•On-chip silica monoliths are functionalized with proteins for use as porous supports in microfluidic immunoassays.•Index matching enhances sensitivity and dynamic range through volumetric ...detection.•Off-chip monolith functionalization enables highly scalable microfabrication.•Sub-pM (ng/mL) detection limits are achieved in a flow-through sandwich assay.
A sensitive and rapid absorbance based immunosensor that utilizes ex situ functionalized porous silica monoliths as volumetric optical detection elements are demonstrated in this study. The porous monolith structure facilitates high capture probe density and short diffusion length scales, enabling sensitive and rapid assays. Silica monoliths, synthesized and functionalized with immunocapture probes off-chip before integration into a sealed thermoplastic microfluidic device, serve to capture target antigens during perfusion through the porous structure. Gold nanoparticle immunoconjugates are combined with silver enhancement to create microscale silver clusters, followed by perfusion of an aqueous sucrose solution to limit light scattering and enhance optical signal. Using this approach, detection limits as low as 1ng/mL are achieved for a sandwich assay, with a dynamic range of at least 4 logs. The results confirm that the combination of on-chip index matching with functionalized porous silica monoliths can enable simple and practical flow-through immunoassays for the sensitive and rapid detection of target antigens.
To improve the image quality in cone-beam computerized tomography, a detector containing an insulator layer made of parylene-C was utilized in this study. In HgI2 sensors with photoconducting ...materials, we analyzed the signal based on the thickness of the parylene-C layer and leakage current. In addition, we tried to evaluate the reproducibility of Hgl2 that decreases gradually based on the continuous X-ray study. For the signal-to-noise ratio, we evaluated the photocurrent/darkcurrent (P/D) ratio according to the reduction in the leakage current. Our results indicated a detector reproducibility of 0.82% for a parylene-layer thickness of 18 μm, which represents an improvement of 0.43% over that of a “parylene-free” detector. Compared with the parylene-free sensors, the ones with a parylene layer displayed an approximately linear increase of the P/D ratio with increasing parylene layer thickness. For layers 18 or 20 μm thick this ratio, indicative of image quality, exhibited an improvement of ∼70 times or more in comparison to a parylene-free sensor.
Background: Capecitabine (Xeloda®) is a novel, oral, selectively tumor-activated fluoropyrimidine with proven activity in the treatment of advanced colorectal cancer. This trial was conducted to ...evaluate the efficacy, safety and feasibility of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer, with a view to replacing 5-fluorouracil (5-FU) in such patients. Patients and methods: Forty-four patients received capecitabine 1250 mg/m2 twice daily (2500 mg/m2/day) for 14 days followed by 7 days of rest, for up to six cycles. Results: Capecitabine produced an objective response rate of 34% (all partial responses) and stable disease in 14 patients (30%). The median time to disease progression (TTP) was 3.2 months 95% confidence interval (CI) 2.7–6.4 months and median overall survival was 9.5 months (95% CI 6.9–13.2 months). Hand-foot syndrome (HFS), nausea, anorexia, diarrhea and vomiting were the most common adverse events. While HFS was the most frequent grade 3/4 toxicity (National Cancer Institute Common Toxicity Criteria), only 9% of patients experienced grade 3 HFS. Severe myelosuppression was not reported during the study. Conclusions: Capecitabine monotherapy is active and well tolerated as first-line therapy in patients with advanced/metastatic gastric cancer. Larger comparative trials investigating capecitabine-based combination regimens in patients with advanced gastric cancer are warranted.
Abstract Background To overcome a shortage of donors, cadaveric pediatric en bloc kidneys can be used to expand the donor pool. Recent evidence shows that en bloc kidney transplantation (EBKT) has ...better outcomes than standard-criteria deceased adult donor kidney transplantation. We reviewed our experiences of EBKT and their outcomes. Methods From September 1996 to January 2016, 15 EBKTs were performed in Asan Medical Center. The characteristics of donors and recipients were analyzed. Graft survival was analyzed by means of serum creatinine levels. Results Nine male and 6 female donors were used. The mean age and body weight of donors was 2.79 years (range, 0.25–14) and 13.14 kg (range, 5.5–35). The mean weight of en bloc kidneys was 117.43 g (range, 36–146). Recipient median age was 39.13 years and body weight was 49.47 kg. Ureteral anastomosis was performed by means of side-to-side anastomosis and then bladder anastomosis in 9 patients and by bladder patch anastomosis in 4 patients. Serum creatinine levels at discharge and latest follow-up were 0.97 mg/dL (range, 0.7–1.54) and 0.89 mg/dL (range, 0.44–2.58). Delayed graft function developed in 3 patients and clinical rejection developed in 2 patients. We performed graftectomy on post-operative day 1 because of graft thrombosis. The rest maintained their graft function well. Graft survival was comparable with that of kidney transplantation from standard donors. Conclusions EBKT showed excellent graft function and outcomes at our center. As an approach to expand the donor pool and improve graft utilization, EBKT is acceptable and should be more widely used.
