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In this randomized, double-blind trial involving patients with type 2 diabetes at high risk for cardiovascular events, basal insulin degludec was noninferior to glargine with respect to major cardiovascular events.

Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I–IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab. The heterogeneity of colorectal cancer has important clinical and therapeutic implications. Here the authors analysed the responses of a large biobank of organoids and xenografts derived from colorectal patients to a panel of clinically relevant therapeutic agents to identify genes signatures associated with drug response.

Models can be applied to extrapolate consequences of climate change for complex ecological systems in the future. The acknowledged systems’ behaviour at present is projected into the future considering climate projection data. Such an approach can be used to addresses the future activity and density of the castor bean tick Ixodes ricinus , the most widespread tick species in Europe. It is an important vector of pathogens causing Lyme borreliosis and tick-borne encephalitis. The population dynamics depend on several biotic and abiotic factors. Such complexity makes it difficult to predict the future dynamics and density of I . ricinus and associated health risk for humans. The objective of this study is to force ecological models with high-resolution climate projection data to extrapolate I . ricinus tick density and activity patterns into the future. We used climate projection data of temperature, precipitation, and relative humidity for the period 1971–2099 from 15 different climate models. Tick activity was investigated using a climate-driven cohort-based population model. We simulated the seasonal population dynamics using climate data between 1971 and 2099 and observed weather data since 1949 at a specific location in southern Germany. We evaluated derived quantities of local tick ecology, e.g. the maximum questing activity of the nymphal stage. Furthermore, we predicted spatial density changes by extrapolating a German-wide tick density model. We compared the tick density of the reference period (1971–2000) with the counter-factual densities under the near-term scenario (2012–2041), mid-term scenario (2050–2079) and long-term scenario (2070–2099). We found that the nymphal questing peak would shift towards early seasons of the year. Also, we found high spatial heterogeneity across Germany, with predicted hotspots of up to 2,000 nymphs per 100 m 2 and coldspots with constant density. As our results suggest extreme changes in tick behaviour and density, we discuss why caution is needed when extrapolating climate data-driven models into the distant future when data on future climate drive the model projection.

Background The emerging adulthood is traditionally viewed as a time of optimal health, but also as a critical life span, characterized by changing life circumstances and the establishment of an individual lifestyle. Especially university life seems to hold several challenges impeding the manifestation of a health supporting manner, as many students tend to show a poorer health behavior and a higher amount of health-related problems than comparable age groups. This, along with a steady growth of the higher education sector, brings increased attention to the university setting in the context of prevention. To date, there are few empirical longitudinal and coherent cross-sectional data on the status of students’ health literacy, health status, and health behaviors, and on the impact of the study format on students’ health. The aim of this prospective cohort study is to reduce this research gap. Methods Starting during winter semester 2020/21, the prospective cohort study collects data on health literacy, health status and health behavior on a semester-by-semester basis. All enrolled students of the IST University of Applied Sciences, regardless of study format and discipline, can participate in the study at the beginning of their first semester. The data are collected digitally via a specifically programmed app. A total of 103 items assess the subjectively perceived health status, life and study satisfaction, sleep quality, perceived stress, physical activity, diet, smoking, alcohol consumption, drug addiction and health literacy. Statistical analysis uses (1) multivariate methods to look at changes within the three health dimensions over time and (2) the association between the three health dimensions using multiple regression methods and correlations. Discussion This cohort study collects comprehensive health data from students on the course of study. It is assumed that gathered data will provide information on how the state of health develops over the study period. Also, different degrees of correlations of health behavior and health literacy will reveal different impacts on the state of students’ health. Furthermore, this study will contribute to empirically justified development of target group-specific interventions. Trial registration German Clinical Trials Register: DRKS00023397 (registered on October 26, 2020).

Solid‐state batteries represent a new approach to energy storage, offering superior safety, higher energy density, and extended cycle life compared to conventional liquid electrolyte‐based lithium‐ion batteries. However, the practical application of solid‐state batteries is hindered by degradation phenomena, particularly on interfaces between components, compromising their long‐term performance. In this work, the kinetics of the state‐of‐charge‐dependent electrolyte degradation at the LiNi0.83Co0.11Mn0.06O2│Li6PS5Cl interface, as well as its influence on cycling performance, are systematically studied electrochemically in solid‐state battery half cells. Combining cycling and C‐rate experiments with electrochemical impedance spectroscopy reveals that half cells charged to higher cutoff potentials (≥3.8 V versus In/InLi; ≥4.4 V versus Li+/Li) exhibit significantly faster degradation kinetics. These influence the cycling performance leading to a plateau in the charge capacity at ≥3.8 V versus In/InLi, while the electrolyte degradation does not affect the bulk electrode transport. Overall, this work emphasizes the importance to investigate state‐of‐charge‐dependent decomposition kinetics in composite electrodes to better understand cycling behavior.

