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IEEE Transactions on Intelligent Transportation Systems, 23 (10), ISSN:1524-9050, ISSN:1558-0016

Purpose Surgical documentation is an important yet time-consuming necessity in clinical routine. Beside its core function to transmit information about a surgery to other medical professionals, the surgical report has gained even more significance in terms of information extraction for scientific, administrative and judicial application. A possible basis for computer aided reporting is phase detection by convolutional neural networks (CNN). In this article we propose a workflow to generate operative notes based on the output of the TeCNO CNN. Methods Video recordings of 15 cholecystectomies were used for inference. The annotation of TeCNO was compared to that of an expert surgeon (HE) and the algorithm based annotation of a scientist (HA). The CNN output then was used to identify aberrance from standard course as basis for the final report. Moreover, we assessed the phenomenon of ‘phase flickering’ as clusters of incorrectly labeled frames and evaluated its usability. Results The accordance of the HE and CNN was 79.7% and that of HA and CNN 87.0%. ‘Phase flickering’ indicated an aberrant course with AUCs of 0.91 and 0.89 in ROC analysis regarding number and extend of concerned frames. Finally, we created operative notes based on a standard text, deviation alerts, and manual completion by the surgeon. Conclusion Computer-aided documentation is a noteworthy use case for phase recognition in standardized surgery. The analysis of phase flickering in a CNN’s annotation has the potential of retrieving more information about the course of a particular procedure to complement an automated report.

The linear scattering theory of short pulse reflectometry is presented. An expression for the scattering signal is obtained by applying the perturbation theory approach for solving the Helmholtz equation. Based on these analytical results, a method for measuring the radial wavenumber spectrum of the turbulence is suggested. Analytical results are validated against full-wave numerical modelling.

Life‐history studies are often conducted in a laboratory environment where it is easy to assay individual animals. However, factors such as temperature, photoperiod, and nutrition vary greatly between laboratory and field environments, making it difficult to compare results. Consequently, there is a need to study individual life histories in the field, but this is currently difficult in systems such as Daphnia where it is not possible to mark and track individual animals. Here, we present a proof of principle study showing that field cages are a reliable method for collecting individual‐level life‐history data in Daphnia magna. As a first step, we compared the life history of paired animals reared outside and inside cages to test the hypothesis that cages allow free flow of algal food resources. We then used a seminatural mesocosm setting to compare the performance of individual field cages versus glass jars refilled with mesocosm water each day. We found that cages did not inhibit food flow and that differences in life histories between three clones detected in the jar assays were also detectable using the much less labor‐intensive field cages. We conclude that field cages are a feasible approach for collecting individual‐level life‐history data in systems such as Daphnia where individual animals cannot be marked and tracked., There is a need to study individual life histories in the field, but this is currently difficult in systems such as Daphnia where it is not possible to mark and track individual animals. Here, we test the hypothesis that field cages are a useful method for collecting individual‐level life‐history data in Daphnia magna. We provide evidence that our cage design allows the collection of realistic, reliable, and repeatable measurements of life‐history data in the natural setting, as animals inside the cages experience the environment in the same way as those outside.

Introduction Benzodiazepines are recommended as first line sedative agent in ventilated cardiogenic shock patients, although data regarding the optimal sedation strategy are sparse. On our cardiac ICU, midazolam was used as first line sedation until 2016, whereas soybean oil formulated propofol was used preferentially since 2017. Purpose The aim of this study was to investigate the hemodynamic effects of propofol versus midazolam sedation in our cardiogenic shock registry. Methods Mechanically ventilated patients suffering from cardiogenic shock were retrospectively enrolled from a cardiogenic shock registry. 174 patients treated predominantly with propofol were matched by propensity-score to 174 patients treated predominantly with midazolam. Results Catecholamine doses were similar on admission but significantly lower in the propofol group on days 1–4 of ICU stay (Figure 1). Mortality rate was 38% in the propofol and 52% in the midazolam group after 30 days (p=0.002, Figure 2). Rate of ≥BARC3 bleeding was significantly lower in the propofol group compared to the midazolam group (p=0.008). Age, gender, first lactate measured on ICU, first GFR measured on ICU, cardiac arrest, coaxial left ventricular assist device and sedation with midazolam were significantly associated with ICU mortality. Conclusion In this observational cohort study, sedation with propofol in comparison to midazolam was linked to a reduced dose of catecholamines, decreased mortality and bleeding rates for patients with cardiogenic shock. Based on this study and in contrast to current recommendations, propofol should be given consideration for sedation in cardiogenic shock patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft

