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Summary: Background: People with complex symptomatology but unclear diagnosis presenting to a centre for rare diseases (CRD) may present with mental (co-)morbidity. We hypothesised that combining an expert in somatic medicine with a mental health specialist working in tandem will improve the diagnostic outcome. Methods: Patients aged 12 years and older who presented to one of the 11 participating German CRDs with an unknown diagnosis were recruited into this prospective cohort trial with a two-phase cohort design. From October 1, 2018 to September 30, 2019, participants were allocated to standard care (SC, N = 684), and from October 1, 2019 to January 31, 2021 to innovative care (IC, N = 695). The cohorts consisted mainly of adult participants with only a minority of children included (N = 67). IC included the involvement of a mental health specialist in all aspects of care (e.g., assessing medical records, clinic visits, telehealth care, and case conferences). Clinicaltrials.gov identifier: NCT03563677. Findings: The proportion of patients with diagnoses established within 12 months after the first visit to the CRD explaining the entire symptomatology (primary outcome) was 19% (N = 131 of 672) in the SC and 42% (N = 286 of 686) in the IC cohort (OR adjusted for centre effects 3.45 [95% CrI: 1.99–5.65]). The difference was mainly due to a higher prevalence of mental disorders and non-rare somatic diseases in the IC cohort. The median time to explaining diagnoses was one month shorter with IC (95% CrI: 1–2), and significantly more patients could be referred to local regular care in the IC (27.5%; N = 181 of 659) compared to the SC (12.3%; N = 81 of 658) cohort (OR adjusted for centre effects 2.70 [95% CrI: 2.02–3.60]). At 12-month follow-up, patient satisfaction with care was significantly higher in the IC compared to the SC cohort, while quality of life was not different between cohorts. Interpretation: Our findings suggested that including a mental health specialist in the entire evaluation process of CRDs for undiagnosed adolescents and adults should become an integral part of the assessment of individuals with a suspected rare disease. Funding: The study was funded by the Global Innovation Fund from the Joint Federal Committee in Germany (Innovationsfonds des Gemeinsamen Bundesausschusses), grant number 01NVF17031.

Thermography is a well-established non-destructive testing technique in materials research and defect detection. In addition, it is used on cultural heritage in the form of buildings and paintings. This contribution explores the utilisation of active thermography on an object of technical heritage – a historic aircraft of the Second World War, the Messerschmitt Me 163 b, as a part of an exhibition in the Deutsches Museum in Munich. Unfortunately, the appearances of many exhibits in museums have been altered before or during their time with the museum and are not in a historically accurate condition. Furthermore, the active service history is often not documented in detail or might have been lost. Both features are equally important in the presentation of information on a displayed item and destructive techniques cannot be employed on historic objects. Hence a non-destructive, non-contact way of examination was chosen in the form of thermography. With the help of phase analysis, flash thermography is also an invaluable tool for the evaluation of layered systems and can differentiate between paint layers. During the research presented herein, traces of abrasion and chemical stripping of older paint layers were visible. This complicates the compilation of sufficient information for a historically accurate restauration with any technique. Nonetheless, flash or pulsed thermography proves to be capable of finding not only identifying markings, defects, and different paint layers, but also the inner workings and substructure of the object under investigation.

Thermography is a non-destructive testing technique which is non-contacting as well as imaging and therefore advantageous for delicate materials. It is more widely used for qualitative evaluation but can also provide data for a quantitative analysis when the heat source is actively controlled. With flash thermography, fast diffusion or conduction processes can be monitored, providing an effective method for the inspection of metals and thin coatings. Ceramic layered systems are used as thermal barrier coatings, for example on turbine blades. Gas turbines with such blades can be operated at higher temperatures, which leads to an increase in efficiency. To fully exploit this advantage, the properties and thickness of the coating must be within a predefined parameter range. Due to the challenging and hard to monitor manufacturing process, the coating must be examined afterwards. With the help of a numerical model using a finite difference solution, multiple material parameters such as thermal conductivity and layer thickness can be determined simultaneously with nonlinear regression fitting. During the research presented herein, a four-stepped sample of ceramic coatings on an Inconel steel basis is examined and the thermographic data analysed. After the thermographic measurements, the sample was cut, embedded in resin, and polished. The scanning electron microscopy images and measurements serve as the reference values to compare the extracted parameters to.

Time-domain spectroscopy (TDS) in the terahertz (THz) frequency range is gaining in importance in nondestructive testing of dielectric materials. One application is the layer thickness measurement of a coating layer. To determine the thickness from the measurement data, the refractive index of the coating layer must be known in the surveyed frequency range. For perpendicular incidence of the radiation, methods exist to extract the refractive index from the measurement data themselves without prior knowledge. This paper extends these methods for non-perpendicular incidence, where the polarization of the radiation becomes important. Furthermore, modifications considering effects of surface roughness of the coating are introduced. The new methods are verified using measurement data of a sample of Inconel steel coated with yttria-stabilized zirconia (YSZ) and with COMSOL simulations of the measurement setup. To validate the thickness measurements, scanning electron microscopy (SEM) images of the layer structure are used. The results show good agreement with an average error of 1% for the simulation data and under 4% for the experimental data compared to reference measurements.

Cladribine triphosphate is the active compound of the anti-cancer and multiple sclerosis drug Mavenclad (cladribine). Biosynthesis of such non-natural deoxyribonucleotides is challenging but important in order to study the pharmaceutical modes of action. In this study, we developed a novel one-pot enzyme cascade for the biosynthesis of cladribine triphosphate, starting with the nucleobase 2Cl-adenine and the generic co-substrate phosphoribosyl pyrophosphate. The cascade is comprised of the three enzymes, namely, adenine phosphoribosyltransferase (APT), polyphosphate kinase (PPK), and ribonucleotide reductase (RNR). APT catalyzes the binding of the nucleobase to the ribose moiety, followed by two consecutive phosphorylation reactions by PPK. The formed nucleoside triphosphate is reduced to the final product 2Cl-deoxyadenonsine triphosphate (cladribine triphosphate) by the RNR. The cascade is feasible, showing comparative product concentrations and yields to existing enzyme cascades for nucleotide biosynthesis. While this study is limited to the biosynthesis of cladribine triphosphate, the design of the cascade offers the potential to extend its application to other important deoxyribonucleotides.