Search

The anti-metastasis effect of oridonin in combination with oxaliplatin on colorectal cancer liver metastasis was studied using a BALB/c nude mouse model. The liver condition, bloody ascites, cholestasis, and liver metastasis scores in the three groups receiving oxaliplatin combined with oridonin were significantly milder than in the control group and importantly the anti-migratory effect of oxaliplatin combined with oridonin was obviously the strongest (p

Objective: The present study evaluated the effectiveness of a transdiagnostic group-based cognitive-behavioural therapy (CBT) programme for treating anxiety, comorbid depression, and functional imp...

This study evaluated the bioequivalence of China-manufactured biosimilar, HLX02, to reference China (CN)- and European Union (EU)-sourced trastuzumab. This was a two-part Phase 1 study conducted in healthy Chinese males. Part 1 evaluated the safety of different doses of HLX02 (2, 4, 6 or 8 mg/kg; intravenous infusion over 90 min, n = 3 per group). Part 2, a randomized, double-blind study, investigated the pharmacokinetics (PK), safety and immunogenicity of study drugs (HLX02 [n = 37], CN-trastuzumab [n = 35] or EU-trastuzumab [n = 37] at the dose suggested by Part 1 results). The primary PK endpoint was the area under the serum concentration–time curve from time 0 to infinity (AUCinf). Equivalence was concluded if the 90% confidence interval (CI) for the geometric least squares mean ratio (GLSMR) fell in the equivalence criteria of 0.80–1.25. In Part 1, all doses of HLX02 were well tolerated and 6 mg/kg was suggested for Part 2. The GLSMRs and 90% CIs for AUCinf were: 0.950 (0.891–1.013), 0.914 (0.858–0.973) and 0.962 (0.902–1.025) for HLX02 versus CN-trastuzumab, HLX02 versus EU-trastuzumab and CN-trastuzumab versus EU-trastuzumab, respectively. Secondary endpoints comparisons also fell in the equivalence criteria. Treatment-emergent adverse events were reported in 75.7, 86.5 and 70.3% of the subjects in HLX02, CN-trastuzumab, and EU-trastuzumab groups, respectively. No serious adverse events or deaths occurred. No treatment-related anti-drug antibodies were detected. This study demonstrated comparable safety profiles and PK bioequivalence among HLX02, CN-trastuzumab and EU-trastuzumab in healthy Chinese male subjects. ClinicalTrials.gov, NCT02581748, registered at October 19, 2015.

How to use modern information technology to efficiently and quickly obtain the personalized recommendation information required by students, and to provide high-quality intelligent services for schools, parents and students has become one of the hot issues in college research. This paper uses FP-growth association rule mining algorithm to infer student behavior and then use the collaborative filtering recommendation method to push information according to the inference result, and then push real-time and effective personalized information for students. The experimental results show that an improved FP-growth algorithm is proposed based on the classification of students. The algorithm combines the student behavior inference method of FP-growth algorithm with the collaborative filtering hybrid recommendation method, which not only solves the FP-tree tree branch. Excessive and collaborative filtering recommendation algorithm data sparseness problem, can also analyze different students' behaviors and activities, and accurately push real-time, accurate and effective personalized information for students, to promote smart campus and information intelligence The development provides better service.

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

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.

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

Background Previous studies have reported changes within grey matter (GM) volume in children with autism spectrum disorder (ASD); however, little is known about GM volume changes and the relation with symptom severity in Chinese boys with low functioning autism spectrum disorder (LFASD). Method GM volume was analysed using SPM 8 and compared between 16 boys with LFASD as well as 16 typically developing (TD) boys (using REST 1.8). Additionally, the correlation between GM volume and clinical symptoms was analysed, using subscales within the Autism Behaviour Checklist (ABC). Results The comparison showed a reduced volume of GM in 11 clusters in the boys with LFASD (i.e., the left inferior frontal gyrus, orbital part; right superior temporal gyrus, superior frontal gyrus, dorsolateral; precuneus and postcentral; bilateral rectus and middle temporal gyrus) and 1 area with increased GM volume (right caudate) compared to the TD group. Additionally, the GM volume of the left inferior frontal gyrus, orbital part was negatively correlated with the Social subscale score of the ABC (r = -0.765, P = 0.002), and the GM volume of the left Rectus was negatively associated with the Language, Body concept and Self-care subscale scores and the total score on the ABC(r = -0.624, P = 0.023; r = -0.657, P = 0.011; r = -0.618, P = 0.025; r = -0.625, P = 0.022). Further, the GM volume of the right Caudate was negatively correlated with the Sensory subscale on the ABC (r = -0.593, P = 0.033). Conclusion In conclusion, the current study's findings display that the GM volume was widely reduced in Chinese boys with LFASD compared to TD boys and negatively correlated with the clinical symptoms, indicating a possible pathological mechanism of LFASD.

