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Institute
Im Rahmen des Bund-Länder-Programms "Qualitätspakt Lehre" hat die Goethe-Universität Frankfurt erfolgreich das Programm "Starker Start ins Studium" eingeworben. Dadurch verfügt das Institut für Psychologie nun über die personellen Möglichkeiten, die fachliche und soziale Integration neuer Psychologiestudierender im sechssemestrigen Bachelorstudiengang Psychologie zu verbessern. Hierzu wurden zwei obligate je zweisemestrige Lehrmodule entwickelt. In dem vorliegenden Beitrag wird das übergeordnete Lehrkonzept beschrieben und dessen Implementierung im Fach Psychologie als Praxisbeispiel illustriert.
Although chest radiograph (CXR) is commonly used in diagnosing pediatric community acquired pneumonia (pCAP), limited data on interobserver agreement among radiologists exist. PedCAPNETZ is a prospective, observational, and multicenter study on pCAP. N = 233 CXR from patients with clinical diagnosis of pCAP were retrieved and n = 12 CXR without pathological findings were added. All CXR were interpreted by a radiologist at the site of recruitment and by two external, blinded pediatric radiologists. To evaluate interobserver agreement, the reporting of presence or absence of pCAP in CXR was analyzed, and prevalence and bias-adjusted kappa (PABAK) statistical testing was applied. Overall, n = 190 (82%) of CXR were confirmed as pCAP by two external pediatric radiologists. Compared with patients with pCAP negative CXR, patients with CXR-confirmed pCAP displayed higher C-reactive protein levels and a longer duration of symptoms before enrollment (p < .007). Further parameters, that is, age, respiratory rate, and oxygen saturation showed no significant difference. The interobserver agreement between the onsite radiologists and each of the two independent pediatric radiologists for the presence of pCAP was poor to fair (69%; PABAK = 0.39% and 76%; PABAK = 0.53, respectively). The concordance between the external radiologists was fair (81%; PABAK = 0.62). With regard to typical CXR findings for pCAP, chance corrected interrater agreement was highest for pleural effusions, infiltrates, and consolidations and lowest for interstitial patterns and peribronchial thickening. Our data show a poor interobserver agreement in the CXR-based diagnosis of pCAP and emphasized the need for harmonized interpretation standards.
Background: Rare Diseases (RDs) are difficult to diagnose. Clinical Decision Support Systems (CDSS) could support the diagnosis for RDs. The Medical Informatics in Research and Medicine (MIRACUM) consortium developed a CDSS for RDs based on distributed clinical data from eight German university hospitals. To support the diagnosis for difficult patient cases, the CDSS uses data from the different hospitals to perform a patient similarity analysis to obtain an indication of a diagnosis. To optimize our CDSS, we conducted a qualitative study to investigate usability and functionality of our designed CDSS. Methods: We performed a Thinking Aloud Test (TA-Test) with RDs experts working in Rare Diseases Centers (RDCs) at MIRACUM locations which are specialized in diagnosis and treatment of RDs. An instruction sheet with tasks was prepared that the participants should perform with the CDSS during the study. The TA-Test was recorded on audio and video, whereas the resulting transcripts were analysed with a qualitative content analysis, as a ruled-guided fixed procedure to analyse text-based data. Furthermore, a questionnaire was handed out at the end of the study including the System Usability Scale (SUS). Results: A total of eight experts from eight MIRACUM locations with an established RDC were included in the study. Results indicate that more detailed information about patients, such as descriptive attributes or findings, can help the system perform better. The system was rated positively in terms of functionality, such as functions that enable the user to obtain an overview of similar patients or medical history of a patient. However, there is a lack of transparency in the results of the CDSS patient similarity analysis. The study participants often stated that the system should present the user with an overview of exact symptoms, diagnosis, and other characteristics that define two patients as similar. In the usability section, the CDSS received a score of 73.21 points, which is ranked as good usability. Conclusions: This qualitative study investigated the usability and functionality of a CDSS of RDs. Despite positive feedback about functionality of system, the CDSS still requires some revisions and improvement in transparency of the patient similarity analysis.
