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Abstract Van der Waals heterostructures provide a versatile platform for tailoring electronic properties through the integration of two-dimensional materials. Among these combinations, the interaction between bilayer graphene and transition metal dichalcogenides (TMDs) stands out due to its potential for inducing spin–orbit coupling (SOC) in graphene. Future devices concepts require the understanding of the precise nature of SOC in TMD/bilayer graphene heterostructures and its influence on electronic transport phenomena. Here, we experimentally confirm the presence of two distinct types of SOC – Ising (Δ I = 1.55 meV) and Rashba (Δ R = 2.5 meV) – in bilayer graphene when interfaced with molybdenum disulfide. Furthermore, we reveal a non-monotonic trend in conductivity with respect to the electric displacement field at charge neutrality. This phenomenon is ascribed to the existence of single-particle gaps induced by the Ising SOC, which can be closed by a critical displacement field. Our findings also unveil sharp peaks in the magnetoconductivity around the critical displacement field, challenging existing theoretical models.

Abstract Identifying cellular identities is a key use case in single-cell transcriptomics. While machine learning has been leveraged to automate cell annotation predictions for some time, there has been little progress in scaling neural networks to large data sets and in constructing models that generalize well across diverse tissues. Here, we propose scTab, an automated cell type prediction model specific to tabular data, and train it using a novel data augmentation scheme across a large corpus of single-cell RNA-seq observations (22.2 million cells). In this context, we show that cross-tissue annotation requires nonlinear models and that the performance of scTab scales both in terms of training dataset size and model size. Additionally, we show that the proposed data augmentation schema improves model generalization. In summary, we introduce a de novo cell type prediction model for single-cell RNA-seq data that can be trained across a large-scale collection of curated datasets and demonstrate the benefits of using deep learning methods in this paradigm.

Abstract Small‐scale robots offer significant potential in minimally invasive medical procedures. Due to the nature of soft biological tissues, however, robots are exposed to complex environments with various challenges in locomotion, which is essential to overcome for useful medical tasks. A single mini‐robot often provides insufficient force on slippery biological surfaces to carry medical instruments, such as a fluid catheter or an electrical wire. Here, for the first time, a team of millirobots (TrainBot) is reported to generate around two times higher actuating force than a TrainBot unit by forming a convoy to collaboratively carry long and heavy cargos. The feet of each unit are optimized to increase the propulsive force around three times so that it can effectively crawl on slippery biological surfaces. A human‐scale permanent magnetic set‐up is developed to wirelessly actuate and control the TrainBot to transport heavy and lengthy loads through narrow biological lumens, such as the intestine and the bile duct. The first electrocauterization performed by the TrainBot is demonstrated to relieve a biliary obstruction and open a tunnel for fluid drainage and drug delivery. The developed technology sheds light on the collaborative strategy of small‐scale robots for future minimally invasive surgical procedures.

Aims: To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health. Methods: Patient-reported outcome measure (PROM) data measuring knee health were obtained from the NHS PROMs dataset and Total or Partial Knee Arthroplasty Trial (TOPKAT). Assumptions for common scale modelling were tested. A graded response model (fitted to OKS item responses in the NHS PROMs dataset) was used as an anchor to calibrate paired HAAS items from the TOPKAT dataset. Information curves for the combined OKS-HAAS model were plotted. Bland-Altman analysis was used to compare common scale scores derived from OKS and HAAS items. A conversion table was developed to map between HAAS, OKS, and the common scale. Results: We included 3,329 response sets from 528 patients undergoing knee arthroplasty. These generally met the assumptions of unidimensionality, monotonicity, local independence, and measurement invariance. The HAAS items provided more information than OKS items at high levels of knee health. Combining both instruments resulted in higher test-level information than either instrument alone. The mean error between common scale scores derived from the OKS and HAAS was 0.29 logits. Conclusion: The common scale allowed more precise measurement of knee health than use of either the OKS or HAAS individually. These techniques for mapping PROM instruments may be useful for the standardization of outcome reporting, and pooling results across studies that use either PROM in individual-patient meta-analysis. Cite this article: Bone Joint Res 2023;12(10):624–635.

