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Background: Inpatient nursing documentation facilitates multi-disciplinary team care and tracking of patient progress. In both high- and low- and middle-income settings, it is largely paper-based and may be used as a template for electronic medical records. However, there is limited evidence on how they have been developed. Objective: To synthesise evidence on how paper-based nursing records have been developed and implemented in inpatient settings to support documentation of nursing care. Design: A scoping review guided by the Arksey and O'Malley framework and reported using PRISMA-ScR guidelines. Eligibility criteria: We included studies that described the process of designing paper-based inpatient records and excluded those focussing on electronic records. Included studies were published in English up to October 2019. Sources of evidence: PubMed, CINAHL, Web of Science and Cochrane supplemented by free-text searches on Google Scholar and snowballing the reference sections of included papers. Results: 12 studies met the eligibility criteria. We extracted data on study characteristics, the development process and outcomes related to documentation of inpatient care. Studies reviewed followed a process of problem identification, literature review, chart (re)design, piloting, implementation and evaluation but varied in their execution of each step. All studies except one reported a positive change in inpatient documentation or the adoption of charts amid various challenges. Conclusions: The approaches used seemed to work for each of the studies but could be strengthened by following a systematic process. Human-centred Design provides a clear process that prioritises the healthcare professional's needs and their context to deliver a usable product. Problems with the chart could be addressed during the design phase rather than during implementation, thereby promoting chart ownership and uptake since users are involved throughout the design. This will translate to better documentation of inpatient care thus facilitating better patient tracking, improved team communication and better patient outcomes. Relevance to clinical practice: Paper-based charts should be designed in a systematic and clear process that considers patient's and healthcare professional's needs contributing to improved uptake of charts and therefore better documentation.

International audience; Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.

Multi-touch technology is increasingly being used to support collaborative learning activities. However, to know how this technology can be used most effectively, we need to understand if collaborative interactions differ when groups are using multi-touch technology compared with other tools. In this paper, we compare the interactions of groups of 10 to 11-year-old students working collaboratively to solve three math problems in either a multi-touch or paper condition. The number of ideas raised, who proposed them and whether they were responded to, were coded to identify differences in idea development and interactions across conditions. Responses by students to ideas proposed by other students were coded. Results indicate that similar numbers of ideas were raised across conditions; student responses to ideas raised by other students were more likely to elaborate on the idea or combine it with other ideas in the multi-touch condition than in the paper condition. These results reinforce prior findings that show higher levels of collaborative engagement around ideas when using multi-touch than paper and extend our understanding of how this occurs.

High-impact review papers describe and synthesize the current state of the art, the open questions and controversies, and provide ideas for future investigations. They are written not only for a specific scientific discipline but also for the broader Earth and space science community. They not only summarize the literature, but they also create a framework from which to understand the progress, problems, and connections between different communities, observations, models, and approaches. Here we describe how to write a high-impact review paper, and why you should consider writing one for Reviews of Geophysics.

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.

COVID-19 mitigating practices such as 'hand-washing', 'social distancing', or 'social isolating' are constructed as 'moral imperatives', required to avert harm to oneself and others. Adherence to COVID-19 mitigating practices is presently high among the general public, and stringent lockdown measures supported by legal and policy intervention have facilitated this. In the coming months, however, as rules are being relaxed and individuals become less strict, and thus, the ambiguity in policy increases, the maintenance of recommended social distancing norms will rely on more informal social interactional processes. We argue that the moralization of these practices, twinned with relaxations of policy, may likely cause interactional tension between those individuals who do vs. those who do not uphold social distancing in the coming months: that is, derogation of those who adhere strictly to COVID-19 mitigating practices and group polarization between 'distancers' and 'non-distancers'. In this paper, we explore how and why these processes might come to pass, their impact on an overall societal response to COVID-19, and the need to factor such processes into decisions regarding how to lift restrictions.

Inefficient packaging constitutes a global problem that costs hundreds of billions of dollars, not to mention the additional environmental impacts. An insufficient level of packaging increases the occurrence of product damage, while an excessive level increases the packages' weight and volume, thereby increasing distribution cost. This problem is well known, and for many years, engineers have tried to optimize packaging to protect products from transport hazards for minimum cost. Road vehicle shocks and vibrations, which is one of the primary causes of damage, need to be accurately simulated to achieve optimized product protection. Over the past 50 years, road vehicle vibration physical simulation has progressed significantly from simple mechanical machines to sophisticated computer-driven shaking tables. There now exists a broad variety of different methods used for transport simulation. Each of them addresses different particularities of the road vehicle vibration. Because of the nature of the road and vehicles, different sources and processes are present in the vibration affecting freight. Those processes can be simplified as the vibration generated by the general road surface unevenness, road surface aberrations (cracks, bumps, potholes, etc.) and the vehicle drivetrain system (wheels, drivetrain, engine, etc.). A review of the transport vibration simulation methods is required to identify and critically evaluate the recent developments. This review begins with an overview of the standardized methods followed by the more advanced developments that focus on the different random processes of vehicle vibration by simulating non-Gaussian, non-stationary, transient and harmonic signals. As no ideal method exists yet, the review presented in this paper is a guide for further research and development on the topic.

The history of slavery in Britain and the British empire has placed the legislative milestones of anti-slavery - the abolition of the slave trade in 1807 and the abolition of slavery in 1833 - at the centre of historical inquiry. This essay considers why the passing of anti-slavery laws, rather than the implementation of anti-slavery reforms, has been so pivotal in the historiography. It asks what the history of slavery in Britain and the British empire would look like if turned toward the continuities between slavery and freedom, rather than emphasizing the bright line of emancipation. It places British approaches to the history of slavery into a wider historiographical context, and considers how renewed emphasis on the physical experience and everyday routines of slavery and anti-slavery and a rigorous rethinking of the archives might shape the future of the field.

In this study, we aim to compare the performance of systems and forensic facial comparison experts in terms of likelihood ratio computation to assess the potential of the machine to support the human expert in the courtroom. In forensics, transparency in the methods is essential. Consequently, state‐of‐the‐art free software was preferred over commercial software. Three different open‐source automated systems chosen for their availability and clarity were as follows: OpenFace, SeetaFace, and FaceNet; all three based on convolutional neural networks that return a distance (OpenFace, FaceNet) or similarity (SeetaFace). The returned distance or similarity is converted to a likelihood ratio using three different distribution fits: parametric fit Weibull distribution, nonparametric fit kernel density estimation, and isotonic regression with pool adjacent violators algorithm. The results show that with low‐quality frontal images, automated systems have better performance to detect nonmatches than investigators: 100% of precision and specificity in confusion matrix against 89% and 86% obtained by investigators, but with good quality images forensic experts have better results. The rank correlation between investigators and software is around 80%. We conclude that the software can assist in reporting officers as it can do faster and more reliable comparisons with full‐frontal images, which can help the forensic expert in casework.

