Search

In order to improve the accuracy and anti-interference of underground environment positioning, a coal mine underground ultra wideband based positioning system is designed. Aiming at the problems of large accidental errors and poor robustness in traditional UWB positioning, the extended Kalman filter algorithm is added to improve the accuracy of the positioning system. Aiming at the problems of large accidental errors and poor robustness in traditional UWB positioning, the extended Kalman filter algorithm is added to improve the accuracy of the positioning system. The experimental results show that the Kalman filter can improve the positioning accuracy and reduce the system accidental error.

TGF-β1 has long been considered as a key mediator in diabetic kidney disease (DKD) but anti-TGF-β1 treatment fails clinically, suggesting a diverse role for TGF-β1 in DKD. In the present study, we examined a novel hypothesis that latent TGF-β1 may be protective in DKD mice overexpressing human latent TGF-β1. Streptozotocin-induced Type 1 diabetes was induced in latent TGF-β1 transgenic (Tg) and wild-type (WT) mice. Surprisingly, compared to WT diabetic mice, mice overexpressing latent TGF-β1 were protected from the development of DKD as demonstrated by lowing microalbuminuria and inhibiting renal fibrosis and inflammation, although blood glucose levels were not altered. Mechanistically, the renal protective effects of latent TGF-β1 on DKD were associated with inactivation of both TGF-β/Smad and nuclear factor-κB (NF-κB) signaling pathways. These protective effects were associated with the prevention of renal Smad7 from the Arkadia-induced ubiquitin proteasomal degradation in the diabetic kidney, suggesting protection of renal Smad7 from Arkadia-mediated degradation may be a key mechanism through which latent TGF-β1 inhibits DKD. This was further confirmed in vitro in mesangial cells that knockdown of Arkadia failed but overexpression of Arkadia reversed the protective effects of latent TGF-β1 on high glucose-treated mesangial cells. Latent TGF-β1 may protect kidneys from TGF-β1/Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation in diabetes through inhibiting Arkadia-mediated Smad7 ubiquitin degradation.

BACKGROUND AND PURPOSE: Efficient detection of metastases is important for patient’ treatment. This prospective study was to explore the clinical value of contrast-enhanced T2 FLAIR in imaging brain metastases using half-dose gadobenate dimeglumine. MATERIALS AND METHODS: In vitro signal intensity of various gadolinium concentrations was explored by spin-echo T1-weighted imaging and T2 FLAIR. Then, 46 patients with lung cancer underwent nonenhanced T2 FLAIR before administration of half-dose gadobenate dimeglumine and 3 consecutive contrast-enhanced T2 FLAIR sequences followed by 1 spin-echo T1WI after administration of half-dose gadobenate dimeglumine. After an additional dose of 0.05 mmol/kg, 3D brain volume imaging was performed. All brain metastases were classified as follows: solid-enhancing, ≥ 5 mm (group A); ring-enhancing, ≥ 5 mm (group B); and lesion diameter of

P138 Table 1Employment status of COVID-19 dischargesN 138 Essential services 41 (30) Office/admin 37 (27) Healthcare 16 (12) Non essential services 15 (11) Public transport 10 (7) Enforcement 4 (3) Heavy Goods Vehicle driver 3 (2) Carers 2 (1) Unknown 10 (7) ConclusionOur preliminary data suggests significant symptom burden within 6 weeks post discharge after a COVID-19 infection admission, which may impact on the ability of patients to return to work. In the present analysis there was no significant interaction between return-to-work status and covid severity.

Macrophage migration inhibitory factor (MIF) is pleiotropic cytokine that has multiple effects in many inflammatory and immune diseases. This study reveals a potential role of MIF in acute kidney injury (AKI) in patients and in kidney ischemic reperfusion injury (IRI) mouse model in MIF wild‐type (WT) and MIF knockout (KO) mice. Clinically, plasma and urinary MIF levels were largely elevated at the onset of AKI, declined to normal levels when AKI was resolved and correlated tightly with serum creatinine independent of disease causes. Experimentally, MIF levels in plasma and urine were rapidly elevated after IRI‐AKI and associated with the elevation of serum creatinine and the severity of tubular necrosis, which were suppressed in MIF KO mice. It was possible that MIF may mediate AKI via CD74/TLR4‐NF‐κB signalling as mice lacking MIF were protected from AKI by largely suppressing CD74/TLR‐4‐NF‐κB associated renal inflammation, including the expression of MCP‐1, TNF‐α, IL‐1β, IL‐6, iNOS, CXCL15(IL‐8 in human) and infiltration of macrophages, neutrophil, and T cells. In conclusion, our study suggests that MIF may be pathogenic in AKI and levels of plasma and urinary MIF may correlate with the progression and regression of AKI.

Interior noise substantially influences the physiological and psychological sensations of passengers in pure electric vehicles (EVs). Numerous studies have examined the development of acoustic prediction models and acoustic metrics to evaluate EV interior sound quality. However, the existing studies have the following four deficiencies: (1) the interior noise of EVs was studied only on general roads, and few EV samples were tested; (2) the physical acoustical metrics and psychoacoustic metrics did not comprehensively reflect all the characteristics of the interior noise of EVs; (3) features added to the acoustic prediction models were manually extracted and selected and were highly dependent on prior knowledge of acoustic theory and experience; and (4) the most common acoustic prediction models used to evaluate interior noise have shallow architectures. To overcome these deficiencies, we introduce a novel intelligent acoustic model based on deep neural networks (DNNs) called the Laplacian score-deep belief network (LS-DBN). We used the LS-DBN to evaluate the sound quality of EV interior noise. To verify the effectiveness of the proposed method, the interior noises of ten EVs were recorded on eight different road surfaces and corresponding subjective evaluations were conducted. In addition, noise features were extracted adaptively using the LS-DBN, and adaptively extracted features and manually extracted features were compared. The performance of the LS-DBN was validated against a conventional DBN and a back-propagation neural network (BPNN). The results show that the proposed LS-DBN model is superior to the conventional DBN and BPNN in terms of accuracy and stability, and it is highly efficient. Thus, the LS-DBN can achieve good prediction results when evaluating the interior sound quality of EVs.

