Development of a protocol for standardized use of a water-soluble contrast agent with polyethylene glycol in post-mortem CT angiography.

Computed tomography angiography (PMCTA) is increasingly used in postmortem cases. Standardized validated protocols permit to compare different PMCTA images and make it more easily to defend a case in court. In addition to the well-known technique by Grabherr et al. (2011) which is using paraffin oil as a carrier substance, water-soluble polyethylene glycol 200 (PEG200) can be used in combination with the contrast agent Accupaque® 300. As to date, there exists no standardized protocol for the use of this contrast agent mixture, the aim of this study was to develop a protocol using it. Between 2012 and 2022, 23 PMCTA with PEG200 and Accupaque®300 were performed at the University Centre of Legal Medicine Lausanne (Switzerland) and the Institute of Forensic Medicine Munich (Germany). The images obtained were evaluated regarding the opacification of the vessels and possible artefacts. The best image quality was obtained with a mixing ratio of 1:15 (Accupaque®300:PEG200) and a perfusion volume of 1000 ml in the arterial, 1400 ml in the venous and 350 ml in the dynamic phase. The infusion rates described by Grabherr et al. were confirmed for the three phases. Overall, the opacification of the vessels was diagnostically sufficient. In 13 cases no opacification of the right coronary artery was observed due to a stratification artefact. By using the PMCTA protocol with PEG200 as a carrier, a good overall image quality can be achieved. This protocol offers the possibility to standardize PMCTA with PEG200.

Development and psychometric evaluation of item banks for memory and attention - supplements to the EORTC CAT Core instrument.

BACKGROUND: Cancer patients may experience a decrease in cognitive functioning before, during and after cancer treatment. So far, the Quality of Life Group of the European Organisation for Research and Treatment of Cancer (EORTC QLG) developed an item bank to assess self-reported memory and attention within a single, cognitive functioning scale (CF) using computerized adaptive testing (EORTC CAT Core CF item bank). However, the distinction between different cognitive functions might be important to assess the patients' functional status appropriately and to determine treatment impact. To allow for such assessment, the aim of this study was to develop and psychometrically evaluate separate item banks for memory and attention based on the EORTC CAT Core CF item bank. METHODS: In a multistep process including an expert-based content analysis, we assigned 44 items from the EORTC CAT Core CF item bank to the memory or attention domain. Then, we conducted psychometric analyses based on a sample used within the development of the EORTC CAT Core CF item bank. The sample consisted of 1030 cancer patients from Denmark, France, Poland, and the United Kingdom. We evaluated measurement properties of the newly developed item banks using confirmatory factor analysis (CFA) and item response theory model calibration. RESULTS: Item assignment resulted in 31 memory and 13 attention items. Conducted CFAs suggested good fit to a 1-factor model for each domain and no violations of monotonicity or indications of differential item functioning. Evaluation of CATs for both memory and attention confirmed well-functioning item banks with increased power/reduced sample size requirements (for CATs ≥ 4 items and up to 40% reduction in sample size requirements in comparison to non-CAT format). CONCLUSION: Two well-functioning and psychometrically robust item banks for memory and attention were formed from the existing EORTC CAT Core CF item bank. These findings could support further research on self-reported cognitive functioning in cancer patients in clinical trials as well as for real-word-evidence. A more precise assessment of attention and memory deficits in cancer patients will strengthen the evidence on the effects of cancer treatment for different cancer entities, and therefore contribute to shared and informed clinical decision-making.

Final Results of GERDA on the Two-Neutrino Double-ß Decay Half-Life of

We present the measurement of the two-neutrino double-ß decay rate of ^{76}Ge performed with the GERDA Phase II experiment. With a subset of the entire GERDA exposure, 11.8 kg yr, the half-life of the process has been determined: T_{1/2}^{2ν}=(2.022±0.018_{stat}±0.038_{syst})×10^{21} yr. This is the most precise determination of the ^{76}Ge two-neutrino double-ß decay half-life and one of the most precise measurements of a double-ß decay process. The relevant nuclear matrix element can be extracted: M_{eff}^{2ν}=(0.101±0.001).

