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Abstract Leadership has become an increasingly important issue in medicine as leadership skills, job satisfaction and patient outcomes correlate positively. Various leadership training and physician psychological well-being programmes have been developed internationally, yet no standard is established in primary care. The IMPROVEjob leadership program was developed to improve job satisfaction among German general practitioners and practice personnel. Its acceptance and effectiveness were evaluated. The IMPROVEjob intervention is a participatory, interdisciplinary and multimodal leadership intervention that targets leadership, workflows and communication in general practices using three elements: (1) two leadership workshops with skills training; (2) a toolbox with printed and online material, and (3) a 9-month implementation phase supported by facilitators. A cluster-randomised trial with a waiting-list control evaluated the effectiveness on the primary outcome job satisfaction assessed by the Copenhagen Psychosocial Questionnaire (range 0–100). A mixed-methods approach with questionnaires and participant interviews evaluated the acceptance of the intervention and factors influencing the implementation of intervention content. Statistical analyses respected the clustered data structure. The COVID-19 pandemic necessitated intervention adjustments: online instead of on-site workshops, online material instead of facilitator practice visits. Overall, 52 of 60 practices completed the study, with altogether 70 practice leaders, 16 employed physicians, and 182 practice assistants. According to an intention-to-treat analysis, job satisfaction decreased between baseline and follow-up (not significantly) in the total study population and in both study arms, while the subgroup of practice leaders showed a non-significant increase. A mixed multilevel regression model showed no effect of the intervention on job satisfaction (b = − 0.36, p > 0.86), which was influenced significantly by a greater sense of community (b = 0.14, p

Objectives Strong primary care leaders are needed to assure high quality services for patient populations. This study analysed general practitioners’ (GP) leadership skills comparing practice-level self and staff assessments based on the full range of leadership model and the leader-member exchange (LMX).Setting The questionnaire survey was conducted among German general practice leaders and their staff participating in the IMPROVEjob trial.Participants The study population comprised 60 German general practices with 366 participants: 84 GP practice leaders and 282 employees (28 physicians and 254 practice assistants).Primary and secondary outcome measures Leadership skills of the practice leaders were measured using the Integrative Leadership Questionnaire (German Fragebogen für integrative Führung) and the LMX-7 questionnaire. Leaders rated themselves and practice staff rated their leaders. The data was analysed by paired mean comparisons on the practice level.Results For most leadership dimensions, practice leaders rated themselves higher than their employees rated them. Differences were found for transformational leadership (p

BackgroundHigh-dose glucocorticoids are the standard treatment for acute relapses in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Therapeutic apheresis can be considered for the escalation of relapse therapy, but some patients still do not recover sufficiently. We aimed to explore the effects of apheresis on humoral and cellular immune parameters and to identify features that correlate with beneficial clinical outcomes.MethodsWe studied two cohorts comprising a total of 63 patients with MS or NMOSD who were undergoing relapse therapy with either methylprednisolone or apheresis. Blood samples were collected immediately before and after therapy to isolate plasma or serum as well as immune cells. We then measured (1) concentrations of the immunoglobulin isotypes IgG, IgM and IgA, (2) antibody reactivities against 12 peptides derived from potential autoantigens and Epstein-Barr virus proteins, (3) frequencies of CD19+ B cells, CD3+ T cells and CD14+ monocytes, (4) transcriptome profiles of CD19+ B cells and CD4+ T cells and (5) mRNA levels of 7 cytotoxicity-related genes in CD4+ T cells. The data were compared with regard to changes under therapy and with regard to differences between clinical responders and non-responders.ResultsThe initial therapy with methylprednisolone had no significant effect on immunoglobulin levels and (auto)antibody reactivities (nmax=27 MS patients). In contrast, MS patients who underwent apheresis (nmax=27) showed strong immunoglobulin reduction rates, especially for IgG, and decreased antibody reactivities against all tested peptides. EBNA1 (amino acids 391-410) was the only peptide that also reached the significance level in NMOSD patients (n=9). Non-responders to apheresis (n=12) had on average higher anti-EBNA1 (391-410) reactivities than responders (n=24) at baseline. Apheresis also led to a decrease in the proportion of monocytes, an increase in the proportion of T cells (n=29 patients with MS or NMOSD) and moderate transcriptome changes (nmax=4 MS patients). A gene expression signature that is characteristic of CD4+ cytotoxic T lymphocytes (CD4-CTLs) was found to be elevated at baseline in non-responders to apheresis, although this could not be validated with statistical significance (n=19 MS patients).ConclusionOur data reveal that therapeutic apheresis in MS rapidly leads to a significant decrease in IgG reactivities against EBNA1 (391-410) and cross-reactive targets such as GlialCAM (370-389) and also has an impact on the gene expression of B cells and T cells. Further studies are required to verify whether anti-EBNA1 (391-410) antibody reactivities and the expression of CD4-CTL-related genes may be indicative of the individual clinical response to this therapy.

Abstract Socio-cognitive impairment is frequent in multiple sclerosis (MS). However, little is known about the relationship between other potentially relevant clinical symptoms (i.e., cognition, depression, fatigue) and the degree of socio-cognitive impairment, and neural mechanisms underlying socio-cognitive deficits in MS. Therefore, we meta-analytically quantified socio-cognitive impairment in MS. A systematic literature search in MEDLINE Ovid, Web of Science Core Collection, CENTRAL, and PsycInfo was conducted until December 2022. Studies investigating affective or cognitive theory of mind (a/cToM), visual perspective taking (VPT) and social decision making (SDM) in MS patients relative to healthy controls were included. Risk-of-bias (RoB) was assessed using the CLARITY group “Tool for Assessing RoB in Cohort Studies”. Mediation analysis investigated the contribution of clinical symptoms to socio-cognitive impairment. In total, n = 8534 studies were screened, 58 were included in the systematic review, 27 in the meta-analyses. Most studies were rated with a moderate RoB. Meta-analyses confirmed impairment of both aToM and cToM in MS patients, with larger effect sizes for aToM. Mediation analysis demonstrated that higher levels of fatigue selectively predicted the degree of cToM impairment. There was insufficient data available to quantify impairment in other socio-cognitive domains. Fourteen structural and functional imaging studies were identified and characterized by substantial heterogeneity. Summarized, this study confirmed substantial socio-cognitive impairment in MS and highlights the potential exacerbating role of comorbid clinical symptoms. We identify several evidence gaps that need to be addressed in future large-scale studies using comprehensive and coordinated assessments of socio-cognitive parameters, potential mediators, and neural correlates. Trial registration: The pre-registered review protocol can be assessed at www.crd.york.ac.uk/PROSPERO/ (ID: CRD42020206225).

Transcutaneous auricular vagus nerve stimulation (taVNS) is becoming increasingly established in the treatment of various neurological and psychiatric diseases. However, only a few studies have focused on the overall influence of taVNS on cortical excitability in general. The planned study will investigate the effect of taVNS on the excitability of the motor cortex in young healthy subjects. The aim of the study is to gain better understand of the physiological mechanism of taVNS to contribute to new fields of application of taVNS in new areas such as the treatment of stroke or multiple sclerosis. This protocol describes a single-center, prospective, double blind, sham-controlled trial that evaluates the effect of taVNS on motor cortex excitability with a planned sample size of 30 participants. The effect of taVNS is investigated by neuronavigation and electromyography (EMG) coupled transcranial magnetic stimulation (TMS) applied before and after taVNS stimulation. The following parameters are assessed: resting motor threshold (RMT), active motor threshold (AMT), recruitment curve (RC), short intracortical inhibition (SICI), intracortical facilitation (ICF). All parameters will be assessed for taVNS on the basis of perception threshold and tolerance threshold. All investigations performed in the study were reviewed and approved by the local ethics committee of the University Medical Center Greifswald (study reference number: BB048/22).Clinical trial registrationwww.drks.de, number: DRKS00029937.

Abstract The Hayabusa2 mission provided a unique data set of asteroid Ryugu that covers a wide range of spatial scale from the orbiter remote sensing instruments to the returned samples. The MASCOT lander that was delivered onto the surface of Ryugu aimed to provide context for these data sets by producing in situ data collected by a camera (MasCam), a radiometer (MARA), a magnetometer (MasMag) and a spectrometer (MicrOmega). In this work, we evaluate the success of MASCOT as an integrated lander to bridge the gap between orbiter and returned sample analysis. We find that MASCOT’s measurements and derivatives thereof, including the rock morphology, colour in the visible wavelengths, possible meteorite analogue, density, and porosity of the rock at the landing site are in good agreement with those of the orbiter and the returned samples. However, it also provides information on the spatial scale (sub-millimetres to centimetres) at which some physical properties such as the thermal inertia and reflectance undergo scale-dependent changes. Some of the in situ observations such as the presence of clast/inclusions in rocks and the absence of fine particles at the landing site was uniquely identified by MASCOT. Thus, we conclude that the delivery of an in situ instrument like MASCOT provides a valuable data set that complements and provides context for remote sensing and returned sample analyses. Graphical Abstract

This paper presents a dataset of fine-grained film analytical annotations (Melgar and Estrada and Koolen 2018) for a corpus study of feature films, documentaries, and television news on the Global Financial Crisis (2007-), generated by the research group Affektrhetoriken des Audiovisuellen (Freie Universität Berlin and Hasso-Plattner-Institute Potsdam, 2016-2021, see Bakels et. al. 2020a). The semantic video annotations are based on the AdA Filmontology (v1.8), which consists of eight annotation levels, 78 annotation types, and 501 annotation values (Bakels et. al. 2020b). Each level, type, and value has a unique resource identifier (URI) as well as an English and German name and description. In our paper, we reflect on the specific challenges of capturing film-analytical claims of embodied viewing experiences in an ontology-based taxonomy. We further critically discuss aspects such as intercoder-reliability, consistency, as well as the requirements of training and synchronising expert annotators. The dataset contains more than 92,000 manual and semi-automatic annotations authored in the open-source-software Advene (Aubert/Prié 2005) by expert annotators, as well as more than 400,000 automatically-generated annotations for wider corpus exploration. The annotations are published as Linked Open Data under the CC BY-SA 3.0 licence and available as rdf triples in ttl files and in Advene’s non-proprietary azp-file format, which allows instant access through the graphical interface of the software. Via a web application all annotations can be downloaded, queried, and visualised in conjunction with password-protected access to the source video files (Agt-Rickauer 2022). This dataset is of interest for research on the financial crisis discourse or the specific films and broadcasts; also, the dataset serves as a proof of concept for ontology-based video annotation and as a provider of training data on film analytical concepts such as shot length, camera movements, or affective tonalities.

BackgroundThe aim of this study was to examine the societal costs of polypharmacy in patients with multiple sclerosis (MS). We therefore focused on the association between the number of medications on the level of care (LOC), the German classification of the need for care, and the number of therapy sessions (TTU).MethodsIn addition to demographic information and medication, 101 MS patients performed the Multiple Sclerosis Health Resource Utilization Survey (MS-HRS). Medications were subdivided into a total number of medications (TD), MS-related medication [MSD, i.e., disease-modifying drugs (DMDs) and symptomatic treatment (SD)], and medication for comorbidities (CDs). Multivariate linear regression models were performed to estimate if the amount of each medication type affects LOC or TTU.ResultsPolypharmacy appeared in 54 patients at the time of the survey. The relative risk (RR) of LOC 1 increased significantly by 2.46 (p = 0.001) per TD and by 2.55 (p = 0.004) per MSD, but not per CD (RR 1.44; p = 0.092). The effect of RR on MSD was driven by SD (RR 2.2; p = 0.013) but not DMD (RR 2.6; p = 0.4). RR of MSD remained significant for LOC 2 (1.77; p = 0.009) and LOC 3/4 (1.91; p = 0.015), with a strong trend in RR of SD, but not DMD. TTU increased significantly per MSD (p = 0.012), but not per TD (p = 0.081) and CD (p = 0.724).ConclusionThe number of MSDs is related to the likelihood of a higher level of care and the number of therapy sessions and is therefore a good indication of the extent of the societal costs.

Abstract Background The interest in non-intubated video-assisted thoracic surgery (NIVATS) has risen over the last decade and numerous terms have been used to describe this technique. They all have in common, that the surgical procedure is performed in a spontaneously breathing patient under locoregional anaesthesia in combination with intravenous sedation but have also been performed on awake patients without sedation. Evidence has been generated favouring NIVATS compared to one-lung-ventilation under general anaesthesia. Main body We want to give an overview of how NIVATS is performed, and which different techniques are possible. We discuss advantages such as shorter length of hospital stay or (relative) contraindications like airway difficulties. Technical aspects, for instance intraoperative handling of the vagus nerve, are considered from a thoracic surgeon’s point of view. Furthermore, special attention is paid to the cohort of patients with interstitial lung diseases, who seem to benefit from NIVATS due to the avoidance of positive pressure ventilation. Whenever a new technique is introduced, it must prove noninferiority to the state of the art. Under this aspect current literature on NIVATS for lung cancer surgery has been reviewed. Conclusion NIVATS technique may safely be applied to minor, moderate, and major thoracic procedures and is appropriate for a selected group of patients, especially in interstitial lung disease. However, prospective studies are urgently needed.

Abstract Background Therapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing–remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape. Methods We conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions. Results Under siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy. Conclusion Treatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE.

Background: Epileptic seizures can occur throughout the course of multiple sclerosis (MS) and are associated with increasing disability progression over time. However, there are no data on whether epileptic seizures at the onset of MS also lead to increasing disability. Objective: To examine disease progression over time for MS patients with epileptic seizures at onset. Methods: We analyzed the data of 30,713 patients on the German Multiple Sclerosis Register in a case–control study for more than 15 years. MS patients with seizures at onset were further divided into subgroups with polysymptomatic and monosymptomatic onset to assess the impact of additional symptoms on disease progression. Results: A total of 46 patients had seizures as onset symptoms. Expanded Disability Status Scale (EDSS) within the first year was lower in the group with seizures at onset compared to controls (0.75 versus 1.6, p

The execution of voluntary movements is primarily governed by the cerebral hemisphere contralateral to the moving limb. Previous research indicates that the ipsilateral motor network, comprising the primary motor cortex (M1), supplementary motor area (SMA), and premotor cortex (PM), plays a crucial role in the planning and execution of limb movements. However, the precise functions of this network and its interplay in different task contexts have yet to be fully understood. Twenty healthy right-handed participants (10 females, mean age 26.1 ± 4.6 years) underwent functional MRI scans while performing biceps brachii representations such as bilateral, unilateral flexion, and bilateral flexion-extension. Ipsilateral motor evoked potentials (iMEPs) were obtained from the identical set of participants in a prior study using transcranial magnetic stimulation (TMS) targeting M1 while employing the same motor tasks. The voxel time series was extracted based on the region of interest (M1, SMA, ventral PM and dorsal PM). Directed functinal connectivity was derived from the extracted time series using time-resolved partial directed coherence. We found increased connectivity from left-PMv to both sides M1, as well as right-PMv to both sides SMA, in unilateral flexion compared to bilateral flexion. Connectivity from left M1 to left-PMv, and left-SMA to right-PMd, also increased in both unilateral flexion and bilateral flexion-extension compared to bilateral flexion. However, connectivity between PMv and right-M1 to left-PMd decreased during bilateral flexion-extension compared to unilateral flexion. Additionally, during bilateral flexion-extension, the connectivity from right-M1 to right-SMA had a negative relationship with the area ratio of iMEP in the dominant side. Our results provide corroborating evidence for prior research suggesting that the ipsilateral motor network is implicated in the voluntary movements and underscores its involvement in cognitive processes such as movement planning and coordination. Moreover, ipsilateral connectivity from M1 to SMA on the dominant side can modulate the degree of ipsilateral M1 activation during bilateral antagonistic contraction.