Background Osseointegration is crucial for the long-term success of dental implants and depends on the tissue reaction at the tissue-implant interface. Mechanical properties and biocompatibility make zirconia a suitable material for dental implants, although surface processings are still problematic. The aim of the present study was to compare osteoblast behavior on structured zirconia and titanium surfaces under standardized conditions. Methods The surface characteristics were determined by scanning electron microscopy (SEM). In primary bovine osteoblasts attachment kinetics, proliferation rate and synthesis of bone-associated proteins were tested on different surfaces. Results The results demonstrated that the proliferation rate of cells was significantly higher on zirconia surfaces than on titanium surfaces (p < 0.05; Student's t-test). In contrast, attachment and adhesion strength of the primary cells was significant higher on titanium surfaces (p < 0.05; U test). No significant differences were found in the synthesis of bone-specific proteins. Ultrastructural analysis revealed phenotypic features of osteoblast-like cells on both zirconia and titanium surfaces. Conclusion The study demonstrates distinct effects of the surface composition on osteoblasts in culture. Zirconia improves cell proliferation significantly during the first days of culture, but it does not improve attachment and adhesion strength. Both materials do not differ with respect to protein synthesis or ultrastructural appearance of osteoblasts. Zirconium oxide may therefore be a suitable material for dental implants.
Background Titanium and titanium alloys are widely used for fabrication of dental implants. Since the material composition and the surface topography of a biomaterial play a fundamental role in osseointegration, various chemical and physical surface modifications have been developed to improve osseous healing. Zirconia-based implants were introduced into dental implantology as an altenative to titanium implants. Zirconia seems to be a suitable implant material because of its tooth-like colour, its mechanical properties and its biocompatibility. As the osseointegration of zirconia implants has not been extensively investigated, the aim of this study was to compare the osseous healing of zirconia implants with titanium implants which have a roughened surface but otherwise similar implant geometries. Methods Forty-eight zirconia and titanium implants were introduced into the tibia of 12 minipigs. After 1, 4 or 12 weeks, animals were sacrificed and specimens containing the implants were examined in terms of histological and ultrastructural techniques. Results Histological results showed direct bone contact on the zirconia and titanium surfaces. Bone implant contact as measured by histomorphometry was slightly better on titanium than on zirconia surfaces. However, a statistically significant difference between the two groups was not observed. Conclusion The results demonstrated that zirconia implants with modified surfaces result in an osseointegration which is comparable with that of titanium implants.
Background The successful use of zirconia ceramics in orthopedic surgery led to a demand for dental zirconium-based implant systems. Because of its excellent biomechanical characteristics, biocompatibility, and bright tooth-like color, zirconia (zirconium dioxide, ZrO2) has the potential to become a substitute for titanium as dental implant material. The present study aimed at investigating the osseointegration of zirconia implants with modified ablative surface at an ultrastructural level. Methods A total of 24 zirconia implants with modified ablative surfaces and 24 titanium implants all of similar shape and surface structure were inserted into the tibia of 12 Gottinger minipigs. Block biopsies were harvested 1 week, 4 weeks or 12 weeks (four animals each) after surgery. Scanning electron microscopy (SEM) analysis was performed at the bone implant interface. Results Remarkable bone attachment was already seen after 1 week which increased further to intimate bone contact after 4 weeks, observed on both zirconia and titanium implant surfaces. After 12 weeks, osseointegration without interposition of an interfacial layer was detected. At the ultrastructural level, there was no obvious difference between the osseointegration of zirconia implants with modified ablative surfaces and titanium implants with a similar surface topography. Conclusion The results of this study indicate similar osseointegration of zirconia and titanium implants at the ultrastructural level.
EUROTRANS is a European research program for the transmutation of high level nuclear waste in an accelerator-driven system (ADS). As proposed, the driver linac needs to deliver a 2.5–4 mA, 600 MeV continuous-wave (CW) proton beam and later a 20 mA, 800 MeV one to the spallation target in the prototype-scale and industrial-scale demonstration phases, respectively. This paper is focusing on the conceptual studies performed with respect to the 17 MeV injector. First, the special beam dynamics strategies and methods, which have been developed and applied to design a current-variable injector up to 30 mA for allowing an easy upgrade without additional R&D costs, will be introduced. Then the error study made for evaluating the tolerance limits of the designed injector will be presented as well.
