A multiscale geoarchaeological approach from the Laurentine shore (Castelporziano, Lazio, Italy)

The ability to investigate meaningful geoarchaeological questions is driven by appropriate scale-process focus fundamentally informing sampling strategies. This in turn, is driven by site-specific characteristics such as topography, sedimentology, geochemistry and climate. The Laurentine Shore is the Roman-period palaeo-shoreline preserved up to 1 km inland of the modern coastline of the Tiber Delta at the southern distal end. Mid- to late-Holocene progradation of the Tiber Delta linked to sediment supply in the context of changing relative sea level drives the macro-scale (103+) development of the region. Archaeological remains preserved within the Presidential Estate of Castelporziano must be interpreted within this macro-scale context. Using a multiscale, transect-based approach, SAAD-IRSL luminescence dating of relict foredune ridges has provided an age model constraining the development of the Tiber delta during the late Holocene. Both radiocarbon (Giraudi et al., 2009) and luminescence chronologies of dune ridge phases are in good agreement. Due to the protected status of the Castelporziano Estate the Holocene coastal dune topography is better preserved than at the central delta area and two additional phases of dune ridge formation are observed. Four macro-scale phases of delta progradation are recorded by the dune ridge record with increased mean rates of progradation observed during the Roman period and within the last 500 years. On the meso-scale (102) the high-status villas on the Laurentine Shore, and the Vicus Augustanus that serviced the villas are specifically located on the Roman-period shoreline. The timing of settlement (from around 2050 BP, i.e., 1st century BC) occurs during a pronounced Tiber delta progradation phase. Within this macro-scale context issues of sediment supply, frequency of Tiber flooding and the expression of shoreline advance at the Laurentine Shore have important meso-scale consequences for the development of the archaeological sites. It is likely that during the 2-phase development of the Vicus Augustanus that shoreline progradation was an observable phenomenon on decadal to multi-decadal timescales. Indeed the second, major seaward construction phase of the Vicus Augustanus likely occurred upon land that did not exist during the first phase, directly linked to delta progradation and the macro-scale processes acting upon the development of the site including anthropogenic activity in the Tiber catchment during the Roman period.La pertinence des questions géoarchéologiques est directement conditionnée par le choix d’une échelle de travail adaptée dans le but de proposer par la suite des stratégies d’échantillonnage appropriées et efficaces. Ces dernières sont localement influencées par les caractéristiques propres d’un site telles que sa topographie, la nature des sédiments sur lesquels il a été bâti, son environnement (paramètres géochimiques) et son climat. Le littoral laurentin correspond à l’ancienne ligne de rivage datée de l’époque romaine et qui est aujourd’hui localisé à 1 km du trait de côte actuel, dans la partie méridionale du delta du Tibre. La progradation de ce dernier, au cours de l’Holocène moyen et récent, est à mettre en liaison directe avec l’apport sédimentaire de son bassin versant dans un contexte de stabilisation du niveau relatif de la mer, cela permet notamment d’appréhender l’évolution morphologique de la région concernée (la superficie de la zone considérée de l’ordre de 103 km2). Des vestiges archéologiques particulièrement bien conservés dans la région de Castelporziano doivent être justement replacés dans un contexte morphologique régional pour pouvoir être interprétés sur le plan géoarchéologique. En privilégiant une échelle régionale d’étude et en se fondant sur l’établissement de transects, ainsi que sur la datation par Luminescence SAAD-IRSL de cordons dunaires fossiles, on parvient à fournir un modèle évolutif du delta du Tibre au cours de l’Holocène. Les datations obtenues permettent de reconstituer les différentes phases d’édification des cordons dunaires. En raison de la position d’abri de la région de Castelporziano, la topographie des cordons dunaires d’âge holocène y est mieux conservée que dans la partie centrale du delta, il est d’ailleurs possible d’y observer deux cordons supplémentaires. A une échelle régionale, quatre phases majeures de progradation deltaïque ont ainsi été identifiées avec une hausse particulièrement bien marquée du rythme d’avancée du trait de côte durant la période romaine et au cours des cinq cent dernières années. A une échelle moyenne de travail (superficie de la zone considérée de l’ordre de 102 km2), il est possible d’observer que les villas romaines et le Vicus Augustanus sont implantés sur le littoral laurentin. Cette période d’occupation (environ 2050 BP-1er siècle ap. J.-C.) correspond d’ailleurs à une avancée significative du delta du Tibre. La progradation du trait de côte a eu des conséquences directes sur le développement des sites archéologiques. C’est essentiellement pendant la seconde phase de l’expansion du Vicus Augustanus que la progradation est un phénomène observable à l’échelle décennale voire pluri décennale. En effet, l’expansion vers la mer du Vicus Augustanus est intervenue alors qu’aucun territoire n’existait pendant la première phase. Cela est à mettre en relation directe avec la progradation deltaïque et les processus morphologiques affectant le bassin versant du Tibre pendant la période romaine, incluant en particulier les activités d’origine anthropique

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease