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We present a multi-stage and multi-resolution deformable image registration framework for image-guidance at a small animal proton irradiation platform. The framework is based on list-mode proton radiographies acquired at different angles, which are used to deform a 3D treatment planning CT relying on normalized mutual information (NMI) or root mean square error (RMSE) in the projection domain.We utilized a mouse X-ray micro-CT expressed in relative stopping power (RSP), and obtained Monte Carlo simulations of proton images in list-mode for three different treatment sites (brain, head and neck, lung). Rigid transformations and controlled artificial deformation were applied to mimic position misalignments, weight loss and breathing changes. Results were evaluated based on the residual RMSE of RSP in the image domain including the comparison of extracted local features, i.e. between the reference micro-CT and the one transformed taking into account the calculated deformation.The residual RMSE of the RSP showed that the accuracy of the registration framework is promising for compensating rigid (>97% accuracy) and non-rigid (∼95% accuracy) transformations with respect to a conventional 3D-3D registration. Results showed that the registration accuracy is degraded when considering the realistic detector performance and NMI as a metric, whereas the RMSE in projection domain is rather insensitive.This work demonstrates the pre-clinical feasibility of the registration framework on different treatment sites and its use for small animal imaging with a realistic detector. Further computational optimization of the framework is required to enable the use of this tool for online estimation of the deformation.

Background: Data regarding multiple switches including reverse switching between infliximab and its biosimilars are scarce in the field of inflammatory bowel diseases (IBD). Objectives: We investigated the clinical effectiveness as primary outcome measure after repeated switches. Secondary endpoints included C-reactive protein (CRP) levels, immunogenicity (trough levels (TL); anti-drug antibodies (ADA), safety and drug persistence. Design: This study is a prospective, single-centre, observational cohort study. IBD patients receiving originator infliximab were switched to biosimilar SB2 and then reverse switched after 96 weeks and followed up for another 48 weeks. Methods: Clinical disease activity (Harvey–Bradshaw-index (HBI) in Crohn’s disease (CD), partial Mayo score (pMS) in ulcerative colitis (UC)), CRP, TL, ADA, therapy-discontinuations and (serious) adverse events ((S)AE)) were monitored throughout the study. Results: Ninety-five patients (60 CD, 38 female) were enrolled. The median HBI was 2 (interquartile range (IQR) 1–4) at baseline and 2 (1–4) at week 48, resulting in a mean intra-individual change of 0.0 (standard deviation (SD) 1.5). The median pMS was 1 (IQR 0–1) at baseline and 0.5 (0–1) at week 48 resulting in a mean intra-individual change of 0.0 (SD 0.8). Clinical remission was achieved in 80% at baseline and 82% at week 48. Median CRP 2.0 mg/l (IQR 1.0–4.1) at baseline and 2.4 mg/l (1.1–5.2) at week 48 resulted in a mean change of 1.7 (SD 5.8) and no significant differences in CD ( p = 0.3) and UC ( p = 0.9). Median TL were 7.2 µg/ml (IQR 3.8–19.3) at baseline and 5.5 µg/ml (3.5–13.1) at week 48, resulting in a mean change of −1.0 (SD 7.4) with no statistical significance (CD p = 0.26, UC p = 0.41). De-novo-ADA were developed by 3.4%. The discontinuation rate was 14.7%. Safety signals were consistent with previous studies. Conclusion: Reverse switching had no impact on efficacy of infliximab therapy in our cohort of IBD patients. The switch didn’t influence immunogenicity or safety of therapy.

Abstract Magnetic skyrmions have raised high hopes for future spintronic devices. For many applications, it would be of great advantage to have more than one metastable particle-like texture available. The coexistence of skyrmions and antiskyrmions has been proposed in inversion-symmetric magnets with exchange frustration. However, so far only model systems have been studied and the lifetime of coexisting metastable topological spin structures has not been obtained. Here, we predict that skyrmions and antiskyrmions with diameters below 10 nm can coexist at zero magnetic field in a Rh/Co bilayer on the Ir(111) surface—an experimentally feasible system. We show that the lifetimes of metastable skyrmions and antiskyrmions in the ferromagnetic ground state are above one hour for temperatures up to 75 and 48 K, respectively. The entropic contribution to the nucleation and annihilation rates differs for skyrmions and antiskyrmions. This opens the route to the thermally activated creation of coexisting skyrmions and antiskyrmions in frustrated magnets with Dzyaloshinskii–Moriya interaction.