Abstract Background The PROMIS Preference score (PROPr) is a new health state utility (HSU) score that aims to comprehensively incorporate the biopsychosocial model of health and apply favorable psychometric properties from the descriptive PROMIS system to HSU measurements. However, minimal evidence concerning comparisons to the EQ-5D-3L and the PROPr’s capability to differentiate clinical severity are available. Therefore, the aim of this study was to compare the PROPr to the EQ-5D-3L in terms of scale agreement, ceiling/floor effects, distribution, construct validity, discriminatory power, and relative efficiency (RE) in terms of the Oswestry Disability Index (ODI) for patients with low back pain (LBP). Methods We used intra-class correlation coefficients (ICC) and Bland–Altman plots to compare the PROPr and EQ-5D-3L with regared to scale agreement in a cross-sectional routine sample of LBP patients. For distribution, we used the Pearson’s coefficient for skewness and for ceiling/floor effects, a 15%-top/bottom threshold. For convergent validity, we used Pearson’s correlation coefficients. For known-groups validity, we applied a linear regression with interaction terms (predictors sex, age, and ODI level) and an analysis of variance (ANOVA). For discriminatory power, we calculated the effect size (ES) using Cohen’s d and the ratio of the area under the receiver-operating characteristics curves (AUROC-ratio = AUROCPROPr/AUROCEQ-5D-3L). RE was measured using the ratio of F-values (RE = FPROPr/FEQ-5D-3L). Results Of 218 LBP patients, 50.0% were female and the mean age was 61.8 years. The mean PROPr (0.20, 95%CI: 0.18; 0.22) and EQ-5D-3L scores (0.55, 95%CI: 0.51; 0.58) showed low agreement (d = 0.35, p ESPROPr and RE 1 in lower ODI severity. AUROC-ratios did not show significant differences in terms of ODI severity. Conclusions All PROPr and EQ-5D-3L biopsychosocial dimensions of health showed impairment in LPB patients. The capability of EQ-5D-3L and PROPr to differentiate ODI levels depends on ODI severity. Joint application of both tools may provide additional information.

Selecting only the relevant subsets from all gathered data has never been as challenging as it is in these times of big data and sensor fusion. Multiple complementary methods have emerged for the observation of similar phenomena; oftentimes, many of these techniques are superimposed in order to make the best possible decisions. A pathologist, for example, uses microscopic and spectroscopic techniques to discriminate between healthy and cancerous tissue. Especially in the field of spectroscopy in medicine, an immense number of frequencies are recorded and appropriately sized datasets are rarely acquired due to the time-intensive measurements and the lack of patients. In order to cope with the curse of dimensionality in machine learning, it is necessary to reduce the overhead from irrelevant or redundant features. In this article, we propose a feature selection callback algorithm (FeaSel-Net) that can be embedded in deep neural networks. It recursively prunes the input nodes after the optimizer in the neural network achieves satisfying results. We demonstrate the performance of the feature selection algorithm on different publicly available datasets and compare it to existing feature selection methods. Our algorithm combines the advantages of neural networks’ nonlinear learning ability and the embedding of the feature selection algorithm into the actual classifier optimization.

Background Cut-offs on self-report depression screening tools are designed to identify many more people than those who meet criteria for major depressive disorder. In a recent analysis of the European Health Interview Survey (EHIS), the percentage of participants with Patient Health Questionnaire-8 (PHQ-8) scores ≥10 was reported as major depression prevalence.Objective We used a Bayesian framework to re-analyse EHIS PHQ-8 data, accounting for the imperfect diagnostic accuracy of the PHQ-8.Methods The EHIS is a cross-sectional, population-based survey in 27 countries across Europe with 258 888 participants from the general population. We incorporated evidence from a comprehensive individual participant data meta-analysis on the accuracy of the PHQ-8 cut-off of ≥10. We evaluated the joint posterior distribution to estimate the major depression prevalence, prevalence differences between countries and compared with previous EHIS results.Findings Overall, major depression prevalence was 2.1% (95% credible interval (CrI) 1.0% to 3.8%). Mean posterior prevalence estimates ranged from 0.6% (0.0% to 1.9%) in the Czech Republic to 4.2% (0.2% to 11.3%) in Iceland. Accounting for the imperfect diagnostic accuracy resulted in insufficient power to establish prevalence differences. 76.4% (38.0% to 96.0%) of observed positive tests were estimated to be false positives. Prevalence was lower than the 6.4% (95% CI 6.2% to 6.5%) estimated previously.Conclusions Prevalence estimation needs to account for imperfect diagnostic accuracy.Clinical implications Major depression prevalence in European countries is likely lower than previously reported on the basis of the EHIS survey.

Nonequilibrium time evolution of large quantum systems is a strong candidate for quantum advantage. Variational quantum algorithms have been put forward for this task, but their quantum optimization routines suffer from trainability and sampling problems. Here, we present a classical preprocessing routine for variational Hamiltonian simulation that circumvents the need for a quantum optimization by expanding rigorous error bounds in a perturbative regime for suitable time steps. The resulting cost function is efficiently computable on a classical computer. We show that there always exists potential for optimization with respect to a Trotter sequence of the same order and that the cost value has the same scaling as Trotter in simulation time and system size. Unlike previous work on classical preprocessing, the method is applicable to any Hamiltonian system independent of locality and interaction lengths. Via numerical experiments for spin-lattice models, we find that our approach significantly improves digital quantum simulation capabilities with respect to Trotter sequences for the same resources. For short times, we find accuracy improvements of more than three orders of magnitude for our method as compared to Trotter sequences of the same gate number. Moreover, for a given gate number and accuracy target, we find that the preoptimization we introduce enables simulation times that are consistently more than ten times longer for a target accuracy of 0.1%.

