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We present results of simulations performed with a physical–biogeochemical ocean model of the Mediterranean Sea for the Last Glacial Maximum (LGM) and analyse the differences in physical and biochemical states between the historical period and the LGM. Long-term simulations with an Earth system model based on ice sheet reconstructions provide the necessary atmospheric forcing data, oceanic boundary conditions at the entrance to the Mediterranean Sea, and river discharge to the entire basin. Our regional model accounts for changes in bathymetry due to ice sheet volume changes, reduction in atmospheric CO2 concentration, and an adjusted aeolian dust and iron deposition. The physical ocean state of the Mediterranean during the LGM shows a reduced baroclinic water exchange at the Strait of Gibraltar, a more sluggish zonal overturning circulation, and the relocation of intermediate and deep-water-formation areas – all in line with estimates from palaeo-sediment records or previous modelling efforts. Most striking features of the biogeochemical realm are a reduction in the net primary production, an accumulation of nutrients below the euphotic zone, and an increase in the organic matter deposition at the seafloor. This seeming contradiction of increased organic matter deposition and decreased net primary production challenges our view of possible changes in surface biological processes during the LGM. We attribute the origin of a reduced net primary production to the interplay of increased stability of the upper water column, changed zonal water transport at intermediate depths, and lower water temperatures, which slow down all biological processes during the LGM. Cold water temperatures also affect the remineralisation rates of organic material, which explains the simulated increase in the organic matter deposition, which is in good agreement with sediment proxy records. In addition, we discuss changes in an artificial tracer which captures the surface ocean temperature signal during organic matter production. A shifted seasonality of the biological production in the LGM leads to a difference in the recording of the climate signal by this artificial tracer of up to 1 K. This could be of relevance for the interpretation of proxy records like, e.g., alkenones. Our study not only provides the first consistent insights into the biogeochemistry of the glacial Mediterranean Sea but will also serve as the starting point for transient simulations of the last deglaciation.

ObjectivesThe COVID-19 pandemic affected patients’ access to health services, including patients with severe chronic pain. Since limited data on pandemic-caused changes in pain therapy is available, we analyzed its effect on hospital-based pain treatment.MethodsFor this retrospective claims data analysis conducted in n = 37 hospitals, we included patients treated for a chronic pain-related diagnosis. Discharge rates stratified by region and pain unit size were analyzed for different time periods between January 2019 and June 2022.ResultsThere was a significant decrease in day-care, inpatient interdisciplinary multimodal pain management, from a total of 5,533 hospital pre-pandemic treatments in 2019, to 3,942 in 2020 and 4,262 in 2021, with a slight increase in the first half of 2022. The extent of COVID-19-related changes differed depending on region and pain unit size.ConclusionThe decreased number of hospital pain treatments during the pandemic implies a relevant analgesic undertreatment. During future pandemics, the ethical dimension of potentially non-sufficient pain treatment should be weighted against social, medical and hygienic restrictions influencing the hospitalization rate.

Changing climatic conditions can shape the strength and extent of the oxygen minimum zone (OMZ). The presence and variability of the OMZ in the Arabian Sea is of importance to the latter's ecosystem. The state of oxygenation has, for instance, an impact on the pelagic and benthic faunal community or the nitrogen and carbon cycles. It is important to understand the dynamics of the OMZ and related marine environmental conditions because of their climate feedbacks. In this study, we combined three independent proxies to reconstruct the oxygenation state of the water column and bottom water in the Gulf of Oman for the past 43 kyr approximately. This multi-proxy approach is done for the first time at the northeastern Oman margin located in the Gulf of Oman. We used bulk sedimentary nitrogen isotopes (δ15N) and the alkane ratio (lycopane +n-C35)/n-C31 and benthic foraminiferal faunal analysis to reconstruct the strength of the OMZ in the water column and bottom water oxygenation, respectively. Our results show that the Gulf of Oman experienced strong pronounced OMZ and bottom water deoxygenation during the Holocene. In contrast, during Marine Isotope Stage 2 (MIS 2), including the Last Glacial Maximum (LGM), the Gulf of Oman was very well ventilated, with a highly diverse benthic foraminiferal community. This may have been caused by stronger wind-induced mixing and better ventilation by oxygen-rich water masses. Our results also show moderate oxygenation during MIS 3, with deoxygenation events during most of the warmer Dansgaard–Oeschger (D–O) events. We propose two distinct oxygenation modes for the Gulf of Oman: (1) a stable period of either strongly pronounced water column OMZ and bottom water deoxygenation or well-oxygenated water column and bottom water conditions and (2) an unstable period of oscillating oxygenation states between moderately oxygenated (stadials) and deoxygenated (interstadials, D–O events) conditions. The unstable period may be triggered by an interstadial Atlantic meridional overturning circulation (AMOC) mode, which is required to initiate D–O events.