Reduction in stimulated Brillouin scattering (SBS) from National Ignition Facility Hohlraums has been predicted through the use of multi-ion species materials on Hohlraum walls. This approach to controlling SBS is based upon introducing a lighter ion species to the heavier ion species Hohlraum wall in order to greatly increase the ion Landau damping of ion acoustic waves (IAWs). In a collisionless plasma, if the IAWs driven by SBS reach sufficient amplitudes, this increased damping is reduced or even eliminated by ion trapping in the IAWs. Here, the nonlinear behavior of IAWs is simulated with a multi-ion species Vlasov code, including interspecies ion–ion collisions, self-collisions, and electron–ion pitch-angle collisions. The effect of collisions on the trapping of ions and electrons in a large-amplitude IAW is studied in a regime of relevance to current Inertial Confinement Fusion experiments. Our simulations show that collisions can scatter trapped particles out of resonance with the IAW, suppressing trapping and helping to maintain an effective Landau damping of the IAW. The IAW amplitude required to trap particles in the presence of strong collisions is estimated analytically. These estimates are tested for strongly damped IAWs in tantalum oxide and pure helium plasmas. Our simulations show that, above a threshold amplitude, the damping is reduced by an amount inversely proportional to the wave amplitude. Thus, the success of controlling SBS using a multispecies plasma may depend sensitively on laser power and pulse length.

Esophagobronchial and esophagotracheal fistulas are rare but complex diseases with a heterogeneous spectrum of underlying etiologies. Common causes are locally advanced tumors of the esophagus and larynx, traumatic perforation from the esophageal or tracheal side as well as postoperative fistulas. The management of esophagotracheal and esophagobronchial fistulas always involves different health care providers and in most cases patients require a multidisciplinary treatment on the intensive care unit. The therapeutic concept primarily depends on the underlying cause, localization and size of the fistula but decision making is also influenced by the severity of the course of sepsis and the extent of the respiratory dysfunction. Endoscopic management with esophageal and/or tracheobronchial stenting is the most common treatment. Surgical reconstructive procedures are predominantly reserved for patients with a treatment refractory fistula or a septic multiple organ failure. The prognosis is particularly influenced by the underlying disease.

Isotopic-labeling experiments have been valuable to monitor the flux of metabolic reactions in biological systems, which is crucial to understand homeostatic alterations with disease. Experimental determination of metabolic fluxes can be inferred from a characteristic rearrangement of stable isotope tracers (e.g., 13C or 15N) that can be detected by mass spectrometry (MS). Metabolites measured are generally members of well-known metabolic pathways, and most of them can be detected using both gas chromatography (GC)-MS and liquid chromatography (LC)-MS. In here, we show that GC methods coupled to chemical ionization (CI) MS have a clear advantage over alternative methodologies due to GC's superior chromatography separation efficiency and the fact that CI is a soft ionization technique that yields identifiable protonated molecular ion peaks. We tested diverse GC-CI-MS setups, including methane and isobutane reagent gases, triple quadrupole (QqQ) MS in SIM mode, or selected ion clusters using optimized narrow windows (∼10 Da) in scan mode, and standard full scan methods using high resolution GC-(q)TOF and GC-Orbitrap systems. Isobutane as a reagent gas in combination with both low-resolution (LR) and high-resolution (HR) MS showed the best performance, enabling precise detection of isotopologues in most metabolic intermediates of central carbon metabolism. Finally, with the aim of overcoming manual operations, we developed an R-based tool called isoSCAN that automatically quantifies all isotopologues of intermediate metabolites of glycolysis, TCA cycle, amino acids, pentose phosphate pathway, and urea cycle, from LRMS and HRMS data.

