This chapter deals with the dating of dust archives, and mainly focuses on loess archives that are the most common terrestrial dust archives. It explores the various methods used for loess dating, including cyclostratigraphy based on observed patterns of variations of physical, chemical, and (or) biological parameters along loess-paleosol sequences, magnetostratigraphy, tephrostratigraphy, aminostratigraphy, luminescence dating (OSL/IRSL), radiocarbon dating, and others. It provides fundamental concepts and practical aspects and examines the challenges and limitations of these techniques. The discussion is based on examples that illustrate each of the approaches. The chapter ends with applications of these methods to the elaboration of robust chronostratigraphic frameworks and paleoclimatological and paleoenvironmental reconstructions.

The Upper Rhine Plain is part of a Cenozoic graben, which is approximately 40 km wide and 300 km long. This geological structure determines the geometry and the thicknesses of the Quaternary sediments, with a subsiding central zone and loess-covered alluvial terraces on its margins. In Alsace, most of the recorded Paleolithic remains are concentrated on the margins while the central area appears to be devoid of occupation. Recent investigations have been carried out in the region within the framework of the PaleoEls Project, and in the course of rescue excavations. They indicate that the sedimentary deposits, which are locally very thick, pose an obstacle for studying archaeological sites and are partly responsible for the observed distribution pattern. However, they also provide a chronological and palaeoenvironmental framework for the Middle Paleolithic. For the Upper Pleistocene, loess sequences attest to the establishment of pine forests during the first half of the period (from approximately 100,000 to 70,000 years ago), phases of erosion around the middle of the period (from approximately 100,000 to 30,000 years ago) and significant levels of deposition which fossilize tundra gleys over the course of the second half of the period (from approximately 30,000 to 20,000 years ago). Loess sequences also indicate environmental conditions that were dryer and richer in biodiversity than those in northern France. Around Strasbourg, alluvial clayey loams, more than 20 m deep, indicate the existence of a flood plain occupied by wet meadowlands and few trees during Pleistocene interstadial or interglacial times that was conducive to human occupation. While these deposits are currently only accessible through coring, Late Glacial and Holocene formations, which are easy to study, can serve as a model for studying the more discontinuous records from the earlier periods. They show the tendency for shrinkage in that part of the plain submitted to flooding from the Pleniglacial to the recent Holocene, leading us to envisage a situation where the plain was easy to cross during the Middle Paleolithic. Thus, from a geomorphological point of view, there is no reason to believe that the Rhine River acted as a boundary or posed an obstacle to human movement.

OBJECTIVE:Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk.METHODS:In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay.RESULTS:A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups.CONCLUSION:We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo.TRIAL REGISTRATION NUMBER:ClinicalTrials.gov number, NCT01855841).

The Upper Rhine Graben in Central Europe, and notably its depocentre in the Heidelberg Basin, is an archive of complex and long-lasting deposition throughout the Quaternary. A new drill core, 136 m long, from the southern Heidelberg Basin is investigated by characterising sedimentary facies, sediment provenance, as well as analysing the pollen and mollusc content. The chronological framework is based on post-infrared infrared-stimulated luminescence dating, and complemented with amino acid geochronology. The sediment sequence consists of fluvial, colluvial, and palustrine deposits that represent at least the last similar to 500 ka, interrupted by some, major and minor, hiatuses. In the lower part, fluvial gravel and colluvial diamicts of a lateral alluvial fan into the Upper Rhine Graben prevail. The central part of the succession consists of a large-scale fining upward cycle that contains increasing amounts of material from the Alps delivered by the Rhine river. This sequence terminates with palustrine fines with rich mollusc and pollen assemblages that allow for a detailed reconstruction of environmental conditions. The results of pIRIR dating place the palustrine deposits in marine isotope stage 11. However, the pollen profile shares similarities with the Mannheim Interglacial that has previously been assigned to the Cromerian, a correlation that is supported by the amino acid geochronology, which poses a chronostratigraphical problem. In the upper part, Alpine sediments are progressively replaced by a new alluvial fan from the graben margin with striking variations in grain size. Overall, the diverse succession is the result of an interplay of tectonic activity and climatic factors. While subsidence triggers the generation of accommodation space and river deflection, pulses of coarse sediment are probably related to periglacial weathering, mass wasting and short-scale transport during cold periods.

