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ObjectiveSepsis and septic shock are major challenges and economic burdens to healthcare, impacting millions of people globally and representing significant causes of mortality. Recently, a large number of quality improvement programs focused on sepsis resuscitation bundles have been instituted worldwide. These educational initiatives have been shown to be associated with improvements in clinical outcomes. We aimed to evaluate the impact of a multi-faceted quality implementing program (QIP) on the compliance of a “simplified 1-h bundle” (Sepsis 6) and hospital mortality of severe sepsis and septic shock patients out of the intensive care unit (ICU).MethodsEmergency departments (EDs) and medical wards (MWs) of 12 academic and non-academic hospitals in the Lombardy region (Northern Italy) were involved in a multi-faceted QIP, which included educational and organizational interventions. Patients with a clinical diagnosis of severe sepsis or septic shock according to the Sepsis-2 criteria were enrolled in two different periods: from May 2011 to November 2011 (before-QIP cohort) and from August 2012 to June 2013 (after-QIP cohort).Measurements and main resultsThe effect of QIP on bundle compliance and hospital mortality was evaluated in a before–after analysis. We enrolled 467 patients in the before-QIP group and 656 in the after-QIP group. At the time of enrollment, septic shock was diagnosed in 50% of patients, similarly between the two periods. In the after-QIP group, we observed increased compliance to the “simplified rapid (1 h) intervention bundle” (the Sepsis 6 bundle – S6) at three time-points evaluated (1 h, 13.7 to 18.7%, p = 0.018, 3 h, 37.1 to 48.0%, p = 0.013, overall study period, 46.2 to 57.9%, p

An overview is presented of the progress since 2021 in the construction and scientific programme preparation of the Divertor Tokamak Test (DTT) facility. Licensing for building construction has been granted at the end of 2021. Licensing for Cat. A radiologic source has been also granted in 2022. The construction of the toroidal field magnet system is progressing. The prototype of the 170 GHz gyrotron has been produced and it is now under test on the FALCON facility. The design of the vacuum vessel, the poloidal field coils and the civil infrastructures has been completed. The shape of the first DTT divertor has been agreed with EUROfusion to test different plasma and exhaust scenarios: single null, double null, X-divertor and negative triangularity plasmas. A detailed research plan is being elaborated with the involvement of the EUROfusion laboratories.

Introduction Although numerous effective antidepressant (AD) strategies are available for the treatment of major depressive disorder (MDD), many patients do not achieve satisfactory treatment response. Objectives The aims of the present European, cross-sectional, multicenter, naturalistic study were (1) to determine the proportion of patients suffering from primary MDD who received additional psychotherapy to their ongoing psychopharmacotherapy and (2) to identify the associated socio-demographic and clinical patterns. Methods Patients receiving both treatments were compared to those lacking concomitant additional psychotherapy that was manual-driven psychotherapy (MDP) in all cases. Results While 68.8% of a total of 1279 MDD patients received exclusively psychopharmacotherapy, 31.2% underwent a psychopharmacotherapy-MDP combination. The latter patient population was rather younger, higher educated, employed, exhibited an earlier mean age of MDD onset, lower severity of current depressive symptoms with lower odds of suicidality and higher rates of melancholic features, and comorbid asthma and migraine, and was generally treated with lower daily doses of their first-line ADs. Whereas agomelatine was more commonly dispensed in these patients, selective serotonin reuptake inhibitors were more often prescribed in MDD patients lacking additional MDP. No significant between-group differences were detected in terms of treatment outcome. Conclusions The fact that the employment of additional MDP was not related to better treatment outcome in MDD represents our major and clinically most relevant finding. Generally, MDP was employed in a minority of our patients who experienced rather beneficial socio-demographic and clinical characteristics. This might reflect an inferior accessibility of these psychotherapeutic techniques for patients who are more severely ill and less socio-economically privileged. Disclosure References Bartova L, Fugger G, Dold M, Swoboda MMM, Zohar J, Mendlewicz J, Souery D, Montgomery S, Fabbri C, Serretti A, Kasper S. Combining psychopharmacotherapy and psychotherapy is not associated with better treatment outcome in major depressive disor

