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Abstract Background Reports from case series suggest that operative outcomes are comparable amongst different age groups following surgery with curative intent for non-small cell lung cancer (NSCLC). The purpose of this study was to compare morbidity and mortality after NSCLC surgery in older patients (≥ 75 years) versus younger patients (

Abstract Introduction Magnetic resonance guided radiotherapy (MRgRT) allows daily adaptation of treatment plans to compensate for positional changes of target volumes and organs at risk (OARs). However, current adaptation times are relatively long and organ movement occurring during the adaptation process might offset the benefit gained by adaptation. The aim of this study was to evaluate the dosimetric impact of these intrafractional changes. Additionally, a method to predict the extent of organ movement before the first treatment was evaluated in order to have the possibility to compensate for them, for example by adding additional margins to OARs. Materials & methods Twenty patients receiving adaptive MRgRT for treatment of abdominal lesions were retrospectively analyzed. Magnetic resonance (MR) images acquired at the start of adaptation and immediately before irradiation were used to calculate adapted and pre-irradiation dose in OARs directly next to the planning target volume. The extent of organ movement was determined on MR images acquired during simulation sessions and adaptive treatments, and their agreement was evaluated. Correlation between the magnitude of organ movement during simulation and the duration of simulation session was analyzed in order to assess whether organ movement might be relevant even if the adaptation process could be accelerated in the future. Results A significant increase in dose constraint violations was observed from adapted (6.9%) to pre-irradiation (30.2%) dose distributions. Overall, OAR dose increased significantly by 4.3% due to intrafractional organ movement. Median changes in organ position of 7.5 mm (range 1.5–10.5 mm) were detected within a median time of 17.1 min (range 1.6–28.7 min). Good agreement was found between the range of organ movement during simulation and adaptation (66.8%), especially if simulation sessions were longer and multiple MR images were acquired. No correlation was determined between duration of simulation sessions and magnitude of organ movement. Conclusion Intrafractional organ movement can impact dose distributions and lead to violations of OAR tolerance doses, which impairs the benefit of daily on-table plan adaptation. By application of simulation images, the extent of intrafractional organ movement can be predicted, which possibly allows to compensate for them.

Summary: Background: Open partial pancreatoduodenectomy (OPD) represents the current gold standard of surgical treatment of a wide range of diseases of the pancreatic head but is associated with morbidity in around 40% of cases. Robotic partial pancreatoduodenectomy (RPD) is being used increasingly, yet, no randomised controlled trials (RCTs) of RPD versus OPD have been published, leaving a low level of evidence to support this practice. Methods: This investigator-initiated, exploratory RCT with two parallel study arms was conducted at a high-volume pancreatic centre in line with IDEAL recommendations (stage 2b). Patients scheduled for elective partial pancreatoduodenectomy (PD) for any indication were randomised (1:1) to RPD or OPD with a centralised web-based tool. The primary endpoint was postoperative cumulative morbidity within 90 days, assessed via the Comprehensive Complication Index (CCI). Biometricians were blinded to the intervention, but patients and surgeons were not. The trial was registered prospectively (DRKS00020407). Findings: Between June 3, 2020 and February 14, 2022, 81 patients were randomly assigned to RPD (n = 41) or OPD (n = 40), of whom 62 patients (RPD: n = 29, OPD: n = 33) were analysed in the modified intention to treat analysis. Four patients in the OPD group were randomised, but did not undergo surgery in our department and one patient was excluded in the RPD group due to other reason. Nine patients in the RPD group and 3 patients in the OPD were excluded from the primary analysis because they did not undergo PD, but rather underwent other types of surgery. The CCI after 90 days was comparable between groups (RPD: 34.02 ± 23.48 versus OPD: 36.45 ± 27.65, difference in means [95% CI]: −2.42 [−15.55; 10.71], p = 0.713). The RPD group had a higher incidence of grade B/C pancreas-specific complications compared to the OPD group (17 (58.6%) versus 11 (33.3%); difference in rates [95% CI]: 25.3% [1.2%; 49.4%], p = 0.046). The only complication that occurred significantly more often in the RPD than in the OPD group was clinically relevant delayed gastric emptying. Procedure-related and overall hospital costs were significantly higher and duration of surgery was longer in the RPD group. Blood loss did not differ significantly between groups. The intraoperative conversion rate of RPD was 23%. Overall 90-day mortality was 4.8% without significant differences between RPD and OPD. Interpretation: In the setting of a very high-volume centre, both RPD and OPD can be considered safe techniques. Further confirmatory multicentre RCTs are warranted to uncover potential advantages of RPD in terms of perioperative and long-term outcomes. Funding: Federal Ministry of Education and Research (BMBF: 01KG2010).

