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Engineered gold nanoparticles (GNPs) have become a useful tool in various therapeutic and diagnostic applications. Uncertainty remains regarding the possible impact of GNPs on the immune system. In this regard, we investigated the interactions of polymer-coated GNPs with B cells and their functions in mice. Surprisingly, we observed that polymer-coated GNPs mainly interact with the recently identified subpopulation of B lymphocytes named age-associated B cells (ABCs). Importantly, we also showed that GNPs did not affect cell viability or the percentages of other B cell populations in different organs. Furthermore, GNPs did not activate B cell innate-like immune responses in any of the tested conditions, nor did they impair adaptive B cell responses in immunized mice. Together, these data provide an important contribution to the otherwise limited knowledge about GNP interference with B cell immune function, and demonstrate that GNPs represent a safe tool to target ABCs

Introduction Urothelial bladder cancer (UBC) with clinical suspicion of locally advanced growth or pelvic lymphogenic spread has a high risk of progression and death. Patients and methods Bladder cancer patients with locally advanced (cT3/4) tumor growth or suspected pelvic lymphogenic spread (cN+) were treated with preoperative cisplatin-containing chemotherapy and consolidative cystectomy with pelvic lymphadenectomy. We aimed to identify prognostic factors and describe the patients’ oncological outcome. Results A complete dataset including follow-up data was available for 96 patients. In a univariate analysis, we identified cN stage (cN+ vs cN-, HR 2.7, 95% CI 1.3–6.0), response to chemotherapy (HR 0.2, 95% CI 0.1–0.5), ypT stage (ypT0/is/1 vs ypT2-4, HR 3.1, 95% CI 1.4–6.8), ypN stage (ypN + vs ypN-, HR 7.9, 95% CI 3.7–17.0), resection status (HR 4.4, 95% CI HR 1.5–13.0) as significantly associated with cancer-specific survival. In a multivariate regression analysis, both cN and ypN statuses were validated as independent prognostic factors for cancer-specific survival (cN: HR 2.6, 95% CI 1.1–6.1; ypN: HR 5.5, 95% CI 2.0–15.1). Discussion Lymph node status was identified as a prognostic marker in a high-risk cohort of UBC patients treated with inductive chemotherapy and cystectomy. Establishing cN status as a prognosticator underlines the necessity to aggressively treat these patients despite reported impreciseness of imaging procedures in UCB. Patients with histologically positive lymph nodes following preoperative chemotherapy have a very poor prognosis, and thus, the need for adjuvant systemic treatment is emphasized. Conclusion Both clinically and pathologically affected lymph nodes convey a poor prognosis in bladder cancer and necessitate aggressive treatment.

The Arctic warms four times faster than the global average, resulting in widespread permafrost thaw. Organic matter that was stored in permanently frozen soil for up to millennia now becomes available to microbial decomposition. Warming might also alter microbial community composition and physiology and thus change the decomposition potential of soils. Our current knowledge about permafrost soil organic matter (SOM) composition and decomposition is limited, particularly in regard to the heterogeneity of permafrost landscapes, thus hampering our ability to predict possible permafrost soil feedbacks to climate change. The objective of this study was to characterize SOM and microbial community composition of the active layer and the upper permanently frozen soil from permafrost-affected polygonal lowland tundra.We collected more than 80 soil samples from four different soil layers (organic, mineral, cryoturbated, permanently frozen) from three developmental stages of ice-wedge polygons (low-center, flat-center, high-center polygons) in NW Canada, and analyzed organic matter composition by a pyrolysis-GC/MS fingerprinting approach and microbial community composition by amplicon sequencing of the 16S rRNA gene (bacteria, archaea) and the ITS1 region (fungi).Our results suggest that the spatial heterogeneity of permafrost soils is not only reflected in soil physical parameters, but also in the chemical composition of organic matter and the composition of microbial communities. The organic soil layer comprised both the highest microbial diversity and the most diverse SOM composition. The distribution of major compound classes (carbohydrates, lignins, lipids, N-compounds, phenols & aromatics) differed between organic, mineral, cryoturbated and permanently frozen organic matter. This pattern followed a gradient from low to high organic matter degradation with soil depth. Soil organic matter composition also differed among polygon types, indicating different decomposition pathways, likely depending on differences in vegetation and soil water availability. We also found distinct microbial communities for soils from low-center polygons, possibly driven by prevailing anoxic conditions in this landscape unit. Bacterial and archaeal communities differed among all soil layers, while only fungal communities from the organic soils differed from the other layers.The observed differences in SOM and microbial community composition among soil layers and polygon types highlight the importance of considering spatial heterogeneity when studying permafrost soils. Moreover, our results might help to explain observed differences in microbial decomposition patterns on different spatial scales and emphasize the need to include aspects of permafrost soil heterogeneity to finetune current ecosystem and climate models.This study is part of the EU H2020 project “Nunataryuk”.