Abstract Background Despite the progress of research and treatment for breast cancer, still up to 30% of the patients afflicted will develop distant disease. Elongation of survival and maintaining the quality of life (QoL) become pivotal issues guiding the treatment decisions. One possible approach to optimise survival and QoL is the use of patient-reported outcomes (PROs) to timely identify acute disease-related burden. We present the protocol of a trial that investigates the effect of real-time PRO data captured with electronic mobile devices on QoL in female breast cancer patients with metastatic disease. Methods This study is a randomised, controlled trial with 1:1 randomisation between two arms. A total of 1000 patients will be recruited in 40 selected breast cancer centres. Patients in the intervention arm receive a weekly request via an app to complete the PRO survey. Symptoms will be assessed by study-specific optimised short forms based on the EORTC QLQ-C30 domains using items from the EORTC CAT item banks. In case of deteriorating PRO scores, an alarm is sent to the treating study centre as well as to the PRO B study office. Following the alarm, the treating breast cancer centre is required to contact the patient to inquire about the reported symptoms and to intervene, if necessary. The intervention is not specified and depends on the clinical need determined by the treating physician. Patients in the control arm are prompted by the app every 3 months to participate in the PRO survey, but their response will not trigger an alarm. The primary outcome is the fatigue level 6 months after enrolment. Secondary endpoints include among others hospitalisations, use of rescue services and overall QoL. Discussion Within the PRO B intervention group, we expect lower fatigue levels 6 months after intervention start, higher levels of QoL, less unplanned hospitalisations and less emergency room visits compared to controls. In case of positive results, our approach would allow a fast and easy transfer into clinical practice due to the use of the already nationwide existing IT infrastructure of the German Cancer Society and the independent certification institute OnkoZert. Trial registration DRKS (German Clinical Trials Register) DRKS00024015 . Registered on 15 February 2021

Small-scale robots hold great potential for targeted cargo delivery in minimally invasive medicine. However, current robots often face challenges in locomoting efficiently on slippery biological tissue surfaces, especially when loaded with heavy cargo. Here, we report a magnetic millirobot that can walk on rough and slippery biological tissues by anchoring itself on the soft tissue surface alternatingly with two feet and reciprocally rotating the body to move forward. We experimentally studied the locomotion, validated it with numerical simulations, and optimized the actuation parameters to fit various terrains and loading conditions. Furthermore, we developed a permanent magnet set-up to enable wireless actuation within a human-scale volume that allows precise control of the millirobot to follow complex trajectories, climb vertical walls, and carry cargo up to four times its own weight. Upon reaching the target location, it performs a deployment sequence to release the liquid drug into tissues. The robust gait of our millirobot on rough biological terrains, combined with its heavy load capacity, makes it a versatile and effective miniaturized vehicle for targeted cargo delivery.

Early career researchers (ECRs) are important stakeholders leading efforts to catalyze systemic change in research culture and practice. Here, we summarize the outputs from a virtual unconventional conference (unconference), which brought together 54 invited experts from 20 countries with extensive experience in ECR initiatives designed to improve the culture and practice of science. Together, we drafted 2 sets of recommendations for (1) ECRs directly involved in initiatives or activities to change research culture and practice; and (2) stakeholders who wish to support ECRs in these efforts. Importantly, these points apply to ECRs working to promote change on a systemic level, not only those improving aspects of their own work. In both sets of recommendations, we underline the importance of incentivizing and providing time and resources for systems-level science improvement activities, including ECRs in organizational decision-making processes, and working to dismantle structural barriers to participation for marginalized groups. We further highlight obstacles that ECRs face when working to promote reform, as well as proposed solutions and examples of current best practices. The abstract and recommendations for stakeholders are available in Dutch, German, Greek (abstract only), Italian, Japanese, Polish, Portuguese, Spanish, and Serbian.

Introduction: Chronic cerebral hypoperfusion caused by asymptomatic high-grade stenosis of the internal carotid artery (ICA) has been associated with impaired cognitive function. Only few studies exist on underlying changes of functional connectivity (FC). Methods: 20 patients with unilateral high-grade ICA stenosis without MRI lesions and 25 aged-match controls underwent resting-state functional MRI (rsfMRI) and neuropsychological assessment. Patients were examined within ten days before and 6–10 weeks after surgical or interventional revascularization of carotid stenosis. We examined mean resting-state FC ipsi- and contralateral to stenosis and network topology using graph-theoretical measures. Results: At baseline, intrahemispheric FC was similar for patients and healthy controls. After revascularization mean FC increased moderately without an effect on network topology. Patients performed worse in TMT B and Stroop test, while performance in global screening tests for dementia (Mini Mental Status Examination, DemTect) were comparable. Test results did not improve after revascularization. Conclusion: In our study population, we find no effect of chronic hypoperfusion on FC and global cognitive function, although we observe minor impairments in processing speed and mental flexibility. The subtle increase of FC after revascularization could indicate excessive upregulation after restoration of perfusion. However, it might as well be a coincidental finding due to the limited sample size.

