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Background Per- and polyfluoroalkyl substances (PFAS) were used or are being used in the manufacturing of products, including consumer-use products. The resulting environmental contamination has led to widespread human exposure. This review aimed to scope the characteristics of evidence covered and applied methodology of evidence to understand -- regardless of any results on the association of gestational diabetes mellitus (GDM) and PFAS -- if a new systematic review would be justified. Methods We systematically identified reports investigating associations of PFAS with GDM following a pre-specified and pre-registered PECO framework and protocol. Results The previous systematic reviews included 8-11 reports and either conducted meta-analyses stratified by comparator, analyzed results based on only high and low exposure categories, or pooled results across comparators. Included 20 reports presented data on 24 PFAS with PFOA, PFOS, PFHxS, PFNA, and PFDA being examined in almost all. The comparators employed were heterogeneous across the reports. Conclusions Because data from at least one new report on GDM is available since the previous systematic reviews and heterogeneous comparators, an updated systematic review using SWiM could add value to the literature.

Large bone defects of the distal radius and/or carpus following tumor resection, trauma, or infection are extremely rare. There are few case reports and series in the literature on the reconstruction approaches required in such cases. Therefore, large studies cannot be used to guide the therapeutic decisions of reconstructive plastic and hand surgeons. The objective of this study is to propose a treatment algorithm to predict the functional outcome and quality of life for the different techniques of free vascularized bone reconstruction in the interval between the distal radius, the carpus, and/or the proximal metacarpal. The algorithm was developed based on our own case studies and the few treatment approaches described in the literature. It can be applied to rare cases of massive bone defects in the wrist. The flowchart enables surgeons to develop an individualized reconstruction concept for various intervals of bone defects in the area of the distal radius and proximal metacarpal bones. Ultimately, the treatment algorithm aims to maximize future quality of life (QoL) and function of the distal upper extremity in rare cases of massive wrist-bone defects.

Regulations of cosmetic ingredients and products have been the most advanced in embracing new approach methodologies (NAMs). Consequently, the cosmetic industry has assumed a forerunner role in the development and implementation of animal-free next-generation risk assessment (NGRA) that incorporates defined approaches (DAs) to assess the skin sensitization potency of ingredients. A Bayesian network DA predicting four potency categories (SkinSens-BN) was constructed against reference Local Lymph Node Assay data for a total of 297 substances, achieving a predictive performance similar to that of other DAs. With the aim of optimally informing risk assessment with a continuous point of departure (PoD), a weighted sum of the SkinSens-BN probabilities for four potency classes (non-, weak, moderate, and strong/extreme sensitizer) was calculated, using fixed weights based on associated LLNA EC3-values. The approach was promising, e.g., the derived PoDs for substances classified as non-sensitizers did not overlap with any others and 77% of PoDs were similar or more conservative than LLNA EC3. In addition, the predictions were assigned a level of confidence based on the probabilities to inform the evaluation of uncertainty in an NGRA context. In conclusion, the PoD derivation approach can substantially contribute to reliable skin sensitization NGRAs.

Abstract Background Isoflurane is used as an inhalation anesthetic in medical, paramedical, and veterinary practice. Epidemiological studies suggest an increased risk of miscarriages and malformations at birth related to maternal exposure to isoflurane and other inhalation anesthetics. However, these studies cannot be used to derive an occupational exposure level (OEL), because exposure was not determined quantitatively and other risk factors such as co-exposures to other inhalation anesthetics and other work-related factors may also have contributed to the observed adverse outcomes. The aim of this systematic review project is to assess all available evidence on the effects of isoflurane in studies of controlled exposures in laboratory animals to derive a health-based recommended OEL. Methods A comprehensive search strategy was developed to retrieve all animal studies addressing isoflurane exposure from PubMed, EMBASE, and Web of Science. Title-abstract screening will be performed by machine learning, and full-text screening by one reviewer. Discrepancies will be resolved by discussion. We will include primary research in healthy, sexually mature (non human) vertebrates of single exposure to isoflurane. Studies describing combined exposure and treatments with > = 1 vol% isoflurane will be excluded. Subsequently, details regarding study identification, study design, animal model, and intervention will be summarized. All relevant exposure characteristics and outcomes will be extracted. The risk of bias will be assessed by two independent reviewers using an adapted version of the SYRCLE’s risk of bias tool and an addition of the OHAT tool. For all outcomes for which dose–response curves can be derived, the benchmark dose (BMD) approach will be used to establish a point of departure for deriving a recommended health-based recommended OEL for 8 h (workshift exposure) and for 15 min (short-term exposure). Discussion Included studies should be sufficiently sensitive to detect the adverse health outcomes of interest. Uncertainties in the extrapolation from animals to humans will be addressed using assessment factor. These factors are justified in accordance with current practice in chemical risk assessment. A panel of experts will be involved to reach consensus decisions regarding significant steps in this project, such as determination of the critical effects and how to extrapolate from animals to humans. Systematic review registration PROSPERO CRD42022308978