The ductile fracture of the clinched joint is studied by the experiments and simulations using a modified Rousselier model. Although tension failure has been successfully predicted by the classical ...Rousselier damage model, its predictive capability on shear failure is seldom discussed. The microstructure of the clinched joint reveals that the ductile fracture occurs in the neck thickness under the shear and tensile force. So this paper is mainly concerned with application of a modified Rousselier damage model developed by the Guo on the description of the failure behavior of the clinched joint. The three experimental specimens were designed in order to calibrate the damage coefficients kω and the initial void volume fraction f0. The material parameters of the modified Rousselier model were identified by an inverse method comparing the experimental results with the numerical results. The modified Rousselier model could capture both tension and shear failure behavior of the clinched joint. The numerical results and the experimental results indicate the Lode parameters in the new damage evolution model can capture the failure behavior and the evolution process during the clinching process.
Topic 3 of the Model Inter-Comparison Study for Asia (MICS-Asia) Phase III examines how online coupled air quality models perform in simulating high aerosol pollution in the North China Plain region ...during wintertime haze events and evaluates the importance of aerosol radiative and microphysical feedbacks. A comprehensive overview of the MICS-Asia III Topic 3 study design, including descriptions of participating models and model inputs, the experimental designs, and results of model evaluation, are presented. Six modeling groups from China, Korea and the United States submitted results from seven applications of online coupled chemistry–meteorology models. Results are compared to meteorology and air quality measurements, including data from the Campaign on Atmospheric Aerosol Research Network of China (CARE-China) and the Acid Deposition Monitoring Network in East Asia (EANET). The correlation coefficients between the multi-model ensemble mean and the CARE-China observed near-surface air pollutants range from 0.51 to 0.94 (0.51 for ozone and 0.94 for PM2.5) for January 2010. However, large discrepancies exist between simulated aerosol chemical compositions from different models. The coefficient of variation (SD divided by the mean) can reach above 1.3 for sulfate in Beijing and above 1.6 for nitrate and organic aerosols in coastal regions, indicating that these compositions are less consistent from different models. During clean periods, simulated aerosol optical depths (AODs) from different models are similar, but peak values differ during severe haze events, which can be explained by the differences in simulated inorganic aerosol concentrations and the hygroscopic growth efficiency (affected by varied relative humidity). These differences in composition and AOD suggest that future models can be improved by including new heterogeneous or aqueous pathways for sulfate and nitrate formation under hazy conditions, a secondary organic aerosol (SOA) formation chemical mechanism with new volatile organic compound (VOCs) precursors, yield data and approaches, and a more detailed evaluation of the dependence of aerosol optical properties on size distribution and mixing state. It was also found that using the ensemble mean of the models produced the best prediction skill. While this has been shown for other conditions (for example, the prediction of high-ozone events in the US (McKeen et al., 2005)), this is to our knowledge the first time it has been shown for heavy haze events.
In the egg production industry, trace elements are required as additional dietary supplements to play vital roles in performance and egg quality. Compared to inorganic microelements (ITs), ...appropriate dose of organic trace microelements (OTs) are environmentally friendly and sufficient to satisfy the needs of hens. In order to evaluate the extent to which low-dose OTs replace whole ITs, the effects of organic copper, zinc, manganese, and iron compound on the performance, eggshell quality, antioxidant capacity, immune function, and mineral deposition of old laying hens were investigated. A total of 1 080 57-week-old Jing Hong laying hens were assigned to five groups with six replicates of 36 layers each for an 8-week experimental period. The birds were fed either a basal diet (control treatment (CT)) or the basal diet supplemented with commercial levels of inorganic trace elements (IT 100%) or the equivalent organic trace elements at 20%, 30%, and 50% of the inorganic elements (OT 20%, OT 30%, and OT 50%, respectively). Results showed that compared with those in the CT treatment, feeding hens with inorganic or organic microelement diet had significant effects on the eggshell quality, antioxidant capacity, immune function, and mineral deposition of old laying hens (P < 0.05). The eggshell strength and ratio between OT 30%, OT 50%, and IT 100% were similar at weeks 4 and 8, and the eggshell thickness of these groups was also similar at weeks 6 and 8. At week 8, the eggshell colour in OT 50% was darker than that in IT 100%. The mineral content in the eggshells of OT 50% and IT 100% significantly increased (P < 0.001), with no significant difference in effective thickness, mammillary thickness, and mammillary knob width between groups. There were no differences in the malondialdehyde content, total antioxidant capacity, and total superoxide dismutase activity in serum between OT 30%, OT 50%, and IT100%. While the catalase activities, the interleukin-1β, interleukin-10, immunoglobulin G, and immunoglobulin M concentrations in serum were not significantly different between OT 50% and IT 100%. The mineral contents in the faeces of the organic groups were considerably reduced compared with those in IT 100% (P < 0.001). In conclusion, dietary supplementation with 30–50% organic compound microelements has the potential to replace 100% inorganic microelements in the hen industry for improving eggshell quality, mineral deposition in the eggshell, antioxidant capacity, and immune function, and reducing emissions to the environment without negative effects on laying performance.
