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BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Zhiming Zhao,1 Huiwen Jin,1 Yang Yin,1 Yanwei Hou,1 Jingyan Wang,1 Chunling Tang,2 Jun Fu1 1Health Center of Screening and Prevention of Diseases, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, People’s Republic of China; 2Department of Psychiatry, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, People’s Republic of ChinaCorrespondence: Jun FuHealth Center of Screening and Prevention of Diseases, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, People’s Republic of ChinaTel +86 451 85553111Email fujunyk@hotmail.comPurpose: The relationship between food allergy caused by food specific IgG antibodies and migraine has received increased attention in recent years. Here, we aimed to evaluate the effects of food specific IgG antibodies on headache, gastrointestinal symptoms, anxiety, depression, sleep disorders, dermatosis, and serum inflammatory cytokines in migraine patients, and to quantitatively assess the effect of IgG levels on the severity of headache and its comorbidities.Methods: Of 89 migraine patients, those who had one or more food specific IgG antibodies ≥ 50 U/mL were classified into the IgG positive group, which was then further divided into subgroups based on differing numbers of food allergens. All other subjects were classified into the IgG negative group. We compared the frequency and severity of migraine, anxiety, depression, sleep disorders, dermatosis, and inflammatory cytokines between groups. A regression model was performed to further assess the effect of overall positive IgG concentration and the mediation effect of inflammatory cytokines.Results: Participants in the positive IgG group (n = 67) were more likely to have longer time elapsed since diagnosis, more frequent and severe migraine, a higher risk of developing anxiety and gastrointestinal symptoms, along with higher IL-6 and TNF-α. Subgroups with more food allergens generally had worse conditions as well. After adjusting for the inflammatory cytokines, the effect of IgG was reduced.Conclusion: Migraine patients with positive food specific IgG antibodies had worse migraine, anxiety, and gastrointestinal symptoms. Inflammatory cytokines partially mediate the causal pathway between food specific IgG antibodies, migraine, and migraine comorbidities.Keywords: migraine, food, immunoglobulin G antibody, gastrointestinal symptoms, anxiety, interleukin-6, tumor necrosis factor- &#x03B1

Background and aim Westernized high-fat diet increases the risk for inflammatory bowel diseases (IBDs), yet with insufficient understanding of the role of high-protein diet. We aimed to identify the effect of high-protein diets from different dietary proteins (casein, whey protein, soy protein) on experimental colitis and its impact on microbiota, structure and function of colonic mucus layer. Methods Female BALB/c mice were fed by standard diet, high-casein diet (HCD), high whey protein diet or high soy protein diet for 4 weeks. The susceptibility of dextran sulfate sodium (DSS)-induced colitis in mice and thickness of colonic mucus layer were compared after different dietary interventions, associated with the identification of the reversal effect of broad-spectrum antibiotic intervention (0.5 g/L of vancomycin and 1 g/L of neomycin sulfate, metronidazole and ampicillin in drinking water). Further analysis was performed on the synthesis of mucin, microbiota and sialidase involved in degradation of mucus layer. Results High-protein diets aggravated acute DSS-induced colitis independent of protein composition, while broad-spectrum antibiotics reversed this effect. HCD significantly altered the composition of bacteria in the colonic mucus layer, especially Bacteroides thetaiotaomicron and total mucin-degrading bacteria; besides, it increased sialidase concentration and reduced the thickness of mucus layer. However, it exhibited no significant effect on the synthesis of Muc2. Broad-spectrum antibiotics decreased the abundance of mucin-degrading bacteria and sialidase concentration while increased the thickness of mucus layer. Conclusion High-protein diet shifts microbial composition and thickness of colonic mucus layer, leading to the aggravation of acute DSS-induced colitis.

BACKGROUND AND OBJECTIVES There has been reports on fractional CO2 laser successfully improving contracture scars that impair the function of a joint. It seems that certain contracture problems could be solved by laser instead of surgery. However, the clinical application could be difficult when the efficacy of the method remains unknown. The purpose of this study is to report the releasing capacity of the fractional CO2 laser on contracture scars based on a defined treatment method. STUDY DESIGN/MATERIALS AND METHODS We conducted a retrospective study in patients with limited function in joints caused by contracture scars. Fractional CO2 laser and our "3D mesh releasing" protocol were applied. The primary outcome was the improvement measured in range of motion (ROM) of the relevant joint before all intervention and 6 months after the last treatment. RESULT From November 2016 to January 2018, 11 joints of 10 cases were treated by the fractional CO2 laser. Patients went through 2.27 (standard deviation [SD] 1.42, 1-5) sessions. The average progress of ROM before and 6 months after all treatments was 19.13° (SD 10.25, P

Veterans with posttraumatic stress disorder (PTSD) frequently report dream enactment behavior (DEB). Although DEBs are associated with PTSD symptoms, their relationship with other sleep disorders, including REM behavior disorder, warrants reexamination of their clinical correlates.The investigators used a cross-sectional, exploratory analysis to compare demographic and clinical characteristics of veterans endorsing regularly occurring DEB compared with those endorsing no or infrequent DEB. The participants comprised a convenience sample of servicemembers who were previously deployed to Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) and enrolled in an ongoing cohort study.Of the 78 eligible participants, 19 (24.4%) endorsed DEBs occurring at least once per week in the past month. Compared with participants who reported no or infrequent DEBs, participants with regularly occurring DEBs had poorer sleep quality, greater PTSD severity, a higher number of reported mild traumatic brain injuries (mTBI) with loss of consciousness, and a higher likelihood of being diagnosed with sleep disorders. After adjustment for global sleep quality, a significant association persisted between DEBs and the number of mTBI with loss of consciousness but not between DEBs and the severity of PTSD symptoms.These results suggest that mTBI may disrupt neural circuits regulating sleep among OIF/OEF/OND veterans. Prospective, polysomnographic assessment of muscle tone and behavioral events during REM sleep is needed to characterize the physiology of DEBs in this population.

Resveratrol (Res) is a natural active antioxidant that is effective in relieving inflammatory bowel disease (IBD). However, the specific mechanism for its function is unknown. In our study, dextran sodium sulfate (DSS)-induced mouse IBD disease model was constructed. All mice were randomly divided into three groups. The treatment effects of resveratrol on IBD were evaluated by observing the body weight, fecal traits, colon/spleen gross appearance, tissue hematoxylin-eosin (H&E)/immunohistochemistry (IHC) and inflammatory factors. The expression of small ubiquitin-like modifier protein 1 (SUMO1) and its Wnt/β-catenin pathway-related genes was analyzed by IHC, Western blot, Real-time PCR (RT-PCR) and Immunofluorescence. The outcome indicated that resveratrol treatment significantly relieved the symptoms of IBD. The expression level of anti-inflammatory cytokines was increased while that of pro-inflammatory cytokines was decreased in both colon and spleen tissues of resveratrol-treated mice. SUMO1 expression and Wnt/β-catenin pathway were suppressed in colon and spleen tissues of IBD mice treated with resveratrol. In addition, we provided evidence that resveratrol inhibited SUMO1 and β-catenin expression and their nuclear localization in human colonic epithelial cell line (FHC). Moreover, we found that SUMO1 and β-catenin had higher expression levels in colorectal cancer patients than in health and colitis patients. In conclusions, resveratrol alleviates DSS-induced IBD by modulating SUMO1 through Wnt/β-catenin pathway.

