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Purpose: To introduce quantitative rapid gradient‐echo (QRAGE), a novel approach for the simultaneous mapping of multiple quantitative MRI parameters, including water content, T1, T2*, and magnetic susceptibility at ultrahigh field strength. Methods: QRAGE leverages a newly developed multi‐echo MPnRAGE sequence, facilitating the acquisition of 171 distinct contrast images across a range of TI and TE points. To maintain a short acquisition time, we introduce MIRAGE2, a novel model‐based reconstruction method that exploits prior knowledge of temporal signal evolution, represented as damped complex exponentials. MIRAGE2 minimizes local Block‐Hankel and Casorati matrices. Parameter maps are derived from the reconstructed contrast images through postprocessing steps. We validate QRAGE through extensive simulations, phantom studies, and in vivo experiments, demonstrating its capability for high‐precision imaging. Results: In vivo brain measurements show the promising performance of QRAGE, with test–retest SDs and deviations from reference methods of < 0.8% for water content, < 17 ms for T1, and < 0.7 ms for T2*. QRAGE achieves whole‐brain coverage at a 1‐mm isotropic resolution in just 7 min and 15 s, comparable to the acquisition time of an MP2RAGE scan. In addition, QRAGE generates a contrast image akin to the UNI image produced by MP2RAGE. Conclusion: QRAGE is a new, successful approach for simultaneously mapping multiple MR parameters at ultrahigh field. [ABSTRACT FROM AUTHOR]

Summary: Mitochondrial diseases are rare genetic disorders often accompanied by severe sleep disorders. We present the case of a 12‐year‐old boy diagnosed with a severe primary mitochondrial disease, exhibiting ataxia, spasticity, progressive external ophthalmoplegia, cardiomyopathy and severely disrupted sleep, but no cognitive impairment. Interestingly, his parents reported improved sleep during night train rides. Based on this observation, we installed a rocking bed in the patient's bedroom and performed different interventions, including immersive multimodal vestibular, kinesthetic and auditory stimuli, reminiscent of the sensory experiences encountered during train rides. Over a 5‐month period, we conducted four 2‐week nocturnal interventions, separated by 1‐week washout phases, to determine the subjectively best‐perceived stimulation parameters, followed by a final 4‐week intervention using the optimal parameters. We assessed sleep duration and quality using the Mini Sleep Questionnaire, monitored pulse rate changes and used videography to document nocturnal interactions between the patient and caregivers. Patient‐reported outcome measures, clinical examinations and personal outcomes of specific interests were used to document daytime sleepiness, restlessness, anxiety, fatigue, cognitive performance and physical posture. In the final 4‐week intervention, sleep duration increased by 25%, required caregiver interactions reduced by 75%, and caregiving time decreased by 40%. Subjective fatigue, assessed by the Checklist Individual Strength, decreased by 40%, falling below the threshold of severe fatigue. Our study suggests that rocking beds could provide a promising treatment regime for selected patients with persistent severe sleep disorders. Further research is required to validate these findings in larger patient populations with sleep disorders and other conditions. [ABSTRACT FROM AUTHOR]

Background: In ovo MR presents a promising and viable alternative to traditional in vivo small animal experiments. Sodium MRI complements proton MRI by providing potential access to tissue cellular metabolism. Despite its abundance, sodium MRI is challenged by lower MR sensitivity and faster relaxation times compared to proton MRI. Ensuring a high signal‐to‐noise ratio and effective B0 shimming is essential. Double‐tuned coils combining 23Na and 1H are frequently employed to achieve structural imaging and efficient shim adjustment. Purpose: This study introduces a novel, highly optimized, double‐tuned coil design, specifically for MR scans of chick embryos. Methods: A tapered‐spiral, double‐tuned coil was designed and constructed following careful consideration of design parameters. The performance of the coil was rigorously assessed through bench tests, and final validation was conducted on a 7 T MRI scanner using a chick embryo. Results: Bench tests demonstrated that the return losses for both 1H and 23Na coils were better than − 30 dB, and isolation factors were better than − 21 dB, indicating that the double‐tuned coil was well‐set, with negligible coupling between channels. MR images of chick embryos, obtained using the coil, validated the feasibility of utilizing the design concept for in ovo applications. Conclusions: The innovative design of the proposed double‐tuned coil, characterized by its unique arrangement, offers improved performance. This design has the potential to significantly enhance the quality of in ovo1H and 23Na measurements. [ABSTRACT FROM AUTHOR]

Purpose: Demonstration of a high dynamic‐range and high SNR method for acquiring absolute B1+$$ {\mathrm{B}}_1^{+} $$ maps from a combination of gradient echo and actual‐flip‐angle measurements that is especially useful during the construction of parallel‐transmit arrays. Methods: Low flip angle gradient echo images, acquired when transmitting with each channel individually, are used to compute relative B1+$$ {\mathrm{B}}_1^{+} $$ maps. Instead of computing these in a conventional manner, the equivalence of the problem to the ESPIRiT parallel image reconstruction method is used to compute B1+$$ {\mathrm{B}}_1^{+} $$ maps with a higher SNR. Absolute maps are generated by calibration against a single actual flip‐angle acquisition when transmitting on all channels simultaneously. Results: Depending on the number of receiver channels and the location of the receive elements with respect to the subject being investigated, moderate to high gains in the SNR of the acquired B1+$$ {\mathrm{B}}_1^{+} $$ maps can be achieved. Conclusions: The proposed method is especially suited for the acquisition of B1+$$ {\mathrm{B}}_1^{+} $$ maps during the construction of transceiver arrays. Compared to the original method, maps with higher SNR can be computed without the need for additional measurements, and maps can also be generated using previously acquired data. Furthermore, easy adoption and fast estimation of receiver channels is possible because of existing highly optimized open‐source implementations of ESPIRiT, such as in the BART toolbox. [ABSTRACT FROM AUTHOR]