Abstract Background Agricultural yields have increased continuously over the last few decades. However, a focus solely on production can harm the environment. Diversification of agriculture has been suggested to increase production and sustainability. Biodiversity experiments showed positive effects on ecosystems and productivity. However, application of these results to intensively managed grasslands has been questioned due to differences in plant species and management regimes. Research on whether diversity can benefit multifunctionality, that is, an integrated index of multiple ecosystem functions, under intensive management, is still scarce. Methods To address this, we manipulated plant species richness from one to six species spanning three functional groups (legumes, herbs, and grasses) in intensively managed multispecies grassland leys and examined seven ecosystem functions. Results We found that multifunctionality increased with functional group and species richness. Legume+herb mixtures showed high multifunctionality, while grass monocultures and mixtures with high proportions of grasses had low multifunctionality. Different plant species and plant communities drove different ecosystem functions. Legumes and herbs improved productivity and water availability, while grasses enhanced invasion resistance. These results indicate that multifunctionality and individual ecosystem functions can be promoted through targeted combinations of plants with complementary ecological traits. Conclusions Plant diversity can improve multifunctionality also under intensive management, potentially benefitting agroeconomics and sustainability.

Background and Purpose: The lack of dedicated tools in commercial planning systems currently restricts efficient review and planning for re-irradiation. The aim of this study was to develop an automated re-irradiation planning framework based on cumulative doses. Materials and Methods: We performed a retrospective study of 14 patients who received spine SBRT re-irradiation near a previously irradiated treatment site. A fully-automated workflow, DART (Dose Accumulation-based Re-irradiation Tool), was implemented within Eclipse by leveraging a combination of a dose accumulation script and a proprietary automated optimization algorithm. First, we converted the prior treatment dose into equivalent dose in 2 Gy fractions (EQD2) and mapped it to the current anatomy, utilizing deformable image registration. Subsequently, the intersection of EQD2 isodose lines with relevant organs at risk defines a series of optimization structures. During plan optimization, the residual allowable dose at a specified tissue tolerance was treated as a hard constraint. Results: All DART plans met institutional physical and cumulative constraints and passed plan checks by qualified medical physicists. DART demonstrated significant improvements in target coverage over clinical plans, with an average increase in PTV D99% and V100% of 2.3 Gy [range −0.3–7.7 Gy] and 3.4 % [range −0.4 %−7.6 %] (p 105 %) outside the PTV was reduced by up to 7 cm3. The homogeneity index for DART plans was improved by 19 % (p

Abstract Background Severe dementia is one of the most challenging conditions when caring for people in nursing homes. A manualised non-pharmacological, psychosocial group intervention especially adapted to the needs of people with severe dementia (PWSDs) is currently still lacking. To close this gap, we adapted the evidence-based multicomponent non-pharmacological MAKS intervention (Motor stimulation, ADL stimulation, Cognitive [german: Kognitive] stimulation, and Social functioning in a group setting) to the special needs of PWSDs called the MAKS-s intervention, where the s stands for severe dementia. Methods In a prospective, multicentre, cluster-randomised trial with a waitlist control group design, 26 nursing homes comprising 152 PWSDs were randomly assigned to either the MAKS-s intervention group (IG) or control group (CG) – 121 PWSDs were still alive after the 6-month intervention period (t6) and included in the intention-to-treat (ITT) sample. The two primary outcomes, behavioural and psychological symptoms (BPSDs, measured with NPI-NH) and quality of life (QoL, measured with QUALIDEM), and the secondary outcome, activities of daily living (ADLs, measured with ADCS-ADL-sev), were assessed at baseline (t0) and at t6. Mixed ANOVAs were computed to investigate possible effects of the MAKS-s intervention on the outcomes. Results In the ITT sample, BPSDs and QoL did not change significantly over time, and group assignment did not affect them, although the IG participants had significantly better overall QoL than the CG participants. ADLs decreased significantly over time, but group assignment did not affect them. Analyses in the per protocol (PP) sample showed comparable results, with the exception that the IG participants showed a significantly greater increase in BPSDs than the CG participants did. Discussion Under the situational conditions of the Covid-19 pandemic, no beneficial effects of the MAKS-s intervention on BPSDs, QoL, or ADLs were observed. This finding also means that under ‘normal circumstances’ (i.e., if there had been no pandemic), we could not make any statements about the effect or non-effect of MAKS-s. In order to be able to address the hypotheses formulated here, the study will have to be repeated incorporating helpful experiences of the present study. Trial registration https://doi.org/10.1186/ISRCTN15722923 (Registered prospectively, 07. August 2019).