Introduction Anxiety disorders are leading contributors to the global disease burden, highly prevalent across the lifespan, and associated with substantially increased morbidity and early mortality. Objectives The aim of this study was to examine age-related changes across a wide range of physiological measures in middle-aged and older adults with a lifetime history of anxiety disorders compared to healthy controls. Methods The UK Biobank study recruited >500,000 adults, aged 37-73, between 2006-2010. We used generalised additive models to estimate non-linear associations between age and hand-grip strength, cardiovascular function, body composition, lung function and heel bone mineral density in cases vs. controls. Results The main dataset included 332,078 adults (mean age = 56.37 years; 52.65% females). In both sexes, individuals with anxiety disorders had lower hand-grip strength and blood pressure than healthy controls, while their pulse rate and body composition measures were higher. Case-control differences were larger when considering individuals with chronic and/or severe anxiety disorders, and differences in body composition were modulated by depression comorbidity status. Differences in age-related physiological changes between female anxiety disorder cases and healthy controls were most evident for blood pressure, pulse rate and body composition, while in males for hand-grip strength, blood pressure and body composition. Most differences in physiological measures between cases and controls tended to decrease with age increase. Conclusions Individuals with a lifetime history of anxiety disorders differed from healthy controls across multiple physiological measures, with some evidence of case-control differences by age. The differences observed varied by chronicity/severity and depression comorbidity. Disclosure JM receives studentship funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Eli Lilly and Company Limited. CML is a member of the Scientific Advisory Board of Myriad Neuroscience. CF and THH declare no relevant conflict of

Abstract Wild boar (Sus scrofa L.) is one of the large mammals most spread worldwide, highly adaptable, and its population rapidly increased in many areas in Europe, including Italy, where Tuscany is considered particularly suitable for wild boar. Wild boars are potential hosts for different etiological agents, such as Brucella spp., Leptospira spp. and Pseudorabies virus and they can contribute to maintain and/or to disseminate some bacterial or viral pathogens to humans and domestic animals, above all-in free-range farms. In order to identify hypothetical genomic regions associated with these infection diseases, 96 samples of wild boars hunted in Tuscany during the 2018–2019 and 2019–2020 hunting seasons were considered. Diagnosis was achieved by serological tests and 42 Pseudorabies, 31 Leptospira and 15 Brucella positive animals were identified. All animals were genotyped with Geneseek Genomic Profiler Porcine HD (70 k) and a genome-wide scan was then performed. Significant markers were highlighted for Pseudorabies (two SNPs), Brucella (seven SNPs), and Leptospira (four SNPs) and they were located within, or nearby, 29 annotated genes on chromosome 6, 9, 12, 13, 14 and 18. Eight genes are implicated in viral (SEC14L1, JMJD6, SRSF2, TMPRSS2, MX1, MX2) or bacterial (COL8A1, SPIRE1) infections, seven genes (MFSD11, METTL23, CTTNBP2, BACE2, IMPA2, MPPE1 and GNAL) are involved in mental disorders and one gene (MGAT5B) is related to the Golgi complex. Results presented here provide interesting starting points for future research, validation studies and fine mapping of candidate genes involved in bacterial and viral infections in wild boar.

Abstract Mass movements constitute major natural hazards in the Alpine realm. When triggered on slopes adjacent to lakes, these mass movements can generate tsunami-like waves that may cause additional damage along the shore. For hazard assessment, knowledge about the occurrence, the trigger and the geomechanical and hydrogeological mechanisms of these mass movements is necessary. For reconstructing mass movements that occurred in or adjacent to lakes, the lakes’s sedimentary record can be used as an archive. Here, we present a prehistorical mass-movement event, of which the traces were found in an alpine lake, Lake Thun, in central Switzerland. The mass movement is identified by large blocks on the bathymetric map, a chaotic to transparent facies on the reflection seismic profiles, and by a mixture of deformed lake sediments and sandy organic-rich layers in the sediment-core record. The event is dated at 2642–2407 cal year BP. With an estimated volume of ~ 20 × 106 m3 it might have generated a wave with an initial amplitude of > 30 m. In addition to this prehistorical event, two younger deposits were identified in the sedimentary record. One could be dated at 1523–1361 cal year BP and thus can be potentially related to an event in 598/599 AD documented in historical reports. The youngest deposit is dated at 304–151 cal year BP (1646–1799 AD) and is interpreted to be related to the artificial Kander river deviation into Lake Thun (1714 AD).

