Left atrial fibrosis is prominent in patients with atrial fibrillation (AF). Extensive atrial tissue fibrosis identified by delayed enhancement magnetic resonance imaging (MRI) has been associated with poor outcomes of AF catheter ablation.To characterize the feasibility of atrial tissue fibrosis estimation by delayed enhancement MRI and its association with subsequent AF ablation outcome.Multicenter, prospective, observational cohort study of patients diagnosed with paroxysmal and persistent AF (undergoing their first catheter ablation) conducted between August 2010 and August 2011 at 15 centers in the United States, Europe, and Australia. Delayed enhancement MRI images were obtained up to 30 days before ablation.Fibrosis quantification was performed at a core laboratory blinded to the participating center, ablation approach, and procedure outcome. Fibrosis blinded to the treating physicians was categorized as stage 1 (<10% of the atrial wall), 2 (≥10%-<20%), 3 (≥20%-<30%), and 4 (≥30%). Patients were followed up for recurrent arrhythmia per current guidelines using electrocardiography or ambulatory monitor recording and results were analyzed at a core laboratory. Cumulative incidence of recurrence was estimated by stage at days 325 and 475 after a 90-day blanking period (standard time allowed for arrhythmias related to ablation-induced inflammation to subside) and the risk of recurrence was estimated (adjusting for 10 demographic and clinical covariates).Atrial tissue fibrosis estimation by delayed enhancement MRI was successfully quantified in 272 of 329 enrolled patients (57 patients [17%] were excluded due to poor MRI quality). There were 260 patients who were followed up after the blanking period (mean [SD] age of 59.1 [10.7] years, 31.5% female, 64.6% with paroxysmal AF). For recurrent arrhythmia, the unadjusted overall hazard ratio per 1% increase in left atrial fibrosis was 1.06 (95% CI, 1.03-1.08; P < .001). Estimated unadjusted cumulative incidence of recurrent arrhythmia by day 325 for stage 1 fibrosis was 15.3% (95% CI, 7.6%-29.6%); stage 2, 32.6% (95% CI, 24.3%-42.9%); stage 3, 45.9% (95% CI, 35.5%-57.5%); and stage 4, 51.1% (95% CI, 32.8%-72.2%) and by day 475 was 15.3% (95% CI, 7.6%-29.6%), 35.8% (95% CI, 26.2%-47.6%), 45.9% (95% CI, 35.6%-57.5%), and 69.4% (95% CI, 48.6%-87.7%), respectively. Similar results were obtained after covariate adjustment. The addition of fibrosis to a recurrence prediction model that includes traditional clinical covariates resulted in an improved predictive accuracy with the C statistic increasing from 0.65 to 0.69 (risk difference of 0.05; 95% CI, 0.01-0.09).Among patients with AF undergoing catheter ablation, atrial tissue fibrosis estimated by delayed enhancement MRI was independently associated with likelihood of recurrent arrhythmia. The clinical implications of this association warrant further investigation.
This paper investigates the balancing and scheduling of integrated energy systems (IESs) spanning across geographically adjacent areas and regions that involve multiple energy vectors and multiple stakeholders. This is through an extremely complex problem to be formulated and solved, but often leading to enormous technical and economic benefit if the synergies among different energy vectors and the aggregated demand response (ADR) are fully utilized. To achieve the objective, a multiple interconnected-integrated energy systems (MI-IESs) model based on energy interaction and ADR is first established to capture the coupling relationship between different energy vectors. Then, an ADR mechanism is proposed, based on centralized dispatching by the IES operator (IESO) and distribution coordination of IESs, and further assisted with a dynamic interactive pricing mechanism based on load time distribution and renewable energy consumption level. To optimize the operation of such a complex energy system, the MI-IESs model is first decoupled, then an adaptive step size regularized alternating direction multiplier method (AR-ADMM) is proposed to solve the energy dispatch problem, while the information privacy of each IES is also preserved. The simulation results show that the proposed scheduling strategy can not only effectively balance the benefits of individual IES and MI-IESs, but also achieve a win-win situation between MI-IESs and the IESO, and the adopted solution algorithm protects the data privacy of MI-IESs. Furthermore, the solution time of the proposed AR-ADMM algorithm is 13% less than that of the conventional ADMM (C-ADMM) algorithm.