Background and purpose: Aluminum can be released into food by aluminum-containing food-contact materials (Al-FCM) during preparation or storage. There is considerable concern that extra aluminum intake may have negative effects on public health, especially with regard to its high background exposure and neurotoxic properties of aluminum in high exposures. Human in-vivo data on the additional aluminum load from Al-FCM, however, are lacking. As such, the objective of this study was to explore whether the consumption of a diet highly exposed to such products leads to an increased systemic Al load in real-world conditions. Materials and methods: An exploratory, single-arm intervention study with a partially standardized diet was designed and carried out with 11 participants. The same 10-day sequence of dishes was repeated three times. Participants were exposed to Al-FCM from Days 11 to 20, whereas control-phase meals were prepared without Al-FCM during the first and last 10–day periods. Spot urine samples were collected each morning and evening and analyzed for their aluminum concentration; appropriate contamination countermeasures were taken.Principal results: Urinary aluminum excretion showed a strong dependency on the creatinine concentration in urine and required adjustment in further analyses. The creatinine-adjusted aluminum excretion during the exposure phase (median 1.98 µg/g creatinine) was higher than in both control phases (1.78 µg/g creatinine each). Two different mixed-effects regression models showed a significant effect in the exposure phase. Considering a discrete time effect, the creatinine-adjusted mean increase in the exposure phase was estimated to be 0.19 µg/L (95% CI: 0.07–0.31; p = 0.0017).Major conclusions: This study demonstrated a measurable but fully reversible additional Al burden in humans from subacute Al-FCM exposure under real-world conditions. The estimated increase from Al-FCM corresponds to 8% of the baseline concentration. These data enable a more robust assessment of human health risks by Al-FCM.

Proton computed tomography (pCT) is a promising tomographic imaging modality allowing direct reconstruction of proton relative stopping power (RSP) required for proton therapy dose calculation. In this review article, we aim at highlighting the role of Monte Carlo (MC) simulation in pCT studies. After describing the requirements for performing proton computed tomography and the various pCT scanners actively used in recent research projects, we present an overview of available MC simulation platforms. The use of MC simulations in the scope of investigations of image reconstruction, and for the evaluation of optimal RSP accuracy, precision and spatial resolution omitting detector effects is then described. In the final sections of the review article, we present specific applications of realistic MC simulations of an existing pCT scanner prototype, which we describe in detail.

A novel irradiation platform for preclinical proton therapy studies foresees proton imaging for accurate setup and treatment planning. Imaging at modern synchrocyclotron-based proton therapy centers with high instantaneous particle flux is possible with an integration mode setup. The aim of this work is to determine an object’s water-equivalent thickness (WET) with a commercially available large-area CMOS sensor. Image contrast is achieved by recording the proton energy deposition in detector pixels for several incoming beam energies (here, called probing energies) and applying a signal decomposition method that retrieves the water-equivalent thickness. A single planar 114 mm × 65 mm CMOS sensor (49.5 µm pixel pitch) was used for this study, aimed at small-animal imaging. In experimental campaigns, at two isochronous cyclotron-based facilities, probing energies suitable for small-animal-sized objects were produced once with built-in energy layer switching and the other time, using a custom degrader wheel. To assess water-equivalent thickness accuracy, a micro-CT calibration phantom with 10 inserts of tissue-mimicking materials was imaged at three phantom-to-detector distances: 3 mm, 13 mm, and 33 mm. For 3 mm and 13 mm phantom-to-detector distance, the average water-equivalent thickness error compared to the ground truth was about 1% and the spatial resolution was 0.16(3) mm and 0.47(2) mm, respectively. For the largest separation distance of 33 mm air gap, proton scattering had considerable impact and the water-equivalent thickness relative error increased to 30%, and the spatial resolution was larger than 1.75 mm. We conclude that a pixelated CMOS detector with dedicated post-processing methods can enable fast proton radiographic imaging in a simple and compact setup for small-animal-sized objects with high water-equivalent thickness accuracy and spatial resolution for reasonable phantom-to-detector distances.