Electrochemical reduction of CO2 poses a vast potential to contribute to a defossilized industry. Despite tremendous developments within the field, mass transport limitations, carbonate salt formation, and electrode degradation mechanisms still hamper the process performance. One promising approach to tweak CO2 electrolysis beyond today's limitations is pulsed electrolysis with potential cycling between an operating and a regeneration mode. Here, we rigorously model the boundary layer at a silver electrode in pulsed operation to get profound insights into the dynamic reorganization of the electrode microenvironment. In our simulation, pulsed electrolysis leads to a significant improvement of up to six times higher CO current density and 20 times higher cathodic energy efficiency when pulsing between −1.85 and −1.05 V vs SHE compared to constant potential operation. We found that elevated reactant availability in pulsed electrolysis originates from alternating replenishment of CO2 by diffusion and not from pH‐induced carbonate and bicarbonate conversion. Moreover, pulsed electrolysis substantially promotes carbonate removal from the electrode by up to 83 % compared to constant potential operation, thus reducing the risk of salt formation. Therefore, this model lays the groundwork for an accurate simulation of the dynamic boundary layer modulation, which can provide insights into manifold electrochemical conversions. [ABSTRACT FROM AUTHOR]

Since their discovery, [2.2]paracyclophane (pCp) and its derivatives have fascinated the scientific community due to their original molecular architecture and unusual electronic behavior. Over the years, significant efforts have been devoted to the development of substituted pCps for a variety of applications in different fields, ranging from organic synthesis and asymmetric catalysis to polymer chemistry and material science. This review describes a series of useful approaches that allow chemists to selectively decorate pCps, control the planar chirality that these molecules can display as soon as they are functionalized, and tune their photophysical behaviors. For each of these aspects of paracyclophane chemistry, selected examples of major advances are presented, and possible directions for future research are outlined. The application of pCp as central core for the development of uncommon 3D luminophores is finally highlighted. Emphasis is placed on the potential use of planar chiral luminescent paracyclophanes as antennas or ligands for the design of multifunctional lanthanide complexes, a quite underdeveloped but highly promising area for future research endeavors. [ABSTRACT FROM AUTHOR]

The persistence of multiple educational pathways into the nursing profession continues to occupy scholars internationally. In the Netherlands, various groups within the Dutch healthcare sector have tried to differentiate nursing practice on the basis of educational backgrounds for over 50 years. Proponents argue that such reforms are needed to retain bachelor‐trained nurses, improve quality of care and strengthen nurses' position in the sector. Opponents have actively resisted reforms because they would mainly benefit bachelor‐trained nurses and neglect practical experience and technical skills. This historical case study aims to provide insight in this apparent stalemate. Our analysis of this debate is informed by literature on institutional work and current debates within the historiography of nursing. This study contributes to a better understanding of this contemporary debate by examining a broader timeframe than is usually studied, and by highlighting nurses' roles in complex processes of change. We argue that, rather than being stuck in their professional development, different groups of nurses have forged their own path forward in their professional development, albeit via different strategies. [ABSTRACT FROM AUTHOR]

Background: Given that changes in brain water content are often correlated with disease, investigating water content non‐invasively and in vivo could lead to a better understanding of the pathogenesis of several neurologic diseases. Purpose: To adapt a super‐resolution‐based technique, previously developed for humans, to the rat brain and report in vivo high‐resolution (HR) water content maps in comparison with ex vivo wet/dry methods. Study Type: Prospective. Animal Model: Eight healthy male Wistar rats. Field Strength/Sequence: 9.4‐T, multi‐echo gradient‐echo (mGRE) sequence. Assessment: Using super‐resolution reconstruction (SRR), a HR mGRE image (200 μm isotropic) was reconstructed from three low‐resolution (LR) orthogonal whole‐brain images in each animal, which was followed by water content mapping in vivo. The animals were subsequently sacrificed, the brains excised and divided into five regions (front left, front right, middle left, middle right, and cerebellum–brainstem regions), and the water content was measured ex vivo using wet/dry measurements as the reference standard. The water content values of the in vivo and ex vivo methods were then compared for the whole brain and also for the different regions separately. Statistical Tests: Friedman's non‐parametric test was used to test difference between the five regions, and Pearson's correlation coefficient was used for correlation between in vivo and ex vivo measurements. A P‐value <0.05 was considered statistically significant. Results: Water content values derived from in vivo MR measurements showed strong correlations with water content measured ex vivo at a regional level (r = 0.902). Different brain regions showed significantly different water content values. Water content values were highest in the frontal brain, followed by the midbrain, and lowest in the cerebellum and brainstem regions. Data Conclusion: An in vivo technique to achieve HR isotropic water content maps in the rat brain using SRR was adopted in this study. The MRI‐derived water content values obtained using the technique showed strong correlations with water content values obtained using ex vivo wet/dry methods. Level of Evidence: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Due to processes of financialisation, financial parties increasingly penetrate the healthcare domain and determine under which conditions care is delivered. Their influence becomes especially visible when healthcare organisations face financial distress. By zooming‐in on two of such cases, we come to know more about the considerations, motives and actions of financial parties in healthcare. In this research, we were able to examine the social dynamics between healthcare executives, banks and health insurers involved in a Dutch hospital and mental healthcare organisation on the verge of bankruptcy. Informed by interviews, document analysis and translation theory, we reconstructed the motives and strategies of executives, banks and health insurers and show how they play a crucial role in decision‐making processes surrounding the survival or downfall of healthcare organisations. While parties are bound by legislation and company procedures, the outcome of financial distress can still be influenced. Much depends on how executives are perceived by financial stakeholders and how they deal with threats of destabilisation of the network. We further draw attention to the consequences of financialisation processes on the practices of healthcare organisations in financial distress. [ABSTRACT FROM AUTHOR]

We use the smooth ambiguity model to show that ambiguity aversion increases the value of and demand for genetic information for low prior beliefs of carrying a genetic mutation. We also examine an extension based on the ex ante uncertainty of the test results. The extended model, which accommodates ambiguity aversion only in the presence of new information, lowers the value of genetic information and leads to information avoidance. If this behavior is sufficiently strong, it could explain the low demand observed for genetic tests. [ABSTRACT FROM AUTHOR]