The prevalence of hepatitis B virus (HBV) infection was an imbalance in different provinces of China. This study aimed to investigate the prevalence of HBV infection and evaluate the prophylactic measures in a public hospital of northeast China over the preceding 13 years. A total of 13,948 patients in 2004 and 15,256 patients in 2017 of Shengjing Hospital of China Medical University were tested of serum HBsAg, HBeAg, HBsAb, HBeAb, and HBcAb levels with Abbott MEIA Kits. In people born before 1992, HBsAg-positive rate was 5.45% and 6.47%; isolated HBsAb positive rate was 14.62% and 21.24%; HBV marker negative rate was 54.27% and 42.77% in 2004 and 2017 survey, respectively. The males had a significant higher HBsAg-positive rate than the females. In people born during 1992-2004, HBsAg positive rate was 0.58% and 0.57%, isolated HBsAb positive rate was 41.47% and 46.57%; and HBV marker negative rate was 51.97% and 46.86% in 2004 and 2017 survey, respectively. Males and females had no difference of HBsAg-positive rate. In children born after 2005, HBsAg positive rate was 0.11%, isolated HBsAb positive rate was 76.68%, and HBV marker negative rate was 18.51% in 2017 survey. No difference of HBsAg-positive rate was found between the genders. A dramatic decrease of HBsAg positive rate and a progressive increase of HBsAb-positive rate were found among people born after 1992 and progressed further in those born after 2005. Immunization of infants and timely birth dose was the key method for prevention of HBV infection. Expanded HB vaccination would be needed for people born before 2005, especially those born between 1992 and 2004.

Inflammatory bowel disease (IBD) can be caused by a variety of factors, including hereditary and environmental influences, that lead to dysfunction of the intestinal immune system. Mesenchymal stem cells (MSCs) exhibit important regulatory roles in relieving inflammation and repairing damaged tissues. Although neutrophils are important participants in the development of inflammatory reactions, they are also essential for maintaining intestinal balance during the process of mitigation of IBD by MSCs. Here, we constructed a dextran sulfate sodium (DSS)-induced mouse IBD model and evaluated the effects of treatment with human umbilical cord MSCs. Mouse body weight, faecal traits, colon/spleen gross morphology, tissue histology and immunohistochemical staining, and inflammatory factors were analysed. Magnetic beads were used to sort infiltrating neutrophils from intestinal tissues, and their phenotypes were identified. The neutrophil inflammatory environment was also simulated in vitro, and signalling pathways involved in MSC regulation of neutrophil phenotype were analysed. Human umbilical cord MSCs effectively alleviated DSS-induced weight loss, colon shortening, and intestinal mucosal injury, and reduced clinical disease activity index. The number of neutrophils that infiltrated the intestines of mice treated with human umbilical cord MSCs were decreased and polarised toward the N2 phenotype; at the same time, ERK phosphorylation was inhibited. In vitro experiments showed that addition of the ERK phosphorylation inhibitor, PD98059, down-regulated the expression of N1 neutrophils, while up-regulating that of N2 neutrophils. The colon tissues from patients with IBD were infiltrated with neutrophils. Further, relative to healthy controls, the markers of N1 neutrophils (ICAM-1, FAS, and CCL3) were highly expressed in colon tissues from patients with IBD, whereas the markers of N2 neutrophils (VEGF, CCL2, and CXCR4) were almost undetectable. In conclusion, during alleviation of IBD, human umbilical cord MSCs polarise neutrophils toward the "N2" phenotype by inhibiting activation of ERK signalling.

The aim of this study was to determine the disease spectrum and drug types causing drug-induced liver injury (DILI) in northeast China, so that the affected population can be reminded of the need to increase their post-medication monitoring.A total of 470 DILI patients hospitalized at Shengjing Hospital between 2013 and 2016 were involved in this retrospective study.There were significant differences in the disease spectrum of the different age groups (P 0.001) and genders (P = 0.009). Drugs used to treat osteopathies, dermatitis and infections, as well as health care supplements, each accounted for 10% of all drugs that caused DILI. The percentage of DILIs related to Chinese herbal medicines (CHMs) gradually increased with patient age (P = 0.002). The percentage of males taking health supplements or CHMs was significantly lower compared with females. Total bilirubin (β = 0.01, OR = 1.01, P 0.001) and INR (β = 0.74, OR = 2.11, P 0.001) were found to be independent predictors of liver damage.The main type of drug that causes DILI in northeast China is a CHM. There are differences in the disease spectrum found in DILI patients of different ages and gender. Making appropriate changes in the drug-taking habits of high-risk groups and the drugs used to treat high-risk underlying diseases, as well as increasing patient monitoring, may help to reduce the incidence of DILIs.

BACKGROUND AND PURPOSE To explore the application value and clinical significance of transcranial Doppler(TCD)in assessing leptomeningeal collateral flow (LMF) status in patients with unilateral middle cerebral artery (MCA) occlusion. METHODS Medical records of patients with unilateral MCA occlusion confirmed by digital subtraction angiography (DSA) were analyzed retrospectively. The patients were divided into three groups according to LMF status, and the laboratory and imaging results were collected. Cerebral blood flow velocity (CBFV) of MCA, anterior cerebral artery (ACA), and posterior cerebral artery (PCA) on the affected side (ipsilateral, i) and the healthy side (contralateral, c) were measured and recorded by TCD. The results of CBFV changes detected by TCD were compared with those of DSA, and the correlation between CBFV changes and LMF status was analyzed. RESULTS Eighty-four patients with unilateral MCA occlusion were included. CBFViACA and CBFViPCA were significantly faster than CBFVcACA and CBFVcPCA in patients with good LMF status (p

OBJECTIVE Ovarian hyperstimulation syndrome (OHSS) is mainly caused by human chorionic gonadotropin (hCG) through vasoactive mediators such as vascular endothelial growth factor (VEGF) and various inflammatory factors. Our previous study showed that soluble receptor for advanced glycation end products (sRAGE) played a protective role in PCOS by inhibiting VEGF, so wanted to explore the role of sRAGE in OHSS. METHODS Two sets of experiments were performed in this study. In part one, sRAGE protein levels in follicular fluid (FF) samples from 60 patients with OHSS and 60 non-OHSS patients were measured by ELISA. In part two, ovarian granulosa cells were isolated from an additional 25 patients with OHSS and cultured. Then, ovarian granulosa cells were treated with different concentrations of sRAGE. Granulosa cells cultured without sRAGE stimulation were used as the control group. The levels of VEGF, amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG) mRNA were examined by quantitative RT-PCR. The protein levels of VEGF, AREG, BTC, and EREG were measured by ELISA. RESULTS Compared with non-OHSS patients, patients with OHSS exhibited lower sRAGE levels in both serum and FF (p