Abstract Metallic ball seat valves are an essential component in almost every hydraulic system in the form of check valves. Despite their wide usage in real‐life applications, the physical sealing mechanism is not yet fully understood and still debated. One promising method is the contact mechanics theory which has been developed by Persson et al. for rubber seals. It can predict the leakage of rubber seals successfully, but its application for metallic seals, where plastic deformation plays an import role, has only been developed recently and is not yet fully validated. This theory is combined with surface scans of investigated seats and simulations that are performed using the finite element method (FEM) for different geometric configurations. This combination allows an efficient calculation of the leakage of ball seat valves depending on their specific design and applied forces and pressures. In this work, the predictions by simulations according to Persson's theory are compared with experimental results. This comparison is done by analyzing the dependency of the leakage of ball seat valves in relation to applied normal forces and for different surfaces in contact. This validates the applicability of Persson's method in this field. The presented experimental method allows the measurement of the leakage of ball seat valves under realistic conditions.

With the notion of the zero-level digital divide, questions of technological structure have become more pressing for matters of agency. In this, design plays a major role, as it is assumed to be of structural significance, predetermining the architecture of a given technology and, thereby, what one can actually do with it. When also considering the daily importance of digital technologies, the question arises, regarding how these designed technologies impact the way we come to realize reality and, ultimately, the self. How self-determinedly does one utilize digital technologies? As digital products, such as apps lack material elements, which could be adjusted to suit one’s personal needs, they are very much dependent on design being available to the senses. Building upon this insight, designers aim at creating user experiences. As experience is a highly personal process, design is dependent on the subject’s compliance to cognitively realize such experience. This paper will theoretically explore how design is individually constituted and how education can provide for possibilities to self-determinedly act within the designed environments of digital technologies. Starting with the notion of ‹imagineering›, it will be suggested to conceptualize design as a mental image in order to better understand how design can be cognitively adjusted once it is constituted.

Abstract In the context of energy transition and climate change, a combination of highly efficient modern solid oxide fuel cells (SOFC) and thermo‐chemical conversion of biogenic residues could complement other intermittent renewable sources such as wind and solar. In order to reduce required gas cleaning efforts and to increase the process efficiency, the influence of hydrocarbons on SOFC performance is experimentally investigated in this study. For the first time, the operation of Ni/YSZ anode‐supported cells in Jülich F10 stacks is performed with pre‐reformed and with bio‐syngas containing full hydrocarbon content at realistic current densities. Sulfur and other impurities were removed in both cases. No degradation could be observed within normal operation on clean gas. With the tar reformer bypassed, the pressure drop over the stack increased due to severe carbon deposition on the anode substrate and the nickel current collector mesh inside the SOFC stack, so that operation had to be terminated after five hours. This behavior is different from single‐cell tests, where electrochemical degradation is the limiting factor. The results show that improvements are not only necessary for cell materials and that future research must also consider other stack components.

Abstract Background We investigated changes of cortical thickness and its association with cognitive performance in patients with high-grade carotid artery stenosis without ischemic brain lesions. Methods We studied 25 patients with unilateral carotid artery stenosis ≥50% and 25 age-matched controls. All subjects underwent T1-weighted MRI, and cortical thickness was measured in 33 regions of interest in each hemisphere, as well as in brain regions belonging to the vascular territory of the middle cerebral artery (MCA). General linear mixed models were fitted to the dependent variable cortical thickness. Cognitive assessment comprised the Stroop Test and Trail Making Test B. Results In the linear mixed model, presence of carotid stenosis had no effect on cortical thickness. There was a significant interaction of stenosis and region with a trend towards lower cortical thickness in the MCA region on the side of carotid stenosis. Patients with carotid stenosis performed significantly worse on the Stroop test than controls, but there was no correlation with cortical thickness. Conclusion In patients with carotid stenosis without ischemic brain lesions, neither a clear pattern of reduced cortical thickness nor an association of cortical thickness with cognitive function was observed. Our data do not support the hypothesized association of cortical thinning and cognitive impairment in carotid stenosis.

There is an increasing prevalence of obesity and metabolic syndrome, which promote the development of non–alcoholic fatty liver disease (NAFLD), a disease that can evolve into cirrhosis and hepatocellular carcinoma. Repin1 loss was previously shown to have beneficial effects on lipid and glucose metabolism and obesity regulation. Herein, we characterized NAFLD in mice with hepatic deletion of Repin1 (LRep1−/−). For this purpose, liver disease was analysed in male LRep1−/− and wild-type mice treated with streptozotocin/high fat diet or a control diet over a period of 20 wks. Streptozotocin/high fat diet treated LRep1−/− mice showed a significant decrease in systemic and hepatic lipid accumulation, accompanied by diminished chronic inflammation and a subsequent reduction in liver injury. Remarkably, Repin1-deficient mice exhibited a lower tumour prevalence and tumour frequency, as well as a reduced liver weight/body weight index. A therapeutic approach using Repin1 siRNA in the early phase of NAFLD verified the observed beneficial effects of Repin1 deficiency. This study provides evidence that loss of Repin1 in the liver attenuates NAFLD progression, most likely by reducing fat accumulation and alleviating chronic tissue inflammation. Thus, modulating Repin1 expression may become a novel strategy and potential tool to inhibit NAFLD progression. Keywords: Lipid accumulation, Metabolic disorder, siRNA, Non-alcoholic fatty liver disease, Fibrosis, Liver tumour

