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Abstract Thermoelectric generators are very attractive devices for waste heat energy harvesting as they transform a temperature difference into electrical power. However, commercially available generators show poor power density and limited operation temperatures. Research focuses on high‐temperature materials and innovative generator designs. Finding the optimal design for a given material system is challenging. Here, a theoretical framework is provided that allows appropriate generator design selection based on the particular material properties. For high‐temperature thermoelectric oxides, it can be clearly deduced that unileg multilayer generators have the highest potential for effective energy harvesting. Based on these considerations, prototype unileg multilayer generators from the currently best thermoelectric oxide Ca3Co4O9 are manufactured for the first time by industrially established ceramic multilayer technology. These generators exhibit a power density of 2.2 mW cm−2 at a temperature difference of 260 K, matching simulated values and confirming the suitability of the technology. Further design improvements increase the power density by a factor of 22 to facilitate practicable power output at temperature differences as low as 7 K. This work demonstrates that reasonable energy harvesting at elevated temperatures is possible with oxide materials and appropriate multilayer design.

Abstract Background The timing of the launch of a new drug is an important factor that determines access for patients. We evaluated patient access to pharmaceuticals in 30 European markets over the past two decades. Methods Launch dates were extracted from the IQVIA (formerly IMS) database for 30 European countries for all pharmaceuticals launched internationally between 2000 and 2017. We defined launch delay as the difference between the first international launch date and the corresponding national launch date, and calculated these for each country in our sample over time. Additionally, we ranked countries according to their launch delays and looked at changes in the ranking order over time. Lastly, we determined the availability of new pharmaceuticals in each country, calculating this as the percentage of these pharmaceuticals that were available in each country during a pre-specified interval. Results There was a clear trend towards a decrease in launch delays across all countries from 2000 (37.2 months) to 2017 (11.8 months). Over the entire observation period, the three fastest launching countries were the Netherlands, Sweden, and Germany, whereas the three slowest were Bosnia-Herzegovina, Serbia, and Turkey. Germany had the highest availability of new pharmaceuticals with 85.7%, followed by the United Kingdom (83.1%) and Norway (82.9%). Countries with the lowest availability of pharmaceuticals were Bosnia-Herzegovina, Serbia, and Latvia. Gross domestic product per capita was negatively correlated with launch delay (-0.67, p

Background: The freezing process of tissue samples is crucial for the preservation of morphological and molecular features. Several biobanking guidelines describe freezing techniques for optimal outcomes. As the Vetbiobank standard freezing protocol does not comply with those recommendations in detail, a process validation was performed to demonstrate that samples are suitable for downstream applications. Here we give a formal example of a process validation in the biobanking setting, as required by the biobanking guideline ISO 20387 (2018).Methods: Three different freezing protocols, freezing in liquid nitrogen, freezing via isopentane precooled on dry ice and freezing via liquid nitrogen vapor, were assessed based on morphological integrity of mouse liver and muscle tissue samples. Samples were either frozen in cryotubes (without Optimal Cutting Temperature compound, OCT) or in cryomolds (with OCT). The protocol providing the best results was validated for reproducibility and robustness in terms of defined acceptance criteria for morphological evaluability, A260/A280 ratio, and RNA integrity number values (RIN). In addition, performance tests were run by gene expression analyzes of selected, tissue specific biomarkers to confirm that processed samples are fit for purpose.Results: From the three applied freezing protocols, freezing in liquid nitrogen generated best results. Reproducibility acceptance criteria were met for both, morphological integrity and RNA quality. The freezing method was robust for the tested tissue types and the application of OCT, with exception of liver tissue, where it led to a significant decrease of the RIN value. Gene expression analyzes showed good comparability of results regardless of the applied freezing method.Conclusion: Freezing of tissue samples in liquid nitrogen provides samples of adequate quality for subsequent RNA investigations. A negative impact of OCT on the RIN value of liver samples was observed, which was independent from the applied freezing protocol and showed no impact on subsequent gene expression analysis.