In the contemporary globalized landscape characterized by international and intercultural decision-making processes, interconnected supply chains, and diverse customer relations, susceptibility to biases and heuristics poses a substantial threat to the efficiency of decision making. This research explores the relatively understudied influence of culture on individuals’ susceptibility to concepts derived from behavioral economics. Employing the Individual Cultural Values Scale (CVSCALE), we examine the impact of culture on the allure of choice, mental accounting, and overconfidence among 837 participants from Australia (AU), China (CN), Germany (GE), and the United States (US) through logistic regression analysis. At the individual level, discernible interactions between power–distance, allure of choice, and overconfidence are observed. On the national scale, power–distance (AU, US), uncertainty avoidance (US), and masculinity (CN) significantly impact the allure of choice, while overconfidence is influenced by power–distance (US) and masculinity (US). Our analysis shows that culture plays a pivotal role in shaping susceptibility to biases and heuristics, thereby influencing decision-making processes. The findings advocate for a culturally differentiated approach to behavioral economics, emphasizing the need to tailor strategies and interventions based on cultural nuances.

Representation learning has proven to be a powerful methodology in a wide variety of machine-learning applications. For atmospheric dynamics, however, it has so far not been considered, arguably due to the lack of large-scale, labeled datasets that could be used for training. In this work, we show how to sidestep the difficulty and introduce a self-supervised learning task that is applicable to a wide variety of unlabeled atmospheric datasets. Specifically, we train a neural network on the simple yet intricate task of predicting the temporal distance between atmospheric fields from distinct but nearby times. We demonstrate that training with this task on the ERA5 reanalysis dataset leads to internal representations that capture intrinsic aspects of atmospheric dynamics. For example, when employed as a loss function in other machine-learning applications, the derived AtmoDist distance leads to improved results compared to the $ {\mathrm{\ell}}_2 $ -loss. For downscaling one obtains higher resolution fields that match the true statistics more closely than previous approaches and for the interpolation of missing or occluded data the AtmoDist distance leads to results that contain more realistic fine-scale features. Since it is obtained from observational data, AtmoDist also provides a novel perspective on atmospheric predictability.

Background: “Biological plausibility” is a concept frequently referred to in environmental and public health when researchers are evaluating how confident they are in the results and inferences of a study or evidence review. Biological plausibility is not, however, a domain of one of the most widely-used approaches for assessing the certainty of evidence (CoE) which underpins the findings of a systematic review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) CoE Framework. Whether the omission of biological plausibility is a potential limitation of the GRADE CoE Framework is a topic that is regularly discussed, especially in the context of environmental health systematic reviews. Objectives: We analyse how the concept of “biological plausibility”, as applied in the context of assessing certainty of the evidence that supports the findings of a systematic review, is accommodated under the processes of systematic review and the existing GRADE domains. Results and discussion: We argue that “biological plausibility” is a concept which primarily comes into play when direct evidence about the effects of an exposure on a population of concern (usually humans) is absent, at high risk of bias, is inconsistent, or limited in other ways. In such circumstances, researchers look toward evidence from other study designs in order to draw conclusions. In this respect, we can consider experimental animal and in vitro evidence as “surrogates” for the target populations, exposures, comparators and outcomes of actual interest. Through discussion of 10 examples of experimental surrogates, we propose that the concept of biological plausibility consists of two principal aspects: a “generalisability aspect” and a “mechanistic aspect”. The “generalisability aspect” concerns the validity of inferences from experimental models to human scenarios, and asks the same question as does the assessment of external validity or indirectness in systematic reviews. The “mechanistic aspect” concerns certainty in knowledge of biological mechanisms and would inform judgements of indirectness under GRADE, and thus the overall CoE. While both aspects are accommodated under the indirectness domain of the GRADE CoE Framework, further research is needed to determine how to use knowledge of biological mechanisms in the assessment of indirectness of the evidence in systematic reviews.

