Summary Background China has a quarter of all patients with multidrug-resistant tuberculosis (MDRTB) worldwide, but less than 5% are in quality treatment programmes. In a before-and-after study we ...aimed to assess the effect of a comprehensive programme to provide universal access to diagnosis, treatment, and follow-up for MDRTB in four Chinese cities (population 18 million). Methods We designated city-level hospitals in each city to diagnose and treat MDRTB. All patients with smear-positive pulmonary tuberculosis diagnosed in Center for Disease Control (CDC) clinics and hospitals were tested for MDRTB with molecular and conventional drug susceptibility tests. Patients were treated with a 24 month treatment package for MDRTB based on WHO guidelines. Outpatients were referred to the CDC for directly observed therapy. We capped total treatment package cost at US$4644. Insurance reimbursement and project subsidies limited patients' expenses to 10% of charges for services within the package. We compared data from a 12 month programme period (2011) to those from a retrospective survey of all patients with MDRTB diagnosed in the same cities during a baseline period (2006–09). Findings 243 patients were diagnosed with MDRTB or rifampicin-resistant tuberculosis during the 12 month programme period compared with 92 patients (equivalent to 24 per year) during the baseline period. 172 (71%) of 243 individuals were enrolled in the programme. Time from specimen collection for resistance testing to treatment initiation decreased by 90% (from median 139 days IQR 69–207 to 14 days 10–21), the proportion of patients who started on appropriate drug regimen increased 2·7 times (from nine 35% of 26 patients treated to 166 97% of 172), and follow-up by the CDC after initial hospitalisation increased 24 times (from one 4% of 23 patients to 163 99% of 164 patients). 6 months after starting treatment, the proportion of patients remaining on treatment increased ten times (from two 8% of 26 patients to 137 80% of 172), and 116 (67%) of 172 patients in the programme period had negative cultures or clinical–radiographic improvement. Patients' expenses for hospital admission after MDRTB diagnosis decreased by 78% (from $796 to $174), reducing the ratio of patients' expenses to annual household income from 17·6% to 3·5% (p<0·0001 for all comparisons between baseline and programme periods). However, 36 (15%) patients did not start or had to discontinue treatment in the programme period because of financial difficulties. Interpretation This comprehensive programme substantially increased access to diagnosis, quality treatment, and affordable treatment for MDRTB. The programme could help China to achieve universal access to MDRTB care but greater financial risk protection for patients is needed. Funding Bill & Melinda Gates Foundation.
Abstract Background Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be ...accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources. Objectives The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD. Methods A cohort of 2,324 patients from 4 independent centers was studied. Patients underwent coronary angiography for suspected CAD. Groups were divided as follows: normal coronary artery (NCA), nonobstructive coronary atherosclerosis (NOCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). Plasma metabolomic profiles were determined by liquid chromatography–quadrupole time-of-flight mass spectrometry and were analyzed by multivariate statistics. Results We made 12 cross-comparisons to and within CAD to characterize metabolic disturbances. We focused on comparisons of NOCA versus NCA, SA versus NOCA, UA versus SA, and AMI versus UA. Other comparisons were made, including SA versus NCA, UA versus NCA, AMI versus NCA, UA versus NOCA, AMI versus NOCA, AMI versus SA, significant CAD (SA/UA/AMI) versus nonsignificant CAD (NCA/NOCA), and acute coronary syndrome (UA/AMI) versus SA. A total of 89 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism, increased amino acid metabolism, increased short-chain acylcarnitines, decrease in tricarboxylic acid cycle, and less biosynthesis of primary bile acid. For differential diagnosis, 12 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.938 to 0.996 in the discovery phase (n = 1,086), predictive values of 89.2% to 96.0% in the test phase (n = 933), and 85.3% to 96.4% in the 3-center external sets (n = 305). Conclusions Plasma metabolomics are powerful for characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression.
Graphene has emerged as the most popular topic in the active research field since graphene's discovery in 2004 by Andrei Geim and Kostya Novoselov. Since then, graphene research has exponentially ...accelerated because of its extraordinary properties, which have attracted the interest of researchers all over the world. For example, among the key properties are its thermal conductivity, electrical conductivity, optical transparency, and mechanical properties. These remarkable properties of graphene show its promise for applications in different industries including optical electronics, photovoltaic systems and others. However, the large-scale production and transfer method onto target substrates of monolayer graphene for commercial and industrial applications are still under study in the improvement stage. Therefore, this review presents the state-of-the-art research activities and latest advancement in the synthesis of graphene using various carbon precursors including solid, liquid and gas carbon feedstocks. The characterization methods have also been critically discussed in this review. In addition, the advancement in the transfer methods onto target substrates for achieving clean and high-quality transferred graphene have been thoroughly reviewed. Furthermore, the current growth mechanisms of single and multilayer graphene have also been discussed.
Graphene has emerged as the most popular topic in the active research field since graphene's discovery in 2004 by Andrei Geim and Kostya Novoselov.