While carbon fibers (CFs) are still the most attractive reinforcement material for lightweight structures, they are mostly manufactured using crude oil-based process chains. To achieve a higher eco-efficiency, the partial substitution of polyacrylonitrile (PAN) by renewable materials, such as lignin, is investigated. So far, this investigation has only been carried out for batch manufacturing studies, neglecting the transfer and validation to continuous CF manufacturing. Therefore, this work is the first to investigate the possibility of partial substituting lignin for PAN in a continuous process. Lignin/PAN-blended CFs with up to 15 wt.-% lignin were able to attain mechanical properties comparable to unmodified PAN-based carbon fibers, achieving tensile strengths of up to 2466 MPa and a Young’s Modulus of 200 Pa. In summary, this study provides the basis for continuous Lignin/PAN-blended CF manufacturing.

The dopaminergic system is susceptible to dysfunction in numerous neurological diseases, including Parkinson’s disease (PD). In addition to motor symptoms, some PD patients may experience non-motor symptoms, including cognitive and memory deficits. A possible explanation for their manifestation is a disturbed pattern of dopamine release in brain regions involved in learning and memory, such as the hippocampus. Therefore, investigating neuropathological alterations in dopamine release prior to neurodegeneration is imperative. This study aimed to characterize evoked hippocampal dopamine release and assess the impact of the neurotoxin MPP+ using a genetically encoded dopamine sensor and gene expression analysis. Additionally, considering the potential neuroprotective attributes demonstrated by apoptosis signal-regulating kinase 1 (Ask1) in various animal-disease-like models, the study also aimed to determine whether Ask1 knockdown restores MPP+-altered dopamine release in acute hippocampal slices. We applied variations of low- and high-frequency stimulation to evoke dopamine release within different hippocampal regions and discovered that acute application of MPP+ reduced the amount of dopamine released and hindered the recovery of dopamine release after repeated stimulation. In addition, we observed that Ask1 deficiency attenuated the detrimental effects of MPP+ on the recovery of dopamine release after repeated stimulation. RNA sequencing analysis indicated that genes associated with the synaptic pathways are involved in response to MPP+ exposure. Notably, Ask1 deficiency was found to downregulate the expression of Slc5a7, a gene encoding a sodium-dependent high-affinity choline transporter that regulates acetylcholine levels. Respective follow-up experiments indicated that Slc5a7 plays a role in Ask1 deficiency-mediated protection against MPP+ neurotoxicity. In addition, increasing acetylcholine levels using an acetylcholinesterase inhibitor could exacerbate the toxicity of MPP+. In conclusion, our data imply that the modulation of the dopamine-acetylcholine balance may be a crucial mechanism of action underlying the neuroprotective effects of Ask1 deficiency in PD.