Assessing anatomy in a way that tests higher cognitive domains and clinical application is not always straightforward. The old "spotter" examination has been criticized for only testing low level "identify" knowledge, whereas other assessment modalities such as multiple choice questions do not reflect the three dimensional and application nature of clinical anatomy. Medical curricula are frequently integrated and subject specific examinations do not reflect the case based, spiral, integrative nature of the curricula. The integrated anatomy practical paper (IAPP) is a hybrid of the old "spotter" and an objective structured clinical examination but it demonstrates how higher levels of taxonomy can be assessed, together with clinical features and integrates well with other disciplines. Importantly, the IAPP has shown to be reliable and practical to administer. Data gathered from the Bachelor of Medicine five-year program over two academic years for four IAPP examinations, each being 40 minutes with (K = 60 items) based on 440 students revealed consistently strong reliability coefficients (Cronbach alpha) of up to 0.923. Applying Blooms taxonomy to questions has shown a marked shift resulting in an increase in the complexity level being tested; between 2009 and 2013 a reduction of 26% in the number of low level "remember knowledge" domain questions was noted with up to an increase of 15% in "understanding" domain and 12% increase in the "applying" knowledge domain. Our findings highlight that it is possible to test, based in a laboratory, anatomy knowledge and application that is integrated and fit for practice. Anat Sci Educ. © 2014 American Association of Anatomists.

Summary Polyploidization is pervasive in plants, but little is known about the niche divergence of wild allopolyploids (species that harbor polyploid genomes originating from different diploid species) relative to their diploid progenitor species and the gene expression patterns that may underlie such ecological divergence. We conducted a fine‐scale empirical study on habitat and gene expression of an allopolyploid and its diploid progenitors.We quantified soil properties and light availability of habitats of an allotetraploid Cardamine flexuosa and its diploid progenitors Cardamine amara and Cardamine hirsuta in two seasons. We analyzed expression patterns of genes and homeologs (homeologous gene copies in allopolyploids) using RNA sequencing.We detected niche divergence between the allopolyploid and its diploid progenitors along water availability gradient at a fine scale: the diploids in opposite extremes and the allopolyploid in a broader range between diploids, with limited overlap with diploids at both ends. Most of the genes whose homeolog expression ratio changed among habitats in C. flexuosa varied spatially and temporally.These findings provide empirical evidence for niche divergence between an allopolyploid and its diploid progenitor species at a fine scale and suggest that divergent expression patterns of homeologs in an allopolyploid may underlie its persistence in diverse habitats.

In 1963, Peter Medawar gave a talk, Is the scientific paper a fraud?, in which he argued that scientific journal articles give a false impression of the real process of scientific discovery. In answering his question, he argued that, “The scientific paper in its orthodox form does embody a totally mistaken conception, even a travesty, of the nature of scientific thought.” His main concern was that the highly formalized structure gives only a sanitized version of how scientists come to a conclusion and that it leaves no room for authors to discuss the thought processes that led to the experiments. Medawar explained that papers were presented to appear as if the scientists had no pre-conceived expectations about the outcome and that they followed an inductive process in a logical fashion. In fact, scientists do have expectations and their observations and analysis are made in light of those expectations. Although today’s scientific papers are increasingly presented as being hypothesis-driven, the underlying thought processes remain hidden; scientists appear to follow a logical and deductive process to test their idea and the results of these tests lead them to support or reject the hypothesis. However, even the trend toward more explicit framing of a hypothesis is often misleading, as hypotheses may be framed to explain a set of observations post hoc, suggesting a linear process that does not describe the actual discovery.

A universal anti-Xa assay for the determination of rivaroxaban, apixaban and edoxaban drug concentrations would simplify laboratory procedures and facilitate widespread implementation. Following two pilot studies analysing spiked samples and material from 698 patients, we conducted a prospective multicentre cross-sectional study, including 867 patients treated with rivaroxaban, apixaban or edoxaban in clinical practice to comprehensively evaluate a simple, readily available anti-Xa assay that would accurately measure drug concentrations and correctly predict relevant levels in clinical practice. Anti-Xa activity was measured by an assay calibrated with low-molecular-weight heparin (LMWH) in addition to ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). As an external validation, LMWH-calibrated anti-Xa activity was also determined in nine external laboratories. The LMWH-calibrated anti-Xa activity correlated strongly with rivaroxaban, apixaban or edoxaban drug levels [r s = 0·98, 95% confidence interval (CI) 0·98-0·98]. The sensitivity for the clinically relevant cut-off levels of 30, 50 and 100 µg/l was 96·2% (95% CI 94·4-97·4), 96·4% (95% CI 94·4-97·7) and 96·7% (95% CI 94·3-98·1) respectively. Concordant results were obtained in the external validation study. In conclusion, a universal, LMWH-calibrated anti-Xa assay accurately measured rivaroxaban, apixaban and edoxaban concentrations and correctly predicted relevant drug concentrations in clinical practice.

BACKGROUND: Dietitians play an important role in the intervention and prevention of being overweight and obesity. More and more blended care interventions are being implemented. The present study aimed to evaluate the delivery by Dutch dietitians of a multicomponent, evidence-based weight-loss programme (SMARTsize), including counselling for relapse prevention. The aim of this qualitative study was to identify facilitators and barriers to the delivery of SMARTsize.METHODS: Nine semi-structured interviews were conducted with 10 dietitians who participated in a larger implementation study. Each interview was recorded and transcribed verbatim. Determinants of theory of implementation, including characteristics of the user, the innovation, organisational context and setting, and innovation strategy guided interviews and analysis. Data were coded and analysed using the framework approach.RESULTS: According to dietitians, the SMARTsize intervention had a positive influence on patients. The main implementation facilitators were the availability of implementation materials, such as a manual, training in relapse prevention and social support from other dietitians. The main barriers to implementation were organisation and financial reimbursement of cooking classes, the belief that patients need more individual counselling in the starting phase, and the unsuitability for people with low levels of health literacy.CONCLUSIONS: Most dietitians considered that implementation of the SMARTsize intervention consisting of e-health, written information and cooking classes and face-to-face counselling is challenging but feasible. Further development of the SMARTsize intervention and implementation tools is needed to lower experienced barriers. It is also recommended that a version of the intervention to be developed that is suitable for patients with lower levels of health literacy.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion. Jaarsma, T (corresponding author), Univ Linkoping, Fac Hlth Sci, Kungsgatan 40, S-60174 Norrkoping, Sweden. tiny.jaarsma@liu.se