Abstract The electrochemical conversion of biobased intermediates offers an attractive and sustainable process for the production of green chemicals. One promising synthesis route is the production of the total vanillin-based polymer polyvanillin, which can be produced by electrochemical pinacolization of divanillin (5–5´bisvanillyl). Divanillin can be easily enzymatically generated from vanillin, a renewable intermediate accessible from lignin on an industrial scale. This study investigates systematically the electrochemical production of polyvanillin in a divided plane parallel flow reactor in recirculation mode. Several analytic methods, such as online UV–VIS spectroscopy, size exclusion chromatography (SEC), 2D-NMR (HSQC, 13C/1H), TGA and DSC were used to monitor the reaction progress and to characterize the reaction products under different galvanostatic reaction conditions revealing new insights into the reaction mechanism and structural features of the polymer. Further, by using an electrochemical engineering-based approach determining the limiting current densities, we readily achieved high current densities over 50 mA cm−2 for the polyvanillin synthesis and reached averaged molecular weights up to Mw = 4100 g mol−1 and Mn = 2700 g mol−1. The cathodic polymerization to polyvanillin offers an innovative approach for the electrochemical production of biobased polymers presented on flow cell level. Graphical Abstract

The oceanography of the Red Sea is controlled by the restricted exchange of water masses with the Indian Ocean and by high evaporation rates due to the arid climate of the surrounding land areas. In the northern Red Sea, the formation of oxygen-rich subsurface water ventilates the deeper parts of the basin, but little is known about the variability in this process in the past. The stable oxygen and carbon isotope records of epibenthic foraminifera from a sediment core of the central Red Sea and comparison with existing isotope records allow for the reconstruction of changes in the Red Sea overturning circulation (ROC) during Marine Isotope Stage 3. The isotope records imply millennial-scale variations in the ROC, in phase with the climate variability in the high northern latitudes. This suggests an immediate response of dense-water formation to the regional climate and hydrology of the northern Red Sea. Deep-water formation was intensified under the influence of cold and hyper-arid conditions during Heinrich stadials and was diminished during Dansgaard–Oeschger interstadials. While these changes are reflected in both stable oxygen and carbon isotope records, the latter data also exhibit changes in phase with the African–Indian monsoon system. The decoupling of the stable carbon and oxygen isotope records at the summer monsoon maximum centered around 55–60 ka may be associated with an increased inflow of nutrient-rich intermediate waters from the Arabian Sea to the central Red Sea. This process fueled local surface water productivity, resulting in enhanced remineralization of sinking organic matter and release of 12C at intermediate water depths.

Climatic and associated hydrological changes controlled the transport processes and composition of the sediments in the central Red Sea during the last ca. 200 kyr. Three different source areas for mineral dust are identified. The dominant source is located in the eastern Sahara (Sudan and southernmost Egypt). We identify its imprint on Red Sea sediments by high smectite and Ti contents, low 87Sr / 86Sr, and high εNd. The availability of deflatable sediments was controlled by the intensity of tropical rainfall and vegetation cover over North Africa linked to the African monsoon. Intense dust input to the Red Sea occurred during arid phases, and low input occurred during humid phases. A second, less significant source indicated by palygorskite input is probably located on the eastern Arabian Peninsula and/or Mesopotamia, while the presence of kaolinite suggests an additional minor dust source in northern Egypt. Our grain size data reflect episodes of fluvial sediment discharge to the central Red Sea and document the variable strength in response to all of the precession-paced insolation maxima during our study interval including both those that were strong enough to trigger sapropel formation in the eastern Mediterranean Sea and those that were not. The African humid period most strongly expressed in our Red Sea record was the one during the Eemian last interglacial at ca. 125 ka (when the Baraka River was far more active than today), followed by those at 198, 108, 84, and 6 ka.

