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Abstract: —J. Blunden and T. Boyer In 2023, La Niña conditions that generally prevailed in the eastern Pacific Ocean from mid-2020 into early 2023 gave way to a strong El Niño by October. Atmospheric concentrations of Earth’s major greenhouse gases—carbon dioxide, methane, and nitrous oxide—all increased to record-high levels. The annual global average carbon dioxide concentration in the atmosphere rose to 419.3±0.1 ppm, which is 50% greater than the pre-industrial level. The growth from 2022 to 2023 was 2.8 ppm, the fourth highest in the record since the 1960s. The combined short-term effects of El Niño and the long-term effects of increasing levels of heat-trapping gases in the atmosphere contributed to new records for many essential climate variables reported here. The annual global temperature across land and oceans was the highest in records dating as far back as 1850, with the last seven months (June–December) having each been record warm. Over land, the globally averaged temperature was also record high. Dozens of countries reported record or near-record warmth for the year, including China and continental Europe as a whole (warmest on record), India and Russia (second warmest), and Canada (third warmest). Intense and widespread heatwaves were reported around the world. In Vietnam, an all-time national maximum temperature record of 44.2°C was observed at Tuong Duong on 7 May, surpassing the previous record of 43.4°C at Huong Khe on 20 April 2019. In Brazil, the air temperature reached 44.8°C in Araçuaí in Minas Gerais on 20 November, potentially a new national record and 12.8°C above normal. The effect of rising temperatures was apparent in the cryosphere, where snow cover extent by June 2023 was the smallest in the 56-year record for North America and seventh smallest for the Northern Hemisphere overall. Heatwaves contributed to the greatest average mass balance loss for Alpine glaciers around the world since the start of the record in 1970. Due to rapid volume loss beginning in 2021, St. Anna Glacier in Switzerland and Ice Worm Glacier in the United States disappeared completely. In August, as a direct result of glacial thinning over the past 20 years, a glacial lake on a tributary of the Mendenhall Glacier in Alaska burst through its ice dam and caused unprecedented flooding on Mendenhall River near Juneau. Across the Arctic, the annual surface air temperature was the fourth highest in the 124-year record, and summer (July–September) was record warm. Smaller-than-normal snow cover extent in May and June contributed to the third-highest average peak tundra greenness in the 24-year record. In September, Arctic minimum sea ice extent was the fifth smallest in the 45-year satellite record. The 17 lowest September extents have all occurred in the last 17 years. In Antarctica, temperatures for much of the year were up to 6°C above average over the Weddell Sea and along coastal Dronning Maud Land. The Antarctic Peninsula also experienced well-above-average temperatures during the 2022/23 melt season, which contributed to its fourth consecutive summer of above-average surface melt. On 21 February, Antarctic sea ice extent and sea ice area both reached all-time lows, surpassing records set just a year earlier. Over the course of the year, new daily record-low sea ice extents were set on 278 days. In some instances, these daily records were set by a large margin, for example, the extent on 6 July was 1.8 million km2 lower than the previous record low for that day. Across the global oceans, the annual sea surface temperature was the highest in the 170-year record, far surpassing the previous record of 2016 by 0.13°C. Daily and monthly records were set from March onward, including an historic-high daily global mean sea surface temperature of 18.99°C recorded on 22 August. Approximately 94% of the ocean surface experienced at least one marine heatwave in 2023, while 27% experienced at least one cold spell. Globally averaged ocean heat content from the surface to 2000-m depth was record high in 2023, increasing at a rate equivalent to ∼0.7 Watts per square meter of energy applied over Earth’s surface. Global mean sea level was also record high for the 12th consecutive year, reaching 101.4 mm above the 1993 average when satellite measurements began, an increase of 8.1±1.5 mm over 2022 and the third highest year-over-year increase in the record. A total of 82 named tropical storms were observed during the Northern and Southern Hemispheres’ storm seasons, below the 1991–2020 average of 87. Hurricane Otis became the strongest landfalling hurricane on record for the west coast of Mexico at 140 kt (72 m s−1), causing at least 52 fatalities and $12–16 billion U.S. dollars in damage. Freddy became the world’s longest-lived tropical cyclones on record, developing into a tropical cyclone on 6 February and finally dissipating on 12 March. Freddy crossed the full width of the Indian Ocean and made one landfall in Madagascar and two in Mozambique. In the Mediterranean Sea—outside of traditional tropical cyclone basins—heavy rains and flooding from Storm Daniel killed more than 4300 people and left more than 8000 missing in Libya. The record-warm temperatures in 2023 created conditions that helped intensify the hydrological cycle. Measurements of total-column water vapor in the atmosphere were the highest on record, while the fraction of cloud area in the sky was the lowest since records began in 1980. The annual global mean precipitation total over land surfaces for 2023 was among the lowest since 1979, but global one-day maximum totals were close to average, indicating an increase in rainfall intensity. In July, record-high areas of land across the globe (7.9%) experienced extreme drought, breaking the previous record of 6.2% in July 2022. Overall, 29.7% of land experienced moderate or worse categories of drought during the year, also a record. Mexico reported its driest (and hottest) year since the start of its record in 1950. In alignment with hot and prolonged dry conditions, Canada experienced its worst national wildfire season on record. Approximately 15 million hectares burned across the country, which was more than double the previous record from 1989. Smoke from the fires were transported far into the United States and even to western European countries. August to October 2023 was the driest three-month period in Australia in the 104-year record. Millions of hectares of bushfires burned for weeks in the Northern Territory. In South America, extreme drought developed in the latter half of the year through the Amazon basin. By the end of October, the Rio Negro at Manaus, a major tributary of the Amazon River, fell to its lowest water level since records began in 1902. The transition from La Niña to El Niño helped bring relief to the prolonged drought conditions in equatorial eastern Africa. However, El Niño along with positive Indian Ocean dipole conditions also contributed to excessive rainfall that resulted in devastating floods over southeastern Ethiopia, Somalia, and Kenya during October to December that displaced around 1.5 million people. On 5 September, the town of Zagora, Greece, broke a national record for highest daily rainfall (754 mm in 21 hours, after which the station ceased reporting) due to Storm Daniel; this one-day accumulation was close to Zagora’s normal annual total.