Journal of synchrotron radiation 28(1), - (2021). doi:10.1107/S1600577520015052, This paper reports on nonlinear spectral broadening of 1.1 ps pulses in a gas-filled multi-pass cell to generate sub-100 fs optical pulses at 1030 nm and 515 nm at pulse energies of 0.8 mJ and 225 µJ, respectively, for pump–probe experiments at the free-electron laser FLASH. Combining a 100 kHz Yb:YAG laser with 180 W in-burst average power and a post-compression platform enables reaching simultaneously high average powers and short pulse durations for high-repetition-rate FEL pump–probe experiments., Published by Wiley-Blackwell, [S.l.]

The selective recognition of tyrosine residues in peptides is an appealing approach to inhibiting their tyrosine kinase (TK)‐mediated phosphorylation. Herein, we describe pseudopeptidic cages that efficiently protect substrates from the action of the Src TK enzyme, precluding the corresponding Tyr phosphorylation. Fluorescence emission titrations show that the most efficient cage inhibitors strongly bind the peptide substrates with a very good correlation between the binding constant and the inhibitory potency. Structural insights and additional control experiments further support the proposed mechanism of selective supramolecular protection of the substrates. Moreover, the approach also works in a completely different kinase‐substrate system. These results illustrate the potential of supramolecular complexes for the efficient and selective modulation of TK signaling., How to spare Tyr: The selective recognition of tyrosine residues by pseudopeptidic cages protects the substrates from Src kinase‐promoted phosphorylation. The Tyr kinase‐inhibiting activity of the cages can be satisfactorily explained by the formation of host‐guest complexes. This supramolecular approach represents an appealing alternative to modulating Tyr kinase activity by substrate recognition.

Journal of synchrotron radiation 28(1), 176 - 180 (2021). doi:10.1107/S1600577520015568, Dichroism is one of the most important optical effects in both the visible and the X-ray range. Besides absorption, scattering can also contribute to dichroism. This paper demonstrates that, based on the example of polyimide, materials can show tiny dichroism even far from electronic resonances due to scattering. Although the effect is small, it can lead to a measurable polarization change and might have influence on highly sensitive polarimetric experiments., Published by Wiley-Blackwell, [S.l.]

HIV‐1 entry requires the redistribution of envelope glycoproteins (Env) into a cluster and the presence of cholesterol (chol) in the viral membrane. However, the molecular mechanisms underlying the specific role of chol in infectivity and the driving force behind Env clustering remain unknown. Here, gp41 is demonstrated to directly interact with chol in the viral membrane via residues 751–854 in the cytoplasmic tail (CT751–854). Super‐resolution stimulated emission depletion (STED) nanoscopy analysis of Env distribution further demonstrates that both truncation of gp41 CT751–854 and depletion of chol leads to dispersion of Env clusters in the viral membrane and inhibition of virus entry. This work reveals a direct interaction of gp41 CT with chol and indicates that this interaction is an important orchestrator of Env clustering., The authors are grateful to Barbara Müller, N. Landau, and Tom Hope for providing the plasmids pCHIV and pCAGGS NL4‐3 Env, pMM310, and peGFP‐Vpr, respectively. Proteomic analysis was performed by the SGIKER service of the University of the Basque Country. The authors would like to thank Advanced Light Microscopy Unit at the Centre for Genomic Regulation (CRG), Barcelona, Spain for the access to Leica STED microscope. The following reagents were obtained through the NIH AIDS Reagent Program (Division of NIAID, NIH): Anti‐HIV‐1 gp41 Hybridome (Chessie 8) (Cat# 526) from Dr. George Lewis; Antiviral bicyclam JM‐2987 (hydrobromide salt of AMD‐3100) from NIAID, DAIDS (cat# 8128). This project was supported by the Basque Government (grant number IT1264‐19 to M.L. and F.‐X.C.) and the Spanish Ministry of Science, Innovation, and Universities (BFU‐2015‐68981‐P). This work was supported in part by the Fundación Biofísica Bizkaia and the Basque Excellence Research Centre (BERC) program of the Basque Government. J.A.N.‐G. was supported by a FI predoctoral fellowship from the Basque Government and currently by Fundación Biofísica Bizkaia. A.A. was supported by Fundación Biofísica Bizkaia. S.O. was supported by an IKASIKER fellowship from the Basque Government. J.C. was supported by European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No. 793830. H.G.‐K. was supported by a grant from the Deutsche Forschungsgemeischaft within TRR86.

BACKGROUND: The occurrence of pharmaceutical compounds in wastewater has become a major concern for human health and the environment. Therefore, it is an important challenge to improve conventional wastewater treatment to remove these compounds. Coupling biological treatment with advanced oxidation technology has been widely studied in the literature, but only sequential associations of the two processes have been used. This study proposes an innovative concept based on a real integration of the photocatalytic oxidation process in a continuous recycling loop on a membrane bioreactor. The role of the oxidation here is not to completely degrade pharmaceuticals, but instead to oxidize them moderately to increase their biodegradability so that they can be eliminated by the biological process. RESULTS: Preliminary experiments on the oxidation process indicated that a flux density of 5 W m−2 was sufficient to increase biodegradability and decrease the toxicity of a cocktail of three pharmaceuticals. Then the performance of a 20-L continuous membrane bioreactor treating wastewater with seven pharmaceuticals, without and with pre-oxidation at 5 W m−2, were compared. Pre-oxidation increased the global removal for some recalcitrant pharmaceuticals (from 3% to 47% for diclofenac and from 1% to 44% for furosemide) without affecting either the removal of carbon, nitrogen or phosphorous by activated sludge, or of already highly removed pharmaceuticals. CONCLUSION: This work proves the feasibility of an innovative concept of a continuous hybrid process coupling a photocatalytic oxidation process and a membrane bioreactor for the treatment of pharmaceuticals in wastewater, with low cost and size. © 2020 Society of Chemical Industry (SCI)., This work was supported by the Program ‘SUDOE’ on the project Innovec'EAU 2016-2019 under award number SUDOE SOE1/P1/F0173. We thank R. Garcia and J. J. Huc for their help in designing and building the demonstrator, and Victor Pueyo for doing the analysis.

