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Abstract Recent progress in image-based spatial RNA profiling enables to spatially resolve tens to hundreds of distinct RNA species with high spatial resolution. It presents new avenues for comprehending tissue organization. In this context, the ability to assign detected RNA transcripts to individual cells is crucial for downstream analyses, such as in-situ cell type calling. Yet, accurate cell segmentation can be challenging in tissue data, in particular in the absence of a high-quality membrane marker. To address this issue, we introduce ComSeg, a segmentation algorithm that operates directly on single RNA positions and that does not come with implicit or explicit priors on cell shape. ComSeg is applicable in complex tissues with arbitrary cell shapes. Through comprehensive evaluations on simulated and experimental datasets, we show that ComSeg outperforms existing state-of-the-art methods for in-situ single-cell RNA profiling and in-situ cell type calling. ComSeg is available as a documented and open source pip package at https://github.com/fish-quant/ComSeg .

Abstract Genome-wide ensemble sequencing methods improved our understanding of chromatin organization in eukaryotes but lack the ability to capture single-cell heterogeneity and spatial organization. To overcome these limitations, new imaging-based methods have emerged, giving rise to the field of spatial genomics. Here, we present pyHiM, a user-friendly python toolbox specifically designed for the analysis of multiplexed DNA-FISH data and the reconstruction of chromatin traces in individual cells. pyHiM employs a modular architecture, allowing independent execution of analysis steps and customization according to sample specificity and computing resources. pyHiM aims to facilitate the democratization and standardization of spatial genomics analysis.

Additive Manufacturing (AM) Direct Laser Fabrication (DLF) of Ti-5Al-5V-5Mo-3Cr (Ti5553) is being developed as a method for producing aircraft components. The additive manufacturing process can produce flaws near the surface, such as porosity and material voids, which act as stress raisers, leading to potential component failure. Eddy current testing was investigated to detect flaws on or near the surface of DLF Ti5553 bar samples. For this application, the objective was to develop an eddy current probe capable of detecting flaws 500 µm in diameter, located 1 mm below the component’s surface. Two initial sets of coil parameters were chosen: The first, based on successful experiments that demonstrated detection of a near surface flaw in Ti5553 using a transmit-receive array probe, and the second, derived from simulation by Finite Element Method (FEM). An optimized transmit receive coil design, based on the FEM simulations, was constructed. The probe was evaluated on Ti5553 samples containing sub-surface voids of the target size, as well as samples with side-drilled holes and samples with holes drilled from the opposing inspection surface. The probe was able to effectively detect 80% of the sub-surface voids. Limitations included the probe’s inability to detect sub-surface voids near sample edges and a sensitivity to surface roughness, which produces local changes in lift-off. Multifrequency mixing improved signal-to-noise ratio when surface roughness was present on average by 22%. A probe based on that described in this paper could benefit quality assurance of additively manufactured aircraft components.

Abstract Radiation Induced Lung Injury (RILI) is one of the main limiting factors of thorax irradiation, which can induce acute pneumonitis as well as pulmonary fibrosis, the latter being a life-threatening condition. The order of cellular and molecular events in the progression towards fibrosis is key to the physiopathogenesis of the disease, yet their coordination in space and time remains largely unexplored. Here, we present an interactive murine single cell atlas of the lung response to irradiation, generated from C57BL6/J female mice. This tool opens the door for exploration of the spatio-temporal dynamics of the mechanisms that lead to radiation-induced pulmonary fibrosis. It depicts with unprecedented detail cell type-specific radiation-induced responses associated with either lung regeneration or the failure thereof. A better understanding of the mechanisms leading to lung fibrosis will help finding new therapeutic options that could improve patients’ quality of life.

Abstract Targeted radionuclide therapy is a revolutionary tool for the treatment of highly spread metastatic cancers. Most current approaches rely on the use of vectors to deliver radionuclides to tumor cells, targeting membrane‐bound cancer‐specific moieties. Here, we report the embryonic navigation cue netrin‐1 as an unanticipated target for vectorized radiotherapy. While netrin‐1, known to be re‐expressed in tumoral cells to promote cancer progression, is usually characterized as a diffusible ligand, we demonstrate here that netrin‐1 is actually poorly diffusible and bound to the extracellular matrix. A therapeutic anti‐netrin‐1 monoclonal antibody (NP137) has been preclinically developed and was tested in various clinical trials showing an excellent safety profile. In order to provide a companion test detecting netrin‐1 in solid tumors and allowing the selection of therapy‐eligible patients, we used the clinical‐grade NP137 agent and developed an indium‐111‐NODAGA‐NP137 single photon emission computed tomography (SPECT) contrast agent. NP137‐111In provided specific detection of netrin‐1‐positive tumors with an excellent signal‐to‐noise ratio using SPECT/CT imaging in different mouse models. The high specificity and strong affinity of NP137 paved the way for the generation of lutetium‐177‐DOTA‐NP137, a novel vectorized radiotherapy, which specifically accumulated in netrin‐1‐positive tumors. We demonstrate here, using tumor cell‐engrafted mouse models and a genetically engineered mouse model, that a single systemic injection of NP137‐177Lu provides important antitumor effects and prolonged mouse survival. Together, these data support the view that NP137‐111In and NP137‐177Lu may represent original and unexplored imaging and therapeutic tools against advanced solid cancers.

A tremendous number of landmines has been buried during the last decade. In recent years, various autonomous platforms equipped with ground-penetrating radars (GPRs) have been proposed for the detection of landmines. These systems have already demonstrated their performance in controlled environments with known ground truth. However, it has been observed that the influence of surface conditions in the form of vegetation and roughness as well as soil moisture content significantly reduce the detection probability. The influence of these individual factors on a ground-offset GPR is presented and discussed in this work. Each of these factors significantly degrades the backscattered signal. With increasing soil moisture, the signal gets attenuated more strongly; however, the signature is maintained in the phase of the C-Scans. An increase in surface roughness deteriorates the target pattern making it difficult to detect buried objects unambiguously. Vegetation, especially with irregular leaf structures, can appear as a ghost target and scatter the electromagnetic waves. In most cases, the target is easier to detect in the phase of the B- or C-Scan.