Abstract Background Many cancer patients are interested in complementary and integrative medicine during and after regular cancer treatment. Given the high number of users it is important that physicians and patients engage in a dialog about useful complementary and integrative medicine therapies during cancer treatment. In a prospective, multi-center, cluster-randomized evaluation study we will develop, implement and evaluate a training program for oncology physicians advising their patients on complementary and integrative medicine. The main objective of the study is to evaluate whether training physicians in a blended-learning approach (e-learning + skills-training workshop) in providing advice to their cancer patients on complementary and integrative medicine, in addition to handing out an information leaflet about reputable websites, has different effects on the outcomes of patients, physicians, and their interaction level, compared to only giving out the information leaflet. Methods/design Forty-eight oncology physicians will be included into a cluster-randomized trial to either participate or not in the blended-learning training. Physicians will then advise 10 cancer patients each, resulting in 480 patients participating in the trial. The blended learning consists of nine units of up to 45 min of e-learning and 18 units of up to 45 min of on-site skills-training workshop focusing. Outcomes will be measured on the physician, patient, and physician-patient-interaction level. Discussion A blended-learning program for oncology physicians to advise their cancer patients in a systematic way and a reasonable time frame on complementary and integrative medicine will be evaluated in depth in a large cluster-randomized trial. Trial registration German Clinical Trials Register, ID: DRKS00012704. Registered on 28 August 2017.

Three-dimensional (3D) organoid culture recapitulating patient-specific histopathological and molecular diversity offers great promise for precision medicine in cancer. In this study, we established label-free imaging procedures, including Raman microspectroscopy (RMS) and fluorescence lifetime imaging microscopy (FLIM), for in situ cellular analysis and metabolic monitoring of drug treatment efficacy. Primary tumor and urine specimens were utilized to generate bladder cancer organoids, which were further treated with various concentrations of pharmaceutical agents relevant for the treatment of bladder cancer (i.e., cisplatin, venetoclax). Direct cellular response upon drug treatment was monitored by RMS. Raman spectra of treated and untreated bladder cancer organoids were compared using multivariate data analysis to monitor the impact of drugs on subcellular structures such as nuclei and mitochondria based on shifts and intensity changes of specific molecular vibrations. The effects of different drugs on cell metabolism were assessed by the local autofluorophore environment of NADH and FAD, determined by multiexponential fitting of lifetime decays. Data-driven neural network and data validation analyses (k-means clustering) were performed to retrieve additional and non-biased biomarkers for the classification of drug-specific responsiveness. Together, FLIM and RMS allowed for non-invasive and molecular-sensitive monitoring of tumor-drug interactions, providing the potential to determine and optimize patient-specific treatment efficacy.

BackgroundStress is a major risk factor for the impairment of psychological well-being. The present study aimed to evaluate the empirical evidence of the Transactional Stress Model proposed by Lazarus and Folkman in patients with psychosomatic health conditions.MethodsA structural equation model was applied in two separate subsamples of inpatients from the Department of Psychosomatic Medicine (total n = 2,216) for consecutive model building (sample 1, n = 1,129) and confirmatory analyses (sample 2, n = 1,087) using self-reported health status information about perceived stress, personal resources, coping mechanisms, stress response, and psychological well-being.ResultsThe initial model was created to reflect the theoretical assumptions by Lazarus and Folkman about their transactional stress concept. This model was modified until a sufficient model fit was reached (sample 1: CFI = 0.904, TLI = 0.898, RMSEA = 0.072 [0.071–0.074], SRMR = 0.061). The modified model was confirmed in a second sample (sample 2: CFI = 0.932, TLI = 0.928, RMSEA = 0.066 [0.065–0.068], SRMR = 0.052). Perceived external stressors and personal resources explained 91% of the variance of the stress response, which was closely related to symptoms of depression (63% variance explained). The attenuating effect of resources on stress response was higher (standardized β = -0.73, p < 0.001) than the impact of perceived stressors on stress response (standardized β = 0.34, p < 0.001).ConclusionThe empirical data largely confirmed the theoretical assumption of the Transactional Stress Model, which was first presented by Lazarus and Folkman, in patients with a wide range of psychosomatic conditions. However, data analyses were solely based on self-reported health status. Thus, proposed inner psychological mechanisms such as the appraisal process could not be included in this empirical validation. The operationalization and understanding of coping processes should be further improved.

Graphene nanoribbons show promise for high-performance field-effect transistors, however they often suffer from short lengths and wide band gaps. Here, the authors use a bottom-up synthesis approach to fabricate 9- and 13-atom wide ribbons, enabling short-channel transistors with 105 on-off current ratio.