The growth of high-quality single crystals of graphene by chemical vapor deposition on copper (Cu) has not always achieved control over domain size and morphology, and the results vary from lab to ...lab under presumably similar growth conditions. We discovered that oxygen (O) on the Cu surface substantially decreased the graphene nucleation density by passivating Cu surface active sites. Control of surface O enabled repeatable growth of centimeter-scale single-crystal graphene domains. Oxygen also accelerated graphene domain growth and shifted the growth kinetics from edge-attachment-limited to diffusion-limited. Correspondingly, the compact graphene domain shapes became dendritic. The electrical quality of the graphene films was equivalent to that of mechanically exfoliated graphene, in spite of being grown in the presence of O.
Summary Background China scaled up a tuberculosis control programme (based on the directly observed treatment, short-course DOTS strategy) to cover half the population during the 1990s, and to the ...entire population after 2000. We assessed the effect of the programme. Methods In this longitudinal analysis, we compared data from three national tuberculosis prevalence surveys done in 1990, 2000, and 2010. The 2010 survey screened 252 940 eligible individuals aged 15 years and older at 176 investigation points, chosen by stratified random sampling from all 31 mainland provinces. All individuals had chest radiographs taken. Those with abnormal radiographs, persistent cough, or both, were classified as having suspected tuberculosis. Tuberculosis was diagnosed by chest radiograph, sputum-smear microscopy, and culture. Trained staff interviewed each patient with tuberculosis. The 1990 and 2000 surveys were reanalysed and compared with the 2010 survey. Findings From 1990 to 2010, the prevalence of smear-positive tuberculosis decreased from 170 cases (95% CI 166–174) to 59 cases (49–72) per 100 000 population. During the 1990s, smear-positive prevalence fell only in the provinces with the DOTS programme; after 2000, prevalence decreased in all provinces. The percentage reduction in smear-positive prevalence was greater for the decade after 2000 than the decade before (57% vs 19%; p<0·0001). 70% of the total reduction in smear-positive prevalence (78 of 111 cases per 100 000 population) occurred after 2000. Of these cases, 68 (87%) were in known cases—ie, cases diagnosed with tuberculosis before the survey. Of the known cases, the proportion treated by the public health system (using the DOTS strategy) increased from 59 (15%) of 370 cases in 2000 to 79 (66%) of 123 cases in 2010, contributing to reduced proportions of treatment default (from 163 43% of 370 cases to 35 22% of 123 cases) and retreatment cases (from 312 84% of 374 cases to 48 31% of 137 cases; both p<0·0001). Interpretation In 20 years, China more than halved its tuberculosis prevalence. Marked improvement in tuberculosis treatment, driven by a major shift in treatment from hospitals to the public health centres (that implemented the DOTS strategy) was largely responsible for this epidemiological effect. Funding Chinese Ministry of Health.
China is in a critical stage of ambient air quality management after global attention on pollution in its cities. Industrial development and urbanization have led to alarming levels of air pollution ...with serious health hazards in densely populated cities. The quantification of cause-specific PM2.5-related health impacts and corresponding economic loss estimation is crucial for control policies on ambient PM2.5 levels. Based on ground-level direct measurements of PM2.5 concentrations in 338 Chinese cities for the year 2016, this study estimates cause-specific mortality using integrated exposure-response (IER) model, non-linear power law (NLP) model and log-linear (LL) model followed by morbidity assessment using log-linear model. The willingness to pay (WTP) and cost of illness (COI) methods have been used for PM2.5-attributed economic loss assessment. In 2016 in China, the annual PM2.5 concentration ranged between 10 and 157 μg/m3 and 78.79% of the total population was exposed to >35 μg/m3 PM2.5 concentration. Subsequently, the national PM2.5-attributable mortality was 0.964 (95% CI: 0.447, 1.355) million (LL: 1.258 million and NPL: 0.770 million), about 9.98% of total reported deaths in China. Additionally, the total respiratory disease and cardiovascular disease-specific hospital admission morbidity were 0.605 million and 0.364 million. Estimated chronic bronchitis, asthma and emergency hospital admission morbidity were 0.986, 1.0 and 0.117 million respectively. Simultaneously, the PM2.5 exposure caused the economic loss of 101.39 billion US$, which is 0.91% of the national GDP in 2016. This study, for the first time, highlights the discrepancies associated with the three commonly used methodologies applied for cause-specific mortality assessment. Mortality and morbidity results of this study would provide a measurable assessment of 338 cities to the provincial and national policymakers of China for intensifying their efforts on air quality improvement.
The spatial distributions of annual mean PM2.5 concentrations (μg/m3) (left) and corresponding total premature mortality per 100,000 population attributable to PM2.5 (right) in 338 cities in China. Display omitted
•This study provides a comprehensive analysis of PM2.5 associated health risk in China using three most prevalent methods.•Total PM2.5-related death was 0.964 million using IER method, 1.258 million using LL and 0.770 million using NPL method.•Cities with high premature mortality were largely located in heavily polluted and densely populated regions.•Total economic loss due to PM2.5 exposure was 101.39 billion US$, about 0.91% of the total Chinese GDP.•Only 8.3% of total premature deaths could be avoided by meeting national PM2.5-target in 2030.