The LPMWPC can be used as the Δ E detector for the low-energy charged particle detection. In order to increase the transmittance, the wires were adopted as the cathode. This work investigated the LPMWPC signal characteristics of this configuration and measured the gas gain with a mixture of 90%Ar and 10% CO2 from 1E3 to 1E5 Pa. From the test, the second pulse after the avalanche signal was observed, which proved to be caused by the ions' drifting near the cathode wire.

ObjectivesTo describe the experiences, priorities, and needs of patients with rheumatic disease and their parents during transition from paediatric to adult healthcare.SettingFace-to-face and telephone semistructured interviews were conducted from December 2018 to September 2019 recruited from five hospital centres in Australia.ParticipantsFourteen young people and 16 parents were interviewed. Young people were included if they were English speaking, aged 14–25 years, diagnosed with an inflammatory rheumatic disease (eg, juvenile idiopathic arthritis, juvenile dermatomyositis, systemic lupus erythematosus, panniculitis, familial Mediterranean fever) before 18 years of age. Young people were not included if they were diagnosed in the adult setting.ResultsWe identified four themes with respective subthemes: avoid repeat of past disruption (maintain disease stability, preserve adjusted personal goals, protect social inclusion); encounter a daunting adult environment (serious and sombre mood, discredited and isolated identity, fear of a rigid system); establish therapeutic alliances with adult rheumatology providers (relinquish a trusting relationship, seek person-focused care, redefine personal–professional boundaries, reassurance of alternative medical supports, transferred trust to adult doctor) and negotiate patient autonomy (confidence in formerly gained independence, alleviate burden on patients, mediate parental anxiety).ConclusionsDuring transition, patients want to maintain disease stability, develop a relationship with their adult provider centralised on personal goals and access support networks. Strategies to comprehensively communicate information between providers, support self-management, and negotiate individualised goals for independence during transition planning may improve satisfaction, and health and treatment outcomes.

Purpose The aim of this study is to describe the technique of subpalpebral antibiotic lavage (SAL), which is a highly therapeutic, efficient, and cost-effective method for managing severe bacterial keratitis. Methods This case report describes a 26-year-old woman with severe bacterial keratitis in the right eye due to contact lens overwear, with progressive corneal thinning, a hypopyon, impending perforation, and marked visual loss to perception of light despite treatment with intensive topical antibiotics. This was managed with SAL that involves the insertion of a cannula transcutaneously into the upper conjunctival fornix to provide continuous antibiotic irrigation of the ocular surface. Results By 11 weeks after presentation, the cornea and anterior chamber appeared clinically quiescent, and visual acuity improved to 20/40 corrected in the right eye. Conclusions Bacterial keratitis is a potentially blinding condition for which contact lens wear is an important risk factor. Most cases are successfully managed with topical medications; however, in cases of treatment failure, a second-line approach such as SAL can be sight-saving. SAL uses readily available equipment for the delivery of high concentrations of antibiotics to the ocular surface, thus increasing therapeutic efficacy and reducing nursing staff workload. Despite its advantages, the literature reveals apparent underutilization of this technique.

In recent years, with high accuracy, high frequency, considerable coverage of remote sensing images, map tiles, video surveillance, web crawlers, social networking platforms and other types of spatiotemporal data have exploded in geometric progression. Human society has come into the era of big data in time and space. In view of the characteristics of multi-attribute, multi-dimensional, multisource and heterogeneous spatiotemporal big data, how to make use of the emerging information technology means, combined with the geographic information data analysis means, the rapid mining and utilization of spatiotemporal big data has become a key problem to be solved. Built on the background of spatiotemporal big data and the process of geospatial cognition, this paper proposes a "cell-cube" spatiotemporal object data model. This paper constructs a model system of geo-spatiotemporal big data from the aspects of data organization, data storage and data partition, and abstracts the geo-space into an infinite number of geo-cells, and the adjacent geo-cells gather around the core cells to form geographical clusters, and the geographical clusters with similar attributes are clustered into geographical blocks. At the level of data organization, the spatial and temporal characteristics of structured data and unstructured data are considered as organizational dimensions, and a multi-factor extended cube data model is proposed. In the aspect of data storage, the organization model is further abstracted into the cell-cube structure of distributed data warehouse, and then the spatiotemporal data is stored uniformly. At the level of data segmentation, the mathematical table and space calculation method of multi-feature extended cube are proposed, and the geographical cell data division model based on connection is established. It solves the organization and management problem of spatiotemporal big data, provides a more complete data organization framework and solution for the application of geo-spatiotemporal big data, and promotes the development of deep mining of spatiotemporal extensive data in GIS. And to achieve space-time big data in the geographical space microscopic and the macroscopic unification cognition.

