Marginale Wirksamkeit als Posteriorisierungskriterium – Begriffsklärungen und ethisch relevante Vorüberlegungen

Definition of the problem Rationing fairly remains a problem of great importance in most health care systems. While the scientific debate of this challenge is longstanding, few criteria of allocation have gained general approval within the literature and in policy making. In this article, we analyse the fairness and applicability of marginal effectiveness as a rationing criterion. Arguments In the so-called “futility-debate” of the 1990s, arguments for and against the concept of futile medical care were weighted against each other from the point of view of clinical medicine. At the time, the use of “futility” as a rationing criterion was strictly refused. In this article, we concentrate on a specific class of interventions which figured in this dispute, namely medical interventions with marginal effectiveness. We define two dimensions of marginal effectiveness and discuss several arguments in favour and against using these as rationing criteria. Arguments in favour are in particular: 1) the ethical advantages in comparison with cost-benefit-analyses, 2) the potential of transparent resource allocation, 3) the absence of discrimination, and 4) the compatibility with arguments from good clinical practice. However, we explore several problematic issues of definition and implementation which also have to be taken into account. Conclusion We argue that, barring pragmatic issues, marginal effectiveness is a fair and transparent rationing criterion which has many advantages when compared to other controversial criteria.     

Ergonomic workplace design in the fast pick area

The aging society in many developed countries has made an ergonomic workplace design to an important topic among researchers and practitioners alike. We investigate the workplace design for order pickers that manually collect items from the shelves of a warehouse. Specifically, we treat the storage assignment, i.e., the placement of products in shelves of different height, and zoning, i.e., the partitioning of the storage space into areas assigned to separate pickers, in the fast pick area of a warehouse. A fast pick area unifies the most fast-moving items in a compact area, so that workers are relieved from unproductive travel, but face extraordinary ergonomic risks due to the frequent repetition of picking operations. Concerning the health of (aged) workers, it is crucial to reduce such risks. Thus, we define a combined ergonomic storage assignment and zoning problem with the objective of minimizing the maximum ergonomic burden among all workers. This problem is formalized, and two construction heuristics and a tabu search procedure are proposed. Our results show that neglecting ergonomic aspects and only focusing on picking performance leads to much higher ergonomic risks of the workforce.

     

Leptin in persons with simple obesity

Obesity is a disease with distinct genetic determination and its phenotype is defined by the still unknown number of genes whose expression can be influenced by environmental factors. Several years ago, "obesity gene" was isolated in animals. This gene, coding protein which consists of 165 amino acids, is called leptin. Leptin is supposed to be a key substance controlling homeostasis of body weight and energy balance; it is produced by adipocytes and its value correlates highly significantly with anthropometric parameters that characterize physical constitution and amount of subcutaneous fatty tissue. The obese individuals often display hyperleptinemia which is frequently caused by a postreceptor disorder; sporadically, a different leptin structure or hypoleptinemia (caused by genetic anomaly) are reported. It is supposed that either absolute or relative leptin deficiency in obese persons are associated with causal obesity (e.g. appetite stimulation). Leptinemia values correlate with percentage of subcutaneous fatty tissue, insulinemia and sometimes with glycemia. In our study we examined 200 probands, patients of the Metabolic and Diabetologic Out-Patient Department, Hospital in Sternberk. A very close correlation between the amount of subcutaneous fatty tissue (measured by a caliper in 10 skinfolds) and the leptine serum concentration was found. The values of leptinemia in men of normal constitution ranged within 1-11 ng/ml, non-obese women had 3-4 times higher values. Leptinemia in some obese individuals reached up to 70 ng/ml. However, the currently calculated and reported parameters of physical constitution (BMI, WHR, Grant index) did not correlate significantly with leptinemia. Similarly, biochemical parameters considered as general markers of insulin resistance (often associated with obesity) did not correlate significantly with leptinemia. This finding indicates that some calculated parameters, quantifying and gualifying physical constitution, may be ambiguous and leptinemia was found to give more detailed information about the amount of subcutaneous fatty tissue than WHR or BMI. An accidental finding was an important positive correlation between myoglobin concentration and creatinemia. At monitoring the effect of hypolipidemic agents we use the myoglobin examination and therefore we consider this correlation to be very important and every physician performing this analysis should be informed about it. The present study thus confirmed that a more accurate quantification of subcutaneous fatty tissue is required. On the other hand, we believe that examination of leptinemia can contribute significantly to stratification of patients into risk groups (with respect to clinical, economic and time differentiation) and subsequently to the treatment of these patients. In future, criteria for quantification of leptinemia and leptine resistance should be defined precisely.     