Purpose: To improve neuroendocrine neoplasm (NEN) management, the European Neuroendocrine Tumor Society (ENETS) recognised 62 Centers of Excellence (CoE). This retrospective study compares conformity of patients’ initial management within vs outside an ENETS CoE with clinical practice guidelines (CPGs). Methods: Patients diagnosed with a NEN between August 2018 and July 2020 and presented in the Lyon-CoE Multidisciplinary Tumour Board (MDT) were included. Factors potentially associated with the conformity of initial management (work-up and first treatment) to CPG underwent univariate and multivariate analyses. Results: Among the 615 included patients, 170 (27.6%) were initially managed in the CoE and 445 (72.4%) were only presented at the CoE-MDT. Patients in the CoE group more often had intestinal or pancreatic primaries, metastatic disease (61.8% vs 33%), hereditary syndrome, and a functioning tumour. Work-up conformity was 37.1% in the CoE (vs 29.9%, P = 0.09); this was 95.8% for the first treatment (vs 88.7%, P = 0.01). After multivariate analysis, CPG conformity was significantly higher for patients managed in the CoE, for younger patients, for those having a grade 1–2 tumour, and a genetic syndrome. Pancreatic and small intestinal (SI) NET surgeries performed in the CoE had a higher splenic preservation rate during left pancreatectomy, better detection of multiple tumours in SI surgeries, and higher number of resected lymph nodes. Conclusions: Given the widespread observance of CPG, not all patients require management in the CoE. Referral should be considered for more complex cases such as metastatic diseases, G2 tumours, or carcinoid syndromes. Finally, we should encourage the centralization of NET surgery.

According to the neuroendocrine tumour (NET) characteristics, 3 to 7 different treatment options are available, corresponding to 6 to 5,040 theoretical different sequences. Even though each patient is unique and despite a large heterogeneity in NET characteristics, the present review aims to discuss the main sequences and addresses how one can propose the best sequence to treat metastatic NET (mNET) on a case-by-case basis. Each treatment must be discussed during dedicated multi-disciplinary meetings, and inclusions in clinical trials should be favoured. After a thorough characterization of patients and their mNET, and taking into account the availability of drugs, the first-line treatment should be chosen according to the treatment aim. The latter is determined based on three main topics (efficacy, safety, and patient preferences) that do not necessarily converge and must be defined a priori . At baseline, physicians should design an a priori full therapeutic sequence, which may evolve at each step depending on the response to previous treatment, the occurrence of chronic toxicities, and the patients’ perception of the prior treatment. To improve knowledge in terms of effectiveness and risk of cumulative toxicities regarding the different sequences, real-world data using long follow-up durations are necessary; such issues will not be resolved by randomized clinical trials.

Background and Objectives: To analyze the patient outcome and complication rate of axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients who could not be weaned from cardiopulmonary bypass after cardiothoracic surgery. Materials and Methods: We analyzed the data of 179 patients who were supported with VA-ECMO with femoral–axillary access (FA VA-ECMO) after cardiothoracic surgery between January 2014 and January 2019 in our department. Patients requiring central aortic cannulation and patients with respiratory failure requiring veno-venous ECMO were excluded. Primary outcomes were in-hospital mortality and 1-year survival rate of patients who were weaned from VA-ECMO support. Secondary outcomes were cannulation-related complications at the axillary site, VA-ECMO-related complications, and systemic complications. Results: In our cohort, 60 (33.5%) patients were female. Mean age was 67.0 ± 10.9 years. Overall, 78 (43.5%) patients were operated upon electively, 37 (20.7%) patients underwent urgent surgery, and 64 (35.8%) patients underwent emergency surgical treatment. Sixty-seven patients (37.4%) were resuscitated preoperatively. The mean duration of VA-ECMO support was 8.4 ± 5.1 days. Weaning from VA-ECMO was successful in 87 (48.6%) patients; 62 (34.6%) patients survived the hospital stay. The 1-year survival rate was 74%. Subclavian bleeding occurred in 24 (13.4%) patients, femoral bleeding in 4 (2.2%) patients, ischemia of the upper limb in 11 (6.1%) patients, intracerebral bleeding in 9 (5%) patients, and stroke in 19 (10.6%) patients. Conclusions: In patients with acute LV dysfunction after cardiothoracic surgery who cannot be weaned from cardiopulmonary bypass, right axillary artery cannulation is a safe and reliable method for VA-ECMO support with an acceptable complication rate.

Today’s warning systems for floods or droughts require sensor applications that provide a vast array of information. Current systems provide insight into either the water level or the river velocity. In order to obtain additional parameters for the characterization of the flow behavior in a noncontact manner, a frequency-modulated continuous-wave radar with chirp sequence is used. Since these sensors provide range and velocity information but also enable gathering of additional parameters. The presented measurements in this contribution were performed at four different rivers with a commercially available radar sensor. The results of the classical postprocessed 2-D fast Fourier transform are used as basis for an imagewise processing approach to obtain additional features for classifying the behavior of the river surface. For this purpose, the framewise enveloping velocities are depicted in a time sequence. Due to processing the detected reflection patterns in relation to time, a characteristic pattern for river flow profiles can be extracted. By reducing the information using time averaging, characteristic features for different flows can be extracted from the spatial envelope velocity distribution. In particular, the resulting insights lead to characteristic features for single flow distributions that enable novel monitoring systems with new possibilities to classify rivers using radar sensors.

