Predominantly defective CD8+ T cell immunity to SARS-CoV-2 mRNA vaccination in lung transplant recipients.

BACKGROUND: Although mRNA vaccines have overall efficacy preventing morbidity/mortality from SARS-CoV-2 infection, immunocompromised persons remain at risk. Antibodies mostly prevent early symptomatic infection, but cellular immunity, particularly the virus-specific CD8+ T cell response, is protective against disease. Defects in T cell responses to vaccination have not been well characterized in immunocompromised hosts; persons with lung transplantation are particularly vulnerable to vaccine failure with severe illness. METHODS: Comparison groups included persons with lung transplantation and no history of COVID-19 (21 and 19 persons after initial mRNA vaccination and a third booster vaccination respectively), 8 lung transplantation participants recovered from COVID-19, and 22 non-immunocompromised healthy control individuals after initial mRNA vaccination (without history of COVID-19). Anti-spike T cell responses were assayed by stimulating peripheral blood mononuclear cells (PBMCs) with pooled small overlapping peptides spanning the SARS-CoV-2 spike protein, followed by intracellular cytokine staining (ICS) and flow cytometry for release of cytokines in response to stimulation, including negative controls (no peptide stimulation) and positive controls (phorbol myristate acetate [PMA] and ionomycin stimulation). To evaluate for low frequency memory responses, PBMCs were cultured in the presence of the mRNA-1273 vaccine for 14 days before this evaluation. RESULTS: Ionophore stimulation of PBMCs revealed a less inflammatory milieu in terms of interleukin (IL)-2, IL-4, and IL-10 profiling in lung transplantation individuals, reflecting the effect of immunosuppressive treatments. Similar to what we previously reported in healthy vaccinees, spike-specific responses in lung transplantation recipients were undetectable (< 0.01%) when tested 2 weeks after vaccination or later, but were detectable after in vitro culture of PBMCs with mRNA-1273 vaccine to enrich memory T cell responses. This was also seen in COVID-19-recovered lung transplantation recipients. Comparison of their enriched memory responses to controls revealed relatively similar CD4+ T cell memory, but markedly reduced CD8+ T cell memory both after primary vaccination or a booster dose. These responses were not correlated to age or time after transplantation. The vaccine-induced CD4+ and CD8+ responses correlated well in the healthy control group, but poorly in the transplantation groups. CONCLUSIONS: These results reveal a specific defect in CD8+ T cells, which have key roles both in transplanted organ rejection but also antiviral effector responses. Overcoming this defect will require strategies to enhance vaccine immunogenicity in immunocompromised persons.

Clinical application of breathing-adapted 4D CT: image quality comparison to conventional 4D CT.

PURPOSE: 4D CT imaging is an integral part of 4D radiotherapy workflows. However, 4D CT data often contain motion artifacts that mitigate treatment planning. Recently, breathing-adapted 4D CT (i4DCT) was introduced into clinical practice, promising artifact reduction in in-silico and phantom studies. Here, we present an image quality comparison study, pooling clinical patient data from two centers: a new i4DCT and a conventional spiral 4D CT patient cohort. METHODS: The i4DCT cohort comprises 129 and the conventional spiral 4D CT cohort 417 4D CT data sets of lung and liver tumor patients. All data were acquired for treatment planning. The study consists of three parts: illustration of image quality in selected patients of the two cohorts with similar breathing patterns; an image quality expert rater study; and automated analysis of the artifact frequency. RESULTS: Image data of the patients with similar breathing patterns underline artifact reduction by i4DCT compared to conventional spiral 4D CT. Based on a subgroup of 50 patients with irregular breathing patterns, the rater study reveals a fraction of almost artifact-free scans of 89% for i4DCT and only 25% for conventional 4D CT; the quantitative analysis indicated a reduction of artifact frequency by 31% for i4DCT. CONCLUSION: The results demonstrate 4D CT image quality improvement for patients with irregular breathing patterns by breathing-adapted 4D CT in this first corresponding clinical data image quality comparison study.