Melatonin is an important player in the regulation of many physiological functions within the body and in the retina. Melatonin synthesis in the retina primarily occurs during the night and its levels are low during the day. Retinal melatonin is primarily synthesized by the photoreceptors, but whether the synthesis occurs in the rods and/or cones is still unclear. Melatonin exerts its influence by binding to G protein‐coupled receptors named melatonin receptor type 1 (MT1) and type 2 (MT2). MT1 and MT2 receptors activate a wide variety of signaling pathways and both receptors are present in the vertebrate photoreceptors where they may form MT1/MT2 heteromers (MT1/2h). Studies in rodents have shown that melatonin signaling plays an important role in the regulation of retinal dopamine levels, rod/cone coupling as well as the photopic and scotopic electroretinogram. In addition, melatonin may play an important role in protecting photoreceptors from oxidative stress and can protect photoreceptors from apoptosis. Critically, melatonin signaling is involved in the modulation of photoreceptor viability during aging and other studies have implicated melatonin in the pathogenesis of age‐related macular degeneration. Hence melatonin may represent a useful tool in the fight to protect photoreceptors—and other retinal cells—against degeneration due to aging or diseases. [ABSTRACT FROM AUTHOR]

Background: While most cutaneous squamous cell carcinomas (cSCCs) are treatable, certain high‐risk cSCCs, such as those in recessive dystrophic epidermolysis bullosa (RDEB) patients, are particularly aggressive. Owing to repeated wounding, inflammation and unproductive healing, RDEB patients have a 68% cumulative risk of developing life‐threatening cSCCs by the age of 35, and a 70% risk of death by the age of 45. Despite aggressive treatment, cSCC represents the leading cause of premature mortality in these patients, highlighting an unmet clinical need. Increasing evidence points to a role of altered metabolism in the initiation and maintenance of cSCC, making metabolism a potential therapeutic target. Objectives: We sought to determine the feasibility of targeting tumour cell energetics as a strategy to selectively hinder the growth advantage of aggressive cSCC. Methods: We evaluated the cell energetics profiles of RDEB‐SCC cells by analysing available gene expression data against multiple gene signatures and single‐gene targets linked to metabolic reprogramming. Additionally, we employed real‐time metabolic profiling to measure glycolysis and respiration in these cells. Furthermore, we investigated the anti‐neoplastic properties of the metformin against human and murine high‐risk cSCCs in vitro and in vivo. Results: Gene expression analyses highlighted a divergence in cell energetics profiles between RDEB‐SCC and non‐malignant RDEB keratinocytes, with tumour cells demonstrating enhanced respiration and glycolysis scores. Real‐time metabolic profiling supported these data and additionally highlighted a metabolic plasticity of RDEB‐SCC cells. Against this background, metformin exerted an anti‐neoplastic potential by hampering both respiration and glycolysis, and by inhibiting proliferation in vitro. Metformin treatment in an analogous model of fast‐growing murine cSCC resulted in delayed tumour onset and slower tumour growth, translating to a 29% increase in median overall survival. Conclusions: Our data indicate that metformin exerts anti‐neoplastic properties in aggressive cSCCs that exhibit high‐risk features by interfering with respiration and glycolytic processes. [ABSTRACT FROM AUTHOR]

Comparative phylogenetic analyses are of potential value to establish the essential components of genetic networks underlying physiological traits. For species that naturally lack particular lymphocyte lineages, we show here that this strategy readily distinguishes trait‐specific actors from pleiotropic components of the genetic network governing lymphocyte differentiation. Previously, three of the four members of the DNA polymerase X family have been implicated in the junctional diversification process during the somatic assembly of antigen receptors. Our phylogenetic analysis indicates that the presence of terminal deoxynucleotidyl transferase is strictly associated with the facility of V(D)J recombination, whereas PolL and PolM genes are retained even in species lacking Rag‐mediated somatic diversification of antigen receptor genes. [ABSTRACT FROM AUTHOR]

Thin glass products have a giant field of application in several engineering branches such as for example, electronics, medical equipment, and the automotive industry. The non‐isothermal glass molding is a novel replicative glass processing technology enabling the realization of a cost‐efficient production of surface shapes with high accuracy and complexity. However, the application of this technology to thin glass production still causes shape distortions, cracks, and surface defects in molded parts. Therefore, these glass‐forming processes should be simulated by means of the combination of experimental investigation and mechanical modeling of glass above the glass transition temperature at finite strains. Previous experimental studies have shown that the Maxwell model is a reasonable approach for an appropriate prediction of the material behavior. Based on this viscoelastic formulation, a thermo‐mechanically consistent material law is used enabling the prediction of rheological effects noticed during the experiments. More specifically, the relaxation behavior can be described by a stress‐dependent relaxation time and the dissipation generated is considered as well. Furthermore, isothermal uniaxial compression tests above the glass transition temperature are conducted for different strain rates and temperatures within the experimental investigation. Combining the experimental data with the simulation, a multi‐curve‐fitting leads to suitable material parameters with respect to distinct temperatures employing a nonlinear optimization. [ABSTRACT FROM AUTHOR]

Within this contribution, we propose a fully thermo‐mechanical coupled isotropic damage model for polymeric adhesives under finite strains. This model is based on the multiplicative decomposition of the deformation gradient into mechanical and thermal parts. We consider rate‐dependent damage behaviour (e.g. creep damage) of the material by applying a Perzyna‐type ansatz for the damage evolution equations. To overcome the pronounced mesh dependencies which would result from the usage of a local damage model, we make use of a gradient‐extended damage formulation. Besides the main aspects of model, we show the thermodynamically consistent derivation of constitutive quantities as well as the numerical treatment of the governing equations. Finally, we show selected numerical examples to demonstrate the capabilities of the model. [ABSTRACT FROM AUTHOR]