In this research, we examine polarization as a form of rapid social change resulting from the interplay between small group processes and perceptions of society at large. Specifically, we investigate how a negative (or hostile) norm regarding minoritiesy groups at the societal level can fuel polarization between majority subgroups at the local level. By employing a novel analytic approach that uses variances to capture polarization processes, we were able to study non-linear societal change. In three studies among high school and university students (N = 347), we manipulated the societal norm about a minority outgroup category (positive vs. negative). Subsequently, participants read about a minority member’s ambiguous behavior and evaluated this target. All studies used a similar paradigm, but they varied in whether or not the ambiguous behavior was discussed within local groups. Results showed that the societal norm only affected perceptions of the minority member’s behavior when people discussed this behavior in a local group, but not when they reflected on it individually. Specifically, group discussions led to between-group polarization between local groups within a broader social category, but only in the context of a negative societal norm. It appeared that the negative climate of the societal debate increased polarization between local groups, which was influenced by the a priori perception of the local group norm. Results are discussed in terms of the integration of societal level and group level processes when studying the development of intergroup attitudes, and practical implications for the coarsening climate of the debate about current societal issues.

We report the working of a novel detector design based on a Bessel Box (BB) electron energy analyser in a scanning electron microscope (SEM). We demonstrate the application of our detector for elemental identification through Auger electron detection in an SEM environment and its potential as a complementary technique to energy dispersive X‐ray (EDX) spectroscopy. We also demonstrate energy‐filtered secondary electron imaging of a copper‐on‐silicon sample using an electron pass energy of 12 eV., Journal of Microscopy, 279 (3), ISSN:0022-2720, ISSN:1365-2818

XFEL radiation based on the stochastic SASE principle can be described by a low-dimensional configuration space. This space of pulse shapes can be sufficiently sampled before an imaging experiment. This approach is used to implement near-field holography of dynamic processes, demonstrated for the example of a micro-fluidic jet illuminated by the divergent wavefront emanating from a compound refractive lens nano-focus. Droplet formation in the break-up regime of the jet, as well as the hydrodynamic phenomena following plasma generation by an intense infrared laser pulse, can be imaged, based on flat-field corrected holograms and subsequent phase retrieval., X-ray free-electron lasers (XFELs) have opened up unprecedented opportunities for time-resolved nano-scale imaging with X-rays. Near-field propagation-based imaging, and in particular near-field holography (NFH) in its high-resolution implementation in cone-beam geometry, can offer full-field views of a specimen’s dynamics captured by single XFEL pulses. To exploit this capability, for example in optical-pump/X-ray-probe imaging schemes, the stochastic nature of the self-amplified spontaneous emission pulses, i.e. the dynamics of the beam itself, presents a major challenge. In this work, a concept is presented to address the fluctuating illumination wavefronts by sampling the configuration space of SASE pulses before an actual recording, followed by a principal component analysis. This scheme is implemented at the MID (Materials Imaging and Dynamics) instrument of the European XFEL and time-resolved NFH is performed using aberration-corrected nano-focusing compound refractive lenses. Specifically, the dynamics of a micro-fluidic water-jet, which is commonly used as sample delivery system at XFELs, is imaged. The jet exhibits rich dynamics of droplet formation in the break-up regime. Moreover, pump–probe imaging is demonstrated using an infrared pulsed laser to induce cavitation and explosion of the jet.

A general description of magnetic dichroism effects in X-ray absorption spectroscopy using a few fundamental spectra extracted from experimental measurements is provided. The accuracy of the procedure is investigated theoretically., A procedure to build the optical conductivity tensor that describes the full magneto-optical response of the system from experimental measurements is presented. Applied to the Fe L 2,3-edge of a 38.85 nm Fe3O4/SrTiO3 (001) thin-film, it is shown that the computed polarization dependence using the conductivity tensor is in excellent agreement with that experimentally measured. Furthermore, the magnetic field angular dependence is discussed using a set of fundamental spectra expanded on spherical harmonics. It is shown that the convergence of this expansion depends on the details of the ground state of the system in question and in particular on the valence-state spin–orbit coupling. While a cubic expansion up to the third order explains the angular-dependent X-ray magnetic linear dichroism of Fe3+ well, higher-order terms are required for Fe2+ when the orbital moment is not quenched.

Journal of synchrotron radiation 28(5), 1518 - 1527 (2021). doi:10.1107/S1600577521007074, Many processes and materials in heterogeneous catalysis undergo dynamic structural changes depending on their chemical environment. Monitoring such dynamic changes can be challenging using conventional spectroscopic characterization tools, due to the high time resolution required. Here, a high-resolution 2D X-ray camera operating at 50 Hz full-frame rate was synchronized with a QEXAFS monochromator, enabling rapid spectro-microscopic imaging with chemical contrast over individual pixels. This was used to monitor chemical gradients within a model Pt/Al2O3 catalyst during catalytic partial oxidation of methane to synthesis gas. The transition from methane combustion (partly oxidized Pt) to combustion-reforming and partial oxidation (fully reduced Pt) was observed by a characteristic reduction front, which progressed from the end of the catalyst bed towards its beginning on the second time scale. The full-field QEXAFS imaging method applied here allows acquisition of entire XANES spectra `on the fly' in a rapid and spatially resolved manner. The combination of high spatial and temporal resolution with spectroscopic data offers new opportunities for observing dynamic processes in catalysts and other functional materials at work. The methodology is flexible and can be applied at beamlines equipped with a QEXAFS or other fast-scanning monochromators and a suitable sample environment for gas phase analytics to allow for catalytic studies at the same time., Published by Wiley-Blackwell, [S.l.]

