Sympathetic Cooling of a Single Individually-Trapped Proton in a Cryogenic Penning Trap

A method to prepare arbitrary stored ions with low energy in the mK range would improve many high-precision Penning trap experiments and is essential for high-precision measurements of the antiproton and proton g-factors. In this thesis, we investigate sympathetic cooling of a single individually-trapped proton by laser-cooled 9Be+ ions stored in a separate trap. Both ions are coupled by image currents induced in a common electrode and the coupling is enhanced by a connected cryogenic superconducting radio-frequency RLC oscillator. The image-current based coupling makes the technique applicable to arbitrary ions. We describe the new experimental setup, based on a significant modification of the previous proton g-factor experiment, and the installation and optimization of new image-current detectors. We further describe the development and characterization of a single-photon sensitive fluorescence detection system based on silicon photomultipliers integrated into the cryogenic Penning trap. We demonstrate laser-cooling of the 9Be+ ions and measure their temperature to 1.1(2) mK using fluorescence detection. The simultaneous detection of fluorescence photons and image currents of laser-cooled 9Be+ ions enables a measurement of the laser-induced damping. We further demonstrate sympathetic cooling of the axial mode of a single proton to 2.6(2.5) K, limited by the applied temperature measurement method. With a newly developed temperature measurement trap, we improve this value to 160(30) mK, almost two orders of magnitude below the environment temperature. Finally, we argue that the technique can be optimized to reach temperatures in the low double-digit mK range, which would enable a future generation of antiproton and proton g-factor measurements with an order of magnitude improved precision. For other high-precision Penning trap experiments, the method will be an attractive tool to prepare arbitrary ions for measurement

Trap-integrated fluorescence detection based on silicon photomultipliers in a cryogenic Penning trap

We present a fluorescence-detection system for laser-cooled 9Be+ ions based on silicon photomultipliers (SiPM) operated at 4 K and integrated into our cryogenic 1.9 T multi-Penning-trap system. Our approach enables fluorescence detection in a hermetically-sealed cryogenic Penning-trap chamber with limited optical access, where state-of-the-art detection using a telescope and photomultipliers at room temperature would be extremely difficult. We characterize the properties of the SiPM in a cryocooler at 4 K, where we measure a dark count rate below 1/s and a detection efficiency of 2.5(3) %. We further discuss the design of our cryogenic fluorescence-detection trap, and analyze the performance of our detection system by fluorescence spectroscopy of 9Be+ ion clouds during several runs of our experiment.Comment: 12 pages, 11 figure

Evidence based medicine in physical medicine and rehabilitation (English version)

In the last twenty years the term “Evidence Based Medicine (EBM)” has spread into all areas of medicine and is often used for decision-making in the medical and public health sector. It is also used to verify the significance and/or the effectiveness of different therapies. The definition of EBM is to use the physician’s individual expertise, the patient’s needs and the best external evidence for each individual patient. Today, however, the term EBM is often wrongly used as a synonym for best “external evidence”. This leads not only to a misuse of evidence based medicine but suggests a fundamental misunderstanding of the model which was created by Gordon Guyatt, David Sackett and Archibald Cochrane. This problem becomes even greater the more social insurance institutions, public healthcare providers and politicians use external evidence alone as a main guideline for financing therapies in physical medicine and general rehabilitation without taking into account the physician’s expertise and the patient’s needs.The wrong interpretation of EBM can lead to the following problems: well established clinical therapies are either questioned or not granted and are therefore withheld from patients (for example physical pain management). Absence of evidence for individual therapy methods does not prove their ineffectiveness! In this short statement the significance of EBM in physical medicine and general rehabilitation will be analysed and discussed

Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trial

IntroductionAccumulating evidence suggests that the adoptive transfer of ex vivo expanded regulatory T cells (Treg) may overcome colitogenic immune responses in patients with inflammatory bowel diseases. The objective of the ER-TREG 01 trial is to assess safety and tolerability of a single infusion of autologous ex vivo expanded Treg in adults with ulcerative colitis.Methods and analysisThe study is designed as a single-arm, fast-track dose-escalation trial. The study will include 10 patients with ulcerative colitis. The study intervention consists of (1) a baseline visit; (2) a second visit that includes a leukapheresis to generate the investigational medicinal product, (3) a third visit to infuse the investigational medicinal product and (4) five subsequent follow-up visits within the next 26 weeks to assess safety and tolerability. Patients will intravenously receive a single dose of 0.5×106, 1×106, 2×106, 5×106 or 10×106 autologous Treg/kg body weight. The primary objective is to define the maximum tolerable dose of a single infusion of autologous ex vivo expanded Treg. Secondary objectives include the evaluation of safety of one single infusion of autologous ex vivo expanded Treg, efficacy assessment and accompanying immunomonitoring to measure Treg function in the peripheral blood and intestinal mucosa.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany (number 417_19 Az). In addition, the study was approved by the Paul-Ehrlich Institute, Federal Institute for Vaccines and Biomedicines, Langen, Germany (number 3652/01). The study is funded by the German Research Foundation (DFG, KFO 257 project 08 and SFB/TransRegio 241 project C04). The trial will be conducted in compliance with this study protocol, the Declaration of Helsinki, Good Clinical Practice and Good Manufacturing Practice. The results will be published in peer-reviewed scientific journals and disseminated in scientific conferences and media.Trial registration numberNCT04691232

Limited capability of MRI radiomics to predict primary tumor histology of brain metastases in external validation

Background Growing research demonstrates the ability to predict histology or genetic information of various malignancies using radiomic features extracted from imaging data. This study aimed to investigate MRI-based radiomics in predicting the primary tumor of brain metastases through internal and external validation, using oversampling techniques to address the class imbalance. Methods This IRB-approved retrospective multicenter study included brain metastases from lung cancer, melanoma, breast cancer, colorectal cancer, and a combined heterogenous group of other primary entities (5-class classification). Local data were acquired between 2003 and 2021 from 231 patients (545 metastases). External validation was performed with 82 patients (280 metastases) and 258 patients (809 metastases) from the publicly available Stanford BrainMetShare and the University of California San Francisco Brain Metastases Stereotactic Radiosurgery datasets, respectively. Preprocessing included brain extraction, bias correction, coregistration, intensity normalization, and semi-manual binary tumor segmentation. Two-thousand five hundred and twenty-eight radiomic features were extracted from T1w (± contrast), fluid-attenuated inversion recovery (FLAIR), and wavelet transforms for each sequence (8 decompositions). Random forest classifiers were trained with selected features on original and oversampled data (5-fold cross-validation) and evaluated on internal/external holdout test sets using accuracy, precision, recall, F1 score, and area under the receiver-operating characteristic curve (AUC). Results Oversampling did not improve the overall unsatisfactory performance on the internal and external test sets. Incorrect data partitioning (oversampling before train/validation/test split) leads to a massive overestimation of model performance. Conclusions Radiomics models’ capability to predict histologic or genomic data from imaging should be critically assessed; external validation is essential

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Design und Implementierung einer neuen Optik für einen Strahl aus atomarem Wasserstoff für das Antiwasserstoff-Hyperfinestruktur-Spektroskopie-Experiment von ASACUSA.

