Procedures and Criteria for the regulation of innovative non-medicinal technologies into the benefit catalogue of solidly financed health care insurances

Because great interest in an efficient range of effective medicinal innovations and achievements has arisen, many countries have introduced procedures to regulate the adoption of innovative non-medicinal technologies into the benefit catalogue of solidly financed health care insurances. With this as a background, this report will describe procedures for the adoption of innovative non-medicinal technologies by solidly financed health care insurances in Germany, England, Australia and Switzerland. This report was commissioned by the German Agency for Health Technology Assessment at the German Institute for Medical Documentation and Information

Methods for assessment of innovative medical technologies during early stages of development

Conventional Health Technology Assessment (HTA) is usually conducted at a point in time at which the development of the respective technology may no longer be influenced. By this time developers and/or purchasers may have misinvested resources. Thus the demand for Technology Assessment (TA) which incorporates appropriate methods during early development stages of a technology becomes apparent. Against this health political background, the present report describes methods for a development-accompanying assessment of innovative medical technologies. Furthermore, international research programmes set out to identify or apply such methods will be outlined. A systematic literature search as well as an extensive manual literature search are carried out in order to obtain literature and information. The greatest units of the identified methods consist of assessment concepts, decision support methods, modelling approaches and methods focusing on users and their knowledge. Additionally, several general-purpose concepts have been identified. The identified research programmes INNO-HTA and MATCH (Multidisciplinary-Assessment-of-Technology-Centre-for-Healthcare) are to be seen as pilot projects which so far have not been able to generate final results. MATCH focuses almost entirely on the incorporation of the user-perspective regarding the development of non-pharmaceutical technologies, whereas INNO-HTA is basically concerned with the identification and possible advancement of methods for the early, socially-oriented technology assessment. Most references offer only very vague descriptions of the respective method and the application of greatly differing methods seldom exceeds the character of a pilot implementation. A standardisation much less an institutionalisation of development-accompanying assessment cannot be recognized. It must be noted that there is no singular method with which development-accompanying assessment should be carried out. Instead, a technology and evaluation specific method selection seem to be necessary as medical innovations are diverse and none of the methods are exhaustive. Because of a variety of issues (e. g. ideal time of evaluation, lack of data and uncertainty of data) a development-accompanying assessment should not replace a comprehensive HTA, but rather form a possible preceding step in a multi-staged HTA-process. A final appraisal of the methods for development-accompanying assessment cannot be made based on the available sources. However, the present review may serve as a starting point for further development and application of these methods as well as further examination of the concept of development-accompanying assessment. There is a substantial need for further research concerning the application, validation and comparison of the various methods for development-accompanying assessment

Remotely controlled isomer selective molecular switching

Nonlocal addressing—the “remote control”—of molecular switches promises more efficient processing for information technology, where fast speed of switching is essential. The surface state of the (111) facets of noble metals, a confined two-dimensional electron gas, provides a medium that enables transport of signals over large distances and hence can be used to address an entire ensemble of molecules simultaneously with a single stimulus. In this study we employ this characteristic to trigger a conformational switch in anthradithiophene (ADT) molecules by injection of hot carriers from a scanning tunneling microscope (STM) tip into the surface state of Cu(111). The carriers propagate laterally and trigger the switch in molecules at distances as far as 100 nm from the tip location. The switching process is shown to be long-ranged, fully reversible, and isomer selective, discriminating between cis and trans diastereomers, enabling maximum control.PostprintPeer reviewe