Abstract Increasing plant species richness has been shown to positively affect the diversity of a range of other organisms, both above‐ and belowground. Although ants have a multitude of interactions with other organisms through their role as predators and mutualists, ants are a taxon that has rarely been investigated in studies of biodiversity effects. Ants are known to respond to changes in microclimatic conditions such as temperature and humidity, and these microclimatic conditions are known to be affected by vegetation characteristics such as standing biomass, which in turn can be affected by plant diversity. We investigated the effects of plant species richness (1–60), the number of plant functional groups (FGs; 1–4), and the presence of particular FGs on the occurrence and activity of ants, in the context of a grassland biodiversity experiment. Ant abundance, estimated as the mean number of workers in pitfall traps, and the number of colonies within plots, but not ant species richness, were negatively affected by plant species richness, and also by the identity of plant FGs, particularly legumes (negative effects) and grasses (positive effects). Statistical approaches showed that these effects were largely mediated by biotic (aboveground plant biomass: negative effect) and abiotic variables (soil temperature: positive effect). Notably, ant activity, measured as the mean number of workers foraging on baits and with a disproportionate dominance of a single species (Lasius niger), showed a more complex pattern, where plant species richness and number of FGs interacted to explain differential attractiveness to different resources (represented by sugar and tuna baits), likely representing current nutritional requirements for ants. Similarly, increasing soil temperature increased the level of ant activity, indicating that abiotic factors might impose thermal constraints on ectotherms inhabiting temperate grasslands. Our results indicate that a higher number of plant species and higher plant biomass had a negative effect on ants in experimental grasslands. Understanding the responses of an ecologically important group such as ants will allow us to infer the effects that biodiversity loss could have on animal‐mediated ecosystem processes.

Abstract The dark-field signal measures the small-angle scattering strength and provides complementary diagnostic information. This is of particular interest for lung imaging due to the pronounced small-angle scatter from the alveolar microstructure. However, most dark-field imaging techniques are relatively complex, dose-inefficient, and require sophisticated optics and highly coherent X-ray sources. Speckle-based imaging promises to overcome these limitations due to its simple and versatile setup, only requiring the addition of a random phase modulator to conventional X-ray equipment. We investigated quantitatively the influence of sample structure, setup geometry, and source energy on the dark-field signal in speckle-based X-ray imaging with wave-optics simulations for ensembles of micro-spheres. We show that the dark-field signal is accurately predicted via a model originally derived for grating interferometry when using the mean frequency of the speckle pattern power spectral density as the characteristic speckle size. The size directly reflects the correlation length of the diffuser surface and did not change with energy or propagation distance within the near-field. The dark-field signal had a distinct dependence on sample structure and setup geometry but was also affected by beam hardening-induced modifications of the visibility spectrum. This study quantitatively demonstrates the behavior of the dark-field signal in speckle-based X-ray imaging.

The functioning and service provisioning of ecosystems in the face of anthropogenic environmental and biodiversity change is a cornerstone of ecological research. The last three decades of biodiversity–ecosystem functioning (BEF) research have provided compelling evidence for the significant positive role of biodiversity in the functioning of many ecosystems. Despite broad consensus of this relationship, the underlying ecological and evolutionary mechanisms have not been well understood. This complicates the transition from a description of patterns to a predictive science. The proposed Research Unit aims at filling this gap of knowledge by applying novel experimental and analytical approaches in one of the longest-running biodiversity experiments in the world: the Jena Experiment. The central aim of the Research Unit is to uncover the mechanisms that determine BEF relationships in the short- and in the long-term. Increasing BEF relationships with time in long-term experiments do not only call for a paradigm shift in the appreciation of the relevance of biodiversity change, they likely are key to understanding the mechanisms of BEF relationships in general. The subprojects of the proposed Research Unit fall into two tightly linked main categories with two research areas each that aim at exploring variation in community assembly processes and resulting differences in biotic interactions as determinants of the long-term BEF relationship. Subprojects under “Microbial community assembly” and “Assembly and functions of animal communities” mostly focus on plant diversity effects on the assembly of communities and their feedback effects on biotic interactions and ecosystem functions. Subprojects under “Mediators of plant-biotic interactions” and “Intraspecific diversity and micro-evolutionary changes” mostly focus on plant diversity effects on plant trait expression and micro-evolutionary adaptation, and subsequent feedback effects on biotic interactions and ecosystem functions. This unification of evolutionary and ecosystem processes requires collaboration across the proposed subprojects in targeted plant and soil history experiments using cutting-edge technology and will produce significant synergies and novel mechanistic insights into BEF relationships. The Research Unit of the Jena Experiment is uniquely positioned in this context by taking an interdisciplinary and integrative approach to capture whole-ecosystem responses to changes in biodiversity and to advance a vibrant research field.