Advances in technology and introduction of new regulations have transformed the equity market over last few decades, giving rise to a new breed of trading—high-frequency trading (HFT). This article investigates transformations that have shaped today’s equity trading ecology in detail with a particular focus on HFT. HFT accounts for an increasingly significant share of equity trading volumes, and is associated with lower transaction costs, greater liquidity, improved price discovery, and overall market efficiency. At times of increasing order toxicity, however, HFTs may withdraw liquidity due to higher probability of adverse selection. In this new era of equity trading, further research on a complete ecosystem of liquidity provision that ensures full provision of liquidity even during stressed periods is much needed. TOPICS:Fundamental equity analysis, accounting and ratio analysis, technical analysis

Mesenchymal stem cells (MSCs) exert powerful immunosuppression in inflammatory bowel disease (IBD). Macrophages are the dominant inflammatory cells in enteritis regulated via MSCs. However, the roles of macrophages in the process of MSCs attenuating IBD and the mechanisms of MSCs regulating macrophages are largely unknown. In this study, DSS- (dextran sulfate sodium salt-) induced IBD in macrophage-depleted models of CD11b-DTR mice was used to study the relationship between hucMSCs (human umbilical cord mesenchymal stromal cells) and macrophage. Body weights, disease activities, and pathological changes were documented to assess the therapeutic effects of hucMSCs. Furthermore, hucMSCs transfected with miR148b-5p mimics and miR148b-5p inhibitors were cocultured with LPS-induced RAW264.7 cells to investigate the role of miR148b-5p in hucMSC-regulated colitis. The outcome indicated that hucMSCs attenuated the IBD by downregulating 15-lox-1 expression in macrophages. Further findings pointed out that hucMSCs transfected with miR148b-5p mimics could be elevated to promote the tissue repair and inhibit the expression of 15-lox-1 but failed to perform the function of easing enteritis when treated with miR148b-5p inhibitors. In conclusions, we propose that hucMSCs attenuate IBD by releasing miR148b-5p to inhibit the expression of 15-lox-1 in macrophages.

Background: Understanding minimum clinically important differences (MCID) in patient-reported outcomes is essential in interpreting the magnitude of changes in these measures. No MCID from patients’ perspectives has ever been published for peripheral artery disease–specific health status assessment tools. The Peripheral Artery Questionnaire (PAQ) is a commonly used, validated peripheral artery disease–specific health status instrument for which we sought to prospectively establish its MCID from patients’ perspectives. Methods and Results: Patients presenting to vascular clinics with new or worsened claudication in the US cohort of the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry who completed baseline and follow-up PAQ assessments along with the Global Assessment of Functioning scale were included. Mean change in PAQ summary scores from 3- to 6-month follow-up was calculated according to Global Assessment of Functioning category. MCID was defined as the mean difference in scores between those with small improvement or deterioration and those with no change. Multivariable linear regression was used to provide an MCID estimate after adjusting for patients’ 3-month PAQ score. Of the 483 patients who completed the Global Assessment of Functioning score at 6 months and who had available 3- and 6-month PAQ assessments, the mean age was 69 years, 42% were female, and 71% were White. The MCIDs for PAQ summary scale improvement and worsening were 8.7 (2.9–14.5) and −11.0 (−18.6 to −3.3), respectively. After multivariable adjustment, these were 8.9 (3.0–14.8) and −11.2 (−18.2 to −4.2), respectively. There was no significant interaction between treatment (invasive versus noninvasive) and Global Assessment of Functioning response ( P =0.75). Conclusions: In patients with new or worsened claudication, a 10-point change in PAQ summary score represents an MCID. This estimate needs external validation and may inform the interpretation of PAQ scores when used as outcomes in clinical trials or in routine clinical care. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01419080.

We present several photonic integrated WDM cross-connect switch architectures to realize disaggregated metro nodes and high performance intra datacenter networks. The WDM switches exploit SOAs for loss-less and nanoseconds wavelength, space, and time switching operation.

This paper presents a detailed examination of a novel data center network (DCN) that can satisfy the high capacity and low latency requirements of modern cloud computing applications. This reconfigurable architecture called AgileDCN uses fast-switching optical components with a centralized control function and workload scheduler. By providing a highly flexible optical network fabric between server racks, very high network efficiencies can be achieved even under imbalanced loading patterns. Our simulation results show that, at high (70%) loads, TCP flow completion times in the AgileDCN are significantly lower than in an equivalent electronic leaf-spine network.

Imaging can help guide management in peripheral arterial disease (PAD) with symptoms refractory to medical treatment. However, there are no set guidelines to determine when physicians should seek further imaging in patients with PAD for the assessment of new, persistent or worsening symptoms. This study describes the rates and variability in non-invasive and invasive imaging for patients presenting to vascular specialty clinics for symptomatic PAD.Patients (n=1,275) with a new PAD diagnosis or exacerbation of PAD symptoms were enrolled from 16 vascular clinics. Hierarchical logistic regression models were used to estimate the referral rates for 1) non-invasive and 2) invasive imaging tests, after adjusting for patient demographics, disease characteristics, PAQ summary score, PAD performance measures and country. Median Odds Ratios (MOR) were calculated to examine the variability across sites and providers.Mean ABI was 0.67 ± 0.19. There were 690 (54.1%) patients who had imaging, of which 62 (9.0%) had invasive imaging. Imaging rates ranged from 8.6% to 98.6% across sites. The MOR for use of imaging for site was 3.36 (p0.001) and provider 3.49 (p0.001). The variability was explained primarily by (RThere is wide variation in the use of imaging for patients presenting with new onset or recent exacerbations of their PAD. Country, followed by provider and site, were most strongly associated with this variability after adjusting for patient characteristics.

In the context of China&rsquo, s electric power reform, issued in May 2019, the "Transmission and Distribution Pricing Supervision Measures" have changed asset accounting in grid enterprises and therefore affected cost accounting in grid projects. This paper proposes a dynamic cost calculation model based on system dynamics and takes a power grid company as an example. On this basis, a sensitivity analysis of power grid engineering was conducted to determine the impacts of key factors of power reform on life cycle cost (LCC). Finally, suggestions for cost accounting and cost management were proposed.

Background A prophylactic antimalarial drug that is both effective for protection and improves compliance is in high demand. Methods We conducted a randomized, placebo-controlled, double-blinded phase 3 trial to evaluate the 1:1 fixed-dose combination of naphthoquine-azithromycin (NQAZ) for safety and protection against Plasmodium infections in villages along the China-Myanmar border. A total of 631 residents, 5–65 years of age, were randomized into the drug group (n = 319) and the placebo group (n = 312) to receive NZAQ and placebo, respectively, as a single-dose monthly treatment. Follow-ups were conducted weekly to monitor for adverse events and malaria infections. Results Of the 531 subjects completing the trial, there were 46 and 3 blood smear–positive Plasmodium infections in the placebo and treatment groups, respectively. For the intent-to-treat analysis, the single-dose monthly NQAZ treatment had 93.62% protective efficacy (95% confidence interval [CI]: 91.72%–95.52%). For the per-protocol analysis, NQAZ treatment provided a 93.04% protective efficacy (95% CI: 90.98%–95.1%). Three smear-positive cases in the NQAZ group were all due to acute falciparum malaria. In comparison, NQAZ treatment provided 100% protection against the relapsing malaria Plasmodium vivax and Plasmodium ovale. The treatment group had 5.6% of participants experiencing transient elevation of liver aminotransferases compared with 2.2% in the placebo group (P > .05). Conclusions Monthly prophylaxis with NQAZ tablets was well tolerated and highly effective for preventing Plasmodium infections. It may prove useful for eliminating P. vivax in areas with a high prevalence of glucose-6-phosphate dehydrogenase deficiency in the population. Clinical Trials Registration ChiCTR1800020140.