PURPOSE/OBJECTIVE(S) Absolute lymphocyte count (ALC) and systemic immune-inflammation index (SII) have been identified as predictive biomarkers for several malignancies. We aim to investigate the impact of SII and ALC on outcomes in patients with HCC (Hepatocellular Carcinoma) treated with two cycles of anti-PD-1 therapy. MATERIALS/METHODS Totally 110 HCC patients treated with anti-PD-1 therapy were enrolled in our study. Clinicopathological data were retrospectively collected and reviewed. Kaplan-Meier analysis and the log-rank test were used to calculate and compare overall survival (OS) and progression-free survival (PFS) between ALC < 0.785 Vs. ≥ 0.785 and SII < 968.2 Vs. ≥ 968.2. All potential risk factors were analyzed by univariate and multivariate cox regression analysis. RESULTS There are 98 (89.1%) patients had Child-Pugh class A liver function. The most choric liver disease was hepatitis B virus (HBV) infection in 106 (96.4%) patients. Barcelona Clinic Liver Cancer (BCLC) stage was C in 92 (83.6%) patients and B in 18 (16.4%). The mean PFS and OS are 5.5 month and 6.5 month respectively. The Kaplan-Meier survival curves showed that elevated SII correlated decreased PFS (P < 0.0001) and low ALC correlated with decreased PFS (P = 0.0011). And elevated SII correlated with decreased OS (P < 0.001) and low ALC correlated with decreased OS (P = 0.0056). Multivariable Cox regression analyses demonstrated that ALC, systemic immune inflammation index (SII), liver-directed therapy, China liver cancer staging (CNLC) and albumin-bilirubin (ALBI) score correlated with PFS (P = 0.001, P < 0.0001, P = 0.003, P = 0.014, P = 0.017, respectively). And ALC, systemic immune inflammation index (SII), liver-directed therapy and China liver cancer staging (CNLC) correlated with OS (P = 0.001, P < 0.0001, P = 0.004, P = 0.024, respectively). CONCLUSION The ALC and SII may predict PFS and OS in HCC patients who receive the anti-PD-1 therapy. ALC and SII may be useful biomarkers for patient's risk stratification and individualized therapeutic decision-making.

CUPID-Mo is a cryogenic detector array designed to search for neutrinoless double-beta decay (0νββ) of 100Mo. It uses 20 scintillating 100Mo-enriched Li2MoO4 bolometers instrumented with Ge light detectors to perform active suppression of α backgrounds, drastically reducing the expected background in the 0νββ signal region. As a result, pileup events and small detector instabilities that mimic normal signals become non-negligible potential backgrounds. These types of events can in principle be eliminated based on their signal shapes, which are different from those of regular bolometric pulses. We show that a purely data-driven principal component analysis based approach is able to filter out these anomalous events, without the aid of detector response simulations.

In order to analyze the expression of nuclear-associated antigen Ki-67 protein in adenocarcinoma of esophagogastric junction and its correlation with clinicopathological features and prognosis, immunohistochemistry was used to detect the expression of nuclear-associated antigen Ki-67 protein in 165 tissues of adenocarcinoma of esophagogastric junction. The clinical data such as age, gender, tumor size, differentiation degree, pathological stage, TNM stage, lymphatic metastasis, surgical approaches and overall survival(OS) of 165 cases of adenocarcinoma of esophagogastric junction patients admitted to the First Affiliated Hospital of Guangdong Pharmaceutical University from January 2007 to June 2015 were analysed, retrospectively. Kaplan-Meier was used for univariate survival analysis and Cox regression was used for multivariate survival analysis to explore the independent risk factors for the prognosis of adenocarcinoma of esophagogastric junction. The value of p

Background. Several comorbidities contribute to an increased risk of infections in Parkinson’s disease (PD) as the disease progresses. However, few studies have examined the correlation between sepsis and PD. Aim. The aim of this study is to disclose the presentation and outcome of serious infection in patients with PD in the emergency department. Methods. This retrospective cohort study enrolled patients with PD who had serious infection and were admitted to the emergency department between January 2007 and December 2013. For clinical comparison, we compared the clinical features, laboratory data, and outcomes with those of age- and sex-matched patients who had serious infection but not PD. Results. There were a total of 1,200 episodes of infected PD patients and 2,400 age- and sex-matched infected patients without PD as disease controls. PD patients had fewer comorbidities and lower severity of infectious disease but longer hospital stays than control group patients. The incidences of respiratory tract and urinary tract infections were higher in PD patients. The levels of inflammatory and organ dysfunction biomarkers in PD were lower and compatible with the severity of infectious disease. A total of 86 (7.2%) infected PD patients died during the 28-day admission compared to 339 (14.1%) in non-PD patients. Serum C-reactive protein, bandemia, and lactate could be used to predict mortality in infected PD patients. Conclusions. In infected patients with PD, respiratory and urinary tract infections were the two most common infectious sources. Empiric therapy based on experience could treat both respiratory and urinary tract infections. Early diagnosis and treatment are essential for survival.

Background.Peritoneal dialysis (PD) is an increasingly popular therapeutic option for patients with advanced renal failure. However, intra-abdominal adhesions (IAA) represent a major unsolved problem in adequate PD performance. In this study, we investigated the role of previous abdominal surgery on the presence of subsequent IAA as well as outcomes in those patients with PD who had subsequent IAA.Methods.Two hundred and two patients who received continuous ambulatory peritoneal dialysis were prospectively enrolled in this study. We compared the PD adequacy indices and outcomes for technical failure in patients with and without subsequent IAA at presentation and a minimum of 2 years of follow-up.Results.Subsequent IAA accounted for 19% (38/202) of patients. Patients who had previous abdominal surgery had higher risks of subsequent IAA especially those patients who had higher mean ages (P=0.023). PD adequacy indices including both 24-hour dialysate volume and peritoneal WCcr L/week/1.73 m2were significantly lower in patients who had, as compared to those who did not have subsequent IAA (P=0.003 and 0.018, respectively). Although patients who had subsequent IAA had decreased PD adequacy, the development of technical failures during PD maintenance did not show significant differences at the 2-year minimum follow-up study.Conclusions.Subsequent IAA is not rare, especially in high-risk patients including those with previous abdominal surgery and higher mean ages. Although decreased PD adequacy after IAA was found, the development of technical failures was not significantly different at the 2-year minimum follow-up study.

Study Objective To evaluate the feasibility, efficiency, and safety of manual morcellation in laparoendoscopic single-site (LESS) supracervical hysterectomy. Design Retrospective study (Canadian Task Force classification II-2). Setting A teaching hospital. Patients One hundred and ninety patients with symptomatic uterine leiomyomas and/or adenomyosis who underwent LESS supracervical hysterectomy. Interventions Manual morcellation through the umbilical wound. Measurements and Main Results Time of operation, blood loss volume, specimen weights, rate of morcellation, requirement for blood transfusion, hospital length of stay, and prevalence of postoperative cyclic spotting were recorded. The median weight of the uterine corpus was 245 g (range, 100–1960 g). The median total operation time was 69 minutes (range, 36–183 minutes). The median volume of blood loss was 50 mL (range, 10–850 mL). The median level of hemoglobin reduction was 1 g/dL (range, −1 to 3.2 g/dL). The incidence of intraoperative blood transfusion was 3.2%, and the mean manual morcellation rate was 38.9 ± 15 g/minute. The incidence of postoperative cyclic spotting was 10.5%. Conclusion Safe and effective LESS surgery requires a minimal surgical incision compared with conventional laparoscopic surgery and laparotomy. Manual morcellation was found to be effective and safe in removing solid tumors in this population.