The need for replication of initial results has been rediscovered only recently in many fields of research. In preclinical biomedical research, it is common practice to conduct exact replications with the same sample sizes as those used in the initial experiments. Such replication attempts, however, have lower probability of replication than is generally appreciated. Indeed, in the common scenario of an effect just reaching statistical significance, the statistical power of the replication experiment assuming the same effect size is approximately 50%-in essence, a coin toss. Accordingly, we use the provocative analogy of "replicating" a neuroprotective drug animal study with a coin flip to highlight the need for larger sample sizes in replication experiments. Additionally, we provide detailed background for the probability of obtaining a significant p value in a replication experiment and discuss the variability of p values as well as pitfalls of simple binary significance testing in both initial preclinical experiments and replication studies with small sample sizes. We conclude that power analysis for determining the sample size for a replication study is obligatory within the currently dominant hypothesis testing framework. Moreover, publications should include effect size point estimates and corresponding measures of precision, e.g., confidence intervals, to allow readers to assess the magnitude and direction of reported effects and to potentially combine the results of initial and replication study later through Bayesian or meta-analytic approaches.

Introduction: There is evidence suggesting a detrimental effect of asymptomatic carotid artery stenosis on cognitive function even in the absence of ischemic cerebral lesions. Hypoperfusion has been suggested as pathophysiological mechanism causing cognitive impairment. We aimed to assess cognitive performance and cerebral perfusion changes in patients with carotid artery stenosis without ischemic lesions by arterial spin labeling (ASL) and contrast enhanced (CE) perfusion MRI before and after revascularization therapy. Methods: 17 asymptomatic patients with unilateral high-grade (≥70%) carotid artery stenosis without evidence of structural brain lesions underwent ASL and CE perfusion MRI and cognitive testing (MMSE, DemTect, Clock-Drawing Test, Trail-Making Test, Stroop Test) before and 6–8 weeks after revascularization therapy by endarterectomy or stenting. Multiparametric perfusion maps (ASL: cerebral blood flow (ASL-CBF), bolus arrival time (ASL-BAT); CE: cerebral blood flow (CE-CBF), mean transit time (CE-MTT), cerebral blood volume (CE-CBV)) were calculated and analyzed by vascular territory. Relative perfusion values were calculated. Results: Multivariate analysis revealed a significant impact of revascularization therapy on all perfusion measures analyzed. At baseline post-hoc testing showed significant hypoperfusion in MCA borderzones as assessed by ASL-CBF, ASL-BAT, CE-MTT and CE-CBV. All perfusion alterations normalized after revascularization. We did not observe any significant correlation of cognitive test results with perfusion parameters. There was no significant change in cognitive performance after revascularization. Conclusion: We found evidence of traceable perfusion alterations in patients with high grade carotid artery stenosis in the absence of structural brain lesions, which proved fully reversible after revascularization therapy. In this cohort of asymptomatic patients we did not observe an association of hypoperfusion with cognitive performance. Keywords: Magnetic resonance imaging, Perfusion imaging, Carotid artery stenosis, Carotid artery stenting, Cognitive function

Purpose . To report on a telephone consultation service with cancer patients and their relatives about complementary and alternative medicine (CAM) between 1999 and 2011. Methods . We offered a Germany-wide, free-of-charge telephone consultation service about CAM led by oncology clinicians from a comprehensive cancer center. The consultations followed a patient-centered approach with the aim to provide guidance and evidence-based information. Sociodemographic, disease-related data as well as information about the consultations’ content were collected in a standardized manner, and feedback questionnaires were sent out immediately after the consultations. Results . Overall, 5269 callers from all over Germany used the service (57% patients, 43% relatives). The “big 4” cancer types (breast, gastrointestinal, prostate, and lung) accounted for 55% of all calls. In 67% of calls, patients had just received the diagnosis or commenced anticancer therapy; 69% of patients had advanced or metastatic diseases. More than half of the callers (55%) had vague concerns like “what else can I do?” rather than specific questions related to CAM. The consultations covered a broad spectrum of issues from CAM therapies to cancer treatment and measures supportive of health, nutrition, and psychosocial support. Callers highly valued the service. Conclusions . Consulting about CAM addresses important unmet needs from cancer patients and their relatives. It provides clinicians with the opportunity to engage in open and supportive dialogues about evidence-based CAM to help with symptom management, psychological support, and individual self-care. Consulting about CAM cannot be separated from consulting about conventional care and should be provided from the beginning of the cancer journey.

Previous studies on the safety of gas-cooled high-temperature reactors (HTR) have analyzed the corrosion and oxidation behavior of the primary circuit components under normal and accident conditions. Through the use of graphite components, graphite particles can be formed by mechanical and chemical means whose influence on the structural change of metal surfaces must be analyzed in a comprehensive manner. The dust resuspension and deposition in tank geometry (DRESDEN-TANK) test facility was set up to thermally anneal metallic samples (Alloy 800H, Inconel 617) loaded with graphite particles under typical HTR conditions (helium, 750 °C, 6 MPa) for the investigation of interactions over a long-term range. In addition to the carrying out of a description of the processes occurring on the material surface, the gaseous reaction products have been analyzed. The results show that the presence of graphite particles in the near-surface layer has a significant impact on corrosion processes due to thermally-induced interactions. In this case iron and chromium are degraded in the metallic alloys, which leads to a structural change in the near-surface layer. Furthermore, the graphite particles significantly influence the formation of the oxide layers on the alloys; for example, they influence the formation speed of the layer and the layer height. The originally deposited particles thus exhibit a chemically-altered composition and a different geometric shape.