Aberrant innate immune responses to the gut microbiota are causally involved in the pathogenesis of inflammatory bowel diseases (IBD). The exact triggers and main signaling pathways activating innate immune cells and how they modulate adaptive immunity in IBD is still not completely understood. Here, we report that the PI3K/PTEN signaling pathway in dendritic cells enhances IL-6 production in a model of DSS-induced colitis. This results in exacerbated Th1 cell responses and increased mortality in DC-specific PTEN knockout (PTENΔDC) animals. Depletion of the gut microbiota using antibiotics as well as blocking IL-6R signaling rescued mortality in PTENΔDC mice, whereas adoptive transfer of Flt3L-derived PTEN-/- DCs into WT recipients exacerbated DSS-induced colitis and increased mortality. Taken together, we show that the PI3K signaling pathway in dendritic cells contributes to disease pathology by promoting IL-6 mediated Th1 responses.

Background: This project aims to develop a new concept in training pediatric cardiologists to meet the requirements of interventional cardiac catheterizations today in terms of complexity and importance. This newly developed hands-on training program is supposed to enable the acquisition of certain skills which are necessary when investigating and treating patients in a catheter laboratory. Methods: Based on anonymous CT-scans of pediatric patients’ digital 3D heart models with or without cardiac defects were developed and printed three-dimensionally in a flexible material visible under X-ray. Hands-on training courses were offered using models of a healthy heart and the most common congenital heart defects (CHD). An evaluation was performed by quantifying fluoroscopy times (FL-time) and a questionnaire. Results: The acceptance of theoretical and practical contents within the hands-on training was very positive. It was demonstrated that it is possible to master various steps of a diagnostic procedure and an intervention as well as to practice and repeat them independently which significantly reduced FL-time. The participants stated that the hands-on training led to more confidence in interventions on real patients. Conclusion: With the development of a training module using 3D-printed heart models, basic and advanced training in the field of diagnostic cardiac examinations as well as interventional therapies of CHD is possible. The learning effect for both, practical skills and theoretical understanding, was significant which underlines the importance of integrating such hands-on trainings on 3D heart models in education and practical training., Zielsetzung: Ziel dieses Projektes ist die Entwicklung eines neuen Aus- und Weiterbildungskonzepts in der Kinderkardiologie, um der zunehmenden Komplexität und dem Stellenwert interventioneller Eingriffe mittels Herzkatheter (HK) gerecht zu werden. Das neu entwickelte Hands-on Training soll den Erwerb entsprechender Fertigkeiten für die Durchführung der HK-Untersuchung an Patient*innen ermöglichen. Methodik: Basierend auf anonymisierten CT-Bildern von pädiatrischen Patient*innen wurden digitale 3D-Herzmodelle entwickelt und in einem flexiblen, unter Röntgenstrahlung sichtbaren Material dreidimensional ausgedruckt. Es fanden Hands-on Trainingskurse statt, bei denen Modelle eines gesunden Herzens sowie der häufigsten angeborenen Herzfehler (AHF) zum Einsatz kamen. Eine Evaluation erfolgte anhand der Quantifizierung von Durchleuchtungszeiten (DL-Zeit) und eines Fragebogens. Ergebnisse: Die Akzeptanz der theoretischen und praktischen Inhalte des Hands-on Trainings war sehr gut. Es hat sich gezeigt, dass sowohl das Erlernen diverser Schritte als auch selbstständiges Üben und Wiederholen und eine damit verbundene signifikante Verkürzung der benötigten DL-Zeit möglich sind. Die Teilnehmenden gaben an, dass das Hands-on Training zu mehr Sicherheit bei der Intervention an Patient*innen führen würde. Schlussfolgerung: Mit der Entwicklung eines Trainingsmoduls unter dem Einsatz 3D-gedruckter Herzmodelle sind Aus- und Weiterbildung im Bereich diagnostischer HK-Untersuchungen sowie interventioneller Therapien von AHF möglich. Der signifikante Lerneffekt sowohl für die praktischen Fähigkeiten als auch für das theoretische Verständnis spricht für die Integration des Simulationstrainings an 3D-Herzmodellen in Aus- und Weiterbildung.