Introduction: Growing evidence suggests that some common infections are causally associated with cognitive impairment; however, less is known about the burden of multiple infections. Methods: We investigated the cross‐sectional association of positive antibody tests for herpes simplex virus, cytomegalovirus (CMV), Epstein‐Barr virus (EBV), varicella zoster virus (VZV), and Toxoplasma gondii (TOX) with Mini‐Mental State Examination (MMSE) and delayed verbal recall performance in 575 adults aged 41–97 from the Baltimore Epidemiologic Catchment Area Study. Results: In multivariable‐adjusted zero‐inflated Poisson (ZIP) regression models, positive antibody tests for CMV (p =.011) and herpes simplex virus (p =.018) were individually associated with poorer MMSE performance (p =.011). A greater number of positive antibody tests among the five tested was associated with worse MMSE performance (p =.001). Discussion: CMV, herpes simplex virus, and the global burden of multiple common infections were independently associated with poorer cognitive performance. Additional research that investigates whether the global burden of infection predicts cognitive decline and Alzheimer's disease biomarker changes is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Nurse clinician‐scientists are increasingly expected to show leadership aimed at transforming healthcare. However, research on nurse clinician‐scientists' leadership (integrating researcher and practitioner roles) is scarce and hardly embedded in sociohistorical contexts. This study introduces leadership moments, that is, concrete events in practices that are perceived as acts of empowerment, in order to understand leadership in the daily work of newly appointed nurse clinician‐scientists. Following the learning history method we gathered data using multiple (qualitative) methods to get close to their daily practices. A document analysis provided us with insight into the history of nursing science to illustrate how leadership moments in the everyday work of nurse clinician‐scientists in the "here and now" can be related to the particular histories from which they emerged. A qualitative analysis led to three acts of empowerment: (1) becoming visible, (2) building networks, and (3) getting wired in. These acts are illustrated with three series of events in which nurse clinician‐scientists' leadership becomes visible. This study contributes to a more socially embedded understanding of nursing leadership, enables us to get a grip on crucial leadership moments, and provides academic and practical starting points for strengthening nurse clinician‐scientists' leadership practices. Transformations in healthcare call for transformed notions of leadership. [ABSTRACT FROM AUTHOR]

Aim: Return to intended oncologic treatment (RIOT) is an important paradigm for surgically resected cancers requiring multimodal treatment. Benefits of minimally invasive colectomy (MIC) may allow earlier initiation of adjuvant chemotherapy (ACT) and have associated survival benefits. We sought to determine if operative approach affects RIOT timing in resected stage III colon cancer. Methods: NCDB identified pathological stage III colon adenocarcinoma patients who underwent resection and received ACT. Propensity score matching and kernel density estimation compared operative approaches and conversion impact on intervals to RIOT. Results: A total of 15,132 open colectomies (OC) versus 14,107 MIC were included. MIC patients had two‐days shorter median length of stay (LOS) (4 vs. 6 days; p < 0.001), one‐week shorter median time to RIOT (6 vs. 7 weeks; p = 0.015) comparing 12,867 matched pairs. There was no difference in time interval to RIOT between the LC versus RC, converted MIC vs. OC groups. MIC was a favourable predictor of earlier RIOT (HR 1.14 [1.07–1.22]; p < 0.001). Conclusion: MIC in stage III colon cancer is associated with a shorter time to RIOT when compared to OC. Since timely initiation of ACT may influence cancer outcome, MIC may be oncologically preferable. Prospective studies are needed to assess RIOT and survival outcomes in stage III colon cancer. [ABSTRACT FROM AUTHOR]

Summary: The United Nations Convention on the Rights of the Child emphasizes the importance of allowing children and adolescents to influence decisions that are important to them following their age and maturity. This paper explores the principles, practices, and implications around using parental versus child/adolescent consent when participating in social science research and policy development. Experiences from two studies are presented: The Confronting Obesity: Co‐creating policy with youth (CO‐CREATE) and the Health Behaviour in School‐aged Children (HBSC) study, a World Health Organization (WHO) Collaborative Cross‐National study. Although parental consent may be an important gatekeeper for protecting children and adolescents from potentially harmful research participation, it may also be considered an obstacle to the empowerment of children and adolescents in case they want to share their views and experiences directly. This paper argues that evaluation of possible harm should be left to ethics committees and that, if no harm related to the research participation processes is identified and the project has a clear perspective on collaborating with the target group, adolescents from the age of 12 years should be granted the legal capacity to give consent to participate in the research project. Collaboration with adolescents in the development of the research project is encouraged. [ABSTRACT FROM AUTHOR]

Worldwide research groups and funding bodies have highlighted the need for imaging biomarkers to predict osteoarthritis (OA) progression and treatment effectiveness. Changes in trabecular architecture, which can be detected with non‐destructive high‐resolution CT imaging, may reveal OA progression before apparent articular surface damage. Here, we analysed the tibial epiphyses of STR/Ort (OA‐prone) and CBA (healthy, parental control) mice at different ages to characterise the effects of mouse age and strain on multiple bony parameters. We isolated epiphyseal components using a semi‐automated method, and measured the total epiphyseal volume; cortical bone, trabecular bone and marrow space volumes; mean trabecular and cortical bone thicknesses; trabecular volume relative to cortical volume; trabecular volume relative to epiphyseal interior (trabecular BV/TV); and the trabecular degree of anisotropy. Using two‐way ANOVA (significance level ≤0.05), we confirmed that all of these parameters change significantly with age, and that the two strains were significantly different in cortical and trabecular bone volumes, and trabecular degree of anisotropy. STR/Ort mice had higher cortical and trabecular volumes and a lower degree of anisotropy. As the two mouse strains reflect markedly divergent OA predispositions, these parameters have potential as bioimaging markers to monitor OA susceptibility and progression. Additionally, significant age/strain interaction effects were identified for total epiphyseal volume, marrow space volume and trabecular BV/TV. These interactions confirm that the two mouse strains have different epiphyseal growth patterns throughout life, some of which emerge prior to OA onset. Our findings not only propose valuable imaging biomarkers of OA, but also provide insight into ageing 3D epiphyseal architecture bone profiles and skeletal biology underlying the onset and development of age‐related OA in STR/Ort mice. [ABSTRACT FROM AUTHOR]

Thermoplastics are gaining interest for various industrial applications, since they can be widely used for thermoforming and injection moulding processes due to their thermostable material behavior. In combination with the material's low density and high strength to mass ratio, they are especially of interest in times where an improved environmental balance is more and more important. Hence, why they are for example frequently used in the automotive industry to reduce the weight of automotive components. Semi‐crystalline polymers as a subcategory of thermoplastics, partly crystallize after cool‐down from the molten state. During the thermoforming process, they are subjected to large deformations as well as thermal loads and show strong thermo‐mechanical coupling effects in addition to the influence of the evolution of the crystalline phase on the macroscopic material behavior. Therefore, computational models are needed to predict the complex material response reliably and minimize production errors. This work presents a thermomechanically consistent material formulation at finite strains. In order to account for the highly nonlinear material behavior, elasto‐plastic and visco‐elastic contributions are combined in the Helmholtz free energy and a dependency on temperature as well as the degree of cristallinity (DOC) is incorporated. Special attention is devoted to the choice of yield function and hardening behavior. A comparison of the simulation results to experiments at varying degrees of crystallinity and temperatures is presented to review the changes in the formulation. Therefore a special blending technique is used to ensure stable crystallinity conditions in the test samples. [ABSTRACT FROM AUTHOR]