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. Inflammation and the nutritional status of patients with GC are important factors affecting the therapeutic effect and prognosis. Inflammatory and nutrition-related markers have been shown to be prognostic factors for patients with GC. However, few studies have investigated the relationship of the prealbumin-to-globulin ratio (PGR) with the prognosis of GC patients. The objective of the present study was to examine whether pretreatment PGR is related to the prognosis and chemotherapy outcomes of in-patients with advanced GC undergoing first-line chemotherapy. We retrospectively reviewed the data of 281 patients with unresectable GC from January 2013 to January 2018. The receiver operating characteristic curve analysis determined the cut-off values for the PGR. The relationship between the PGR and chemotherapy effectiveness was evaluated using the chi-square test. Kaplan-Meier’s method was used to plot progression-free survival (PFS) and overall survival (OS) curves, using multivariable Cox regression analysis to identify promising predictors of mortality. The cut-off value for the PGR was 7.21. The high-PGR (≥7.21) group had a higher disease control rate than that of the low-PGR group (93.66% vs. 78.42%, p<0.001). Kaplan-Meier’s analysis showed significantly higher median PFS (189 vs. 125 days, p<0.001) and OS (350 vs. 288 days, p<0.001) in the high-PGR group. The multivariate analyses revealed that a high PGR is an independent protective factor in patients with advanced GC, both in terms of PFS (hazard ratio [HR]: 0.672; 95% confidence interval [CI]: 0.527–0.857; p<0.001) and OS (HR: 0.675; 95% CI: 0.530–0.861; p=0.002). In conclusion, the prechemotherapy PGR can accurately predict the chemotherapy outcome, PFS, and OS of patients with advanced GC. Therefore, medical practitioners can utilize the PGR as a novel dependable prognostic tool to weigh the prognosis of patients with GC.

Regional integrated energy system (RIES) contains multiple energy coupling equipment and differential energy demand, which demonstrates that establishing a complete source-grid-load-storage energy supply chain is conducive to renewable energy consumption, and improves RIES economy and energy utilization efficiency. This paper proposes a synergy planning approach for RIES energy stations (ESs) and pipeline networks (PNs) with energy interaction and equipment selection. First, this paper analyzes a RIES structure involving equipment selection and energy interaction, and describes the problem to be addressed in this paper. Secondly, ten equipment output models are built based on energy coupling methods, and a RIES synergy planning model is further developed to minimize the annual total costs (ATCs) and the total electricity abandonment rate (TEAR) with various constraints. Subsequently, Elitist Non-Dominated Sorting Genetic Algorithm (NSGA-II) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) are applied to solve the Pareto solution set and best compromise solution (BCS) of this mixed-integer nonlinear model (MINLP), respectively. Finally, optimal planning combinations are selected in three scenarios so as to verify the feasibility and validity of the proposed models and method. Innovations as well as further extensions of the proposed methods, are also discussed. Optimal equipment selection and output strategy help reduce 52.42% ATCs and 19.81% TEAR. Moreover, with considerations for energy interactions, RIES synergy planning achieves higher excess electricity consumption efficiency and further 1.40 M$ savings.

Background The ACC/AHA cholesterol guidelines recommend patients with peripheral artery disease (PAD) be treated with a moderate to high-intensity statin. The extent to which patients with new or worsening PAD symptoms are offered guideline therapy is unknown. Hypothesis There is significant variability in rate of guideline-directed statin intensification across clinical practices. Methods In the PORTRAIT registry, patterns of statin therapy were assessed in 1144 patients at 16 PAD specialty clinics between June 2011 and December 2015 before and after an evaluation for new or worsening claudication symptoms. We documented whether patients were treated with a guideline statin as well as the incidence of statin intensification. Statin intensification was defined as transitioning from no statin or low-intensity statin to moderate or high-intensity statin treatment. Patient factors associated with intensification were examined. Site and provider-level variation in intensification was summarized using an adjusted median odds ratio (aMOR). Results Among 1144 patients, 810 (70.8%) were initially on guideline therapy compared to 334 (29.2%) that were not. In the latter, 103 (30.8%) received intensification following evaluation. Patients with typical symptoms displayed greater odds of intensification (OR 3.74; 95% CI: 1.23-11.41) while older patients had lower odds of intensification (OR 0.60/decade; 95% CI: 0.41-0.88). Site variability for statin intensification was observed across sites (aMOR = 3.15; 95% CI 1.22-9.60, [P = 0.02]) but not providers (aMOR = 1.89; 95% CI 1.00-3.90, [P = 0.14]). Conclusions Most patients evaluated at a PAD specialty clinic for new or worsening claudication symptoms arrived on guideline statin therapy. Only 31% not receiving appropriate therapy underwent statin intensification. These findings highlight an important opportunity to optimize medical therapy for patients with PAD.

BACKGROUND Hepatocellular carcinoma (HCC) remains difficult to diagnose at an early stage. Aldo-keto reductase family 1 member B10 (AKR1B10) is an oxidoreductase that is upregulated in some chronic liver diseases. The aim of this study was to use immunohistochemistry to evaluate the expression of AKR1B10 in liver tissue from patients with HCC of different stages. MATERIAL AND METHODS Forty-four patients with a tissue diagnosis of HCC (35 males and 9 females) with 37 control samples of liver tissue containing liver cirrhosis were studied using immunohistochemistry for the expression of AKR1B10. Histological examination determined the grade of HCC; the stage of HCC was determined according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Serum alpha-fetoprotein (AFP) levels were measured and compared between the patients with HCC. RESULTS Immunohistochemistry showed increased expression of AKR1B10 in moderately-differentiated HCC compared with well-differentiated HCC, poorly-differentiated HCC, and liver cirrhosis (P

