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Objective This study was conducted to evaluate the effects of tannins and cellulase on growth performance, nutrient digestibility, blood profiles, intestinal morphology, and carcass characteristics in Hu sheep. Methods A total of 48 three-month-old meat Hu sheep (25.05±0.9 kg) were blocked based on body weight, and randomly allotted to 4 treatments with 3 replicates of 4 sheep each. The experiment lasted for 80 d, and dietary treatments were as follows: i) CON, control diet; ii) TAN, CON+0.1% tannins; iii) CEL, CON+0.1% cellulase; iv) TAN+CEL, CON+0.1% tannins and 0.1% cellulase. Results Compared with CON, CEL, and TAN+CEL had greater (p

OBJECTIVE: Bietti crystalline dystrophy (BCD) is a rare degenerative eye disease caused by mutations in the CYP4V2 gene, and Cyp4v3 is the murine ortholog to CYP4V2. To better understand the molecular pathogenesis of this disease and to explore the potential treatment we have established a Cyp4v3 knock-out mouse model. METHODS: Cyp4v3(-/-) mice were generated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 in embryonic stem cells of C57BL/6J mice. Ocular morphologic characteristics were evaluated via fundus imaging, histologic analysis of rods and cones via immunofluorescence, and phalloidin stain to observe retinal pigment epithelium (RPE) in whole-mounts, electroretinogram (ERG) was also conducted to examine the retinal function. RESULTS: The characteristic features of BCD recurred in the Cyp4v3(-/-) mice, including retinal crystalline deposits, atrophy and degeneration of RPE cells, and ERG amplitude decline of dark and light adapted a- and b- wave; however, the immunofluorescence stain of rod and cone cells did not show obvious differences when compared with the wild type (WT) mice. In the early stage of the disease, no crystal-like deposits were found in the fundus, ERG detection of the retinal function did not find a significant decline, and the morphological structure and quantity of the neural retina and RPE did not change significantly. Crystalline deposits occurred and converged when the Cyp4v3(-/-) mice at the end of 6 months, and the deposits disappeared when the Cyp4v3(-/-) mice at the end of 12 months. The ERG amplitude started to decline when the Cyp4v3(-/-) mice at the end of 6 months and deteriorated at the end of 12 months. The RPE cells of the 12-month old Cyp4v3(-/-) mice showed irregular shape by phalloidin staining of F-actin. The Cyp4v3(-/-) mice behaved normally and were viable and fertile when maintained under specific pathogen-free (SPF) housing conditions. CONCLUSION: Just like BCD patients, the disease progress of Cyp4v3(-/-) mouse is correlated with the age, which provides a good model for pathogenesis and gene therapy study in the future. The atrophy and degeneration of RPE take the lead in progressing of the disease, but the mechanism is not clear yet.

Commercial nuclear power plants extensively rely on fission energy from uranium dioxide (UO2) fuel pellets that provide thermal energy; consequently, generating carbon-free power in current generation reactors. UO2 fuel incurs damage and fractures during operation due to large thermal gradients that develop across the fuel pellet during normal operation. The underlying mechanisms by which these processes take place are still poorly understood. This work is a part of our combined experimental and computational effort for quantifying the UO2 fuel fracture behavior induced by thermal shock. In this work, we describe an experimental study performed to understand the fuel fracturing behavior of sintered powder UO2 pellets when exposed to thermal shock conditions, as well as a multiphysics phase-field fracture model which accurately predicts the experimental results. Parametric studies and sensitivity analysis are used to assess uncertainty. Experimental data was collected from multiple experiments by exposing UO2 pellets to high-temperature conditions (900-1200C), which are subsequently quenched in sub-zero water. We exhibit that the fracture results gathered in the experimental setting can be consistently recreated by this work phase-field fracture model, demonstrating a reliable ability to our model in simulating the thermal shock gradients and subsequent fracture mechanics in the primary fuel source for Light-Water Reactors (LWRs). This model advanced the fundamental understanding of thermal shock and property correlations to advance utilization of UO2 as a fuel for nuclear reactors., Submitted to Journal of Nuclear Materials, in review

儿童中枢神经系统神经免疫疾病是一组复杂的、病理生理学机制和临床表现具有明显异质性的疾病，包括脱髓鞘、炎症性、围感染性和感染后免疫调节紊乱疾病。近年来，随着对这些疾病的分子机制和检测技术的不断深入研究，针对这些免疫功能障碍关键分子的分子诊断和生物治疗技术得到迅速发展，这些疾病的预后有了很大改善。因此儿科医生需要及时掌握和应用这些新进展，提高诊断及治疗水平。.