IntroductionHigh consumption of red and processed meat increases the risk of several chronic diseases. Many people, especially in high-income countries, eat more meat than recommended by nutritional and health agencies. Meat production also has negative impacts on the environment and contributes to climate change. Therefore, climate protection, besides health or animal welfare, could motivate individuals to eat less meat. Willingness to reduce meat consumption and motives to do so are not yet fully understood.Methods and analysisBased on the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) extended guidelines, a scoping review of peer-reviewed original studies will be conducted to address three questions: What is the evidence regarding (1) the willingness of individuals to reduce meat consumption to mitigate climate change, (2) the awareness of individuals about the link between their meat consumption and the potential to mitigate climate change and (3) individuals having reduced meat consumption for the reason of climate protection? We will search the databases Medline (via PubMed), Scopus, Embase, Greenfile (via Ebsco) and PsynDex/CurrentContent/Agris (via Livivo) using a systematic search string. Studies from 2015 onwards, published in English, German, Danish or Dutch, will be included. We will include observational studies, qualitative studies, intervention studies (if they include surveys) and reviews. Data will be summarised in a narrative synthesis, comprising methods, population characteristics, meat type under study, indicators measured and limitations. Key findings will be grouped according to the research questions. This scoping review will help clarify the role of climate protection in individual reduction of meat consumption and identify research gaps in this field.Ethics and disseminationFormal ethical approval is not required, as primary data will not be collected in this study. Findings of this scoping review will be presented at scientific conferences and published in a peer-reviewed journal.Trial registration numberhttps://doi.org/10.17605/OSF.IO/MWB85.

Climate change threatens the Earth’s biggest terrestrial organic carbon reservoir: permafrost soils. With climate warming, frozen soil organic matter may thaw and become available for microbial decomposition and subsequent greenhouse gas emissions. Permafrost soils are extremely heterogenous within the soil profile and between landforms. This heterogeneity in environmental conditions, carbon content and soil organic matter composition, potentially leads to different microbial communities with different responses to warming. The aim of the present study is to (1) elucidate these differences in microbial community compositions and (2) investigate how these communities react to warming.We performed short-term warming experiments with permafrost soil organic matter from northwestern Canada. We compared two sites characterized by different glacial histories (Laurentide Ice Sheet cover during LGM and without glaciation), three landscape types (low-center, flat-center, high-center polygons) and four different soil horizons (organic topsoil layer, mineral topsoil layer, cryoturbated soil layer, and the upper permanently frozen soil layer). We incubated aliquots of all soil samples at 4 °C and at 14 °C for 8 weeks and analyzed microbial community compositions (amplicon sequencing of 16S rRNA gene and ITS1 region) before and after the incubation, comparing them to microbial growth, microbial respiration, microbial biomass and soil organic matter composition.We found distinct bacterial, archaeal and fungal communities for soils of different glaciation history, polygon types and for different soil layers. Communities of low-center polygons differ from high-center and flat-center polygons in bacterial, archaeal and fungal community compositions, while communities of organic soil layers are significantly different from all other horizons. Interestingly, permanently frozen soil layers differ from all other horizons in bacterial and archaeal, but not fungal community composition.The 8-week incubations led to minor shifts in bacterial and archaeal community composition between initial soils and those subjected to 14 °C warming. We also found a strong warming effect on the community compositions in some of the extreme habitats: microbial community compositions of (i) the upper permanently frozen layer and of (ii) low-center polygons differ significantly for incubations at 4 °C and 14 °C. Yet, the lack of a community change in horizons of the active layer suggests that microbes are adapted to fluctuating temperatures due to seasonal thaw events.Our results suggest that warming responses of permafrost soil organic matter, if not frozen or water-saturated, may be predictable by current models. Process changes induced by short-term warming can be rather attributed to changes in microbial physiology than community composition.This work is part of the EU H2020 project “Nunataryuk”.

Incurable gliomas are characterized by their infiltration into the whole brain. Recently, we described tumor microtubes as a novel structure contributing to glioma cell invasion and uncovered synaptic contacts on glioma cells that drive brain tumour progression. However, the exact effects of neuronal activity on glioma cell motility are yet unclear. Here, we show how a recently described neuronal-like cellular transcription state of glioblastoma cells is correlated to glioma cell invasion in vivo. To unravel the details of neuronal features of glioma invasion in space and time, we established a novel approach of intravital imaging for brain tumor cells with a membrane-bound GFP combined with deep learning algorithms that are used to track glioma cell processes with a high temporal resolution over several hours. This approach uncovers how invading tumor microtubes use Levy-like movement patterns indicative of efficient search patterns often employed by animal predators searching for scarce resources such as food. Neuronal activity is able to accelerate the tumor microtube dynamics, accelerate the Levy-like movement patterns and increase the overall invasion speed of glioma cells. These processes are mediated by local calcium transients in glioma cell somata and tumor microtubes. In accordance, genetic manipulation and pharmacological perturbation of AMPA receptors reduces tumor microtube length, number and branching points by interfering with intracellular calcium transients. All in all, the work here uncovers novel neuronal activity-mediated mechanisms of glioma cell invasion, a hallmark of this yet fatal disease.