Journal of applied crystallography 54(6), 1730 - 1737 (2021). doi:10.1107/S1600576721009973, Single-particle x-ray diffractive imaging (SPI) of small (bio-)nanoparticles (NPs) requires optimized injectors to collect sufficient diffraction patterns to reconstruct the NP structure with high resolution. Typically, aerodynamic-lens-stack injectors are used for single NP injection. However, current injectors were developed for larger NPs (100 nm) and their ability to generate high-density NP beams suffers with decreasing NP size. Here, an aerodynamic-lens-stack injector with variable geometry and the geometry-optimization procedure are presented. The optimization for 50 nm gold NP (AuNP) injection using a numerical simulation infrastructure capable of calculating the carrier gas flow and the particle trajectories through the injector is introduced. The simulations are experimentally validated using spherical AuNPs and sucrose NPs. In addition, the optimized injector is compared to the standard-installation ���Uppsala-injector��� for AuNPs and results for these heavy particles show a shift in the particle-beam focus position rather than a change in beam size, which results in a lower gas background for the optimized injector. Optimized aerodynamic-lens stack injectors will allow to increase NP beam density, reduce the gas background, discover the limits of current injectors, and contribute to structure determination of small NPs using SPI., Published by Wiley-Blackwell

Journal of synchrotron radiation 28(1), 3 - 17 (2021). doi:10.1107/S160057752001382X, The emerging concept of `beam by design' in free-electron laser (FEL) accelerator physics aims for accurate manipulation of the electron beam to tailor spectral and temporal properties of the radiation for specific experimental purposes, such as X-ray pump/X-ray probe and multiple wavelength experiments. `Beam by design' requires fast, efficient, and detailed feedback on the spectral and temporal properties of the generated X-ray radiation. Here a simple and cost-efficient method to extract information on the longitudinal Wigner distribution function of emitted FEL pulses is proposed. The method requires only an ensemble of measured FEL spectra and is rather robust with respect to accelerator fluctuations. The method is applied to both the simulated SASE spectra with known radiation properties as well as to the SASE spectra measured at the European XFEL revealing underlying non-linear chirp of the generated radiation. In the Appendices an intuitive understanding of time���frequency representations of chirped SASE radiation is provided., Published by Wiley-Blackwell, [S.l.]

Coordinate‐free expressions for the form factors of arbitrary polygons and polyhedra are derived using the divergence theorem and Stokes's theorem. Apparent singularities, all removable, are discussed in detail. Cancellation near the singularities causes a loss of precision that can be avoided by using series expansions. An important application domain is small‐angle scattering by nanocrystals., Coordinate‐free expressions for the form factors of arbitrary polygons and polyhedra are derived using the divergence theorem and Stokes's theorem. Series expansions are used to ensure numeric precision close to apparent singularities. image

Journal of synchrotron radiation 28(6), 1891 - 1908 (2021). doi:10.1107/S1600577521010511, The small time gaps of synchrotron radiation in conventional multi-bunch mode (100-500 MHz) or laser-based sources with high pulse rate (similar to 80 MHz) are prohibitive for time-of-flight (ToF) based photoelectron spectroscopy. Detectors with time resolution in the 100ps range yield only 20-100 resolved time slices within the small time gap. Here we present two techniques of implementing efficient ToF recording at sources with high repetition rate. A fast electron-optical beam blanking unit with GHz bandwidth, integrated in a photoelectron momentum microscope, allows electron-optical 'pulse-picking' with any desired repetition period. Aberration-free momentum distributions have been recorded at reduced pulse periods of 5 MHz (at MAXII) and 1.25 MHz (at BESSYII). The approach is compared with two alternative solutions: a bandpass pre-filter (here a hemispherical analyzer) or a parasitic four-bunch island-orbit pulse train, coexisting with the multi-bunch pattern on the main orbit. Chopping in the time domain or bandpass pre-selection in the energy domain can both enable efficient ToF spectroscopy and photoelectron momentum microscopy at 100-500 MHz synchrotrons, highly repetitive lasers or cavity-enhanced high-harmonic sources. The high photon flux of a UV-laser (80 MHz, Published by Wiley-Blackwell, [S.l.]

Acta crystallographica / B 77(4), 594 - 604 (2021). doi:10.1107/S2052520621005655, The crystal structure of CrAs was investigated using synchrotron X-ray single-crystal diffraction for separate dependences on temperature (30–400 K) and on pressure (0–9.46 GPa). The isosymmetrical magnetostructural phase transition at T$_N$ = 267 K can induce a change in the microstructure by twinning due to a crossing of the orthohexagonal setting of the unit-cell parameter ratio c/b. Within the crystal structure, one particular Cr–Cr distance exhibits anomalous behavior in that it is nearly unaffected by temperature and pressure in the paramagnetic phase, which is stable above 267 K and at high pressures. The distinction of this shortest Cr–Cr distance might be of importance for the superconducting properties of CrAs., Published by Wiley-Blackwell, Oxford [u.a.]

BACKGROUND AND PURPOSE Reliable prediction of pro-arrhythmic side effects of novel drug candidates is still a major challenge. Although drug-induced pro-arrhythmia occurs primarily in patients with pre-existing repolarisation disturbances, healthy animals are employed for pro-arrhythmia testing. To improve current safety screening, transgenic long QT (LQTS) rabbit models with impaired repolarisation reserve were generated by overexpressing loss-of-function mutations of human HERG (HERG-G628S, loss of IKr ; LQT2), KCNE1 (KCNE1-G52R, decreased IKs ; LQT5), or both transgenes (LQT2-5) in the heart. EXPERIMENTAL APPROACH Effects of K+ channel blockers on cardiac repolarisation and arrhythmia susceptibility were assessed in healthy wild-type (WT) and LQTS rabbits using in vivo ECG and ex vivo monophasic action potential and ECG recordings in Langendorff-perfused hearts. KEY RESULTS LQTS models reflect patients with clinically "silent" (LQT5) or "manifest" (LQT2 and LQT2-5) impairment in cardiac repolarisation reserve: they were more sensitive in detecting IKr -blocking (LQT5) or IK1 /IKs -blocking (LQT2 and LQT2-5) properties of drugs compared to healthy WT animals. Impaired QT-shortening capacity at fast heart rates was observed due to disturbed IKs function in LQT5 and LQT2-5. Importantly, LQTS models exhibited higher incidence, longer duration, and more malignant types of ex vivo arrhythmias than WT. CONCLUSION AND IMPLICATIONS LQTS models represent patients with reduced repolarisation reserve due to different pathomechanisms. As they demonstrate increased sensitivity to different specific ion channel blockers (IKr blockade in LQT5 and IK1 and IKs blockade in LQT2 and LQT2-5), their combined use could provide more reliable and more thorough prediction of (multichannel-based) pro-arrhythmic potential of novel drug candidates.