Abstract Background Limb loss has a drastic impact on a patient’s life. Severe trauma to the extremities is common in current military conflicts. Among other aspects, “life before limb” damage control surgery hinders immediate replantation within the short post-traumatic timeframe, which is limited in part by the ischemic time for successful replantation. Ex vivo limb perfusion is currently being researched in animal models and shows promising results for its application in human limb replantation and allotransplantation. Presentation of the hypothesis The current lack of replantation possibilities in military operations with high rates of amputation can be addressed with the development of a portable ex vivo limb perfusion device, as there are several opportunities present with the introduction of this technique on the horizon. We hypothesize that ex vivo limb perfusion will enable overcoming the critical ischemic time, provide surgical opportunities such as preparation of the stump and limb, allow for spare-part surgery, enable rigorous antibiotic treatment of the limb, reduce ischemia-reperfusion injuries, enable a tissue function assessment before replantation, and enable the development of large limb transplant programs. Testing the hypothesis Data from in vivo studies in porcine models are limited by the relatively short perfusion time of 24 h. In the military setting, notably longer perfusion times need to be realized. Therefore, future animal studies must focus especially on long-term perfusion, since this represents the military setting, considering the time for stabilization of the patient until evacuation to a tertiary treatment center. Implications of the hypothesis The development and clinical introduction of ex vivo limb perfusion in the military setting could lead to a drastic reduction in the number of limb amputations among service members. Ex vivo limb perfusion enables replantation surgery in Role 4 facilities and changes the clinical setting from a highly urgent, life-threatening situation to a highly methodical, well-prepared starting point for optimal treatment of the wounded service member. With its introduction, the principle of “life before limb” will change to “life before limb before elective replantation/allotransplantation after ex vivo limb perfusion”.

In-depth forensic investigation and analysis of historic vehicles is a relatively new field of research. However, such examinations are becoming an important tool in the face of rising market values and the associated increase of manipulations and forgeries. We review various forensic approaches used in our interdisciplinary work in this field, including vehicle specialists, metallurgists, restorers, and archaeometry laboratories. The related investigations cover a general examination of the vehicle including detailed analysis of its materials and construction techniques, which are cross-referenced with the techniques and materials used in period. We illustrate our theoretical and analytical approach with practical examples from our work on collector vehicles. Finally, we consider methods and approaches currently under development.

Phosphorylation of CENP-A on serine 7 has been proposed to control centromere assembly and function. Here, the authors use gene targeting at both endogenous CENP-A alleles and gene replacement in human cells to demonstrate that CENP-A that cannot be phosphorylated at serine 7 maintains correct CENP-C recruitment, faithful chromosome segregation and long-term cell viability.

Background: There are several standards that offer explicit guidance on good practice in systematic reviews (SRs) for the medical sciences; however, no similarly comprehensive set of recommendations has been published for SRs that focus on human health risks posed by exposure to environmental challenges, chemical or otherwise. Objectives: To develop an expert, cross-sector consensus view on a key set of recommended practices for the planning and conduct of SRs in the environmental health sciences. Methods: A draft set of recommendations was derived from two existing standards for SRs in biomedicine and developed in a consensus process, which engaged international participation from government, industry, non-government organisations, and academia. The consensus process consisted of a workshop, follow-up webinars, email discussion and bilateral phone calls. Results: The Conduct of Systematic Reviews in Toxicology and Environmental Health Research (COSTER) recommendations cover 70 SR practices across eight performance domains. Detailed explanations for specific recommendations are made for those identified by the authors as either being novel to SR in general, specific to the environmental health SR context, or potentially controversial to environmental health SR stakeholders. Discussion: COSTER provides a set of recommendations that should facilitate the production of credible, high-value SRs of environmental health evidence, and advance discussion of a number of controversial aspects of conduct of EH SRs. Key recommendations include the management of conflicts of interest, handling of grey literature, and protocol registration and publication. A process for advancing from COSTER’s recommendations to developing a formal standard for EH SRs is also indicated.