Trichlorosilane is the key intermediate for the large‐scale production of polycrystalline silicon in the Siemens and Union Carbide processes. Both processes, however, are highly inefficient, and over two thirds of the trichlorosilane employed is converted to unwanted silicon tetrachloride accumulating in millions of tons per year on a global scale. In this combined experimental and theoretical study we report an energetically and environmentally benign synthetic protocol for the highly selective conversion of SiCl4 to HSiCl3 using organohydridosilanes as recyclable hydrogen transfer reagents in combination with onium chlorides as efficient catalysts. We put the same protocol to further use demonstrating the quantitative conversion of higher oligosilane residues, which form as another unwanted and potentially hazardous byproduct of Siemens processes, to HSiCl3 in a low‐temperature recycling step. [ABSTRACT FROM AUTHOR]

Accurately modeling the material behavior of paper and paperboard is proven to be highly demanding. Most difficulties arise from the pronounced anisotropic nature of the material. Additionally, differences in the in‐plane and out‐of‐plane behavior as well as non‐isochoric plasticity, which affects the elastic behavior, further deepen the issue at hand. Therefore, an material model is proposed, capable of capturing the anisotropic elasto‐plastic behavior of paper and paperboard. The constitutive framework was derived in a thermodynamically consistent manner, valid for finite deformations, and accounting for the coupling of in‐plane and out‐of‐plane behavior. The influence of the orthotropic anisotropy on the elasto‐plastic material response was introduced through the concept of structural tensors. A slight generalization of the elastic part of the free energy was made in order to incorporate the densification effect. A well known yield criterion was modified in order to account for some inconsistencies. Non‐isotropic hardening was considered by defining a set of coupled internal variables. The model's capabilities were demonstrated by simulating the process of folding and creasing. [ABSTRACT FROM AUTHOR]

Summary: This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan‐Hu‐1 RBD of SARS‐CoV‐2. We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human‐like, highly homogenous N‐linked glycans that has potential to impart greater potency and safety as a therapeutic. The epitope of 11D7 was mapped by competitive binding with well‐characterized mAbs, suggesting that it is a Class 4 RBD‐binding mAb that binds to the RBD outside the ACE2 binding site. Of note, 11D7 maintains recognition against the B.1.1.529 (Omicron) RBD, as well neutralizing activity. We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. Taken together, 11D7 is a unique mAb that neutralizes SARS‐CoV‐2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety‐friendly alternative platform for generating mAbs to address the evolving SARS‐CoV‐2 crisis. [ABSTRACT FROM AUTHOR]

Antibiotics are essential for modern medicine, they are employed frequently in hospitals and, therefore, present in hospital wastewater. Even in concentrations, that are lower than the minimum inhibitory concentrations (MICs) of susceptible bacteria, antibiotics may exert an influence and select resistant bacteria, if they exceed the MSCs (minimal selective concentrations) of resistant strains. Here, we compare the MSCs of fluorescently labelled Acinetobacter baylyi strains harboring spontaneous resistance mutations or a resistance plasmid with antibiotic concentrations determined in hospital wastewater. Low MSCs in the μg/L range were measured for the quinolone ciprofloxacin (17 μg/L) and for the carbapenem meropenem (30 μg/L). A 24 h continuous analysis of hospital wastewater showed daily fluctuations of the concentrations of these antibiotics with distinctive peaks at 7–8 p.m. and 5–6 a.m. The meropenem concentrations were always above the MSC and MIC values of A. baylyi. In addition, the ciprofloxacin concentrations were in the range of the lowest MSC for about half the time. These results explain the abundance of strains with meropenem and ciprofloxacin resistance in hospital wastewater and drains. [ABSTRACT FROM AUTHOR]

We previously demonstrated that natural product‐inspired 3,4‐dihydropyrrolo[1,2‐a]pyrazin‐1(2H)‐ones derivatives delivered potent and selective PIM kinases inhibitors however with non‐optimal ADME/PK properties and modest oral bioavailability. Herein, we describe a structure‐based scaffold decoration and a stereoselective approach to this chemical class. The synthesis, structure–activity relationship studies, chiral analysis, and pharmacokinetic data of compounds from this inhibitor class are presented herein. Compound 20c demonstrated excellent potency on PIM1 and PIM2 with exquisite kinases selectivity and PK properties that efficiently and dose‐dependently promoted c‐Myc degradation and appear to be promising lead compounds for further development. [ABSTRACT FROM AUTHOR]

This article draws on ethnographic research to conceptualise how nurses mobilise assemblages of caring to organise and deliver COVID care; particularly so by reorganising organisational infrastructures and practices of safe and good care. Based on participatory observations, interviews and nurse diaries, all collected during the early phase of the pandemic, the research shows how the organising work of nurses unfolds at different health‐care layers: in the daily care for patients and their families, in the coordination of care in and between hospitals, and at the level of the health‐care system. These findings contrast with the dominant pandemic‐image of nurses as 'heroes at the bedside', which fosters the classic and microlevel view of nursing and leaves the broader contribution of nurses to the pandemic unaddressed. Theoretically, the study adds to the literature on translational mobilisation and assemblage theory by focussing on the layered and often invisible organising work of nurses in health care. [ABSTRACT FROM AUTHOR]

We give a generalization of the notion of finite Blaschke products from the perspective of generalized inner functions in various reproducing kernel Hilbert spaces. Further, we study precisely how these functions relate to the so‐called Shapiro–Shields functions and shift‐invariant subspaces generated by polynomials. Applying our results, we show that the only entire inner functions on weighted Hardy spaces over the unit disk are multiples of monomials, extending recent work of Cobos and Seco. [ABSTRACT FROM AUTHOR]