This study examined (a) psychosocial health care needs of people with type 2 diabetes from the perspective of patients and diabetes healthcare providers in primary care, in terms of topics, attention in diabetes care and preferences and (b) factors associated with a positive attitude towards specialized psychosocial health care.Qualitative focus group study.Using purposive sampling, participants were selected from general practices. In 2012-2013, three focus groups were conducted in people with type 2 diabetes (N = 20) and three with healthcare providers (N = 18).Opinions differed considerably on whether there was a need for psychosocial health care. Topics focused mainly on diabetes-specific issues ranging from a need for additional diabetes education to attention and support in regular diabetes care. However, not all healthcare providers felt competent enough to address psychosocial problems. Some participants reported a need for specialized psychosocial help. A positive attitude towards specialized psychosocial health care appeared to be influenced by care setting (e.g., in the primary care practice or 'outside' mental health care), care accessibility, proactive discussion of psychosocial issues with and referral by healthcare providers and previous experiences with psychosocial health care.Although only few participants expressed a need for specialized psychosocial care, attention for psychosocial well-being in regular diabetes care was generally appreciated.People with type 2 diabetes generally felt psychosocial care could be provided as part of regular diabetes care. Suggestions for healthcare providers to meet psychosocial health care needs include training and discussion tools.目的: 本研究从初级保健中的患者和糖尿病医疗保健提供者的角度,从话题、对糖尿病护理的关注和偏好方面,审查了(a)II型糖尿病患者的心理社会医疗保健需求,以及(b)与对专业心理社会医疗保健的积极态度相关因素。 设计: 定性焦点小组研究。 方法: 通过采用有目的抽样,从 全科医生中选取了参与者。 在2012至2013年间,对II型糖尿病患者(20名)和医疗保健提供者(18名)进行了三次分组座谈会。 结果: 关于是否需要心理社会医疗保健,意见分歧很大。话题主要关注糖尿病特有的问题,从需要额外的糖尿病教育到常规糖尿病护理的关注和支持。然而,并不是所有的医疗保健提供者都觉得能够解决心理社会问题。一些参与者报告说需要专门的心理社会帮助。对专门心理社会医疗保健的积极态度似乎受到保健环境(例如,初级保健实践或‘外部’心理健康护理)、保健可及性、与医疗保健提供者积极讨论心理社会问题和通过他们进行转诊以及以往心理社会医疗保健经验的影响。 结论: 尽管只有少数参与者表示需要专门的心理社会护理,但在常规糖尿病护理中对心理社会健康的关注还是得到了普遍认可。 影响: II型糖尿病患者通常认为心理社会护理可以作为常规糖尿病护理的一部分。医疗保健提供者满足心理社会医疗保健需求的建议包括培训工具和讨论工具。.

Ligand‐based NMR techniques to study protein–ligand interactions are potent tools in drug design. Saturation transfer difference (STD) NMR spectroscopy stands out as one of the most versatile techniques, allowing screening of fragments libraries and providing structural information on binding modes. Recently, it has been shown that a multi‐frequency STD NMR approach, differential epitope mapping (DEEP)‐STD NMR, can provide additional information on the orientation of small ligands within the binding pocket. Here, the approach is extended to a so‐called DEEP‐STD NMR fingerprinting technique to explore the binding subsites of cholera toxin subunit B (CTB). To that aim, the synthesis of a set of new ligands is presented, which have been subject to a thorough study of their interactions with CTB by weak affinity chromatography (WAC) and NMR spectroscopy. Remarkably, the combination of DEEP‐STD NMR fingerprinting and Hamiltonian replica exchange molecular dynamics has proved to be an excellent approach to explore the geometry, flexibility, and ligand occupancy of multi‐subsite binding pockets. In the particular case of CTB, it allowed the existence of a hitherto unknown binding subsite adjacent to the GM1 binding pocket to be revealed, paving the way to the design of novel leads for inhibition of this relevant toxin., Fingerprinting: A powerful protocol by using NMR spectroscopy and molecular dynamics to study multi‐subsite binding pockets has been developed. For cholera toxin subunit B (CTB), the combination of differential epitope mapping saturation transfer difference (DEEP‐STD) NMR, STD competition experiments, transfer‐NOESY, and Hamiltonian replica exchange molecular dynamics (HREMD) unveiled the presence of a novel subsite adjacent to the known subsites of GM1 on CTB.

BACKGROUND AND PURPOSE: 3', 5'-cyclic adenosine monophosphate (cAMP) is a central second messenger that broadly regulates cell function and can underpin pathophysiology. In chronic obstructive pulmonary disease (COPD), a lung disease primarily provoked by cigarette smoke (CS), the induction of cAMP-dependent pathways, via inhibition of hydrolyzing phosphodiesterases (PDEs), is a prime therapeutic strategy. Mechanisms that disrupt cAMP signaling in airway cells, in particular regulation of endogenous PDEs are poorly understood.EXPERIMENTAL APPROACH: We used a novel Förster resonance energy transfer (FRET) based cAMP biosensor in mouse in vivo, ex vivo precision cut lung slices (PCLS), and in human in vitro cell models to track the effects of CS exposure.KEY RESULTS: Under fenoterol stimulated conditions, FRET responses to cilostamide were significantly increased in in vivo, ex vivo PCLS exposed to CS and in human airway smooth muscle cells exposed to CS extract. FRET signals to rolipram were only increased in the in vivo CS model. Under basal conditions, FRET responses to cilostamide and rolipram were significantly increased in in vivo, ex vivo PCLS exposed to CS. Elevated FRET signals to rolipram correlated with a protein upregulation of PDE4 subtypes. In ex vivo PCLS exposed to CS extract, rolipram reversed downregulation of ciliary beating frequency, whereas only cilostamide significantly increased airway relaxation of methacholine pre-contracted airways.CONCLUSION AND IMPLICATIONS: We show that CS upregulates expression and activity of both PDE3 and PDE4, which regulate real-time cAMP dynamics. These mechanisms determine the availability of cAMP and can contribute to CS-induced pulmonary pathophysiology.

Spider mites are destructive arthropod pests on many crops. The generalist herbivorous mite Tetranychus urticae induces defenses in tomato (Solanum lycopersicum) and this constrains its fitness. By contrast, the Solanaceae‐specialist Tetranychus evansi maintains a high reproductive performance by suppressing tomato defenses. Tetranychus evansi outcompetes T. urticae when infesting the same plant, but it is unknown whether this is facilitated by the defenses of the plant.We assessed the extent to which a secondary infestation by a competitor affects local plant defense responses (phytohormones and defense genes), mite gene expression and mite performance.We observed that T. evansi switches to hyper‐suppression of defenses after its tomato host is also invaded by its natural competitor T. urticae. Jasmonate (JA) and salicylate (SA) defenses were suppressed more strongly, albeit only locally at the feeding site of T. evansi, upon introduction of T. urticae to the infested leaflet. The hyper‐suppression of defenses coincided with increased expression of T. evansi genes coding for salivary defense‐suppressing effector proteins and was paralleled by an increased reproductive performance.Together, these observations suggest that T. evansi overcompensates its reproduction through hyper‐suppression of plant defenses in response to nearby competitors. We hypothesize that the competitor‐induced overcompensation promotes competitive population growth of T. evansi on tomato.