To evaluate the impact of water pollutants, water levels and meteorological factors on theThe snail density appeared a fluctuation in Eastern Dongting Lake regions during the period from 2007 to 2014, with the highest density on October, 2010 (52.79 snails/0.1 mPermenganate index, total phosphorus and the date of the start of submergence affect the

Three patients diagnosed with focal cortical dysplasia (FCD) in the First Hospital of Peking University from September to November 2020 were recruited in the study. Based on stereotactic electroencephalogram (SEEG) or electrocorticogram (ECoG) analysis to localize the seizure onset zone (SOZ), RNA sequencing (RNA-seq) analysis was performed for the SOZ and para-SOZ tissue obtained from surgery. The differentially expressed genes between SOZ and para-SOZ samples were analyzed by performing Go (Gene ontology) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis."Extracellular matrix"was significantly enriched, which included collagen synthesis genes (e.g., COL1A1)."Ether lipid metabolism"was enriched in the KEGG pathway enrichment analysis. These differences could be the potential biological markers for SOZ localization.本研究纳入2020年9—11月就诊于北京大学第一医院的脑局灶性皮质发育不良（FCD）患者共3例，利用立体定向脑电图（SEEG）或皮质脑电图（ECoG）确定致痫灶，留取患者手术标本中致痫灶及灶旁对照组织，进行RNA-seq测序，对差异表达基因进行Go分析及KEGG信号通路富集分析。差异表达基因中，编码细胞外基质，特别是胶原成分相关的基因如COL1A1等存在显著差异表达；KEGG分析提示差异表达基因主要富集于醚酯代谢相关信号通路。FCD患者中致痫灶和自身对照组织相比，细胞外基质合成（特别是胶原成分）及醚酯代谢等生物过程存在差异，可以作为潜在的致痫灶生物标记物。.

Objective: To study the optimal cut-off value of thyroglobulin measurement in a fine-needle aspiration (FNA-Tg) in diagnosing malignant lymph nodes and benign lymph nodes (LNs) according to the thyroid tissue status.Methods: A total of 517 LNs were aspirated: 401 preoperative LNs, 42 LNs after subtotal thyroidectomy and 74 suspected LNs after total thyroidectomy. The cut-off value of FNA-Tg was obtained from receiver operating characteristic (ROC) analysis. The cut-off value with the best diagnostic performance was then obtained by comparing different cut-off values from other studies.Results: LN FNA-Tg levels differed between preoperative and total thyroid disease (p < 0.001) and subtotal thyroidectomy and total thyroidectomy (p = 0.03), but not between preoperative and subtotal thyroidectomy (p = 1.00). Accordingly, those 443 LNs with preoperative and subtotal thyroidectomy were compared to those 74 without thyroid tissue. The optimal cut-off value in thyroid tissue group was 19.4 ng/ml and the area under the ROC curve (AUC) was 0.95 (95% CI 0.92–0.97). The optimal cut-off value in thyroid tissue absence group was 1.2 ng/ml and the AUC was 0.93 (0.85–0.98). After the analysis and comparison of multiple cut-off values, the optimal diagnostic performance was still found to be 19.4 ng/ml and 1.2 ng/ml.Conclusion: The influential factors of FNA-Tg are still controversial, and the optimal cut-off value of FNA-Tg can be determined based on the presence or absence of thyroid tissue. FNA-Tg can be used as an important auxiliary method for diagnosing cervical metastatic LNs of thyroid cancer.

Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83‰. The crude incidence rate of adult HZ in females (7.26‰) was higher than that in males (6.40‰). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ (基于宜昌健康大数据平台，纳入2018年9月至2019年9月期间的850 608例就诊患者为研究对象，根据出生日期将研究对象分为儿童早期饥荒暴露组、胎儿期饥荒暴露组和非饥荒暴露组，分析宜昌市成人带状疱疹（HZ）发病情况并分析生命早期饥荒暴露与成年HZ的相关性。2019年宜昌市城区成年HZ粗发病率6.83‰，女性（7.26‰）高于男性（6.40‰）。与非饥荒暴露组相比，胎儿期饥荒暴露与成年HZ发病相关（

转甲状腺素蛋白心脏淀粉样变（ATTR-CA）是由转甲状腺素蛋白发生异常解离并聚集在心肌间质所导致，其中野生型（ATTRwt）为无TTR基因突变者。由于该病临床表现缺乏特异性，易被漏诊、误诊。该文报道了1例初诊为肥厚型心肌病最终确诊为ATTRwt患者的诊治过程。.

Background Patients with atrial fibrillation (AF) who initiated vitamin K antagonist (VKA) were at highest risk of stroke and bleeding in the first few months of therapy. Understanding of the temporal trend of clinical events in AF patients on non-VKA oral anticoagulant (NOAC) therapy should aid therapeutic decisions. Purpose To evaluate the temporal trend of clinical events in AF patients receiving edoxaban in routine clinical practice in the Global ETNA-AF program. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program evaluating the safety and effectiveness of edoxaban in patients from European and Asian countries. Thromboembolic, bleeding and death events were analysed separately for the 1st and 2nd year of the follow-up period, using a time-to-first-event estimation of cumulative incidence and annual rate via Kaplan-Meier method. Results A total of 27,617 patients were included in this analysis, 48.6% from Europe and 51.4% from Japan, Korea, and Taiwan. Baseline characteristics were consistent with typical AF population in real world studies (Table 1). Approximately 83% of patients received the recommended edoxaban dose. Annualized rates of ischaemic stroke and major bleeding (ISTH) were lower in the 2nd year than in the 1st year: ischaemic stroke 0.59% (95% CI, 0.50–0.70) vs 0.86% (95% CI, 0.75–0.98), p=0.015; major bleeding 0.87% (95% CI, 0.75–1.00) vs 1.15% (95% CI, 1.02–1.29), p=0.036. The trend toward lower rates of ischaemic stroke and major bleeding in the 2nd year was consistent across regions. All-cause mortality increased slightly from the 1st year to the 2nd year, which was not statistically significant and was not driven by cardiovascular (CV) mortality (Table 2). Conclusion In routine clinical practice in the Global ETNA-AF program, major bleeding and ischaemic stroke rates in >27,000 patients on edoxaban therapy declined from 1st year to 2nd year. Further analyses will investigate whether such trend is influenced by selection for healthier patients over time. Longer follow-up is needed to better understand long-term trends. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Table 1. Baseline characteristicsTable 2. Annualised clinical event rates

Background The ESC atrial fibrillation management guidelines recommend a risk-based approach to oral anticoagulant (OAC) therapy. How clinical practice aligns with these recommendations is of interest. Purpose To analyse real world data from Global ETNA-AF program in patient groups stratified by stroke and bleeding risk scores according to ESC guidelines. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program evaluating the safety and effectiveness of edoxaban in patients from European and Asian countries. Baseline characteristics and clinical event data at 2-year follow-up were analysed in 4 subgroups defined by CHA2DS2-VASc score (≥3 for female / ≥2 for male [OAC recommended] vs 2 for female / 1 for male [OAC should be considered]) and HAS-BLED score (≥3 [Bleeding risk high] vs Results Of 27,616 patients included in this analysis, 23,152 (83.8%) were in the “OAC recommended” category and 3,539 (12.8%) were in the “OAC should be considered” category. Only 3.3% of patients did not meet ESC guideline criteria for OAC initiation. Among patients with high bleeding risk, 98% were in the “OAC recommended” category. A similar distribution was observed across regions (Table 2). The recommended edoxaban dose was used in the vast majority (>80%) of patients across all risk stratification subgroups. In the “OAC recommended” category, patients with high bleeding risk had higher rates of thromboembolic, bleeding, and death events than those with low bleeding risk. Conclusion Data from routine clinical practice in Global ETNA-AF demonstrate high concordance of edoxaban treatment with ESC guidelines. Edoxaban dose is consistent with label recommendation in the vast majority (>80%) of patients. Clinical event rates were generally low across all risk groups, including acceptable bleeding rates in anticoagulated patients with high bleeding risk. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Table 1. Subgroups as per ESC guidelinesTable 2. Patient characteristics & events