Summary: Bacteriophages are highly selective in targeting bacteria. This selectivity relies on the specific adsorption of phages to the host cell surface. In this study, a Tn5 transposon mutant library of Erwinia amylovora, the causative agent of fire blight, was screened to identify bacterial receptors required for infection by the podovirus S6. Phage S6 was unable to infect mutants with defects in the bacterial cellulose synthase operon (bcs). The Bcs complex produces and secretes bacterial cellulose, an extracellular polysaccharide associated with bacterial biofilms. Deletion of the bcs operon or associated genes (bcsA, bcsC and bcsZ) verified the crucial role of bacterial cellulose for S6 infection. Application of the cellulose binding dye Congo Red blocked infection by S6. We demonstrate that infective S6 virions degraded cellulose and that Gp95, a phage‐encoded cellulase, is involved to catalyse the reaction. In planta S6 did not significantly inhibit fire blight symptom development. Moreover, deletion of bcs genes in E. amylovora did not affect bacterial virulence in blossom infections, indicating that sole application of cellulose targeting phages is less appropriate to biologically control E. amylovora. The interplay between cellulose synthesis, host cell infection and maintenance of the host cell population is discussed. [ABSTRACT FROM AUTHOR]

Background: Stigma is a formidable burden for survivors of lung cancer that can reduce the quality of life (QOL), resulting in physical, social and psychological challenges. This study investigates associations between stigma and depression, QOL and demographic and health‐related characteristics, including race. Design: An adapted conceptual model derived from the Cataldo Lung Cancer Stigma Scale guided this descriptive correlation study assessing stigma in African American and Caucasian survivors of lung cancer. Self‐reported, written surveys measuring depression, QOL, lung cancer stigma and demographics were administered. Statistical analysis was conducted to assess associations between stigma and depression, stigma and QOL and stigma and race, while adjusting for demographic characteristics. Results: Participants (N = 56) included 30 Caucasian and 26 African American survivors of lung cancer recruited from a cancer registry of an American College of Surgeons‐accredited programme, a survivors' support club and an ambulatory oncology practice in the southeastern United States. Statistical analysis yielded (1) a significant moderate positive association between depression and lung cancer stigma; (2) a significant moderate negative association between QOL and lung cancer stigma; and (3) significant relationships between race and lung cancer stigma, specifically higher degree of stigma among African Americans compared to Caucasians. Conclusion: Stigma affects many aspects of survivors' lives. Healthcare professionals need to consider how health‐related stigma may further complicate the physical burdens, psychological distresses and social challenges that accompany the disease, especially among African American survivors. Additional enquiry and interventions are needed to assist with mitigating the negative effects of stigma on survivors and their family members and friends. Patient or Public Contribution: Fifty‐six survivors of lung cancer participated in this descriptivecorrelation study. They completed written surveys measuring depression, QOL, and lung cancer stigma, plus an investigator‐developed demographic information form. [ABSTRACT FROM AUTHOR]

Conductive polymer devices with tunable resistance allow low‐energy, linear programming for efficient neuromorphic computing. Depolarizing impurities, however, are difficult to exclude and limit device performance through nonideal writes and self‐discharge. It is shown that these phenomena can be numerically described by combining two‐phase charge transport models with electrochemical self‐discharge. The simulations accurately reproduce the experimental data, including cyclic voltammetry and standard neuromorphic functions, such as linear programming of discrete states and short‐term potentiation. Impurities affect device write accuracy significantly for long programming times above 1000 ms. The effect is reduced to 0.03% for shorter times. Self‐discharge is impacted by device potential as well as impurity concentration. A model‐based trade‐off between operating parameters nearly triples the number of usable conductance states at ambient conditions. Understanding these device limitations as well as workarounds is a vital step toward the implementation of neuromorphic device networks. [ABSTRACT FROM AUTHOR]

The growing demand for precise and reliable biomarkers in psychiatry is fueling research interest in the hope that identifying quantifiable indicators will improve diagnoses and treatment planning across a range of mental health conditions. The individual properties of brain networks at rest have been highlighted as a possible source for such biomarkers, with the added advantage that they are relatively straightforward to obtain. However, an important prerequisite for their consideration is their reproducibility. While the reliability of resting‐state (RS) measurements has often been studied at standard field strengths, they have rarely been investigated using ultrahigh‐field (UHF) magnetic resonance imaging (MRI) systems. We investigated the intersession stability of four functional MRI RS parameters—amplitude of low‐frequency fluctuations (ALFF) and fractional ALFF (fALFF; representing the spontaneous brain activity), regional homogeneity (ReHo; measure of local connectivity), and degree centrality (DC; measure of long‐range connectivity)—in three RS networks, previously shown to play an important role in several psychiatric diseases—the default mode network (DMN), the central executive network (CEN), and the salience network (SN). Our investigation at individual subject space revealed a strong stability for ALFF, ReHo, and DC in all three networks, and a moderate level of stability in fALFF. Furthermore, the internetwork connectivity between each network pair was strongly stable between CEN/SN and moderately stable between DMN/SN and DMN/SN. The high degree of reliability and reproducibility in capturing the properties of the three major RS networks by means of UHF‐MRI points to its applicability as a potentially useful tool in the search for disease‐relevant biomarkers. [ABSTRACT FROM AUTHOR]

Due to its biocompatibility, electrical conductivity, and tissue‐like elasticity, poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) constitutes a highly promising material regarding the fabrication of smart cell culture substrates. However, until now, high‐throughput synthesis of pure PEDOT:PSS geometries was restricted to flat sheets and fibers. In this publication, the first microfluidic process for the synthesis of spherical, highly porous, pure PEDOT:PSS particles of adjustable material properties is presented. The particles are synthesized by the generation of PEDOT:PSS emulsion droplets within a 1‐octanol continuous phase and their subsequent coagulation and partial crystallization in an isopropanol (IPA)/sulfuric acid (SA) bath. The process allows to tailor central particle characteristics such as crystallinity, particle diameter, pore size as well as electrochemical and mechanical properties by simply adjusting the IPA:SA ratio during droplet coagulation. To demonstrate the applicability of PEDOT:PSS particles as potential cell culture substrate, cultivations of L929 mouse fibroblast cells and MRC‐5 human fibroblast cells are conducted. Both cell lines present exponential growth on PEDOT:PSS particles and reach confluency with cell viabilities above 95 vol.% on culture day 9. Single cell analysis could moreover reveal that mechanotransduction and cell infiltration can be controlled by the adjustment of particle crystallinity. [ABSTRACT FROM AUTHOR]