During their exploitation, the quarries of Achenheim and Hangenbieten (Alsace, France) provided access to an exceptional loess-paleosol sequence, totalling over 40 m in thickness and spanning at least four glacial-interglacial cycles. As early as 1914, E. Schumacher identified thirty stratigraphic units, in which, over the course of almost a century, numerous large faunal remains and lithic artefacts scattered within various levels would be revealed, although only two of these levels were extensively excavated. In particular, the site offers an almost complete key sequence to understand early settlement dynamics in the Rhine valley and particularly the transition between Lower and Middle Palaeolithic, at the boundary between western and central Europe. Nevertheless, data are old and artefacts were recovered by quarry workers and repositioned after their collection. Moreover, while many chronostratigraphic and paleoenvironmental studies have been made during the last decade, the data are dispersed and rarely combined. Due to these biases Achenheim's archaeological data could be disregarded. In the present study, we aim to take a fresh look at the reliability of Achenheim's lithic assemblages. We focus on Lower and Middle Palaeolithic lithic remains, re-examined here in detail. In parallel, their chronostratigraphic position in terms of marine isotope stages, as well as the contemporaneous palaeoenvironmental characteristics, have been checked by combining all available data scattered in many publications concerning older quarries that are no longer accessible or difficult to access. By comparing the archaeological data from this site with the most recent discoveries, both in Alsace and elsewhere in north-western and central Europe, we can show that the lithic industries, though largely incomplete, represent an interesting sample which sheds new light on the succession of lithic technocomplexes of early settlement in the Upper Rhine area. The various technical manifestations identified at Achenheim seem to match the overall techno-typological sequence observed for the Middle and Late Pleistocene of either northwestern or central Europe.

Over the last glacial period, the climate of the Northern Hemisphere experienced numerous abrupt variations on millennial to centennial timescales known as Dansgaard-Oeschger events. These events, characterised by rapid warming at the beginning of interstadials and gradual cooling back to stadial conditions are best documented in Greenland ice cores and North Atlantic marine records, while their propagation onto the continents and potential feedbacks are less well documented. In this context, loess palaeosol sequences in central Europe are valuable archives, often recording these climatic changes in the form of brown soils and tundra gley horizons - indicating milder interstadial conditions - intercalated with primary loess deposits reflecting cold stadial conditions.To reconstruct palaeoclimate changes at high resolution we use singular material from loess sediments: fossil earthworm calcite granules (ECG). ECGs, composed of aggregated sparite crystals formed in the calciferous earthworm glands, are secreted daily at the soil surfacemostly by Lumbricus species and experience limited vertical mixing within the loess sedimentary column. ECGs are thus an excellent terrestrial material for palaeoclimate reconstructions using stable isotopic geochemistry and radiocarbon dating. ECGs have been collected from two temporally overlapping loess-palaeosol sequences along an NNW-SSE transect in the Rhine River valley of western Germany. We present warm-season land-surface temperature and precipitation estimates at millennial timescales spanning ~ 45-22 cal kBP (late OIS 3 - OIS 2). We demonstrate that OIS 3-2 climate in the Rhine Valley was significantly cooler during the warm season and overall drier with annual precipitation reduced by up to 70%, compared to the present day. Interstadials were only slightly warmer (1-4°C) than stadial indicating strong attenuation compared to Greenland records. In combination with mesoscale wind and moisture transport modelling we can show that this region was dominated by westerlies and thereby inextricably linked to North Atlantic climate forcing.The approach combining high-resolution age-depth modelling and geochemical proxy-based climate reconstruction can be readily adopted at other loess palaeosol sequences. We envisage a widespread application of this approach that would improve our understanding of regional variability over the European continent in response to North Atlantic climate changes over millennial to centennial timescales.