In the present study, the WRF-Chem model is used to assess contributions of residential coal combustion (RCC) emissions to the air quality in Beijing–Tianjin–Hebei (BTH) during a persistent air pollution episode from 9 to 25 January 2014. In general, the predicted temporal variations and spatial distributions of the mass concentrations of air pollutants are in good agreement with observations at monitoring sites in BTH. The WRF-Chem model also reasonably reproduces the temporal variations in aerosol species when compared with the aerosol mass spectrometer measurements in Beijing. The RCC emissions play an important role in the haze formation in BTH, contributing about 23.1 % of PM2.5 (fine particulate matter) and 42.6 % of SO2 during the simulation period on average. Organic aerosols dominate the PM2.5 from the RCC emissions in BTH, with a contribution of 42.8 %, followed by sulfate (17.1 %). The air quality in Beijing is remarkably improved when the RCC emissions in BTH and the surrounding areas are excluded in model simulations, with a 30 % decrease in PM2.5 mass concentrations. However, if only the RCC emissions in Beijing are excluded, the local PM2.5 mass concentration is decreased by 18.0 % on average. Our results suggest that the implementation of the residential coal replacement by clean energy sources in Beijing is beneficial to the local air quality. Should residential coal replacement be carried out in BTH and its surrounding areas, the air quality in Beijing would be improved remarkably. Further studies would need to consider uncertainties in the emission inventory and meteorological fields.

Background Angiotensin-converting enzyme inhibitors (ACEi) are widely employed to deter the progression of chronic kidney disease (CKD). Besides controlling hypertension and reduction of intra-glomerular pressure, ACEi appear to have anti-fibrotic effects in the renal cortex. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), an endogenous tetrapeptide that is degraded by ACE, has also been shown to ameliorate the pro-fibrotic phenotype displayed in CKD in our recent study. Whether the anti-fibrotic properties of ACEi are mediated by Ac-SDKP has not been fully investigated. Methods To delineate the role of Ac-SDKP in ACE blockade, 12-week-old male BALB/c mice underwent sham operation or unilateral ureteric obstruction (UUO). UUO mice were subjected to: i) vehicle; ii) captopril or iii) captopril in conjunction with S17092, a prolyl oligopeptidase inhibitor. After 7 days, mice were sacrificed and kidneys harvested for analyses. Results After UUO, there were heightened expressions of collagen I, collagen III, fibronectin and α-SMA associated with significant levels of tubulointerstitial injury on histological examination. Furthermore, p44/42 Mitogen-Activated Protein Kinase (MAPK) and Transforming Growth Factor Beta 1(TGF-β1) signaling were up-regulated. These were significantly ameliorated by captopril treatment alone but unaffected by co-administration of captopril with S17092. Captopril treatment had resulted in elevated urinary Ac-SDKP levels, an effect which was eliminated by the co-administration with S17092. Conclusion This study allowed the investigation of the renoprotective property of ACEi in the absence of Ac-SDKP and proved conclusively that Ac-SDKP is the prime anti-fibrotic mediator of captopril, acting via p44/42 MAPK and TGF-β1 signaling pathways. Future research to expand CKD armamentarium should explore the utility of augmenting Ac-SDKP levels. This article is protected by copyright. All rights reserved.

COVID‐19 is infected by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and can cause severe multiple organ injury and death. Kidney is one of major target organs of COVID‐19 and acute kidney injury (AKI) is common in critically ill COVID‐19 patients. However, mechanisms through which COVID‐19 causes AKI remain largely unknown and treatment remains unspecific and ineffective. Here, the authors report that normal kidney‐specifically overexpressing SARS‐CoV‐2 N develops AKI, which worsens in mice under ischemic condition. Mechanistically, it is uncovered that SARS‐CoV‐2 N‐induced AKI is Smad3‐dependent as SARS‐CoV‐2 N protein can interact with Smad3 and enhance TGF‐β/Smad3 signaling to cause tubular epithelial cell death and AKI via the G1 cell cycle arrest mechanism. This is further confirmed in Smad3 knockout mice and cells in which deletion of Smad3 protects against SARS‐CoV‐2 N protein‐induced cell death and AKI in vivo and in vitro. Most significantly, it is also found that targeting Smad3 with a Smad3 pharmacological inhibitor is able to inhibit SARS‐CoV‐2 N‐induced AKI. In conclusion, the authors identify that SARS‐CoV‐2 N protein is a key mediator for AKI and induces AKI via the Smad3‐dependent G1 cell cycle arrest mechanism. Targeting Smad3 may represent as a novel therapy for COVID‐19‐asscoaited AKI., In this article, the authors discover that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) N protein can bind and activate Smad3 to induce kidney cell death and cause acute kidney injury (AKI) via p21‐dependent G1 cell cycle arrest mechanism. Targeting Smad3 with a pharmacological inhibitor SIS3 can inhibit SARS‐CoV‐2 N‐induced AKI.

Background Pembrolizumab is a check point inhibitor that targets programmed cell death receptor ligand 1 (PD-L1). However, check-point inhibitors are associated with its characteristic adverse event know as immune related adverse events that can affect a myriad of organ systems. In the hepatobiliary system, the most commonly described iRAE is hepatitis/hepatotoxicity and latest oncology guidelines offer recommendations on treatment and followup of immunotherapy related hepatitis (1). However, a more rare presentation of iRAE, that have only been described as case reports or case series, is secondary cholangitis. We report one of such a case. Aims Case report Methods Case report Results The patient is a 55 year-old Caucasian female know for lung adenocarcinoma presented to the emergency room on May 5th, 2020, having received her 8th cycle of pembrolizumab. Her blood works mildly elevated transaminitis; ALT 78 U/L, AST 11 U/L, alkaline phosphate of 130 U/L, and total bilirubin of 3.5 umol/L. MRI of the abdomen showed a normal appearing liver without focal parenchymal lesion, no biliary stones or obstructing masses, dilated common bile duct at 11 mm with small pericholecystic free fluid, and normal gall badder thickness of 2 mm. There was also notion of minimally prominent intrahepatic biliary radicles seen within the CBD. Etiology workup of cholestatic transaminitis was negative. A diagnosis of immunotherapy related sclerosing cholangitis was posed and the patient was treated with MMF and prednisone with good response. Conclusions Discussion This patient seems to have developed immunotherapy mediated cholangitis. Liver biopsy when performed in liver injury tend to show lobular hepatitis, with liver parenchyma infiltrated with lymphocytes and focal necrosis with acidophilic bodies. However, there seems to be another, less frequent pattern of injury described with pembrolizumab and associated with cholangiopathy, resembling primary biliary cholangitis. It is characterized with portal tracts enlarged with fibrosis and inflammatory cells infiltration; infiltrating cells are lymphocytes (2). Biliary epithelium with fibrosis with CD8+ T cells infiltration seem to be recurrently reported in case reports. (3, 4). Other cases have been describe in the literature. In many cases, steroid therapy was attempted, but response rates seem to be inconsistent. Nivolumab related cholangitis have been also been described and characterized by extra hepatic bile duct dilatation along with negative immunological markers such as ANA and IgG4 in patients with non-small cell lung cancer, and seems to respond only moderately to steroid therapy (6). Retrospective data of nivolumab related cholangiopathy seems to suggest that there is favourable response to the combination of MMF and steroid therapy (7). Funding Agencies None