Background: To determine whether there is a significant saving of time when using a digital cataract workflow for digital data transfer compared to a manual approach of biometry assessment, data export, intraocular lens calculation, and surgery time. Methods: In total, 48 eyes of 24 patients were divided into two groups: 24 eyes were evaluated using a manual approach, whereas another 24 eyes underwent a full digital lens surgery workflow. The primary variables for comparison between both groups were the overall time as well as several time steps starting at optical biometry acquisition until the end of the surgical lens implantation. Other outcomes, such as toric intraocular lens misalignment, reduction of cylinder, surgically induced astigmatism, prediction error, and distance visual acuity were measured. Results: Overall, the total diagnostic and surgical time was reduced from 1364.1 ± 202.6 s in the manual group to 1125.8 ± 183.2 s in the digital group (p < 0.001). The complete time of surgery declined from 756.5 ± 82.3 s to 667.3 ± 56.3 (p < 0.0005). Compared to the manual approach of biometric data export and intraocular lens calculation (76.7 ± 12.3 s) as well as the manual export of the reference image to a portable external storage device (26.8 ± 5.5 s), a highly significant saving of time was achieved (p < 0.0001). Conclusions: Using a software-based digital approach to toric intraocular lens implantation is convenient, more efficient, and thus more economical than a manual workflow in surgery practice.

Adipose tissue macrophages (ATMs) display tremendous heterogeneity depending on signals in their local microenvironment and contribute to the pathogenesis of obesity. The phosphoinositide 3-kinase (PI3K) signalling pathway, antagonized by the phosphatase and tensin homologue (PTEN), is important for metabolic responses to obesity. We hypothesized that fluctuations in macrophage-intrinsic PI3K activity via PTEN could alter the trajectory of metabolic disease by driving distinct ATM populations. Using mice harbouring macrophage-specific PTEN deletion or bone marrow chimeras carrying additional PTEN copies, we demonstrate that sustained PI3K activity in macrophages preserves metabolic health in obesity by preventing lipotoxicity. Myeloid PI3K signalling promotes a beneficial ATM population characterized by lipid uptake, catabolism and high expression of the scavenger macrophage receptor with collagenous structure (MARCO). Dual MARCO and myeloid PTEN deficiencies prevent the generation of lipid-buffering ATMs, reversing the beneficial actions of elevated myeloid PI3K activity in metabolic disease. Thus, macrophage-intrinsic PI3K signalling boosts metabolic health by driving ATM programmes associated with MARCO-dependent lipid uptake. The PI3K–PTEN signalling pathway is a central regulator of metabolic homeostasis. Brunner et al. find that cell-intrinsic PI3K signalling allows adipose tissue macrophages to buffer obesity-induced lipotoxicity by promoting lipid uptake and catabolism.

Two series of isostructural tetravalent actinide amidinates [AnX((S)-PEBA)3] (An = Th, U, Np; X = Cl, N3) bearing the chiral (S,S)-N,N’-bis-(1-phenylethyl)benzamidinate ((S)- PEBA) ligand have been synthesized and thoroughly characterized in solid and in solution. This study expands the already reported tetravalent neptunium complexes to the lighter actinides thorium and uranium. Furthermore, a rare Ce(IV) amidinate [CeCl((S)-PEBA)3] was synthesized to compare its properties to those of the analogous tetravalent actinide complexes. All compounds were characterized in the solid state using single crystal XRD and infrared spectroscopy and in solution using NMR spectroscopy. Quantum chemical bonding analysis including also the isostructural Pa and Pu complexes was used to characterize the covalent contributions to any bond involving the metal cation. Th shows the least covalent character throughout the series, even substantially smaller than for the Ce complex. For U, Np, and Pu similar covalent bonding contributions are found, but a natural population analysis reveals different origins. The 6d participation is the highest for U and decreases afterwards, whereas the 5f participation increases continuously from Pa to Pu.

The tokamak à configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019–20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T e/T i ∼ 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with ‘small’ (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019–20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations.