Abstract Spatial modelling approaches to aid land‐use decisions which benefit both wildlife and humans are often limited to the comparison of pre‐determined landscape scenarios, which may not reflect the true optimum landscape for any end‐user. Furthermore, the needs of wildlife are often under‐represented when considered alongside human financial interests in these approaches. We develop a method of addressing these gaps using a case‐study of wild bees in the UK, an important group whose declines may adversely affect both human economies and surrounding ecosystems. By combining the genetic algorithm NSGA‐II with a process‐based pollinator model which simulates bee foraging and population dynamics, Poll4pop, we ‘evolve’ a typical UK agricultural landscape to identify optimum land cover configurations for three different guilds of wild bee. These configurations are compared to those resulting from optimisations for farm income alone, as well as optimisations that seek a compromise between bee populations and farm income objectives. We find that the land cover proportions in landscapes optimised for each bee guild reflect their nesting habitat preferences rather than foraging preferences, highlighting a limiting resource within the study landscape. The spatially explicit nature of these optimised landscapes illustrates how improvement for a given target species may be limited by differences between their movement range and the scale of the units being improved. Land cover composition and configuration differ significantly in landscapes optimised for farm income and bee population growth simultaneously and illustrate how human agents are required to compromise much more when the multifaceted nature of biodiversity is recognised and represented by multiple objectives within an optimisation framework. Our methods provide a way to quantify the extent to which real‐life landscapes promote or compromise objectives for different landscape end‐users. Our investigation suggests that optimisation set‐up (decision‐unit scales, traditional choice of a single biodiversity metric) can bias outcomes towards human‐centric solutions. It also demonstrates the importance of representing the individual requirements of different actors with different landscape‐level needs when using genetic algorithms to support biodiversity‐inclusive decision‐making in multi‐functional landscapes.

Abstract Background General practitioners (GPs) play a crucial role in identifying cognitive impairment and dementia and providing post-diagnostic care. This study investigates (1) how promising GP consider lifestyle changes to maintain cognitive performance in general, (2) GP beliefs about the power of modifiable health and lifestyle factors to maintain cognitive performance, and (3) whether those beliefs vary by GP age. Methods As part of the AgeWell.de trial, GPs (n = 72) completed a process evaluation questionnaire assessing their perspectives on lifestyle changes to preserve cognitive performance in elderly patients. In greater detail, their perceived efficacy of established risk and protective factors was investigated using a 5-point Likert scale. Descriptive statistical analyses were performed for research question (1) and (2). Spearman´s rank correlations and ordinal logistic regressions were used to answer research question (3). All results were interpreted exploratively. Results GPs rated the overall chance of lifestyle changes maintaining cognitive performance quite neutral with a median score of 3.0 (IQR = 2.0). They rated the efficacy of all the modifiable health and lifestyle factors high, with increase in physical and social activity ((Mdn = 5.0, IQR = 1.0) receiving the highest ratings with the narrowest range. Spearman's rank correlation indicated a significant positive relationship between age and the belief in “Optimization of nutrition” for preventing cognitive decline and dementia (ρ = .255, p = .041). However, ordinal logistic regressions showed no significant relationships between age and GP ratings of lifestyle change efficacy. Conclusion These findings highlight the positive perception of GPs on the efficacy of modifiable health and lifestyle factors for preventing cognitive decline and dementia. Trial registration The AgeWell.de trial is registered in the German Clinical Trials Register (DRKS; trial identifier: DRKS00013555, Registration Date 07 December 2017).

IntroductionHealth disparities pose a considerable challenge for older adults individuals, particularly those with a heightened risk of developing dementia. Discrepancies in health status among various income brackets are only partially attributable to structural factors such as working and living conditions or the quality of food. The aim of this study was therefore to explore whether and to what extent various health-promoting behaviors can explain the association between household income and self-rated health among older people at risk of dementia.MethodsThe sample consisted of 845 participants (average age 68.9 years; 52.6% female) from the AgeWell.de study, an intervention trial aiming to preserve cognitive function. The participants exhibited an increased risk of dementia, defined by a CAIDE (Cardiovascular Risk Factors, Aging and Dementia) score of at least nine points. To explore the relationship between household income and self-rated health, measured using the EQ-5D-VAS, a regression analysis was conducted. This association was then examined using four mediation analyses that included health-promoting behaviors such as fruit and vegetable consumption, social participation, physical activities, and cognitive activities.ResultsThe results reveal a positive association between higher income and self-rated health. This relationship is mediated by social participation. Additionally, cognitive activities were found to partially mediate this correlation. Neither physical activities nor fruit and vegetable consumption could account for the association between income and self-rated health.ConclusionThe findings have the potential to advance research on the correlation between income and health among older age cohorts at risk of developing dementia. They highlight the potential significance of social engagement and cognitive activities for health and may inspire the development of strategies aimed at enhancing accessibility to activities such as cultural events, educational institutions, and participation in courses for a wider audience.