Glioblastoma (GBM) is a debilitating disease associated with poor prognosis and a limited response to therapies. At present, patients receive chemotherapy with temozolomide, following radiation therapy and surgery; however, none of the treatments are curative, and clinical trials are recommended as the preferred option for eligible patients. Regrettably, only 3-5% of GBM patients survive 3 years or more. Therefore, it is imperative to develop efficacious therapies. To achieve this goal, we have developed a computation method that allows us to impute drug sensitivity when transcriptome data is available. We have applied this imputation method to several publicly available normal brain tissue, low grade glioma (LGG), and GBM patient datasets to identify compounds of interest. We also compared the leads from these patient/in vivo data analyses with those generated from previous imputations made using a novel GBM avatar model; this model was created by introducing different genetic driver mutations using CRISPR-Cas9 into human induced pluripotent stem cells, followed by differentiation to GBM-associated mutations containing neural progenitor cells (NPC) and animal engraftment to develop human adult GBM models. We applied the drug imputation to over 1200 human normal brain, LGG and GBM samples as well as 18 NPC, tumor sphere and engrafted GBM tumor avatar samples. For each sample, we imputed over 700 drug sensitivity scores. Our model was trained independently using one of two separate high throughput in vitro drug screening datasets (GDSC and CTRP). To identify drugs showing higher sensitivity in GBM than in normal tissues, we compared the imputed drug sensitivity for each compound between samples belonging to the precancerous or the non-high grade glioma state (represented by the normal tissue and LGG data) and samples representing the cancerous or high grade glioma state (GBM). We identified a number of compounds showing higher imputed sensitivity in samples belonging to the cancerous state when compared to those in the precancerous or LGG state. We were also able to cross check compounds of interest with our avatar data. Among them, some agents have been used in the clinic to treat GBM, supporting the validity of integration of our computational tool with novel ex vivo GBM avatars and GBM clinical data in the development of new therapeutic strategy for GBM. More importantly, we have identified other compounds with various mechanism of action that show higher efficacy in GBM and will be further evaluated with the goal to quickly translate into clinic. Therefore, we can successfully integrate ovel experimental and computational models to speed up drug discovery with the goal of finding new therapeutics for GBM. Citation Format: Danielle Maeser, Robert Gruener, Robert Galvin, Tomoyuki Koga, Frank B. Furnari, David Largaespada, Clark C. Chen, Stephanie R. Huang. Identification of efficacious treatment for glioblastoma (GBM) by applying computational drug sensitivity imputation to novel GBM avatars and GBM clinical datasets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1300.

In this paper, a harmonic field current injection method is proposed for torque ripple reduction in 6-stator/4-rotor-pole (6s/4r) variable flux reluctance machines (VFRMs). Initially, the torque production of VFRM is analyzed based on an analytical torque model and harmonic analysis. The torque ripple of 6s/4r VFRM is found to have multiples of third harmonics. Then, one finite-element analysis (FEA)-based and one analytical equation-based method are developed to calculate the magnitude of the injected harmonic current. Both methods are proved to be effective in torque ripple reduction. Finally, the influence of the inductance mismatch on the proposed method is investigated. It shows that the torque ripple reduction performance is not affected much unless the fundamental component of nominal inductance is underestimated. The feasibility and effectiveness of the proposed methods are validated by both 2-D FEA and experimental test.

Background Among the adaptive immune cells, B cells, dominated by IgA producing plasma cells (PC), are critical for intestinal homeostasis. However, the B-cell response remains under studied in ulcerative colitis (UC). Methods Using single-cell RNA sequencing (scRNA seq), single-cell IgH sequencing (sc IgH seq), multiparameter flow cytometry (FC), mass cytometry (MC) and immunofluorescent microscopy (IF), we have comprehensively defined the landscape of intestinal and circulating B cells in patients with UC. A Cohort of 88 patients with active UC, 14 patients with quiescent UC and 43 healthy volunteers were recruited. Two validation cohorts comprising of 53 patients with active UC, 59 patients with quiescent UC and 65 healthy volunteers (Validation cohort 1) and 65 patients with active UC, 42 patients with quiescent UC and 36 healthy volunteers (Validation cohort 2) were also studied. Results scRNA seq and FC demonstrate a dramatic increase in proliferating (Ki67+) plasmablasts (PB) as well as IgG+ PC in the inflamed colon of UC patients. Additionally, a significant increase in short-lived (CD19+CD45+) PC was observed during colonic inflammation. scIgH seq further demonstrates a significant decrease in somatic hypermutations and the diversity of intestinal PC of patients with active UC. Genes associated with Fc-dependent macrophage signalling were enriched in areas of active disease and were associated with non-response to TNF therapy. In circulation, a significant increase in a4b7+ gut-homing PC was noted that related to disease extent, severity and complications (defined by treatment non-response, hospitalisations and surgery). Conclusion Active UC results in an immature, IgG-dominated PB/PC response in inflamed GI tissue and an increase in the frequency of gut-homing PC in circulation that relates to disease activity and complications and may be used to monitor disease course. These data provide novel insights into the pathogenesis of UC with major implications for existing and emerging therapeutic agents.

The Toxicology for the 21st Century (Tox21) program is an initiative between multiple U.S. federal agencies aiming to predict chemical toxicity based on the data from in vitro assays, which would greatly reduce the effort of traditional whole animal studies. The program has constructed a library of ∼10 000 environmental chemicals and drugs, representing a wide range of structural diversity, which is being tested in triplicate against a battery of cell-based assays in a quantitative high-throughput screening (qHTS) format. A standardised process has also been established to enable assay development, automated robotic screening, massive data acquisition, new data analysis approaches needed to integrate and characterise the data, and data sharing. To date, the Tox21 program has generated over 120 million data points that have been made publicly available, thus contributing to the big data in toxicology. In this chapter, examples are given to show how to build in vivo toxicity prediction models based on in vitro activity profiles of compounds and prioritise compounds for further in-depth toxicological studies. These data sets were also successfully used in a “crowd-source” challenge with its goal to encourage public participation to develop new methods and models for toxicity prediction.

GPRs (Ground Penetrating Radar) are widely adopted in underground space survey and mapping, because of their advantages of fast data acquisition, convenience, high imaging resolution and NDT (Non Destructive Testing) inspection. However, at present, the automation of the GPR data post-processing is low and the identification of underground objects needs expert interpretation. The heavy manual interpretation labor limits the GPR applications in large-scale urban scenarios. According to the latest research, it is still an unsolved problem to detect targets or defects in GPR data automatically and needs further exploration. In this paper, we propose a deep learning method for real-time detection of underground targets from GPR data. Seven typical targets in urban underground space are identified and labelled to construct the training dataset. The constructed dataset is consist of 489 labelled samples including rainwater wells, cables, metal/nonmetal pipes, sparse/dense steel reinforcement, voids. The training dataset is further augmented to produce more samples. DarkNet53 convolutional neural network (CNN) is trained using the constructed training dataset including realistic data and augmented data to extract features of the buried objects. And then the end-to-end YOLO detection framework is used to classify and locate the seven specific categories buried targets in the GPR data in real time. Experiments show that the automatic real-time detection method proposed in this paper can effectively detect the buried objects in the ground penetrating radar image in real time at Shenzhen test site (typical urban road scene).