Geocoding is a fundamental task of Geographic Information System (GIS) processing and analysis. It allows the transformation between a location reference (i.e., an address or an alphanumeric code) and coordinates, which is often an essential step when performing spatial analysis, mapping, and other geolocation related processes. Providing software functionality through RESTful APIs is a common practice in geospatial applications. Client programs are able to access or process geospatial data easily through a lightweight and scalable RESTful web service. Existing geocoding RESTful API providers include Google Maps Geocoding API, ArcGIS Geocoding REST API, MapQuest Open Geocoding API and what3words (w3w) Geocoding API. Extensions of what3words geocoding system have recently been proposed to overcome its limitation of fixed resolution and lack of consideration of the third dimension. This paper considers one of the extensions, the Quadtree Extension Model (QTEM) and introduces a RESTful API that provides operations for forward geocoding, reverse geocoding, single line and polygon encoding, and centre points encoding for a given area. The resources published by the web service could be implemented by software programs performing indoor and outdoor location referencing, location marking and path finding. This API could facilitate various geographic applications such as facility management, emergency evacuation, navigation and student survey data management in a university campus environment.

Objectives We aimed to describe patients’ attitudes and experiences of transition from paediatric to adult healthcare in rheumatology to inform patient-centred transitional care programmes. Methods We searched MEDLINE, EMBASE, PsycINFO and CINAHL to August 2019 and used thematic synthesis to analyse the findings. Results From 26 studies involving 451 people with juvenile-onset rheumatic conditions we identified six themes: a sense of belonging (comfort in familiarity, connectedness in shared experiences, reassurance in being with others of a similar age, desire for normality and acceptance); preparedness for sudden changes (confidence through guided introductions to the adult environment, rapport from continuity of care, security in a reliable point of contact, minimizing lifestyle disruptions); abandonment and fear of the unknown (abrupt and forced independence, ill-equipped to hand over medical information, shocked by meeting adults with visible damage and disability, vulnerability in the loss of privacy); anonymous and dismissed in adult care (deprived of human focus, sterile and uninviting environment, disregard of debilitating pain and fatigue); quest for autonomy (controlled and patronized in the paediatric environment, liberated from the authority of others, freedom to communicate openly); and tensions in parental involvement (overshadowed by parental presence, guilt of excluding parents, reluctant withdrawal of parental support). Conclusion Young people feel dismissed, abandoned, ill-prepared and out of control during transition. However, successful transition can be supported by preparing for changes, creating a sense of belonging and negotiating parental involvement and autonomy. Incorporating patient-identified priorities into transitional services may improve satisfaction and outcomes in young people with juvenile-onset rheumatic conditions.

The main idea of developing Near Infrared Phase Contrast Imaging (NI-PCI) diagnostic on HL-2A tokamak is presented. Compared to the traditional PCI diagnostic which injects CO2 laser beam with a wavelength of 10.6 μm into plasma, NI-PCI using 1.55 μm laser has more advantages in measuring plasma density fluctuations due to shorter wavelength. This novel diagnostic is designed to detect plasma density perturbations with a wavenumber ranging from 2 cm−1 to over 30 cm−1 without significant phase scintillation effect. Comparison of diffraction effects between 10.6 μm and 1.55 μm laser beam shows that NI-PCI has a better response than PCI with a size-limited diagnostic window on HL-2A.