Abstract. The study of geological archives of dust is of great relevance as they are directly linked to past atmospheric circulation and bear the potential to reconstruct dust provenance and flux relative to climate changes. Among the dust sinks, loess–palaeosol sequences (LPSs) represent the only continental and non-aquatic archives that are predominantly built up by dust deposits close to source areas, providing detailed information on Quaternary climatic and terrestrial environmental changes. Upper Pleistocene LPSs of western central Europe have been investigated in great detail showing their linkage to millennial-scale northern hemispheric climate oscillations, but comprehensive data on dust composition and potential source–sink relationships as well as inferred past atmospheric circulation patterns for this region are still fragmentary. Here, we present an integrative approach that systematically combines sedimentological, rock magnetic, and bulk geochemical data, as well as information on Sr and Nd isotope composition, enabling a synthetic interpretation of LPS formation. We focus on the Schwalbenberg RP1 profile in the Middle Rhine Valley in Germany and integrate our data into a robust age model that has recently been established based on high-resolution radiocarbon dating of earthworm calcite granules. We show that Schwalbenberg RP1 is subdivided into a lower section corresponding to late oxygen isotope stage 3 (OIS; ∼ 40–30 ka) and an upper section dating into the Last Glacial Maximum (LGM; ∼ 24–22 ka), separated by a major stratigraphic unconformity. Sedimentological proxies of wind dynamics (U ratio) and pedogenesis (finest clay) of the lower section attest to comparable and largely synchronous patterns of northern hemispheric climatic changes supporting the overall synchronicity of climatic changes in and around the North Atlantic region. The anisotropy of magnetic susceptibility (AMS) reveals a clear correlation between finer grain size and increasing AMS foliation within interstadials, possibly owing to continuous accumulation of dust during pedogenic phases. Such a clear negative correlation has so far not been described for any LPS on stadial–interstadial scales. Distinct shifts in several proxy data supported by changes in isotope composition (87Sr/86Sr and εNd) within the lower section are interpreted as changes in provenance and decreasing weathering simultaneously with an overall cooling and aridification towards the end of OIS 3 (after ∼ 35 ka) and enhanced wind activity with significant input of coarse-grained material recycled from local sources related to increased landscape instability (after ∼ 31.5 ka). We find that environmental conditions within the upper section, most likely dominated by local to regional environmental signals, significantly differ from those in the lower section. In addition, AMS-based reconstructions of near-surface wind trends may indicate the influence of north-easterly winds beside the overall dominance of westerlies. The integrative approach contributes to a more comprehensive understanding of LPS formation including changes in dust composition and associated circulation patterns during Quaternary climate changes.

Background and Aims: Bilomas most frequently result from postoperative bile leaks. The endoscopic conventional treatment is sphincterotomy +/- stent placement. In complex cases, such as altered anatomy or failure of conventional treatment, transpapillary/transfistulary (TP/TF) drainage or EUS-guided transmural drainage (EUS-TD) may obviate additional biliary surgery. This study reports our experience with treating biloma secondary to refractory biliary leak with TP/TF drainage or EUS-TD and evaluates the safety and outcomes associated with this approach. Methods: This observational study focused on consecutive patients managed for biliary leakage (diagnosis based on imaging and/or bile outflow from a surgical drain) at a tertiary care hospital (2007-2017). TP/TF drainage was performed by double-pigtail stent(s) placement to drain the biloma through the leak during ERCP. For EUS-TD, plastic stent(s) were placed under EUS control. Primary outcomes were a composite of clinical success (patient free of sepsis after percutaneous drain removal and, in patients with benign disease, removal of all endoscopically placed stents, without need for reintervention) and biloma regression (<3 cm) at last follow-up. Results: Thirty patients (men, 57%; median age, 55 years) were included. Most biliary leaks resulted from cholecystectomy (27%) and hepatectomy (50%). Initial EUS-TD and TP/TF drainage were performed in 14 (47%) and 16 (53%) patients, respectively. At last follow-up (median, 33.2 months), clinical success and primary outcome were achieved in 70.4% of patients (EUS-TD, 75%; TP/TF, 67%). Additional surgery was necessary in 1 patient. Rate of serious adverse events was 23% (7/30), of which 13% (4/30) were procedure related. There were 4 deaths during the course of treatment, 2 of which were related to endoscopic interventions (hemorrhage and fibrillation). Conclusions: TP/TF drainage or EUS-TD is technically feasible with high clinical success and may avoid the need for additional surgery in complex cases or in patients with altered anatomy.