Aims Prenatal alcohol exposure is common with 20%–40% of mothers in the UK drinking in pregnancy. The serious effects of alcohol on the developing fetus have been well described: with effects on growth, facial morphology and the central nervous system(CNS). Some regions of the brain appear to be disproportionately affected e.g. corpus callosum and caudate nucleus. The primary aim of this study was to produce an objective evaluation of the morphological relationship between the face, brain structure and cognitive outcome. By measuring the face-brain morphology of the newborn infant, then it might be possible to predict future outcome at the earliest possible stage. Methods Structural brain MRI and high-resolution 3D facial images were obtained of prenatal alcohol exposed (n=76) and unexposed control(n=45) Caucasian children (age range 6.8–17.7 years). Extending existing 3D modelling techniques allowed us to build morphometric shape models of individual regions of the face, together with the shape of the corpus callosum. These joint models enable statistical analysis of correlations between neurocognitive measures and joint face-brain shape variation. in both unexposed and alcohol exposed individuals. In the second phase of this analysis, we are acquiring 3D and 2D images of the face, and a midline representation of the corpus callosum using transfontanelle ultrasound in newborn infants. Results Using individual analysis of facial form and brain regions in 3D, we were able to accurately identify individuals with foetal alcohol syndrome, a diagnosis at the most severe end of the alcohol-exposed spectrum. Using combined modelling of face and brain, these results improved the accuracy of discrimination (ROC >0.95). Additionally, we observed a loss of normal pattern and asymmetry in the caudate nucleus, which were correlative with neurocognitive performance. In the latter phase of this study, we designed a protocol for imaging corpus callosum, and applying statistical modelling techniques for face-brain morphological analysis in neonates. Conclusions There is growing evidence of a correlation between central facial and central brain morphology. Identifying facial dymorphia, structural brain anomalies and the relations between them and cognition is important as it could ultimately help determine the extent of neuro-structural damage caused by in utero alcohol exposure, allowing identification of risk groups and improving earlier diagnosis.

Rationale: TGF-β/Smad signaling is the central mediator for renal fibrosis, however, its functional role in acute kidney injury (AKI) is not fully understood. We previously showed Smad2 protects against renal fibrosis by limiting Smad3 signaling, but details on its role in acute phase are unclear. Recent evidence showed that TGF-β/Smad3 may be involved in the pathogenesis of AKI, so we hypothesized that Smad2 may play certain roles in AKI due to its potential effect on programmed cell death. Methods: We established a cisplatin-induced AKI mouse model with TGF-β type II receptor or Smad2 specifically deleted from renal tubular epithelial cells (TECs). We also created stable in vitro models with either Smad2 knockdown or overexpression in human HK2 cells. Importantly, we evaluated whether Smad2 could serve as a therapeutic target in both cisplatin- and ischemic/reperfusion (I/R)-induced AKI mouse models by silencing Smad2 in vivo. Results: Results show that disruption of TGF-β type II receptor suppressed Smad2/3 activation and attenuated renal injury in cisplatin nephropathy. Furthermore, we found that conditional knockout of downstream Smad2 in TECs protected against loss of renal function, and alleviated p53-mediated cell apoptosis, RIPK-mediated necroptosis and p65 NF-κB-driven renal inflammation in cisplatin nephropathy. This was further confirmed in cisplatin-treated Smad2 knockdown and overexpression HK2 cells. Additionally, lentivirus-mediated Smad2 knockdown protected against renal injury and inflammation while restoring renal function in established nephrotoxic and ischemic AKI models. Conclusions: These findings show that unlike its protective role in renal fibrosis, Smad2 promoted AKI by inducing programmed cell death and inflammation. This may offer a novel therapeutic target for acute kidney injury.

The squeak and rattle (S&R) noise of a vehicle’s suspension shock absorber substantially influences the psychological and physiological perception of passengers. In this paper, a state-of-the-art method, specifically, a genetic algorithm-optimized support vector machine (GA-SVM), which can select the most effective feature subsets and optimize the model’s free parameters, is proposed to identify this specific noise. A vehicular road test and a shock absorber rig test are conducted to investigate the relationship between these features, and then an approach for quantifying the shock absorber S&R noise is given. Pre-processed signals are decomposed through a wavelet packet transform (WPT), and two criteria, namely, the wavelet packet energy (WPE) and wavelet packet sample entropy (WPSE), are introduced as the feature extraction methods. Then, the two extracted feature sets are compared based on this genetic algorithm. Another advanced method, known as the genetic algorithm-optimized back propagation neural network (GA-BPNN), is introduced for comparison to illustrate the superiority of the newly developed GA-SVM model. The result shows that the WPSE can extract more useful features than the WPE and that the GA-SVM is more effective and efficient than the GA-BPNN. The proposed approach could be retrained and extended to address other fault identification problems.

The sound quality of vehicle interior noise strongly influences passengers’ psychological and physiological perceptions. To predict the sound quality of interior noise, a vehicle road test with four compact cars has been conducted. All recorded interior noise signals have been denoised via a discrete wavelet transform (DWT) denoising procedure and subsequently evaluated subjectively through the anchor semantic differential (ASD) test by a jury. In addition, a novel prediction method, namely, regression-based deep belief networks (DBNs), which substitute the support vector regression (SVR) layer for the linear softmax classification layer at the top of the general DBN’s structure, has been proposed to predict the interior sound quality. The parameter selection of the DBN model has been compared and studied using a grid search. In addition, four conventional machine-learning-based methods have been introduced to enable a comparison of the performance with the newly developed DBNs. Furthermore, the feature fusion ability of DBNs has been studied by varying the amount of information that the dataset offers. The results show the following: (1) The accuracy and robustness of the proposed DBN-based sound quality prediction approach are better than those of the 4 other referenced methods. (2) The multiple-feature fusing process can strongly affect the prediction performance. (3) Finally, the unsupervised pre-training process of the DBNs can enhance the information fusing ability. Finally, the newly proposed regression-based DBN approach may be extended to address other vehicle noises in the future.

In this paper, a detailed finite element model of the combined connection with bolts and welds is elaborated to analyze the failure mode and bearing capacity of this connection under shear load. The main focus of this study is the evaluation of the coupled behavior of bolts and welds. Failure modes and load sharing are analyzed via several finite element numerical tests for different weld sizes. Varying the weld height and length, bearing capacity utilization rates of bolts and welds are also assessed. The results obtained indicate that the weld contribution to tensile load-bearing capacity is always dominant in the combined connection with bolts and welds. As the weld-to-bolt strength ratio (the ratio of the design value of the weld joints to the bolt joints’ bearing capacity) is about 1.0, the welds and bolts in the combined connection can work together with a good performance. With the increasing weld-to-bolt strength ratio, the load share of the bolts decreases. When the weld-to-bolt strength ratio exceeds 2.0, the contribution of bolts in the combined connection is negligible.