Abstract Background Aim of this study was to detect predictors of better adherence to the AgeWell.de-intervention, a two-year randomized multi-domain lifestyle intervention against cognitive decline. Methods Data of 317 intervention group-participants comprising a risk group for dementia (Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) score of ≥ 9; mean age 68.9 years, 49.5% women) from the AgeWell.de intervention study were analysed. Regression models with four blocks of predictors (sociodemographic, cognitive and psychosocial, lifestyle factors and chronic conditions) were run on adherence to the components of nutrition, enhancement of social and physical activity and cognitive training. Adherence to each component was operationalised by assessing the degree of goal achievement per component at up to seven time points during the intervention period, measured using a 5-point Likert scale (mean score of goal achievement). Results Increasing age was negatively associated with adherence, while higher education positively predicted adherence. Participants with better mental state (Montreal Cognitive Assessment (MoCA)-score > 25) at baseline and higher self-efficacy adhered better. Diabetes and cardiovascular conditions were not associated with adherence, whereas smoking negatively affected adherence. Highest education and quitting smoking in the past were the only predictors associated with all four intervention components. Conclusion Results identified predictors for better and worse adherence. Particularly self-efficacy seems to be of considerable influence on adherence. This should be considered when designing future intervention trials. Trial registration German Clinical Trials Register (ref. number: DRKS00013555).

Introduction Germany and the European Union have experienced successive waves of refugees since 2014, resulting in over 1.6 million arrivals, including families with young children. These vulnerable populations often face xenophobia, discrimination, substandard living conditions and limited healthcare access, contributing to a high prevalence of mental health problems (MHP). Our primary goal is to proactively address MHP in refugee parents and prevent its potential impact on their children through effective early interventions. Using a low-threshold, primary care-based approach, we aim to enhance parenting skills and address parental psychopathology, creating a supportive environment for parents and children.Methods and analysis In this randomised controlled trial, 188 refugee parents of 6-year-old children or younger who meet the clinical cut-off on the MHP scale will participate. They are randomly assigned to either the experimental psychotherapeutic intervention, delivered by general practitioners (10-week Improve intervention), or treatment as usual, in a ratio of 1:1. The randomisation will be masked only for outcome assessors. Improve includes face-to-face sessions with general practitioners, an interactive online parenting programme (Triple P Online) and regular protocol-based telephone calls by psychologists. Primary outcomes will assess the intervention’s effects on parental and child MHP and parenting skills, with secondary outcomes including psychosocial and physical health indicators. Outcomes will be assessed at pre, post and at 3-month and 6-month follow-ups. The study is scheduled to run from February 2019 to July 2025.Ethics and dissemination The project Improve-MH (application number 602) was approved by the local ethics committee of Ruhr-University of Bochum and is being conducted in accordance with the Declaration of Helsinki. The study is also conducted in full accordance with the German Data Protection Act, and the Good Clinical Practice guideline (GCP) and is sensitive to specific ethical considerations. Results will be disseminated at scientific conferences, published in peer-reviewed journals and provided to consumers of healthcare.Trial registration number The trial was prospectively registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS-ID: DRKS00019072) on 16 March 2020.

Introduction The early detection of pancreatic cancer is an important step in reducing mortality by offering patients curative treatment. Screening strategies in risk populations and by means of different detection methods have been economically evaluated. However, a synthesis of screening studies to inform resource allocation towards early detection within the disease area has not been done. Therefore, studies evaluating the cost-effectiveness and costs of screening for pancreatic cancer should be systematically reviewed.Methods and analysis A systematic review of economic evaluations reporting the cost-effectiveness or costs of pancreatic cancer screening will be conducted. The electronic databases Medline, Web of Science and EconLit will be searched without geographical or time restrictions. Two independent reviewers will select eligible studies based on predefined criteria. The study quality will be assessed using the Consolidated Health Economic Evaluation Reporting Standards statement and the Bias in Economic Evaluation checklist. One reviewer will extract relevant data and a second reviewer will cross-check compliance with the extraction sheet. Key items will include characteristics of screened individuals, the screening strategies used, and costs, health effects and cost-effectiveness as study outputs. Differences of opinion between the reviewers will be solved by consulting a third reviewer.Ethics and dissemination Ethics approval is not required for this study since no original data will be collected. The results will be disseminated through presentations at conferences and publication in a peer-reviewed journal. The results of the systematic review will inform future economic evaluations of pancreatic screening, which provide guidance for decision-making in healthcare resource prioritisation.PROSPERO registration number CRD42023475348.

IntroductionEvidence points toward the early life being crucial for preventing nutrition-related diseases. As promotion of healthier food preferences in toddlerhood and preschool age might still modulate the trajectories of disease risk, understanding diet in these age groups is necessary. The objective was to analyze food consumption and diet quality of 1–5-year-old children living in Germany in relation to age and sex.MethodsData from 890 children, a subsample of the representative, cross-sectional Children’s Nutrition Survey to Record Food Consumption (KiESEL) conducted by the German Federal Institute for Risk Assessment in 2014–2017, were analyzed. Dietary data were collected using food records (3 consecutive plus 1 independent day). Diet quality was evaluated against the German food-based dietary guidelines (FBDG).ResultsConsumption of unfavorable foods (e.g., sweets, soft drinks) exceeded the recommended maximum of 10% of energy intake (E%) by a multiple in all age and sex groups (medians: 24.8–35.8 E%). Preschoolers consumed more unfavorable foods than toddlers and boys more than girls. More than half of the children exceeded the recommendation for meat intake (medians: 2.3–3.2% of the total food consumption (%TFC) vs. 2 %TFC), especially preschoolers. In nearly all children, vegetable consumption was too low (medians: 4.2–4.5 %TFC vs. 12 %TFC). Also, milk/milk product consumption was below recommendations, more so in preschoolers (median: 12.0 %TFC ♂, 11.9 %TFC ♀ vs. 18 %TFC) than in toddlers (median: 16.1 %TFC ♂, 19.6 %TFC ♀). In toddlers and preschoolers with overweight or obesity, adherence to dietary recommendations of these food groups was largely similar to that of the total sample. Overall, 5-year-olds showed an unhealthier dietary pattern than 1-year-olds, which already emerged at age 2 years and became more evident at age 3 years.DiscussionAn adverse dietary pattern arises and even deteriorates at a very young age, showing sex-specific aspects. High attention from public health and research needs to be given to toddlerhood and even earlier life phases, e.g., to develop more age-specific FBDGs, aiming at reducing unhealthy food consumption.