Bullous pemphigoid (BP) is a blistering autoimmune disease mainly observed in elderly patients. Several triggers are known for this autoimmune disease and some drugs are known to be a cause of BP. However, there are only few case reports on the induction of BP under adalimumab therapy. Other autoimmune diseases, such as lupus erythematosus, are also known to occur under TNF inhibition. Here, we report on an 81-year-old patient who received adalimumab for ulcerative colitis and subsequently developed BP. Other causes of BP (tumors, other drugs, viral or toxoplasma infections) were excluded. We initiated a topical and systemic therapy (prednisolone 1 mg/kg/day) and stopped the adalimumab injections. The patient’s symptoms resolved quickly and we were able to taper corticosteroid therapy. This rare case highlights the importance to monitor for autoimmune events during TNF inhibition.

Systematic review (SR) is a rigorous, protocol-driven approach designed to minimise error and bias when summarising the body of research evidence relevant to a specific scientific question. Taking as a comparator the use of SR in synthesising research in healthcare, we argue that SR methods could also pave the way for a “step change” in the transparency, objectivity and communication of chemical risk assessments (CRA) in Europe and elsewhere. We suggest that current controversies around the safety of certain chemicals are partly due to limitations in current CRA procedures which have contributed to ambiguity about the health risks posed by these substances. We present an overview of how SR methods can be applied to the assessment of risks from chemicals, and indicate how challenges in adapting SR methods from healthcare research to the CRA context might be overcome. Regarding the latter, we report the outcomes from a workshop exploring how to increase uptake of SR methods, attended by experts representing a wide range of fields related to chemical toxicology, risk analysis and SR. Priorities which were identified include: the conduct of CRA-focused prototype SRs; the development of a recognised standard of reporting and conduct for SRs in toxicology and CRA; and establishing a network to facilitate research, communication and training in SR methods. We see this paper as a milestone in the creation of a research climate that fosters communication between experts in CRA and SR and facilitates wider uptake of SR methods into CRA. Keywords: Risk assessment, Research synthesis, Environment, Chemicals, Systematic review, Toxicology

Assessments of methodological and reporting quality are critical to adequately judging the credibility of a study's conclusions and to gauging its potential reproducibility. To aid those seeking to assess the methodological or reporting quality of studies relevant to toxicology, we conducted a scoping review of the available guidance with respect to four types of studies: in vivo and in vitro, (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and human observational studies. Our aims were to identify the available guidance in this diverse literature, briefly summarize each document, and distill the common elements of these documents for each study type. In general, we found considerable guidance for in vivo and human studies, but only one paper addressed in vitro studies exclusively. The guidance for (Q)SAR studies and physico-chemical studies was scant but authoritative. There was substantial overlap across guidance documents in the proposed criteria for both methodological and reporting quality. Some guidance documents address toxicology research directly, whereas others address preclinical research generally or clinical research and therefore may not be fully applicable to the toxicology context without some translation. Another challenge is the degree to which assessments of methodological quality in toxicology should focus on risk of bias – as in clinical medicine and healthcare – or be broadened to include other quality measures, such as confirming the identity of test substances prior to exposure. Our review is intended primarily for those in toxicology and risk assessment seeking an entry point into the extensive and diverse literature on methodological and reporting quality applicable to their work. Keywords: Methodological quality, Reporting quality, Risk of bias, Scoping review, Toxicity studies