Acute kidney injury (AKI) is exacerbated in C-reactive protein transgenic mice but alleviated in Smad3 knockout mice. Here we used C-reactive protein transgenic/Smad3 wild-type and C-reactive protein transgenic/Smad3 knockout mice to investigate the signaling mechanisms by which C-reactive protein promotes AKI. Serum creatinine was elevated, and the extent of tubular epithelial cell necrosis following ischemia/reperfusion-induced AKI was greater in C-reactive protein transgenics but was blunted when Smad3 was deleted. Exacerbation of AKI in C-reactive protein transgenics was associated with increased TGF-β/Smad3 signaling and expression of the cyclin kinase inhibitor p27, but decreased phosphorylated CDK2 and expression of cyclin E. Concomitantly, tubular epithelial cell proliferation was arrested at the G1 phase in C-reactive protein transgenics with fewer cells entering the S-phase cell cycle as evidenced by fewer bromodeoxyuridine-positive cells. In contrast, the protection from AKI in C-reactive protein transgenic/Smad3 knockout mice was associated with decreased expression of p27 and promotion of CDK2/cyclin E–dependent G1/S transition of tubular epithelial cells. In vitro studies using tubular epithelial cells showed that C-reactive protein activates Smad3 via both TGF-β–dependent and ERK/MAPK cross talk mechanisms, Smad3 bound directly to p27, and blockade of Smad3 or the Fc receptor CD32 prevented C-reactive protein–induced p27-dependent G1 cell cycle arrest. In vivo , treatment of C-reactive protein transgenics with a Smad3 inhibitor largely improved AKI outcomes. Thus, C-reactive protein may promote AKI by impairing tubular epithelial cell regeneration via the CD32-Smad3-p27–driven inhibition of the CDK2/cyclin E complex. Targeting Smad3 may offer a new treatment approach for AKI.

Purpose: Oxidative stress has been shown to reflect on the development of sepsis and disease severity. In the present study, we evaluated the effects of increased levels of oxidative stress and decreased antioxidant coactivity in patients with sepsis, and the importance of oxidative stress on treatment outcomes. Methods: Biomarkers of oxidative stress (thiobarbituric acid-reactive substances [TBARS]) and antioxidant capacity (glutathione peroxidase [GPx] and glutathione content [thiol]) were prospectively evaluated along with biochemical and clinical data in 100 patients with sepsis on days 1, 4, and 7 after admission. Results: The TBARS level of the non-survivor group was significantly higher than that of the survivor group on day 1 and day 4 and negatively correlated with thiol upon admission. However, thiol was positively correlated with lactate concentration. The TBARS and lactate levels upon admission were independent predictors of fatality. Conclusions: We conclude that a TBARS cut-off value of 18.30 μM can be used to predict fatality, and an increase in the TBARS concentration by 1 μM will increase the fatality rate by 0.94%. In the panel of biomarkers, the TBARS assay can be considered as a prognostic biomarker for the treatment of patients with sepsis.

This document describes monitoring features related to media streams in Web real-time communication (WebRTC). It provides a list of RTCP Sender Report, Receiver Report and Extended Report metrics, which may need to be supported by RTP implementations in some diverse environments. It lists a set of identifiers for the WebRTC's statistics API. These identifiers are a set of RTCP SR, RR, and XR metrics related to the transport of multimedia flows.

Background Rheumatoid arthritis (RA) is one of the most common autoimmune diseases and it affects 0.5%–2.0% of the human population worldwide.1Though disease modifying anti-rheumatic drugs (DMARDs) can improve the clinical condition of patients with RA, toxicities of these drugs will be accumulated with long-term use and the unwanted side effects still cannot be avoided. 18β-glycyrrhetinic acid (18β-GA), an active component of licorice, exhibits potential anti-cancer, anti-inflammatory, anti-allergic, and anti-microbial activities.2 Moreover, 18β-GA has been elucidated to attenuate hepatotoxicity or nephrotoxicity caused by chemical drugs, included methotrexate(MTX)[.2 These evidences suggested 18 β-GA may become a candidate for low toxicity RA therapy as the mechanism was revealed. Objectives The aim of this study is to investigate the underline mechanism of 18β-GA on anti-inflammation and anti-proliferation in in vivo and in vitro models of RA. Methods CIA rats were treated with 18β-GA, methotrexate, celecoxib and three combination therapies for 30 days. Paw swelling volume, thromboxane synthase (TxAS), proliferating cell nuclear antigenprotein (PCNA), interleukin (IL)−1β, IL-6, and thromboxane B2 (TxB2) were detected to assess the anti-inflammation and anti-proliferation effects of different treatments. To further study the potential mechanism, TNF-α-induced in vitro model was applied. With different treatments, cell proliferation was detected using MTS, meanwhile, cell cycle distribution and apoptosis were examined by flow cytometric analysis. Western blotting and real-time quantitative PCR were conducted to evaluate many moleculars that involved in interested pathways like COX-2/TxA2 pathway and AKT/FOXO3a pathway. Results The paw swelling volume and histological data indicate that 18β-GA administration attenuates arthritis severity in rats with CIA. Lower level of IL-1β, IL-6, and TxB2 were observed in serum of 18β-GA group as compared with model group. In addition, synovial immunohistochemistry data shows that 18β-GA decreased about half of PCNA intensity induced by collagen. However, in vivo, all data exhibited no significant differences among groups with monotherapy and combination therapy. In vitro, 18β-GA inhibited the mRNA and protein levels of COX-2 and TxAS that induced by TNF-α in MH7A cell line. Both p-JNK and NF-κB1 (p50) were inhibited by 18β-GA as well as TxAS siRNA transfection. Moreover, 18β-GA inhibited MH7A proliferation in a time- and dose- dependent manner from MTS assay. Flow cytometric analysis revealed that 18β-GA induced cell apoptosis and caused G1-phase cell cycle arrest. Finally, AKT and FOXO3a were predominantly phosphorylated by TNF-α, whereas such effect was blocked by18β-GA treatment. Conclusions This study has for the first time shown that 18β-GA has an inhibitory role in synovial cell inflammation and proliferation, which is, at least in part, dependent on the regulation of COX-2/TxA2pathway and AKT/FOXO3a pathway. Thus,18β-GA should be regarded as a new potential drug candidate for RA therapy. References [1] Korczowska I. Rheumatoid arthritis susceptibility genes: An overview. World J Orthop2014;5(4):544–9. [2] Mahmoud AM, et al. Methotrexate hepatotoxicity is associated with oxidative stress, and down-regulation of PPARgamma and Nrf2: Protective effect of 18beta-Glycyrrhetinic acid. Chem Biol Interact2017;270:59–72. Disclosure of Interest None declared

The high average power from pulsed good quality mode laser emitting at fundamental wavelength of 1066.3 nm is needed for obtaining of high-fidelity pulsed radiation with wavelength centered at 589.15 nm for spaceborne Na Doppler resonance fluorescence LIDAR. The conversion of radiation from 1066.3 nm to 589.15 nm can be achieved through one stage of Raman lasing and subsequent frequency doubling using qualified nonlinear crystals. Although efficient scaling of average power at 1064 nm using a-cut Nd:YVO4 to multiple of 10W was demonstrated for more than a decade ago, the efficient demonstration of 1066 nm power scaling from single Watt level to 10W level of average power is yet to be done. Multiple publications with a-cut Nd:YVO4 laser host with fundamental emission wavelength at 1064 nm showed good conversion efficiencies to both 1176 nm and to 588 nm using intracavity Raman lasing and frequency doubling. We experimentally demonstrated efficient lasing at 1066 nm with output average power in excess of 15W using single c-cut Nd:YV04 crystal end-pumped with 888 nm diode pump laser. The achieved optical-to-optical efficiency of converting absorbed 888 nm pump to 1066 nm with short linear test cavity and output coupler of 84% was in excess of 32% while maximum reached optical-to-optical slope efficiency 50%. We discuss challenges of efficient 1066 nm generation and overall electro-optical efficiencies reachable for potential spaceborne LIDAR Sodium transmitter laser.