Pediatric postmortem CT angiography: validation of vascular access for PMCT angiography in stillbirths, babies and toddlers.

PURPOSE: The use of angiography in postmortem CT angiography (PMCTA) has several advantages. In adults, femoral vascular access is well established. Due to the small and specific anatomy in fetuses and infants, the technique has to be adapted, especially regarding the vascular access. The aim of this study was to evaluate vascular access for pediatric PMCTA (pedPMCTA). MATERIALS AND METHODS: Ten pedPMCTAs were performed in stillbirths, babies, and one toddler. A femoral approach by cannulation of the femoral artery and vein, an umbilical approach by cannulation of the umbilical vessels, and an intraosseous approach by an intraosseous needle were evaluated by handling and resulting imaging. RESULTS: The insertion of a cannula with a size of 18-20 G in the femoral vessels was possible in babies. An umbilical access with peripheral venous cannulas with a size of 14-20 G was feasible in stillbirths and newborns. An intraosseous access is advisable as equal alternative to umbilical and in cases where a femoral access is not possible. The most significant problem with the vascular access is the extravasation of contrast media, but this can be reduced significantly with practice. CONCLUSION: When performing pedPMCTA, an umbilical vascular access is recommended if an umbilical cord with open vessels is still present. Otherwise, a bone marrow access should be preferred in the presence of an arteriovenous shunt or if only the venous system needs to be shown. If that is not the case, the femoral access with the possibility to separate venous and arterial scan should be used.

Search for tri-nucleon decays of 76Ge in GERDA.

We search for tri-nucleon decays of 76Ge in the dataset from the GERmanium Detector Array (GERDA) experiment. Decays that populate excited levels of the daughter nucleus above the threshold for particle emission lead to disintegration and are not considered. The ppp-, ppn-, and pnn-decays lead to 73Cu, 73Zn, and 73Ga nuclei, respectively. These nuclei are unstable and eventually proceed by the beta decay of 73Ga to 73Ge (stable). We search for the 73Ga decay exploiting the fact that it dominantly populates the 66.7 keV 73mGa state with half-life of 0.5 s. The nnn-decays of 76Ge that proceed via 73mGe are also included in our analysis. We find no signal candidate and place a limit on the sum of the decay widths of the inclusive tri-nucleon decays that corresponds to a lower lifetime limit of 1.2×1026 yr  (90% credible interval). This result improves previous limits for tri-nucleon decays by one to three orders of magnitude.

Liquid argon light collection and veto modeling in GERDA Phase II.

The ability to detect liquid argon scintillation light from within a densely packed high-purity germanium detector array allowed the Gerda experiment to reach an exceptionally low background rate in the search for neutrinoless double beta decay of 76 Ge. Proper modeling of the light propagation throughout the experimental setup, from any origin in the liquid argon volume to its eventual detection by the novel light read-out system, provides insight into the rejection capability and is a necessary ingredient to obtain robust background predictions. In this paper, we present a model of the Gerda liquid argon veto, as obtained by Monte Carlo simulations and constrained by calibration data, and highlight its application for background decomposition.

[The interoperability of IIEF-5 with EPIC-26 : Sexual function after radical prostatectomy]. / Die Übertragbarkeit von IIEF-5 (International Index of Erectile Function 5 Item Short Form) auf EPIC-26 (Expanded Prostate Cancer Index Composite 26) : Sexuelle Funktion nach radikaler Prostatektomie.