In this publication, a radar scenario generation approach for chirp sequence frequency modulated continuous wave radars simulating targets in the near-range of vehicle surroundings is presented. Key interest is the generation and the replay of arbitrary signals for a CS-FMCW radar by directly modulating the carrier signal. This approach enables the reproduction of traffic scenarios including significant micro-Doppler signatures of traffic participants. In the presented approach, the received E band signal is converted from the RF to an IF band, in which the information about velocity and range of a target is modulated with the usage of an IQ modulator. Since the working principle of the radar target simulator is not based on a delay line, the target profiles can solely be generated on the PC from where they are modulated onto the radar signal via digital-analog conversion. The modulation signals can either be generated in the time or frequency domain which allows an accurate and fast reproduction of real-world scenarios. When generated in the frequency domain, the 2D-IFFT provides an efficient way of transforming commonly used range Doppler maps into the desired modulation signals. This way, range-velocity profiles of complex traffic participants such as pedestrians or cyclists can be generated and simulated in arbitrary circumstances.

High-content screening (HCS) provides an excellent tool to understand the mechanism of action of drugs on disease-relevant model systems. Careful selection of fluorescent labels (FLs) is crucial for successful HCS assay development. HCS assays typically comprise (a) FLs containing biological information of interest, and (b) additional structural FLs enabling instance segmentation for downstream analysis. However, the limited number of available fluorescence microscopy imaging channels restricts the degree to which these FLs can be experimentally multiplexed. In this article, we present a segmentation workflow that overcomes the dependency on structural FLs for image segmentation, typically freeing two fluorescence microscopy channels for biologically relevant FLs. It consists in extracting structural information encoded within readouts that are primarily biological, by fine-tuning pre-trained state-of-the-art generalist cell segmentation models for different combinations of individual FLs, and aggregating the respective segmentation results together. Using annotated datasets that we provide, we confirm our methodology offers improvements in performance and robustness across several segmentation aggregation strategies and image acquisition methods, over different cell lines and various FLs. It thus enables the biological information content of HCS assays to be maximized without compromising the robustness and accuracy of computational single-cell profiling.

The abyssal plains are vast areas without large scale relief that occupy much of the ocean floor. Although long considered relatively featureless, they are now known to display substantial biological heterogeneity across different spatial scales. Ecological research in these regions benefits increasingly from non-destructive visual sampling of epifaunal organisms with imaging technology. We analysed images from ultra-high-definition towed camera transects at depths of around 3500 m across three stations (100–130 km apart) in the Bering Sea, to ask whether the density and distribution of visible epifauna indicated any substantial heterogeneity. We identified 71 different megafaunal taxa, of which 24 occurred at only one station. Measurements of the two most abundant faunal elements, the holothurian Elpidia minutissima and two xenophyophores morphotypes (the more common identifiable as Syringammina limosa), indicated significant differences in local densities and patchy aggregations that were strikingly dissimilar among stations. One station was dominated by xenophyophores, one was relatively depauperate in both target taxa as well as other identified megafauna, and the third station was dominated by Elpidia. This is an unexpected level of variation within comparable transects in a well-mixed oceanic basin, reinforcing the emerging view that abyssal habitats encompass biological heterogeneity at similar spatial scales to terrestrial continental realms.

We report a case of metastatic pancreatic neuroendocrine carcinoma associated with paraneoplastic Cushing’s syndrome, successively treated with five lines of treatment (platin-etoposide, LV5FU2-dacarbazine, FOLFIRINOX, pembrolizumab, and paclitaxel) and anti-secretory treatment. Circulating-free DNA (cfDNA) was analysed at each morphological evaluation starting from the second-line treatment. cfDNA changes were well correlated with the disease course, and cfDNA may be used as a predictive marker and/or as an early marker of response. In addition, the absolute count of atypical cells was elevated upon disease progression.

Abstract Background Sixty percent of all species are insects, yet despite global efforts to monitor animal movement patterns, insects are continuously underrepresented. This striking difference between species richness and the number of species monitored is not due to a lack of interest but rather to the lack of technical solutions. Often the accuracy and speed of established tracking methods is not high enough to record behavior and react to it experimentally in real-time, which applies in particular to small flying animals. Results Our new method of real-time tracking relates to frequencies of solar radiation which are almost completely absorbed by traveling through the atmosphere. For tracking, photoluminescent tags with a peak emission (1400 nm), which lays in such a region of strong absorption through the atmosphere, were attached to the animals. The photoluminescent properties of passivated lead sulphide quantum dots were responsible for the emission of light by the tags and provide a superb signal-to noise ratio. We developed prototype markers with a weight of 12.5 mg and a diameter of 5 mm. Furthermore, we developed a short wave infrared detection system which can record and determine the position of an animal in a heterogeneous environment with a delay smaller than 10 ms. With this method we were able to track tagged bumblebees as well as hawk moths in a flight arena that was placed outside on a natural meadow. Conclusion Our new method eliminates the necessity of a constant or predictable environment for many experimental setups. Furthermore, we postulate that the developed matrix-detector mounted to a multicopter will enable tracking of small flying insects, over medium range distances (>1000m) in the near future because: a) the matrix-detector equipped with an 70 mm interchangeable lens weighs less than 380 g, b) it evaluates the position of an animal in real-time and c) it can directly control and communicate with electronic devices.

The automatic analysis of stained histological sections is becoming increasingly popular. Deep Learning is today the method of choice for the computational analysis of such data, and has shown spectacular results for large datasets for a large variety of cancer types and prediction tasks. On the other hand, many scientific questions relate to small, highly specific cohorts. Such cohorts pose serious challenges for Deep Learning, typically trained on large datasets. In this article, we propose a modification of the standard nested cross-validation procedure for hyperparameter tuning and model selection, dedicated to the analysis of small cohorts. We also propose a new architecture for the particularly challenging question of treatment prediction, and apply this workflow to the prediction of response to neoadjuvant chemotherapy for Triple Negative Breast Cancer.