Zusammenfassung in deutscher SpracheAbweichender Titel nach Übersetzung der Verfasserin/des VerfassersDie ASACUSA (Atomic Spectroscopy And Collisions Using Slow Antiprotons) Kollaboration am CERN wird ein Experiment unter Nutzung der Magnetresonanz-Methode von I. I. Rabi durchführen um die Frequenzen der Hyperfeinstruktur-Übergänge des Grundzustands von Antiwasserstoff zu vermessen. Da Antiwasserstoff der CPT-symmetrische Partner von Wasserstoff ist, und die Frequenzen dieser Übergänge in Wasserstoff sehr gut bekannt sind, stellen solche Messungen einen sehr empfindlichen Test der CPT Symmetrie dar. Um den Spektroskopieapparat für den Betrieb mit Antiwasserstoffatomen vorzubereiten werden Messungen mit Wasserstoffatomen durchgeführt. Es wird ein Strahl von atomarem Wasserstoff anstelle der ASACUSA Antiwasserstoffquelle und ein Quadrupol-Massenspektrometer anstelle des Annihilations-Detektors verwendet. Ein Spektrometer (bestehend aus einer Kavität um einen der beiden möglichen Übergänge, den sogenannten σ- Übergang, zu messen und einem supraleitenden Sextupolmagneten) wurde bereits gebaut und charakterisiert und ist derzeit im Einsatz am ASACUSA Antiwasserstoff-Hyperfeinstruktur Experiment am CERN. In dieser Arbeit wird eine zweite Kavität vorbereitet, die eine gleichzeitige Messung beider möglicher Übergänge (der σ- und TT-Übergänge) erlaubt. Für den Betrieb mit Wasserstoff wird der supraleitende Sextupolmagnet durch permanente Sextupolmagnete ersetzt, die im Zuge dieser Arbeit gebaut und charakterisiert werden. Die Geschwindigkeits- und Zustandsselektion eines Duplets aus Sextupolmagneten wird simuliert und vermessen. Numerische Simulationen zu den Trajektorien der Wasserstoffatome in dem Spektroskopieapparat werden durchgeführt, um ein quantitatives Verständnis des Strahltransports zu erhalten. Diese Simulationen führen zu einer neuen Strahloptik, basierend auf Ringblenden, die implementiert und getestet werden. Schließlich werden die σ und TT- Hyperfein Übergänge des Grundzustands von Wasserstoff mit dem Spektroskopieapparat im Erdmagnetfeld vermessen.The ASACUSA (Atomic Spectroscopy And Collisions Using Slow Antiprotons) collaboration at CERN will perform an experiment using Rabi's magnetic resonance method to measure the frequencies of ground state hyperfine transitions of antihydrogen. Since antihydrogen is the CPT symmetric partner of hydrogen and the frequency of these transitions in hydrogen are very well known, such measurements will provide a very sensitive test of CPT symmetry. To prepare and characterize the spectroscopy apparatus for measurements with antihydrogen atoms, measurements with hydrogen atoms are performed. A beam of atomic hydrogen is used instead of the ASACUSA antihydrogen source, and a quadrupole mass spectrometer instead of an annihilation detector. A hyperfine spectroscopy apparatus (consisting of a cavity tuned to measure one of the two possible transitions, the σ-transition, and a superconducting sextupole magnet) has already been commissioned and is currently in operation at the ASACUSA antihydrogen hyperfine structure experiment at CERN. In this work a second cavity is prepared, which enables simultaneous measurement of the two possible transitions, the σ - and TT transition. For operation with hydrogen the superconducting sextupole magnet is replaced by permanent sextupole magnets, which are built and characterized in the course of this work. The velocity and state selection properties of a sextupole doublet are simulated and measured. Numerical simulations of trajectories of hydrogen atoms in the spectroscopy apparatus are performed to obtain a quantitative understanding of the beam transport. These simulations lead to a new beam optics, based on ring apertures, which is implemented and tested. Finally, the σ and TT hyperfine transitions of ground state hydrogen are measured with the spectroscopy apparatus in earth's magnetic field.8

Future Image Acquisition Trends for PET/MRI

Hybrid PET/MRI scanners have become commercially available in the past years but are not yet widely distributed. The combination of a state-of-the-art PET with a state-of-the-art MRI scanner provides numerous potential advantages compared with the established PET/CT hybrid systems, namely, increased soft tissue contrast; functional information from MRI such as diffusion, perfusion, and blood oxygenation level-dependent techniques; true multiplanar data acquisition; and reduced radiation exposure. On the contrary, current PET/MRI technology is hampered by several shortcomings compared with PET/CT, the most important issues being how to use MR data for PET attenuation correction and the low sensitivity of MRI for small-scale pulmonary pathologies compared with high-resolution CT. Moreover, the optimal choice for hybrid PET/MRI acquisition protocols needs to be defined providing the highest possible degree of sensitivity and specificity within the constraints of the available measurement time. A multitude of new acquisition strategies of PET and MRI not only offer to overcome current obstacles of hybrid PET/MRI but also provide deeper insights into the pathophysiology of oncological, inflammatory, or degenerative diseases from the combination of molecular and functional imaging techniques