Bipolar conductance switching of single anthradithiophene molecules

The authors acknowledge funding by the Emmy-Noether-Program of the Deutsche Forschungsgemeinschaft, the SFB 767, and the Baden-Württemberg Stiftung. R.P. and A.A. thank the Basque Departamento de Universidades e Investigacion (grant no. IT-756-13) and the Spanish Ministerio de Economia y Competitividad (grant no. FIS2013-48286-C2-8752-P) for financial support.Single molecular switches are basic device elements in organic electronics. The pentacene analogue anthradithiophene (ADT) shows a fully reversible binary switching between different adsorption conformations on a metallic surface accompanied by a charge transfer. These transitions are activated locally in single molecules in a low-temperature scanning tunneling microscope . The switching induces changes between bistable orbital structures and energy level alignment at the interface. The most stable geometry, the “off” state, which all molecules adopt upon evaporation, corresponds to a short adsorption distance at which the electronic interactions of the acene rings bend the central part of the molecule toward the surface accompanied by a significant charge transfer from the metallic surface to the ADT molecules. This leads to a shift of the lowest unoccupied molecular orbital down to the Fermi level (EF). In the “on” state the molecule has a flat geometry at a larger distance from the surface; consequently the interaction is weaker, resulting in a negligible charge transfer with an orbital structure resembling the highest occupied molecular orbital when imaged close to EF. The potential barrier between these two states can be overcome reversibly by injecting charge carriers locally into individual molecules. Voltage-controlled current traces show a hysteresis characteristic of a bipolar switching behavior. The interpretation is supported by first-principles calculations.PostprintPeer reviewe

Roadmap to Gigahertz Organic Transistors

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Evaluation of a duplex real-time PCR in human serum for simultaneous detection and differentiation of Schistosoma mansoni and Schistosoma haematobium infections - cross-sectional study

Background: We evaluated a one-tube multiplex real-time PCR targeting DNA of Schistosoma haematobium complex and S. mansoni complex in serum samples obtained at different German diagnostic centers. Methods: Simplex real-time PCR protocols for the detection of the multi-copy DNA-repeats Dra1 of S. haematobium complex and Sm1-7 of S. mansoni complex in serum were combined to a new one-tube multiplex format. The new PCR was subjected to full validation including evaluation in a diagnostic real-life setting with travelers and migrants. PCR results were compared with those of stool and urine microscopy, serology, and circulating cathodic antigen (CCA) rapid diagnostic tests in urine. Sensitivity and specificity of the diagnostic approaches were analyzed using latent class analysis (LCA). Results: LCA assessment indicated sensitivity and specificity of 94.9% and 98.4%, respectively, for serum PCR if serology was included in the calculation, and 100% and 95.6%, respectively, if serology was not included as a parameter not necessarily associated with active infection. Agreement between the compared diagnostic procedures at genus level was fair (kappa 0.273) if serology was included and moderate (kappa 0.420) if serology was not included. Discussion: The PCR assay proved to be highly reliable for the diagnosis of schistosomiasis in travelers and migrants

Multicentric Evaluation of SeeGene Allplex Real-Time PCR Assays Targeting 28 Bacterial, Microsporidal and Parasitic Nucleic Acid Sequences in Human Stool Samples

Prior to the implementation of new diagnostic techniques, a thorough evaluation is mandatory in order to ensure diagnostic reliability. If positive samples are scarcely available, however, such evaluations can be difficult to perform. Here, we evaluated four SeeGene Allplex real-time PCR assays amplifying a total of 28 bacteria, microsporidal and parasitic nucleic acid sequence targets in human stool samples in a multicentric approach. In the assessments with strongly positive samples, sensitivity values ranging between 13% and 100% were recorded for bacteria, between 0% and 100% for protozoa and between 7% and 100% for helminths and microsporidia; for the weakly positive samples, the recorded sensitivity values for bacteria ranged from 0% to 100%; for protozoa, from 0% to 40%; and for helminths and microsporidia, from 0% to 53%. For bacteria, the recorded specificity was in the range between 87% and 100%, while a specificity of 100% was recorded for all assessed PCRs targeting parasites and microsporidia. The intra- and inter-assay variations were generally low. Specifically for some helminth species, the sensitivity could be drastically increased by applying manual nucleic acid extraction instead of the manufacturer-recommended automatic procedure, while such effects were less obvious for the bacteria and protozoa. In summary, the testing with the chosen positive control samples showed varying degrees of discordance between the evaluated Allplex assays and the applied in-house reference assays associated with higher cycle threshold values in the Allplex assays, suggesting that samples with very low pathogen densities might be missed. As the targeted species can occur as harmless colonizers in the gut of individuals in high-endemicity settings as well, future studies should aim at assessing the clinical relevance of the latter hint.Peer Reviewe