Are airbags a dangerous safety measure? A meta-analysis of the effects of frontal airbags on driver fatalities

A meta-analysis has been conducted of the effectiveness of frontal airbags in reducing driver fatalities, and some potential moderator variables for airbag effectiveness have been investigated. The results confirm the assumption that airbags reduce accident fatalities among belted drivers, but the results are too heterogeneous for drawing conclusions about the size of the overall effect. No support has been found for the hypothesis that airbags increase overall fatality risk, as has been found in the study by Meyer and Finney (Meyer, M., Finney, T., 2005. Who wants Airbags? Chance, 18 (19) 3–16). The results do not seem to be affected by publication bias, and no indications of confounding effects of vehicle characteristics or impact velocity have been found. In frontal collisions belted driver fatalities were found to be reduced by about 22% when all types of airbags are regarded together. The revision of the test criteria for airbags in the USA in 1997 has improved airbag effectiveness. For unbelted drivers airbags are neither effective nor counterproductive, but may increase fatality risk in single vehicle accidents. The results show that there is a lack of knowledge about the effects of airbags in accidents that are not frontal collisions.     

The Reactivity of Azidonitrobenzofuroxans towards 1,3-Dicarbonyl Compounds: Unexpected Formation of Amino Derivative via the Regitz Diazo Transfer and Tautomerism Study

Herein, we report on the reaction of nitro-substituted azidobenzofuroxans with 1,3-dicarbonyl compounds in basic media. The known reactions of benzofuroxans and azidofuroxans with 1,3-dicarbonyl compounds in the presence of bases are the 1,3-dipolar cycloaddition and the Beirut reaction. In contrast with this, azidonitrobenzofuroxan reacts with 1,3-carbonyl compounds through Regitz diazo transfer, which is the first example of this type of reaction for furoxan derivatives. This difference is seemingly due to the strong electron-withdrawing effect of the superelectrophilic azidonitrobenzofuroxan, which serves as the azido transfer agent rather than 1,3-dipole in this case.     

Reactive polymers. XXVI. Sorption properties of the glycidylmethacrylate-ethylenedimethacrylate copolymer modified with ammonia

Sorption properties of the glycidylmethacrylate-ethylenedimethacrylate copolymer with the ? OH and ? NH₂ groups were characterized by using the static and dynamical procedure. Hg(II) was found to be sorbed selectively from the acetate buffer. Using sorption and desorption isoplanes determined in the measurements, conditions of the sorption of Hg(II) and its separation from an excess of some metal ions (Cu(II), Pb(II), Cd(II), Co(II), Zn(II), Ca(II), Mg(II)) were determined.     

The Role of Nonshivering Thermogenesis Genes on Leptin Levels Regulation in Residents of the Coldest Region of Siberia