Electronically monitored occlusion therapy in amblyopia with eccentric fixation.

PURPOSE: Amblyopia with eccentric fixation, especially when not diagnosed early, is a therapeutic challenge, as visual outcome is known to be poorer than in amblyopia with central fixation. Consequently, treatment after late diagnosis is often denied. Electronic monitoring of occlusion provides us the chance to gain first focussed insight into age-dependent dose response and treatment efficiency, as well as the shift of fixation in this rare group of paediatric patients. METHODS: In our prospective pilot study, we examined amblyopes with eccentric fixation during 12 months of occlusion treatment. We evaluated their visual acuity, recorded patching duration using a TheraMon®-microsensor, and determined their fixation with a direct ophthalmoscope. Dose-response relationship and treatment efficiency were calculated. RESULTS: The study included 12 participants with strabismic and combined amblyopia aged 2.9-12.4 years (mean 6.5). Median prescription of occlusion was 7.7 h/day (range 6.6-9.9) and median daily received occlusion was 5.2 h/day (range 0.7-9.7). At study end, median acuity gain was 0.6 log units (range 0-1.6) and residual interocular visual acuity difference (IOVAD) 0.3 log units (range 0-1.8). There was neither significant acuity gain nor reduction in IOVAD after the 6th month of treatment. Children younger than 4 years showed best response with lowest residual IOVAD at study end. Efficiency calculation showed an acuity gain of approximately one line from 100 h of patching in the first 2 months and half a line after 6 months. There was a significant decline of treatment efficiency with age (p = 0.01). Foveolar fixation was achieved after median 3 months (range 1-6). Three patients (> 6 years) did not gain central fixation. CONCLUSION: Eccentric fixation is a challenge to therapy success. Based on electronic monitoring, our study quantified for the first time the reduction of treatment efficiency with increasing age in amblyopes with eccentric fixation. Despite some improvement in patients up to 8 years, older patients showed significantly lower treatment efficiency. In younger patients with good adherence, despite poor initial acuity, central fixation and low residual IOVAD could be attained after median 3 months. Hence, the necessity of early diagnosis and intensive occlusion should be emphasized.

HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes.

Certain Major Histocompatibility-I (MHC-I) types are associated with superior immune containment of HIV-1 infection by CD8+ cytotoxic T lymphocytes (CTLs), but the mechanisms mediating this containment are difficult to elucidate in vivo. Here we provide controlled assessments of fitness landscapes and CTL-imposed constraints for immunodominant epitopes presented by two protective (B*57 and B*27) and one non-protective (A*02) MHC-I types. Libraries of HIV-1 with saturation mutagenesis of CTL epitopes are propagated with and without CTL selective pressure to define the fitness landscapes for epitope mutation and escape from CTLs via deep sequencing. Immunodominant B*57- and B*27- present epitopes are highly limited in options for fit mutations, with most viable variants recognizable by CTLs, whereas an immunodominant A*02 epitope-presented is highly permissive for mutation, with many options for CTL evasion without loss of viability. Generally, options for evasion overlap considerably between CTL clones despite highly distinct T cell receptors. Finally, patterns of variant recognition suggest population-wide CTL selection for the A*02-presented epitope. Overall, these findings indicate that these protective MHC-I types yield CTL targeting of highly constrained epitopes, and underscore the importance of blocking public escape pathways for CTL-based interventions against HIV-1.

Neuroradiological and clinical features in ophthalmoplegia.

PURPOSE: Especially in acute onset of ophthalmoplegia, efficient neuroradiological evaluation is necessary to assist differential diagnosis, clinical course, and treatment options. METHODS: Different manifestations of ophthalmoplegia are explained and illustrated by characteristic neuroradiological and clinical findings. RESULTS: To present those ophthalmoplegic disorders in a clear manner, this review refers to different neuroanatomical structures and compartments. From neuroophthalmological point of view, diseases going ahead with ophthalmoplegia can be divided into (1) efferent infranuclear/peripheral disturbances involving oculomotor cranial nerves, (2) conjugate gaze abnormalities due to internuclear or supranuclear lesions, and (3) diseases of the extraocular eye muscles or their impairment due to intraorbital pathologies. CONCLUSION: The knowledge of the relationship between neurological findings in ophthalmoplegia and involved neuroanatomical structures is crucial, and neuroradiology can be focused on circumscribed anatomical regions, using optimized investigation protocols.