Large‐scale atmospheric circulation patterns, such as the East Asian monsoon, have been proposed as possible feedbacks of the mid‐Pleistocene transition (MPT). Marine sediments of the Japan Sea (JS) record variations in the East Asian monsoon over long timescales and may be crucial for understanding of the MPT. To interpret these sediments correctly an understanding of the JS palaeoceanography is necessary. So far, the JS palaeoceanography has been extrapolated across the MPT from studies of the most recent glacial‐interglacial cycles. These suggest a good connection and unrestricted water‐mass exchange with the open ocean during interglacial sea‐level highstands, while during glacial sea‐level lowstands the JS is nearly isolated. Glacial isolation often results in poor carbonate preservation and unusually low oxygen isotope (δ18O) ratios from low‐saline/low‐δ18O waters accumulating in the basin. Using the sediments of Integrated Ocean Drilling Program (IODP) Site U1427, a shallow‐water site in the southern JS, we present a continuous foraminiferal δ18O record encompassing the MPT. This record shows the JS‐typical low glacial δ18O values in the late phase of the MPT, across Marine Isotope Stages (MIS) 24‐17, while earlier MPT glacials, across MIS 39‐25, are characterized by high δ18O values. We propose that high glacial δ18O values are the result of an improved connection between the shallow, southern JS and adjacent ocean during early MPT glacials. The impact of this palaeoceanographic mode, if continued to deep‐water sites, would make the interpretation of dark/light sediment layers as glacial/interglacial deposits uncertain. Key Points: A high‐resolution, continuous benthic foraminiferal oxygen isotope record is presented using sediments of IODP Site U1427 (Exp. 346)MIS 24‐17 are characterized by the glacial near isolation of the Japan Sea, while for stages 39‐25 an improved connection is suggestedPresenting a new core‐top Mg/Ca‐temperature calibration for Uvigerina spp. from the Japan Sea and revised age model for IODP Site U1427 [ABSTRACT FROM AUTHOR]

Objective: Treatment of high‐grade serous ovarian cancer (HGSOC) will benefit from early detection of cancer. Here, we provide proof‐of‐concept data supporting the hypothesis that circulating immune cells, because of their early recognition of tumors and the tumor microenvironment, can be considered for biomarker discovery. Methods: Longitudinal blood samples from C57BL/6 mice bearing syngeneic ovarian tumors and peripheral blood mononuclear cells (PBMC) from healthy postmenopausal women and newly diagnosed for HGSOC patients were subjected to RNASeq. The results from human immune cells were validated using Affymetrix microarrays. Differentially expressed transcripts in immune cells from tumor‐bearing mice and HGSOC patients were compared to matching controls. Results: A total of 1282 transcripts (798 and 484, up‐ and downregulated, respectively) were differentially expressed in the tumor‐bearing mice as compared with controls. Top 100 genes showing longitudinal changes in gene expression 2, 4, 7, and 18 days after tumor implantation were identified. Analysis of the PBMC from healthy post‐menopausal women and HGSOC patients identified 4382 differentially expressed genes and 519 of these were validated through Affymetrix microarray analysis. A total of 384 genes, including IL‐1R2, CH3L1, Infitm1, FP42, CXC42, Hdc, Spib, and Sema6b, were differentially expressed in the human and mouse datasets. Conclusion: The PBMC transcriptome shows longitudinal changes in response to the progressing tumor. Several potential biomarker transcripts were identified in HGSOC patients and mouse models. Monitoring their expression in individual PBMC subsets can serve as additional discriminator for the diagnosis of HGSOC. [ABSTRACT FROM AUTHOR]

This short review focuses on enantiopure planar chiral [2.2]paracyclophanes (pCps), a fascinating class of molecules that possess an unusual three‐dimensional core and intriguing physicochemical properties. In the first part of the review, different synthetic strategies for preparing optically active pCps are described. Although classical resolution methods based on the synthesis and separation of diastereoisomeric products still dominate the field, recent advances involving the kinetic resolution of racemic compounds and the desymmetrization of meso derivatives open up new possibilities to access enantiopure key intermediates on synthetically useful scales. Due to their advantageous properties including high configurational and chemical stability, [2.2]paracyclophanes are increasingly employed in various research fields, ranging from stereoselective synthesis to material sciences. The applications of [2.2]paracyclophanes in asymmetric organocatalysis are described in the second part of the review. While historically enantiopure pCps have been mainly employed by organic chemists as chiral ligands in transition‐metal catalysis, these compounds can also be used as efficient catalysts in metal‐free reactions and may inspire the development of new transformations in the near future. [ABSTRACT FROM AUTHOR]

Background: The impact of socioeconomic status (SES) has been described for screening and accessing treatment for colon cancer. However, little is known about the “downstream” effect in patients who receive guideline-concordant treatment. This study assessed the impact of SES on cancer-specific survival (CSS) and overall survival (OS) for stage III colon cancer patients. Methods: The SEER Census Tract-Level SES Dataset from 2004 to 2015 was used to identify stage III colon adenocarcinoma patients who received curative-intent surgery and adjuvant chemotherapy. The predictor variable was census tract SES. SES was analyzed as quintiles. The outcome variables were OR and CSS. Statistical analysis included chi square tests for association, Kaplan–Meier, Cox, Fine and Gray regression for survival analysis. Results: In total, 27,222 patients met inclusion criteria. Lower SES was associated with younger age, Black or Hispanic race/ethnicity, Medicaid/uninsured, higher T stage, and lower grade tumors. CSS at the 25th percentile was 54 months for the lowest SES quintile and 80 for the highest. Median OS was 113 months for the lowest SES quintile and not reached for highest. The 5-year CSS rate was 72.4% for the lowest SES quintile compared to 78.9% in the highest (p < 0.001). The 5-year OS rate was 66.5% for the lowest SES quintile and 74.6% in the highest (p < 0.001). Conclusion: This is the first study to evaluate CSS and OS in an incidence-based cohort of stage III colon cancer patients using a granular, standardized measure of SES. Despite receipt of guideline-based treatment, SES was associated with disparities in CSS and OS. [ABSTRACT FROM AUTHOR]