This paper looks at the historic developments that led to the use of transparent acrylic construction elements from the 1950s onwards. The analysis is based on archive material from the record group Rohm of Evonik Industries AG, the Deutsches Museum (DM), and two key objects: the Opel Olympia (1930s) of the DM and the roof of the Olympic sports facilities (1970s) in Munich. In terms of their construction, usage, and meaning, these objects show the main differences between transparent acrylics before and after 1950. For the Opel, the polymer poly(methyl methacrylate) was thermoformed, showcasing German technological innovations for propaganda purposes. In contrast, the Plexiglas© for the Olympic roof contains several additives, including flame retardant and UV-absorber. It was biaxially stretched and cold formed into aluminium frames. Expressing the democratic ideals of an open society, acrylics presented a progressive, forward looking architecture of seemingly light structures.

It has been suggested that interleukin-6 (IL-6) produced by adipocytes in obesity leads to liver insulin resistance, although this hypothesis has never been definitively tested. Accordingly, we did so by generating adipocyte-specific IL-6-deficient (AdipoIL-6−/−) mice and studying them in the context of diet-induced and genetic obesity. Mice carrying two floxed alleles of IL-6 (C57Bl/6J) were crossed with Cre recombinase-overexpressing mice driven by the adiponectin promoter to generate AdipoIL-6−/− mice. AdipoIL-6−/− and floxed littermate controls were fed a standard chow or high-fat diet (HFD) for 16 wk and comprehensively metabolically phenotyped. In addition to a diet-induced obesity model, we also examined the role of adipocyte-derived IL-6 in a genetic model of obesity and insulin resistance by crossing the AdipoIL-6−/− mice with leptin-deficient ( ob/ob) mice. As expected, mice on HFD and ob/ob mice displayed marked weight gain and increased fat mass compared with chow-fed and ob/+ (littermate control) animals, respectively. However, deletion of IL-6 from adipocytes in either model had no effect on glucose tolerance or fasting hyperinsulinemia. We concluded that adipocyte-specific IL-6 does not contribute to whole body glucose intolerance in obese mice.

Dendritic cells (DCs) induce peripheral T cell tolerance, but cell-intrinsic signaling cascades governing their stable tolerogenesis remain poorly defined. Janus Kinase 1 (JAK1) transduces cytokine-receptor signaling, and JAK inhibitors (Jakinibs), including JAK1-specific filgotinib, break inflammatory cycles in autoimmunity. Here, we report in heterogeneous DC populations of multiple secondary lymphoid organs that JAK1 promotes peripheral T cell tolerance during experimental autoimmune encephalomyelitis (EAE). Mice harboring DC-specific JAK1 deletion exhibit elevated peripheral CD4

Obesity-induced white adipose tissue (WAT) hypertrophy is associated with elevated adipose tissue macrophage (ATM) content. Overexpression of the triggering receptor expressed on myeloid cells 2 (TREM2) reportedly increases adiposity, worsening health. Paradoxically, using insulin resistance, elevated fat mass, and hypercholesterolemia as hallmarks of unhealthy obesity, a recent report demonstrated that ATM-expressed TREM2 promoted health. Here, we identified that in mice, TREM2 deficiency aggravated diet-induced insulin resistance and hepatic steatosis independently of fat and cholesterol levels. Metabolomics linked TREM2 deficiency with elevated obesity-instigated serum ceramides that correlated with impaired insulin sensitivity. Remarkably, while inhibiting ceramide synthesis exerted no influences on TREM2-dependent ATM remodeling, inflammation, or lipid load, it restored insulin tolerance, reversing adipose hypertrophy and secondary hepatic steatosis of TREM2-deficient animals. Bone marrow transplantation experiments revealed unremarkable influences of immune cell–expressed TREM2 on health, instead demonstrating that WAT-intrinsic mechanisms impinging on sphingolipid metabolism dominate in the systemic protective effects of TREM2 on metabolic health.