This article presents a general framework for recovering missing dynamical systems using available data and machine learning techniques. The proposed framework reformulates the prediction problem as a supervised learning problem to approximate a map that takes the memories of the resolved and identifiable unresolved variables to the missing components in the resolved dynamics. We demonstrate the effectiveness of the proposed framework with a strong convergence error bound of the resolved variables up to finite time and numerical tests on prototypical models in various scientific domains. These include the 57-mode barotropic stress models with multiscale interactions that mimic the blocked and unblocked patterns observed in the atmosphere, the nonlinear Schrodinger equation which found many applications in physics such as optics and Bose-Einstein-Condense, the Kuramoto-Sivashinsky equation which spatiotemporal chaotic pattern formation models trapped-ion modes in plasma and phase dynamics in reaction-diffusion systems. While many machine learning techniques can be used to validate the proposed framework, we found that recurrent neural networks outperform kernel regression methods in terms of recovering the trajectory of the resolved components and the equilibrium one-point and two-point statistics. This superb performance suggests that a recurrent neural network is an effective tool for recovering the missing dynamics that involves approximation of highdimensional functions. (c) 2020 Elsevier Inc. All rights reserved.

Objective To improve neurologists’ awareness of spine gout by showing a rare case of tophaceous gout in thoracic spine and a summary of vertebral gout in order. Material and methods We reported a case of a 36-year-old male with a 2-year-history of hyperuricemia. Neurological examination suggested that the strength of his lower limbs decreased. Bilateral Babinski's sign and ankle clonus were positive. He had no bladder or bowel dysfunction. Computed tomography of the thoracic spine showed occupied lesions at the T9, T10 levels which led to the spinal stenosis. Magnetic resonance imaging of the thoracic spine revealed epidural disease at T9, T10 levels. A resection of the occupying lesion in the thoracic spinal canal was performed, tophaceous gout was diagnosed by the pathological examination. We also provide a brief review of literature on 30 cases of spine tophaceous gout. Result Spinal tophaceous gout is rare, gout can involved in any spine level, but the probability of occurrence of thoracic spine is the least. Most patients had a history of hyperuricemia or peripheral tophus, the most common symptoms are back pain, when the pain stone compression spinal cord or nerve root, there will be the corresponding neurological symptoms or signs. Conclusions The spinal gout should be considered when a patient has chronic or acute back pain and/or neurological symptoms, with mass on sides of the vertebras on MRI, especially when the patient has a history of hyperuricemia, the pathology examination can confirm the diagnosis.

Water body identifying is critical to climate change, water resources, ecosystem service and hydrological cycle. Multi-layer perceptron(MLP) is the popular and classic method under deep learning framework to detect target and classify image. Therefore, this study adopts this method to identify the water body of Landsat8. To compare the performance of classification, the maximum likelihood and water index are employed for each study area. The classification results are evaluated from accuracy indices and local comparison. Evaluation result shows that multi-layer perceptron(MLP) can achieve better performance than the other two methods. Moreover, the thin water also can be clearly identified by the multi-layer perceptron. The proposed method has the application potential in mapping global scale surface water with multi-source medium-high resolution satellite data.

Circular RNAs (CircRNAs) are a type of non-coding RNAs (NcRNAs) with a closed annular structure. Until next-generation sequencing (NGS) is developed, the misunderstanding of circRNAs 'splicing error' has changed, and the mysterious veil of circRNAs has been revealed. NGS provides an approach to investigate circRNAs. Many scholars point out that circRNAs may play an important role in many diseases, especially cancer. At the same time, exosomes, as a kind of extracellular vesicles loaded with many contents, are a hotspot in recent years. They can act as 'messengers' between cells, especially in cancer. Lately, it is interesting circRNAs are enriched and stable in exosomes, also called exo-circRNAs, and there have been several articles on circRNAs associated with exosomes. In this review, we summarize the characteristics of circRNAs, especially its main functions. Then, we briefly introduce exosomes and their function in cancer. Finally, the known relation between circRNAs and exosomes is discussed. With further researches, exo-circRNAs may be a novel pathway for cancer diagnosis and targeted therapy.

A new type of fully passive power generator based on oscillating foil is proposed and numerically tested. The shedding vortexes drive the foil to pitch around the pitching center, and the resulting periodic lift force drives the foil to swing around an arm. Nonlinear spring is utilized to improve the adaptation and energy extraction performance of the power generator. Two-dimensional Navier-Stokes simulation at Re = 1100 are carried out to study the fluid-foil interaction as well as the robustness and performance of energy extraction. Numerical results demonstrate that small pitching amplitudes (0°–90°) lead to higher power coefficient but smaller efficiency and drag force than the large pitching amplitudes (100°–170°). What's more, the range of synchronization is extended from 0.4–1.3 to 0.4–2.5 in terms of speed ratio by the nonlinear spring, indicating that the nonlinear spring can increase the adaptation of the system. Besides, the power coefficient can be improved at some off-design points and reach maximum value of 1.04. In general, the nonlinear spring provides the simplest way to improve the adaptation or robustness of the power generator without increasing the cost and complexity of the system or reducing the performance of the generator.