Identification of C-terminal Regions in Arabidopsis thaliana Phytochelatin Synthase 1 Specifically Involved in Activation by Arsenite.

Phytochelatins (PCs) are major chelators of toxic elements including inorganic arsenic (As) in plant cells. Their synthesis confers tolerance and influences within-plant mobility. Previous studies had shown that various metal/metalloid ions differentially activate PC synthesis. Here we identified C-terminal parts involved in arsenite- [As(III)] dependent activation of AtPCS1, the primary Arabidopsis PC synthase. The T-DNA insertion in the AtPCS1 mutant cad1-6 causes a truncation in the C-terminal regulatory domain that differentially affects activation by cadmium (Cd) and zinc (Zn). Comparisons of cad1-6 with the AtPCS1 null mutant cad1-3 and the double mutant of tonoplast PC transporters abcc1/2 revealed As(III) hypersensitivity of cad1-6 equal to that of cad1-3. Both cad1-6 and cad1-3 showed increased As distribution to shoots compared with Col-0, whereas Zn accumulation in shoots was equally lower in cad1-6 and cad1-3. Supporting these phenotypes of cad1-6, PC accumulation in the As(III)-exposed plants were at trace level in both cad1-6 and cad1-3, suggesting that the truncated AtPCS1 of cad1-6 is defective in PCS activity in response to As(III). Analysis of a C-terminal deletion series of AtPCS1 using the PCS-deficient mutant of fission yeast suggested important regions within the C-terminal domain for As(III)-dependent PC synthesis, which were different from the regions previously suggested for Cd- or Zn-dependent activation. Interestingly, we identified a truncated variant more strongly activated than the wild-type protein. This variant could potentially be used as a tool to better restrict As mobility in plants.

Phytochelatin Synthase has Contrasting Effects on Cadmium and Arsenic Accumulation in Rice Grains.

Phytochelatin (PC) synthesis has been well demonstrated as a major metal tolerance mechanism in Arabidopsis thaliana, whereas its contribution to long-distance element transport especially in monocots remains elusive. Using rice as a cereal model, we examined physiological roles of Oryza sativa phytochelatin synthase 1 (OsPCS1) in the distribution and detoxification of arsenic (As) and cadmium (Cd), two toxic elements associated with major food safety concerns. First, we isolated four different transcript variants of OsPCS1 as well as one from OsPCS2. Quantitative real-time reverse transcription-PCR (RT-PCR) of each OsPCS transcript in rice seedlings suggested that expression of OsPCS1full, the longest OsPCS1 variant, was most abundant, followed by OsPCS2. Heterologous expression of OsPCS variants in PCS-deficient mutants of Schizosaccharomyces pombe and A. thaliana suggested that OsPCS1full possessed PCS activity in response to As(III) and Cd while the activity of other PCS variants was very low. To address physiological functions in toxic element tolerance and accumulation, two independent OsPCS1 mutant rice lines (a T-DNA and a Tos17 insertion line) were identified. The OsPCS1 mutants exhibited increased sensitivity to As(III) and Cd in hydroponic experiments, showing the importance of OsPCS1-dependent PC synthesis for rice As(III) and Cd tolerance. Elemental analyses of rice plants grown in soil with environmentally relevant As and Cd concentrations showed increased As accumulation and decreased Cd accumulation in grains of the T-DNA line. The Tos17 mutant also exhibited the reduced Cd accumulation phenotype. These contrasting effects on As and Cd distribution to grains suggest the existence of at least partially distinct PC-dependent pathways for As and Cd.