Isolated skyrmions with diameters below 10 nm stabilized at zero magnetic field are of great technological relevance to the future spintronic applications. Here the authors report stabilization of zero field isolated skyrmions with diameters smaller than 5 nm in Rh/Co atomic bilayers on the Ir(111) surface.

Behavioral variant frontotemporal dementia (bvFTD) is characterized by severe changes in personality/behavior. Recent studies have provided evidence that a decrease in serotonin receptors and neuronal loss in the raphe nuclei play a role in the bvFTD pathology. Serotonergic antidepressants have been reported to diminish behavioral disturbances in bvFTD, particularly repetitive behaviors, disinhibition, apathy, sexually inappropriate behaviors, and hyperorality. Here, we present the case of an 80-year-old Caucasian male patient with clinically and biomarker supported bvFTD (“probable” bvFTD; disease-specific alterations in 18F-fluorodesoxyglucose positron emission tomography and magnetic resonance imaging). The patient exhibited behavioral disinhibition, apathy, a loss of empathy, perseverative behavior during testing, hyperorality, changes in diet, and executive deficits in neuropsychological testing. Remarkably, he failed in solving crosswords by systematically filling in the blanks by letters in alphabetical order (A, B, C, D, etc.), indicating obsessive-compulsive behavior. One year later, the patient visited the clinic again for a follow-up investigation. He had taken 20 mg of citalopram per day for 1 consecutive year. Remarkably, he had regained the ability to fill in crossword puzzles correctly, although the neuropsychiatric inventory showed overall only small improvement in behavioral impairment. A regimen of 20 mg citalopram per day over the course of 1 year led to a specific improvement in one of the bvFTD core symptoms, obsessive-compulsive behavior, most pronounced in solving crossword puzzles. This case contributes to the understanding of the neuropharmacological correlates of bvFTD and supports the treatment of bvFTD’s behavioral symptoms with selective serotonin reuptake inhibitors.

Background: Long-term data on inflammatory bowel disease (IBD) patients switched from originator to biosimilar infliximab SB2 are lacking. The aim of the conducted study was to investigate the effectiveness, immunogenicity and safety of a large prospectively followed-up IBD patient cohort that was entirely switched from originator infliximab to biosimilar SB2 treatment. Methods: This was a prospective, single-center, longitudinal, observational study describing clinical outcomes in IBD patients, over an 80-week period following switch from originator infliximab to SB2. Primary outcome measures were change of disease activity [Harvey-Bradshaw Index for Crohn’s disease (CD), partial Mayo Score for ulcerative colitis (UC)], C-reactive protein (CRP), infliximab trough levels (TLs), anti-drug antibodies (ADAs) and adverse events. Results: One hundred and forty-four IBD patients (94 CD, 50 UC), with median duration of 30.5 months’ (range 2–110) treatment with originator infliximab were evaluated. Mean change of disease activity compared with baseline was −0.9 (SD 2.6), –0.4 (2.2) and –0.4 (2.0) in CD; 0.1 (1.1), 0.1 (1.1) and 0.1 (1.3) in UC patients at weeks 24, 48 and 72. Median infliximab TLs were 6.2 µg/ml (interquartile range 2.3–12.2), 5.0 µg/ml (2.7–10.0), 6.6 µg/ml (3.5–12.4) and 5.1 µg/ml (2.7–10.9) at baseline and weeks 24, 48 and 72. Median CRP levels were within normal ranges throughout the study. After the switch, 9.8% of the patients developed new ADAs. Persistence on SB2 was 90% (95% confidence interval 0.85–0.95), 79% (0.72–0.86), 72% (0.64–0.80) at weeks 26, 52 and 78. Serious adverse events occurred in 11 patients. Conclusion: Over the individual patient follow-up of 80 weeks, switch to biosimilar SB2 from originator infliximab does not result in increased disease activity or changed immunogenicity patterns. The switch to SB2 was well tolerated.