Purpose: To evaluate the efficacy and safety of nucleos(t)ide analogues, especially telbivudine (LdT) for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in women with high viremia. Methods: We conducted a prospective, open-label, multicenter study of LdT for treating pregnant women having high viral loads of hepatitis B virus (HBV DNA>5 log10 IU/mL) but normal levels of alanine aminotransferase (ALT). Maternal HBV DNA, HBV serologic status and ALT were measured at baseline, 4 weeks after therapy, before delivery, 4 weeks after delivery, and 12 weeks after delivery. Infant HBV serologic status and HBV DNA levels were measured at 7 months. We calculated the MTCT rate of LdT-treated and LdT-untreated groups and analyzed the efficacy and safety of LdT. Results: Ninety-one women (the treatment group) were treated with LdT, and twenty-one patients (the observation group) did not undergo antiviral therapy. The baseline HBV DNA levels were 8.15±0.82 log10 IU/mL in the treatment group, and 8.09±1.04 log10 IU/mL in the observation group. The MTCT rate was 0% in the treatment group, and 9.5% in the observation group (p=0.042). In the treatment group, HBV DNA levels were 5.02±0.74 log10 IU/mL at one month after therapy, and 3.95±0.94 log10 IU/mL before delivery. Both groups had significant differences from baseline levels in HBV DNA levels (p

We examined the prevalence of cardio-renal-metabolic (CaReMe) conditions and their combinations among 530 747 adults with type 2 diabetes in a USA-based outpatient registry of 271 primary care, cardiology and endocrinology offices. We evaluated the following CaReMe conditions: hypertension, hyperlipidaemia, coronary artery disease (CAD), chronic kidney disease (CKD), cerebrovascular disease, peripheral artery disease, atrial fibrillation, heart failure, and gout or hyperuricaemia; prevalence estimates were adjusted based on the distribution of diabetes by age in the US population in 2015. We found that it was uncommon for patients to have isolated type 2 diabetes without other CaReMe conditions, with only 6.4% having no other CaReMe conditions and 51% having ≥3 other CaReMe conditions. The most prevalent individual conditions were hypertension (83%), hyperlipidemia (81%), CAD (32%) and CKD (20%), and the most common combinations included various groupings of hypertension, hyperlipidaemia, atherosclerotic cardiovascular disease and CKD. Older age, male sex and tobacco use were each associated with increased numbers of CaReMe conditions. These findings highlight the clinical need for novel treatment strategies for diabetes that address both glycaemia and coexisting disease states.

Objectives To examine the proportion of older adults with diabetes mellitus treated with tight glucose control and the factors associated with this practice. Design Cross‐sectional analysis. Setting Outpatient sites in the Diabetes Collaborative Registry (N=151). Participants Adults aged 75 and older with type 2 diabetes mellitus (N=42,669). Measurements Participants were categorized based on glycosylated hemoglobin (HbA1c) and glucose‐lowering medications: poor control (HbA1c >9%), moderate control (HbA1c 8–9%), conservative control (HbA1c 7–8%), tight control (HbA1c

Purpose We examined the efficacy and safety of thalidomide (THD) for the prevention of delayed nausea and vomiting in patients who received highly emetogenic chemotherapy (HEC). Patients and Methods In a randomized, double-blind, active-controlled, phase III trial, chemotherapy-naive patients with cancer who were scheduled to receive HEC that contained cisplatin or cyclophosphamide-doxorubicin/epirubincin ≥ 50 mg/m2 regimens were randomly assigned to a THD group (100 mg twice daily on days 1 to 5) or placebo group, both with palonosetron (0.25 mg on day 1) and dexamethasone (12 mg on day 1; 8 mg on days 2 to 4). Primary end point was complete response to vomiting—no emesis or use of rescue medication—in the delayed phase (25 to 120 h). Nausea and anorexia on days 1 to 5 were evaluated by the 4-point Likert scale (0, no symptoms; 3, severe). Quality of life was assessed by the European Organization for Research and Treatment of Cancer QLQ-C30 version 3 questionnaire on days −1 and 6. Results Of 656 patients, 638 were evaluable: 317 in the THD group and 321 in the control group. Compared with placebo, delayed and overall (0 to 120 h) complete response rates to vomiting were significantly higher with THD: 76.9% versus 61.7% ( P < .001) and 66.1% versus 53.3% ( P = .001), respectively. Rates of no nausea were also higher in the THD group (delayed: 47.3% v 33.3%; P < .001; overall: 41% v 29.6%; P = .003), and mean scores of anorexia were lower overall (0.44 ± 0.717 v 0.64 ± 0.844; P = .003). Adverse effects were mild to moderate. The THD group had increased sedation, dizziness, constipation, and dry mouth, but experienced better quality of life after chemotherapy. Conclusion Thalidomide combined with palonosetron and dexamethasone significantly improved HEC-induced delayed nausea and vomiting prevention in chemotherapy-naive patients.

Oral anticoagulation (OAC) with warfarin is underused for atrial fibrillation (AF). The availability of direct oral anticoagulants (DOACs) may improve overall OAC rates in AF patients, but a large-scale evaluation of their effects has not been conducted.This study assessed the effect of DOAC availability on overall OAC rates for nonvalvular AF.Between April 1, 2008 and September 30, 2014, we identified 655,000 patients with nonvalvular AF and a CHAOverall OAC rates increased from 52.4% to 60.7% among eligible AF patients (p for trend 0.01). Warfarin use decreased from 52.4% to 34.8% (p for trend 0.01), and DOAC use increased from 0% to 25.8% (p for trend 0.01). An increasing CHAIntroduction of DOACs in routine practice was associated with improved rates of overall OAC use for AF, but significant gaps remain. In addition, there is significant practice-level variation in OAC and DOAC use.

Pressure waveform analysis has the potential for facilitated assessment of pulmonary vein occlusion during cryoballoon ablation for atrial fibrillation. Data on clinical outcomes using this method are lacking. We sought to validate through clinical outcomes the use of pressure waveform analysis as the primary method of determining pulmonary vein occlusion during cryoballoon ablation. A study was performed of 122 consecutive patients with atrial fibrillation (85% paroxysmal) undergoing cryoballoon ablation from May 2014 through July 2015 at a single institution using pressure waveform analysis as the primary method of assessing pulmonary vein occlusion. Cryoballoon ablation, with additional segmental radiofrequency ablation in 13.7%, resulted in complete pulmonary vein isolation in 100% of patients. The single procedure freedom from recurrence of atrial arrhythmia beyond the initial 3-month post-ablation was 81.2% at a mean follow-up of 237 days. Recurrence of atrial arrhythmia within 3-month post-ablation was 11.1%, and predicted recurrence beyond 3 months. Repeat ablation was performed in 12.0% of patients. In the largest study to date on this topic and the only study to focus on clinical outcomes, pressure waveform analysis as the primary method of determining pulmonary vein occlusion in cryoballoon ablation of atrial fibrillation resulted in acute and long-term procedural success rates comparable to those reported with use of routine pulmonary venography. Controlled study is needed to confirm these findings and to determine if this technique affects variables such as procedure duration and radiation exposure.