Abstract The navigation cue netrin‐1 is well‐documented for its key role in cancer development and represents a promising therapeutic target currently under clinical investigation. Phase 1 and 2 clinical trials are ongoing with NP137, a humanized monoclonal antibody against netrin‐1. Interestingly, the epitope recognized by NP137 in netrin‐1 shares 90% homology with its counterpart in netrin‐3, the closest member to netrin‐1 in humans, for which little is known in the field of cancer. Here, we unveiled that netrin‐3 appears to be expressed specifically in human neuroblastoma (NB) and small cell lung cancer (SCLC), two subtypes of neuroectodermal/neuroendocrine lineages. Netrin‐3 and netrin‐1 expression are mutually exclusive, and the former is driven by the MYCN oncogene in NB, and the ASCL‐1 or NeuroD1 transcription factors in SCLC. Netrin‐3 expression is correlated with disease stage, aggressiveness, and overall survival in NB. Mechanistically, we confirmed the high affinity of netrin‐3 for netrin‐1 receptors and we demonstrated that netrin‐3 genetic silencing or interference using NP137, delayed tumor engraftment, and reduced tumor growth in animal models. Altogether, these data support the targeting of netrin‐3 in NB and SCLC.

Centrosomes function as microtubule organizing centers where several mRNAs accumulate. By employing high-throughput single molecule FISH screening, the authors discover that 8 human mRNAs localize to centrosomes with unique cell cycle dependent patterns using an active polysome targeting mechanism.

OBJECTIVES/GOALS: Treatment options for glioblastoma (GBM) are limited. Prognosis remains dismal, with an 18 month on average survival rate following diagnosis due to treatment resistance and disease recurrence. The goal of this project is to investigate hallmarks of cancer progression that contribute to temozolomide (TMZ) resistance, a first tine treatment for GBM. METHODS/STUDY POPULATION: Two signaling pathways were investigated in TMZ-sensitive and -resistant GBM cell lines and in primary and recurrent patient-derived xenograft (PDX) tumor cells by genetically and pharmacologically inhibiting methionine adenosyltransferase 2A (MAT2A) and adenosylhomocysteinase (AHCY). Cell growth and survival were assessed by measuring protein expression of proliferation, oxidative stress and cell cycle arrest markers. EPIC array analysis and targeted bisulfite sequencing were conducted to identify changes in genome-wide and specific CpG island methylation. The Seahorse XF Analyzer measured mitochondrial respiratory capacity and oxidative metabolism. Induced pluripotent stem cell organoids were co-cultured with PDX tumor cells to determine if treatments mitigate tumor cell invasiveness. RESULTS/ANTICIPATED RESULTS: Compared to parental cells (PC), MAT2A gene expression was increased by 1.7-fold in acquired resistant and de novo resistant GBM cells (RC) [(transcript per million): PC, 7386 ± 0.012; RC, 12925 ± 0.023; n=2; p=2.10e-8]. Compared to TMZ-sensitive cells (TS), TMZ-resistant cells (TR) demonstrated a 56% increase in baseline oxygen consumption rate [(pmol/min): TS, 179 ± 6.7; TR, 279 ± 13; n=18; p=.0012] and 64% increase in maximal respiratory capacity [(pmol/min): TS, 403 ± 29; TR, 659 ± 35; n=6; p DISCUSSION/SIGNIFICANCE: MAT2A and AHCY contribute to TMZ resistance and recurrence by dysregulating methylation programs and upregulating antioxidant programs, respectively. These findings provide a foundation for developing novel combinatory therapeutic strategies and inform clinical studies intended to increase remission and reduce recurrence for GBM patients.

Objective: First-line chemotherapy in metastatic neuroendocrine carcinomas (NECs) is based on etoposide and platinum. However, there is no standard concerning second-line treatment. The objective of this study was to evaluate effic acy and tolerance of dacarbazine or temozolomide in metastatic digestive NEC as post first-line treatment. Material and methods: This study included patients with a metastatic NEC of digestive or unknown primary site. All patients received platinum-etoposi de as first-line chemotherapy. Primary endpoint was progression-free survival (PFS). Secondary endpoints were clinical/morphological responses, toxicity, and overall survival (OS). Results: Twenty-seven patients were included: 17 received dacarbazine and 10 temozolomide as post-first line treatments. Median PFS was 3.0 ( 95%CI (2.2;3.7)) months. There was no significant difference between dacarbazine and temoz olomide on PFS. Clinical and morphological responses were found in 12 and 9 pat ients, respectively. Median OS was 7.2 (95%CI (2.2;12.2)) months. The toxicity profil e was that expected with such treatments. Conclusion: LV5FU2-dacarbazine or temozolomide-capecitabine chemotherapies allow a temporary clinical response for almost half of patients and/or a morphological response for a third of patients.

Unoccupied aircraft systems (UAS) are developing into fundamental tools for tackling the grand challenges in volcanology; here, we review the systems used and their diverse applications. UAS can typically provide image and topographic data at two orders of magnitude better spatial resolution than space-based remote sensing, and close-range observations at temporal resolutions down to those of video frame rates. Responsive deployments facilitate dense time-series measurements, unique opportunities for geophysical surveys, sample collection from hostile environments such as volcanic plumes and crater lakes, and emergency deployment of ground-based sensors (and robots) into hazardous regions. UAS have already been used to support hazard management and decision-makers during eruptive crises. As technologies advance, increasing system capabilities, autonomy and availability, supported by more diverse and lighter-weight sensors, will offer unparalleled potential for hazard monitoring. UAS will provide opportunities for pivotal advances in our understanding of complex physical and chemical volcanic processes.