The performance of geothermal heat extraction in shallow aquifers depends on both Borehole Heat Exchanger (BHE) and soil or aquifer properties. In this work, an analysis of the thermal yield of a shallow geothermal reservoir was made numerically with the finite element method used to simulate heat and mass transfer in the three-dimensional reservoir. The main parameters for analysis which have been considered are the geometry and physical parameters of the BHE and grout, as well as aquifer matrix and groundwater fluid. Physical parameters are thermal conductivity, flow conductivity, expansion coefficient, porosity, volumetric heat capacity, anisotropy and dispersivity. The numerical tests have been performed in single BHE line source configuration representing numerically modelled thermal response test for the estimation of sustainable heat extraction. The domain size was a 100x100 meter rectangle with a depth of 200 meters. Three main lithological configurations have been modelled: gravel aquifer with low and high convection of groundwater fluid, as well as a shallow geothermal reservoir dominated by clay material without convection. For selected cases, the analysis for temporal and spatial discretization was also made. Three-dimensional transient modelling was made in FEFLOW® software with pre- and post-processing done in user-defined Python scripts. The results show the most influential parameters to be considered when setting up the real case simulation of geothermal heating and cooling, as well as optimal temporal and spatial discretization set-up with respect to expected thermal gradients in the reservoir.

PurposeThe present study aimed to investigate age-group-specific incidence rates and risk factors for depressive symptoms in the highest age groups.MethodsData were derived from a prospective multicenter cohort study conducted in primary care – the AgeCoDe/AgeQualiDe study. In total, 2,436 patients 75 years and older were followed from baseline to ninth follow-up. To assess depressive symptoms, the short version of the Geriatric Depression Scale (GDS-15, cutoff score 6) was used. Age-specific competing risk regressions were performed to analyze risk factors for incident depressive symptoms in different age groups (75 to 79, 80 to 84, 85+ years), taking into account the accumulated mortality.ResultsThe age-specific incidence rate of depression was 33 (95% CI 29-38), 46 (95% CI 40-52) and 63 (95% CI 45-87) per 1,000 person years for the initial age groups 75 to 79, 80 to 84 and 85+ years, respectively. In competing risk regression models, female sex, mobility as well as vision impairment, and subjective cognitive decline (SCD) were found to be risk factors for incident depression for age group 75 to 79, female sex, single/separated marital status, mobility as well as hearing impairment, and SCD for age group 80 to 84, and mobility impairment for age group 85+.ConclusionDepressive symptoms in latest life are common and the incidence increases with increasing age. Modifiable and differing risk factors across the highest age groups open up the possibility of specifically tailored prevention concepts.

In Plasma Medicine studies, the effect of non-thermal plasma (NTP) on biological targets is typically correlated with the amount of stable reactive oxygen and nitrogen species produced in a liquid medium. The effect of NTP and the response of the biological target on cellular redox mechanisms is overlooked in these investigations. Additionally, the influence of electrical properties of cells on the physical properties of NTP is neglected. Therefore, we used a floating electrode dielectric barrier discharge plasma to explore the impact of cell structure, size, and viability of the biological target on the physical properties of NTP. Lissajous figures were used to determine circuit capacitance and energy per cycle during NTP exposure of different cell suspensions. We show that both, structural integrity and active enzymic processes of cells change the electrical properties of NTP. Correlations were also drawn between NTP-produced hydrogen peroxide and nitrite with measured capacitance. Our studies indicate that the observed changes between different cell suspensions may be due to a feedback loop between the biological target and the NTP source. In future studies, a more detailed analysis is needed to improve the control of clinical NTP devices.

BackgroundNutrition in the first years of life is a cornerstone for child development and long-term health, yet there is a lack of current data on energy and nutrient intake among toddlers and preschoolers in Germany.ObjectiveTo analyze energy and nutrient intake in toddlers (1- to 2-year-olds) and preschoolers (3- to 5-year-olds) in Germany and compare the results with the Dietary Reference Values (DRVs) by the European Food Safety Authority.DesignDietary intake was assessed by weighed food record data (3 + 1 day) of 890 children from the representative cross-sectional Children’s Nutrition Survey to Record Food Consumption (KiESEL), carried out in 2014–2017 as a module of the German Health Interview and Examination Survey for Children and Adolescents Wave 2. For the calculation of energy and nutrient intake, the German Nutrient Database BLS 3.02, LEBTAB, and a supplement database were used.ResultsMedian intakes of energy and most nutrients met or exceeded the DRVs in both toddlers and preschoolers. However, low intakes relative to DRVs were found for vitamin D (6–9% of DRV, including supplements) and iodine (57–65% of DRV). Age specific downward deviations were observed for iron intake in toddlers (75% of DRV) and for calcium intake in preschoolers (67–77% of DRV). In contrast, intakes were high for saturated fatty acids (SFA) (14–16 E%), mono-/disaccharides (60–87 g/day), and protein [2.1–2.6 g/(kg body weight*day)].ConclusionNutrient imbalances in toddlers and preschoolers in Germany, which are partly age-related, give rise to concern. Research is needed to determine if routine vitamin D supplementation should be extended beyond infancy. Public health efforts to increase the rate of use of iodized salt and to reduce the intake of SFA and mono-/disaccharides in children’s diets are to be strengthened.