Leptin plays an important role in thermoregulation and is possibly associated with the microevolutionary processes of human adaptation to a cold climate. In this study, based on the Yakut population (n = 281 individuals) living in the coldest region of Siberia (t°minimum −71.2 °C), we analyze the serum leptin levels and data of 14 single nucleotide polymorphisms (SNPs) of 10 genes (UCP1, UCP2, UCP3, FNDC5, PPARGC1A, CIDEA, PTGS2, TRPV1, LEPR, BDNF) that are possibly involved in nonshivering thermogenesis processes. Our results demonstrate that from 14 studied SNPs of 10 genes, 2 SNPs (the TT rs3811787 genotype of the UCP1 gene and the GG rs6265 genotype of the BDNF gene) were associated with the elevated leptin levels in Yakut females (p < 0.05). Furthermore, of these two SNPs, the rs3811787 of the UCP1 gene demonstrated more indications of natural selection for cold climate adaptation. The prevalence gradient of the T-allele (rs3811787) of UCP1 increased from the south to the north across Eurasia, along the shore of the Arctic Ocean. Thereby, our study suggests the potential involvement of the UCP1 gene in the leptin-mediated thermoregulation mechanism, while the distribution of its allelic variants is probably related to human adaptation to a cold climate.     

Risk Governance of Emerging Technologies Demonstrated in Terms of its Applicability to Nanomaterials

Nanotechnologies have reached maturity and market penetration that require nano‐specific changes in legislation and harmonization among legislation domains, such as the amendments to REACH for nanomaterials (NMs) which came into force in 2020. Thus, an assessment of the components and regulatory boundaries of NMs risk governance is timely, alongside related methods and tools, as part of the global efforts to optimise nanosafety and integrate it into product design processes, via Safe(r)‐by‐Design (SbD) concepts. This paper provides an overview of the state‐of‐the‐art regarding risk governance of NMs and lays out the theoretical basis for the development and implementation of an effective, trustworthy and transparent risk governance framework for NMs. The proposed framework enables continuous integration of the evolving state of the science, leverages best practice from contiguous disciplines and facilitates responsive re‐thinking of nanosafety governance to meet future needs. To achieve and operationalise such framework, a science‐based Risk Governance Council (RGC) for NMs is being developed. The framework will provide a toolkit for independent NMs' risk governance and integrates needs and views of stakeholders. An extension of this framework to relevant advanced materials and emerging technologies is also envisaged, in view of future foundations of risk research in Europe and globally.     

Novel LDPE/vermiculite/ciclopiroxolamine hybrid nanocomposites: Structure,surface properties,and antifungal activity

The increasing number of indwelling medical materials and devices are connected with infections caused by yeast, especially Candida albicans. This pathogen produces biofilms on synthetic materials, which facilitates adhesion of the organisms to devices and renders them relatively refractory to medical therapy. Since antimicrobial polymer nanocomposites present one of the promising possibilities, this study explores a new approach to achieving this goal by developing nanocomposite based on low density polyethylene (LDPE) with clay mineral vermiculite as an active carrier for antifungal compound. The set of LDPE/clay nanocomposite with increasing amount of antifungal nanofiller was prepared by melt compounding procedure. As antifungal agent was selected generally used active substance ciclopiroxolamine and this compound was loaded into natural vermiculite through ultrasound technique. The structure of all prepared samples was studied by X-ray diffraction analysis and Fourier transforms infrared spectroscopy. Further thermal properties of polyethylene/clay nanocomposites were investigated by thermogravimetric analysis and the surface properties were evaluated by light optical microscopy, scanning electron microscopy and atomic force microscopy. From mentioned characteristics, we conclude that presence of nanofiller in LDPE primarily causes shift of thermal degradation to higher temperatures and increasing of microhardness. All prepared LDPE nanocomposites possess an excellent and prolonged antifungal activity against Candida albicans.     

Quantitative interpretation of MALDI-TOF mass spectra of imperfect carbosilane dendrimers

A general relationship is derived for the abundance of an imperfect dendrimer with a given number of missing constitutional repeating units in the two outmost layers. The relationship is used in the interpretation of the MALDI TOF mass spectrum of the second-generation carbosilane dendrimer prepared by the iterative divergent method. The model quantitatively describes the spectrum of the dendrimer and correctly predicts the MALDI TOF mass spectrum of its first-generation precursor. Thus, the use of well-resolved MALDI TOF mass spectra for assessing the purity of low-generation dendrimers with uniform end groups is substantiated for carbosilane dendrimers and to lesser extent for dendrimers in general.