A 20-channel edge Lyman-Alpha-Based Beam emission spectroscopy (LAB) system, which diagnoses edge density fluctuations by measuring the Doppler-shifted Lyman-alpha line (n= 2 → 1, 121.53 nm) emitting via the interaction of neutral beams and plasma particles, is under developing on the HL-2A tokamak. The radial observation range covers the main plasma from R= 1.98 m to 2.05 m with a spatial resolution of about 0.33 cm and a temporal resolution of 1 μs. The overall design for this system is completed, including the reflective collection optics, the spectrometer with a reflective toroidal grating, the detector array, and the vacuum system. Compared with the traditional beam emission spectroscopy (BES) which measures the Balmer-alpha line (n= 3 → 2, 656.10 nm), LAB promises to achieve higher signal-to-noise measurements of smaller-scale fluctuations and therefore detect previously unobserved low-amplitude pedestal turbulence.

In this article we present the design of a phase contrast imaging (PCI) system on the HL-2A tokamak. This diagnostic is developed to infer line integrated plasma density fluctuations by measuring the phase shift of an expanded CO2 laser beam passing through magnetically confined high temperature plasmas. This system is designed to diagnose plasma density fluctuations with the maximum wavenumber of 15 cm−1. The designed wavenumber resolution is 2 cm−1, and the time resolution can reach 2 μs. The broad kρs ranging from 0.2 to 3 makes it suitable for turbulence measurement.

Casestudy Gene fusions involving tropomyosin receptor kinase genes, NTRK (NTRK1-3), are important in tumorigenesis. Larotrectinib, a selective NTRK inhibitor, is recently approved to treat NTRK fusion positive solid tumors. We herein report a case of soft tissue sarcoma harboring two STRN-NTRK2 gene fusions, with good clinical response to firstline larotrectinib treatment. Results A 35 year-old female presented with pain in the right gluteal region, and a large solid mass without overlying erythema, edema and induration was identified. Initial MRI study showed a heterogenous, vascular and partially necrotic mass (16.5 x 12.9 x 10.4 cm) centered in the right gluteus medius and maximus muscles. A core biopsy of the mass showed a cellular mesenchymal neoplasm with round/ovoid cells, high mitosis (21 per 10 HPFs) and focal staghorn type vessels, reminiscent of solitary fibrous tumor. However, STAT6 immunostaining was negative. Additional immunostains show no specific lineage. Our in-house NGS fusion panel showed two in-frame STRN- NTRK2 fusions, containing the same 5’ partner sequence (exon 1-3) of STRN, with the 3’ fusion partner starting from either the exon 15 or the exon 16 of NTRK2. Due to the large size and location of the tumor, larotrectinib was initiated as firstline therapy. The patient noticed a quick amelioration of tumor related pain, and a significant shrinkage of the size of tumor following the initial 7-day treatment. On post-treatment day 52, MRI showed the tumor significantly decreased in size to 7.7 x 7.4 x 6.6 cm with satisfactory symptomatic relief. Conclusion NTRK2 fusions are relatively rare when compared with NTRK1 and NTRK3, especially in sarcoma. Of note, the only other report in the literature of NRTK2 fusion- positive sarcoma also showed SFT-like morphology, and the patient responded well to larotrectinib as second line therapy.

Cloud and Shadow removal is a significant step in remote sensing image process. As we all know, the ground object coverage type of the same area of the remote sensing image has little change in the short term. But for cloud and shadow coverage areas, the ground object coverage type has large change. Therefore, according to the difference between the two Landsat / OLI images caused by changes in the cover, this paper presents a method of extracting clouds and shadows based on differences in luminance values. This method selects two thresholds for the difference of brightness values, and extracts the clouds and shadows respectively, and validates them with random point method, which can obtain high precision of extracting cloud and shadow and satisfy the actual application needs.