As a novel X-ray focusing technology, lobster eye micro-pore optics (MPO) feature both a wide observing field of view and true imaging capability, promising sky monitoring with significantly improved sensitivity and spatial resolution in soft X-rays. Since first proposed by Angel (1979), the optics have been extensively studied, developed and trialed over the past decades. In this Letter, we report on the first-light results from a flight experiment of the Lobster Eye Imager for Astronomy ($LEIA$), a pathfinder of the wide-field X-ray telescope of the Einstein Probe mission. The piggyback imager, launched in July 2022, has a mostly un-vignetted field of view of $18.6^\circ \times 18.6^\circ $. Its spatial resolution is in the range of 4$-$7 arcmin in FWHM and the focal spot effective area is 2$-$3 cm$^2$, both showing only mild fluctuations across the field of view. We present images of the Galactic center region, Sco X-1 and the diffuse Cygnus Loop nebular taken in snapshot observations over 0.5$-$4 keV. These are truly wide-field X-ray images of celestial bodies observed, for the first time, by a focusing imaging telescope. Initial analyses of the in-flight data show excellent agreement between the observed images and the on-ground calibration and simulations. The instrument and its characterization are briefly described, as well as the flight experiment. The results provide a solid basis for the development of the present and proposed wide-field X-ray missions using lobster eye MPO., Comment: 11 pages, 4 figures. Accepted for publication in Astrophysical Journal Letter

This work introduces a neuromorphic chip featuring energy-efficient transfer learning capability using a new learning rule, Delta- Spike Time Dependent Plasticity (STDP). Delta STDP enables the neuromorphic chip to leverage on its previous knowledge to learn and to solve different but related tasks at a faster rate and with a limited number (few shots) of training samples. Compared to the unsupervised on-chip learning (OCL) rules, Delta STDP offers lower learning overheads as it has ~20% lower memory utilization and is operated only on the last layer of the Spiking Neural Network (SNN). A test chip fabricated in 40nm demonstrates this on-chip learning concept using DVS gesture and MNIST datasets. It achieves an accuracy of >80% for DVS gesture (using 9.8K training samples) with the total energy/learning is 5.2J at 0.5V. For MNIST, using only 2K training samples, it attains an accuracy of 97% and this learning convergence rate is >10x the conventional OCLs. The total energy/learning for MNIST dataset is 8.6mJ at 0.5V. Overall, the chip consumes 2.1 pJ/SOP at 0.5V, which is 12.3x-91.4x lower compared to the existing state-of-the-art.

ObjectivesThe Australian Government funded a nationwide diabetic retinopathy screening programme to improve visual outcomes for people with diabetes. This study examined the benefits and barriers of the programme, image interpretation pathways and assessed the characteristics of people who had their fundus photos graded by a telereading service which was available as a part of the programme.DesignMultimethod: survey and retrospective review of referral forms.SettingTwenty-two primary healthcare facilities from urban, regional, rural and remote areas of Australia, and one telereading service operated by a referral-only eye clinic in metropolitan Sydney, Australia.ParticipantsTwenty-seven primary healthcare workers out of 110 contacted completed a survey, and 145 patient referrals were reviewed.ResultsManifest qualitative content analysis showed that primary healthcare workers reported that the benefits of the screening programme included improved patient outcomes and increased awareness and knowledge of diabetic retinopathy. Barriers related to staffing issues and limited referral pathways. Image grading was performed by a variety of primary healthcare workers, with one responder indicating the utilisation of a diabetic retinopathy reading service. Of the people with fundus photos graded by the reading service, 26.2% were reported to have diabetes. Overall, 12.3% of eyes were diagnosed with diabetic retinopathy. Photo quality was rated as excellent in 46.2% of photos. Referral to an optometrist for diabetic retinopathy was recommended in 4.1% of cases, and to an ophthalmologist in 6.9% of cases.ConclusionsThis nationwide diabetic retinopathy screening programme was perceived to increase access to diabetic retinopathy screening in regional, rural and remote areas of Australia. The telereading service has diagnosed diabetic retinopathy and other ocular pathologies in images it has received. Key barriers, such as access to ophthalmologists and optometrists, must be overcome to improve visual outcomes.