Wide bandgap semiconductors such as group III-nitrides and SiC are considered as key materials for the fabrication of smaller, more reliable and efficient power electronics. Fabrication of robust and durable power devices requires an optimized design based on the understanding of the interfacial adhesion properties of the constituent thin-film heterostructures. In this study, the adhesion properties of GaN/AlN layers grown on Si substrates were investigated. Particularly, the influence of the AlN buffer layers, necessary for GaN growth on Si, on the delamination response was determined. The interfacial adhesion strength was obtained using cross-sectional nanoindentation (CSN) and four-point bending (4PB) tests. Analytical models based on beam- and elastic plate theory which were applied respectively to calculate the interfacial fracture energy (Gic) for both methods are found to be in good agreement provided the loading conditions are similar. Detailed transmission and scanning electron microscopy investigations prior and subsequent to delamination reveal the microstructural details of the relevant interfaces and provide insights into the encountered mechanisms of interfacial failure. Finally, the probability of delamination along the weakest interface is discussed based on a fracture mechanics model.

In this paper, we report on our benchmark results of the LiDAR sensors Livox Horizon, Robosense M1, Blickfeld Cube, Blickfeld Cube Range, Velodyne Velarray H800, and Innoviz Pro. The idea was to test the sensors in different typical scenarios that were defined with real-world use cases in mind, in order to find a sensor that meet the requirements of self-driving vehicles. For this, we defined static and dynamic benchmark scenarios. In the static scenarios, both LiDAR and the detection target do not move during the measurement. In dynamic scenarios, the LiDAR sensor was mounted on the vehicle which was driving toward the detection target. We tested all mentioned LiDAR sensors in both scenarios, show the results regarding the detection accuracy of the targets, and discuss their usefulness for deployment in self-driving cars.

Abstract Background Normal mammalian development and homeostasis are dependent upon the gut microbiota. Antibiotics, essential for the treatment and prophylaxis of bacterial infections, can have collateral effects on the gut microbiota composition, which can in turn have far-reaching and potentially deleterious consequences for the host. However, the magnitude and duration of such collateral effects appear to vary between individuals. Furthermore, the degree to which such perturbations affect the host response is currently unclear. We aimed to test the hypothesis that different human microbiomes have different responses to a commonly prescribed antibiotic and that these differences may impact the host response. Methods Germ-free mice (n = 30) humanized with the microbiota of two unrelated donors (A and B) were subjected to a 7-day antibiotic challenge with amoxicillin-clavulanate (“co-amoxiclav”). Microbiome and colonic transcriptome analysis was performed, pre (day 0) and post antibiotics (day 8) and subsequently into recovery (days 11 and 18). Results Unique community profiles were evident depending upon the donor, with donor A recipient mice being dominated by Prevotella and Faecalibacterium and donor B recipient mice dominated by Bacteroides and Parabacteroides. Donor A mice underwent a marked destabilization of their microbiota following antibiotic treatment, while donor B mice maintained a more stable profile. Dramatic and overlapping alterations in the host transcriptome were apparent following antibiotic challenge in both groups. Despite this overlap, donor A mice experienced a more significant alteration in gene expression and uniquely showed correlations between host pathways and key microbial genera. Conclusions Germ-free mice humanized by different donor microbiotas maintain distinct microbiome profiles, which respond in distinct ways to antibiotic challenge and evince host responses that parallel microbiome disequilibrium. These results suggest that inter-individual variation in the gut microbiota may contribute to personalized host responses following microbiota perturbation.

Automated analysis of RNA localisation in smFISH data has been elusive. Here, the authors simulate and use a large dataset of images to design and validate a framework for highly accurate classification of sub-cellular RNA localisation patterns from smFISH experiments.

Only few descriptions of intraoperative carcinoid syndrome (ioCS) have been reported. The primary objective of this study was to describe ioCS. A second aim was to identify risk factors of ioCS. We retrospectively analysed patients operated for small-bowel neuroendocrine tumour in our institution between 2007 and 2015, and receiving our preventive local regimen of octreotide continuous administration. ioCS was defined as highly probable in case of rapid (

This paper proposes a 3-D local pose estimation system for a small Unmanned Aerial Vehicle (UAV) with a weight limit of 200 g and a very small footprint of 10 cm×10cm. The system is realized by fusing 3-D position estimations from an Ultra-Wide Band (UWB) transceiver network with Inertial Measurement Unit (IMU) sensor data and data from a barometric pressure sensor. The 3-D position from the UWB network is estimated using Multi-Dimensional Scaling (MDS) and range measurements between the transceivers. The range measurements are obtained using Double-Sided Two-Way Ranging (DS-TWR), thus eliminating the need for an additional clock synchronization mechanism. The sensor fusion is accomplished using a loosely coupled Extended Kalman Filter (EKF) architecture. Extensive evaluation of the proposed system shows that a position accuracy with a Root-Mean-Square Error (RMSE) of 0.20cm can be obtained. The orientation angle can be estimated with an RMSE of 1.93°.