Phytochelatin Synthesis Promotes Leaf Zn Accumulation of Arabidopsis thaliana Plants Grown in Soil with Adequate Zn Supply and is Essential for Survival on Zn-Contaminated Soil.

Phytochelatin (PC) synthesis is essential for the detoxification of non-essential metals such as cadmium (Cd). In vitro experiments with Arabidopsis thaliana seedlings had indicated a contribution to zinc (Zn) tolerance as well. We addressed the physiological role of PC synthesis in Zn homeostasis of plants under more natural conditions. Growth responses, PC accumulation and leaf ionomes of wild-type and AtPCS1 mutant plants cultivated in different soils representing adequate Zn supply, Zn deficiency and Zn excess were analyzed. Growth on Zn-contaminated soil triggers PC synthesis and is strongly impaired in PC-deficient mutants. In fact, the contribution of AtPCS1 to tolerating Zn excess is comparable with that of the major Zn tolerance factor MTP1. For plants supplied with a normal level of Zn, a significant reduction in leaf Zn accumulation of AtPCS1 mutants was detected. In contrast, AtPCS1 mutants grown under Zn-limited conditions showed wild-type levels of Zn accumulation, suggesting the operation of distinct Zn translocation pathways. Contrasting phenotypes of the tested AtPCS1 mutant alleles upon growth in Zn- or Cd-contaminated soil indicated differential activation of PC synthesis by these metals. Experiments with truncated versions identified a part of the AtPCS1 protein required for the activation by Zn but not by Cd.

Benchmarking machine learning-based real-time respiratory signal predictors in 4D SBRT.

BACKGROUND: Stereotactic body radiotherapy of thoracic and abdominal tumors has to account for respiratory intrafractional tumor motion. Commonly, an external breathing signal is continuously acquired that serves as a surrogate of the tumor motion and forms the basis of strategies like breathing-guided imaging and gated dose delivery. However, due to inherent system latencies, there exists a temporal lag between the acquired respiratory signal and the system response. Respiratory signal prediction models aim to compensate for the time delays and to improve imaging and dose delivery. PURPOSE: The present study explores and compares six state-of-the-art machine and deep learning-based prediction models, focusing on real-time and real-world applicability. All models and data are provided as open source and data to ensure reproducibility of the results and foster reuse. METHODS: The study was based on 2502 breathing signals ( t t o t a l ≈ 90 $t_{total} \approx 90$  h) acquired during clinical routine, split into independent training (50%), validation (20%), and test sets (30%). Input signal values were sampled from noisy signals, and the target signal values were selected from corresponding denoised signals. A standard linear prediction model (Linear), two state-of-the-art models in general univariate signal prediction (Dlinear, Xgboost), and three deep learning models (Lstm, Trans-Enc, Trans-TSF) were chosen. The prediction performance was evaluated for three different prediction horizons (480, 680, and 920 ms). Moreover, the robustness of the different models when applied to atypical, that is, out-of-distribution (OOD) signals, was analyzed. RESULTS: The Lstm model achieved the lowest normalized root mean square error for all prediction horizons. The prediction errors only slightly increased for longer horizons. However, a substantial spread of the error values across the test signals was observed. Compared to typical, that is, in-distribution test signals, the prediction accuracy of all models decreased when applied to OOD signals. The more complex deep learning models Lstm and Trans-Enc showed the least performance loss, while the performance of simpler models like Linear dropped the most. Except for Trans-Enc, inference times for the different models allowed for real-time application. CONCLUSION: The application of the Lstm model achieved the lowest prediction errors. Simpler prediction filters suffer from limited signal history access, resulting in a drop in performance for OOD signals.

A New Iterative Metal Artifact Reduction Algorithm for Both Energy-Integrating and Photon-Counting CT Systems.

