Patients' and professionals' views related to ethical issues in precision medicine: a mixed research synthesis

Results Many patients and professionals expect high benefits from precision medicine and have a positive attitude towards it. However, patients and professionals also perceive some risks. Commonly perceived risks include: lack of evidence for accuracy of tests and efficacy of treatments; limited knowledge of patients, which makes informed consent more difficult; possible unavailability of access to precision medicine for underprivileged people and ethnic minorities; misuse of data by insurance companies and employers, potential of racial stigmatization due to genetic information; unwanted communication of incidental findings; changes in doctor-patient-relationship through focusing on data; and the problem that patients could feel under pressure to optimize their health. Conclusions National legislation and guidelines already minimize many risks associated with precision medicine. However, from our perspective some problems require more attention. Should hopes for precision medicine's benefits be fulfilled, then the ethical principle of justice would require an unlimited access to precision medicine for all people. The potential for autonomous patients' decisions must be greatly enhanced by improvements in patient education. Harm from test results must be avoided in any case by the highest possible data security level and communication guidelines. Changes in the doctor-patient relationship and the impact of precision medicine on the quality of life should be further investigated. Additionally, the cost-effectiveness of precision medicine should be further examined, in order to avoid malinvestment

Vergleichende biomechanische Untersuchung zur Stabilität einer Azetabulumfraktur (vorderer Pfeiler) mit Platten- bzw. Zugschraubenosteosynthesen (Titan vs. Stahl vs. Biodegradierbar)

Der Goldstandard zur operativen Therapie von Azetabulumfrakturen ist die offene Reposition und Fixation durch Plattenosteosynthesen. Alternativ existieren weniger invasive Schraubenosteosynthesen, wenn eine geschlossene anatomische Rekonstruktion möglich ist. Biodegradierbare Implantate haben einen Vorteil gegenüber konventionellen Osteosynthesematerialien, da bei einem späteren Gelenkersatz keine Implantatentfernung notwendig ist. Ziele der Arbeit Die Ziele der Arbeit sind die Untersuchung der optimalen Schraubenpositionierung bei einer Schraubenosteosynthese von vorderen Pfeilerfrakturen, als auch der biomechanische Vergleich der Primärstabilität unterschiedlicher Osteosyntheseverfahren (konventionelle Platten vs. winkelstabile Platten vs. Schraubenosteosynthesen) und Schraubenmaterialien (Titan vs. Stahl vs. biodegradierbares PLA)

Гамма-спектрометрический метод контроля активности и нуклидного состава низкоактивных твердых радиоактивных отходов

Разработан гамма-спектрометрический метод контроля низкоактивных твердых радиоактивных отходов, основанный на непосредственном измерении активности и нуклидного состава. Измерения проводятся в геометрии стандартного стального контейнера объемом 200 л, в который помещаются низкоактивные отходы. Для учета неравномерности распределения твердых радиоактивных отходов по измеряемой геометрии используется специальная вращающаяся площадка, на которую помещается контейнер. Проведена метрологическая аттестация и определены основные погрешности предлагаемого метода для доверительной вероятности 95 %

Multiclass cancer classification in fresh frozen and formalin-fixed paraffin-embedded tissue by DigiWest multiplex protein analysis

Histomorphology and immunohistochemistry are the most common ways of cancer classification in routine cancer diagnostics, but often reach their limits in determining the organ origin in metastasis. These cancers of unknown primary, which are mostly adenocarcinomas or squamous cell carcinomas, therefore require more sophisticated methodologies of classification. Here, we report a multiplex protein profiling-based approach for the classification of fresh frozen and formalin-fixed paraffin-embedded (FFPE) cancer tissue samples using the digital western blot technique DigiWest. A DigiWest-compatible FFPE extraction protocol was developed, and a total of 634 antibodies were tested in an initial set of 16 FFPE samples covering tumors from different origins. Of the 303 detected antibodies, 102 yielded significant correlation of signals in 25 pairs of fresh frozen and FFPE primary tumor samples, including head and neck squamous cell carcinomas (HNSC), lung squamous cell carcinomas (LUSC), lung adenocarcinomas (LUAD), colorectal adenocarcinomas (COAD), and pancreatic adenocarcinomas (PAAD). For this signature of 102 analytes (covering 88 total proteins and 14 phosphoproteins), a support vector machine (SVM) algorithm was developed. This allowed for the classification of the tissue of origin for all five tumor types studied here with high overall accuracies in both fresh frozen (90.4%) and FFPE (77.6%) samples. In addition, the SVM classifier reached an overall accuracy of 88% in an independent validation cohort of 25 FFPE tumor samples. Our results indicate that DigiWest-based protein profiling represents a valuable method for cancer classification, yielding conclusive and decisive data not only from fresh frozen specimens but also FFPE samples, thus making this approach attractive for routine clinical applications