Aboveground vegetation biomass in northern treeless landscapes - peatlands and Arctic tundra - has been modelled with spectral information derived from optical remote sensing in several studies. However, synthesized overviews of biomass patterns across circumpolar sites have been limited. Based on data from eight study sites in Europe, Siberia and Canada, we ask (1) how biomass is divided between plant functional types (PFTs) and (2) how well biomass patterns can be detected with widely available, moderate spatial resolution (3-10 m) satellite imagery and topographic data. We explain biomass patterns using random forest regressions with the predictors being spectral bands and indices calculated from multi-temporal Sentinel-2 and PlanetScope imagery and topographic information calculated from ArcticDEM data. Our results indicate that there are notable differences in vegetation composition between northern landscapes with mosses, graminoids and deciduous shrubs being the most dominant PFTs. Remote sensing data detects biomass patterns, but regression performance varies between sites (explained variance 36-70%, normalized root mean square error 9-19%). There is also variability between sites whether Sentinel-2 or PlanetScope data is more suitable to detect biomass patterns and which the most important predictors are. Topographic information has a minor or negligible importance in most of the sites. Our results suggest that there is no easily generalizable relationship between satellite-derived vegetation greenness and biomass.

The European Commission has been setting the course for an EU-wide reform of the traditional corporate tax system of separate accounting (SA) to a unitary taxation with formula apportionment (FA). The underlying claim of this formula is that it allocates profits more precisely than SA to the country where the value is created, as SA can be distorted by intra-group profit shifting. We analyze and evaluate the proposed CCCTB apportionment formula in terms of how well FA approximates the “undistorted” profit. After identifying potential determinants of misapportionment in the CCCTB formula, we test the formula empirically by randomly grouping pairs of European groups to fictitious metagroups. We allocate profits to the metagroup members according to the formula and compare the apportioned FA profit with the observed SA profit (our proxy for “undistorted” profit). We find huge profit misallocations under FA. Restricting the sample to metagroup years with positive profit of each metagroup member, the mean negative (positive) profit deviation is − 4.2% (6.2%) of total assets. Compared to the mean return on assets of the sample, this results in an average error of − 49.5% or + 74.1%, respectively. The deviation caused by FA is systematic. The main drivers for profit misallocations are the profitability of a firm as well as the within-group heterogeneity in firm size and in profitability. The inclusion of loss years shows that loss firms would suffer from considerable additional tax payments under FA. An adjustment of the apportionment weights would slightly increase the performance of the formula. All in all, the CCCTB apportionment formula performs remarkably badly.

Porous silicon photoluminescence is characterized by a broad emission band that displays unusually long (tens to hundreds of micro-seconds), wavelength-dependent emissive lifetimes. The photoluminescence is associated with quantum confinement of excitons in silicon nanocrystallites contained within the porous matrix, and the broad emission spectrum derives from the wide distribution of nanocrystallite sizes in the material. The longer emissive lifetimes in the ensemble of quantum-confined emitters correspond to the larger nanocrystallites, with their longer wavelengths of emission. The quenching of this photoluminescence by aromatic, redox-active molecules aminochrome (AMC), dopamine, adrenochrome, sodium anthraquinone-2-sulfonate, benzyl viologen dichloride, methyl viologen dichloride hydrate, and ethyl viologen dibromide is studied, and dynamic and static quenching mechanisms are distinguished by the emission lifetime analysis. Because of the dependence of the emission lifetime on emission wavelength from the silicon nanocrystallite ensemble, a pronounced blue shift is observed in the steady-state emission spectrum upon exposure to dynamic-type quenchers. Conversely, static-type quenching systems show uniform quenching across all emission wavelengths. Thus, the difference between static and dynamic quenching mechanisms is readily distinguished by ratiometric photoluminescence spectroscopy. The application of this concept to imaging of AMC, the oxidized form of the neurotransmitter dopamine that is of interest for its role in neurodegenerative diseases, is demonstrated. It is found that static electron acceptors result in no ratiometric contrast, while AMC shows a strong contrast, allowing ready visualization in a 2-D imaging experiment.

Recent decades have shown phases of very rapid warming in the Canadian Arctic. This raises a concern, also in reference to potential changes in permafrost active layer deepening, enhancing the fact that seawater, snow and soils are becoming important secondary sources remobilizing persistent organic pollutants (POPs). This work investigates the potential influence of permafrost on POPs distribution in the soils of two small coastal catchments at the Canadian Beaufort coast. One catchment is located south of Herschel Island on the mainland and was covered by the Laurentide ice sheet during the last glacial maximum (LGM), the second catchment is located westerly at Komakuk Beach and was ice-free during the LGM.Soils were sampled by horizon in the Active Layer from an open soil pit and by coring into the permafrost, near the top of the permafrost table and at 90 cm depth from the soil surface (99 samples form Ptarmigan Bay and 89 from Komakuk Beach). The total sampling depth was 1,0 m (including Active Layer and Permafrost). A random distribution of the points over the areas guaranteed the sampling over different Landforms, aiming to understand the contaminant concentration and distribution. Quantification of PAHs, PCBs, HCB was performed using GC-MS technique, a 7890A gas chromatographer coupled with a 5975C MSD System, Agilent Technologies, at CNR-ISP Venice, Italy.Preliminary results confirm that the mechanism responsible for the transport of POPs into the soil are believed to be gravity drainage and capillary suction into fissures and cracks. An accumulation of PAHs has been detected in the permafrost transient layer. It is probably related, as demonstrate in literature, to the accumulation and transport of soil organic carbon influence, as well as the changing in hydraulic barriers. The role of cryoturbation in the vertical transport and accumulation of POPs is also considered and discussed.The study has been conducted thanks to Grant Agreement number: 773421 — Nunataryuk — H2020-BG-2016-2017/H2020-BG-2017-1 ‘Permafrost thaw and the changing arctic coast: science for socio-economic adaptation — Nunataryuk’