The Sahel region currently faces various social, political, security, and environmental issues. However, the scientific and media discourse tends to oversimplify the underlying causes of these issues. While some authors attribute them to the heavy impact of climate change-induced scarcity, others focus on political factors such as bad governance. This article aims to merge the perspectives of Environmental Security and Political Ecology into one framework to provide a more holistic explanation of the problems in the Sahel. It shows how local political inequalities, marginalization, economic problems, military coups, corruption, and climate change mutually intersect in a mechanism that creates conflicts and insecurity. This is exacerbated by the geographical character of the Sahel states and their type of governance, which provides an operational space for many armed groups. By understanding the intersection of these conditions, the article contributes to the empirical understanding of the mechanism of conflicts in the Sahel and better conceptualizes the relationship between scarcity, climate change, and conflict.

Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe. Clusters were established for "ethanol"-, formaldehyde-based ("FA"), and "other" embalming procedures, depending on the chemicals considered the most relevant for each protocol. The logistical framework, volumes of chemicals, and infrastructure were found to be highly diverse between the groups and protocols. Formaldehyde quantities deployed per annum were three-fold higher in the "FA" (223 L/a) compared to the "ethanol" (71.0 L/a) group, but not for "other" (97.8 L/a), though the volumes injected per body were similar. "FA" was strongly related to table-borne air ventilation and total fixative volumes =1000 L. "Ethanol" was strongly related to total fixative volumes >1000 L, ceiling- and floor-borne air ventilation, and explosion-proof facilities. Air ventilation was found to be installed symmetrically in the mortuary and dissection facilities. Certain predictors exist for the interplay between the embalming used in a given infrastructure and technical measures. The here-established cluster analysis may serve as decision supportive tool when considering altering embalming protocols or establishing joint protocols between institutions, following a best practice approach to cater toward best-suited tissue characteristics for educational purposes, while simultaneously addressing future demands on exposure limits.

Abstract Eutrophication is accelerating the recent expansion of oxygen-depleted coastal marine environments. Several bolivinid foraminifera are abundant in these oxygen-depleted settings, and take up nitrate through the pores in their shells for denitrification. This makes their pore density a possible nitrate proxy. This study documents three aspects related to the porosity of bolivinids. 1. A new automated image analysis technique to determine the number of pores in bolivinids is tested. 2. The pore patterns of Bolivina spissa from five different ocean settings are analysed. The relationship between porosity, pore density and mean pore size significantly differs between the studied locations. Their porosity is mainly controlled by the size of the pores at the Gulf of Guayaquil (Peru), but by the number of pores at other studied locations. This might be related to the presence of a different cryptic Bolivina species in the Gulf of Guayaquil. 3. The pore densities of closely related bolivinids in core-top samples are calibrated as a bottom-water nitrate proxy. Bolivina spissa and Bolivina subadvena showed the same correlation between pore density and bottom-water nitrate concentrations, while the pore density of Bolivina argentea and Bolivina subadvena accumeata is much higher.