Abstract Background The ability to perform activities of daily living (ADLs) is a central marker in the diagnosis and progression of the dementia syndrome. ADLs can be identified as basic ADLs (BADLs), which are fairly easy to perform, or instrumental ADLs (IADLs), which involve more complex activities. Presently, the only performance-based assessment of IADL capabilities in persons with cognitive impairment is the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM). The aim of the present study was to revalidate the ETAM in persons with mild cognitive impairment (MCI) or mild dementia and to analyze its application to persons with moderate dementia. Methods We used baseline data from a cluster randomized controlled trial involving a sample of 443 users of 34 day-care centers in Germany. We analyzed groups of persons with MCI, mild dementia, and moderate dementia, categorized on the basis of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). An item analysis was performed, and new discriminant validities were calculated. We computed a confirmatory factor analysis (CFA) to examine the postulated theoretical model of the ETAM with all six items loading on a single IADL factor. This was the first time that the ETAM’s sensitivity to change was analyzed after a time period of 6 months. Results The overall sample scored on average 17.3 points (SD = 7.2) on the ETAM (range: 0–30 points). Persons with MCI scored on average 23.2 points, persons with mild dementia scored 18.4 points, and persons with moderate dementia scored 12.9 points, p

Magnesium–silver alloys are of high interest for the use as temporary bone implants due to their antibacterial properties in addition to biocompatibility and biodegradability. Thin wires in particular can be used for scaffolding, but the determination of their degradation rate and homogeneity using traditional methods is difficult. Therefore, we have employed 3D imaging using X-ray near-field holotomography with sub-micrometer resolution to study the degradation of thin (250 μm diameter) Mg-2Ag and Mg-6Ag wires. The wires were studied in two states, recrystallized and solution annealed to assess the influence of Ag content and precipitates on the degradation. Imaging was employed after degradation in Dulbecco’s modified Eagle’s medium and 10% fetal bovine serum after 1 to 7 days. At 3 days of immersion the degradation rates of both alloys in both states were similar, but at 7 days higher silver content and solution annealing lead to decreased degradation rates. The opposite was observed for the pitting factor. Overall, the standard deviation of the determined parameters was high, owing to the relatively small field of view during imaging and high degradation inhomogeneity of the samples. Nevertheless, Mg-6Ag in the solution annealed state emerges as a potential material for thin wire manufacturing for implants.

The availability of geocoded health data and the inherent temporal structure of communicable diseases have led to an increased interest in statistical models and software for spatio-temporal data with epidemic features. The open source R package surveillance can handle various levels of aggregation at which infective events have been recorded: individual-level time-stamped geo-referenced data (case reports) in either continuous space or discrete space, as well as counts aggregated by period and region. For each of these data types, the surveillance package implements tools for visualization, likelihoood inference and simulation from recently developed statistical regression frameworks capturing endemic and epidemic dynamics. Altogether, this paper is a guide to the spatio-temporal modeling of epidemic phenomena, exemplified by analyses of public health surveillance data on measles and invasive meningococcal disease.

Purpose: Frontotemporal lobar degeneration (FTLD) is a common cause of early onset dementia. Behavioral variant frontotemporal dementia (bvFTD), its most common subtype, is characterized by deep alterations in behavior and personality. In 2011, new diagnostic criteria were suggested that incorporate imaging criteria into diagnostic algorithms. The study aimed at validating the potential of imaging criteria to individually predict diagnosis with machine learning algorithms. Materials & methods: Brain atrophy was measured with structural magnetic resonance imaging (MRI) at 3 Tesla in a multi-centric cohort of 52 bvFTD patients and 52 healthy control subjects from the German FTLD Consortium's Study. Beside group comparisons, diagnosis bvFTD vs. controls was individually predicted in each subject with support vector machine classification in MRI data across the whole brain or in frontotemporal, insular regions, and basal ganglia known to be mainly affected based on recent meta-analyses. Multi-center effects were controlled for with a new method, “leave one center out” conjunction analyses, i.e. repeatedly excluding subjects from each center from the analysis. Results: Group comparisons revealed atrophy in, most consistently, the frontal lobe in bvFTD beside alterations in the insula, basal ganglia and temporal lobe. Most remarkably, support vector machine classification enabled predicting diagnosis in single patients with a high accuracy of up to 84.6%, where accuracy was highest in a region-of-interest approach focusing on frontotemporal, insular regions, and basal ganglia in comparison with the whole brain approach. Conclusion: Our study demonstrates that MRI, a widespread imaging technology, can individually identify bvFTD with high accuracy in multi-center imaging data, paving the road to personalized diagnostic approaches in the future.