The climate of the last 50,000 years has been punctuated by oscillations on millennial-to-centennial timescales. Our understanding of this variability derives predominantly from proxy information in ice and marine cores; high-resolution records from land are scarce. Here we quantify land-surface temperature and soil moisture at millennial timescales over continental Europe, for the period spanning 45,000 to 22,000 years before present. We provide the first quantitative terrestrial counterpart to marine and ice-core derived reconstructions for the North Atlantic region. Our terrestrial reconstruction derives from novel isotopic geochemistry and radiocarbon dating of earthworm calcite granules, collected from two temporally overlapping loess palaeosol sequences in the Rhine Valley, Germany. We combine our proxy reconstructions with mesoscale wind and moisture transport modelling. We find that compared with polar and Mediterranean regions, climatic warming from stadial to interstadial phases is attenuated in central-western Europe. The region was dominated by westerly air masses during the last glacial maximum but experienced seasonal variability in wind steadiness. We observe a strong correlation between abrupt temperature variability recorded in the Greenland ice core and the periglacial environments further south. This correlation is likely due to air masses arriving to the Rhine valley are deriving from the North Atlantic.

Loess-Palaeosol-Sequences (LPS) are the most widespread aeolian sedimentary deposits providing climatic- and environmental records across continents. As dust sinks, they may archive information on dust source dynamics, if targeted source signals survived processes operating during production, transport, and syn- and post-depositional alteration of particles and sediments. Yet, our knowledge about such dynamics through palaeoenvironmental changes during the Upper Pleistocene remains vague. This limits our understanding of thresholds that may have (de-) activated dust sources causing major environmental changes in prevalent areas. We thus combine results of isotope- (87/86Sr, 143/144Nd) and major element (Si/Al) provenance proxies that react differently to pre-, syn- and post depositional alteration processes, with granulometry (U-ratio) and the anisotropy of magnetic susceptibility (AMS). Granulometry is recognised as an indicator for wind strengths and the primary magnetic fabric of loess deposits has been successfully used to reconstruct surface near wind directions. We apply our approach on the RP1 profile of the Schwalbenberg LPS that covers the late OIS 3 and the OIS 2 in centennial-scale resolution. The site is embedded in the Middle Rhine Valley (Germany) dividing the Rhenish Massif in its western and eastern part. Consequently, the Schwalbenberg seems appropriate to trace provenance shifts as it is linked to a distal dust source via the Rhine and as it is surrounded by potential local dust sources of the Rhenish Massif. Our results indicate shifts in source areas NNE-SSW off the site, contemporary with increasing frost dynamics and aridification. Both factors seem to enhance dust inputs from the Rhine system up to a threshold where the Rhenish Massif gets activated as a dominant source. Geochemical fingerprinting and AMS at the Schwalbenberg RP1 LPS reveal insights into dust source dynamics that allow for estimating their emission potential during Upper Pleistocene palaeoenvironmental changes.