The spread of multidrug-resistant bacteria from humans or livestock is a critical issue. However, the epidemiology of resistant pathogens across wastewater pathways is poorly understood. Therefore, we performed a detailed comparison of third-generation cephalosporin-resistant Escherichia coli (3GCREC) from wastewater treatment plants (WWTPs) to analyze dissemination pathways. A total of 172 3GCREC isolated from four WWTPs were characterized via whole genome sequencing. Clonal relatedness was determined using multi-locus sequence typing (MLST) and core genome MLST. Resistance genotypes and plasmid replicons were determined. A total of 68 MLST sequence types were observed with 28 closely related clusters. Resistance genes to eight antibiotic classes were detected. In fluoroquinolone-resistant isolates, resistance was associated with three-or-more point mutations in target genes. Typing revealed high genetic diversity with only a few clonal lineages present in all WWTPs. The distribution paths of individual lines could only be traced in exceptional cases with a lack of enrichment of certain lineages. Varying resistance genes and plasmids, as well as fluoroquinolone resistance-associated point mutations in individual isolates, further corroborated the high diversity of 3GCREC in WWTPs. In total, we observed high diversity of 3GCREC inside the tested WWTPs with proof of resistant strains being released into the environment even after treatment processes.

Abstract The Japanese MMX sample return mission to Phobos by JAXA will carry a rover developed by CNES and DLR that will be deployed on Phobos to perform in situ analysis of the Martian moon’s surface properties. Past images of the surface of Phobos show that it is covered by a layer of regolith. However, the mechanical and compositional properties of this regolith are poorly constrained. In particular, from current remote images, very little is known regarding the particle sizes, their chemical composition, the packing density of the regolith as well as other parameters such as friction and cohesion that influence surface dynamics. Understanding the properties and dynamics of the regolith in the low-gravity environment of Phobos is important to trace back its history and surface evolution. Moreover, this information is also important to support the interpretation of data obtained by instruments onboard the main MMX spacecraft, and to minimize the risks involved in the spacecraft sampling operations. The instruments onboard the Rover are a Raman spectrometer (RAX), an infrared radiometer (miniRad), two forward-looking cameras for navigation and science purposes (NavCams), and two cameras observing the interactions of regolith and the rover wheels (WheelCams). The Rover will be deployed before the MMX spacecraft samples Phobos’ surface and will be the first rover to drive on the surface of a Martian moon and in a very low gravity environment. Graphic Abstract

The cortical silent period (CSP), assessed with transcranial magnetic stimulation (TMS), provides insights into motor cortex excitability. Alterations in the CSP have been observed in multiple sclerosis (MS), although a comparison of the sometimes contradictory results is difficult due to methodological differences. The aim of this study is to provide a more profound neurophysiological understanding of fatigue’s pathophysiology and its relationship to the CSP. Twenty-three patients with MS, along with a matched control group, underwent comprehensive CSP measurements at four intensities (125, 150, 175, and 200% resting motor threshold), while their fatigue levels were assessed using the Fatigue Scale for Motor and Cognitive Functions (FSMC) and its motor and cognitive subscore. MS patients exhibited a significantly increased CSP duration compared to controls (p = 0.02), but CSP duration was not associated with the total FSMC, or the motor or cognitive subscore. Our data suggest a systematic difference in MS patients compared to healthy controls in the CSP but no association with fatigue when measured with the FSMC. Based on these results, and considering the heterogeneous literature in the field, our study highlights the need for a more standardized approach to neurophysiological data collection and validation. This standardization is crucial for exploring the link between TMS and clinical impairments in diseases like MS.

Abstract The Martian Moons eXploration (MMX) mission will study the Martian moons Phobos and Deimos, Mars, and their environments. The mission scenario includes both landing on the surface of Phobos to collect samples and deploying a small rover for in situ observations. Engineering safeties and scientific planning for these operations require appropriate evaluations of the surface environment of Phobos. Thus, the mission team organized the Landing Operation Working Team (LOWT) and Surface Science and Geology Sub-Science Team (SSG-SST), whose view of the Phobos environment is summarized in this paper. While orbital and large-scale characteristics of Phobos are relatively well known, characteristics of the surface regolith, including the particle size-distributions, the packing density, and the mechanical properties, are difficult to constrain. Therefore, we developed several types of simulated soil materials (simulant), such as UTPS-TB (University of Tokyo Phobos Simulant, Tagish Lake based), UTPS-IB (Impact-hypothesis based), and UTPS-S (Simpler version) for engineering and scientific evaluation experiments.