BACKGROUND: In the past, the IIEF­5 (International Index of Erectile Function 5 ) was predominantly used to measure erectile function in prostate cancer patients. Following international developments, the domain "sexuality" of the EPIC-26 (Expanded Prostate Cancer Index Composite 26) is increasingly used in Germany. OBJECTIVE: The aim of this work is to create a practicable comparison of the domain "sexuality" of the EPIC-26 with the IIEF­5 for treatment in Germany. This is particularly necessary for the evaluation of historical patient collectives. MATERIALS AND METHODS: For the evaluation, 2123 patients with prostate cancer confirmed by biopsy from 2014-2017 who completed both the IIEF­5 and the EPIC-26 were considered. Linear regression analyses are calculated to convert IIEF­5 sum scores to EPIC-26 sexuality domain scores. RESULTS: The correlation between IIEF­5 and the EPIC-26 domain score "sexuality" was 0.74, suggesting a high degree of content convergence between the constructs measured. While the standard error of the predicted values is relatively small, the prediction intervals are very wide. For example, for the critical IIEF­5 value of 22, the predicted value is 78.88 with a 95% prediction interval of 55.09 to 102.66. CONCLUSION: IIEF­5 and the Sexuality scale of the EPIC-26 measure a similar construct. The analysis shows that conversion of individual values is associated with great uncertainty. However, at the group level, the observed EPIC-26 "sexuality" score could be predicted quite accurately. This opens up the possibility of comparing the erectile function of cohorts of patients/test persons, even if this was collected with different measuring instruments.

On shape forming by contractile filaments in the surface of growing tissues.

Growing tissues are highly dynamic, and flow on sufficiently long timescales due to cell proliferation, migration, and tissue remodeling. As a consequence, growing tissues can often be approximated as viscous fluids. This means that the shape of microtissues growing in vitro is governed by their surface stress state, as in fluid droplets. Recent work showed that cells in the near-surface region of fibroblastic or osteoblastic microtissues contract with highly oriented actin filaments, thus making the surface properties highly anisotropic, in contrast to what is expected for an isotropic fluid. Here, we develop a model that includes mechanical anisotropy of the surface generated by contractile fibers and we show that mechanical equilibrium requires contractile filaments to follow geodesic lines on the surface. Constant pressure in the fluid forces these contractile filaments to be along geodesics with a constant normal curvature. We then take this into account to determine equilibrium shapes of rotationally symmetric bodies subjected to anisotropic surface stress states and derive a family of surfaces of revolution. A comparison with recently published shapes of microtissues shows that this theory accurately predicts both the surface shape and the direction of the actin filaments on the surface.

Erratum: First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c

This corrects the article DOI: 10.1103/PhysRevLett.125.011801.

Pulse shape analysis in Gerda Phase II.

The GERmanium Detector Array (Gerda) collaboration searched for neutrinoless double- ß decay in 76 Ge using isotopically enriched high purity germanium detectors at the Laboratori Nazionali del Gran Sasso of INFN. After Phase I (2011-2013), the experiment benefited from several upgrades, including an additional active veto based on LAr instrumentation and a significant increase of mass by point-contact germanium detectors that improved the half-life sensitivity of Phase II (2015-2019) by an order of magnitude. At the core of the background mitigation strategy, the analysis of the time profile of individual pulses provides a powerful topological discrimination of signal-like and background-like events. Data from regular 228 Th calibrations and physics data were both considered in the evaluation of the pulse shape discrimination performance. In this work, we describe the various methods applied to the data collected in Gerda Phase II corresponding to an exposure of 103.7 kg year. These methods suppress the background by a factor of about 5 in the region of interest around Q ß ß = 2039  keV, while preserving ( 81 ± 3 ) % of the signal. In addition, an exhaustive list of parameters is provided which were used in the final data analysis.

Psychometric properties of the PROMIS Preference score (PROPr) in patients with rheumatological and psychosomatic conditions.