Ice core and marine archives provide detailed quantitative records of last glacial climate changes, whereas comparable terrestrial records from the mid-latitudes remain scarce. Here we quantify warm season land-surface temperatures and precipitation over millennial timescales for central Europe for the period spanning 45,000–22,000 years before present that derive from two temporally overlapping loess-palaeosol-sequences, dated at high resolution by radiocarbon on earthworm calcite granules. Interstadial temperatures were 1–4 °C warmer than stadial climate, a temperature difference which is strongly attenuated compared to Greenland records. We show that climate in the Rhine Valley was significantly cooler during the warm season and overall drier with annual precipitation values reduced by up to 70% compared to the present day. We combine quantitative estimates with mesoscale wind and moisture transport modelling demonstrating that this region was dominated by westerlies and thereby inextricably linked to North Atlantic climate forcing, although ameliorated.

Given the current scarcity of curative treatment of COVID-19, the search for an effective treatment modality among all available medications has become a priority. This study aimed at investigating the role of functional inhibitors of acid sphingomyelinase (FIASMAs) on in-hospital COVID-19 mortality. In this retrospective cohort study, we included adult in-patients with laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged hospital or deceased) from Erasme Hospital (Brussels, Belgium). We used univariate and multivariate logistic regression models to explore the risk factors associated with in-hospital mortality. We included 350 patients (205 males, 145 females) with a mean age of 63.24 years (SD = 17.4, range: 21–96 years). Seventy-two patients died in the hospital and 278 were discharged. The four most common comorbidities were hypertension (184, 52.6%), chronic cardiac disease (110, 31.4%), obesity (96, 27.8%) and diabetes (95, 27.1%). Ninety-three participants (26.6%) received a long-term prescription for FIASMAs. Among these, 60 (64.5%) received amlodipine. For FIASMAs status, multivariable regression showed increasing odds ratio (OR) for in-hospital deaths associated with older age (OR 1.05, 95% CI: 1.02–1.07; p = 0.00015), and higher prevalence of malignant neoplasm (OR 2.09, 95% CI: 1.03–4.22; p = 0.039). Nonsignificant decreasing OR (0.53, 95% CI: 0.27–1.04; p = 0.064) was reported for FIASMA status. For amlodipine status, multivariable regression revealed increasing OR of in-hospital deaths associated with older age (OR 1.04, 95% CI: 1.02–1.07; p = 0.0009), higher prevalence of hypertension (OR 2.78, 95% CI: 1.33–5.79; p = 0.0062) and higher prevalence of malignant neoplasm (OR 2.71, 95% CI: 1.23–5.97; p = 0.013), then secondarily decreasing OR of in-hospital death associated with long-term treatment with amlodipine (OR 0.24, 95% CI: 0.09–0.62; p = 0.0031). Chronic treatment with amlodipine could be significantly associated with low mortality of COVID-19 in-patients.

ABSTRACTThe Amiens‐Renancourt 1 site recently yielded one of the most important Upper Palaeolithic human occupations of northern France by the number of flint artefacts and especially by the presence of Venus figurines. All the material comes from a single archaeological layer located in a tundra gley bracketed by loess units. A multi‐proxy study combining a detailed stratigraphy, luminescence and radiocarbon datings and high‐resolution (5 cm per sample) grain size and molluscan analyses was therefore carried out to reconstruct and date the associated environmental changes and to determine the exact context of the human occupation. The chronological frame thus established supports the correlations of the archaeology‐bearing tundra gley and of an underlying arctic brown soil with Greenland interstadials GI‐4 and GI‐3. Composition changes in the molluscan population enabled the identification of transitional and optimum phases and sub‐phases within these two pedogenetic horizons. A conceptual correlation model linking molluscan phases with millennial‐scale variations of Greenland ice‐core and Sieben Hengste speleothem climate records is proposed. The Human occupation appears contemporaneous to the end of the stadial–interstadial transition of GI‐3. Synchronous in Amiens‐Renancourt 1 and Nussloch, subsequent micro‐gleys may also result from a regional/global forcing. Such a level of detail is unprecedented in a loess sequence.