Approximately 18.1×106 new cases of cancer were recorded globally in 2018, out of which 9.6 million died. It is known that people who have Inflammatory Bowel Disease (IBD) turn to be prone to increased risks of developing colorectal cancer (CRC), which has global incident and mortality rates of 10.2% and 9.2%, respectively. Over the years, conventional treatments of IBD and its associated CRC have been noted to provide scarce desired results and often with severe complications. The introduction of biological agents as a better therapeutic approach has witnessed a great deal of success in both experimental and clinical models. With regard to mesenchymal stem cell (MSC) therapy, the ability of these cells to actively proliferate, undergo plastic differentiation, trigger strong immune regulation, exhibit low immunogenicity, and express abundant trophic factors has ensured their success in regenerative medicine and immune intervention therapies. Notwithstanding, MSC-based therapy is still confronted with some challenges including the likelihood of promoting tumor growth and metastasis, and possible overestimated therapeutic potentials. We review the success story of MSC-based therapy in IBD and its associated CRC as documented in experimental models and clinical trials, examining some of the challenges encountered and possible ways forward to producing an optimum MSC therapeutic imparts.

OBJECTIVE Peripheral artery disease (PAD) has been shown to affect health status and quality of life; however, the disability associated by specific anatomic level of disease is unknown. We evaluated patients presenting with claudication by anatomic level and used the Peripheral Artery Questionnaire (PAQ), a PAD-specific validated tool, to quantify patients' symptoms, function, treatment satisfaction, and quality of life. METHODS The Patient-centered Outcomes Related to Treatment Practices in peripheral Arterial disease: Investigating Trajectories (PORTRAIT) registry is a multicenter, international, prospective study of patients with PAD. Anatomic level of PAD was stratified as follows: aortoiliac only, femoral-popliteal only, infrapopliteal only, and multilevel disease. Health status information was collected at baseline and at 3, 6, and 12 months using the PAQ. Student t-test, χ2 test, and linear mixed effects models were examined. RESULTS Anatomic data were present in 623 (48.9%) of 1275 patients: 127 aortoiliac (20.4%), 221 femoral-popliteal (35.5%), 39 infrapopliteal (6.3%), and 236 multilevel disease (37.9%). Groups were similar by sex and race. Baseline PAQ summary scores differed between lesions, with multilevel disease having the lowest (poorest) estimated PAQ summary score (P = .014). Patients with aortoiliac disease were significantly younger, were more likely to be smokers, and presented with higher ankle-brachial index (all P < .05). Almost one-fourth of patients underwent an intervention by 3 months, 83% of which were endovascular. Repeated-measures analyses demonstrated a significant association between anatomic lesion and PAQ scores over time (P = .016), even after adjustment for age, sex, work status, ankle-brachial index, smoking, history of diabetes and chronic kidney disease, and country. Multilevel disease had the lowest adjusted average PAQ summary score over time (63.1; 95% confidence interval [CI], 60.8-65.5) and was significantly lower than aortoiliac (68.1; 95% CI, 64.8-71.4; P = .02) and femoral-popliteal (68.2; 95% CI, 65.8-70.6; P = .002) but not infrapopliteal (66.2; 95% CI, 60.5-72.0; P = .32). CONCLUSIONS Overall, patients with claudication had similar health status on presentation by level of disease, yet patients with isolated aortoiliac disease fared significantly better over time with regard to quality of life and PAQ scores. Subset analysis demonstrated that patients undergoing interventions for aortoiliac disease and multilevel disease, which were primarily endovascular procedures, appeared to improve health status more over time compared with femoral-popliteal and infrapopliteal interventions. No significant benefits were found with intervention for femoral-popliteal disease or infrapopliteal disease compared with medical management. Treatment of aortoiliac and multilevel disease for claudication should be considered by clinicians as it may represent the greatest potential benefit for improving overall health status in patients with PAD. Further studies evaluating intervention compared with medical management alone are needed to further evaluate this finding.

Patient-reported difficulties in affording health care and their association with health status outcomes in peripheral artery disease (PAD) have never been studied. We sought to determine whether financial barriers affected PAD symptoms at presentation, treatment patterns, and patient-reported health status in the year following presentation. A total of 797 United States (US) patients with PAD were identified from the Patient-centered Outcomes Related to TReatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) study, a prospective, multicenter registry of patients presenting to vascular specialty clinics with PAD. Financial barriers were defined as a composite of no insurance and underinsurance. Disease-specific health status was measured by Peripheral Artery Questionnaire (PAQ) and general health-related quality of life was measured by EuroQol 5 (EQ5D) dimensions at presentation and at 3, 6, and 12 months of follow-up. Among 797 US patients, 21% ( n = 165) of patients reported financial barriers. Patients with financial barriers presented at an earlier age (64 ± 9.5 vs 70 ± 9.4 years), with longer duration of symptoms (59% vs 49%) (all p ⩽ 0.05), were more depressed and had higher levels of perceived stress and anxiety. After multivariable adjustment, health status was worse at presentation in patients with financial barriers (PAQ: –7.0 [–10.7, –3.4]; p < 0.001 and EQ5D: –9.2 [–12.74, –5.8]; p < 0.001) as well as through 12 months of follow-up (PAQ: –8.4 [–13.0, –3.8]; p < 0.001 and EQ5D: –9.7 [–13.2, –6.2]; p < 0.001). In conclusion, financial barriers are associated with later presentation as well as poorer health status at presentation and at 12 months. ClinicalTrials.gov Identifier: NCT01419080

Purpose: To characterise labial articulatory pattern variability using the spatiotemporal index (STI) in speakers with idiopathic Parkinson's disease (PD) across different speaking rates and syllable-sentence conditions compared to age- and sex-matched healthy controls.Method: Ten speakers with mild-severe idiopathic PD and 10 controls produced "pa" and the Rainbow Passage at slow, typical and fast speech rates. Upper lip and lower lip kinematics were digitised during a motion capture system. Data were analysed using linear mixed modelling.Result: Regardless of the participant group, a high STI value was observed in the fast speech rate for the "pa" syllable condition, particularly for movements of the lower lip. As utterance rate increased, the control group showed the highest variability, followed by PD OFF and PD ON conditions. Syllable "pa" showed a greater STI value compared to both the first and second utterance of Rainbow Passage.Conclusion: PD manifests sufficient residual capacity to achieve near-normal motor compensation to preserve the consistency of lower lip movements during speech production. The lack of a significant difference in lip STI values between ON-OFF medication states suggests that dopaminergic treatment does not influence stability of speech for individuals with mild-moderate stage PD.

Evidence-Based Medicine (EBM) gathers evidence by analyzing large databases of medical literatures and retrieving relevant clinical thematic texts. However, the abstracts of medical articles generally show the themes of clinical practice, populations, research methods and experimental results of the thesis in an unstructurized manner, rendering inefficient retrieval of medical evidence. Abstract sentences contain contextual information, and there are complex semantic and grammatical correlations between them, making its classification different from that of independent sentences. This paper proposes a category detection algorithm based on Hierarchical Multi-connected Network (HMcN), regarding the category detection of EBM as a matter of classification of sequential sentences. The algorithm contains multiple structures: (1) The underlying layer produces a sentence vector by combining the pre-trained language model with Bi-directional Long Short Term Memory Network (Bi-LSTM), and applies a multi-layered self-attention structure to the sentence vector so as to work out the internal dependencies of the sentences. (2) The upper layer uses the multi-connected Bi-LSTMs model to directly read the original input sequence to add the contextual information for the sentence vector in the abstract. (3) The top layer optimizes the tag sequence by means of the conditional random field (CRF) model. The extensive experiments on public datasets have demonstrated that the performance of the HMcN model in medical category detection is superior to that of the state-of-the-art text classification method, and the F1 value has increased by 0.4%–0.9%.