Herein, we report a simple and convenient procedure to prepare para‐disubstituted [2.2]paracyclophanes in a straightforward manner. Our approach relies on a regioselective formylation of N‐substituted 4‐amino[2.2]paracyclophanes, which allows an easy access to a series of products incorporating a reactive aldehyde function para to the electron‐donating group. These compounds can be engaged in a variety of orthogonal late‐stage derivatization processes involving either the carbonyl group or the amine function, and can serve as precursors to rapidly access more complex paracyclophane derivatives. Control of planar chirality is also possible by performing a kinetic resolution of key racemic intermediates through asymmetric transfer hydrogenation. The formylation can be run on a synthetically useful scale, thus confirming the practical applicability of our method. [ABSTRACT FROM AUTHOR]

The use of opaque, uninterpretable artificial intelligence systems in health care can be medically beneficial, but it is often viewed as potentially morally problematic on account of this opacity—because the systems are black boxes. Alex John London has recently argued that opacity is not generally problematic, given that many standard therapies are explanatorily opaque and that we can rely on statistical validation of the systems in deciding whether to implement them. But is statistical validation sufficient to justify implementation of these AI systems in health care, or is it merely one of the necessary criteria? I argue that accountability, which holds an important role in preserving the patient‐physician trust that allows the institution of medicine to function, contributes further to an account of AI system justification. Hence, I endorse the vanishing accountability principle: accountability in medicine, in addition to statistical validation, must be preserved. AI systems that introduce problematic gaps in accountability should not be implemented. [ABSTRACT FROM AUTHOR]

The electrochemical synthesis of hydrogen peroxide (H2O2) using the oxygen reduction reaction (ORR) requires highly catalytic active, selective, and stable electrode materials to realize a green and efficient process. The present publication shows for the first time the application of a facile one-step bottom-up wet-spinning approach for the continuous fabrication of stable and flexible tubular poly(3,4-ethylene dioxythiophene) (PEDOT: PSS) and PEDOT: PSS/carbon nanotube (CNT) hollow fibers. Additionally, electrochemical experiments reveal the catalytic activity of acid-treated PEDOT: PSS and its composites in the ORR forming hydrogen peroxide for the first time. Under optimized conditions, the composite electrodes with 40 wt% CNT loading could achieve a high production rate of 0.01 mg/min/cm2 and a current efficiency of up to 54%. In addition to the high production rate, the composite hollow fiber has proven its long-term stability with 95% current retention after 20 h of hydrogen peroxide production. [ABSTRACT FROM AUTHOR]

Purpose: To propose two innovations to existing eddy current characterization techniques, which include (1) an efficient spatio‐temporal sampling scheme and (2) a model‐based fitting of spherical harmonic eddy current components. Theory and Methods: This work introduces a three‐plane 2D image‐based acquisition scheme to efficiently sample eddy current fields. Additionally, a model‐based spherical harmonic decomposition is presented, which reduces fitting noise using a rank minimization to impose an exponential decay on the eddy current amplitude evolution. Both techniques are applied in combination and analyzed in simulations for their applicability in reconstructing suitable pre‐emphasis parameters. In a proof‐of‐concept measurement, the routine is tested for its propriety to correctly quantify user‐defined field dynamics. Furthermore, based on acquired precompensation and postcompensation eddy current data, the suitability of pre‐emphasis parameters calculated based on the proposed technique is evaluated. Results: Simulation results derived from 500 data sets demonstrate the applicability of the acquisition scheme for the spatio‐temporal sampling of eddy current fields. Compared with a conventional data processing strategy, the proposed model‐based approach yields pre‐emphasis parameters that reduce the average maximum residual field offset within a 10‐cm‐diameter spherical volume from 3.17 Hz to 0.58 Hz. Experimental data prove the proposed routine to be suitable to measure and effectively compensate for eddy currents within 10 minutes of acquisition time. Conclusion: The proposed framework was found to be well‐suited to efficiently characterize and compensate for eddy current fields in a one‐time calibration effort. It can be applied to facilitate pre‐emphasis implementations, such as for dynamic B0 shimming applications. [ABSTRACT FROM AUTHOR]

Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? Recently, a shorter duration of adjuvant therapy in colon cancer has been studied within the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration, with the primary aim of reducing morbidity while not sacrificing oncologic outcome.21 On the basis of favorable results demonstrating the noninferiority of 3 months of capecitabine plus oxaliplatin in patients with T3N1 colon cancer, it is plausible that rectal cancer chemotherapy treatment duration may be affected in the coming years. Historically, most patients received an empirical treatment strategy, with little role for tumor response assessment after neoadjuvant therapy. PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery. [Extracted from the article]

Hydraulic structures are critical for water management. Yet many structures continue to be neglected, in poor condition, and inadequate in adapting to evolving societal challenges associated with shifting climatic events and population growth. In this context, hydraulic structures engineering should be moving from traditional design considerations toward sustainability, that is, continuing to meet current and future social, environmental, and economic needs. This requires this community to embrace and help advance global and multidisciplinary perspectives. Therefore, this article presents the authors' point of view on current trends, concerns, and needs related to hydraulic structures engineering. Furthermore, the authors propose a new, forward‐looking framework for the consideration of the hydraulic structures community that is grounded on the evolution of interconnected research tools and methodologies in addition to emphasizing and bolstering strong links between academia and industry. The evolution of this framework has naturally originated from the pervasive challenge of validating the design and operation of hydraulic structures in the field for frequent and extreme conditions. The authors suggest that future developments of hydraulic structures engineering require (a) continuous updating of complementary tools and methodologies following technological developments, (b) addressing the lack of detailed field observations, (c) increasing interactions of hydraulic specialists with other scientific disciplines and water experts, and (d) restoring a strong collaboration between academia and industry. It is anticipated that in this way the hydraulic structures community, and all of society, will make a new step toward more sustainable and resilient interactions with nature and between communities in water management. This article is categorized under:Engineering Water > Engineering Water [ABSTRACT FROM AUTHOR]