Electric-field-driven direct desulfurization

The ability to elucidate the elementary steps of a chemical reaction at the atomic scale is important for the detailed understanding of the processes involved, which is key to uncover avenues for improved reaction paths. Here, we track the chemical pathway of an irreversible direct desulfurization reaction of tetracenothiophene adsorbed on the Cu(111) closed-packed surface at the submolecular level. Using the precise control of the tip position in a scanning tunneling microscope and the electric field applied across the tunnel junction, the two carbon–sulfur bonds of a thiophene unit are successively cleaved. Comparison of spatially mapped molecular states close to the Fermi level of the metallic substrate acquired at each reaction step with density functional theory calculations reveals the two elementary steps of this reaction mechanism. The first reaction step is activated by an electric field larger than 2 V nm–1, practically in absence of tunneling electrons, opening the thiophene ring and leading to a transient intermediate. Subsequently, at the same threshold electric field and with simultaneous injection of electrons into the molecule, the exergonic detachment of the sulfur atom is triggered. Thus, a stable molecule with a bifurcated end is obtained, which is covalently bound to the metallic surface. The sulfur atom is expelled from the vicinity of the molecule.PostprintPeer reviewe

Chiral and catalytic effects of site-specific molecular adsorption

Open access funded by Max Planck Society. The authors acknowledge the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy-EXC-2123 Quantum Frontiers - 390837967; Core program PC2-PN23080202 and the PN-III-P2-2.1-PED-2021-0378 (contract no. 575PED/2022) granted projects, financed by the Romanian Ministry of Research, Innovation and Digitalization/UEFISCDI; and the generous allocation of computer time at the computing center of Donostia International Physics Center and at the Red Española de Supercomputación (project QHS-2021-2-0019). A.A. acknowledges support from Project No. PID2019-103910GB-I00, funded by MCIN/AEI/10.13039/501100011033/ and FEDER Una manera de hacer Europa, and Project No. IT-1527-22 funded by the Basque Government.The changes of properties and preferential interactions based on subtle energetic differences are important characteristics of organic molecules, particularly for their functionalities in biological systems. Only slightly energetically favored interactions are important for the molecular adsorption and bonding to surfaces, which define their properties for further technological applications. Here, prochiral tetracenothiophene molecules are adsorbed on the Cu(111) surface. The chiral adsorption configurations are determined by Scanning Tunneling Microscopy studies and confirmed by first-principles calculations. Remarkably, the selection of the adsorption sites by chemically different moieties of the molecules is dictated by the arrangement of the atoms in the first and second surface layers. Furthermore, we have investigated the thermal effects on the direct desulfurization reaction that occurs under the catalytic activity of the Cu substrate. This reaction leads to a product that is covalently bound to the surface in chiral configurations.Publisher PDFPeer reviewe

The Role of Dietary Fiber in Rheumatoid Arthritis Patients: A Feasibility Study

Short-chain fatty acids are microbial metabolites that have been shown to be key regulators of the gut–joint axis in animal models. In humans, microbial dysbiosis was observed in rheumatoid arthritis (RA) patients as well as in those at-risk to develop RA, and is thought to be an environmental trigger for the development of clinical disease. At the same time, diet has a proven impact on maintaining intestinal microbial homeostasis. Given this association, we performed a feasibility study in RA patients using high-fiber dietary supplementation with the objective to restore microbial homeostasis and promote the secretion of beneficial immunomodulatory microbial metabolites. RA patients (n = 36) under routine care received daily high-fiber bars or cereals for 28 days. Clinical assessments and laboratory analysis of immune parameters in blood and stool samples from RA patients were done before and after the high-fiber dietary supplementation. We observed an increase in circulating regulatory T cell numbers, favorable Th1/Th17 ratios, as well as decreased markers of bone erosion in RA patients after 28 days of dietary intervention. Furthermore, patient-related outcomes of RA improved. Based on these results, we conclude that controlled clinical studies of high-fiber dietary interventions could be a viable approach to supplement or complement current pharmacological treatment strategies