433 Background: The SLUG gene plays an important role in EMT by repressing E-cadherin and promotes metastasis. Previous data suggest that overexpressed SLUG gene in pancreatic cancer (PC) showing a high frequency of metastasis and poor prognosis. As SLUG contribution to characteristics or metastatic features remains elusive, we clarified its functional roles in PC progression. Methods: A total of 2958 pancreatic tumors were analyzed using Whole Transcriptome sequencing, NextGen Sequencing (NGS) (NextSeq, 592 gene panel) or Whole Exome Sequencing (WES) (NovaSeq) (Caris Life Sciences, Phoenix, AZ). Microsatellite instability (MSI) status was tested by fragment analysis, immunohistochemistry (IHC) and NGS. PD-L1 expression was tested by IHC. Tumor mutational burden (TMB) was measured by counting all mutations found per tumor (a universal cutoff point of ≧10 mutations per MB). Immune cell fraction was calculated by quanTIseq (Finotello 2019, Genome Medicine). Results: A total of 1274 primary and 1684 metastatic pancreatic tumors were included for this study. They were divided equally into four classes in each group, according to their SLUG expression levels. Tumors in the highest quartile of SLUG expression (QH) showed significantly higher frequency in peritoneal-retroperitoneal-omentum metastasis (15.0%) compared to the lowest quartile (QL) (4.8%) (p = .0001). Similar trends were seen in the abdomen (6% vs 1%, p = .001) and bone (2.8% vs 0.0%, p = .005). However, liver (55.0% in QH vs 63.1% in QL) and lung (2.8% vs 14.1%) metastasis occurred most frequently in QL and the least frequently in QH (p = .0197 and p = .001, respectively). This data indicated that tumors with high SLUG gene expression levels tend to lead to disseminated metastasis, and with low expression levels, they tend to spread intravascularly. We detected significant differences among genetic mutations in ATM (5.7% in QL vs 1.8% in QH, p < 0.001) and APC (2.9% vs 0.5%, p < 0.001), and Wnt signaling expressions were higher in QL (4.6%) than QH (0.7%) (p < 0.001). Binary TMB-H and MSI-H tumors had higher frequencies in QL (2.7% and 2.1%) compared to QH (0.3% and 0.1%) (p < 0.001 in both). Contrastingly, PD-L1 expression levels were higher in QH (23.4%) compared to QL (11.0%) (p < 0.001) and had a linear relationship with the expression levels. The median values of the population of B cells, M1 and M2 macrophages were significantly higher in QH compared to QL, but those of myeloid dendritic and CD8+T cells conversely decrease as the SLUG expression increases. Conclusions: Our data indicated the SLUG expression level could determine the tumor characteristics in progression, especially the pattern of metastasis in PC, and it could possibly predict the prognosis and/or therapeutic effects. We also showed immune oncologic markers which have some relationships with SLUG expressions. Further investigation is warranted to better understand SLUG gene functions.

Based on the investigation and analysis of typical users in Beijing and Guangzhou, a comparative analysis of the load characteristics of different types of users is carried out, and the basic characteristics of the load characteristics of various types of users are summarized. In the calculation example, the hourly load of the typical buildings in Beijing and Guangzhou is simulated and analyzed for the whole year. The load stability of the hotel and hospital buildings is poor and the continuity is strong. The load stability of shopping malls, residential and office buildings Stronger and weaker in persistence; the imbalance rate of the cumulative cooling and heating load in the summer hot winter and warm winter area and the cumulative cooling and heating load in the air conditioning season is higher, while the unbalance rate in the cold area is lower.

Aiming to solve the low utilization and high operational cost in current data centers and the diversified resource requirements for different application types, we propose and investigate what we believe to be a novel rack-scale disaggregated optical data center network (RDON). Different types of hardware resources (i.e., CPU, memory, and storage) are deployed in standalone resource pools of the RDON. The RDON architecture encompasses nanosecond distributed fast optical switches for the low latency and high bandwidth interconnects between the computing and memory nodes, while electrical packet switches are utilized to support the traffic of latency insensitivity and low bandwidth between memory nodes and storage nodes. By replacing the onboard data bus with a network interconnection, RDON architecture can provide a fine granularity hardware resource and relieve the constraints of server-centric architecture. To assess the performance of the RDON under realistic scenarios, statistics of diverse applications are captured from the data center lab. The RDON is modeled based on the OMNeT++ discrete event simulator and compared with the server-centric architecture. Numerical results show that the performance of the RDON is closely coupled with the type of deployed application. Compared to the server-centric architecture, the RDON can achieve up to 2.44 × faster running time when running a single application, whereas at most 2.25 × is the fastest running time under coexisting diverse types of applications. Finally, the analysis of costs and power consumption show that, with respect to server-centric architecture, the RDON requires 21.5% extra capital cost but 46.7% less power consumption.

Integrated energy service is a new type of energy service to meet the diversified energy production and consumption of end customers, covering energy planning and design, engineering investment construction, multi-energy operation services and investment and financing services. This paper considers the energy input-output ratio, energy thermal efficiency and pollution gas emissions of the park, and comprehensively constructs an indicator system for the comprehensive energy park, which can provide guidance for the evaluation of comprehensive energy parks in the future.

With the depletion of fossil energy and the popularity of renewable energy, a comprehensive energy system with the goal of improving system energy efficiency and consuming renewable energy is booming. Based on the combined heat, power, and heat generation, this paper builds a comprehensive energy system operation optimization model in conjunction with ground source heat pumps. It aims to find the optimal operation strategy based on the actual situation of the park’s load, equipment capacity, and energy prices. Using the linear programming method, a mathematical model with the best economic efficiency of the integrated energy system is established, the optimal operation strategy for a typical day is analyzed, and the annual operation is simulated. Finally, it compares with conventional energy supply methods and analyzes the contribution to the consumption of renewable energy.

Aiming at guiding the design of fault diagnosis system for spacecraft from top-level, we proposes a new hybrid diagnosis framework in this paper. A variety of possible information is taken into account for better diagnostic ability. First of all, the brief introduction of BEAM architecture is given. The shortage of BEAM and some improvement strategies are analyzed. Then the new hybrid diagnosis framework for spacecraft is given in detail, including the types of knowledge and the modules involved. Finally, an example of how to use kinds of information to design the diagnosis system under the guidance of this framework is given.