Abstract Background Overviews (i.e., systematic reviews of systematic reviews, meta-reviews, umbrella reviews) are a relatively new type of evidence synthesis. Among others, one reason to conduct an overview is to investigate adverse events (AEs) associated with a healthcare intervention. Overviews aim to provide easily accessible information for healthcare decision-makers including clinicians. We aimed to evaluate the clinical utility of overviews investigating AEs. Methods We used a sample of 27 overviews exclusively investigating drug-related adverse events published until 2021 identified in a prior project. We defined clinical utility as the extent to which overviews are perceived to be useful in clinical practice. Each included overview was assigned to one of seven pharmacological experts with expertise on the topic of the overview. The clinical utility and value of these overviews were determined using a self-developed assessment tool. This included four open-ended questions and a ranking of three clinical utility statements completed by clinicians. We calculated frequencies for the ranked clinical utility statements and coded the answers to the open-ended questions using an inductive approach. Results The overall agreement with the provided statements was high. According to the assessments, 67% of the included overviews generated new knowledge. In 93% of the assessments, the overviews were found to add value to the existing literature. The overviews were rated as more useful than the individual included systematic reviews (SRs) in 85% of the assessments. The answers to the open-ended questions revealed two key aspects of clinical utility in the included overviews. Firstly, it was considered useful that they provide a summary of available evidence (e.g., along with additional assessments, or across different populations, or in different settings that have not been evaluated together in the included SRs). Secondly, it was found useful if overviews conducted a new meta-analysis to answer specific research questions that had not been answered previously. Conclusions Overviews on drug-related AEs are considered valuable for clinical practice by clinicians. They can make available evidence on AEs more accessible and provide a comprehensive view of available evidence. As the role of overviews evolves, investigations such as this can identify areas of value.

Abstract In this single-center observational study with 1,206 participants, we prospectively evaluated SARS-CoV-2-antibodies (anti-S RBD) and vaccine-related adverse drug reactions (ADR) after basic and booster immunization with BNT162b2- and ChAdOx1-S-vaccines in four vaccination protocols: Homologous BNT162b2-schedule with second vaccination at either three or six weeks, homologous ChAdOx1-S-vaccination or heterologous ChAdOx1-S/BNT162b2-schedule, each at 12 weeks. All participants received a BNT162b2 booster. Blood samples for anti-S RBD analysis were obtained multiple times over a period of four weeks to six months after basic vaccination, immediately before, and up to three months after booster vaccination. After basic vaccination, the homologous ChAdOx1-S-group showed the lowest anti-S RBD levels over six months, while the heterologous BNT162b2-ChAdOx1-S-group demonstrated the highest anti-S levels, but failed to reach level of significance compared with the homologous BNT162b2-groups. Antibody levels were higher after an extended vaccination interval with BNT162b2. A BNT162b2 booster increased anti-S-levels 11- to 91-fold in all groups, with the homologous ChAdOx1-S-cohort demonstrated the highest increase in antibody levels. No severe or serious ADR were observed. The findings suggest that a heterologous vaccination schedule or prolonged vaccination interval induces robust humoral immunogenicity with good tolerability. Extending the time to boost-immunization is key to both improving antibody induction and reducing ADR rate.

A 500 kyr long record of vegetation change from SE Europe demonstrates that forest resilience is lost when precipitation decreases below a threshold limit, and highlights the vulnerability of Mediterranean forests to near-future climate change

Tidal wetlands are highly dynamic ecosystems that are susceptible to changes in sea level and flooding from storm surges. Among them, salt marshes play a key role in coastal protection as they contribute to wave attenuation through their regulating ecosystem services, thereby promoting sediment deposition and shoreline stabilization. However, the resilience of salt marshes, particularly those that have been modified and cultivated for centuries, is questionable in the face of accelerated sea-level rise (SLR) and increasing run-up heights of storm surges. In this context, this study aims to investigate the historical foraminiferal records of two sedimentary salt marsh archives from the Wadden Sea area (Dithmarschen and North Frisia, Germany) that have been modified to varying degrees by human management activities over the last century. The foraminiferal records document how physico-chemical traits of salt marshes of the central Wadden Sea have responded to storm tide inundation over the last century, providing information about salt marsh stability and vulnerability. Abnormally grown tests of the salt marsh indicator species Entzia macrescens increased in number between 1950 CE and the late 1980s, indicating the concurrent increase of environmental stress caused by the effects of times of increased salt marsh flooding. These trends can be linked to observations of amplified North Sea storm surges, corroborating that salt marsh ecosystems respond to changing climate conditions. Differences in the number of abnormal foraminifera between the studied salt marshes suggest a particularly high vulnerability of intensively human-modified coastal wetland ecosystems to amplified storm climate conditions.