BACKGROUND: The PROMIS Preference score (PROPr) is a new generic preference-based health-related quality of life (HRQoL) score that can be used as a health state utility (HSU) score for quality-adjusted life years (QALYs) in cost-utility analyses (CUAs). It is the first HSU score based on item response theory (IRT) and has demonstrated favorable psychometric properties in first analyses. The PROPr combines the seven PROMIS domains: cognition, depression, fatigue, pain, physical function, sleep disturbance, and ability to participate in social roles and activities. It was developed based on preferences of the US general population. The aim of this study was to validate the PROPr in a German inpatient sample and to compare it to the EQ-5D. METHODS: We collected PROPr and EQ-5D-5L data from 141 patients undergoing inpatient treatment in the rheumatology and psychosomatic departments. We evaluated the criterion and convergent validity, and ceiling and floor effects of the PROPr and compared those characteristics to those of the EQ-5D. RESULTS: The mean PROPr (0.26, 95% CI: 0.23; 0.29) and the mean EQ-5D (0.44, 95% CI: 0.38; 0.51) scores differed significantly (d = 0.18, p < 0.001). Compared to the EQ-5D, the PROPr scores were less scattered across the measurement range which has resulted in smaller confidence intervals of the mean scores. The Pearson correlation coefficient between the two scores was r = 0.72 (p < 0.001). Both scores showed fair agreement with an Intraclass Correlation Coefficient (ICC) of 0.48 (p < 0.05). The PROPr and EQ-5D demonstrated similar discrimination power across sex, age, and conditions. While the PROPr showed a floor effect, the EQ-5D showed a ceiling effect. CONCLUSION: The PROPr measures HSU considerably lower than the EQ-5D as a result of different construction, anchors and measurement ranges. Because QALYs derived with the EQ-5D are widely considered state-of-the-art, application of the PROPr for QALY measurements would be problematic.

Advances in multiscale image processing and its effects on image quality in skeletal radiography.

Multi-frequency processing (MFP) leads to enhanced image quality (IQ) of radiographs. This study is to determine the effect of third generation MFP (M3) on IQ in comparison to standard second-generation MFP (M2). 20 cadavers were examined and post-processing of radiographs was performed with both M2 and M3. Three readers blinded to the MFP used for each image independently compared corresponding image pairs according to overall IQ and depiction of bony structures and soft tissue (+ 2: notably better > 0: equal > - 2: notably worse). A significant deviation of the median grade from grade 0 (equal) (p < 0.01) for each evaluator A, B and C speaks against an equal image quality of M2- and M3-images. M3-images were categorized with better grades (+ 1, + 2) in 87.7% for overall image quality, in 90.4% for soft tissue and 81.8% for bony structures. M3 images showed significant higher averaged SNR and CNR for all investigated lower extremities than that of M2 images (0.031 < p < 0.049). The newest generation of MFP leads to significantly better depiction of anatomical structures and overall image quality than in images processed with the preceding generation of MFP. This provides increased diagnostic accuracy and further decreased radiation exposure.

Characterization of inverted coaxial 76 Ge detectors in GERDA for future double- ß decay experiments.

Neutrinoless double- ß decay of 76 Ge is searched for with germanium detectors where source and detector of the decay are identical. For the success of future experiments it is important to increase the mass of the detectors. We report here on the characterization and testing of five prototype detectors manufactured in inverted coaxial (IC) geometry from material enriched to 88% in 76 Ge. IC detectors combine the large mass of the traditional semi-coaxial Ge detectors with the superior resolution and pulse shape discrimination power of point contact detectors which exhibited so far much lower mass. Their performance has been found to be satisfactory both when operated in vacuum cryostat and bare in liquid argon within the Gerda setup. The measured resolutions at the Q-value for double- ß decay of 76 Ge ( Q ß ß  = 2039 keV) are about 2.1 keV full width at half maximum in vacuum cryostat. After 18 months of operation within the ultra-low background environment of the GERmanium Detector Array (Gerda) experiment and an accumulated exposure of 8.5 kg · year, the background index after analysis cuts is measured to be 4 . 9 - 3.4 + 7.3 × 10 - 4 counts / ( keV · kg · year ) around Q ß ß . This work confirms the feasibility of IC detectors for the next-generation experiment Legend.