The lower energy part of the hard X-ray band, 10–30 keV, still remains unexplored for X-ray polarimetry. A photo-electric polarimetry based on a CMOS imaging sensor typed GMAX0505 was proven to be a candidate polarimeter applied in this energy band, the pixel size is 2.5 μm and X-ray detection depth is around 5 μm. Due to a limitation of its pixel shape, the sensors can not give the polarization angle of incoming X-rays directly, but predict the angle by utilizing the asymmetric response at different polarization angle of X-rays. In this study, we construct a simplified sensor based on the structure of the GMAX0505, utilizing the GEANT4 toolkit. The variation trend of modulation factor in the simulation is similar with those measured in the reference at 12.4-keV and 24.8-keV X-rays. Based on the simulation framework, we change the pixel shape from square to hexagon with the same pixel pitch of 2.5 μm and define three directions along the symmetry axis of a pixel. Comparing the modulation curves obtained by solving the modulation curve function with three parameters, the modulation factor is around 10% and 23% at 12.4 keV and 24.8 keV in response to X-rays with different polarization angle and 100% linear polarization, the difference between predicted and incident polarization angle is less than 2.5° which is an estimate of the systematic error. Meanwhile, the degree of modulation is less than 1% in response to unpolarized X-rays. This study shows that similar sensors with a hexagonal pixel shape can give the modulation curve and directly predict the polarization angle of an X-ray source. It also provides a conceptual design for next photo-electric X-ray polarimetry in the energy band. In addition, the performance characterized by quality factor (QF) was compared for the sensors with different pixel pitch and the same pixel gap, the results show the QF is sensitive to a pixel pitch with different value and the value of the QF is maximum as a pixel pitch of the sensors is 0.75 μm under the same condition of pixel gap of 0.2 μm.

Background Store-and-forward (SAF) teledermatology uses electronically stored information, including patient photographs and demographic information, for clinical decision-making asynchronous to the patient encounter. The integration of SAF teledermatology into clinical practice has been increasing in recent years, especially during the COVID-19 pandemic. Despite this growth, data regarding the outcomes of SAF teledermatology are limited. A key distinction among current literature involves comparing the quality and utility of images obtained by patients and trained clinicians, as these metrics may vary by the clinical expertise of the photographer. Objective This narrative literature review aimed to characterize the outcomes of SAF teledermatology through the lens of patient- versus clinician-initiated photography and highlight important future directions for and challenges of the field. Methods A literature search of peer-reviewed research was performed between February and April 2021. Key search terms included patient-initiated, patient-submitted, clinician-initiated, clinician-submitted, store-and-forward, asynchronous, remote, image, photograph, and teledermatology. Only studies published after 2001 in English were included. In total, 47 studies were identified from the PubMed electronic database and Google Scholar after omitting duplicate articles. Results Image quality and diagnostic concordance are generally lower and more variable with patient-submitted images, which may impact their decision-making utility. SAF teledermatology can improve the efficiency of and access to care when photographs are taken by either clinicians or patients. The clinical outcomes of clinician-submitted images are comparable to those of in-person visits in the few studies that have investigated these outcomes. Coinciding with the onset of the COVID-19 pandemic, asynchronous teledermatology helped minimize unnecessary in-person visits in the outpatient setting, as many uncomplicated conditions could be adequately managed remotely via images captured by patients and referring clinicians. For the inpatient setting, SAF teledermatology minimized unnecessary contact during dermatology consultations, although current studies are limited by the heterogeneity of their outcomes. Conclusions In general, photographs taken by trained clinicians are higher quality and have better and more relevant diagnostic and clinical outcomes. SAF teledermatology helped clinicians avoid unnecessary physical contact with patients in the outpatient and inpatient settings during the COVID-19 pandemic. Asynchronous teledermatology will likely play a greater role in the future as SAF images become integrated into synchronous teledermatology workflows. However, the obstacles summarized in this review should be addressed before its widespread implementation into clinical practice.

The design of an agile 5° irregular ring metamaterial for a 24-cavity relativistic magnetron with diffraction output (MDO) using single-stepped cavities for frequency switching is presented. By inserting six pieces of 5° irregular ring metamaterials in place of the traditional 5° vanes of a slow wave structure, the operating frequency can be tuned. When U = 400 kV high voltage is applied, with an applied magnetic field B = 0.36 T, the operating mode can be switched from the TE41 mode with a frequency of 2.585 GHz to the TE31 mode with a frequency of 2.282 GHz. The 24-cavity anode block is an electromagnetic medium which can support the operating mode working under its cutoff frequency, and the insertion of the irregular ring metamaterials alters its dispersion relation. The results suggest a new technique to achieve frequency agility by changing the dispersion relation of the electromagnetic system using a metamaterial unit cell. This work seeks to design a compact high power microwave source for a narrowband directed microwave wave beam that is suitable for frequency agility.