Abstract The modern, over 250-m-deep basin of Lake Constance represents the underfilled northern part of an over 400-m-deep, glacially overdeepened trough, which reaches well into the Alps at its southern end. The overdeepening was formed by repeated glacial advance-retreat cycles of the Rhine Glacier throughout the Middle to Late Pleistocene. A seismic survey of Lake Constance revealed a Quaternary sediment fill of more than 150 m thickness representing at least the last glacial cycle. The stratified sedimentary fill consists at the base of ice-contact deposits on top of the molasse bedrock, overlain by glaciolacustrine to lacustrine sediments. During the successful field test of a newly developed, mid-size coring system ("HIPERCORIG"), the longest core (HIBO19) ever taken in Lake Constance was retrieved with an overall length of 24 m. The sediments recovered consist of a nearly continuous succession of lacustrine silts and sands including more than 12 m of Late Glacial sediment at the base. 14 lithotypes were identified through petrophysical and geochemical analyses. In combination with a 14C- and OSL-based age-depth model, the core was divided into three main chronostratigraphic units. The basal age of ~ 13.7 ka BP dates the base of the succession back to the Bølling-Allerød interstadial, with overlying strata representing a complete and thick Younger-Dryas to Holocene succession. The sediments offer a high-resolution insight into the evolution of paleo-Lake Constance from a cold, postglacial to a more productive and warmer Holocene lake. The Late Glacial succession is dominated by massive, m-thick sand beds reflecting episodic sedimentation pulses. They are most likely linked to a subaquatic channel system originating in the river Seefelder Aach, which is, despite the Holocene drape, still apparent in today’s lake bathymetry. The overlying Holocene succession reveals a prominent, several cm-thick, double-turbiditic event layer representing the most distal impact of the Flimser Bergsturz, the largest known rockslide of the Alps that occurred over 100 km upstream the river Rhine at ~ 9.5 ka BP. Furthermore, lithologic variations in the Holocene succession document the varying sediment loads of the river Rhine and the endogenic production representing a multitude of environmental changes.

Abstract Non-invasive techniques such as seismic investigations and high-resolution multibeam sonars immensely improved our understanding of the geomorphology and sediment regimes in both the lacustrine and the marine domain. However, only few studies provide quantifications of basin wide-sediment budgets in lakes. Here, we use the combination of high-resolution bathymetric mapping and seismic reflection data to quantify the sediment budget in an alpine lake. The new bathymetric data of Lake Brienz reveal three distinct geomorphological areas: slopes with intercalated terraces, a flat basin plain, and delta areas with subaquatic channel systems. Quasi-4D seismic reflection data allow sediment budgeting of the lake with a total sediment input of 5.54 × 106 t sediment over 15 years of which three-quarter were deposited in the basin plain. Lake Brienz yields extraordinarily high sedimentation rates of 3.0 cm/yr in the basin plain, much more than in other Swiss lakes. This can be explained by (i) its role as first sedimentary sink in a high-alpine catchment, and by (ii) its morphology with subaquatic channel-complexes allowing an efficient sediment transfer from proximal to distal areas of the lake.

The frequency of debris flows is hypothesized to have increased in recent decades with enhanced rainstorm activity. Geological evidence to test the relationship between climate and debris flow activity for prehistoric times is scarce due to incomplete sediment records, complex stratigraphy, and insufficient age control, especially in Alpine environments. In lacustrine archives, the link between onshore debris flow processes and the sedimentary record in lakes is poorly investigated. We present an amphibious characterization of alluvial fan deltas and a continuous 4000-year debris flow record from Plansee (Tyrol, Austria), combining light detection and ranging (lidar) data, swath bathymetry, and sediment core analyses. The geomorphic investigation of two fan deltas in different developmental stages revealed an evolutionary pattern of backfilling and new channel formation onshore, together with active subaqueous progradation on a juvenile fan delta, major onshore sediment deposition, and only few, but larger, subaqueous deposits on a mature fan delta. Geomorphic evidence for stacked and braided debris flow lobes, subaquatic landslide deposits, and different types of turbidites in sediment cores facilitated a process-based event identification, i.e. distinguishing between debris-flow-induced or earthquake-induced turbidites throughout the 4000-year sedimentary record. We directly correlate subaqueous lobe-shaped deposits with high backscatter signals to terrestrial debris flow activity of the last century. Moreover, turbidite thickness distribution along a transect of four cores allows us to pinpoint numerous events as being related to debris flow activity on a juvenile fan delta. In the sediment core, debris-flow-induced turbidites feature a more gradual fining upward grain size trend and higher TOC (total organic carbon) and δ13C values compared to earthquake-induced turbidites. The 4000-year event record contains 138 debris-flow-induced turbidites separated into four phases of similar debris flow activity (df phases). df phase 1 (∼2120 to ∼2040 before the common era – BCE) reflects the second-highest observed event frequencies and is interpreted as being a postseismic landscape response. After a long period of long recurrence intervals without any outstanding increases in debris flow activity during df phase 2 (∼2040 BCE to ∼1520 common era – CE), there are slightly increased event frequencies in df phase 3 (∼1520 to ∼1920 CE). df phase 4 (∼1920 to 2018 CE) exhibits a drastic increase in debris flow activity, followed by the overall highest debris flow frequency of the whole record, which is about 7 times higher than during df phase 3. We show that the frequency increase in the debris-flow-induced turbidite record matches a previously postulated increase in debris flow events derived from aerial photography at Plansee in the last century. The triggering of debris flows is more controlled by short, intense precipitation than any other mass movement process, and we demonstrate that lacustrine debris flow records provide a unique inventory of hazard-relevant rainstorm frequencies over decades, centuries, and millennia. The presented increase in debris flow frequency since the start of the 20th century coincides with a twofold enhanced rainstorm activity in the Northern European Alps and, therefore, provides a novel technique for the systematic understanding of non-stationary debris flow frequencies in a changing climate.