BackgroundThe Symbol Digit Modalities Test (SDMT) is most frequently used to test processing speed in patients with multiple sclerosis (MS). Functional imaging studies emphasize the importance of frontal and parietal areas for task performance, but the influence of frontoparietal tracts has not been thoroughly studied. We were interested in tract-specific characteristics and their association with processing speed in MS patients.MethodsDiffusion tensor imaging was obtained in 100 MS patients and 24 healthy matched controls to compare seed-based tract characteristics descending from the superior parietal lobule [Brodman area 7A (BA7A)], atlas-based tract characteristics from the superior longitudinal fasciculus (SLF), and control tract characteristics from the corticospinal tract (CST) and their respective association with ability on the SDMT.ResultsPatients had decreased performance on the SDMT and decreased white matter volume (each p < 0.05). The mean fractional anisotropy (FA) for the BA7A tract and CST (p < 0.05), but not the SLF, differed between MS patients and controls. Furthermore, only the FA of the SLF was positively associated with SDMT performance even after exclusion of the lesions within the tract (r = 0.25, p < 0.05). However, only disease disability and total white matter volume were associated with information processing speed in a linear regression model.ConclusionsProcessing speed in MS is associated with the structural integrity of frontoparietal white matter tracts.

BackgroundFatigue is a common symptom in patients with multiple sclerosis. Several studies suggest that outdoor temperature can impact fatigue severity, but a systematic study of seasonal variations is lacking.MethodsFatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions (FSMC) in a temperate climatic zone with an average outdoor temperature of 8.8°C. This study included 258 patients with multiple sclerosis from 572 visits temporally distributed over the year. The data were adjusted for age, sex, cognition, depression, disease severity, and follow-up time. Linear regression models were performed to determine whether the temporal course of fatigue was time-independent, linearly time dependent, or non-linearly time dependent.ResultsFatigue was lowest during January (mean FSMC: 49.84) and highest during August (mean FSMC: 53.88). The regression analysis showed the best fit with a model that included months + months2, which was a non-linear time dependency. Mean FSMC per month correlated significantly with the average monthly temperature (ρ = 0.972; p < 0.001).ConclusionIn multiple sclerosis, fatigue showed a natural temporal fluctuation. Fatigue was higher during summer compared to winter, with a significant relationship of fatigue with outdoor temperature. This finding should be carefully taken into account when clinically monitoring patients over time to not interpret higher or lower scores independent of seasonal aspects.

Background The determination of kappa free light chains (KFLC) in cerebrospinal fluid (CSF) is an upcoming biomarker for the detection of an intrathecal immunoglobulin synthesis. Since renal function impairment leads to altered serum KFLC and albumin concentrations, interpretation of KFLC in CSF may be influenced by these parameters. Methods In this two-center study, the influence of renal function (according to the CKD-EPI creatinine equation) on KFLC and albumin concentrations was investigated in patients with “physiological” (n = 139), “non-inflammatory” (n = 146), and “inflammatory” (n = 172) CSF profiles in respect to the KFLC index and the evaluation in quotient diagrams in reference to the hyperbolic reference range (KFLC IF). Results All sample groups displayed declining KFLC indices and KFLC IF values with decreasing renal function ( P -values between

Abstract We have investigated the influence of thin thermally opaque dust layers on the thermal emission of rocks and regolith and determined the thermal response of these dust-covered surfaces to diurnal insolation cycles. Results are computed for Hayabusa2’s target asteroid (162173) Ryugu, which was observed by thermal infrared instruments on the orbiter and in situ. We show that even a very thin (10..100 μm) fine-grained porous dust layer with thermal inertia of 25 J m−2 K−1 s−1/2 can have a significant influence on surface temperatures and alter the apparent thermal inertia of the underlying material derived under the simplified assumption of a homogenous half space by more than 20%. The masking of the underlying material is complete at about 1 diurnal skin depth, corresponding to ~ 10 mm on Ryugu. Between 0.1 and 1 diurnal skin depths, we find a thermal lag smaller than what would be predicted for a surface consisting of dust only. If a dust cover were present on Ryugu, this should be clearly visible in the data returned by the orbiter’s thermal infrared imager (TIR) and the MASCOT lander’s radiometer (MARA), which observed a single boulder at the landing site. However, this appears not to be the case, and dust seems to play a minor role in the thermal emission from the asteroid.

Abstract Background Prenatal risk stratification of women with previous cesarean section (CS) by ultrasound thickness measurement of the lower uterine segment (LUS) is challenging. There is a wide range of proposed cutoff values and a valuable algorithm for selection before birth is not available. Using 3 T magnetic resonance imaging (MRI), we aimed to identify possible shortcomings of the current protocols used for birth selection after CS. Therefore, we evaluated anatomic and morphologic differences of the LUS and its thickness in patients with CS and those without. Possible impact factors on LUS thickness were studied. Methods We retrospectively analyzed 3 T MRI scans of 164 pregnant women in their second or third trimester, with (patient group, n = 60) and without previous CS (control group, n = 104). Sagittal T2-weighted images were studied. Normal findings of the LUS in MRI, reliability of MRI measurements, as well as factors influencing LUS thickness were assessed. MRI findings were compared to intraoperative findings. Results MRI provided good intra- (ICC 0.872) and fair inter-rater reliability (ICC 0.643). The relationship of the LUS and the cesarean scar to the surrounding anatomical structures and also its morphology varied strongly in patients and controls. Scar identification was possible in only 9/60 (15.0%) patients. The LUS was thinner in patients (1.9 ± 0.7 mm) than in controls (2.7 ± 1.3 mm). An LUS thinning up to 1 mm was observed in 23% of women without a previous CS and in 34% of women with normal intraoperative findings. Suspicion of a uterine dehiscence (LUS thickness