New prophylactic drugs against malaria infections are urgently needed. We conducted randomized, double-blind, placebo-controlled, phase 2 trials of a new antimalarial drug combination, naphthoquine-azithromycin (NQAZ), to determine its safety and protective efficacy in a low-endemicity area of Southeast Asia. In the first trial, 127 healthy volunteers were randomized to receive two single doses of either 400 mg of NQAZ (200 mg of each drug), 800 mg of NQAZ (400 mg of each drug), or placebo on day 0 and day 30. Weekly follow-ups were performed for 2 months, and physical and clinical laboratory exams were done during the second and eighth week. Both drug regimens were well tolerated, without any serious adverse events. Four adverse events (transient and slight elevations of serum transaminase concentrations) were found only in the two drug-treated groups and thus might be drug-related. In the second trial, 353 volunteer villagers were randomized into the same three groups as in the first trial, and malaria infections were followed for a month. For the intention-to-treat analysis, both regimens offered greater than 90% prophylactic efficacies against all malaria infections. When the analysis was done according to parasite species, 400 mg and 800 mg NQAZ provided 81.63 and 90.59% prophylactic efficacies, respectively, against Plasmodium falciparum infections, whereas both offered 100% prophylactic efficacy against Plasmodium vivax and Plasmodium ovale. These trials showed that NQAZ had a good safety profile, and monthly single doses of 400 mg or 800 mg for adults offered excellent prophylaxis against malaria infections, especially the two relapsing species.

Comprehensive object understanding is a central challenge in visual recognition, yet most advances with deep neural networks reason about each aspect in isolation. In this work, we present a unified framework to tackle this broader object understanding problem. We formalize a refinement module that recursively develops understanding across space and semantics - "the more it looks, the more it sees." More concretely, we cluster the objects within each semantic category into fine-grained subcategories; our recursive model extracts features for each region of interest, recursively predicts the location and the content of the region, and selectively chooses a small subset of the regions to process in the next step. Our model can quickly determine if an object is present, followed by its class ("Is this a person?"), and finally report finegrained predictions ("Is this person standing?"). Our experiments demonstrate the advantages of joint reasoning about spatial layout and fine-grained semantics. On the PASCAL VOC dataset, our proposed model simultaneously achieves strong performance on instance segmentation, part segmentation and keypoint detection in a single efficient pipeline that does not require explicit training for each task. One of the reasons for our strong performance is the ability to naturally leverage highly-engineered architectures, such as Faster-RCNN, within our pipeline. Source code is available at https://github.com/ jingyanw/recursive-refinement.

To cope with the ever-increasing traffic growth of cloud computing and big-volume data services, a high-throughput, low-latency and energy-efficient data center network (DCN) architecture is desired. Recent advances in photonics make it feasible to exploit advantages of optical networking in designing data centers. In this paper we propose a novel optical DCN architecture that leverages already-available microsecond switching time optical components, together with an efficient traffic scheduler, which features a centralized control plane. Our architecture provides highly flexible connections between racks and has low reconfiguration time. Packet-level simulation results show that, with suitable choices of network dimensioning parameters, the proposed architecture can achieve low latency even with high offered load.

Advanced optical switching architectures, capable of scaling to thousands of ports while achieving low communication latency and reduced power consumption, are becoming a dominant theme for interconnection networks in next-generation data centers and high-performance computing systems. The arrayed waveguide grating (AWG) device, with its inherent ability to perform wavelength routing of many wavelengths in parallel, has been recognized as a promising core component for fast optical switching. Although the AWG is energy efficient (as essentially a passive optical device), has high-bandwidth switching capabilities and has relative simplicity and low cost, an inherent characteristic of switching schemes based on the AWG is potential wavelength oversubscription at switch output ports, which can lead to high packet blocking probabilities. To resolve this traffic congestion, this paper proposes a hybrid optical/electronic buffering scheme and a method for efficiently integrating fiber delay line buffer capacity into the AWG wavelength assignment scheme. The dimensioning of the optical and electronic buffer resources is then carried out using simulations. The results indicate that with the proper dimensioning, the hybrid-buffered AWG switch achieves significantly increased overall energy efficiency, compared to electronic-only buffering, while maintaining low latency and non-blocking performance. We also investigate the computational complexity of the required scheduling algorithm in the hybrid-buffered switch, which in turn allows us to estimate the required processing power of the switch controller.

Background & Aims The morbidity and mortality of spontaneous bacterial peritonitis (SBP) are high among patients with cirrhosis; however, the mechanisms of SBP pathogenesis are poorly understood. This study aimed to determine the role of the vitamin D-LL-37 pathway in the pathogenesis and treatment in patients with cirrhosis and SBP. Methods Serum 25-hydroxyvitamin D concentrations of 119 patients with chronic liver diseases were tested. Vitamin D receptor (VDR) and LL-37 in peritoneal leucocytes of cirrhotic and ascitic patients with SBP were detected and compared with those without SBP. Then the peritoneal macrophages of non-infected patients were cultured and activated by lipopolysaccharide (LPS) to analyse the changes of VDR and LL-37 expressions after incubation with vitamin D. Results Vitamin D deficiency or insufficiency was found in all of patients with cirrhosis. LPS inhibited VDR and LL-37 expression in peritoneal macrophages [1.3-fold decrease (P = 0.003) and 20-fold decrease (P = 0.010) respectively]. However, vitamin D could reverse the inhibition of both VDR and LL-37 [1.5-fold increase (P = 0.001) and 2000-fold increase (P < 0.001) respectively]. The effect of the incubation time following vitamin D supplementation was significant for LL-37 expression, with a peak expression found at 36 h (P < 0.001). Conclusions When vitamin D levels were low, bacteria inhibited VDR and LL-37 responses in peritoneal macrophages as a mechanism to evade antibacterial defence. Vitamin D supplementation could up-regulate peritoneal macrophage VDR and LL-37 expressions, which resulted in an enhanced immunological defence against SBP in patients with cirrhosis and ascites.

Globally, the concentration of large-scale data traffic transport has recently seen a shift from core Internet network infrastructure to include a rapidly growing segment of intra- and inter-datacenter interconnection networks. This trend is being driven by the progression from traditional web server-based service delivery toward massive-scale virtualized datacenter platforms, now serving the majority of Internet applications. With this shift, the development and application of very high-speed, high-capacity optical switching technologies are also being expanded from core metro and wide area networks to include massive-scale datacenter interconnection networks. Given the differences in requirements of the two domains, in terms of switching speeds, switch port densities and traffic load patterns, this is a challenging task that is currently attracting considerable interest from the optical communications and switching research community, optical switch vendors and large datacenter operators alike. In this chapter, we review recent developments in this area, focusing specifically on the various proposals for application of optical circuit switching to support the continued expansion of large-scale datacenter networks.

With healthcare costs sky rocketing and some medical specialties in short supply in some countries, patients are traveling abroad to seek the medical advice and treatments they need. This chapter looks at the availability, cost, and opportunities in the growing field of medical tourism. Medical tourism is evolving into "wellness tourism". In this variation, the core medical clinic is surrounded by ancillary services, such as psychological counseling, exercise facilities, and more. The idea is that health-minded patients can heal their lives and getting treatment for a specific malady. In the future, patients can both enjoy of hospitality form the hotel industry and use the technological advancements in their room while receiving medical service offered by expert staff from the hospitals. The most respected western hospitals and medical colleges have begun to tap the market for medical tourism. Hospitality bridging healthcare model consists of different ways of merging the operations of hospitals and hotels in order to provide superior service quality.