Abstract Background For more than 20 years, restoration measures have been conducted on watercourses in Germany to increase habitat diversity and thus promote biodiversity. However, their ecological efficacy often proved to be limited. While some studies report an increase in species diversity, others show little evidence of improvement even many years after the implementation of restoration measures. In general, ecological efficacy of hydromorphological restoration measures is highest for terrestrial and semiaquatic groups of organisms such as floodplain vegetation and ground beetles. According to the literature, macrophytes responded most strongly to in-stream restoration measures, while fish stocks showed little improvement and macroinvertebrates showed little or no effect in terms of species richness and diversity. These findings raise the question of reasons for the low ecological efficacy of hydromorphological restoration measures, especially for macroinvertebrate communities. The following literature review and a case study for the river Horloff will provide possible indications for failing success of intensive restoration measures. Results One reason for the inadequate ecological status of many restored river stretches is the inappropriate scaling of restoration measures. Often, small-scale restoration measures are planned, although the respective water bodies exhibit stressors at the catchment scale that impair the ecological efficacy of restoration measures. In particular, chemical contamination of running waters is often insufficiently addressed in the planning and implementation of restoration measures and hampers efficacy of hydromorphological restoration measures. For a holistic water resource management, the planning and implementation of measures should therefore be more closely coordinated and harmonized between federal states and neighboring countries. For this purpose, the establishment of so-called river basin communities is suitable, as they already exist today on the rivers Rhine, Danube, Meuse, Weser, Elbe, Ems, Eider, Schlei/Trave, Warnow/Peene. Conclusion The literature review indicated that for a successful recolonization of restored river stretches by macroinvertebrates and the enhancement of the ecological status, large-scale stressors, i.e., stressors acting at the catchment scale, should be eliminated initially by restoration measures focusing on the chemical contamination and the surrounding land use. Structural restoration measures acting on the reach or local scale should ideally be implemented contemporarily to the removal of large-scale stressors like chemical contamination.

Forschungsdaten sind nur im jeweiligen Kontext sinnvoll interpretier- und nachnutzbar – Bestandteil dieses Kontexts ist auch jegliche Software, die zur Erstellung und Verarbeitung der entsprechenden Forschungsdaten genutzt wurde. Im Folgenden werden mit Blick auf gute wissenschaftliche Praxis und die FAIR-Prinzipien primär organisatorische Aspekte im Umgang mit Forschungssoftware untersucht, sowie mit strategische Überlegungen angestellt, wie Forschungssoftware langfristig eingesetzt werden kann. Dazu werden aktuelle Entwicklungen im Bereich rechtlicher und organisatorischer Überlegungen präsentiert und konkrete Empfehlungen ausgesprochen. Dieses Papier wird vom Arbeitskreis der Leiterinnen und Leiter der wissenschaftlichen Rechenzentren in Baden-Württemberg (ALWR) unterstützt.

ABSTRACTIMAB362/Zolbetuximab, a first-in-class IgG1 antibody directed against the cancer-associated gastric-lineage marker CLDN18.2, has recently been reported to have met its primary endpoint in two phase 3 trials as a first-line treatment in combination with standard of care chemotherapy in CLDN18.2-positive Her2 negative advanced gastric cancer. Here we characterize the preclinical pharmacology of BNT141, a nucleoside-modified RNA therapeutic encoding the sequence of IMAB362/Zolbetuximab, formulated in lipid nanoparticles (LNP) for liver uptake. We show that the mRNA-encoded antibody displays a stable pharmacokinetic profile in preclinical animal models, mediates CLDN18.2-restricted cytotoxicity comparable to IMAB362 recombinant protein and inhibits human tumor xenograft growth in immunocompromised mice. BNT141 administration did not perpetrate mortality, clinical signs of toxicity, or gastric pathology in animal studies. A phase 1/2 clinical trial with BNT141 mRNA-LNP has been initiated in advanced CLDN18.2-expressing solid cancers (NCT04683939).

BackgroundWith the outbreak of COVID-19, government measures including social distancing and restrictions of social contacts were imposed to slow the spread of the virus. Since older adults are at increased risk of severe disease, they were particularly affected by these restrictions. These may negatively affect mental health by loneliness and social isolation, which constitute risk factors for depressiveness. We aimed to analyse the impact of perceived restriction due to government measures on depressive symptoms and investigated stress as mediator in an at-risk-population in Germany.MethodsData were collected in April 2020 from the population of the AgeWell.de-study, including individuals with a Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score ≥9, using the depression subscale of the Brief Symptom Inventory (BSI-18) and the Perceived Stress Scale (PSS-4). Feeling restricted due to COVID-19 government measures was surveyed with a standardized questionnaire. Stepwise multivariate regressions using zero-inflated negative binomial models were applied to analyse depressive symptoms, followed by a general structural equation model to assess stress as mediator. Analysis were controlled for sociodemographic factors as well as social support.ResultsWe analysed data from 810 older adults (mean age = 69.9, SD = 5). Feeling restricted due to COVID-19 government measures was linked to increased depressiveness (b = 0.19; p