Crater-detection approaches can be divided into four categories: manual recognition, shape-profile fitting algorithms, machine-learning methods and geological information-based analysis using terrain and spectral data. The mainstream method is Shape-profile fitting algorithms. Many scholars throughout the world use the illumination gradient information to fit standard circles by least square method. Although this method has achieved good results, it is difficult to identify the craters with poor "visibility", complex structure and composition. Moreover, the accuracy of recognition is difficult to be improved due to the multiple solutions and noise interference. Aiming at the problem, we propose a method for the automatic extraction of impact craters based on spectral characteristics of the moon rocks and minerals: 1) Under the condition of sunlight, the impact craters are extracted from MI by condition matching and the positions as well as diameters of the craters are obtained. 2) Regolith is spilled while lunar is impacted and one of the elements of lunar regolith is iron. Therefore, incorrectly extracted impact craters can be removed by judging whether the crater contains "non iron" element. 3) Craters which are extracted correctly, are divided into two types: simple type and complex type according to their diameters. 4) Get the information of titanium and match the titanium distribution of the complex craters with normal distribution curve, then calculate the goodness of fit and set the threshold. The complex craters can be divided into two types: normal distribution curve type of titanium and non normal distribution curve type of titanium. We validated our proposed method with MI acquired by SELENE. Experimental results demonstrate that the proposed method has good performance in the test area.

Objective To assess the effect of maternal low flow oxygen administration during the second stage of labour on umbilical cord artery pH. Design A randomised controlled trial. Setting A tertiary teaching hospital in China. Population Women in the second stage of labour with no complications. Methods About 443 women were randomly allocated to receive either supplemental oxygen at a flow rate of 2 l/min or a sham supplementation by nasal cannula. Healthcare providers, women and outcome assessors were blinded to allocation. Main outcome measures Umbilical cord artery pH and fetal heart rate (FHR) pattern. Results Baseline characteristics were similar between the two groups. There were no significant differences between the two groups in the umbilical cord artery pH [median 7.261, interquartile range (IQR) 7.228–7.295 versus 7.266 (IQR 7.232–7.297), P = 0.64], the proportion with pH less than 7.2 [30/219 versus 34/224, P = 0.66, RR (relative risk) 0.9, 95% CI 0.57–1.42], and the proportion with normal FHR pattern (147/219 versus 153/224, P = 0.79, RR 0.98, 95% CI 0.86–1.12). Maternal partial pressure of dissolved oxygen was significantly higher in the oxygen group than in the sham group [median 150.0 mmHg (IQR 142.6–156.7) versus 112.0 (IQR 104.8–118.3), P

Background: Systemic inflammation is associated with poor prognosis in pts with ABC. The JAK/STAT pathway is a key regulator of inflammatory signaling, associated with tumorigenesis, cell survival, and progression. We evaluated the efficacy and safety of RUX, a JAK1/JAK2 inhibitor, plus CAPE in pts with HER2-negative ABC and high systemic inflammation defined by the modified Glasgow Prognostic Score (mGPS). Methods: In this double-blind phase 2 trial, pts were randomized 1:1 to 21 day cycles of RUX+CAPE or PBO+CAPE: RUX 15 mg or PBO PO BID for 21 d; CAPE 1000 mg/m2 PO BID for 14 d. Key inclusion criteria were systemic inflammation by mGPS of 1 or 2 (ie, CRP >10 mg/L), ECOG performance status ≤2, ≤2 prior chemotherapy regimens, and no prior CAPE. The primary endpoint was overall survival (OS); key secondary endpoints were progression-free survival (PFS), objective response rate (ORR; complete [CR] + partial response [PR]) per RECIST v1.1, clinical benefit rate (CBR; CR + PR + stable disease for ≥6 mo), duration of response, and safety. Treatment differences in OS and PFS were analyzed by the log-rank test; HRs and CIs were analyzed by the Cox proportional hazards model. Results: Baseline characteristics were similar between pts randomized to RUX+CAPE (n=76) vs PBO+CAPE (n=73): mGPS status (1, 82.9% vs 83.6%), hormone receptor (HR) status (positive, 67.1% vs 63.0%), and number of prior chemotherapy regimens for ABC (0, 50.0% vs 50.7%; 1, 38.2% vs 34.2%; 2, 9.2% vs 13.7%). Median treatment durations were 85 d with RUX in the RUX+CAPE group and 65 d with PBO in the PBO+CAPE group. Median OS was 11.2 mo with RUX+CAPE vs 10.9 mo with PBO+CAPE (HR, 0.932; 95% CI, 0.59–1.46; P=0.762). Median OS was 6.1 mo with RUX+CAPE vs 5.5 mo with PBO+CAPE in HR-negative pts and 11.7 mo and 12.2 mo in HR-positive pts. Median PFS was 4.5 mo with RUX+CAPE and 2.5 mo with PBO+CAPE (HR, 0.737; 95% CI, 0.49–1.12; P=0.151). Median PFS was 2.1 mo with RUX+CAPE vs 2.2 mo with PBO+CAPE in HR-negative pts and 6.1 mo and 4.1 mo in HR-positive pts. ORRs were 28.9% and 13.7% (P=0.024) in the RUX+CAPE and PBO+CAPE arms, respectively. The CBRs were 13.2% and 6.8%, respectively (P=0.278). Worsening of hematologic toxicity was higher and rates of grade 3/4 palmar-plantar erythrodysethesia (PPE) were lower (1.4% vs 12.7%, respectively) with RUX+CAPE (Table). Safety RUX+CAPE (n=71)PBO+CAPE (n=71)%All-GradeGrade 3/4All-GradeGrade 3/4Nonhematologic Adverse Event*Fatigue56.35.643.74.2Nausea54.98.549.35.6Diarrhea47.98.526.82.8PPE46.51.438.012.7Vomiting38.05.629.64.2Hypokalemia15.58.57.02.8Worsening of Hematologic Toxicity†Anemia80.323.956.37.0Lymphopenia40.815.545.112.7Neutropenia39.411.322.52.8Thrombocytopenia39.411.315.51.4*Most common all-grade (≥35%) or grade 3/4 (≥5%) events in the RUX+CAPE arm (safety group). †Laboratory abnormalities. Conclusion: These data support the prognostic capabilities of the mGPS. The addition of RUX to CAPE for pts with ABC and high systemic inflammation was associated with an improved ORR compared with PBO+CAPE, but did not improve OS or PFS. Citation Format: O'Shaughnessy J, DeMichele A, Ma C, Richards P, Yardley DA, Wright G, Kalinsky K, Steis R, Diab S, Kennealey G, Geschwindt R, Jiang W, Rugo H. A randomized, double-blind, phase 2 study of ruxolitinib (RUX) or placebo (PBO) in combination with capecitabine (CAPE) in patients (pts) with advanced HER2-negative breast cancer (ABC) and elevated C-reactive protein (CRP), a marker of systemic inflammation [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-04.