Journal of applied crystallography 53(3), 760 - 780 (2020). doi:10.1107/S1600576720005567, A method is presented for the measurement of the phase gradient of a wavefront by tracking the relative motion of speckles in projection holograms as a sample is scanned across the wavefront. By removing the need to obtain an undistorted reference image of the sample, this method is suitable for the metrology of highly divergent wavefields. Such wavefields allow for large magnification factors that, according to current imaging capabilities, will allow for nanoradian angular sensitivity and nanoscale sample projection imaging. Both the reconstruction algorithm and the imaging geometry are nearly identical to that of ptychography, except that the sample is placed downstream of the beam focus and that no coherent propagation is explicitly accounted for. Like other X-ray speckle tracking methods, it is robust to low-coherence X-ray sources, making it suitable for laboratory-based X-ray sources. Likewise, it is robust to errors in the registered sample positions, making it suitable for X-ray free-electron laser facilities, where beam-pointing fluctuations can be problematic for wavefront metrology. A modified form of the speckle tracking approximation is also presented, based on a second-order local expansion of the Fresnel integral. This result extends the validity of the speckle tracking approximation and may be useful for similar approaches in the field., Published by Wiley-Blackwell, [S.l.]

The co‐occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre‐clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time., We describe the co‐occurrence of cancer and heart failure (HF), their potential shared risk factors, and their pathophysiological mechanisms. We advocate intense interaction between cardiologists and oncologists to achieve unifying hypotheses and collaborative pre‐clinical and clinical studies.

Journal of synchrotron radiation 27(3), 625 - 632 (2020). doi:10.1107/S1600577520002192, The unique diagnostic possibilities of X-ray diffraction, small X-ray scattering and phase-contrast imaging techniques applied with high-intensity coherent X-ray synchrotron and X-ray free-electron laser radiation can only be fully realized if a sufficient dynamic range and/or spatial resolution of the detector is available. In this work, it is demonstrated that the use of lithium fluoride (LiF) as a photoluminescence (PL) imaging detector allows measuring of an X-ray diffraction image with a dynamic range of ∼107 within the sub-micrometre spatial resolution. At the PETRA III facility, the diffraction pattern created behind a circular aperture with a diameter of 5 µm irradiated by a beam with a photon energy of 500 eV was recorded on a LiF crystal. In the diffraction pattern, the accumulated dose was varied from 1.7 × 10$^5$ J cm$^{−3}$ in the central maximum to 2 × 10$^{−2}$ J cm$^{−3}$ in the 16th maximum of diffraction fringes. The period of the last fringe was measured with 0.8 µm width. The PL response of the LiF crystal being used as a detector on the irradiation dose of 500 eV photons was evaluated. For the particular model of laser-scanning confocal microscope Carl Zeiss LSM700, used for the readout of the PL signal, the calibration dependencies on the intensity of photopumping (excitation) radiation (λ = 488 nm) and the gain have been obtained., Published by Wiley-Blackwell, [S.l.]

To assess maternal health care service utilisation and associated factors in Somali pastoral communities of eastern Ethiopia.Community-based cross-sectional study complemented by qualitative assessments in Adadle district, Somali region, eastern Ethiopia, among 450 women in six kebeles from August to September 2016. Logistic regression was used to assess factors associated with antenatal care use and skilled delivery care use, controlling for confounders.About 27% [95%CI 22.8-31.2%] of women used antenatal care, and 22.6% [95%CI 18.7-26.5%] received skilled delivery service. None of the respondents reported post-natal care. About 43% reported that they had no knowledge of antenatal care, and 46% did not perceive delivery at a health facility as important. Pastoral lifestyle, husband's educational status, women's attitude towards health care service and financial support from the husband were significantly associated with antenatal care utilisation. Health professionals' attitudes, perceptions of institutional delivery, antenatal care utilisation and information about exemptions from maternal health care fees were associated with skilled delivery service utilisation.Improving community awareness of antenatal care, employing female health professionals and culturally adapted guidelines could improve skilled delivery utilisation. In a patriarchal society, involving male partners in all maternal health issues is essential to increase use of maternal health services and to decrease maternal mortality.Evaluer l'utilisation des services de soins de santé maternelle et les facteurs associés dans les communautés pastorales somaliennes dans l'est de l'Ethiopie. MÉTHODES: Etude transversale basée sur la communauté complétée par des évaluations qualitatives dans le district d'Adadle, région somalienne, dans l'est de l'Ethiopie, portant sur 450 femmes dans six kebeles d'août à septembre 2016. Une régression logistique a été utilisée pour évaluer les facteurs associés à l'utilisation des soins prénatals et à l'accouchement sous soins qualifiés, en ajustant pour les facteurs confusionnels. RÉSULTATS: 27% [IC95%: 22.8-31.2%] des femmes ont utilisé des soins prénatals et 22,6% [IC95%: 18.7-26.5%] ont reçu des services d'accouchement qualifiés. Aucune des répondantes n'a signalé des soins postnatals. 43% ont déclaré qu'elles n'avaient aucune connaissance des soins prénatals et 46% ne percevaient pas l'accouchement dans un établissement de santé comme important. Le mode de vie pastoral, le niveau d'éducation du mari, l'attitude des femmes à l'égard des services de santé et le soutien financier du mari étaient significativement associés à l'utilisation des soins prénatals. Les attitudes des professionnels de la santé, les perceptions de l'accouchement en établissement, l'utilisation des soins prénatals et les informations sur les exemptions des frais de soins de santé maternelle ont été associées à l'utilisation des services d'accouchement qualifiés.Améliorer la sensibilisation de la communauté aux soins prénatals, employer des professionnels de la santé féminins et des directives culturellement adaptées pourrait améliorer l'utilisation de l’accouchement qualifié. Dans une société patriarcale, la participation des partenaires masculins à toutes les questions de santé maternelle est essentielle pour accroître l'utilisation des services de santé maternelle et réduire la mortalité maternelle.