Background: Animal-assisted interventions (AAI) are increasingly applied for people with post-traumatic stress disorder (PTSD) symptoms albeit its effectiveness is unclear.Objectives: To examine the effectiveness of AAI for treating PTSD symptoms.Method: We searched 11 major electronic databases for studies reporting quantitative data on effects of AAI for children and adults with PTSD symptoms. Of 22ʹ211 records identified, we included 41 studies with 1111 participants in the systematic review comprising eight controlled studies with 469 participants in the meta-analysis. We conducted random-effects meta-analyses with all controlled studies based on standardized mean differences (SMD), and calculated standardized mean change (SMC) as effect sizes for studies with a pre-post one-group design. Two independent researchers assessed the quality of the included studies using the NIH Study Quality Assessment Tools. The primary outcome was PTSD or depression symptom severity measured via a standardized measurement at pre- and post-intervention assessments.Results: There was a small but not statistically significant superiority of AAI over standard PTSD psychotherapy (SMD = −0.26, 95% CI: −0.56 to 0.04) in reducing PTSD symptom severity while AAI was superior to waitlist (SMD = −0.82, 95% CI: −1.56 to 0.08). Getting a service dog was superior to waiting for a service dog (SMD = −0.58, 95% CI: −0.88 to −0.28). AAI led to comparable effects in reducing depression as standard PTSD psychotherapy (SMD = −0.03, CI: −0.88 to 0.83). Pre-post comparisons showed large variation for the reduction in PTSD symptom severity, with SMCs ranging from −0.38 to −1.64, and for depression symptom severity, ranging from 0.01 to −2.76. Getting a service dog lowered PTSD symptoms between −0.43 and −1.10 and depression with medium effect size of −0.74.Conclusions: The results indicate that AAI are efficacious in reducing PTSD symptomatology and depression. Future studies with robust study designs and large samples are needed for valid conclusions., HIGHLIGHTS We conducted a systematic review with meta-analysis to provide an up-to-date summary on the state of evidence regarding the effectiveness of animal-assisted interventions in treating people with PTSD symptoms. Results are promising but high-quality research is lacking to date.

Arctic ecosystems outpace the global rate of temperature increases and are exceptionally susceptible to global warming. Concerns are raising that CO2 and CH4 released from thawing permafrost upon warming may induce a positive feedback to climate change. This is based on the assumption, that microbial activity increases with warming and does not acclimate over time. However, we lack a mechanistic understanding of carbon and nutrient fluxes including their spatial control in the very heterogeneous Arctic landscape. The objective of this study therefore was to elucidate the microbial controls over soil organic matter decomposition in different horizons of the active layer and upper permafrost. We investigated different landscape units (high-centre polygons, low-centre polygons and flat polygon tundra) in two small catchments that differ in glacial history, at the Yukon coast, Northwestern Canada.In total, 81 soil samples were subjected to short-term (eight weeks) incubation experiments at controlled temperature (4 °C and 14 °C) and moisture conditions. Heterotrophic respiration was assessed weekly, whereas physiological parameters of soil microbes and their temperature response (Q10) were determined at the end of the incubation period. Microbial growth was estimated by measuring the incorporation of 18O from labelled water into DNA and used to calculate microbial carbon use efficiencies (CUE). Microbial biomass was determined via chloroform fumigation extraction. Potential activities of extracellular enzymes involved in C, N, P and S cycling were measured using microplate fluorimetric assays.Cumulative heterotrophic respiration of investigated soil layers followed the pattern organic layers > upper frozen permafrost > cryoturbated material > mineral layers in both catchments. Microbial respiration responded strongly in all soils to warming in all soils, but the observed response was highest for organic layers and cryoturbated material at the beginning and end of the experiment. Average Q10 values at the beginning of the experiment varied between 1.7 to 4.3 with differences between horizons but converged towards Q10 values between 2.0min to 2.9max after eight weeks of incubation. Even though microbial biomass C did not change with warming, microbial mass specific growth was enhanced in organic, cryoturbated and permafrost soils. Overall, warming resulted in a 65% reduced CUE in organic horizons.Our results show no indication for physiological acclimatization of permafrost soil microbes when subjected to 8-weeks of experimental warming. Given that the duration of the season in which most horizons are unfrozen is rarely longer than 2 months, our results do not support an acclimation of microbial activity under natural conditions. Instead, our data supports the current view of a high potential for prolonged carbon losses from tundra soils with warming by enhanced microbial activity.This work is part of the EU H2020 project “Nunataryuk”.