A new concept of power generator using self-induced oscillating foil to extract energy from fluid is proposed and tested in the present study. The pitching motion of the elliptical foil is induced by the downward shed vortexes of the foil. Two-dimensional Navier-Stokes simulations at Re=104 are conducted to study the fluid-foil interaction as well as the performance of energy extraction. Three kinds of motion trajectories are concerned, i.e. pitching motion, pitching motion combined with streamwise plunging and pitching motion combined with transverse plunging. The investigations are undertaken over a wide range of structural parameters (mass ratio, stiffness factor and damping coefficient). Numerical results reveal that the pitching motion combined with transverse plunging can achieve best energy extraction performance. With well-tuned structural parameters, the power generator can reach maximum power coefficient of 32% and energy extraction efficiency of 20%. Hence, it demonstrates that the promising self-induced oscillating foil can achieve satisfactory energy extraction performance without pitching motion actuator.

A new concept of power generator using self-induced oscillating hydrofoil with upwind arm and downwind arm configurations to extract energy from fluid is proposed and numerically tested in the present study. The pitching motion of the symmetrical hydrofoil with camber is induced by the shedding vortexes downward the hydrofoil, and a pitching damper with critical pitching angle is utilized to control the pitching amplitude. Two-dimensional Navier-Stokes simulation at Re = 1100 are carried out to study the fluid-hydrofoil interaction as well as the performance of energy extraction. The effects of camber, critical pitching angle, arm length and swing direction are systematically studied. Numerical results demonstrate that camber and critical pitching angle have significant effects on the energy extraction performance of the power generator, and optimized camber and critical pitching angle configurations can increase the power coefficient and efficiency dramatically. With best structural parameters and hydrofoil shape, the power generator can reach maximum power coefficient of 0.8 and energy extraction efficiency of 0.285. Besides, the upwind arm configuration achieves better performance over the downwind arm configuration. The effect of arm length is not so profound as other parameters in our study.