Per- and polyfluoroalkyl substances (PFAS) are a group of xenobiotics that are widely distributed throughout the aquatic environment. Many PFAS are possible thyroid hormone (TH) system disrupting compounds, because they have the capacity to -amongst other- inhibit the TH thyroxine (T4) from binding to its transport protein transthyretin (TTR). This study investigated the occurrence of TH-displacing activity in the Dutch water cycle, and more specifically, the contribution of PFAS to this effect. Over one year of monitoring data of 29 PFAS (linear and branched) showed the continuous presence of PFAS in drinking waters and their surface water sources. Secondly, the FITC-T4 and TTR-TRβ-CALUX bioassays were mutually compared using positive (HPLC-grade water spiked with PFOA) and negative control samples (HPLC-grade water), as well as relative potency factors (RPFs) of up to 20 PFAS congeners. Both assays were found to be suitable for measuring TH-displacing activity in water samples. As a third aim, a field study was performed in the Dutch water cycle that was comprised of samples from drinking water, surface water, PFAS contaminated sites, and 2 wastewater treatment plants. All samples were analyzed with 1. chemical analysis for 29 PFAS, 2. the FITC-T4 bioassay, and 3. the TTR-TRβ-CALUX bioassay. The bioassays mutually showed good correlation (R2 0.85). Bioanalytical equivalent concentrations (BEQ) based on chemically-determined concentrations and RPFs (BEQchem) revealed that analyzed PFAS only explained ≤4.1 % of their activity in water extracts measured by both bioassays (BEQbio). This indicated that as yet unknown compounds contribute to the majority of the measured TH-displacing activity. Moreover, water treatment processes (e.g. DW production from SW) showed a larger contribution of target PFAS to the BEQbio. This could be a first lead to identify unknown compounds that contribute to this activity, and as such, enable the assessment of possible risks associated by the occurrence of TH-displacing activity in water.

Abstract Background Hyperspectral imaging (HSI) is a novel imaging technology with the ability to assess microcirculatory impairment. We aimed to assess feasibility of performing HSI, a noninvasive, contactless method to assess microcirculatory alterations, during trauma resuscitation care. Methods This randomized controlled clinical trial was conducted in a dedicated trauma resuscitation room of a level one trauma center. We included adult patients who were admitted to the trauma resuscitation room. Patients were allocated in a 1:1 ratio to the HSI group (intervention) or control group. In addition to the standard of care, patients in the intervention group had two hyperspectral recordings (HSR) of their hand palm taken. Primary outcomes were the treatment duration of the primary survey (until end of ABCDE-evaluation, ultrasound and evaluation by the trauma team) and the total resuscitation room care (until transport to definitive care) as well as the ability to perform measurements from all HSR. Secondary outcomes were analyses from the intervention group compared to HSI measurements of 26 healthy volunteers including an analysis based on the ISS (Injury severity score) (

Background: Children and consumers are exposed to increasingly complex mixtures of known and as-yet-unknown toxic chemicals from toys and products. However traditional chemical analysis methods only evaluate a small number of chemicals at a time thereby restricting consumer awareness of the full range of potentially harmful chemicals in products. Methods: We used high-throughput effect-based non-animal methods to investigate exposures to complex chemical mixtures of several kinds of brominated flame retardants (BFRs) for their dioxin- and thyroid hormone-like activities in various kinds of consumer products and toys from 26 different countries, on four continents (Africa, America, Asia and Europe) in combination with chemical analysis of various polybrominated flame retardants (BFRs) and their impurities (such as polyhalogenated PCDD/Fs and PBDD/Fs). Results: We found high levels of polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) in toys and now, for the first time, also in consumer products that are manufactured from black plastics containing certain brominated flame retardants (BFRs). The presence of PBDD/PBDFs as well as other BFRs in various black plastic materials from additional countries as well as additional kinds of consumer products as confirmed by effect-based in vitro reporter gene DR CALUX and TTR-TRβ CALUX assays as well as congener-specific chemical analysis. We compared total Toxicity Equivalent (TEQ) levels of PBDD/F-TEQs analysed by chemical analysis to by CALUX bioassay measured Biological equivalence (BEQ) concentrations (for further info see at ISO 23196, ISO, 2022). In the case of TBBPA, both chemical and TTR-TRβ CALUX analysis measure direct the amount of TBBPA. Finally, the daily ingestion of 2,3,7,8-TCDD equivalents from PBDD/Fs-contaminated plastic toys by child mouthing habits have been related to our earlier study (Budin et al., 2020). Conclusions: Interaction of children with such contaminated plastics may significantly contribute to the daily uptake of dioxin- and thyroid hormone transport disrupting-like compounds. Effect-based bioassays for dioxin- and thyroid hormone-like activities are relevant to pick-out such complex mixtures of known and yet unknown (and therefore not regulated) substances for safer and more sustainable plastics. Low POPs Content Levels and other mechanisms set under the Basel and Stockholm Conventions are set far too high to prevent a significant flow of BFRs and PBDD/Fs into consumer products.