IntroductionUniversity students are confronted with various demands that can lead to mental health problems, including depression, anxiety, or stress. One significant resource that has been shown to prevent or buffer mental health problems is social support. However, interventions enhancing students’ perception and use of social support are rare in higher education research. This study evaluates the effects of resource-oriented training following the Zurich Resource Model on students’ perception and use of social resources.MethodParticipants included 247 students from a German university who enrolled in the training program and were divided into intervention and waiting control groups.ResultsCompared to the control group, the intervention group reported higher perceived social support, increased quality of received social support, and increased seeking social support as a coping strategy four weeks after the intervention. The study results further reveal changes in support network composition in both groups over time and offer insights into the characterization of energy givers and energy eaters within one’s support network.DiscussionThe discussion concludes with implications, limitations, and directions for future research.

Human activities in coastal areas have intensified over the last 200 years, impacting also high-latitude regions such as the Baltic Sea. Benthic foraminifera, protists often with calcite shells (tests), are typically well preserved in marine sediments and known to record past bottom-water conditions. Morphological analyses of marine shells acquired by microcomputed tomography (µCT) have made significant progress toward a better understanding of recent environmental changes. However, limited access to data processing and a lack of guidelines persist when using open-source software adaptable to different microfossil shapes. This study provides a post-data routine to analyze the entire test parameters: average thickness, calcite volume, calcite surface area, number of pores, pore density, and calcite surface area/volume ratio. A case study was used to illustrate this method: 3D time series (i.e., 4D) of Elphidium clavatum specimens recording environmental conditions in the Baltic Sea entrance from the period early industrial (the 1800s) to present-day (the 2010 s). Long-term morphological trends in the foraminiferal record revealed that modern specimens have ∼28% thinner tests and ∼91% more pores than their historic counterparts. However, morphological variability between specimens and the BFAR (specimens cm−2 yr−1) in E. clavatum were not always synchronous. While the BFAR remained unchanged, morphological variability was linked to natural environmental fluctuations in the early industrial period and the consequences of anthropogenic climate change in the 21st century. During the period 1940–2000 s, the variations in BFAR were synchronous with morphological variability, revealing both the effects of the increase in human activities and major hydrographic changes. Finally, our interpretations, based on E. clavatum morphological variations, highlight environmental changes in the Baltic Sea area, supporting those documented by the foraminiferal assemblages.

The gross anatomy dissection course is considered to be one of the most important subjects in medical school. Advancing technology facilitates the production of e-learning material that can improve the learning of topographic anatomy during the course. The purpose of this study was to examine a locally produced audiovisual dissection manual's effects on performance in dissection, formal knowledge gained, motivation, emotions, learning behavior, and learning efficiency of the medical students. The results, combined with the total effort put into the production of the manual, should support decisions on further implementation of this kind of audiovisual e-learning resource into the university's curriculum. First-year medical students (n = 279) were randomly divided into three groups for two weeks within the regular dissection course hours during the dissection of the anterior and posterior triangles of the neck. Two groups received an audiovisual dissection manual (n = 96) or an improved written manual (n = 94) as an intervention, the control group (n = 89) received the standard dissection manual. After dissection, each student filled out tests and surveys and their dissections were evaluated. The audiovisual dissection manual did not have any significant positive effects on the examined parameters. The effects of the audiovisual dissection manual on the medical students' learning experience, as observed in this study, did not support further curriculum implementation of this kind of e-learning resource. This study can serve as an orientation for further evaluation and design of e-learning resources for the gross anatomy dissection course.

Abstract Background DNA methylation is thought to influence the expression of genes, especially in response to changing environmental conditions and developmental changes. Sugar beet (Beta vulgaris ssp. vulgaris), and other biennial or perennial plants are inevitably exposed to fluctuating temperatures throughout their lifecycle and might even require such stimulus to acquire floral competence. Therefore, plants such as beets, need to fine-tune their epigenetic makeup to ensure phenotypic plasticity towards changing environmental conditions while at the same time steering essential developmental processes. Different crop species may show opposing reactions towards the same abiotic stress, or, vice versa, identical species may respond differently depending on the specific kind of stress. Results In this study, we investigated common effects of cold treatment on genome-wide DNA methylation and gene expression of two Beta vulgaris accessions via multi-omics data analysis. Cold exposure resulted in a pronounced reduction of DNA methylation levels, which particularly affected methylation in CHH context (and to a lesser extent CHG) and was accompanied by transcriptional downregulation of the chromomethyltransferase CMT2 and strong upregulation of several genes mediating active DNA demethylation. Conclusion Integration of methylomic and transcriptomic data revealed that, rather than methylation having directly influenced expression, epigenetic modifications correlated with changes in expression of known players involved in DNA (de)methylation. In particular, cold triggered upregulation of genes putatively contributing to DNA demethylation via the ROS1 pathway. Our observations suggest that these transcriptional responses precede the cold-induced global DNA-hypomethylation in non-CpG, preparing beets for additional transcriptional alterations necessary for adapting to upcoming environmental changes.