Ongoing climate warming in the western Canadian Arctic is leading to thawing of permafrost soils and subsequent mobilization of its organic matter (OM) pool. Part of this mobilized terrestrial OM enters the aquatic system as dissolved organic matter (DOM) and is laterally transported from land to sea. Mobilized DOM is an important source of nutrients for ecosystems as it is available for microbial breakdown, the consequent turnover of the dissolved organic carbon (DOC) fraction of DOM serving as a potential source of greenhouse gases. We are beginning to understand spatial controls on the release of DOM as well as the quantities and fate of this material in large arctic rivers, but these processes remain systematically understudied in small, high-arctic watersheds, despite the fact that these particular watersheds experience strongest warming.We sampled soil (active layer and permafrost) and water (porewater and stream water) from two small catchments along the Yukon coast, Canada, during the summers of 2018 and 2019. We assessed the organic carbon quantity (using DOC and soil OC content), quality (d13C-DOC, C/N ratios and optical properties including components modelled with EEMs-PARAFAC), the turnover of DOM through incubation experiments as well as nutrients and stable water isotopes. We classify and compare different landscape units by quantitative and qualitative change across gradients from soil stocks down to the catchment outflow.Our results show that substantial variation in DOC concentrations exists among various landscape units as well as between active layer and permafrost. We find high soil carbon stocks and leaching potentials from these coastal tundra soils. Moreover, we find that permafrost DOM is utilized rapidly upon thaw. Using remote sensing-based landscape classification, we are planning to upscale carbon and nutrient fluxes for the panarctic coastal zone to account for small yet numerous high-arctic watersheds in lateral terrestrial OM transfer from land to sea Under current climate projections and with continued permafrost thaw altered lateral fluxes may have profound impacts on the arctic aquatic ecosystem and arctic carbon cycling.

Background Spreading of manure on agricultural soils represents an important pathway by which veterinary medicinal and biocidal products enter the environment. To assess their environmental impact in the context of authorization processes, experimental testing of transformation of these compounds in manure is considered in regulatory guidance documents. However, there is no standardized experimental test method available so far. To fill this gap, an experimental test method was developed to examine transformation in liquid cattle and pig manure. Results To account for manure specifics and for a possible influence of manure parameters on transformation rates, a comprehensive data acquisition and statistical analysis were performed. To address the variability of liquid manure of different type and origin, 30 manures were sampled and characterized. Thereof, three cattle and three pig manures were selected to perform anaerobic transformation studies with two radiolabeled veterinary medicinal active substances (14C-salicylic acid and 14C-paracetamol) and a confidential radiolabeled “14C-biocide B” serving as test compounds. Spatial and seasonal variability of manure parameters was quantified, and a sampling technique to obtain homogenous manure samples was developed. Transformation studies with six replicates per sampling point were conducted to examine the influence of test setup, of manure storage conditions, and of parameter variations between manure of the same species and of different species on half-lives, formation of extractable and non-extractable residues and mineralization rates. Finally, a test design was established that yields reproducible results for transformation studies in liquid cattle and pig manure under anaerobic conditions. Conclusions Results give a reliable basis for an experimental test method to perform anaerobic transformation studies in liquid cattle and pig manure. The developed test method comprises detailed guidance on selection of sampling date and site, collection from manure tank, storage duration and temperature in the laboratory, duration of manure acclimation period, and the incubation system design. It proved to give reproducible results in a validation ring test performed in a follow-up project and is planned to be submitted as draft test guideline for approval by the OECD.

Gender-specific probation programs are needed for rising numbers of women on probation, as women’s paths to probation differ from men’s and are not as frequently addressed. Substance use, mental illness, health disparities, and barriers to treatment can contribute to women clients’ unsuccessful completion of probation. The current study describes a process evaluation of the pilot Female Offenders Can Ultimately Succeed (FOCUS) program, which aimed to meet women probation clients’ complex needs and improve their probation outcomes. Two women FOCUS Probation Officers had smaller-than-typical caseloads of 132 Medium- to Greatest-Risk women clients and received ongoing training in motivational and trauma-specific supervision strategies. To facilitate linkage to all needed treatment and social services, clients were referred to a primary care Transitions Clinic. Comparing non-FOCUS to FOCUS women clients with Violations of Probation, FOCUS clients had more successful completions of probation (higher non-punitive Restorations of Probation and lower punitive Revocations of Probation). At the Transitions Clinic, 52% of FOCUS clients received treatment. FOCUS clients and stakeholders provided narrative feedback reflecting a range of experiences in FOCUS, guiding future program implementation efforts. Promising outcomes from FOCUS demonstrate the potential of theory-based supervision and probation-medical collaboration to facilitate women clients’ success in probation.