The record of past environmental conditions and changes archived in lacustrine sediments serves as an important element in paleoenvironmental and climate research. A main barrier in accessing these archives is the undisturbed recovery of long cores from deep lakes. In this study, we have developed and tested a new, environmentally friendly coring tool and modular barge, centered around a down-the-hole hydraulic hammering of an advanced piston coring system, called the Hipercorig. Test beds for the evaluation of the performance of the system were two periglacial lakes, Mondsee and Constance, located on the northern edge of the Alpine chain. These lakes are notoriously difficult to sample beyond ∼ 10 m sediment depths due to dense glacial deposits obstructing deeper coring. Both lakes resemble many global lake systems with hard and coarse layers at depth, so the gained experience using this novel technology can be applied to other lacustrine or even marine basins. These two experimental drilling projects resulted in up to 63 m coring depth and successful coring operations in up to 204 m water depth, providing high-quality, continuous cores with 87 % recovery. Initial core description and scanning of the 63 m long core from Mondsee and two 20 and 24 m long cores from Lake Constance provided novel insights beyond the onset of deglaciation of the northern Alpine foreland dating back to ∼ 18 400 cal BP.

Pockmarks are crater-like depressions formed by upward fluid flow (gas and/or liquid) through the unconsolidated sediment column on the floor of oceans and lakes. While pockmarks are well described in the marine realm, they have essentially been overlooked in lacustrine settings, likely due to a lack in economic interest to apply high-resolution hydroacoustic techniques in lakes. A swath-bathymetry survey on Lake Thun, Switzerland, revealed the existence of three pockmark systems. One pockmark (110 m in diameter) was discovered near a big karst system at Beatenberg at a water depth of ~217 m. Its activity is probably associated with episodic groundwater seepage induced by earthquakes, floods and snowmelt. At another site, Daerligen, we detected at ~60 m water depth the presence of multiple smaller pockmarks (~1.5 to 10 m in diameter) that seem to be active, continuously liberating CH4 gas by bubble ebullition. The CH4 displayed a biogenic carbon isotopic signature, however, the exact origin of the gas remains unknown. The third site, Tannmoos (~35 m water depth), comprises two large pockmarks (20–43 m in diameter) connected to a karst system in gypsum-carrying bedrock. One of these pockmarks is constituted of several unit pockmarks (e.g., sub-pockmarks; 0.3 to 0.8 m in diameter). While strong evidence is still lacking, we suggest that groundwater discharge occasionally occurs through these unit pockmarks during periods of intense precipitation. Hence, this study reveals the existence of three pockmark systems of variable morphology and mechanisms of formation within the same lake, reflecting different hydrological and biogeochemical regimes. Moreover, it underscores the potential importance of pockmarks in influencing hydrological and CH4 budgets in lakes. Clearly more work on quantifying seasonal fluxes of groundwater and CH4 release via lacustrine pockmarks is required, and it needs to be seen whether the observations made in Lake Thun are universal and apply also to many other lacustrine environments worldwide.

The Eastern European Alps are characterized by slow active deformation with low- to moderate seismicity. Recurrence rates of severe earthquakes exceed the time span of historical documentation. Therefore, historical and instrumental earthquake records might be insufficient for seismic hazard assessment and high-quality paleoseismic data is required. However, primary geological observations of postglacial fault activity are scarcely found, because major faults are buried below thick sedimentary sequences in glacially overdeepened valleys. Moreover, high erosion rates, gravitational slope processes and penetrative anthropogenic landscape modification often obscure geomorphic features related to surface ruptures. Here we present one of the rare paleoseismic data sets showing both on-fault evidence as subaqueous surface ruptures and off-fault evidence as multiple coeval mass-transport deposits (MTDs) and megaturbidites within a single high-resolution seismic-stratigraphic framework of the inner-alpine lake Achensee. Co-occurrence of on-fault and off-fault paleoseismic evidence on three stratigraphic levels indicates seismic activity with inferred moment magnitudes MW ∼6–6.5 of the local, lake-crossing Sulzgraben-Eben thrust at ∼8.3 ka BP and twice in Late Glacial times. Additional eight stratigraphic levels with only off-fault paleoseismic evidence document severe seismic shaking related to the historical MW ∼5.7 earthquake in Hall (CE 1670) and seven Holocene earthquakes, which have exceeded a local seismic intensity of ∼VI (EMS-98) at Achensee. Furthermore, we discuss natural and methodological influencing factors and potential pitfalls for the elaboration of a subaqueous paleoseismic record based on surface ruptures and multiple, coeval MTDs.