OBJECTIVES: The aim of this study was to introduce and evaluate a new metal artifact reduction framework (iMARv2) that addresses the drawbacks (residual artifacts after correction and user preferences for image quality) associated with the current clinically applied iMAR. MATERIALS AND METHODS: A new iMARv2 has been introduced, combining the current iMAR with new modular components to remove residual metal artifacts after image correction. The postcorrection image impression is adjustable with user-selectable strength settings. Phantom scans from an energy-integrating and a photon-counting detector CT were used to assess image quality, including a Gammex phantom and anthropomorphic phantoms. In addition, 36 clinical cases (with metallic implants such as dental fillings, hip replacements, and spinal screws) were reconstructed and evaluated in a blinded and randomized reader study. RESULTS: The Gammex phantom showed lower HU errors compared with the uncorrected image at almost all iMAR and iMARv2 settings evaluated, with only minor differences between iMAR and the different iMARv2 settings. In addition, the anthropomorphic phantoms showed a trend toward lower errors with higher iMARv2 strength settings. On average, the iMARv2 strength 3 performed best of all the clinical reconstructions evaluated, with a significant increase in diagnostic confidence and decrease in artifacts. All hip and dental cases showed a significant increase in diagnostic confidence and decrease in artifact strength, and the improvements from iMARv2 in the dental cases were significant compared with iMAR. There were no significant improvements in the spine. CONCLUSIONS: This work has introduced and evaluated a new method for metal artifact reduction and demonstrated its utility in routine clinical datasets. The greatest improvements were seen in dental fillings, where iMARv2 significantly improved image quality compared with conventional iMAR.

Development and Validation of a Deep-Learning-Based Algorithm for Detecting and Classifying Metallic Implants in Abdominal and Spinal CT Topograms.

PURPOSE: To develop and validate a deep-learning-based algorithm (DLA) that is designed to segment and classify metallic objects in topograms of abdominal and spinal CT. METHODS: DLA training for implant segmentation and classification was based on a U-net-like architecture with 263 annotated hip implant topograms and 2127 annotated spine implant topograms. The trained DLA was validated with internal and external datasets. Two radiologists independently reviewed the external dataset consisting of 2178 abdomen anteroposterior (AP) topograms and 515 spine AP and lateral topograms, all collected in a consecutive manner. Sensitivity and specificity were calculated per pixel row and per patient. Pairwise intersection over union (IoU) was also calculated between the DLA and the two radiologists. RESULTS: The performance parameters of the DLA were consistently >95% in internal validation per pixel row and per patient. DLA can save 27.4% of reconstruction time on average in patients with metallic implants compared to the existing iMAR. The sensitivity and specificity of the DLA during external validation were greater than 90% for the detection of spine implants on three different topograms and for the detection of hip implants on abdominal AP and spinal AP topograms. The IoU was greater than 0.9 between the DLA and the radiologists. However, the DLA training could not be performed for hip implants on spine lateral topograms. CONCLUSIONS: A prototype DLA to detect metallic implants of the spine and hip on abdominal and spinal CT topograms improves the scan workflow with good performance for both spine and hip implants.

Optimized raw data selection for artifact reduction of breathing controlled four-dimensional sequence scanning.

Background and purpose: Even with most breathing-controlled four-dimensional computed tomography (4DCT) algorithms image artifacts caused by single significant longer breathing still occur, resulting in negative consequences for radiotherapy. Our study presents first phantom examinations of a new optimized raw data selection and binning algorithm, aiming to improve image quality and geometric accuracy without additional dose exposure. Materials and methods: To validate the new approach, phantom measurements were performed to assess geometric accuracy (volume fidelity, root mean square error, Dice coefficient of volume overlap) for one- and three-dimensional tumor motion trajectories with and without considering motion hysteresis effects. Scans without significantly longer breathing cycles served as references. Results: Median volume deviations between optimized approach and reference of at maximum 1% were obtained considering all movements. In comparison, standard reconstruction yielded median deviations of 9%, 21% and 12% for one-dimensional, three-dimensional, and hysteresis motion, respectively. Measurements in one- and three-dimensional directions reached a median Dice coefficient of 0.970 ± 0.013 and 0.975 ± 0.012, respectively, but only 0.918 ± 0.075 for hysteresis motions averaged over all measurements for the optimized selection. However, for the standard reconstruction median Dice coefficients were 0.845 ± 0.200, 0.868 ± 0.205 and 0.915 ± 0.075 for one- and three-dimensional as well as hysteresis motions, respectively. Median root mean square errors for the optimized algorithm were 30 ± 16 HU2 and 120 ± 90 HU2 for three-dimensional and hysteresis motions, compared to 212 ± 145 HU2 and 130 ± 131 HU2 for the standard reconstruction. Conclusions: The algorithm was proven to reduce 4DCT-related artifacts due to missing projection data without further dose exposure. An improvement in radiotherapy treatment planning due to better image quality can be expected.