MYRRHA is conceived as an accelerator driven system (ADS) for transmutation of high level nuclear waste. The neutron source is created by coupling a proton accelerator of 600 MeV with a 4 mA proton beam, a spallation source and a sub-critical core. The IAP of Frankfurt University is responsible for the development of the 17 MeV injector operated at 176 MHz. The injector consists of a 1.5 MeV 4-Rod-RFQ and six CH-drifttube-structures. The first two CH-structures will be operated at room temperature and the other CH-structures are superconducting cavities assembled in one cryo-module. To achieve the extremely high reliability required by the ADS application, the design of the 17 MeV injector has been intensively studied, with respect to thermal issues, minimum peak fields and field distribution.
Co-design of a trustworthy AI system in healthcare: deep learning based skin lesion classifier
(2021)
This paper documents how an ethically aligned co-design methodology ensures trustworthiness in the early design phase of an artificial intelligence (AI) system component for healthcare. The system explains decisions made by deep learning networks analyzing images of skin lesions. The co-design of trustworthy AI developed here used a holistic approach rather than a static ethical checklist and required a multidisciplinary team of experts working with the AI designers and their managers. Ethical, legal, and technical issues potentially arising from the future use of the AI system were investigated. This paper is a first report on co-designing in the early design phase. Our results can also serve as guidance for other early-phase AI-similar tool developments.
The crossbar H-mode (CH) cavity is an accelerating structure operated in the H21(0) mode. The robustness of the crossbar geometry allows one to realize room temperature as well as superconducting linac cavities. The shunt impedance characteristics of this structure are attractive to develop proton and heavy ion linacs in the low and medium beta range. A first room temperature eight-cell prototype has proven the feasibility of the crossbar design in terms of mechanical construction, copper plating, and cooling. An innovative rf coupling concept has been developed where two CH cavities are connected by a two gap E010-mode resonator which, at the same time, provides transverse focusing by a quadrupole triplet. The concept has been applied in the design of the new FAIR proton linac and a scaled model of the second cavity of this injector has been built and tested too. The full scale prototype is now under construction at the University of Frankfurt. In this paper, the room temperature CH cavity development as well as the general layout of the FAIR proton injector (70 MeV, 325 MHz, 70 mA) is presented and discussed.
Artificial Intelligence (AI) has the potential to greatly improve the delivery of healthcare and other services that advance population health and wellbeing. However, the use of AI in healthcare also brings potential risks that may cause unintended harm. To guide future developments in AI, the High-Level Expert Group on AI set up by the European Commission (EC), recently published ethics guidelines for what it terms “trustworthy” AI. These guidelines are aimed at a variety of stakeholders, especially guiding practitioners toward more ethical and more robust applications of AI. In line with efforts of the EC, AI ethics scholarship focuses increasingly on converting abstract principles into actionable recommendations. However, the interpretation, relevance, and implementation of trustworthy AI depend on the domain and the context in which the AI system is used. The main contribution of this paper is to demonstrate how to use the general AI HLEG trustworthy AI guidelines in practice in the healthcare domain. To this end, we present a best practice of assessing the use of machine learning as a supportive tool to recognize cardiac arrest in emergency calls. The AI system under assessment is currently in use in the city of Copenhagen in Denmark. The assessment is accomplished by an independent team composed of philosophers, policy makers, social scientists, technical, legal, and medical experts. By leveraging an interdisciplinary team, we aim to expose the complex trade-offs and the necessity for such thorough human review when tackling socio-technical applications of AI in healthcare. For the assessment, we use a process to assess trustworthy AI, called 1Z-Inspection® to identify specific challenges and potential ethical trade-offs when we consider AI in practice.
At the Institute for Applied Physics (IAP), University of Frankfurt, a s.c. 325 MHz CH-Cavity is under development for future beam tests at GSI UNILAC, Darmstadt. The cavity with 7 accelerating cells has a geometrical beta of 0.15 corresponding to 11.4 AMeV. The design gradient is 5 MV/m. The geometry of this resonator was optimized with respect to a compact design, low peak fields, surface processing, power coupling and tuning. Furthermore a new tuning system based on bellow tuners inside the resonator will control the frequency during operation. After rf tests in Frankfurt the cavity will be tested with a 10 mA, 11.4 AMeV beam delivered by the GSI UNILAC. In this paper rf simulations, multipacting analysis as well as thermal calculations will be presented.