The tricarboxylic acid (TCA) cycle is a central hub of cellular metabolism, oxidizing nutrients to generate reducing equivalents for energy production and critical metabolites for biosynthetic reactions. Despite the importance of TCA cycle products for cell viability and proliferation, mammalian cells display diversity in TCA cycle activity(1,2). How this diversity is achieved, and whether it is critical for establishing cell fate, remains poorly understood. Here we identify a non-canonical TCA cycle required for changes in cell state. Genetic co-essentiality mapping revealed a cluster of genes sufficient to compose a biochemical alternative to the canonical TCA cycle, wherein mitochondrially-derived citrate exported to the cytoplasm is metabolized via ATP citrate lyase (ACL), ultimately regenerating mitochondrial oxaloacetate to complete this non-canonical TCA cycle. Manipulating expression of ACL or the canonical TCA cycle enzyme aconitase 2 in mouse myoblasts and embryonic stem cells (ESCs) revealed that changes in TCA cycle configuration accompany cell fate transitions. During exit from pluripotency, ESCs switch from canonical to non-canonical TCA cycle metabolism; accordingly, blocking the non-canonical TCA cycle prevents cells from exiting pluripotency. These results establish a context-dependent alternative to the traditional TCA cycle and reveal that appropriate TCA cycle engagement is required for changes in cell state.

Esophagobronchial and esophagotracheal fistulas are rare but complex diseases with a heterogeneous spectrum of underlying etiologies. Common causes are locally advanced tumors of the esophagus and larynx, traumatic perforation from the esophageal or tracheal side as well as postoperative fistulas. The management of esophagotracheal and esophagobronchial fistulas always involves different health care providers and in most cases patients require a multidisciplinary treatment on the intensive care unit. The therapeutic concept primarily depends on the underlying cause, localization and size of the fistula but decision making is also influenced by the severity of the course of sepsis and the extent of the respiratory dysfunction. Endoscopic management with esophageal and/or tracheobronchial stenting is the most common treatment. Surgical reconstructive procedures are predominantly reserved for patients with a treatment refractory fistula or a septic multiple organ failure. The prognosis is particularly influenced by the underlying disease.Ösophagotracheobronchiale (OETB-)Fisteln sind ein insgesamt komplexes Krankheitsbild mit niedriger Inzidenz und einem heterogenen ätiologischen Spektrum. Häufige Ursachen sind lokal fortgeschrittene Malignome des Ösophagus und Larynx, traumatische Perforationen von ösophagealer oder trachealer Seite sowie postoperative Fisteln. Das Management der OETB-Fisteln ist aufgrund der Komplexität immer interdisziplinär und in den meisten Fällen nur unter intensivmedizinischen Bedingungen möglich. Das therapeutische Konzept hängt primär von Ursache, Lokalisation und Größe der Fistel ab, wird aber auch durch die Schwere des septischen Verlaufes, insbesondere durch die respiratorische Insuffizienz, beeinflusst. Interventionelle Verfahren mit Platzierung ösophagealer und/oder tracheobronchialer Stents sind in der Therapie führend; operative rekonstruktive Verfahren bleiben therapierefraktären Fisteln und Patienten mit septischen Multiorganversagen vorbehalten. Die Prognose wird insbesondere durch die Grunderkrankung beeinflusst.

Genotype-by-environment interactions (G x E) underpin the evolution of plastic responses in natural populations. Theory assumes that G x E interactions exist but empirical evidence from natural populations is equivocal and difficult to interpret because G x E interactions are normally univariate plastic responses to a single environmental gradient. We compared multivariate plastic responses of 43Daphnia magnaclones from the same population in a factorial experiment that crossed temperature and food environments. Multivariate plastic responses explained more than 30% of the total phenotypic variation in each environment. G x E interactions were detected in most environment combinations irrespective of the methodology used. However, the nature of G x E interactions was context-dependent and led to environment-specific differences in additive genetic variation (G-matrices). Clones that deviated from the population average plastic response were not the same in each environmental context and there was no difference in whether clones varied in the nature (phenotypic integration) or magnitude of their plastic response in different environments. Plastic responses to food were aligned with additive genetic variation (gmax) at both temperatures, whereas plastic responses to temperature were not aligned with additive genetic variation (gmax) in either food environment. These results suggest that fundamental differences may exist in the potential for our population to evolve novel responses to food versus temperature changes, and challenges past interpretations of thermal adaptation based on univariate studies.