Impact of breathing signal-guided dose modulation on step-and-shoot 4D CT image reconstruction.

BACKGROUND: Breathing signal-guided 4D CT sequence scanning such as the intelligent 4D CT (i4DCT) approach reduces imaging artifacts compared to conventional 4D CT. By design, i4DCT captures entire breathing cycles during beam-on periods, leading to redundant projection data and increased radiation exposure to patients exhibiting prolonged exhalation phases. A recently proposed breathing-guided dose modulation (DM) algorithm promises to lower the imaging dose by temporarily reducing the CT tube current, but the impact on image reconstruction and the resulting images have not been investigated. PURPOSE: We evaluate the impact of breathing signal-guided DM on 4D CT image reconstruction and corresponding images. METHODS: This study is designed as a comparative and retrospective analysis based on 104 4D CT datasets. Each dataset underwent retrospective reconstruction twice: (a) utilizing the acquired clinical projection data for reconstruction, which yields reference image data, and (b) excluding projections acquired during potential DM phases from image reconstruction, resulting in DM-affected image data. Resulting images underwent automatic organ segmentation (lung/liver). (Dis)Similarity of reference and DM-affected images were quantified by the Dice coefficient of the entire organ masks and the organ overlaps within the DM-affected slices. Further, for lung cases, (a) and (b) were deformably registered and median magnitudes of the obtained displacement field were computed. Eventually, for 17 lung cases, gross tumor volumes (GTV) were recontoured on both (a) and (b). Target volume similarity was quantified by the Hausdorff distance. RESULTS: DM resulted in a median imaging dose reduction of 15.4% (interquartile range [IQR]: 11.3%-19.9%) for the present patient cohort. Dice coefficients for lung ( n = 73 $n=73$ ) and liver ( n = 31 $n=31$ ) patients were consistently high for both the entire organs and the DM-affected slices (IQR lung: 0.985 / 0.982 $0.985/0.982$ [entire lung/DM-affected slices only] to 0.992 / 0.989 $0.992/0.989$ ; IQR liver: 0.977 / 0.972 $0.977/0.972$ to 0.986 / 0.986 $0.986/0.986$ ), demonstrating that DM did not cause organ distortions or alterations. Median displacements for DM-affected to reference image registration varied; however, only two out of 73 cases exhibited a median displacement larger than one isotropic 1 mm 3 ${\rm mm}^3$ voxel size. The impact on GTV definition for the end-exhalation phase was also minor (median Hausdorff distance: 0.38 mm, IQR: 0.15-0.46 mm). CONCLUSION: This study demonstrates that breathing signal-guided DM has a minimal impact on image reconstruction and image appearance while improving patient safety by reducing dose exposure.

Human T cells expressing two additional receptors (TETARs) specific for HIV-1 recognize both epitopes.

Adoptive TCR transfer against rapidly mutating targets, such as HIV-1 or cancer, must counteract corresponding immune escape. Hence, we generated T cells expressing two additional receptors (TETARs) specific for HIV-1 by TCR mRNA electroporation. An HLA-A2-restricted gag-specific TCR and an HLA-B13-restricted nef-specific TCR were chosen. When both TCRs were transfected simultaneously, strong competitive effects occurred that were overcome by replacing the human constant domains of one TCR with murine counterparts and adapting the amounts of TCR-RNA used for transfection. The resulting TETAR responded to both epitopes with cytokine secretion and cytotoxic function. Cell sorting revealed that one individual cell indeed recognized both epitopes. The T cells diminished their reactivity to each epitope after stimulation but sequentially killed targets that presented the gag epitope and then targets that presented the nef epitope, or vice versa. Taken together, TETARs represent a sophisticated tool to study TCR functionality and might be a useful strategy in immunotherapy.