Abstract In December 2018, the NASA InSight lander successfully placed a seismometer on the surface of Mars. Alongside, a hammering device was deployed at the landing site that penetrated into the ground to attempt the first measurements of the planetary heat flow of Mars. The hammering of the heat probe generated repeated seismic signals that were registered by the seismometer and can potentially be used to image the shallow subsurface just below the lander. However, the broad frequency content of the seismic signals generated by the hammering extends beyond the Nyquist frequency governed by the seismometer's sampling rate of 100 samples per second. Here, we propose an algorithm to reconstruct the seismic signals beyond the classical sampling limits. We exploit the structure in the data due to thousands of repeated, only gradually varying hammering signals as the heat probe slowly penetrates into the ground. In addition, we make use of the fact that repeated hammering signals are sub‐sampled differently due to the unsynchronized timing between the hammer strikes and the seismometer recordings. This allows us to reconstruct signals beyond the classical Nyquist frequency limit by enforcing a sparsity constraint on the signal in a modified Radon transform domain. In addition, the proposed method reduces uncorrelated noise in the recorded data. Using both synthetic data and actual data recorded on Mars, we show how the proposed algorithm can be used to reconstruct the high‐frequency hammering signal at very high resolution.

Background: The intrathecal humoral response is the characteristic diagnostic finding in the cerebrospinal fluid (CSF) analysis of patients with multiple sclerosis (MS). Although the average age of MS patients increases, little is known about the sensitivity of diagnostic markers in elderly MS patients. Methods: In this retrospective two-center study, intrathecal free light chains kappa fraction (FLCk IF) and oligoclonal bands (OCB) were studied in a large cohort of patients with early and late onset relapsing (RMS) and progressive (PMS) MS. Furthermore, the humoral immune profile in CSF was analyzed, including the polyspecific intrathecal immune response measured as the MRZ reaction. Results: While the frequency of CSF-specific OCB did not differ between early and late onset RMS and PMS, the sensitivity of positive FLCk IF and absolute FLCk IF values were lower in PMS. The positivity of the MRZ reaction was equally frequent in early and late onset RMS and PMS. PMS patients had higher local IgA concentrations than RMS patients (p = 0.0123). Conclusions: OCB are slightly superior to FLCk IF in progressive MS in terms of sensitivity for detecting intrathecal immunoglobulin synthesis. The MRZ reaction, as the most specific parameter for MS, is also applicable in patients with late onset and progressive MS.

Abstract Background Deficits in social cognition can occur in multiple sclerosis (MS) patients, and different methods are utilized for its assessment. The aim of this study was to compare two tests of social cognition in a cohort of multiple sclerosis patients with respect to other clinical variables. Additionally, the impact of social cognition on quality of life was investigated. Methods In total, 50 patients were included in the study. Two tests of social cognition, emotion recognition and theory of mind, were performed and controlled for disease disability, depression, fatigue, and cognition in a multiple linear regression. Assessment of quality of life was also conducted. Results Accuracy on emotion recognition was better compared to theory of mind (86.5 ± 9.5% and 63.6 ± 10.1%, respectively). Cognition was associated with both social cognition tasks, accounting for more variance in the emotion recognition task. Quality of life was not related to social cognition. Conclusion Studies on social cognition in MS have to keep in mind the higher degree of cognitive influence of emotion recognition compared to theory of mind.

Abstract Background Four-dimensional (4D) flow magnetic resonance imaging (MRI) sequences with advanced parallel imaging have the potential to reduce scan time with equivalent image quality and accuracy compared with standard two-dimensional (2D) flow MRI. We compared 4D flow to standard 2D flow sequences using a constant and pulsatile flow phantom at 3 T. Methods Two accelerated 4D flow sequences (GRAPPA2 and k-t-GRAPPA5) were evaluated regarding the concordance of flow volumes, flow velocities, and reproducibility as well as dependency on measuring plane and velocity encoding (V enc). The calculated flow volumes and peak velocities of the phantom were used as reference standard. Flow analysis was performed using the custom-made software “Bloodline”. Results No significant differences in flow volume were found between the 2D, both 4D flow MRI sequences, and the pump reference (p = 0.994) or flow velocities (p = 0.998) in continuous and pulsatile flow. An excellent correlation (R = 0.99–1.0) with a reference standard and excellent reproducibility of measurements (R = 0.99) was achieved for all sequences. A V enc overestimated by up to two times had no impact on flow measurements. However, misaligned measuring planes led to an increasing underestimation of flow volume and mean velocity in 2D flow accuracy, while both 4D flow measurements were not affected. Scan time was significantly shorter for k-t-GRAPPA5 (1:54 ± 0:01 min, mean ± standard deviation) compared to GRAPPA2 (3:56 ± 0:02 min) (p = 0.002). Conclusions Both 4D flow sequences demonstrated equal agreement with 2D flow measurements, without impact of V enc overestimation and plane misalignment. The highly accelerated k-t-GRAPPA5 sequence yielded results similar to those of GRAPPA2.