Calibration of the Gerda experiment.

The GERmanium Detector Array (Gerda) collaboration searched for neutrinoless double- ß decay in 76 Ge with an array of about 40 high-purity isotopically-enriched germanium detectors. The experimental signature of the decay is a monoenergetic signal at Q ß ß = 2039.061 ( 7 )  keV in the measured summed energy spectrum of the two emitted electrons. Both the energy reconstruction and resolution of the germanium detectors are crucial to separate a potential signal from various backgrounds, such as neutrino-accompanied double- ß decays allowed by the Standard Model. The energy resolution and stability were determined and monitored as a function of time using data from regular 228 Th calibrations. In this work, we describe the calibration process and associated data analysis of the full Gerda dataset, tailored to preserve the excellent resolution of the individual germanium detectors when combining data over several years.

Image quality is resilient against tube voltage variations in post-mortem skeletal radiography with a digital flat-panel detector.

In recent phantom studies low-contrast detectability was shown to be independent from variations in tube voltage in digital radiography (DR) systems. To investigate the transferability to a clinical setting, the lower extremities of human cadavers were exposed at constant detector doses with different tube voltages in a certain range, as proposed in the phantom studies. Three radiologists independently graded different aspects of image quality (IQ) in a comparative analysis. The grades show no correlation between IQ and kV, which means that the readers were not able to recognize a significant IQ difference at different kV. Signal-to-noise and contrast-to-noise ratios showed no significant differences in IQ despite the kV-setting variations. These findings were observed from a limited kV range setting. Higher kV-settings resulted in lowest patient exposure at constant IQ. These results confirm the potential of DR-systems to contribute to standardization of examination protocols comparable to computed tomography. This may prevent the trend to overexpose. Further investigations in other body regions and other DR-systems are encouraged to determine transferability.

Development of an experimental facility for the study of microparticle initiated radio frequency vacuum breakdown.

An ongoing objective in the ion cyclotron range of frequencies (ICRF) systems is the improvement of power coupling to the plasma. During the last decade, this goal has been mainly pursued through the study of the coupling resistance, either by optimizing the antenna layout or by tailoring the scrape-off layer profile with gas puffing. Another approach is to increase the voltage handling capability of the ICRF system, limited by breakdown in the launchers or in the transmission lines. This paper describes the design of the ICRF Breakdown EXperiment (IBEX), a device to investigate fundamental aspects of radio frequency arcs under ICRF-relevant conditions. IBEX can achieve a peak voltage of 48 kV at 54 MHz with a 5 kW input power.

[Bed capacity analysis for an intensive care unit : Retrospective analysis and projection for need of intensive care beds in over 65 year olds with selected cardiovascular diseases]. / Bettenkapazitätsanalyse für eine internistische Intensivstation : Retrospektive Analyse und Projektion des Intensivbettenbedarfs bei über 65-Jährigen mit ausgewählten kardiovaskulären Erkrankungen.

BACKGROUND: The increasing number of elderly individuals in the population and the simultaneous increase of the intensive care demand emphasizes the relevance of an efficient bed capacity analysis. Particularly, cardiovascular diseases represent a frequently occurring disease in the population group over 65 years of age. The objective of the following paper is the analysis of the retrospective and prospective intensive care demand by patients over 65 years with 6 selected (cardiovascular) codes of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). METHODS: For the retrospective analysis, data from 2015-2017 were analyzed applying descriptive and bivariate methods. The analysis of the intensive care bed demand was based on the queuing theory. RESULTS: The monthly capacity utilization rates were constantly higher than the target capacity utilization rate of a maximum of 80% and in some cases even higher than 100%. In particular, the demand of patients with I50.14 was very high throughout the entire hospital. The bed demand analysis shows an increase from 9 needed beds in 2017 to 11 beds by 2030 for the 6 diagnosis groups. Regarding the 5 diagnosis groups without I50.14, only approximately half of the required beds were needed, retrospectively and in future. CONCLUSION: The effect of demographic change on the intensive care demand already exists, and a continuing, prospective increase of the demand is expected. The results underline the need of effective and demand-oriented intensive care capacity planning. However, prior to expanding bed capacities, the analysis of admission criteria of intensive care unit patients is necessary to reserve capacities primarily for patients with real intensive care needs.