A practice team-based exercise programme with elements of cognitive behavioural therapy (CBT) and case management for patients with panic disorder with or without agoraphobia in primary care showed significant positive effects. Here, we analyse the long-term effects (>5 years) of this intervention in the stressful context of the Covid-19 pandemic. All participants of the original PARADIES cluster randomized controlled trial (cRCT; 2012-2016) were invited to participate in a follow-up during the Covid-19 pandemic. Clinical outcomes were anxiety symptoms, number and severity of panic attacks, agoraphobic avoidance behaviour, Covid-specific anxiety symptom severity, depression, and patient assessment of chronic illness care. Data were analysed cross-sectionally for group differences (intervention, control) and longitudinally (T0: baseline, T1: 6 months and TCorona: >60 months). Of the original 419 participants, 100 participated in the 60 months follow-up (October 2020-May 2021). In the cross-sectional analysis, the anxiety symptom severity in the intervention group was lower than in the control group (p = .011, Cohen's d = .517). In the longitudinal analysis, both groups showed an increase of anxiety and depression symptoms compared to pre-pandemic level. The intervention may have had a lasting impact regarding anxiety severity despite the challenging context of the Covid-19 pandemic. However, we cannot say to what extend the intervention still played a role in participants' lives; other factors may also have helped with coping. The increase of anxiety and depression symptoms in both groups over time could be attributed to external circumstances.

Artificial Intelligence (AI) is increasingly used within plant science, yet it is far from being routinely and effectively implemented in this domain. Particularly relevant to the development of novel food and agricultural technologies is the development of validated, meaningful and usable ways to integrate, compare and visualise large, multi-dimensional datasets from different sources and scientific approaches. After a brief summary of the reasons for the interest in data science and AI within plant science, the paper identifies and discusses eight key challenges in data management that must be addressed to further unlock the potential of AI in crop and agronomic research, and particularly the application of Machine Learning (AI) which holds much promise for this domain.

Lewy bodies commonly occur in Alzheimer's disease, and Alzheimer's disease pathology is frequent in Lewy body diseases, but the burden of co-pathologies across neurodegenerative diseases is unknown. We assessed the extent of tau, amyloid-β, α-synuclein and TDP-43 proteinopathies in 766 autopsied individuals representing a broad spectrum of clinical neurodegenerative disease. We interrogated pathological Alzheimer's disease (n = 247); other tauopathies (n = 95) including Pick's disease, corticobasal disease and progressive supranuclear palsy; the synucleinopathies (n = 164) including multiple system atrophy and Lewy body disease; the TDP-43 proteinopathies (n = 188) including frontotemporal lobar degeneration with TDP-43 inclusions and amyotrophic lateral sclerosis; and a minimal pathology group (n = 72). Each group was divided into subgroups without or with co-pathologies. Age and sex matched logistic regression models compared co-pathology prevalence between groups. Co-pathology prevalence was similar between the minimal pathology group and most neurodegenerative diseases for each proteinopathy: tau was nearly universal (92-100%), amyloid-β common (20-57%); α-synuclein less common (4-16%); and TDP-43 the rarest (0-16%). In several neurodegenerative diseases, co-pathology increased: in Alzheimer's disease, α-synuclein (41-55%) and TDP-43 (33-40%) increased; in progressive supranuclear palsy, α-synuclein increased (22%); in corticobasal disease, TDP-43 increased (24%); and in neocortical Lewy body disease, amyloid-β (80%) and TDP-43 (22%) increased. Total co-pathology prevalence varied across groups (27-68%), and was increased in high Alzheimer's disease, progressive supranuclear palsy, and neocortical Lewy body disease (70-81%). Increased age at death was observed in the minimal pathology group, amyotrophic lateral sclerosis, and multiple system atrophy cases with co-pathologies. In amyotrophic lateral sclerosis and neocortical Lewy body disease, co-pathologies associated with APOE ɛ4. Lewy body disease cases with Alzheimer's disease co-pathology had substantially lower Mini-Mental State Examination scores than pure Lewy body disease. Our data imply that increased age and APOE ɛ4 status are risk factors for co-pathologies independent of neurodegenerative disease; that neurodegenerative disease severity influences co-pathology as evidenced by the prevalence of co-pathology in high Alzheimer's disease and neocortical Lewy body disease, but not intermediate Alzheimer's disease or limbic Lewy body disease; and that tau and α-synuclein strains may also modify co-pathologies since tauopathies and synucleinopathies had differing co-pathologies and burdens. These findings have implications for clinical trials that focus on monotherapies targeting tau, amyloid-β, α-synuclein and TDP-43.

Abstract Objectives Growing evidence suggests a protective effect of high mental demands at work on cognitive function in later life. However, evidence on corresponding associations in older adults at increased risk for dementia is currently lacking. This study investigates the association between mental demands at work and cognitive functioning in the population of the AgeWell.de-trial. Methods Cross-sectional investigation of the association between global cognitive functioning (Montreal Cognitive Assessment) and mental demands at work in older individuals at increased risk for dementia (Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE)score ≥ 9; n = 941, age: 60–77 years). Occupational information was matched to Occupational Information Network (O*NET)-descriptors. Associations between cognitive function and O*NET-indices executive, verbal and novelty were investigated using generalized linear models. Results Higher values of index verbal (b = .69, p = .002) were associated with better cognitive function when adjusting for covariates. No association was observed for indices executive (b = .37, p = .062) and novelty (b = .45, p = .119). Higher education, younger age, and employment were linked to better cognitive function, while preexisting medical conditions did not change the associations. Higher levels of depressive symptomatology were associated with worse cognitive function. Conclusions Higher levels of verbal demands at work were associated with better cognitive function for older adults with increased dementia risk. This suggests an advantage for older persons in jobs with high mental demands even after retirement and despite prevalent risk factors. Longitudinal studies are warranted to confirm these results and evaluate the potential of workplaces to prevent cognitive decline through increased mental demands.