[Early Psychiatric Patient Registration and the Case of Wuerttemberg]. / Das "Kataster für württembergische Psychiatriepatienten" und der Beginn der systematischen Patientenerfassung in der Psychiatrie.

This article provides both an analysis of the impact of medical statistics on psychiatric research as well as biographical information on one of its central protagonists, Württemberg medical doctor Wilhelm Weinberg. Against the background of the assumption of genetic inheritance of mental illnesses, a paradigm shift took place in the sense of a further development of so-called statistics for the insane. In addition to innovative diagnostics and nosology of the Kraepelin school, the study of human genetics was expected to become a promising step towards the predictability of mental illnesses. In particular, psychiatrist and racial hygienist Ernst Rüdin did thus integrate Weinberg's research findings. Weinberg became the founding figure of a central patient register in Wuerttemberg. During National Socialism, however, usage of this register shifted from being an instrument for research to one of establishing a hereditary biological inventory.

A Multimodal A* Algorithm to Solve the Two-Dimensional Optimization Problem of Accompanying a Person for an Intelligent Wheelchair.

Impaired mobility have far-reaching consequences for handicapped persons and their relatives. Mobile robotic technologies enable intelligent wheelchairs to regain mobility for those affected. Multiple research projects address human aware navigation and the task of following a person for assistive robots. But just a few projects focus on accompanying a person to enable social interaction. Therefore, we present a navigation system for indoor navigation in dynamic and cluttered environments as well as a novel algorithm for accompanying a person.First, we developed an autonomous driving wheelchair for indoor navigation based on the robot operating system (ROS). Thereby, a multi sensor setup using cameras and laser scanner enables localization within a map. People are detected by the same sensors and tracked by a Kalman filter. Afterwards we propose a novel algorithm to achieve a dynamic accompanying behaviour. An attractiveness distribution is introduced to evaluate the possible accompanying positions next to the manually selected target person regarding social interaction. The resulting two-dimensional optimization problem is solved by a novel multimodal extension of the A* algorithm.The proposed intelligent wheelchair is able to navigate in indoor environments and to accompany any person. In addition it allows social interaction while walking to relieve relatives or nursing staff, which otherwise need to push the wheelchair. The aim is to increase participation in everyday life for those affected.

Dose reduction in sequence scanning 4D CT imaging through respiratory signal-guided tube current modulation: A feasibility study.