Background Endothelial dysfunction plays a central role in severe sepsis. Endocan is constitutively expressed in human endothelial cells when sepsis occurs. We tested the hypothesis that endocan concentrations are substantially increased in severe sepsis and decrease after antimicrobial therapy, and that endocan concentrations can predict treatment outcomes. Methods Biomarkers of the endothelium including endocan and cell adhesion molecules were prospectively evaluated in 153 patients with severe sepsis on days 1, 4, and 7 after admission along with biochemical and clinical data. Results Sepsis non-survivors had significantly higher endocan, ICAM-1, and VCAM-1 concentrations and lower platelet concentrations upon admission than the survivors. Non-survivors had significantly higher endocan and VCAM-1 concentrations than the survivors on serial analysis (days 1, 4, and 7). After stepwise logistic regression model and AUC analysis, endocan was revealed as a good predictor of outcome in severe sepsis, and the cut-off value for predicting fatality was 6.28 ng/ml. An increase in the endocan concentration by one ng/ml indicated an increase in fatality rate by 11.1%. Conclusions Based on our results, serial endocan concentration meets the major requirements for predicting outcome in patients with severe sepsis. An assay of endocan concentration may be a good prognostic biomarker in the clinic for severe sepsis.

Fibromyalgia (FM) is a chronic pain syndrome that includes debilitating symptoms such as widespread pain and tenderness, fatigue, and poor physical functioning. Although some research has shown that FM patients’ choice of coping style and relationship quality with their spouse can impact their mental quality of life, no known study has examined the protective nature of relationship quality and coping behaviors on both patient physical and mental quality of life in the context of chronic pain. We used a sample of 204 patients with FM to examine: (a) the simultaneous roles of coping styles and relationship quality on patient quality of life; and (b) the moderating effect of relationship quality on the association between negative coping style and patient quality of life. A series of multiple regressions found that patients’ coping styles were not significantly associated with physical quality of life, but were significantly associated with mental quality of life. Although the quality of patients’ relationship with their spouses was significantly associated with mental quality of life, no significant association was found with physical quality of life and no significant interactions with negative coping style were found. Our results emphasize the important role of coping styles and the quality of the relationship between patients and their spouses in the context of chronic pain. Clinicians have an opportunity to incorporate the patient’s relationship with their spouse as part of a more holistic approach to care and improving patient outcomes.

BACKGROUND: Severe Cytomegalovirus (CMV) colitis is a rare condition, most commonly seen in immunocompromised patients. We describe a case of CMV colitis masquerading as recurrent ischemic colitis in a patient with end-stage renal disease (ESRD). AIMS: Describe a case of severe CMV colitis presenting as recurrent ischemic colitis. METHODS: Case report RESULTS: Case: A 44 year-old man with atherosclerotic risk factors including hypertension, diabetes mellitus, ESRD on hemodialysis and morbid obesity presented twice to our emergency department (ED) within 14 days with hematochezia, acute abdominal pain, fever, leukocytosis, and an elevated serum lactate. Computed tomography scan of the abdomen (CT-Abdo) demonstrated changes consistent with isolated right colon ischemia (IRCI). Colonoscopy showed circumferential ulcerated mucosa with greyish discoloration and sloughing of the mucosa starting at the hepatic flexure and extending proximally, potentially due to ischemic colitis (figure 1). There was a sharp demarcation between the normal and ulcerated mucosa, and, in view of possible ischemia, the endoscope was not introduced further. A colonic biopsy at the edge of demarcation was taken and showed non-specific small ulcerations. The patient improved with conservative management including intravenous fluids and antibiotics. He was discharged home with resolution of symptoms. He unfortunately returned to our ED two weeks later with a third episode of hematochezia, abdominal pain and hemorrhagic shock. Repeat CT-Abdo showed persistent IRCI with new pneumatosis intestinalis. As he failed to improve with vasopressors, blood transfusions, and antibiotic therapy, an urgent right hemicolectomy was performed. On pathology, multiple CMV organisms were identified with ulcerations and perforation, consistent with severe CMV colitis. CMV PCR was only minimally elevated (80copies/mL). IV ganciclovir was initiated. On follow-up visit, the patient demonstrated sustained clinical improvement, and no recurrence of symptoms. CONCLUSIONS: IRCI is an uncommon form of ischemic colitis, but occurs more frequently in patients with significant atherosclerosis and hemodialysis. Despite initial improvement, the patient’s symptomatic recurrence was initially attributed to his severe vasculopathy, coupled with ongoing hemodialysis causing fluid shifts. In a review of the literature of 14 cases with ESRD and CMV GI disease, 72% presented with lower GI bleeding, colonoscopy showed ulceration or polypoid lesions, and was associated with a 35% mortality. CMV colitis should be suspected in atypical cases of ischemic colitis, and early diagnosis may avoid significant morbidity. FUNDING AGENCIES: None

BACKGROUND: Isolated gastric varices (IGV) represent an uncommon condition in cirrhotic patients. We describe a case of IGV disguising as recurrent upper gastrointestinal bleed (UGIB) in a cirrhotic patient. AIMS: Describe a case of IGV presenting as recurrent UGIB. METHODS: Case report RESULTS: Case: A 57 year-old man presented with an upper gastrointestinal bleed. This patient is known for cirrhosis, hypertension, diabetes mellitus, obstructive sleep apnea and obesity. He left against medical advice, reconsulting with rebleeding (hemoglobin (Hb) of 42g/L), and altered mental status requiring intubation. IV crystalloid and blood transfusion were given along with ceftriaxone, pantoprazole and somatostatin. An initial upper endoscopy (EGD) showed a large 5x6cm non-mobile clot in the fundus with no evidence of varices. A second look EGD showed no new findings and no varices were noted. A CT angiography (CTA) was negative apart from hepatosplenomegaly. The next day, hematochezia recurred with drop in Hb to 62 g/L. A third EGD noted brisk blood flow from the cardia/fundus with no clear source. A repeat CTA was normal. An endoscopic ultrasound (EUS) showed isolated gastric varices (IGV). A transjugular intrahepatic portosystemic shunt (TIPS) with embolization was performed. Post TIPS, the patient did not rebleed. DISCUSSION: The patient described above was bleeding from an isolated gastric varices (IGV1 as per Sarin et al. classification). 20% of patients with portal hypertension develop gastric varices, in whom only 8% are IGV1.(1) Multiple studies have demonstrated the superiority of EUS compared to EGD in the detection rate of gastric varices. It is likely due to a poorer sensitivity of EGD in the detection of small gastric varices as well as misdiagnosing them as thickened gastric folds.(2,3) It is important to identify accurately the source of bleeding as gastric varices are typically associated with more severe bleeding episodes than esophageal varices, as well as a higher risk for rebleeding and a high mortality. Fundal varices have significantly higher bleeding incidence (78% for IGV1).(1) Our patient’s acute variceal bleed was treated with TIPS. Placement of TIPS has been shown to be very effective at controlling the episode of active bleeding, achieving a hemostatic rate as high as 90–100%, with a moderate risk of rebleeding (16–41%).(3) However, as per Baveno VI recommendations, TIPS is second line therapy and is indicated when endoscopy guided cyanoacrylate injection fails. CONCLUSIONS: Hence, EUS plays an important role in diagnosis as well as in the management of isolated gastric varices. [Image: see text] Submucosal gastric varices FUNDING AGENCIES: None