Background: Chemical UV filters are common components in sunscreens and cosmetic products and used to protect the skin against harmful effects of sunlight like sunburn. However, the effectiveness of sunscreens in the prevention of skin cancer is in some parts still controversial. Meanwhile, questions about negative effects of the chemical UV filters on human health arise and request an effective risk assessment. Real-life exposure data in humans after application of these products are still rare. Thus, we explored whether and to what extent UV filters are absorbed through the skin into the human body. Material and methods: Plasma and urine samples from 20 healthy volunteers were collected before, during and after a real-life exposure scenario (1st application: 2 mg/cm2; 2nd and 3rd (after 2 and 4 h): 1 mg/cm2 each) using a commercial sunscreen formulation for one day. These samples were analyzed for their content of the currently prominent UV filters octocrylene and avobenzone as well as 2-cyano-3,3-diphenylacrylic acid (CDAA) as the main octocrylene metabolite by using different liquid chromatography electrospray-ionization tandem mass spectrometric procedures. Results: Following dermal sunscreen exposure, avobenzone, octocrylene and CDAA reached concentrations up to 11 μg/L, 25 μg/L and 1352 μg/L in plasma. In urine detection rates of avobenzone and octocrylene were low while CDAA showed a high detection rate and reached up to 5207 μg/g creatinine. Kinetic models could be fitted for octocrylene and CDAA in plasma and CDAA in urine. Concentration peaks were reached between 10 and 16 h after first application and half-life periods were in the range of 1.5 to 2 days. The lipophilic UV filter octocrylene and its metabolite CDAA showed a much slower elimination than other more hydrophilic UV filters. Concordantly, the metabolite CDAA in particular showed a markedly increased renal excretion over the whole sampling period and indicated high internal exposure to OC. Discussion: Real-life sunscreen usage leads to considerable bioavailability of organic UV filters and their metabolites which is rarely seen for other environmental exposures. A combined monitoring of the parent compound and its metabolites is important to fully address internal exposure to the UV filter in humans. Considering the kinetic profiles a prolonged systemic release due to depot formation in skin and a potential accumulation through multi-day exposure is presumed. High in-vivo loads call for a critical toxicological assessment of the UV filters and their metabolites. Keywords: UV filter, Avobenzone, Octocrylene, Biomonitoring, Sunscreen, Exposure assessment, Toxicology

Using spin-polarized scanning tunneling microscopy (STM) we observe a two-dimensional c(2×2) antiferromagnetic state in a pseudomorphic Mn double layer on the W(001) surface. First-principles calculations confirm the antiferromagnetic ground state. Surprisingly, only the surface Mn layer possesses a magnetic moment while the moments of interface Mn atoms vanish. Calculated STM and spin-polarized STM images as well as local vacuum density of states are in good agreement with experiments and provide strong evidence of a dead magnetic interface layer.

It is a relatively new concept to use biochar as soil amendment and for climate change mitigation. For this reason, the national and supranational legislation in the EU is not yet adequately prepared to regulate both the production and the application of biochar. Driven by this “regulatory gap”, voluntary biochar quality standards have been formed in Europe with the European Biochar Certificate, in the UK with the Biochar Quality Mandate and in the USA with the IBI Standard which is intended to be used internationally. In parallel to this, biochar producers and biochar users in a number of EU countries were partly successful in fitting the new biochar product into the existing national legislation for fertilisers, soil improvers and composts. The intended revision of the EC Regulation 2003/2003 on fertilisers offers the opportunity to regulate the use of biochar at the EU level. This publication summarizes the efforts on biochar standardization which have been carried out by voluntary products standards and illustrates existing legislation in EU member states, which apply to the production and use of biochar. It describes existing and planned EU regulations, which impact biochar applications and it develops recommendations on the harmonization of biochar legislation in the EU. First published online: 24 Jan 2017

This article deals with the DFG Viewer for Interoperability, a free and open source web-based viewer for digitised books, and assesses its relevance for interoperability in Germany. First the specific situation in Germany is described, including the important role of the Deutsche Forschungsgemeinschaft (German Research Foundation). The article then moves on to the overall concept of the viewer and its technical background. It introduces the data formats and standards used, it briefly illustrates how the viewer works and includes a few examples.