Structural supercapacitors (SSCs) are multifunctional energy storage composites (MESCs) that combine the mechanical properties of fiber-reinforced polymers and the electrochemical performance of supercapacitors to reduce the overall mass in lightweight applications with electrical energy consumption. These novel MESCs have huge potentials, and their properties have improved dramatically since their introduction in the early 2000’s. However, the current properties of SSCs are not sufficient for complete energy supply of electrically driven devices. To overcome this drawback, the aim of the current study is to identify key areas for enhancement of the multifunctional performance of SSCs. Critical modification paths for the SSC constituents are systematically analyzed. Special focus is given to the improvement of carbon fiber-based electrodes, the selection of structural electrolytes and the implementation of separators for the development of more efficient SSCs. Finally, current SSCs are compared in terms of their multifunctionality including material combinations and modifications.

The hippocampal formation, particularly the CA2 subregion, is critical for social memory formation and memory processing, relying on synaptic plasticity—a fundamental mechanism by which synapses strengthen. Given the role of the ubiquitin–proteasome system (UPS) in various nervous system processes, including learning and memory, we were particularly interested in exploring the involvement of RING-type ubiquitin E3 ligases, such as UHRF2 (NIRF), in social behavior and synaptic plasticity. Our results revealed altered social behavior in mice with systemic Uhrf2 knockout, including changes in nest building, tube dominance, and the three-chamber social novelty test. In Uhrf2 knockout mice, the entorhinal cortex-CA2 circuit showed significant reductions in synaptic plasticity during paired-pulse facilitation and long-term potentiation, while the inability to evoke synaptic plasticity in the Schaffer-collateral CA2 synapses remained unaffected. These changes in synaptic plasticity correlated with significant changes in gene expression including genes related to vesicle trafficking and transcriptional regulation. The effects of Uhrf2 knockout on synaptic plasticity and the observed gene expression changes highlight UHRF2 as a regulator of learning and memory processes at both the cellular and systemic levels. Targeting E3 ubiquitin ligases, such as UHRF2, may hold therapeutic potential for memory-related disorders, warranting further investigation.

Freeze foams are novel and innovative cellular structures that are based on a direct foaming process and that can be manufactured using any material that can be processed by powder technology. The foam formation process is characterized by the highly complex interaction of various process and material parameters that were chosen empirically and that have so far been difficult to reproduce. To allow properties to be specifically tailored towards certain applications, it is necessary to examine the phenomena observed during foam formation as well as the impact of the process and material parameters on the structural constitution to deduce guidelines for manufacturing and quality assessment (e.g., mechanical strength, cell and pore sizes, pore size distribution). The variety of possible applications are a result of the wide spectrum of initial suspensions and especially the foam structure properties derived from process parameters such as the cell geometry, pore size distribution, fraction of open and closed porosity, and the textures of the cell struts. Due to earlier findings, the focus of this paper focuses on adjusting and tailoring the macrostructure (homogenization of the pore sizes and their distribution inside foam cells) to create load- and application-adapted ceramic foams. To this end, an experiment was designed using previously identified pore and characteristic influencers (air and water content, temperature of the suspension, pressure reduction rate) as influencing parameters. Their interconnected impacts on selected target values were examined during the freeze foaming process using an in situ freeze foaming device inside an X-ray.