Abstract Background The aim of this study was to identify clinical risk factors for antimicrobial resistances and multidrug resistance (MDR) in urinary tract infections (UTI) in an emergency department in order to improve empirical therapy. Methods UTI cases from an emergency department (ED) during January 2013 and June 2015 were analyzed. Differences between patients with and without resistances towards Ciprofloxacin, Piperacillin with Tazobactam (Pip/taz), Gentamicin, Cefuroxime, Cefpodoxime and Ceftazidime were analyzed with Fisher’s exact tests. Results were used to identify risk factors with logistic regression modelling. Susceptibility rates were analyzed in relation to risk factors. Results One hundred thirty-seven of four hundred sixty-nine patients who met the criteria of UTI had a positive urine culture. An MDR pathogen was found in 36.5% of these. Overall susceptibility was less than 85% for standard antimicrobial agents. Logistic regression identified residence in nursing homes, male gender, hospitalization within the last 30 days, renal transplantation, antibiotic treatment within the last 30 days, indwelling urinary catheter and recurrent UTI as risk factors for MDR or any of these resistances. For patients with no risk factors Ciprofloxacin had 90%, Pip/taz 88%, Gentamicin 95%, Cefuroxime 98%, Cefpodoxime 98% and Ceftazidime 100% susceptibility. For patients with 1 risk factor Ciprofloxacin had 80%, Pip/taz 80%, Gentamicin 88%, Cefuroxime 78%, Cefpodoxime 78% and Ceftazidime 83% susceptibility. For 2 or more risk factors Ciprofloxacin drops its susceptibility to 52%, Cefuroxime to 54% and Cefpodoxime to 61%. Pip/taz, Gentamicin and Ceftazidime remain at 75% and 77%, respectively. Conclusions We identified several risk factors for resistances and MDR in UTI. Susceptibility towards antimicrobials depends on these risk factors. With no risk factor cephalosporins seem to be the best choice for empiric therapy, but in patients with risk factors the beta-lactam penicillin Piperacillin with Tazobactam is an equal or better choice compared to fluoroquinolones, cephalosporins or gentamicin. This study highlights the importance of monitoring local resistance rates and its risk factors in order to improve empiric therapy in a local environment.

A power distribution unit (PDU) is an electronic module which provides electrical power to the network of electronic devices. For modern distributed computing networks a smart PDU is required which does not only supply the power to all the attached units but also monitors current consumption and the load on each node. In this paper we presented the Hardware and Software module for an intelligent PDU which offers the capabilities to distribute the power and also supervise the current and load consumption and broadcast all it parameters to the administrator. This PDU is based on a state-of-the-art ARMCortex M4 microcontroller which is used under a Real time operating System. A real case scenario is presented at the end of this paper validating the hardware and software design of proposed PDU.

Ground beetles of the alluvial area Rupperswil, Canton Aargau, Switzerland, during the five years after its restoration (Coleoptera, Carabidae) The Rupperswil floodplain (Canton Aargau) was restored in the years 2010–2011. From 2012 to 2016, annual surveys of ground beetles were conducted. Over the five years, a total of 116 species were collected. From these species, 12 are classified as threatened, near threatened, or rare according to the Red List of Switzerland. Moreover, considerable numbers of Bembidion atrocaeruleum, B. prasinum, and Harpalus progrediens were found in the Rupperswil floodplain, for which the Canton Aargau has a particularly high responsibility for conservation. Additionally, 37 of the recorded species are character species for floodplains. Thus, the restoration can be considered very successful for ground beetles. Non-restored areas, characterized by river training measures, harbor generally half as many species at best. The number of species recorded per year varied between 68 and 82. Species turnover rate was between 28 and 45%. This reflects the change in habitats and hydrology over the five years. Open gravel/sand surfaces and annual ruderal habitats were reduced to one-third of their original area, while reed canary grass stands and perennial ruderal habitats tripled in size. On the other hand, the turnover is certainly also due to the low detection probability of rare species. Despite the strong decline in individual ground beetle species which typically occur on open gravel surfaces, it would be premature to initiate interventions to rebuild such areas. During the last year of the study, all typical gravel species observed in the previous years within the study area were found again. If anything, it would be more beneficial to build ponds with flat banks of fine sand within the forested sections of the floodplain or clear some patches to create more ruderal areas. RÉSUMÉ La zone alluviale de Rupperswil (canton d’Argovie) a été renaturée dans les années 2010-2011. De 2012 à 2016, les carabes ont été recensés annuellement. Au total, 116 espèces ont pu être identifiées. Parmi celles-ci, 12 espèces sont considérées comme en danger, potentiellement en danger ou rare selon la Liste Rouge. 37 espèces sont des espèces indicatrices pour les zones alluviales. Ainsi, la renaturation peut être considérée comme très réussie pour les carabes. Dans les surfaces non renaturées avec une dynamique alluviale réduite, causé par des mesures de construction fluviales, la moitié des espèces peuvent au mieux être trouvées. En comparaison de la Suisse dans son ensemble, la responsabilité de l’Argovie est très élevée pour le maintien en particulier de Bembidion atrocaeruleum, très fréquent, de B. prasinum et de Harpalus progrediens nombreux à Rupperswil. Pour un même effort d’échantillonnage, le nombre d’espèces trouvées a varié entre 68 et 82 pour les deux années. Le degré de turnover d’une année à l’autre s’est situé entre 28 et 45%. Ceci reflète d’une part le changement des biotopes et une hydrologie variable sur les cinq ans. Les alluvions sans végétation et les surfaces rudérales annuelles ont diminué d’environ un tiers alors que les Phalaridions et les surfaces rudérales pluriannuelles ont triplé. D’autre part, le turnover doit aussi être attribué à la probabilité réduite de trouver les espèces rares. Malgré un fort recul de certaines espèces particulières qui apparaissent typiquement dans les gravières ouvertes, il serait prématuré de créer de nouveau de telles surfaces par des interventions. Toutes les espèces de gravière ont encore pu être trouvées dans la région la dernière année d’étude. Le cas échéant, l’installation d’étangs dans la forêt de la zone alluviale avec des surfaces à sédiments fins provenant des berges de même qu’un nouvel écorchement de surfaces partielles pour la création de couloirs rudéraux seraient favorables. ZUSAMMENFASSUNG Die Aue Rupperswil (Kanton Aargau) wurde in den Jahren 2010-2011 renaturiert. Von 2012 bis 2016 wurden jährlich die Laufkäfer untersucht. Insgesamt konnten 116 Arten nachgewiesen werden. Davon sind 12 Arten gemäss Roter Liste gefährdet, potenziell gefährdet oder selten. 37 Arten sind Auenkennarten. Damit kann die Renaturierung bezüglich der Laufkäfer als sehr erfolgreich bezeichnet werden. In Gebieten, wo die Auendynamik durch flussbauliche Massnahmen stark reduziert ist, findet man bestenfalls halb so viele Arten. Im gesamtschweizerischen Vergleich ist die Verantwortung des Kanton Aargau für die Erhaltung insbesondere von Bembidion atrocaeruleum, in Rupperswil sehr häufig, B. prasinum, sowie Harpalus progrediens, beide zahlreich, sehr hoch. Die Anzahl der in den einzelnen Jahren bei gleichem Sammelaufwand gefundenen Arten variierte zwischen 68 und 82. Die Turnover-Rate der Arten in den Folgejahren betrug zwischen 28 und 45%. Dies widerspiegelt einerseits die Veränderung der Lebensräume sowie die unterschiedliche Hydrologie in den fünf Jahren. Offene Kies-Sandflächen und einjährige Ruderalfluren sind auf ca. einen Drittel geschrumpft während sich Rohrglanzgrasbestände und mehrjährige Ruderalfluren verdreifacht haben. Andererseits ist der Turnover sicher auch auf die geringe Auffindwahrscheinlichkeit selten vorkommender Arten zurückzuführen. Trotz starken Rückgängen einzelner Laufkäferarten, die typischerweise auf offenen Kiesflächen vorkommen, wäre es verfrüht, solche Flächen durch Eingriffe wieder zu schaffen. Es konnten auch im letzten Untersuchungsjahr noch alle typischen Kiesbank-Arten im Gebiet nachgewiesen werden. Allenfalls förderlich wären die Anlage von Tümpeln mit flachen aus Feinsedimenten bestehenden Uferpartien im Waldgebiet der Aue sowie das erneute Abschürfen einzelner Teilflächen zur Schaffung von Ruderalfluren.