Background: Oligoclonal bands represent intrathecal immunoglobulin G (IgG) synthesis and play an important role in the diagnosis of multiple sclerosis (MS). Kappa free light chains (KFLC) are increasingly recognized as an additional biomarker for intrathecal Ig synthesis. However, there are limited data on KFLC in neurological diseases other than MS. Methods: This study, conducted at two centers, retrospectively enrolled 346 non-MS patients. A total of 182 patients were diagnosed with non-inflammatory and 84 with inflammatory neurological diseases other than MS. A further 80 patients were classified as symptomatic controls. Intrathecal KFLC production was determined using different approaches: KFLC index, Reiber’s diagram, Presslauer’s exponential curve, and Senel’s linear curve. Results: Matching results of oligoclonal bands and KFLC (Reiber’s diagram) were frequently observed (93%). The Reiber’s diagram for KFLC detected intrathecal KFLC synthesis in an additional 7% of the patient samples investigated (4% non-inflammatory; 3% inflammatory), which was not found by oligoclonal band detection. Conclusions: The determination of both biomarkers (KFLC and oligoclonal bands) is recommended for routine diagnosis and differentiation of non-inflammatory and inflammatory neurological diseases. Due to the high sensitivity and physiological considerations, the assessment of KFLC in the Reiber’s diagram should be preferred to other evaluation methods.

Abstract Asteroid (162173) Ryugu is the target object of Hayabusa2, an asteroid exploration and sample return mission led by Japan Aerospace Exploration Agency (JAXA). Ground-based observations indicate that Ryugu is a C-type near-Earth asteroid with a diameter of less than 1 km, but the knowledge of its detailed properties is very limited prior to Hayabusa2 observation. This paper summarizes our best understanding of the physical and dynamical properties of Ryugu based on ground-based remote sensing and theoretical modeling before the Hayabusa2’s arrival at the asteroid. This information is used to construct a design reference model of the asteroid that is used for the formulation of mission operation plans in advance of asteroid arrival. Particular attention is given to the surface properties of Ryugu that are relevant to sample acquisition. This reference model helps readers to appropriately interpret the data that will be directly obtained by Hayabusa2 and promotes scientific studies not only for Ryugu itself and other small bodies but also for the solar system evolution that small bodies shed light on.

Free light chains kappa (FLCκ) in cerebrospinal fluid (CSF) are a part of the intrathecal immune response. This observational study was conducted to investigate the effects of different disease-modifying therapies (DMT) on the humoral intrathecal immune response in the CSF of patients with multiple sclerosis (MS). FLCκ were analyzed in CSF and serum samples from MS patients taking DMT (n = 60) and those in a control cohort of treatment-naïve MS patients (n = 90). DMT was classified as moderately effective (including INFß-1a, INFß-1b, glatiramer acetate, dimethyl fumarate, teriflunomide, triamcinolone); highly effective (including fingolimod, daclizumab) and very highly effective (alemtuzumab, natalizumab, rituximab/ocrelizumab, mitoxantrone). FLCκ were measured using a nephelometric FLCκ kit. Intrathecal FLCκ and IgG concentrations were assessed in relation to the hyperbolic reference range in quotient diagrams. Intrathecal FLCκ concentrations and IgG concentrations were significantly lower in samples from the cohort of MS patients taking very highly effective DMT than in samples from the cohort of MS patients taking highly effective DMT and in the treatment-naïve cohort (FLCκ: p = 0.004, p < 0.0001 respectively/IgG: p = 0.013; p = 0.021). The reduction in FLCκ could contribute to an anti-inflammatory effect in the CNS through this mechanism. There was no difference in the appearance of CSF-specific oligoclonal bands (p = 0.830). Longitudinal analyses are required to confirm these results.

The Mars Exploration Program Analysis Group has identified measurements of the state and the variability of the Martian atmosphere as high priority investigations for the upcoming years. Balloon-borne instruments could bridge the gap in both temporal and spatial resolution in mesoscale distances between local, stationary landers and global orbiter observations. The idea to use a balloon system for such a purpose is not new in essence and has been proposed already in past decades. While those concepts considered an aerial deployment during entry and descent, the concept outlined in this study revisits a launch off the payload deck of a lander from the Martian surface. This deployment option profits today mainly from the technological advance in micro-electronics and sensor miniaturization, which enables the design of a balloon-probe significantly smaller than earlier proposed systems. This paper presents the feasibility assessment for this instrument and gives further details on the scientific and operational concept, a strawman sensor suite, its system components and the associated size and budget estimates. It is complemented by the analysis scheme proposed to assess, manage and mitigate the deployment risk involved in automatically launching such a balloon-system off a planetary surface.

Load-forecasting problems have already been widely addressed with different approaches, granularities and objectives. Recent studies focused not only on deep learning methods but also on forecasting loads on single building level. This study aims to research problems and possibilities arising by using different load-forecasting techniques to manage loads. For that behavior of two neural networks, Long Short-Term Memory and Feed-Forward Neural Network as well as two statistical methods, standardized load profiles and personalized standardized load profiles are analyzed and assessed by using a sliding-window forecast approach. The results show that personalized standardized load profiles (MAE: 3.99) can perform similar to deep learning methods (for example, LSTM MAE: 4.47). However, because of the simplistic approach, load profiles are not able to adapt to new patterns. As a case study for evaluating the support of load-forecasting for applications in energy management systems, the integration of charging stations into an existing building is simulated by using load-forecasts to schedule the charging procedures. It is shown that forecast- based controlled charging can have a significant impact by lowering overload peaks exceeding the house connection point power limit (controlled charging 20.24 kW; uncontrolled charging: 65.15 kW) while slightly increasing average charging duration. It is concluded that integration of high flexible loads can be supported by using forecast-based energy management systems with regards to their limitations.