Purpose Posttraumatic partial or total iris defects often cause significant debilitating glare, photophobia, decreased vision and cosmetic problems. Currently, the best cosmetic results can be obtained with a customized silicone iris prosthesis. However, little is known about the functional results and the rate of complication if this type of iris prosthesis is implanted into severely traumatized eyes. The aim of this study is to analyse the functional and cosmetic outcomes as well as complications after Artificial Iris implantation. Methods A consecutive series of 34 patients who received a customized silicone iris prosthesis after severe globe injury with total or sub-total iris loss was analysed retrospectively. Additionally, patients were interviewed regarding change in subjective complaints. Results Median follow-up was 24 months (range 12.0–48.8). Mean visual acuity prior to Artificial Iris implantation was 1.1 logMAR (range 0.3–2.6). Five patients (15%) had pre-existing glaucoma and eight patients (24%) had pre-existing hypotony. Visual acuity 12 months after surgery was 1.4 logMAR (range 0.2–2.6). Complications included newly diagnosed glaucoma in three eyes (9%) and hypotony in three eyes (9%), persisting intraocular inflammation or macular oedema in seven patients (21%), and corneal endothelial decompensation requiring corneal transplantation in six patients (18%). Patients’ satisfaction increased by reducing glare and enhanced cosmetic appearance. Conclusion The customized silicone iris prosthesis is an individualized treatment approach with appealing cosmetic results. Therefore, especially traumatized eyes with highly different posttraumatic conditions could benefit. However, in some patients, the implantation of this device may cause an increase of intraocular pressure, corneal endothelial decompensation or persisting inflammation.

AIM Flexed knee gait can be treated with distal femoral extension osteotomy (DFEO) and additional patellar tendon advancement (PTA) in children with cerebral palsy (CP). This study assesses changes in hamstring muscle tendon length (MTL) and velocity after DFEO (+PTA). METHOD Nineteen children (mean age 13y [standard deviation 3y] at surgery) with CP and flexed knee gait who were treated with DFEO (15 limbs) or DFEO+PTA (10 limbs) were retrospectively included in this study. Gait analyses were performed preoperatively (E0), 1 year postoperatively (E1), and for 10 limbs additionally 2 to 5 years postoperatively (E2). Hamstring MTL and velocities were assessed at all examination dates using OpenSim. RESULTS Hamstring MTL and velocity did not change significantly over time. From E0 to E1, knee flexion in stance improved for both DFEO and DFEO+PTA (p

The proceedings in front of the International Court of Justice concerning the status of the Chagos Archipelago mark the latest culmination of a decades-long dispute between the United Kingdom and Mauritius. The first and one of the key questions the Court will be faced with is whether it has the jurisdiction to give the requested opinion or whether there are compelling reasons why the Court should use its discretionary power to decline to exercise jurisdiction. The paper reviews the relevant law and the leading cases on this matter while focusing on the importance of state consent in advisory jurisdiction and the famous Eastern Carelia decision of the Court’s predecessor.

In recent years, Europe has experienced a move towards religious diversity and pluralism, which is especially caused by the lasting wave of migrants fleeing conflicts in primarily Muslim countries. While in 2010 Muslims formed 3.8% of Europe’s population, the Muslim population would be expected to rise to 14% by 2050. Even if this scenario does not materialise the European Union and its member states, they will be confronted more and more frequently with new challenges to the law regulating the relations between the state and religious organisations and currently unknown religious conflicts: disputes over religious symbols like the Christian crucifix, the Jewish mezuzah or the Muslim hilal in the public sphere, the debate on the Muslim head scarf, burka and niqab worn by teachers, police women or judges and controversies concerning religious practices in schools and universities – the list is almost endless – are only a few examples impressively demonstrating this. Although many of these problems have been the subject of debate within German higher court, federal administrative, and constitutional court cases, particular decisions as the headscarf ban for teachers (BVerfGE 108, 282, BVerfGE 138, 296) or the crucifix ruling (BVerfGE 93, 1) show that the judicial recognized idea of neutrality between state and religion is characterised by inconsistent results and rules: This leads to the paradox situation that in one and the same country Christian crucifixes in classes and court rooms are (predominantly) allowed and desired whereas on the other hand its strictly prohibited for Muslim teachers or legal clerks to wear a head scarf. Lastly, the current legal situation leaves affected people and legal practitioners helpless. This might be linked to the German model of rules regulating the relation between state and religion. The German Grundgesetz follows the so called hybrid or cooperation model – incorporated from the German constitution of 1918 – which is characterised by a basic separation of state and religion, simultaneously the state is responsible for maintaining religious freedom, diversity and plurality. This middle of the road approach be-tween an established church system and secularity is the most prevalent model in Europe. Particularly also our immediate European neighbours Austria and Italy follow this long-lasting co-operation-based tradition. Key objective of our contribution is to examine whether our neigh-bours are facing similar problems to those we have in Germany. In particular, we will focus our attention on the missing legal certainty and clarity with regard to the – positive and negative – freedom of religion. To ensure a comprehensive picture of the ambiguous legal situation our study will analyse and compare the relevant constitutional provisions, particular laws and jurisdiction in Austria, Italy and Germany and evaluate whether or not European countries still give privileges to their Judeo-Christian roots, (will) develop a religion-friendly attitude of neutrality towards all – also the Muslim – religions and world views or choose a way into a secular society. This question needs to be discussed on a multi-national forum, because it is a matter that concerns all European countries. The International Symposium on Religious Pluralism and European Integration provides a suitable framework to answer this question and to get in touch with experts from different fields of research and different ethical, racial and religious backgrounds.