IntroductionSeveral lifestyle factors promote protection against Alzheimer's disease (AD) throughout a person's lifespan. Although such protective effects have been described for occupational cognitive requirements (OCR) in midlife, it is currently unknown whether they are conveyed by brain maintenance (BM), brain reserve (BR), or cognitive reserve (CR) or a combination of them.MethodsWe systematically derived hypotheses for these resilience concepts and tested them in the population-based AgeCoDe cohort and memory clinic-based AD high-risk DELCODE study. The OCR score (OCRS) was measured using job activities based on the O*NET occupational classification system. Four sets of analyses were conducted: (1) the interaction of OCR and APOE-ε4 with regard to cognitive decline (N = 2,369, AgeCoDe), (2) association with differentially shaped retrospective trajectories before the onset of dementia of the Alzheimer's type (DAT; N = 474, AgeCoDe), (3) cross-sectional interaction of the OCR and cerebrospinal fluid (CSF) AD biomarkers and brain structural measures regarding memory function (N = 873, DELCODE), and (4) cross-sectional and longitudinal association of OCR with CSF AD biomarkers and brain structural measures (N = 873, DELCODE).ResultsRegarding (1), higher OCRS was associated with a reduced association of APOE-ε4 with cognitive decline (mean follow-up = 6.03 years), consistent with CR and BR. Regarding (2), high OCRS was associated with a later onset but subsequently stronger cognitive decline in individuals converting to DAT, consistent with CR. Regarding (3), higher OCRS was associated with a weaker association of the CSF Aβ42/40 ratio and hippocampal volume with memory function, consistent with CR. Regarding (4), OCR was not associated with the levels or changes in CSF AD biomarkers (mean follow-up = 2.61 years). We found a cross-sectional, age-independent association of OCRS with some MRI markers, but no association with 1-year-change. OCR was not associated with the intracranial volume. These results are not completely consistent with those of BR or BM.DiscussionOur results support the link between OCR and CR. Promoting and seeking complex and stimulating work conditions in midlife could therefore contribute to increased resistance to pathologies in old age and might complement prevention measures aimed at reducing pathology.

AimThe aim of this study was to investigate the frequency of and the gender differences in the use of professional home care in Germany.MethodsWe used harmonized data from three large cohort studies from Germany (“Healthy Aging: Gender-specific trajectories into the latest life”; AgeDifferent.de Platform). Data were available for 5,393 older individuals (75 years and older). Mean age was 80.2 years (SD: 4.1 years), 66.6% were female. Professional homecare outcome variables were use of outpatient nursing care, paid household assistance, and meals on wheels' services. Logistic regression models were used, adjusting for important sociodemographic variables.ResultsAltogether 5.2% of older individuals used outpatient nursing care (6.2% women and 3.2% men; p < 0.001), 24.2% used paid household assistance (26.1% women and 20.5% men; p < 0.001) and 4.4% used meals on wheels' services (4.5% women and 4.0% men; p = 0.49). Regression analysis revealed that women had higher odds of using paid household assistance than men (OR = 1.48, 95% CI: [1.24–1.76]; p < 0.001), whereas they had lower odds of using meals on wheels' services (OR = 0.64, 95% CI: [0.42–0.97]; p < 0.05). No statistically significant differences in using outpatient nursing care between women and men were found (OR = 1.26, 95% CI: [0.87–1.81]; p = 0.225). Further, the use of home care was mainly associated with health-related variables (e.g., stroke, Parkinson's disease) and walking impairments.ConclusionsOur study showed that gender differences exist in using paid household assistance and in culinary dependency. For example, meals on wheels' services are of great importance (e.g., for individuals living alone or for individuals with low social support). Gender differences were not identified regarding outpatient nursing care. Use of professional home care services may contribute to maintaining autonomy and independence in old age.

Summary: Background: Telemonitoring of circadian and sleep cycles could identify shift workers at increased risk of poor health, including cancer and cardiovascular diseases, thus supporting personalized prevention. Methods: The Circadiem cross-sectional study aimed at determining early warning signals of risk of health alteration in hospital nightshifters (NS) versus dayshifters (DS, alternating morning and afternoon shifts). Circadian rhythmicity in activity, sleep, and temperature was telemonitored on work and free days for one week. Participants wore a bluetooth low energy thoracic accelerometry and temperature sensor that was wirelessly connected to a GPRS gateway and a health data hub server. Hidden Markov modelling of activity quantified Rhythm Index, rest quality (probability, p1-1, of remaining at rest), and rest duration. Spectral analyses determined periods in body surface temperature and accelerometry. Parameters were compared and predictors of circadian and sleep disruption were identified by multivariate analyses using information criteria-based model selection. Clusters of individual shift work response profiles were recognized. Findings: Of 140 per-protocol participants (133 females), there were 63 NS and 77 DS. Both groups had similar median rest amount, yet NS had significantly worse median rest-activity Rhythm Index (0·38 [IQR, 0·29-0·47] vs. 0·69 [0·60-0·77], p