For the management of diminutive duodenal neuroendocrine tumors (d-NETs), Harshit et al. have proposed – in the work accompanying this editorial – an interesting approach, the endoscopic banding without resection (BWR) technique. Given the risks associated with classic endoscopic resections and surgical procedures, and the likely favorable natural history of diminutive d-NETs, BWR may be an option for these selected patients with a very low risk of LN + and recurrence. However, a close follow-up (endoscopic, EUS and thoraco-abdominal CT scan) is then required to guarantee the safety of this policy.

A new innovative satellite mission, the Innovative CubeSat for Education (InnoCube), is addressed. The goal of the mission is to demonstrate “the wireless satellite”, which replaces the data harness by robust, high-speed, real-time, very short-range radio communications using the SKITH (SKIpTheHarness) technology. This will make InnoCube the first wireless satellite in history. Another technology demonstration is an experimental energy-storing satellite structure that was developed in the previous Wall#E project and might replace conventional battery technology in the future. As a further payload, the hardware for the concept of a software-based solution for receiving signals from Global Navigation Satellite Systems (GNSS) will be developed to enable precise position determination of the CubeSat. Aside from technical goals this work aims to be of use in the teaching of engineering skills and practical sustainable education of students, important technical and scientific publications, and the increase of university skills. This article gives an overview of the overall design of the InnoCube.

Background and objectives: The laryngeal mask is the method of choice for airway management in children during minor surgical procedures. There is a paucity of data regarding optimal management of mechanical ventilation in these patients. The Supreme™ airway laryngeal mask offers the option to insert a gastric tube to empty the stomach contents of air and/or gastric juice. The aim of this investigation was to evaluate the impact of positive end-expiratory positive pressure (PEEP) levels on ventilation parameters and gastric air insufflation during general anesthesia in children using pressure-controlled ventilation with laryngeal mask. Materials and Methods: An observational trial was carried out in 67 children aged between 1 and 11 years. PEEP levels of 0, 3 and 5 mbar were tested for 5 min in each patient during surgery and compared with ventilation parameters (dynamic compliance (mL/cmH2O), etCO2 (mmHg), peak pressure (mbar), tidal volume (mL), respiratory rate (per minute), FiO2 and gastric air (mL)) were measured at each PEEP. Air was aspirated from the stomach at the start of the sequence of measurements and at the end. Results: Significant differences were observed for the ventilation parameters: dynamic compliance (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001), peak pressure (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001) and tidal volume (PEEP 5 vs. PEEP 3: p = 0.0048, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001). All parameters increased significantly with higher PEEP, with the exception of etCO2 (significant decrease) and respiratory rate (no significant difference). We also showed different values for air quantity in the comparisons between the different PEEP levels (PEEP 5: 2.8 ± 3.9 mL, PEEP 3: 1.8 ± 3.0 mL; PEEP 0: 1.6 ± 2.3 mL) with significant differences between PEEP 5 and PEEP 3 (p = 0.0269) and PEEP 5 and PEEP 0 (p = 0.0209). Conclusions: Our data suggest that ventilation with a PEEP of 5 mbar might be more lung protective in children using the Supreme™ airway laryngeal mask, although gastric air insufflation increased with higher PEEP. We recommend the use of a laryngeal mask with the option of inserting a gastric tube to evacuate potential gastric air.

In this paper, the impact of the back contact barrier on the performance of Cu (In, Ga) Se2 solar cells is addressed. This effect is clearly visible at lower temperatures, but it also influences the fundamental parameters of a solar cell, such as open-circuit voltage, fill factor and the efficiency at normal operation conditions. A phototransistor model was proposed in previous works and could satisfactorily explain specific effects associated with the back contact barrier, such as the dependence of the saturated current in the forward bias on the illumination level. The effect of this contribution is also studied in this research in the context of metastable parameter drift, typical for Cu (In, Ga) Se2 thin-film solar cells, as a consequence of different bias or light soaking treatments under high-temperature conditions. The impact of the back contact barrier on Cu (In, Ga) Se2 thin-film solar cells is analyzed based on experimental measurements as well as numerical simulations with Technology Computer-Aided Design (TCAD). A barrier-lowering model for the molybdenum/Cu (In, Ga) Se2 Schottky interface was proposed to reach a better agreement between the simulations and the experimental results. Thus, in this work, the phototransistor behavior is discussed further in the context of metastabilities supported by numerical simulations.