This paper focuses on the description of damage propagation around rivets in multiple joined single lap carbon fiber reinforced plastics (CFRP)-steel structures due to loads as a consequence of different coefficients of thermal expansion. Materials and rivets were chosen according to automotive body shop applications. Specimens were evaluated non-destructively in ultrasonic C-scans to characterize damage behavior of blind and self-piercing rivets in CFRP-steel-connections before and after the application of thermal loads. An algorithm for an automated detection of damage size on ultrasonic C-scan images was developed as the basis for further damage classification. The results show that blind riveting (BR) causes crack-like initial damage that broadens to roundish plane defects due to heating. Initial extensive damage due to self-piercing riveting (SPR) propagates in elliptic shape. Additionally, tension tests revealed a loss in ultimate load by 10–15 % induced by thermal loads and associated with damage propagation. A correlation between initial damage, relative displacement, and thermal loads was observed.

State of the art for producing 3-dimensional formed plastic shields is the use of mould blocks that are milled on machining centers. This paper describes the replacement of traditional mould blocks by a novel automated reusable mould and tooling system that produces good forming results at low investment costs. The reconfigurable tooling system replaces commonly used mould blocks. Two major issues will be addressed. The first aim is to identify principles for low tooling costs, while the second focuses on the improvement of a forming process suitable for the system so that this can be used for a broad range of products.

The derivation of natural killer (NK) cells from human pluripotent stem cells (hPSCs) is an exciting alternative for adoptive immunotherapy strategies in the treatment of cancer. While NK cells are component of the embryonic hematopoietic repertoire, their ontogenic origins remain unclear. During mammalian embryogenesis, hematopoietic development in the early yolk sac consists of the (HSC)-independent primitive and erythro-myeloid progenitor (EMP) hematopoietic programs. Neither population is known to harbor lymphoid potential. As we previously observed NK cell development from extra-embryonic-like progenitors derived from hPSCs, we asked whether a yolk sac-derived program possesses NK cell potential. Surprisingly, we determined that EMPs isolated from the yolk sacs of E9.5 mouse embryos harbor robust NK cell potential. Further, these NK cells exhibited a potent degranulation response following stimulation, making them functionally distinct from HSC-derived NK cells. In parallel studies of hPSCs differentiated as previously described, we found that extra-embryonic-like CD34+ myeloid progenitors, similar to murine EMPs, give rise to NK cells that are biased for cytolytic degranulation. In contrast, hPSC-derived CD34+ lymphoid progenitors give rise to NK cells that are phenotypically similar to those derived from cord blood, since both exhibit a poor degranulation response but robustly produce inflammatory cytokines. Collectively, our studies in mouse embryos and human PSCs point to a novel, hematopoietic stem cell (HSC)-independent origin of embryonic NK cells that differ functionally from HSC-derived NK cells. These findings not only identify a myeloid origin to embryonic NK cells, but also have important implications for the design of hPSC-derived NK cell-based therapeutics.

Although many studies exist on the estimation and monitoring of above-ground biomass (AGB) of forest ecosystems by methods of remote sensing, very little research has been carried out for ecosystems of low primary production, such as grasslands, steppes, or savannas. Our study intends to approach this gap and investigates the correlation between space-borne radar information and AGB at the scale of 10 tons per hectare and below. Additionally, we introduce the integration of passive brightness temperature as an additional covariate for biomass estimation, based on the hypothesis that it contains information complementary to microwave backscatter of the active sensors. Our findings show that large-scale estimates of AGB can be conducted for grasslands and savannas at high accuracy (R2 up to 0.52). Additionally, we found that the integration of passive radar can increase the quality of AGB estimates in terms of explained variance for selected cases. We hope that these indications are a starting point for more integrated approaches toward biomass estimations based on Earth observation methods.

Objective. Being a parent is often associated with less sleep and sleep problems. In addition, young children often suffer from sleep problems. Hence, children’s sleep problems can evoke sleep problems in their parents. However, little is known about sleep of family members.Method. A total of 54 parents with their children between 4 and 12 years of age (mean 7.04 years) participated in this study prior to a universal parent-training. Sleep problems were assessed by the Child Behavior Checklist (CBCL) and the Symptom Checklist 90-R (SCL-90-R). Psychological problems of the children and parental burden were further evaluated with the Eyberg Child Behavior Inventory (ECBI). In addition, parental behavior was assessed with the short form of the Parenting Scale of Arnold (“Erziehungsfragebogen für Eltern”, EFB-K).Results. In sum, 13% of the children showed shorter overall sleep duration than other children, whereas 5.6% slept more. None of the parents reported daytime sleepiness in their children, but 3.9% reported that their children do often have nightmares and also 3.9% often talk during sleep. Altogether 15.4% of the parents thought that their child suffered from sleep problems. Problems falling asleep were reported by 19.6% of mothers and 10.5% of fathers and disturbed sleep was reported by 33.3% of mothers and 12.6% of fathers, whereas 15.8% of mothers and 8.4% of fathers were suffering from waking up too early in the morning. Children with sleep disturbances did not differ significantly from children without sleep problems regarding their psychological disturbances. However, parents differed with regard to parental burden, depression, anxieties, and sleep problems. The main limitations are the small sample size and the lack of a healthy control group.Conclusion. In contrast to their parents, children with or without sleep problems did not differ concerning psychological disturbances. Consequently, even if the child is not affected by sleep problems these issues need to be considered for parents participating in a universal parent-training. Furthermore, fathers also need to be integrated into diagnostics, not only mothers, because sleep problems and other psychological problems are often experienced by both parents.