Bone loss is one of the consequences of aging, leading to diseases such as osteoporosis and increased susceptibility to fragility fractures and therefore considerable morbidity and mortality in humans. Here we identify microRNA 146a as an essential epigenetic switch controlling bone loss with age. Mice deficient in miR-146a show regular development of their skeleton. However, while WT mice start to lose bone with age, animals deficient in miR-146a continue to accrue bone throughout their life span. Increased bone mass is due to increased generation and activity of osteoblasts in miR-146a deficient mice as a result of sustained activation of bone anabolic Wnt signaling during aging. Deregulation of the miR-146a target genes Wnt1 and Wnt5a parallel bone accrual and osteoblast generation, which is accompanied by reduced development of bone marrow adiposity. Furthermore, miR-146a deficient mice are protected from ovariectomy induced bone loss. In humans, levels of miR-146a are increased in patients suffering fragility fractures in comparison to those who do not.These data identify miR-146a as a crucial epigenetic temporal regulator which essentially controls bone homeostasis during aging by regulating bone anabolic Wnt signaling. Therefore, miR-146a might be a powerful therapeutic target to prevent age related bone dysfunction such as the development of bone marrow adiposity and osteoporosis.

The synthesis of a tetravalent neptunium amidinate [NpCl((S)‐PEBA)3] (1) ((S)‐PEBA=(S,S)‐N,N′‐bis‐(1‐phenylethyl)‐benzamidinate) is reported. This complex represents the first structurally characterized enantiopure transuranic compound. Reactivity studies with halide/pseudohalides yielding [NpX((S)‐PEBA)3] (X=F (2), Br (3), N3 (4)) have shown that the chirality‐at‐metal is preserved for all compounds in the solid state. Furthermore, they represent an unprecedented example of a structurally characterized metal–organic Np complex featuring a Np−Br (3) bond. In addition, 4 is the only reported tetravalent transuranic azide. All compounds were additionally characterized in solution using para‐magnetic NMR spectroscopy showing an expected C 3‐symmetry at low temperatures., Enantiopure transuranic complexes: The first structurally characterized enantiopure complexes of neptunium have been synthesized. Starting from a chloro tris(amidinate) complex unprecedented neptunium(IV) fluoro, ‐bromo and ‐azido compounds could be yielded and characterized in solution and in the solid state (see scheme).

Macrophages are professional phagocytes, indispensable for maintenance of tissue homeostasis and integrity. Depending on their resident tissue, macrophages are exposed to highly diverse metabolic environments. Adapted to their niche, they can contribute to local metabolic turnover through metabolite uptake, conversion, storage and release. Disturbances in tissue homeostasis caused by infection, inflammation or damage dramatically alter the local milieu, impacting macrophage activation status and metabolism. In the case of persisting stimuli, defective macrophage responses ensue, which can promote tissue damage and disease. Especially relevant herein are disbalances in lipid rich environments, where macrophages are crucially involved in lipid uptake and turnover, preventing lipotoxicity. Lipid uptake is to a large extent facilitated by macrophage expressed scavenger receptors that are dynamically regulated and important in many metabolic diseases. Here, we review the receptors mediating lipid uptake and summarize recent findings on their role in health and disease. We further highlight the underlying pathways driving macrophage lipid acquisition and their impact on myeloid metabolic remodelling.

Background A reliable and sterile access through the intestinal wall to ease flexible endoscopic transluminal interventions is still appealing but lacks a suitable port system. Methods In a granted industry cooperation, we developed the MIEO-Port, a flexible three components overtube system that provides a temporary hermetic sealing of the intestinal wall to allow endoscopic disinfection and manipulation to gain access to the abdominal cavity. The port features an innovative head part which allows for coupling the port to the intestinal wall by vacuum suction and for controlled jetting the isolated intestinal surface with a disinfectant. The device was tested in vivo in 6 pigs for acute and long-term usability. All animal tests were approved by the local ethics committee. Results In the acute experiment, the port system supported sealed endoscopic mucosa resection and transluminal cholecystectomy. In the survival study on 5 animals, the MIEO-Port proved its reliability after transcolonic peritoneoscopy. In one animal, a port dislocation occurred after extensive retroperitoneal preparation, one animal revealed bacterial contamination at necropsy; however, all animals showed a favourable course over ten days and offered no signs of peritonitis or abscedation during post-mortem examination. Discussion To the best of our knowledge, the MIEO-Port system is the first device to provide a reliable and sterile flexible access to the peritoneal cavity that can be used throughout the entire gastrointestinal tract regardless of the access route and which combines hermetic sealing with local sterilization. Further studies are warranted.