Predicting EQ-5D-5L crosswalk from the PROMIS-29 profile for the United Kingdom, France, and Germany.

BACKGROUND: EQ-5D health state utilities (HSU) are commonly used in health economics to compute quality-adjusted life years (QALYs). The EQ-5D, which is country-specific, can be derived directly or by mapping from self-reported health-related quality of life (HRQoL) scales such as the PROMIS-29 profile. The PROMIS-29 from the Patient Reported Outcome Measures Information System is a comprehensive assessment of self-reported health with excellent psychometric properties. We sought to find optimal models predicting the EQ-5D-5L crosswalk from the PROMIS-29 in the United Kingdom, France, and Germany and compared the prediction performances with that of a US model. METHODS: We collected EQ-5D-5L and PROMIS-29 profiles and three samples representative of the general populations in the UK (n = 1509), France (n = 1501), and Germany (n = 1502). We used stepwise regression with backward selection to find the best models to predict the EQ-5D-5L crosswalk from all seven PROMIS-29 domains. We investigated the agreement between the observed and predicted EQ-5D-5L crosswalk in all three countries using various indices for the prediction performance, including Bland-Altman plots to examine the performance along the HSU continuum. RESULTS: The EQ-5D-5L crosswalk was best predicted in France (nRMSEFRA = 0.075, nMAEFRA = 0.052), followed by the UK (nRMSEUK = 0.076, nMAEUK = 0.053) and Germany (nRMSEGER = 0.079, nMAEGER = 0.051). The Bland-Altman plots show that the inclusion of higher-order effects reduced the overprediction of low HSU scores. CONCLUSIONS: Our models provide a valid method to predict the EQ-5D-5L crosswalk from the PROMIS-29 for the UK, France, and Germany.

Correlation of objective image quality and working length measurements in different CBCT machines: An ex vivo study.

To investigate potential correlations between objective CBCT image parameters and accuracy in endodontic working length determination ex vivo. Contrast-to-noise ratio (CNR) and spatial resolution (SR) as fundamental objective image parameters were examined using specific phantoms in seven different CBCT machines. Seven experienced observers were instructed and calibrated. The order of the CBCTs was randomized for each observer and observation. To assess intra-operator reproducibility, the procedure was repeated within six weeks with a randomized order of CBCT images. Multivariate analysis (MANOVA) did not reveal any influence of the combined image quality factors CNR and SR on measurement accuracy. Inter-operator reproducibility as assessed between the two observations was poor, with a mean intra-class correlation (ICC) of 0.48 (95%-CI  0.38, 0.59) for observation No. 1. and 0.40 (95%-CI 0.30, 0.51) for observation No. 2. Intra-operator reproducibility pooled over all observers between both observations was only moderate, with a mean ICC of 0.58 (95%-CI 0.52 to 0.64). Within the limitations of the study, objective image quality measures and exposure parameters seem not to have a significant influence on accuracy in determining endodontic root canal lengths in CBCT scans. The main factor of variance is the observer.

First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c

We present the first search for bosonic superweakly interacting massive particles (super-WIMPs) as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-ß decay experiment which operates high-purity germanium detectors enriched in ^{76}Ge in an ultralow background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60 keV/c^{2} to 1 MeV/c^{2}. No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120 keV/c^{2} have been set. As an example, at a mass of 150 keV/c^{2} the most stringent direct limits on the dimensionless couplings of axionlike particles and dark photons to electrons of g_{ae}<3×10^{-12} and α^{'}/α<6.5×10^{-24} at 90% credible interval, respectively, were obtained.