Background The introduction of trastuzumab in combination with chemotherapy has significantly improved clinical outcomes for patients with HER2-positive breast cancer. HLX02 was developed as a trastuzumab biosimilar with the potential to increase market competition and treatment accessibility in China and around the world. Methods We conducted a randomised, double-blind, parallel-controlled equivalence study (HLX02-BC01) at 89 study centres in China, Philippines, Poland and Ukraine. Eligible women were aged 18 years or older, had histologically confirmed HER2+ breast cancer, an Eastern Cooperative Oncology Group performance status of 0 to 1, and estimated life expectancy ≥3 months. Patients were randomised at 1:1 to receive an intravenous dose of 8 mg/kg of HLX02 or EU-trastuzumab with docetaxel on Day 1 -Cycle 1 followed by a dose of 6 mg/kg once every 3 weeks in 3-weekly cycles for up to a maximum of 12 months. The primary endpoint was best overall response rate at Week 24 (ORRwk24) evaluated by blinded central imaging review. Secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS), safety outcomes with immunogenicity and incidence of adverse events up to 12 months. Results Of 1046 patients enrolled, 649 were randomly allocated to receive HLX02 (n = 324) or EU-trastuzumab (n = 325). The ORR was 71.0% (230 of 324 patients; 95% CI: 66.0, 75.9) for HLX02 and 71.4% (232 of 325 patients; 95% CI: 66.5, 76.3) for EU-trastuzumab. The p-value at 95% CI (p = 0.952) was completely contained within the pre-defined equivalence boundaries of ± 13.5%. The difference in ORR between the 2 treatments was 0.4 (95% CI: -7.4, 6.6). Safety outcomes and immunogenicity were similar between the treatment groups at Week 24. Conclusions Among women with HER2+ metastatic breast cancer, the use of HLX02 compared with EU-trastuzumab resulted in an equivalent ORR at Week 24. All secondary efficacy and safety analyses at Week 24 also supported the conclusion of therapeutic equivalence; HLX02 does not demonstrate new safety signals in comparison with EU-trastuzumab. Further study results at Month 12 will be reported in August once the study is unblinded. Clinical trial identification NCT03084237; EudraCT: 2016-000206-10. Legal entity responsible for the study Shanghai Henlius Biotech, Inc. Funding Shanghai Henlius Biotech, Inc. Disclosure B. Xu: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. Q. Zhang: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. T. Sun: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. W. Li: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. Y. Teng: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. X. Hu: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. I. Bondarenko: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. H. Adamchuk: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. L. Zhang: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. D. Trukhin: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. B. Li: Full / Part-time employment: Shanghai Henlius Biotech,Inc. B. Shan: Full / Part-time employment: Shanghai Henlius Biotech,Inc. J. Cheng: Full / Part-time employment: Shanghai Henlius Biotech,Inc. T. Peng: Full / Part-time employment: Shanghai Henlius Biotech,Inc. W. Jiang: Full / Part-time employment: Shanghai Henlius Biotech,Inc. S. Liu: Full / Part-time employment: Shanghai Henlius Biotech,Inc. X. Zhang: Full / Part-time employment: Shanghai Henlius Biotech,Inc. Q. Wang: Full / Part-time employment: Shanghai Henlius Biotech, Inc. E. Liu: Full / Part-time employment: Henlix Biotech, Inc. A.Y. Luk: Full / Part-time employment: Shanghai Henlius Biotech,Inc.

Temporal arteritis (TA), or giant cell arteritis, is a systemic autoimmune vasculitis affecting patients over 50 years of age. It can cause rapid, irreversible bilateral vision loss in older adults and is therefore considered an ophthalmological emergency. Many of the symptoms and signs of TA can be vague, non-specific and gradual in onset, often leading to a delayed or inaccurate diagnosis. As such, it is important for a wide variety of primary optometrists and health practitioners to maintain a robust understanding of the clinical presentation, key investigations and time-sensitive management of this disease, as early initiation of treatment for TA can be vision- and life-saving.

Objectives The objective of this study was to determine the prevalence of trial registration in health research, whether trial registration status and timing vary depending on trial characteristics, and the relationship between trial registration status and risk of bias. Study Design and Setting We systematically reviewed all clinical trials published from January to June 2017 in 28 high- and low-impact factor general and specialty medicine journals. Results We identified 370 trials and assessed risk of bias in 183 trials. Trial registration rates were high; 95% of trials were registered prospectively or retrospectively before enrollment completion. Larger sample size, multiple recruitment countries, and primary industry funding were all predictors of earlier trial registration. Prospectively registered trials had a significantly lower risk of bias compared to unregistered trials across all domains. Prospectively registered trials had a similar risk of bias compared to retrospectively registered trials across four out of six domains, and a lower risk of bias across the remaining two domains. Conclusion Trial registration is an imperfect proxy for risk of bias. Systematic reviewers should assess risk of bias on a case-by-case basis and conduct sensitivity analyses excluding high risk of bias studies. In the longer term, mechanisms should be implemented to facilitate prospective registration of all trials.