Aims/hypothesisThe double-blind Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) assessed the cardiovascular safety of insulin degludec. The incidence and rates of adjudicated severe hypoglycaemia, and all-cause mortality were also determined. This paper reports a secondary analysis investigating associations of severe hypoglycaemia with cardiovascular outcomes and mortality.MethodsIn DEVOTE, patients with type 2 diabetes were randomised to receive either insulin degludec or insulin glargine U100 (100 units/ml) once daily (between dinner and bedtime) in an event-driven, double-blind, treat-to-target cardiovascular outcomes trial. The primary outcome was the first occurrence of an adjudicated major adverse cardiovascular event (MACE; cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Adjudicated severe hypoglycaemia was the pre-specified secondary outcome. In the present analysis, the associations of severe hypoglycaemia with both MACE and all-cause mortality was evaluated in the pooled trial population using time-to-event analyses, with severe hypoglycaemia as a time-dependent variable and randomised treatment as a fixed factor. An investigation with interaction terms indicated that the effect of severe hypoglycaemia on the risk of MACE and all-cause mortality were the same for both treatment arms, and so the temporal association for severe hypoglycaemia with subsequent MACE and all-cause mortality is reported for the pooled population.ResultsThere was a non-significant difference in the risk of MACE for individuals who had vs those who had not experienced severe hypoglycaemia during the trial (HR 1.38, 95% CI 0.96, 1.96; p = 0.080) and therefore there was no temporal relationship between severe hypoglycaemia and MACE. There was a significantly higher risk of all-cause mortality for patients who had vs those who had not experienced severe hypoglycaemia during the trial (HR 2.51, 95% CI 1.79, 3.50; p < 0.001). There was a higher risk of all-cause mortality 15, 30, 60, 90, 180 and 365 days after experiencing severe hypoglycaemia compared with not experiencing severe hypoglycaemia in the same time interval. The association between severe hypoglycaemia and all-cause mortality was maintained after adjustment for the following baseline characteristics: age, sex, HbA1c, BMI, diabetes duration, insulin regimen, hepatic impairment, renal status and cardiovascular risk group.Conclusions/interpretationThe results from these analyses demonstrate an association between severe hypoglycaemia and all-cause mortality. Furthermore, they indicate that patients who experienced severe hypoglycaemia were particularly at greater risk of death in the short term after the hypoglycaemic episode. These findings indicate that severe hypoglycaemia is associated with higher subsequent mortality; however, they cannot answer the question as to whether severe hypoglycaemia serves as a risk marker for adverse outcomes or whether there is a direct causal effect.Trial registrationClinicalTrials.gov NCT01959529

Background The German health care system is faced with a serious shortage of nurses. This is associated, amongst other things, with difficult working conditions and work-related health burdens. Workplace health promotion (WHP) is considered a promising approach to promote the health of nurses. The present review aims to give an overview on existing interventions in different nursing settings (acute care hospitals, long-term care (LTC) facilities and home-based long-term care) in Germany. Methods A systematic literature search was conducted in PubMed and PubPsych. Studies were included if published after 2010 and provided data of intervention studies on workplace health promotion among nurses in Germany (RCTs, non-RCTs, non-controlled intervention studies and pilot studies). The setting in which the study was conducted (acute medical care hospital, inpatient LTC facilities, home-based LTC, cross-setting) as well as the health issue assessed (physical health, mental health and/or violence experience) were extracted. The intervention was reported against the background of the quality criteria for prevention measures of the statutory health insurers in Germany. The results of the studies were presented according to the RE-AIM framework. Results Eleven studies on WHP for nurses were included, whereof seven studies were conducted in acute medical care hospitals and four in LTC facilities. No study reported results on WHP for nurses working in the setting of home-based LTC. Most studies aimed at improving mental health. The intervention contents and forms of implementation were heterogeneous. According to the RE-AIM criteria, the reporting of most studies showed several limitations, especially a lack of reporting on Implementation and Adoption . Most studies showed no statistically significant effect on the respective outcomes (Effectiveness) . Four studies reported results on Maintenance indicating a sustained effectiveness. Conclusion Despite the high relevance for health promotion for nurses, our review showed a striking lack of intervention studies in this field. From this we derive a high need of tailored interventions, taking into account the setting-specific development, implementation of WHP interventions for nurses. With regard to the evaluation, the RE-AIM criteria should be taken more into account in order to meet the requirements of evaluating complex interventions and thus contribute to evidence development of WHP in nursing. In terms of content, the topic of violence prevention and dealing with experiences of violence should also be taken into account. Regarding the settings, the working conditions and health burdens in LTC facilities, home-based LTC and acute medical hospitals must be considered. Trial registration PROSPERO registration number: CRD42021231891

Globally, the production of renewable energy is undergoing rapid growth. One of the most pressing issues is the appropriate allocation of renewable power plants, as the question of where to produce renewable electricity is highly controversial. Here we explore this issue through analysis of the efficient and equitable spatial allocation of wind turbines and photovoltaic power plants in Germany. We combine multiple methods, including legal analysis, economic and energy modelling, monetary valuation and numerical optimization. We find that minimum distances between renewable power plants and human settlements should be as small as is legally possible. Even small reductions in efficiency lead to large increases in equity. By considering electricity grid expansion costs, we find a more even allocation of power plants across the country than is the case when grid expansion costs are neglected. As renewable energy technology deployment continues apace, it is increasingly important to consider the optimal spatial allocation of power plants. Towards this end, Drechsler et al. employ a variety of methods to understand the most efficient and equitable distribution of solar and wind plants across Germany.

DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP. Interactions between the C-terminal alpha helix of SLFN12 and residues near the active site of PDE3A are required for complex formation, and are further stabilized by interactions between SLFN12 and DNMDP. Moreover, we demonstrate that SLFN12 is an RNase, that PDE3A binding increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for DNMDP response. This new mechanistic understanding will facilitate development of velcrin compounds into new cancer therapies. The small molecule DNMDP acts as a velcrin by inducing complex formation between phosphodiesterase PDE3A and SLFN12, which kills cancer cells that express sufficient levels of both proteins. Here, the authors present the cryo-EM structure of the DNMDP-stabilized PDE3A-SLFN12 complex and show that SLFN12 is an RNase. PDE3A binding increases SLFN12 RNase activity, and SLFN12 RNase activity is required for DNMDP-mediated cancer cell killing.