Infill development policies have been widely adopted as strategies to reduce urban sprawl and to promote sustainable urban transformation. However, little empirical data are available to analyse infill processes and to facilitate building activity on infill potentials. This is especially true for small-scale residential infill, which often takes place on vacant or underused lots as soft densification. To address this issue, a geospatial method is presented that enables automatic detection of vacant lots for large areas. Cadastral data are used to analyse spatio-temporal development for the period 2011–21 in a German study area, containing large cites as well as rural municipalities. The results show that every fourth vacant lot was mobilised since 2011. However, additional vacant lots emerged in rural areas as new residential development areas are not fully built-up, resulting in a net increase of vacant lots. Although the quantity of vacant lot areas in 2021 suggests a high potential for residential infill, the main development on these infill sites is expected to promote additional single-family housing rather than more dense structures. Practice relevance Automatic identification and monitoring of infill potentials and development are important both for policymaking and for local planning practitioners. For small municipalities with little financial capacities, the approach can provide an overview of their vacant lots and can serve as a basis for strategic planning decisions. For the regional or national level, a yearly monitoring schedule can be established at little cost. Although the approach proves to be robust regarding its precision and is promising for a nationwide application, the data availability for the whole of Germany is awaited and the method needs to be optimised to implement the workflow in practice.

This review compiles information on PCDD/F- and PCB-contaminated eggs from 20 years of global egg monitoring around emission sources in four continents conducted by the International Pollutants Elimination Network (IPEN) and Arnika as well as a compilation of data from scientific literature. IPEN monitored 127 pooled egg samples including samples from 113 chicken flocks at potential PCDD/F- and PCB-contaminated sites around priority sources listed in the Stockholm Convention (e.g. waste incinerators, metal industries, cement plants, and open burning). 99 (88%) of pooled egg samples were above the EU maximum limits for PCDD/Fs (2.5 pg PCDD/F-TEQ/g fat) or the sum of PCDD/Fs and dioxin-like PCBs (5 pg PCDD/F-PCB-TEQ/g fat). Children consuming such eggs exceed the tolerable weekly intake (TWI). This demonstrates that close to 90% of these areas were not safe for the production of free-range eggs. Sixteen out of the 113 egg samples (14%) were contaminated above 50 pg TEQ/g fat and exceeded the EU maximum limit more than 10 times. From the 26 pooled egg samples around incinerators 24 (92%) exceeded the limit with a mean of 43.1 pg TEQ/g fat (2.6–234 pg TEQ/g). All 21 egg samples around metal industries (4.4–112.6 pg TEQ/g fat) were above limits with mean concentration of 26.0 pg TEQ/g fat. Also all 7 egg samples measured at e-waste recycling sites were above limits (mean 308 pg TEQ/g fat). In 58 (51%) pooled egg samples the PCB-TEQ was above 5 pg TEQ/g fat exceeding the EU maximum limit with dioxin-like PCBs alone. This highlights the role of commercial PCBs for global contamination with dioxin-like compounds. It was discovered that around metal industries, shredder plants, open burning sites of e-waste and dump sites, a high share of contamination was caused by dl-PCBs. This clearly shows severe PCB release from the end-of-life management of PCB-containing equipment in developing countries. Also highly contaminated eggs were found at many sites where plastic was incinerated. The highest contaminated egg sample ever measured came from an e-waste site in Ghana and had 856 pg TEQ/g fat plus 300 pg TEQ from brominated dioxins (PBDD/Fs). Other extreme PCDD/F contaminations of eggs were found at a chlor-alkali site (514 pg TEQ/g fat), Agent Orange contaminated areas in Vietnam (490, 249 and 246 pg TEQ/g fat) and e-waste sites (568 and 520 pg TEQ/g fat). Where DR CALUX® bioassay revealed higher TEQ compared to measured PCDD/F-PCB-TEQ in IPEN studies, polybrominated PBDD/F were also measured and detected up to 300 pg TEQ/g fat at e-waste sites. One positive outcome from the IPEN studies is that all 10 pooled supermarket eggs in developing countries were below regulatory limit. Policy recommendations are made including: a systematic assessment of areas around PCDD/Fs and PCBs sources; measures for reduction of exposures of populations; urgent control of emission sources including PCB equipment, the open burning of plastic, and the use of plastic as fuel in boilers/incinerators in developing countries without air pollution control. Furthermore, soil limits need to be re-assessed and lowered for free-range poultry.