BACKGROUND: Respiratory signal-guided 4D CT sequence scanning such as the recently introduced Intelligent 4D CT (i4DCT) approach reduces image artifacts compared to conventional 4D CT, especially for irregular breathing. i4DCT selects beam-on periods during scanning such that data sufficiency conditions are fulfilled for each couch position. However, covering entire breathing cycles during beam-on periods leads to redundant projection data and unnecessary dose to the patient during long exhalation phases. PURPOSE: We propose and evaluate the feasibility of respiratory signal-guided dose modulation (i.e., temporary reduction of the CT tube current) to reduce the i4DCT imaging dose while maintaining high projection data coverage for image reconstruction. METHODS: The study is designed as an in-silico feasibility study. Dose down- and up-regulation criteria were defined based on the patients' breathing signals and their representative breathing cycle learned before and during scanning. The evaluation (including an analysis of the impact of the dose modulation criteria parameters) was based on 510 clinical 4D CT breathing curves. Dose reduction was determined as the fraction of the downregulated dose delivery time to the overall beam-on time. Furthermore, under the assumption of a 10-phase 4D CT and amplitude-based reconstruction, beam-on periods were considered negatively affected by dose modulation if the downregulation period covered an entire phase-specific amplitude range for a specific breathing phase (i.e., no appropriate reconstruction of the phase image possible for this specific beam-on period). Corresponding phase-specific amplitude bins are subsequently denoted as compromised bins. RESULTS: Dose modulation resulted in a median dose reduction of 10.4% (lower quartile: 7.4%, upper quartile: 13.8%, maximum: 28.6%; all values corresponding to a default parameterization of the dose modulation criteria). Compromised bins were observed in 1.0% of the beam-on periods (72 / 7370 periods) and affected 10.6% of the curves (54/510 curves). The extent of possible dose modulation depends strongly on the individual breathing patterns and is weakly correlated with the median breathing cycle length (Spearman correlation coefficient 0.22, p < 0.001). Moreover, the fraction of beam-on periods with compromised bins is weakly anti-correlated with the patient's median breathing cycle length (Spearman correlation coefficient -0.24; p < 0.001). Among the curves with the 17% longest average breathing cycles, no negatively affected beam-on periods were observed. CONCLUSION: Respiratory signal-guided dose modulation for i4DCT imaging is feasible and promises to significantly reduce the imaging dose with little impact on projection data coverage. However, the impact on image quality remains to be investigated in a follow-up study.

Working from home and management controls.

The Covid-19 pandemic and the corresponding shift toward working from home (WFH) amplifies control problems within organizations and poses severe challenges for management control as employees' tasks are difficult to observe under WFH conditions. We examine the association between WFH and action controls. Based on a survey among employees in a large international corporation, we find that under WFH conditions the organization more intensively uses standardization and planning participation. We also examine the association between WFH and employee outcomes. The findings suggest that WFH is associated with more time employees spend in meetings and a higher job focus. Overall, the study adds to the literature by exploring the association between WFH and the use of management controls in organizations.

A nonlinear scaling-based normalized metal artifact reduction to reduce low-frequency artifacts in energy-integrating and photon-counting CT.

BACKGROUND: Metal within the scan plane can cause severe artifacts when reconstructing X-ray computed tomography (CT) scans. Both in clinical use and recent research, normalized metal artifact reduction (NMAR) has established as the reference method for correcting metal artifacts, but NMAR introduces inconsistencies within the sinogram, which can cause additional low-frequency artifacts after image reconstruction. PURPOSE: This paper introduces an extension to NMAR by applying a nonlinear scaling function (NLS-NMAR) to reduce low-frequency artifacts, which get introduced by the reconstruction of interpolation-edge-related sinogram inconsistencies in the normalized sinogram domain. METHODS: After linear interpolation of the metal trace, an NLS function is applied in the prior-normalized sinogram domain to reduce the impact of the interpolation edges during filtered backprojection. After sinogram denormalization and image reconstruction, the low frequencies of the NLS image are combined with different high frequencies to restore anatomic details. An anthropomorphic dental phantom with removable metal inserts was utilized on two different CT systems to quantitatively assess the artifact reduction performance in terms of HU deviations and the root-mean-square-error within relevant regions of interest. Clinical dental examples were assessed to qualitatively demonstrate the problem of the interpolation-related blooming as well as to demonstrate the performance of the NLS function to reduce respective artifacts. To quantitatively prove HU consistency, HU values were assessed in central ROIs in the clinical cases. In addition, single clinical cases of a hip replacement and pedicle screws in the spine are shown to demonstrate the method's results in other body regions. RESULTS: The NLS-NMAR can minimize the effect of interpolation-related sinogram inconsistencies and thus reduce resulting hyperdense blooming artifacts. In the phantom results, the reconstructions with the NLS-NMAR-corrected low frequencies demonstrate the lowest error. In the qualitative assessment of the clinical data, the NLS-NMAR shows a tremendous enhancement in image quality, also performing best within all assessed images series. CONCLUSION: The NLS-NMAR provides a small yet effective extension to conventional NMAR by reducing low-frequency hyperdense metal trace-interpolation-related artifacts in computed tomography.