Der Beitrag rekonstruiert zwei Positionen aus getrennten politischen Kontexten der Zwischenkriegszeit des letzten Jahrhunderts, um die Begriffe »Rhythmus« und »Takt« auf ihren immanenten Geschichtsbegriff zu befragen. In den Rhythmusbegriff, wie ihn der Kreis um Ludwig Klages auffaßte, schreibt sich das Konzept der langen Dauer ein, während in den Arbeiten des sowjetischen Künstlers Alexander Michailowitsch Rodtschenko der Takt die Geschichte gleichsam auslöscht.

Background The built environment plays a critical role in promoting physical activity and health. The association between parks, as a key attribute of the built environment, and physical activity, however, remains inconclusive. This project leverages a natural experiment opportunity to assess the impact of the Community Parks Initiative (CPI), a citywide park redesign and renovation effort in New York City, on physical activity, park usage, psychosocial and mental health, and community wellbeing. Methods The project will use a longitudinal design with matched controls. Thirty intervention park neighborhoods are socio-demographically matched to 20 control park neighborhoods. The study will investigate whether improvements in physical activity, park usage, psychosocial and mental health, and community wellbeing are observed from baseline to 3 years post-renovation among residents in intervention vs. control neighborhoods. Discussion This study represents a rare opportunity to provide robust evidence to further our understanding of the complex relationship between parks and health. Findings will inform future investments in health-oriented urban design policies and offer evidence for addressing health disparities through built environment strategies.

Complement is a key component of the innate immune system, recognizing pathogens and promoting their elimination. Complement component 3 (C3) is the central component of the system. Activation of C3 can be initiated by three distinct routes-the classical, the lectin and the alternative pathways-with the alternative pathway also acting as an amplification loop for the other two pathways. The protease factor D (FD) is essential for this amplification process, which, when dysregulated, predisposes individuals to diverse disorders including age-related macular degeneration and paroxysmal nocturnal hemoglobinuria (PNH). Here we describe the identification of potent and selective small-molecule inhibitors of FD. These inhibitors efficiently block alternative pathway (AP) activation and prevent both C3 deposition onto, and lysis of, PNH erythrocytes. Their oral administration inhibited lipopolysaccharide-induced AP activation in FD-humanized mice. These data demonstrate the feasibility of inhibiting the AP with small-molecule antagonists and support the development of FD inhibitors for the treatment of complement-mediated diseases.

A large body of scientific literature derived from experimental studies emphasizes the vital role of vagal-nociceptive networks in acute pain processing. However, research on vagal activity, indexed by vagally-mediated heart rate variability (vmHRV) in chronic pain patients (CPPs), has not yet been summarized.To systematically investigate differences in vagus nerve activity indexed by time- and frequency-domain measures of vmHRV in CPPs compared to healthy controls (HCs).A systematic review and meta-analysis, including meta-regression on a variety of populations (i.e., clinical etiology) and study-level (i.e., length of HRV recording) covariates.Not applicable (variety of studies included in the meta-analysis).Eight computerized databases (PubMed via MEDLINE, PsycNET, PsycINFO, Embase, CINAHL, Web of Science, PSYNDEX, and the Cochrane Library) in addition to a hand search were systematically screened for eligible studies based on pre-defined inclusion criteria. A meta-analysis on all empirical investigations reporting short- and long-term recordings of continuous time- (root-mean-square of successive R-R-interval differences [RMSSD]) and frequency-domain measures (high-frequency [HF] HRV) of vmHRV in CPPs and HCs was performed. True effect estimates as adjusted standardized mean differences (SMD; Hedges g) combined with inverse variance weights using a random effects model were computed.CPPs show lower vmHRV than HCs indexed by RMSSD (Z = 5.47, P.0001; g = -0.24;95% CI [-0.33, -0.16]; k = 25) and HF (Z = 4.54, P.0001; g = -0.30; 95% CI [-0.44, -0.17]; k = 61).Meta-regression on covariates revealed significant differences by clinical etiology, age, gender, and length of HRV recording.We did not control for other potential covariates (i.e., duration of chronic pain, medication intake) which may carry potential risk of bias.The present meta-analysis is the most extensive review of the current evidence on vagal activity indexed by vmHRV in CPPs. CPPs were shown to have lower vagal activity, indexed by vmHRV, compared to HCs. Several covariates in this relationship have been identified. Further research is needed to investigate vagal activity in CPPs, in particular prospective and longitudinal follow-up studies are encouraged.