In this paper, we extend the class of kernel methods, the so-called diffusion maps (DM) and ghost point diffusion maps (GPDM), to solve the time-dependent advection-diffusion PDE on unknown smooth manifolds without and with boundaries. The core idea is to directly approximate the spatial components of the differential operator on the manifold with a local integral operator and combine it with the standard implicit time difference scheme. When the manifold has a boundary, a simplified version of the GPDM approach is used to overcome the bias of the integral approximation near the boundary. The Monte-Carlo discretization of the integral operator over the point cloud data gives rise to a mesh-free formulation that is natural for randomly distributed points, even when the manifold is embedded in high-dimensional ambient space. Here, we establish the convergence of the proposed solver on appropriate topologies, depending on the distribution of point cloud data and boundary type. We provide numerical results to validate the convergence results on various examples that involve simple geometry and an unknown manifold. Additionally, we also found positive results in solving the one-dimensional viscous Burger's equation where GPDM is adopted with a pseudo-spectral Galerkin framework to approximate nonlinear advection term.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Background Age is a risk factor for ischemic stroke and bleeding in patients with atrial fibrillation (AF). The large dataset from the global prospective, noninterventional ETNA-AF program allows for analysis of the impact of age on clinical events in AF patients treated with edoxaban. Purpose Evaluate the safety and effectiveness of edoxaban by age subgroups and the impact of age on clinical events. Methods Baseline patient characteristics, thromboembolic and bleeding events, and mortality data were collected from patients with 2-year follow-up in ETNA-AF program and analyzed in defined age subgroups. Cox regression analysis was conducted using age as a continuous variable and clinical events as outcome variables. Results A total of 27,617 patients were categorized into four age subgroups: Conclusion Two-year follow-up data from the global ETNA-AF program support the use of edoxaban as a safe and effective treatment for AF patients across all age groups, including the very elderly, in routine clinical care. The impact of age on the risk of ICH was smaller than that of ischemic stroke and major bleeding.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Background and Purpose The large global Edoxaban Treatment in routiNe clinical prActice (ETNA)-AF program was designed to assess the safety and effectiveness of edoxaban, complementing randomized clinical trials. Methods ETNA collects data on patient characteristics and clinical events in unselected AF patients treated with edoxaban for stroke prevention, integrating data from prospective, noninterventional studies conducted in Europe, Japan, South Korea, and Taiwan. Results The 2-year follow-up analysis included 27,617 patients, the majority of whom (82.6%) received the recommended dose according to the local label. At baseline, the mean age was 73.6 ± 9.8 years and 58.1% were male. Half of the patients (50.5%) were 75 years or older. The CHA2DS2-VASc score was 3.3 ± 1.5, and the modified HAS-BLED score was 2.4 ± 1.1. The rate of ischemic stroke was 0.74%/yr, major bleeding 1.02%/yr, intracranial hemorrhage 0.29%/yr, and major gastrointestinal (GI) bleeding 0.51%/yr. All-cause mortality was 3.13%/yr, and cardiovascular (CV) mortality 1.45%/yr (see Table). Conclusion The rates of ischemic stroke and major bleeding events remained low globally and across regions during the two-year follow-up period in AF patients treated with edoxaban. Global(N = 27,617) Japan(N = 11,330) Korea/Taiwan(N = 2,870) Europe(N = 13,417) Age, mean (SD) 73.6 (9.8) 74.2 (10.1) 71.6 (9.5) 73.6 (9.5) Gender, male, % 58.1 59.4 60.2 56.6 Weight [kg], median (IQR) 69 (58, 81) 59 (51, 68) 65 (57, 73) 80 (70, 90) CrCL [mL/min], mean (SD) 68.7 (28.4) 63.9 (25.8) 63.4 (23.7) 74.4 (30.5) CHA2DS2-VASc, mean (SD) 3.3 (1.5) 3.5 (1.7) 3.1 (1.4) 3.2 (1.4) Mod. HAS-BLED≠, mean (SD) 2.4 (1.1) 2.4 (1.1) 2.3 (1.1) 2.5 (1.1) Edoxaban 60mg/30mg, % 53.5 / 46.5 27.6 / 72.4 48.8 / 51.2 76.4 / 23.6 2-year clinical events, N (%/year), [95% CI] Major Bleeding (ISTH) 477 (1.02) [0.93; 1.11] 188 (1.09) [0.94; 1.25] 51 (1.00) [0.74; 1.31] 238 (0.97) [0.85; 1.11] Intracranial Hemorrhage 135 (0.29) [0.24; 0.34] 68 (0.39) [0.30; 0.50] 17 (0.33) [0.19; 0.53] 50 (0.20) [0.15; 0.27] Major GI Bleeding 241 (0.51) [0.45; 0.58] 122 (0.70) [0.58; 0.84] 18 (0.35) [0.21; 0.55] 101 (0.41) [0.33; 0.50] Any Stroke 455 (0.97) [0.88; 1.06] 244 (1.41) [1.24; 1.60] 54 (1.06) [0.80; 1.38] 157 (0.64) [0.54; 0.75] Ischemic Stroke 347 (0.74) [0.66; 0.82] 179 (1.03) [0.89; 1.20] 43 (0.84) [0.61; 1.13] 125 (0.51) [0.42; 0.61] Hemorrhagic Stroke 99 (0.21) [0.17; 0.26] 67 (0.39) [0.30; 0.49] 9 (0.17) [0.08; 0.33] 23 (0.09) [0.06; 0.14] All-cause Death 1479 (3.13) [2.98; 3.30] 470 (2.70) [2.46; 2.96] 72 (1.40) [1.09; 1.76] 937 (3.80) [3.56; 4.05] CV Death 684 (1.45) [1.34; 1.56] 140 (0.80) [0.68; 0.95] 26 (0.50) [0.33; 0.74] 518 (2.10) [1.92; 2.29] ≠Excluding labile INR.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Background The optimal periprocedural management of direct oral anticoagulants (DOAC), including edoxaban, in patients undergoing catheter-based cardiovascular procedures is unknown, and mainly based on physician opinion and experience. Purpose To assess real-world management of edoxaban in patients undergoing cardiovascular procedures, and to report their clinical events. Methods Global EMIT-AF/VTE is a prospective study of periprocedural management in edoxaban-treated patients undergoing diagnostic and therapeutic procedures. We report the data from patients undergoing cardiovascular procedures. Timing and duration of edoxaban interruption were at the treating physician’s discretion. Outcomes were collected from 5 days before until 30 days post procedure. Primary outcome was the incidence of major bleeding (MB); secondary outcomes included incidence of clinically relevant non-major bleeding (CRNMB) and acute thromboembolic events (ATE). Results Data was collected from 301 and 311 procedures with arterial or venous access, respectively. Baseline characteristics are shown in Table 1. Edoxaban was not interrupted in 36.9% of arterial and 52.7% of venous procedures. Edoxaban was interrupted pre-procedure in 41% of arterial and 32.8% of venous procedures. The median periprocedural interruption was 2 days. The overall incidence of bleeding was very low. Any bleeding was reported in 8 patients undergoing arterial and 10 patients undergoing venous procedures (2.7% and 3.2%). MB or CRNMB occurred in 2 arterial and 3 venous procedures (0.7% and 1.0%) and ATE occurred in 5 arterial and 1 venous procedure (1.7% and 0.3%, Table 1). Conclusions In this study, the periprocedural risks of bleeding and thrombotic events were low. About a third of arterial access procedures and half of venous access procedures were performed without edoxaban interruption. Arterial(n = 301) Venous(n = 311) Baseline characteristics Age, year, mean (SD)Male, n (%)Weight (kg), mean (SD) 71.9 (8.5)211 (70.1%)80.8 (16.7) 64.6 (11.1)215 (69.1%)84.1 (17.4) CrCL (mL/min), mean (SD) CHA2DS2-VASc score, mean (SD)HAS-BLED score, mean (SD) 73.5 (29.8) 3.3 (1.5)2.0 (1.0) 88.9 (35.5) 2.2 (1.5)1.3 (1.0) Edoxaban 60 mg / 30 mg, % 73% / 26% 88% / 26% Coronary heart disease, n (%) Congestive heart failure, n (%) 101 (33.6%) 58 (19.3%) 51 (16.4%) 33 (10.6%) Interruption of edoxaban, n (%) No interruption Pre-procedure only Post-procedure only Pre- and post-procedure 111 (36.9%)125 (41.5%)12 (4.0%)53 (17.6%) 164 (52.7%)102 (32.8%)8 (2.6%)37 (11.9%) Clinical events, n (%) MB or CRNMBACSStroke/Transient ischemic attackCV mortalityAll-cause mortality 2 (0.7%)2 (0.7%)3 (1.0%)1 (0.3%)2 (0.7%) 3 (1.0%) 01 (0.3%)00