Abstract Purpose To systematically review studies on HRQOL, measured by the WHOQOL-Bref instrument, of refugees in general and clinical populations who are settled in the community of the hosting country, and outline the differences in scores among the two population groups and across the four domains of WHOQOL-Bref (physical, psychological, social relationships and environment domain) as well as factors impacting those outcomes. Methods Several databases were systematically searched by using a broad search strategy. Additionally, a hand search for grey literature was performed. Studies had to comply with the following inclusion criteria: (a) population of refugees; (b) living in the community of the country of destination; (c) assessing HRQOL through the WHOQOL-Bref instrument. Results 15 studies were identified and divided into two subgroups: (a) general population of refugees (b) clinical population of refugees, who were specifically selected for their mental status or because they had experienced relevant past traumas. Although we can outline common patterns among the two groups, in terms of domains scoring the highest and the lowest, heterogeneous values of HRQOL are observed across the studies included. Conclusions Individuals who were included in the clinical refugee group have a lower quality of life in respect to the general population of refugees. However, among the two groups different patterns can be outlined considering each domain of HRQOL: higher scores for the Physical and lower for the Environment domain when considering the general population of refugees and higher scores for the Environment and lower for the Psychological domain when referring to the clinical one. These lower scores are probably due to having a higher rate of mental distress and being more exposed to somatization, stigmatization and barriers to access the healthcare system of the hosting country.

This paper presents a numerical investigation regarding the possibility of using electrically conductive concrete (ECON) combined with concrete-encased electrode (CEE) technology to develop new substation grounding systems (SGSs) called ECON-EE as a replacement for conventional copper or galvanized steel grounding grids. In the first step, the validation of the commercial FEM software used to perform grounding system analysis was performed in terms of the grid resistance (RG), ground potential rise (GPR), and step and touch voltages, using a symmetrical 70 m × 70 m conventional copper SGS. Next, several numerical simulations of an ECON-EE grounding system with the same dimensions as the conventional copper grid used for FEM software validation were performed. Thus, several parameters of the ECON-EE grounding system were studied, such as the geometry, dimensions, and resistivity of ECON and the diameter of the rebar. The numerical results obtained permit us to demonstrate that ECON-EE grounding systems can perform better than conventional SGSs equipped with vertical rods, particularly in the case of high ground resistivity. Moreover, it was demonstrated that the two main ECON-EE parameters affecting the grounding resistance and the touch and step voltages are the section area and the resistivity of the ECON. As discussed in detail in this paper, the proposed ECON-EE grounding system can offer several advantages compared to conventional SGSs in terms of efficiency and durability, as well as in terms of simplicity of conception and implementation.

INTRODUCTION: Dementia risk scores constitute promising surrogate outcomes for lifestyle interventions targeting cognitive function. We investigated whether dementia risk, assessed using the LIfestyle for BRAin health (LIBRA) index, was reduced by the AgeWell.de intervention. METHODS: Secondary analyses of the AgeWell trial, testing a multicomponent intervention (including optimization of nutrition, medication, and physical, social, and cognitive activity) in older adults with increased dementia risk. We analyzed data from n = 461 participants with complete information on risk/protective factors comprised by LIBRA at the 24‐month follow‐up. Intervention effects on LIBRA and LIBRA components were assessed using generalized linear models. RESULTS: The intervention reduced LIBRA scores, indicating decreased dementia risk at follow‐up (b = –0.63, 95% confidence interval [CI]: –1.14, –0.12). Intervention effects were particularly due to improvements in diet (odds ratio [OR]: 1.60, 95% CI: 1.16, 2.22) and hypertension (OR: 1.61, 95% CI: 1.19, 2.18). DISCUSSION: The AgeWell.de intervention reduced dementia risk. However, several risk factors did not improve, possibly requiring more intensive interventions. Highlights: The AgeWell.de intervention reduced dementia risk according to LIfestyle for BRAin health (LIBRA) scores.Beneficial effects on LIBRA are mainly due to changes in diet and blood pressure.A pragmatic lifestyle intervention is apt to reduce dementia risk in an at‐risk population. [ABSTRACT FROM AUTHOR]

Abstract Introduction Stroke has a long-term impact on functional status and quality of life in multiple health domains. A well-coordinated managed care program for stroke patients is crucial for ameliorating patients’ health and cost-efficient use of resources. The aim of this study is the implementation and evaluation of an optimised cross-sectoral, coordinated and managed care program for stroke patients bridging secondary and tertiary care. Methods In this multi-center mixed method sequentially controlled intervention study, stroke patients with ischemic stroke (I63), transient ischemic attack and related syndromes (G45), or intracerebral haermorrhage (I64) will be invited to participate. For a 12-months period, 235 consecutive patients are expected to be enrolled and assigned standard of care treatment as an active control group. During the following 12 months, 235 consecutive patients will be enrolled and assigned to a post stroke intervention program. The StroCare intervention consists of repeated outpatient visits with specialized stroke teams, the implementation of a case manager, the use of an electronical tool for communication between acute care, rehabilitation facilities, and out-patient care, and the definition of individualized treatment targets. Patients will be followed up for 24 months. The primary outcome is health-related quality of life measured by the Patient-Reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10) at 12 months after the index event, i.e. stroke or TIA. For the qualitative survey of the implementation process, 21 patients in the intervention group will be interviewed after implementation of the interventions. In addition, 20 health care providers and staff members will be interviewed before and after implementation. Additionally, economic outcomes will be evaluated after 6 and 12 months. Perspective The study will not only provide information about the tested intervention but is likely to be helpful for clinicians, suppliers of reimbursement, and researchers in implementing and evaluating complex interventions in stroke care in general. With this program, the health care system will have a reference model at its disposal for transfer to other regions and settings. Trial registration The trial is registered at ClinicalTrials.gov ( NCT04159324 ). Approval of the local ethics committee (Ethik-Kommission der Ärztekammer Hamburg, Niedersachsen, Schleswig-Holstein) has been obtained.