<p>PDF - 194K, Supplementary Figure S1. Immunohistochemistry for PLCE1 protein expression with areas of annotation selected for image quantification (20x.)Supplementary Table S1. PLCE1 mRNA expression in GCA, GNCA and ESCC tumor tissues and tumor-normal expression fold change by characteristics of the subjects. Supplementary Table S2. PLCE1 protein expression in GCA, GNCA and ESCC tumor tissues and tumor-normal expression fold change in ESCC by characteristics of the participants. Supplementary Table S3. The probe-specific association between PLCE1 mRNA expression in tumors and tumor-normal fold change and mortality of ESCC, GCA, and GNCAs. Supplementary Table S4. Spearman correlation coefficients (P values) between PLCE1 mRNA expression in normal tissues of ESCC, GCA, and GNCA and selected PLCE1 SNPs.</p>
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10−8, and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19–1.40) and P= 7.63 × 10−10. An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
Background To explore the efficacy and toxicity of simultaneous modulated accelerated radiotherapy (SMART) concurrently with cisplatin (CDDP) and S1 (tegafur/gimeracil/oteracil) in elderly patients with esophageal squamous cell carcinoma (ESCC). Methods This single-arm, phase II study enrolled pathologically confirmed, stage II–IVa ESCC of 70–80 years old and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2. Patients received SMART (64 Gy to gross tumor volume and 48 Gy to clinical target volume in 30 fractions) with concurrent CDDP (day 1 of each week) and S1 (days 1–14, 22–35). The primary endpoint was objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicities. Results Thirty-seven eligible patients were analyzed with median follow-up of 25.7 months for all and 46.1 months for survivors. The ORR was 88.9%. Patients with baseline weight loss <5% (p=0.050) and nutritional risk index (NRI) ≥105.2 (p=0.023) had better tumor response. Median PFS was 13.8 months with 2-year PFS of 37.5%. Median OS was 27.7 months with 2-year OS of 57.5%. OS was significantly associated with ECOG PS (p=0.005), stage (p=0.014), gross tumor volume (p=0.004), baseline NRI (p=0.036), baseline C-reactive protein (CRP) level (p=0.003) and tumor response (p=0.000). CRP level (p=0.016) and tumor response (p=0.021) were independently prognostic of OS. ≥grade 3 anemia, neutropenia and thrombocytopenia occurred in 2.7%, 10.8% and 13.5% of patients; ≥grade 3 esophagitis and pneumonitis occurred in 18.9% and 2.7% of patient, respectively. Conclusion SMART concurrently with CDDP/S1 yielded satisfactory response rate, survival outcome and tolerable treatment-related toxicities in elderly patients with ESCC. Further studies are warranted to validate the results.
Objective To investigate the corneal morphologic changes induced by wearing rigid gas permeable contact lenses (RGPCL) and soft contact lenses (SCL). Methods It was a case-control study. Sixty high myopia subjects participated in the study. Thirty were given RGPCL and 30 were given SCL Three, 6 and 12 months after wearing the contact lenses, confocal microscopy was used to observe the central and peripheral corneal epithelial cells, the density of the Langerhans cells,nerve fibers, corneal stroma, and endothelial cells of the 2 groups. A two-way ANOVA was used to analyze the data. Results Twelve months after contact lens wearing, the epithelial cell density of the corneal surface was lower in the SCL group than in the RGPCL group (F=4.262, P＜0.05), and corneal vesicles and corneal gutata were occasionally observed. The density of the Langerhans cells both in the central and peripheral cornea was higher in the SCL group (F=5.362, P＜0.05;F=-14.910, P＜0.05), and the tortuosity of the nerve fibers increased significantly in the eyes of those wearing SCL compared with those wearing RGPCL. The density of the anterior stromal cells was lower (P＜0.05) while the microdot densities in the stroma were higher in the SCL group than in the RGPCL group (P＜0.05). The polymorphology of the corneal endothelial cells was more apparent in the SCL group, but the density of the endothelial cells was similar for the 2 groups. The thickness of the central corneal epithelium was thinner for SCL wearers compared to RGPCL wearers (F=-2.061, P＜0.05). There were no differences for all of the indices within the same group at 3 months, 6 months and 12 months. Conclusion The corneal morphologic changes of RGPCL wearers are less severe than those of SCL wearers, suggesting that RGPCL wearing is a safe correction method.
Key words:
Contact lens,rigid gas permeable; Contact lens,soft; Histopathology; Confocal microscopy; Cornea
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