Microplastic (MP) pollution is potentially a major threat to many aquatic organisms. Yet we currently know very little about the mechanisms responsible for the effects of small MPs on phenotypes, and the extent to which effects of MPs are modified by genetic and environmental factors. Using a multivariate approach, we studied the effects of 500 nm polystyrene microspheres on the life history and immunity of eight clones of the freshwater cladoceran Daphnia magna reared at two temperatures (18 °C/24 °C). MP exposure altered multivariate phenotypes in half of the clones we studied but had no effect on others. In the clones that were affected, individuals exposed to MPs had smaller offspring at both temperatures, and more offspring at high temperature. Differences in response to MP exposure were unrelated to differences in particle uptake, but were instead linked to an upregulation of haemocytes, particularly at high temperature. The clone-specific, context-dependent nature of our results demonstrates the importance of incorporating genetic variation and environmental context into assessments of the impact of plastic particle exposure. Our results identify immunity as an important mechanism underpinning genetically variable responses to MP pollution and may have major implications for predicting consequences of MP pollution.

Patient: Male, 56 Final Diagnosis: Hemorrhagic duodenitis Symptoms: Abdominal pain • melena Medication: — Clinical Procedure: CT scan • gastroscopy • colonoscopy • blood transfusion Specialty: General and Internal Medicine Objective: Challenging differential diagnosis Background: Hemorrhagic duodenitis is an exceptionally rare adverse event of sodium polystyrene sulfonate (SPS) treatment and is a common manifestation of cytomegalovirus (CMV) reactivation. SPS is known to cause marked inflammation in the lower gastrointestinal tract, including colonic necrosis, whereas involvement of the small bowel is uncommon. Although its effectiveness and safety has been disputed since its introduction, SPS remains widely used due to lack of alternatives. CMV infection and reactivation are well-known complications after solid-organ transplantation, particularly in seronegative recipients receiving organs from seropositive donors, and is associated with significant morbidity and mortality. The lower gastrointestinal tract is more commonly involved, but infections of all parts of the intestine are observed. Case Report: Here, we report the case of a 56-year-old man who presented with severe upper-gastrointestinal bleeding. Hemorrhagic duodenitis was initially attributed to the use of SPS, as abundant SPS crystals were detected in the duodenal mucosa but we found only 2 CMV-infected endothelial cells. Two weeks later, gastrointestinal bleeding recurred. However, this time, abundant CMV-infected cells were demonstrated in the duodenal biopsies. Conclusions: Our case report highlights an uncommon adverse event after SPS use with a simultaneous CMV reactivation. The main difficulty was to differentiate between CMV reactivation and CMV as an “innocent bystander”. This demonstrates the challenge of decision-making in patients with complex underlying diseases.

The enantiopure mono(borohydride) rare-earth complexes [Ln{(S)-PETA)}2(BH4)] (Ln = Sc (1), Lu (2); PETA = N,N′-bis((S)-1-phenylethyl)-tert-butylamidinate) are reported. The synthesis was achieved by salt metathesis reactions of the homoleoptic tris(borohydrides) [Ln(BH4)3(thf)n] and (S)-LiPETA. Complexes 1 and 2 were fully characterized, including single-crystal X-ray diffraction. Compounds 1 and 2 were evaluated as initiators for the ring-opening polymerization (ROP) of racemic lactide. Both 1 and 2 were found to be active in the ROP of dl-lactide. Polymerizations carried out in toluene show a higher activity for 2 but a lower selectivity in comparison to the scandium derivative.

Metabolic networks support cancer cell survival, proliferation, and malignant progression. Cancer cells take up large amounts of nutrients such as glucose and glutamine whose metabolism provides the energy, reducing equivalents, and biosynthetic precursors required to meet the biosynthetic demands of proliferation. Intermediates of glycolysis and the tricarboxylic acid (TCA) cycle provide critical building blocks for synthesis of non-essential amino acids, nucleotides, and fatty acids. To view this SnapShot, open or download the PDF.