Background: Persistent somatic symptoms are associated with psychological distress, impaired function, and medical help-seeking behavior. The Patient Health Questionnaire (PHQ)-15 is used as a screening instrument for somatization and as a monitoring instrument for somatic symptom severity. A bifactorial model has been described, with one general factor and four orthogonal specific symptom factors. The objective of the present study was to assess and to clarify the factor structure of the PHQ-15 within and between different countries in Western Europe and China.Method: Cross-sectional secondary data analysis performed in three patient data samples from two Western European countries (Germany N = 2,517, the Netherlands N = 456) and from China (N = 1,329). Confirmatory factor analyses (CFA), and structural equation modeling (SEM) analysis were performed.Results: The general factor is found in every sample. However, although the outcomes of the PHQ-15 estimate severity of somatic symptoms in different facets, these subscales may have different meanings in the European and Chinese setting. Replication of the factorial structure was possible in the German and Dutch datasets but not in the dataset from China. For the Chinese dataset, a bifactorial model with a different structure for the cardiopulmonary factor is suggested. The PHQ-15 could discern somatization from anxiety and depression within the three samples.Conclusion: The PHQ-15 is a valid questionnaire that can discern somatization from anxiety and depression within different cultures like Europe or China. It can be fitted to a bifactorial model for categorical data, however, the model can only be recommended for use of the general factor. Application of the orthogonal subscales in non-European samples is not corroborated by the results. The differences cannot be ascribed to differences in health care settings or by differences in concomitant depression or anxiety but instead, a cultural factor involving concepts of disease may play a role in this as they may play a role in the translation of the questionnaire. Further research is needed to explore this, and replication studies are needed regarding the factorial structure of the PHQ-15 in China.

ObjectiveTo investigate the illness perception characteristics of Chinese patients with functional gastrointestinal disorders (FGID), and the mediating role between symptoms, psychopathology, and clinical outcomes.MethodsSix illness groups from four outpatient departments of a general hospital in China were recruited, including the FGID patient group. The modified and validated Chinese version of the illness perception questionnaire-revised was utilized, which contained three sections: symptom identity, illness representation, and causes. The 12-item short-form health survey was utilized to reflect the physical and mental health-related quality of life (HRQoL). The Toronto alexithymia scale was used to measure the severity of alexithymia. Additional behavioral outcome about the frequency of doctor visits in the past 12 months was measured. Pathway analyses with multiple-group comparisons were conducted to test the mediating role of illness perception.ResultsOverall, 600 patients were recruited. The illness perceptions of FGID patients were characterized as with broad non-gastrointestinal symptoms (6.8 ± 4.2), a negative illness representation (more chronic course, worse consequences, lower personal and treatment control, lower illness coherence, and heavier emotional distress), and high numbers of psychological and culture-specific attributions. Fit indices of the three hypothesized path models (for physical and mental HRQoL and doctor-visit frequency, respectively) supported the mediating role of illness perceptions. For example, the severity of alexithymia and non-gastrointestinal symptoms had significant negative effect on mental quality of life through both direct (standardized effect: −0.085 and −0.233) and indirect (standardized effect: −0.045 and −0.231) influence via subscales of consequences, emotional representation, and psychological and risk factor attributions. Multi-group confirmatory factor analysis showed similar psychometric properties for FGID patients and the other disease group.ConclusionThe management of FGID patients should take into consideration dysfunctional illness perceptions, non-gastrointestinal symptoms, and emotion regulation.

The Regional Psychiatry Budget (RPB), as a special arrangement within the German Federal Hospital Refund Regulation, is based on the capitation principle. A lump sum is allocated to a major inpatient care provider in a large region on a yearly basis. Under this model, the provider is free to offer all forms of treatment and to construct individual models of integrated care that specifically suit the region and the needs of community members. The present study aimed to evaluate selected aspects that represent a change in the psychiatric health status of patients in the covered region under the conditions of the RPB. We performed a secondary data analysis of administrative data of 19,913 cases generated by the hospital in a pre-post comparison of the periods before and under RPB conditions. The average length of an inpatient stay was reduced by approximately 22 % and could be partially replaced by day care. Selected indicators suggest equal or higher quality of care with stable cost in the population in need of psychiatric care in the district.