This paper presents an agent-based model (ABM) for residential end-users, which is part of a larger, interdisciplinary co-simulation framework that helps to investigate the performance of future power distribution grids (i.e., smart grid scenarios). Different modes of governance (strong, soft and self-organization) as well as end-users’ heterogeneous behavior represent key influential factors. Feedback was implemented as a measure to foster grid-beneficial behavior, which encompasses a range of monetary and non-monetary incentives (e.g., via social comparison). The model of frame selection (MFS) serves as theoretical background for modelling end-users’ decision-making. Additionally, we conducted an online survey to ground the end-user sub-model on empirical data. Despite these empirical and theoretical foundations, the model presented should be viewed as a conceptual framework, which requires further data collection. Using an example scenario, representing a lowly populated residential area (167 households) with a high share of photovoltaic systems (30%), different modes of governance were compared with regard to their suitability for improving system stability (measured in cumulated load). Both soft and strong control were able to decrease overall fluctuations as well as the mean cumulated load (by approx. 10%, based on weekly observation). However, we argue that soft control could be sufficient and more societally desirable.

Das Simulationsframework „SimCo“ erlaubt es, die Steuerung komplexer, netzwerkförmiger, soziotechnischer (Infrastruktur-)Systeme zu untersuchen – beispielsweise die des Verkehrs- oder Energiesystems. SimCo basiert auf den Prinzipien der agentenbasierten Modellierung und Simulation. Dynamiken auf der Systemebene werden durch die Interaktion einer Vielzahl strategisch handelnder, heterogener Agenten erzeugt. Mit Hilfe von Simulationsexperimenten lassen sich unterschiedliche Szenarien (mit politisch definierten Zielvorstellungen) hinsichtlich ihrer Wirksamkeit sowie möglicher nicht-intendierter Nebenfolgen testen, denn der Steuerungserfolg hängt letztlich von den Reaktionen der Agenten auf der Mikro-Ebene ab. Ein abstraktes, urbanes Verkehrssystem dient als Anwendungsfall und lässt eine Mischung aus weichen und harten Steuerungsmaßnahmen vielversprechend erscheinen.

Background Per- and polyfluoroalkyl substances (PFAS) were used or are being used in the manufacturing of products, including consumer-use products. The resulting environmental contamination has led to widespread human exposure. This review aimed to scope the characteristics of evidence covered and applied methodology of evidence to understand -- regardless of any results on the association of gestational diabetes mellitus (GDM) and PFAS -- if a new systematic review would be justified. Methods We systematically identified reports investigating associations of PFAS with GDM following a pre-specified and pre-registered PECO framework and protocol. Results The previous systematic reviews included 8-11 reports and either conducted meta-analyses stratified by comparator, analyzed results based on only high and low exposure categories, or pooled results across comparators. Included 20 reports presented data on 24 PFAS with PFOA, PFOS, PFHxS, PFNA, and PFDA being examined in almost all. The comparators employed were heterogeneous across the reports. Conclusions Because data from at least one new report on GDM is available since the previous systematic reviews and heterogeneous comparators, an updated systematic review using SWiM could add value to the literature.

In order to build optical transmission systems for 100 Gb/s and above on a single wavelength division multiplexing channel, transition from quadrature phase-shift keying (QPSK) to higher quadrature amplitude modulation (QAM) formats seems to be inevitable. Instead of the usual square constellation QAM, we focus on regular star constellation QAM formats and present a hardware-efficient phase-estimation algorithm that is suitable for all regular star constellations, together with preliminary simulation results.

Background Per- and polyfluoroalkyl substances (PFAS) were used or are being used in the manufacturing of products, including consumer-use products. The resulting environmental contamination has led to widespread human exposure. This review aimed to scope the characteristics of evidence covered and applied methodology of evidence to understand -- regardless of any results on the association of gestational diabetes mellitus (GDM) and PFAS -- if a new systematic review would be justified. Methods We systematically identified reports investigating associations of PFAS with GDM following a pre-specified and pre-registered PECO framework and protocol. Results The previous systematic reviews included 8-11 reports and either conducted meta-analyses stratified by comparator, analyzed results based on only high and low exposure categories, or pooled results across comparators. Included 20 reports presented data on 24 PFAS with PFOA, PFOS, PFHxS, PFNA, and PFDA being examined in almost all. The comparators employed were heterogeneous across the reports. Conclusions Because data from at least one new report on GDM is available since the previous systematic reviews and heterogeneous comparators, an updated systematic review using SWiM could add value to the literature.