Dewetting of Pt Nanoparticles Boosts Electrocatalytic Hydrogen Evolution Due to Electronic Metal-Support Interaction

Solid-state dewetting is the heat-induced agglomeration of thin metal films into defined nanoparticles (NPs). Dewetted Pt nanoparticles are investigated on F-doped SnO2 (FTO) substrates as model binder-free electrodes for the hydrogen evolution reaction (HER). Dewetting of Pt films into particles exposes the FTO substrate and the metal/support (Pt-FTO) contact line. Despite the decrease in Pt electrochemical surface area (ECSA) upon dewetting, dewetted NPs show a &gt;3-fold increase in ECSA-normalized HER activity compared to as-deposited nanocrystalline Pt films. Electrodes designed with dewetted Pt NPs of different sizes show that the HER activity does not only correlate with the ECSA but also increases with increasing the Pt-FTO contact line length. The smaller the NPs, the larger the Pt-FTO contact line, and the higher the activity. This effect is ascribed to electronic metal-support interaction (EMSI), due to electron transfer from FTO to Pt. It is proposed that EMSI effects alter the electronic structure of Pt sites near the Pt-FTO contact line, facilitating the H2 evolution kinetics. When NPs are a few nm-sized, a large mass fraction of Pt is affected by EMSI, resulting in a further increase of HER activity compared to NPs ≥10 nm despite the lower ECSA.</p

Mutations in the gdpP gene are a clinically relevant mechanism for β-lactam resistance in meticillin-resistant Staphylococcus aureus lacking mec determinants

In Staphylococcus aureus, resistance to β-lactamase stable β-lactam antibiotics is mediated by the penicillinbinding protein 2a, encoded by mecA or by its homologues mecB or mecC. However, a substantial number of meticillin-resistant isolates lack known mec genes and, thus, are called meticillin resistant lacking mec (MRLM). This study aims to identify the genetic mechanisms underlying the MRLM phenotype. A total of 141 MRLM isolates and 142 meticillin-susceptible controls were included in this study. Oxacillin and cefoxitin minimum inhibitory concentrations were determined by broth microdilution and the presence of mec genes was excluded by PCR. Comparative genomics and a genome-wide association study (GWAS) approach were applied to identify genetic polymorphisms associated with the MRLM phenotype. The potential impact of such mutations on the expression of PBP4, as well as on cell morphology and biofilm formation, was investigated. GWAS revealed that mutations in gdpP were significantly associated with the MRLM phenotype. GdpP is a phosphodiesterase enzyme involved in the degradation of the second messenger cyclic-di-AMP in S. aureus. A total of 131 MRLM isolates carried truncations, insertions or deletions as well as amino acid substitutions, mainly located in the functional DHH-domain of GdpP. We experimentally verified the contribution of these gdpP mutations to the MRLM phenotype by heterologous complementation experiments. The mutations in gdpP had no effect on transcription levels of pbp4; however, cell sizes of MRLM strains were reduced. The impact on biofilm formation was highly strain dependent. We report mutations in gdpP as a clinically relevant mechanism for β-lactam resistance in MRLM isolates. This observation is of particular clinical relevance, since MRLM are easily misclassified as MSSA (meticillin-susceptible S. aureus), which may lead to unnoticed spread of β-lactam-resistant isolates and subsequent treatment failure.Peer Reviewe

Favorable Mixing Thermodynamics in Ternary Polymer Blends for Realizing High Efficiency Plastic Solar Cells

Ternary blends with broad spectral absorption have the potential to increase charge generation in organic solar cells but feature additional complexity due to limited intermixing and electronic mismatch. Here, a model system comprising the polymers poly[5,5-bis(2-butyloctyl)-(2,2-bithiophene)-4,4-dicarboxylate-alt-5,5-2,2-bithiophene] (PDCBT) and PTB7-Th and PC70BM as an electron accepting unit is presented. The power conversion efficiency (PCE) of the ternary system clearly surpasses the performance of either of the binary systems. The photophysics is governed by a fast energy transfer process from PDCBT to PTB7-Th, followed by electron transfer at the PTB7-Th:fullerene interface. The morphological motif in the ternary blend is characterized by polymer fibers. Based on a combination of photophysical analysis, GIWAXS measurements and calculation of the intermolecular parameter, the latter indicating a very favorable molecular affinity between PDCBT and PTB7-Th, it is proposed that an efficient charge generation mechanism is possible because PTB7-Th predominantly orients around PDCBT filaments, allowing energy to be effectively relayed from PDCBT to PTB7-Th. Fullerene can be replaced by a nonfullerene acceptor without sacrifices in charge generation, achieving a PCE above 11%. These results support the idea that thermodynamic mixing and energetics of the polymer-polymer interface are critical design parameter for realizing highly efficient ternary solar cells with variable electron acceptors