At GSI a new, superconducting (sc) continuous wave (cw) LINAC is under design in cooperation with the Institute for Applied Physics (IAP) of Frankfurt University and the Helmholtz Institut Mainz (HIM). This proposed LINAC is highly requested by a broad community of future users to fulfill the requirements of nuclear chemistry, nuclear physics, and especially in the research field of Super Heavy Elements (SHE). In this context the preliminary layout of the LINAC has been carried out by IAP. The main acceleration of up to 7.3 AMeV will be provided by nine sc Crossbar-H-mode (CH) cavities operated at 217 MHz. Currently, a prototype of the cw LINAC as a demonstrator is under development. The demonstrator comprises a sc CH-cavity embedded between two sc solenoids mounted in a horizontal cryomodule. A full performance test of the demonstrator in 2013/14 by injecting and accelerating a beam from the GSI High Charge Injector (HLI) is one important milestone of the project. The status of the demonstrator is presented.
The superconducting CH-structure (Crossbar-H-mode) is a multi-cell drift tube cavity for the low and medium energy range operated in the H21-mode, which has been developed at the Institute for Applied Physics (IAP) of Frankfurt University. With respect to different high power applications two types of superconducting CH-structures (f = 325 MHz, β = 0.16, seven cells and f = 217 MHz, β = 0.059, 15 cells) are presently under construction and accordingly under development. The structural mechanical simulation is a very important aspect of the cavity design. Furthermore, several simulations with ANSYS Workbench have been performed to predict the deformation of the cavity walls due to the cavity cool-down, pressure effects and mechanical vibrations. To readjust the fast frequency changes in consequence of the cavity shape deformation, a new concept for the dynamic frequency tuning has been investigated, including a novel type of bellow-tuner.
The ARMADILLO bunch compressor currently being designed at IAP is capable of reaching a longitudinal pulse compression ratio of 45 for proton beams of 150 mA at 2 MeV. It will provide one nanosecond proton pulses with a peak current of 7.7 A. The system guides nine linacμbunches deflected by a 5 MHz rf kicker and uses four dipole magnets - two homogeneous and two with field gradients - to merge them on the target. For longitudinal focusing and an energy variation of ±200 keV two multitrack rf cavities are included. ARMADILLO will be installed at the end of the Frankfurt Neutron Source FRANZ making use of the unique 250 kHz time structure. This contribution will provide an overview of the layout of the system as well as recent advances in component design and beam dynamics of the compressor.
This novel kind of neutron beam facility will provide 1 ns short neutron pulses with an approximately thermal energy distribution around 30 keV. The pulse repetition rate will be up to 250 kHz, the total proton number per pulse will be up to 6×1010 in the final stage, starting with a p – source current of 200 mA. A second target station will allow n – activation experiments by cw beam operation. An intense 2 MeV proton beam will drive a neutron source by the 7 Li (p,n) 7 Be reaction. The facility is under construction at the physics experimental hall of the J.W. Goethe – University. The 1m thick concrete tunnel was installed in 2009. In 2011 all rf amplifiers will be delivered and installed. Successful 200 mA proton source experiments in 2010 at a test stand will be followed by experiments on the 120 kV FRANZ terminal in 2011. The 250 kHz, 100 ns chopper in front of the rf linac is under construction, while the 2 MeV bunch compressor design was finished and the technical design of all components has started. The main accelerator cavity is under construction. First 2 MeV beam tests are expected for end of 2012.
Reliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a readout for monitoring the replication of SARS-CoV-2 isolates from different variants, including a remdesivir-resistant strain, and of other coronaviruses in numerous cell culture models, independently of cytopathogenic effect formation. Compared to other models, the Caco-2 subline Caco-2-F03 displayed superior performance. It possesses a stable SARS-CoV-2 susceptibility phenotype and does not produce false-positive hits due to drug-induced phospholipidosis. A proof-of-concept screen of 1,796 kinase inhibitors identified known and novel antiviral drug candidates including inhibitors of phosphoglycerate dehydrogenase (PHGDH), CDC like kinase 1 (CLK-1), and colony stimulating factor 1 receptor (CSF1R). The activity of the PHGDH inhibitor NCT-503 was further increased in combination with the hexokinase II (HK2) inhibitor 2-deoxy-D-glucose, which is in clinical development for COVID-19. In conclusion, caspase 3/7 activity detection in SARS-CoV-2-infected Caco-2-F03 cells provides a simple phenotypic high-throughput screening platform for SARS-CoV-2 drug candidates that reduces false-positive hits.
Reliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a read-out for monitoring the replication of SARS-CoV-2 isolates from different variants, including a remdesivir-resistant strain, and of other coronaviruses in a broad range of cell culture models, independently of cytopathogenic effect formation. Compared to other cell culture models, the Caco-2 subline Caco-2-F03 displayed superior performance, as it possesses a stable SARS-CoV-2 susceptible phenotype and does not produce false-positive hits due to drug-induced phospholipidosis. A proof-of-concept screen of 1796 kinase inhibitors identified known and novel antiviral drug candidates including inhibitors of PHGDH, CLK-1, and CSF1R. The activity of the PHGDH inhibitor NCT-503 was further increased in combination with the HK2 inhibitor 2-deoxy-D-glucose, which is in clinical development for COVID-19. In conclusion, caspase 3/7 activity detection in SARS-CoV-2-infected Caco-2F03 cells provides a simple phenotypic high-throughput screening platform for SARS-CoV-2 drug candidates that reduces false positive hits.
For the research program with cooled antiprotons at FAIR a dedicated 70 MeV, 70 mA proton injector is required. The main acceleration of this room temperature linac will be provided by six CH cavities operated at 325 MHz. Each cavity will be powered by a 2.5 MW Klystron. For the second acceleration unit from 11.5 MeV to 24.2 MeV a 1:2 scaled model has been built. Low level RF measurements have been performed to determine the main parameters and to prove the concept of coupled CH cavities. For this second tank technical and mechanical investigations have been performed in 2010 to develop a complete technical concept for the manufacturing. In Spring 2011, the construction of the first power prototype has started. The main components of this cavity will be ready for measurements in summer 2011. At that time, the cavity will be tested with a preliminary aluminum drift tube structure, which will allow precise frequency and field tuning. This paper will report on the recent technical development and achievements. It will outline the main fabrication steps towards that novel type of proton DTL. Also first low level RF measurements are expected.
Background: Body dysmorphic disorder (BDD) is characterized by an excessive preoccupation with one or more perceived flaws in one’s own appearance. Previous studies provided evidence for deficits in configural and holistic processing in BDD. Preliminary evidence suggests abnormalities at an early stage of visual processing. The present study is the first examining early neurocognitive perception of the own face in BDD by using electroencephalography (EEG). We investigated the face inversion effect, in which inverted (upside-down) faces are disproportionately poorly processed compared to upright faces. This effect reflects a disruption of configural and holistic processing, and in consequence a preponderance of featural face processing.
Methods: We recorded face-sensitive event-related potentials (ERPs) in 16 BDD patients and 16 healthy controls, all unmedicated. Participants viewed upright and inverted (upside-down) images of their own face and an unfamiliar other face, each in two facial emotional expressions (neutral vs. smiling). We calculated the early ERP components P100, N170, P200, N250, and the late positive component (LPC), and compared amplitudes among both groups.
Results: In the early P100, no face inversion effects were found in both groups. In the N170, both groups exhibited the common face inversion effects, with significantly larger N170 amplitudes for inverted than upright faces. In the P200, both groups exhibited larger inversion effects to other (relative to own) faces, with larger P200 amplitudes for other upright than inverted faces. In the N250, no significant group differences were found in face processing. In the LPC, both groups exhibited larger inversion effects to other (relative to own) faces, with larger LPC amplitudes for other inverted than upright faces. These overall patterns appeared to be comparable for both groups. Smaller inversion effects to own (relative to other) faces were observed in none of these components in BDD, relative to controls.
Conclusions: The findings suggest no evidence for abnormalities at all levels of early face processing in our observed sample of BDD patients. Further research should investigate the neural substrates underlying BDD symptomatology.