Age-related decline in interhemispheric connectivity between motor areas has been reported with both transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) measurements. However, not all studies were able to confirm these findings, and previous studies did not apply structural (DTI) and functional (TMS) measurements within each individual appropriately. Here, we investigated age dependency of the ipsilateral silent period (ISP) and integrity of fibers in the corpus callosum as operationalized by fractional anisotrophy (FA), using TMS and DTI, respectively, in 20 participants between 19 and 72 years of age. We found age-dependent increase for ISP, and decrease of FA, both indicating a decrease in interhemispheric inhibition, with a negative association between FA and ISP for the dominant hemisphere (r = −0.39, p = 0.043). Our findings suggest that aging leads to decline of interhemispheric motor connectivity, as evidenced in both structural and functional parameters, which should be taken into account when interpreting disease- or medication-related changes.

Background: Several studies on patients with juvenile myoclonic epilepsy (JME) showed widespread white matter (WM) abnormalities in the brain. The aim of this study was to investigate potential structural abnormalities in JME patients (1) compared to healthy controls, (2) among JME subgroups with or without photoparoxysmal responses (PPR), and (3) in correlation with clinical variables.Methods: A selection of 31 patients with JME (12 PPR positive) and 27 age and gender matched healthy controls (HC) were studied at a tertiary epilepsy center. Fractional anisotropy (FA) was calculated and intergroup differences analyzed using Tract Based Spatial Statistics (TBSS).Results: Compared to HC the JME group showed reduced FA widespread and bilateral in the longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, anterior and posterior thalamic radiation, corona radiata, corpus callosum, cingulate gyrus and external capsule (p < 0.01). Subgroup analysis revealed no significant differences of WM alterations between PPR positive and negative patients and with clinical and epilepsy-related factors.Conclusions: Widespread microstructural abnormalities among patients with JME have been identified.Prior findings of frontal and thalamofrontal microstructural abnormalities have been confirmed. Additionally, microstructural abnormalities were found in widespread extra-frontal regions that may help to validate pathophysiological concepts of JME.

A fully automated transferable predictive approach was developed to predict photovoltaic (PV) power output for a forecasting horizon of 24 h. The prediction of PV power output was made with the help of a long short-term memory machine learning algorithm. The main challenge of the approach was using (1) publicly available weather reports without solar irradiance values and (2) measured PV power without any technical information about the PV system. Using this input data, the developed model can predict the power output of the investigated PV systems with adequate accuracy. The lowest seasonal mean absolute scaled error of the prediction was reached by maximum size of the training set. Transferability of the developed approach was proven by making predictions of the PV power for warm and cold periods and for two different PV systems located in Oldenburg and Munich, Germany. The PV power prediction made with publicly available weather data was compared to the predictions made with fee-based solar irradiance data. The usage of the solar irradiance data led to more accurate predictions even with a much smaller training set. Although the model with publicly available weather data needed greater training sets, it could still make adequate predictions.

Even if lower vaginal delivery success rates and impaired neonatal short-term outcomes have been reported for primiparous women with breech presentation, vaginal breech delivery remains an option for carefully selected patients. Because Magnetic resonance imaging (MRI) pelvimetry can provide additional information on maternal pelvic morphology, we sought to identify new MRI parameters that predict successful vaginal breech delivery.In this retrospective unicentre study, 240 primiparous women with breech presentation at term underwent MRI pelvimetry. For all patients vaginal delivery was planned, according to German guidelines and if the conjugata vera (CV) was ≥12 cm. The patients with uneventful vaginal deliveries and the patients who underwent a secondary caesarean section were compared according to pelvimetric parameters and outcomes. Regression analyses were performed.In the vaginal delivery group (n = 162, (67.5%)), the distance between the spinae ischiadicae (interspinous diameter, ISD) was significantly enlarged. The ISD significantly influenced the mode of delivery in the regression analyses. The CV did not significantly differ between the groups. The patients with successful vaginal deliveries were significantly younger than the patients who underwent caesarean section. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) for ISD was 67.7% (p

The article analyzes the poetics of scaling-up and clashing scales in the documentary/essay film Anthropocene: The Human Epoch by Jennifer Baichwal, Edward Burtynsky and Nicholas de Pencier from 2018. It reconstructs and exemplifies the idea that a poetics of scale can be useful and necessary for a comprehension of the Anthropocene following the arguments of Derek Woods, Eva Horn and Hannes Bergthaller amongst others. For example, a poetics of scale can make graspable the tensions and contradictions between the human as a global force – the multiple assemblages of human beings, technologies, other beings and materialities – and the human as an individual. But, as I argue with Hannah Arendt’s observation on the ‘stature of man’ in the space age, smoothly scaling-up to a global, universal point-of-view also reinforces the distanced world view that is at the root of the global ecological crises. I finally argue for an audiovisuality of the climate crisis that connects understanding and realization to activism and climate justice movements.