Introduction: Many older adults are affected by multimorbidity and subsequent polypharmacy which is associated with adverse outcomes. This is especially relevant for frail older patients. Polypharmacy may be reduced via deprescribing. As part of the complex intervention in the COFRAIL study, we developed a deprescribing manual to be used by general practitioners (GPs) in family conferences, in which GPs, patients and caregivers jointly discuss treatments. Methods: We selected indications with a high prevalence in older adults in primary care (e.g. diabetes mellitus, hypertension) and conducted a literature search to identify deprescribing criteria for these indications. We additionally reviewed clinical practice guidelines. Based on the extracted information, we created a deprescribing manual which was then piloted in an expert workshop and in family conferences with volunteer patients according to the inclusion and exclusion criteria of the study protocol. Results: Initially, 13 indications/topics were selected. The literature search identified deprescribing guides, reviews and clinical trials as well as lists of potentially inappropriate medication and systematic reviews on the risk and benefits of specific drugs and drug classes in older patients. After piloting and revisions, the deprescribing manual now covers 11 indications/topics. In each chapter, patient- and medication-related deprescribing criteria, monitoring and communication strategies, and information about concerns related to the use of specific drugs in older patients are provided. Discussion: We found varying deprescribing strategies in the literature, which we consolidated in our deprescribing manual. Whether this approach leads to successful deprescribing in family conferences is being investigated in the cluster-randomised controlled COFRAIL study. Plain Language Summary Development of a manual to help doctors to identify which medications can be withdrawn Many older adults suffer from chronic diseases and take multiple medications concurrently. This can lead to side effects and other undesired events. We developed a manual to help doctors identify which medications can be withdrawn, so that they can discuss this with their patients. This manual was used in the COFRAIL study where doctors, patients and caregivers met in family conferences to discuss their preferences and decide together how future treatments should be handled. The manual contains information on common medications, symptoms and diseases in older patients such as diabetes and high blood pressure. Before the manual was used in the study, it was tested by volunteer patients and their doctors and caregivers to make sure that it is user-friendly.

Abstract Surface benthic foraminiferal assemblages associated with cold‐water coral mounds and reefs from the Irish margin and Norwegian shelf (North‐east Atlantic) are for the first time compared quantitatively. Results indicate that the considered sites share a common assemblage, dominated by elevated epibenthic and distinct infaunal species. This surface assemblage is typical of environments that are subject to strong bottom‐water turbulence with enhanced food availability. It provides a benchmark for comparison with fossil benthic foraminiferal assemblages from past cold‐water coral environments. Similar to macrofaunal and megafaunal communities, surface benthic foraminiferal diversity is higher on reefs and mounds than in surrounding off‐mound/off‐reef sediments. Benthic foraminiferal diversity is highest within the living coral macrohabitat, possibly as a result of enhanced availability and variety of food sources, and ecological niche separation. Indeed, living coral generally thrives on the summits or flanks of reefs and mounds where food availability is most important. The second part discusses the use of fossil benthic foraminiferal assemblages as palaeoceanographic proxies from past cold‐water coral environments. The overview of previous observations demonstrates that benthic foraminifera are valuable tools to reconstruct past bottom‐water oxygenation, bottom‐water currents and surface productivity, all of which are key environmental variables controlling cold‐water coral growth. Moreover, the advantages of a detailed investigation of benthic foraminiferal assemblages within cold‐water coral environments are compared to other palaeoceanographic proxies. This study highlights that benthic foraminiferal assemblages are an often overlooked proxy within cold‐water coral environments, despite yielding valuable information.