Diabetes and metabolic syndrome are associated with the typical American high glycemia diet and result in accumulation of high levels of advanced glycation end products (AGEs), particularly upon aging. AGEs form when sugars or their metabolites react with proteins. Associated with a myriad of age‐related diseases, AGEs accumulate in many tissues and are cytotoxic. To date, efforts to limit glycation pharmacologically have failed in human trials. Thus, it is crucial to identify systems that remove AGEs, but such research is scanty. Here, we determined if and how AGEs might be cleared by autophagy. Our in vivo mouse and C. elegans models, in which we altered proteolysis or glycative burden, as well as experiments in five types of cells, revealed more than six criteria indicating that p62‐dependent autophagy is a conserved pathway that plays a critical role in the removal of AGEs. Activation of autophagic removal of AGEs requires p62, and blocking this pathway results in accumulation of AGEs and compromised viability. Deficiency of p62 accelerates accumulation of AGEs in soluble and insoluble fractions. p62 itself is subject to glycative inactivation and accumulates as high mass species. Accumulation of p62 in retinal pigment epithelium is reversed by switching to a lower glycemia diet. Since diminution of glycative damage is associated with reduced risk for age‐related diseases, including age‐related macular degeneration, cardiovascular disease, diabetes, Alzheimer's, and Parkinson's, discovery of methods to limit AGEs or enhance p62‐dependent autophagy offers novel potential therapeutic targets to treat AGEs‐related pathologies., AGEs are toxic compounds formed by non‐enzymatic reactions between sugars and proteins. AGEs are prone to aggregate. Insoluble AGEs are efficiently removed via p62‐selective autophagy. The autophagic removal of AGEs is a conserved pathway, and the lack of p62 leads to accumulation of toxic AGEs in mouse and worms. Enhanced autophagy is protective against glycation‐derived damage. p62‐dependent autophagy offers novel potential therapeutic targets to treat AGEs‐related pathologies.

Journal of synchrotron radiation 27(5), 1339 - 1346 (2020). doi:10.1107/S1600577520007407, Hard X-ray nanotomography enables 3D investigations of a wide range of samples with high resolution (, Published by Wiley-Blackwell, [S.l.]

Acta crystallographica / D 75(2), 1-15 (2019). doi:10.1107/S205979831801238X, This article provides a step-by-step guide to the use of the CrystFEL software for processing serial crystallography data from an X-ray free-electron laser or a synchrotron light source. Whereas previous papers have described the theory and algorithms and their rationale, this paper describes the steps to be performed from a user perspective, including command-line examples., Published by Wiley-Blackwell, Oxford

The new phytologist 213(3), 1346-1362 (2017). doi:10.1111/nph.14220, Published by Wiley-Blackwell, Oxford [u.a.]

A comparative study on the self‐assembly of sexiphenyl‐dicarbonitrile on highly oriented pyrolytic graphite and single‐layer graphene on Cu(111) is presented. Despite an overall low molecule–substrate interaction, the close‐packed structures exhibit a peculiar shift repeating every four to five molecules. This shift has hitherto not been reported for similar systems and is hence a unique feature induced by the graphitic substrates.

The new phytologist 221(2), 881-895 (2019). doi:10.1111/nph.15442, Published by Wiley-Blackwell, Oxford [u.a.]

To obtain insights into the dynamics of nutrient exchange in arbuscular mycorrhizal (AM) symbiosis, we modelled mathematically the two‐membrane system at the plant–fungus interface and simulated its dynamics. In computational cell biology experiments, the full range of nutrient transport pathways was tested for their ability to exchange phosphorus (P)/carbon (C)/nitrogen (N) sources. As a result, we obtained a thermodynamically justified, independent and comprehensive model of the dynamics of the nutrient exchange at the plant–fungus contact zone. The predicted optimal transporter network coincides with the transporter set independently confirmed in wet‐laboratory experiments previously, indicating that all essential transporter types have been discovered. The thermodynamic analyses suggest that phosphate is released from the fungus via proton‐coupled phosphate transporters rather than anion channels. Optimal transport pathways, such as cation channels or proton‐coupled symporters, shuttle nutrients together with a positive charge across the membranes. Only in exceptional cases does electroneutral transport via diffusion facilitators appear to be plausible. The thermodynamic models presented here can be generalized and adapted to other forms of mycorrhiza and open the door for future studies combining wet‐laboratory experiments with computational simulations to obtain a deeper understanding of the investigated phenomena.

Fish oil rich in polyunsaturated omega-3 fatty acids is extracted in high yield from anchovy filleting waste using d-limonene as green biosolvent in a simple solid-liquid extraction performed by mechanically stirring and maceration followed by limonene removal via evaporation under reduced pressure. As limonene is renewably obtained from waste orange peel, this method closes the materials cycle and establishes a circular economy process to obtain high quality fish oil from biowaste available worldwide in several million t/year amount. Significant economic, social and environmental benefits are anticipated.

The solution of a structure of human Rab27a suffering from severe anisotropy and translational noncrystallographic symmetry was aided by identifying diffraction measurements with low information content., Data pathologies caused by effects such as diffraction anisotropy and translational noncrystallographic symmetry (tNCS) can dramatically complicate the solution of the crystal structures of macromolecules. Such problems were encountered in determining the structure of a mutant form of Rab27a, a member of the Rab GTPases. Mutant Rab27a constructs that crystallize in the free form were designed for use in the discovery of drugs to reduce primary tumour invasiveness and metastasis. One construct, hRab27aMut, crystallized within 24 h and diffracted to 2.82 Å resolution, with a unit cell possessing room for a large number of protein copies. Initial efforts to solve the structure using molecular replacement by Phaser were not successful. Analysis of the data set revealed that the crystals suffered from both extreme anisotropy and strong tNCS. As a result, large numbers of reflections had estimated standard deviations that were much larger than their measured intensities and their expected intensities, revealing problems with the use of such data at the time in Phaser. By eliminating extremely weak reflections with the largest combined effects of anisotropy and tNCS, these problems could be avoided, allowing a molecular-replacement solution to be found. The lessons that were learned in solving this structure have guided improvements in the numerical analysis used in Phaser, particularly in identifying diffraction measurements that convey very little information content. The calculation of information content could also be applied as an alternative to ellipsoidal truncation. The post-mortem analysis also revealed an oversight in accounting for measurement errors in the fast rotation function. While the crystal of mutant Rab27a is not amenable to drug screening, the structure can guide new modifications to obtain more suitable crystal forms.