In this paper, a new sound metric–Sound Metric based on the Wigner–Ville distribution (SMWVD) – was developed to investigate the relationship between subjective evaluations and vehicle suspension shock absorber rattling noise, which substantially affects passengers’ psychological and physiological perceptions. A complete vehicle road test was conducted to measure the interior shock absorber noises, which were subjectively evaluated by 20 jurors. Conventional psychoacoustic indices, i.e. loudness, sharpness, roughness and fluctuation strength, were used to calculate the correlation coefficients between the objective and subjective evaluations, and then, the results were compared with the performance of the SMWVD. The results show that conventional sound metrics have poor relationships with the subjective ratings, while the SMWVD displayed a high correlation of >0.9 between the objective evaluation and the subjective evaluation. These results indicate that the SMWVD can be used to estimate the rattling noise index of a suspension shock absorber without jury evaluation.

SummaryWhat is known and objective The Adverse Drug Reaction Information Bulletin (ADRIB), issued by China Food and Drug Administration (CFDA), is a major source of information on drugs causing safety concerns in China. As the publication is only published in Chinese, we undertook an analysis of the reports in the ADRIB since its first publication in 2001 to give international readers a better appreciation of the pharmacovigilance issues addressed. Methods Every issue of the ADRIB was scrutinized, and the issues addressed as well as the drugs involved are summarized and discussed. Results and discussion From 2001 to 2014, 109 items of ADR information have been reported. The antimicrobial agents were most often the subject of discussion. There were 28 traditional Chinese medicines (TCMs) discussed. Among the ADRs addressed, the adverse reactions of the skin and its appendages were most frequent. About two-fifths of the ADRs arose from the inherent properties of the active substance, and a majority of the ADRs were caused by off-label use, irrational drug combinations and misuse in special populations. What is new and conclusion Many of the pharmacovigilance issues addressed were similar to those considered by Western Drug Regulatory Agencies. The pharmacovigilance issues relating to Chinese traditional medicines are less well addressed internationally, and these would be of particular value as the use of such medicines increases in the West.

Background Chinese women tend to have small and dense breasts and ultrasound is a common method for breast cancer screening in China. However, its efficacy and cost comparing with mammography has not been evaluated in randomised trials. Methods At 14 breast centres across China during 2008-2010, 13 339 high-risk women aged 30-65 years were randomised to be screened by mammography alone, ultrasound alone, or by both methods at enrollment and 1-year follow-up. Results A total of 12 519 and 8692 women underwent the initial and second screenings, respectively. Among the 30 cancers (of which 15 were stage 0/I) detected, 5 (0.72/1000) were in the mammography group, 11 (1.51/1000) in the ultrasound group, and 14 (2.02/1000) in the combined group (P=0.12). In the combined group, ultrasound detected all the 14 cancers, whereas mammography detected 8, making ultrasound more sensitive (100 vs 57.1%, P=0.04) with a better diagnostic accuracy (0.999 vs 0.766, P=0.01). There was no difference between mammography and ultrasound in specificity (100 vs 99.9%, P=0.51) and positive predictive value (72.7 vs 70.0%; P=0.87). To detect one cancer, the costs of ultrasound, mammography, and combined modality were $7876, $45 253, and $21 599, respectively. Conclusions Ultrasound is superior to mammography for breast cancer screening in high-risk Chinese women.

Background Fos-related antigen 2 (Fra2) is a transcription factor belonging to the Fos family proteins which is part of the AP-1 transcription complex. We recently described a Fra2 transgenic (tg) mouse model which develops a multi-organ inflammatory phenotype affecting skin, lungs, thymus, liver and salivary glands. We have observed abnormalities in the T cell compartment, particularly in regulatory T (Treg) cells, which led us to hypothesize that Fra2 tg mice develop a T cell driven autoimmune phenotype. Objectives To demonstrate the autoimmune phenotype of Fra2 tg mice and to characterize the mechanisms leading to Treg cell abnormality. Methods We used previously generated Fra2 tg overexpressing mice. T lymphocyte populations were analyzed by flow cytometry for expression of activation markers and secretion of cytokines. We transferred purified CD4+ T cells into Rag2-/- mice lacking T and B cells, and we generated Rag2-/-Fra2 tg mice. Bone marrow cells were transferred into lethally irradiated recipients to create Fra2-WT bone marrow chimeric mice. Results Fra2 tg mice backcrossed onto a Rag2-/- background did not develop inflammatory manifestations (n=6), demonstrating the dependence on T and/or B cells of the autoimmune phenotype. In line with this, the transfer of purified CD4+ cells from 16 week-old Fra2 tg mice into Rag2-/- recipients was sufficient to transfer the disease phenotype (n=3). Analysis of T cell populations from Fra2 tg mice showed the presence of activated CD4+ and CD8+ cells in the spleen and lungs. After in vitro stimulation, we found that CD4+ T cells from Fra2 tg mice produced the Th2 cytokines IL-4, IL-5 and IL-13. Thus, these data strongly suggest a T cell-driven autoimmune disease in these mice. We previously reported a striking decrease of Treg cells in Fra2 tg mice, which might explain the autoimmune phenotype observed. Supporting this idea, we found that 3 week-old mice were devoid of organ manifestations and of T cell activation, but presented the same defect in the Treg cell population (n=6, p Conclusions Our data suggest that Fra2 controls tTreg cell development, possibly by modulating IL-2 signaling in T cells, which leads to autoimmunity in this mouse model. This new pathway could be targeted in a translational approach to modulate the capacity of T cells to differentiate in Tregs during autoimmune disease. Disclosure of Interest F. Renoux Grant/research support from: Swisslife, M. Stellato: None declared, D. Impellizzieri: None declared, A. Vogetseder: None declared, R. Huang Employee of: Sanofi-Genzyme, A. Subramaniam Employee of: Sanofi-Genzyme, C. Dees: None declared, J. Distler Shareholder of: 4D Science, Grant/research support from: Anamar, Active Biotech, Array Biopharma, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, GSK, Novartis, Sanofi-Aventis, UCB, Consultant for: Actelion, Active Biotech, Anamar, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi and UCB, G. Kania: None declared, O. Boyman: None declared, O. Distler Grant/research support from: Actelion, Bayer, Boehringer Ingelheim, Pfizer, Sanofi, Consultant for: 4 D Science, Actelion, Active Biotec, Bayer, BiogenIdec, BMS, Boehringer Ingelheim, ChemomAb, EpiPharm, espeRare foundation, Genentech/Roche, GSK, Inventiva, Lilly, medac, Mepha, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Pfizer, Sanofi, Serodapharm, Sinoxa, Speakers bureau: AbbVie, iQone Healthcare, Mepha