Summary Background Human babesiosis is an emerging zoonosis. “ Babesia venatorum ” has been identified in only four asplenic men and a child so far. We aimed to describe the epidemiological, ...clinical, and laboratory characteristics of a series of cases with “ B venatorum ” infection identified in a sentinel hospital in China. Methods We recruited participants with a recent tick bite at Mudanjiang Forestry Central Hospital, Heilongjiang province, China. Cases were diagnosed through PCR followed by sequencing, microscopic identification, or isolation by animal inoculation, or both. Findings 48 individuals (30 women or girls; median age 45 years, range 7 months to 75 years) with “ B venatorum ” infection were identified. 32 of these individuals were confirmed cases and 16 were probable cases. None of the 48 cases had received a blood transfusion or had a splenectomy. Geographically, cases were distributed diffusely throughout the hospital catchment area. Of the 32 confirmed cases, 21 (66%) presented with a fever, 13 (41%) with a headache, 12 (38%) with myalgia or arthralgia, and three (9%) with chills. 14 (44%) patients had fatigue, eight (25%) had dizziness, and eight (25%) had hypersomnia. Six (19%) patients had an erythematous non-pruritic rash around the tick-bite site and two (6%) had lymphadenopathy. Seven (22%) and four (13%) patients had anaemia and thrombocytopenia, respectively, and seven (50%) of 14 patients with confirmed infection had increased hepatic transaminase concentrations. In the confirmed cases, concentrations of intercellular adhesion molecule 3 (p<0·001), P-selectin (p<0·05), and platelet endothelial cell adhesion molecule 1 (p<0·001) were significantly reduced, whereas tumour necrosis factor α (p<0·01) and vascular cell adhesion molecule 1 (p<0·001) were significantly increased. Interpretation “ B venatorum ” infection should be included in the differential diagnosis of patients with a tick-exposure history in areas where this pathogen has previously been identified in ticks or people. Funding Natural Science Foundation of China and Mega-Project for Infectious Diseases.
Contact and projection electron radiography of static targets was demonstrated using a laser-plasma accelerator driven by a kilojoule, picosecond-class laser as a source of relativistic electrons ...with an average energy of 20 MeV. Objects with areal densities as high as 7.7 g/cm
were probed in materials ranging from plastic to tungsten, and radiographs with resolution as good as 90 μm were produced. The effects of electric fields produced by the laser ablation of the radiography objects were observed and are well described by an analytic expression relating imaging magnification change to electric-field strength.
Ovarian cancer spheroids constitute a metastatic niche for transcoelomic spread that also engenders drug resistance. Spheroid-forming cells express active STAT3 signaling and display stem cell-like ...properties that may contribute to ovarian tumor progression. In this study, we show that STAT3 is hyperactivated in ovarian cancer spheroids and that STAT3 disruption in this setting is sufficient to relieve chemoresistance. In an NSG murine model of human ovarian cancer, STAT3 signaling regulated spheroid formation and self-renewal properties, whereas STAT3 attenuation reduced tumorigenicity. Mechanistic investigations revealed that Wnt signaling was required for STAT3-mediated spheroid formation. Notably, the Wnt antagonist DKK1 was the most strikingly upregulated gene in response to STAT3 attenuation in ovarian cancer cells. STAT3 signaling maintained stemness and interconnected Wnt/β-catenin signaling via the miR-92a/DKK1-regulatory pathways. Targeting STAT3 in combination with paclitaxel synergistically reduced peritoneal seeding and prolonged survival in a murine model of intraperitoneal ovarian cancer. Overall, our findings define a STAT3-miR-92a-DKK1 pathway in the generation of cancer stem-like cells in ovarian tumors, with potential therapeutic applications in blocking their progression.
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Background Few studies have investigated the use of postoperative extracorporeal membrane oxygenation (ECMO) in acute type A aortic dissection (aTAAD). We identified aTAAD surgical patients at risk ...of ECMO implantation postoperatively and analyzed the prognosis of these patients. Methods We retrospectively reviewed 162 consecutive aTAAD patients undergoing operations from January 2008 to December 2015. Patient data were analyzed for risk factors leading to an ECMO requirement. Short-term and long-term outcomes in patients who did and did not require ECMO were compared. Results Postoperative ECMO was required in 20 patients (12.3%), and in-hospital mortality was higher in the ECMO group (65.0% vs 8.5%, p < 0.001). Factors predicting postoperative ECMO were preoperative hemodynamic instability ( p = 0.049), aortic cross-clamp time ( p = 0.036), and postoperative peak creatinine kinase-MB ( p = 0.002). ECMO survivors presented at a younger age ( p = 0.036) and had a less postoperative blood transfusion ( p = 0.034) than ECMO nonsurvivors. The postdischarge survival rate was equivalent in patients with or without ECMO support. Conclusions Although postoperative ECMO is an important predictor of in-hospital death, this pilot study showed that aTAAD patients supported with postoperative ECMO who survive to hospital discharge have a long-term survival comparable to patients who did not receive ECMO.
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