BackgroundA novel non-invasive asthma prediction tool from the Leicester Cohort, UK, forecasts asthma at age 8 years based on 10 predictors assessed in early childhood, including current respiratory symptoms, eczema, and parental history of asthma.ObjectiveWe aimed to externally validate the proposed asthma prediction method in a German birth cohort.MethodsThe MAS-90 study (Multicentre Allergy Study) recorded details on allergic diseases prospectively in about yearly follow-up assessments up to age 20 years in a cohort of 1,314 children born 1990. We replicated the scoring method from the Leicester cohort and assessed prediction, performance and discrimination. The primary outcome was defined as the combination of parent-reported wheeze and asthma drugs (both in last 12 months) at age 8. Sensitivity analyses assessed model performance for outcomes related to asthma up to age 20 years.ResultsFor 140 children parents reported current wheeze or cough at age 3 years. Score distribution and frequencies of later asthma resembled the Leicester cohort: 9% vs. 16% (MAS-90 vs. Leicester) of children at low risk at 3 years had asthma at 8 years, at medium risk 45% vs. 48%. Performance of the asthma prediction tool in the MAS-90 cohort was similar (Brier score 0.22 vs. 0.23) and discrimination slightly better than in the original cohort (area under the curve, AUC 0.83 vs. 0.78). Prediction and discrimination were robust against changes of inclusion criteria, scoring and outcome definitions. The secondary outcome 'physicians' diagnosed asthma at 20 years' showed the highest discrimination (AUC 0.89).ConclusionThe novel asthma prediction tool from the Leicester cohort, UK, performed well in another population, a German birth cohort, supporting its use and further development as a simple aid to predict asthma risk in clinical settings.

BACKGROUND:Multiple sclerosis (MS) preferentially affects females at childbearing age. For this reason patients and treating physicians were frequently confronted with questions concerning family planning, pregnancy and birth. OBJECTIVE:The aim of this study was to evaluate the expertise about pregnancy related topics in multiple sclerosis of neurologists in private practice. METHODS:We developed a survey with 16 multiple choice questions about pregnancy related topics and sent it to neurologists in private practice in Berlin, Germany. RESULTS:56 completed questionnaires were sent back. 54% of all questions were answered correctly, 21% of the questions were answered with "I don't know". Correct answers were more often given by physicians who treat more than 400 MS patients per year (p = 0.001). Further positive associations were found for assumed relevance of the topic (p = 0.002) and the degree of counseling (p

Abstract Background Recently, a growing number of Item-Response Theory (IRT) models has been published, which allow estimation of a common latent variable from data derived by different Patient Reported Outcomes (PROs). When using data from different PROs, direct estimation of the latent variable has some advantages over the use of sum score conversion tables. It requires substantial proficiency in the field of psychometrics to fit such models using contemporary IRT software. We developed a web application ( http://www.common-metrics.org ), which allows estimation of latent variable scores more easily using IRT models calibrating different measures on instrument independent scales. Results Currently, the application allows estimation using six different IRT models for Depression, Anxiety, and Physical Function. Based on published item parameters, users of the application can directly estimate latent trait estimates using expected a posteriori (EAP) for sum scores as well as for specific response patterns, Bayes modal (MAP), Weighted likelihood estimation (WLE) and Maximum likelihood (ML) methods and under three different prior distributions. The obtained estimates can be downloaded and analyzed using standard statistical software. Conclusions This application enhances the usability of IRT modeling for researchers by allowing comparison of the latent trait estimates over different PROs, such as the Patient Health Questionnaire Depression (PHQ-9) and Anxiety (GAD-7) scales, the Center of Epidemiologic Studies Depression Scale (CES-D), the Beck Depression Inventory (BDI), PROMIS Anxiety and Depression Short Forms and others. Advantages of this approach include comparability of data derived with different measures and tolerance against missing values. The validity of the underlying models needs to be investigated in the future.

BackgroundIt is speculated that attending Steiner schools, whose pedagogical principles include an account for healthy psycho-physical development, may have long-term beneficial health effects. We examined whether the current health status differed between former attendees of German Steiner schools and adults from the general population. Furthermore, we examined factors that might explain those differences.MethodsWe included former Steiner school attendees from 4 schools in Berlin, Hanover, Nuremberg and Stuttgart and randomly selected population controls. Using a self-report questionnaire we assessed sociodemographics, current and childhood lifestyle and health status. Outcomes were self-reports on 16 diseases: atopic dermatitis, allergic rhinitis, bronchial asthma, chronic obstructive pulmonary disease (COPD), cardiac arrhythmia, cardiac insufficiency, angina pectoris, arteriosclerosis, hypertension, hypercholesterolemia, osteoarthritis, rheumatism, cancer, diabetes, depression and multiple sclerosis. Furthermore, participants rated the symptom burden resulting from back pain, cold symptoms, headache, insomnia, joint pain, gastrointestinal symptoms and imbalance. Unadjusted and adjusted odds ratios were calculated for each outcome.Results1136 Steiner school attendees and 1746 controls were eligible for analysis. Both groups were comparable regarding sex, age and region, but differed in nationality and educational status. After adjusting for possible confounders, we found statistically significant effects of Steiner school attendance for osteoarthritis (OR 0.69 [0.49-0.97]) and allergic rhinitis (OR 0.77, [0.59-1.00]) as well as for symptom burden from back pain (OR 0.80, [0.64-1.00]), insomnia (OR 0.65, [0.50-0.84]), joint pain (OR 0.62, [0.48-0.82]), gastrointestinal symptoms (OR 0.76, [0.58-1.00]) and imbalance (OR 0.60, [0.38-0.93]).ConclusionsThe risk of most examined diseases did not differ between former Steiner school attendees and the general population after adjustment for sociodemographics, current and childhood lifestyle features, but symptom burden from some current health complaints was reported less by former Steiner school attendees. Results must be interpreted with caution since the analysis was exploratory.