Although core needle biopsy was introduced as a diagnostic alternative to fine-needle aspiration, the utility and safety of core needle biopsy for thyroid nodules in a large population has yet to be ...studied comprehensively. We evaluate core needle biopsy yields on a large-scale basis to investigate its potential in the preliminary diagnosis of thyroid nodules.
Between March 2005 and December 2013, 2448 initially detected thyroid nodules from 2120 consecutive patients who underwent core needle biopsy were retrospectively evaluated. Of these, 72 thyroid nodules from 63 patients were excluded due to prior fine-needle aspiration attempts. The inconclusive and conclusive result rates, diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and unnecessary surgery rate of core needle biopsy were evaluated.
With core needle biopsy as the first-line method, the inconclusive result rate was 11.9% (283/2376) and the conclusive result rate was 88.1% (2093/2376). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of core needle biopsy for the diagnosis of malignancy were 96.7% (1160/1200), 89.7% (347/387), 100% (813/813), 100% (347/347), and 95.3% (813/853), respectively. There were no major complications and 12 minor complications.
We have demonstrated that first-line use of core needle biopsy may well improve diagnostic accuracy in thyroid nodules, reducing inconclusive or false-negative results and unnecessary operations. Such benefits underscore the promising role of core needle biopsy in managing thyroid nodules and optimizing related surgical decision-making.
BACKGROUNDThe utility of performing early myocardial revascularization among patients presenting with inducible myocardial ischemia and low left ventricular ejection fraction (LVEF) is currently ...unknown. OBJECTIVESIn this study, we sought to assess the relationship between stress-induced myocardial ischemia, revascularization, and all-cause mortality (ACM) among patients with normal vs low LVEF. METHODSWe evaluated 43,443 patients undergoing stress-rest single-photon emission computed tomography myocardial perfusion imaging from 1998 to 2017. Median follow-up was 11.4 years. Myocardial ischemia was assessed for its interaction between early revascularization and mortality. A propensity score was used to adjust for nonrandomization to revascularization, followed by multivariable Cox modeling adjusted for the propensity score and clinical variables to predict ACM. RESULTSThe frequency of myocardial ischemia varied markedly according to LVEF and angina, ranging from 6.7% among patients with LVEF ≥55% and no typical angina to 64.0% among patients with LVEF <45% and typical angina (P < 0.001). Among 39,883 patients with LVEF ≥45%, early revascularization was associated with increased mortality risk among patients without ischemia and lower mortality risk among patients with severe (≥15%) ischemia (HR: 0.70; 95% CI: 0.52-0.95). Among 3,560 patients with LVEF <45%, revascularization was not associated with mortality benefit among patients with no or mild ischemia, and was associated with decreased mortality among patients with moderate (10%-14%) (HR: 0.67; 95% CI: 0.49-0.91) and severe (≥15%) (HR: 0.55; 95% CI: 0.38-0.80) ischemia. CONCLUSIONSWithin this cohort, early myocardial revascularization was associated with a significant reduction in mortality among both patients with normal LVEF and severe inducible myocardial ischemia and patients with low LVEF and moderate or severe inducible myocardial ischemia.
Curcumin, a natural, biologically active compound extracted from rhizomes of Curcuma species, has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. The ...mechanism by which curcumin initiates apoptosis remains poorly understood. In the present report we investigated the effect of curcumin on the activation of the apoptotic pathway in human renal Caki cells. Treatment of Caki cells with 50 µM curcumin resulted in the activation of caspase 3, cleavage of phospholipase C-γ1 and DNA fragmentation. Curcumin-induced apoptosis is mediated through the activation of caspase, which is specifically inhibited by the caspase inhibitor, benzyloxycarbony-Val-Ala-Asp-fluoromethyl ketone. Curcumin causes dose-dependent apoptosis and DNA fragmentation of Caki cells, which is preceded by the sequential dephosphorylation of Akt, down-regulation of the anti-apoptotic Bcl-2, Bcl-XL and IAP proteins, release of cytochrome c and activation of caspase 3. Cyclosporin A, as well as caspase inhibitor, specifically inhibit curcumin-induced apoptosis in Caki cells. Pre-treatment with N-acetyl-cysteine, markedly prevented dephosphorylation of Akt, and cytochrome c release, and cell death, suggesting a role for reactive oxygen species in this process. The data indicate that curcumin can cause cell damage by inactivating the Akt-related cell survival pathway and release of cytochrome c, providing a new mechanism for curcumin-induced cytotoxicity.
PDF