Alternaria leaf spot (ALS), caused by Alternaria spp., can occur wherever sugarbeet is grown. Infection by Alternaria spp. and disease management has historically been considered a minor issue in sugarbeet production in the United States. An increase of both incidence and severity in 2016 of ALS high enough to cause yield loss has been observed in Michigan. With a renewed need to consider potential management of this disease, the sensitivity was determined for populations of Alternaria spp. to three classes of fungicides currently labeled for management of leaf spot on sugarbeet, including demethylase inhibitor (DMI), quinone outside inhibitor (QoI), and organo-tin fungicides. Leaves with symptoms of ALS were sampled from sugarbeet fields in east-central Michigan and southwestern Ontario, Canada. Monoconidial isolates were obtained to determine sensitivity to each fungicide class above. A spiral gradient dilution method was used to estimate the fungicide effective concentration (in milligrams per liter) that caused a 50% inhibition of fungal growth in vitro for all isolates. Significant temporal shifts were detected in the frequencies of sensitivity phenotypes to DMI and QoI but not organo-tin fungicides from 2016 through 2017. Individual isolates of Alternaria spp. were recovered with cross-resistance to DMI and multiple resistance to DMI, QoI, and triphenyltin hydroxide fungicides. To our knowledge, this is the first report of a fungus other than Cercospora beticola with resistance to organo-tin fungicides. Fungicide sensitivity monitoring indicates that an effective integrated disease management approach combining fungicide efficacy trials and monitoring pathogen biology is essential for developing effective resistance management recommendations.