O presente artigo aborda possibilidades de curadoria de moda. A partir da apresentação de alguns projetos, exploram-se discursos curatoriais e sua relevância para o desenvolvimento de outras perspectivas em torno da moda contemporânea. Embora seja um tema de pesquisa inesgotável, observou-se principalmente o potencial poético e experimental das práticas curatoriais de moda.

Purpose: The purpose of this study was to investigate the kinematic and kinetic variables, which predict anterior tibia shear force during single-leg landing in female athletes. Methods: Forty-three subjects (mean and standard deviation for age 21.12 ± 2.00 y, height 168.58 ± 7.62 cm, and weight 60.27 ± 7.80 kg) participated in this study. Kinematic and kinetic variables of lower extremity and trunk during single-leg landing were collected by 5 Vicon cameras and Kistler force plate. Stepwise multiple regression and Pearson correlation were used to identify predictor variables of anterior shear force (P ≤ 0.05). Results: Peak of extensor moment (P = 0.004, r = -0.394) and maximum knee flexion (P = 0.007, r = -0.370) were the best predictors that explained 30% of the variance of the shear force data. Therefore, rise in maximum extensors moment of knee and knee maximum flexion causes increase and decrease in anterior shear force, respectively. In addition, a significant relationship between trunk flexion (P = 0.039) and knee flexion angular velocity (P = 0.048) at the moment of initial contact with the anterior shear force. Conclusion: On the basis of previous research, and the relationship between clinical findings, the noncontact of anterior cruciate ligament injury during landing was confirmed. These results can be used in prospective studies examining modifiable noncontact risk factors of ACL injury.

Cell microencapsulation in alginate hydrogel has shown interesting applications in regenerative medicine and the biomedical field through implantation of encapsulated tissue or for bioartificial organ development. Although alginate solution is known to have low antiviral activity, the same property regarding alginate gel has not yet been studied. The aim of this work is to investigate the potential protective effect of alginate encapsulation against hepatitis C virus (HCV) infection for a hepatic cell line (HuH-7) normally permissive to the virus. Our results showed that alginate hydrogel protects HuH-7 cells against HCV when the supernatant was loaded with HCV. In addition, alginate hydrogel blocked HCV particle release out of the beads when the HuH-7 cells were previously infected and encapsulated. There was evidence of interaction between the molecules of alginate hydrogel and HCV, which was dose- and incubation time-dependent. The protective efficiency of alginate hydrogel towards HCV infection was confirmed against a variety of viruses, whether or not they were enveloped. This promising interaction between an alginate matrix and viruses, whose chemical mechanisms are discussed, is of great interest for further medical therapeutic applications based on tissue engineering.

Purple urine bag syndrome (PUBS) is a rare condition in which there is purple discoloration of the urine with its collecting bag and associated tubing occurs. It is considered a benign condition. We report an unusual case of PUBS in an 87-year-old female from nursing home who had a history of recurrent UTI. She also had a history of ureteral obstruction requiring left nephrostomy tube. She was brought to emergency department with altered mental status which developed five days after the occurrence of purple discoloration of the urinary bag. Her urine culture grew vancomycin-resistant Enterococci (VRE) and Pseudomonas aeruginosa. She died within three days of hospitalization despite intensive care in tertiary center. This case highlights that PUBS may not always be benign and should be approached on a case-by-case basis because it may signal the underlying UTI which might be very difficult to treat. Failure of recognition of this peculiar color early could delay the appropriate intervention leading to fatal complication. This case also represents the rare occurrence of PUBS in the setting of nephrostomy tube.

Mycoplasma suis, the causative agent of porcine infectious anemia, has never been cultured in vitro and mechanisms by which it causes disease are poorly understood. Thus, the objective herein was to use whole genome sequencing and analysis of M. suis to define pathogenicity mechanisms and biochemical pathways. M. suis was harvested from the blood of an experimentally infected pig. Following DNA extraction and construction of a paired end library, whole-genome sequencing was performed using GS-FLX (454) and Titanium chemistry. Reads on paired-end constructs were assembled using GS De Novo Assembler and gaps closed by primer walking; assembly was validated by PFGE. Glimmer and Manatee Annotation Engine were used to predict and annotate protein-coding sequences (CDS). The M. suis genome consists of a single, 742,431 bp chromosome with low G+C content of 31.1%. A total of 844 CDS, 3 single copies, unlinked rRNA genes and 32 tRNAs were identified. Gene homologies and GC skew graph show that M. suis has a typical Mollicutes oriC. The predicted metabolic pathway is concise, showing evidence of adaptation to blood environment. M. suis is a glycolytic species, obtaining energy through sugars fermentation and ATP-synthase. The pentose-phosphate pathway, metabolism of cofactors and vitamins, pyruvate dehydrogenase and NAD(+) kinase are missing. Thus, ribose, NADH, NADPH and coenzyme A are possibly essential for its growth. M. suis can generate purines from hypoxanthine, which is secreted by RBCs, and cytidine nucleotides from uracil. Toxins orthologs were not identified. We suggest that M. suis may cause disease by scavenging and competing for host' nutrients, leading to decreased life-span of RBCs. In summary, genome analysis shows that M. suis is dependent on host cell metabolism and this characteristic is likely to be linked to its pathogenicity. The prediction of essential nutrients will aid the development of in vitro cultivation systems.