Background: Cooperation is a core feature of integrated healthcare systems and an important link in their value-creating mechanism. The premise is that providers who cooperate can promote more efficient use of health services while improving health outcomes. We studied the performance of an integrated healthcare system in improving regional cooperation. Methods: Using claims data and social network analysis, we constructed the professional network from 2004 to 2017. Cooperation was studied by analyzing the evolution of network properties at network and physician practice (node) level. The impact of the integrated system was studied with a dynamic panel model that compared practices that participated in the integrated system versus nonparticipants. Results: The regional network evolved favourably towards cooperation. Network density increased 1.4% on average per year, while mean distance decreased 0.78%. At the same time, practices participating in the integrated system became more cooperative compared to other practices in the region: Degree (1.64e-03, p = 0.07), eigenvector (3.27e-03, p = 0.06) and betweenness (4.56e-03, p < 0.001) centrality increased more for participating practices. Discussion: Findings can be explained by the holistic approach to patients’ care needs and coordination efforts of integrated healthcare. The paper provides a valuable design for performance assessment of professional cooperation. Highlights • Using claims data and social network analysis, we identify a regional cooperation network and conduct a panel analysis to measure the impact of an integrated care initiative on enhancing professional cooperation. • Physician practices participating in the integrated system became more cooperative and improved their influence in the regional network more than non-participating practices. • Integrated healthcare systems effectively incentivize cooperation through a holistic approach to patient care needs and coordination efforts.

We causally analyzed whether being a member of the European Union (EU) and having access to a centralized marketing authorization procedure (centralized procedure [CP]) affects availability and time to launch of new pharmaceuticals. We employed multiple difference‐in‐differences models, exploiting the eastern enlargement of the EU as well as changes in the indications that fall within the compulsory or voluntary scope of the CP. Results showed that countries experienced a mean decrease in launch delay of 10.9 months (p = 0.004) after joining the EU. Effects were higher among pharmaceuticals that belong to indications that might voluntarily participate in the CP but are not obliged to. These are often financially less attractive to manufacturers than pharmaceuticals within the compulsory scope. Availability of new pharmaceuticals launched remained unaffected. We found signs that the magnitude of the country‐specific effect of centralized marketing authorization on launch delay may be influenced by strategic decisions of manufacturers at the national level (e.g., parallel trade or reference pricing). [ABSTRACT FROM AUTHOR]

Abstract Background Precise regulation of gene expression is of utmost importance for the production of complex membrane proteins (MP), enzymes or other proteins toxic to the host cell. In this article we show that genes under control of a normally Isopropyl β-d-1-thiogalactopyranoside (IPTG)-inducible PT7-lacO promoter can be induced solely with l-arabinose in a newly constructed Escherichia coli expression host BL21-AI, a strain based on the recently published approach of bacteriophage inspired growth-decoupled recombinant protein production. Results Here, we show that BL21-AI is able to precisely regulate protein production rates on a cellular level in an l-arabinose concentration-dependent manner and simultaneously allows for reallocation of metabolic resources due to l-arabinose induced growth decoupling by the phage derived inhibitor peptide Gp2. We have successfully characterized the system under relevant fed-batch like conditions in microscale cultivation (800 µL) and generated data proofing a relevant increase in specific yields for 6 different Escherichia coli derived MP-GFP fusion proteins by using online-GFP signals, FACS analysis, SDS-PAGE and western blotting. Conclusions In all cases tested, BL21-AI outperformed the parental strain BL21-AI, operated in growth-associated production mode. Specific MP-GFP fusion proteins yields have been improved up to 2.7-fold. Therefore, this approach allows for fine tuning of MP production or expression of multi-enzyme pathways where e.g. particular stoichiometries have to be met to optimize product flux.

IntroductionChronic obstructive pulmonary disease (COPD) affects more than 6 million people in Germany. Monitoring the vital parameters of COPD patients remotely through telemonitoring may help doctors and patients prevent and treat acute exacerbations of COPD, improving patients' quality of life and saving costs for the statutory health insurance system.ObjectiveTo evaluate the effects from October 2012 until December 2015 of a structured home telemonitoring program implemented by a statutory health insurer in Germany.MethodsWe conducted a retrospective cohort study using administrative data. After building a balanced control group using Entropy Balancing, we calculated difference-in-difference estimators to account for time-invariant heterogeneity. We estimated differences in mortality rates using Cox regression and conducted subgroup and sensitivity analyses to check the robustness of the base case results. We observed each patient in the program for up to 3 years depending on his or her time of enrolment.ResultsAmong patients in the telemonitoring cohort, we observed significantly higher inpatient costs due to COPD (€524.2, pConclusionOn one hand, telemonitoring was associated with higher health care expenditures, especially in the first year of the program. For example, we were able to identify a statistically significant increase in inpatient costs due to COPD, outpatient contacts and drug prescriptions among individuals participating in the telemonitoring program. On the other hand, the telemonitoring program was accompanied by a survival benefit, which might be related to higher adherence rates, more intense treatment, or an improved understanding of COPD among these patients.