The objectives of the present study were to compare the dynamic of the growth and photosynthetic characteristics of cotton varieties contrasting in waterlogging (WL) tolerance when subjected to hypoxia stress. The growth of the WL-sensitive genotypes was notably inhibited by WL, mainly as a result of a significant reduction in the net photosynthesis (PN) after two days of hypoxia treatment; in the tolerant varieties, no significant changes in PN were observed until 8 d after hypoxia onset. The intercellular CO2 concentration and maximal photochemical efficiency of PSII significantly declined, and the nonphotochemical quenching increased in the sensitive varieties. Infrared thermography showed that a low stomatal conductance resulted in an increased leaf temperature under hypoxia stress. Spectral image analysis suggested that the pigment content and water content rapidly decreased in the leaves of the sensitive varieties. It is concluded that maintaining stomatal opening through the interaction of ethylene and abscisic acid may be an important strategy to improve waterlogging tolerance in cotton.

Plants secrete defense molecules into the extracellular space (the apoplast) to combat attacking microbes. However, the mechanisms by which successful pathogens subvert plant apoplastic immunity remain poorly understood. In this study, we show that PsAvh240, a membrane-localized effector of the soybean pathogen Phytophthora sojae, promotes P. sojae infection in soybean hairy roots. We found that PsAvh240 interacts with the soybean-resistant aspartic protease GmAP1 in planta and suppresses the secretion of GmAP1 into the apoplast. By solving its crystal structure we revealed that PsAvh240 contain six α helices and two WY motifs. The first two α helices of PsAvh240 are responsible for its plasma membrane-localization and are required for PsAvh240’s interaction with GmAP1. The second WY motifs of two PsAvh240 molecules form a handshake arrangement resulting in a handshake-like dimer. This dimerization is required for the effector's repression of GmAP1 secretion. Taken together, these data reveal that PsAvh240 localizes at the plasma membrane to interfere with GmAP1 secretion, which represents an effective mechanism by which effector proteins suppress plant apoplastic immunity.