNA damage responses (DDRs) in host cells. In some cases the DDR presents a block to viral replication that must be overcome, and in other cases the infecting agent exploits the DDR to facilitate replication. We find that low multiplicity infection with the autonomous parvovirus minute virus of mice (MVM) results in the activation of a DDR, characterized by the phosphorylation of H2AX, Nbs1, RPA32, Chk2 and p53. These proteins are recruited to MVM replication centers, where they co-localize with the main viral replication protein, NS1. The response is seen in both human and murine cell lines following infection with either the MVMp or MVMi strains. Replication of the virus is required for DNA damage signaling. Damage response proteins, including the ATM kinase, accumulate in viral-induced replication centers. Using mutant cell lines and specific kinase inhibitors, we show that ATM is the main transducer of the signaling events in the normal murine host. ATM inhibitors restrict MVM replication and ameliorate virus-induced cell cycle arrest, suggesting that DNA damage signaling facilitates virus replication, perhaps in part by promoting cell cycle arrest. Thus it appears that MVM exploits the cellular DNA damage response machinery early in infection to enhance its replication in host cells

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

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