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BACKGROUND AND OBJECTIVES:Little is known about the effect of changes in dialysis hours on patient-reported outcome measures. We report the effect of doubling dialysis hours on a range of patient-reported outcome measures in a randomized trial, overall and separately for important subgroups. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:The A Clinical Trial of IntensiVE Dialysis trial randomized 200 participants to extended or standard weekly hours hemodialysis for 12 months. Patient-reported outcome measures included two health utility scores (EuroQOL-5 Dimensions-3 Level, Short Form-6 Dimension) and their derived quality-adjusted life year estimates, two generic health scores (Short Form-36 Physical Component Summary, Mental Component Summary), and a disease-specific score (Kidney Disease Component Score). Outcomes were assessed as the mean difference from baseline using linear mixed effects models adjusted for time point and baseline score, with interaction terms added for subgroup analyses. Prespecified subgroups were dialysis location (home- versus institution-based), dialysis vintage (≤6 months versus >6 months), region (China versus Australia, New Zealand, Canada), and baseline score (lowest, middle, highest tertile). Multiplicity-adjusted P values (Holm-Bonferroni) were calculated for the main analyses. RESULTS:Extended dialysis hours was associated with improvement in Short Form-6 Dimension (mean difference, 0.027; 95% confidence interval [95% CI], 0.00 to 0.05; P=0.03) which was not significant after adjustment for multiple comparisons (Padjusted =0.05). There were no significant differences in EuroQOL-5 Dimensions-3 Level health utility (mean difference, 0.036; 95% CI, -0.02 to 0.09; P=0.2; Padjusted =0.2) or in quality-adjusted life years. There were small positive differences in generic and disease-specific quality of life: Physical Component Summary (mean difference, 2.3; 95% CI, 0.6 to 4.1; P=0.01; Padjusted =0.04), Mental Component Summary (mean difference, 2.5; 95% CI, 0.5 to 4.6; P=0.02; Padjusted =0.05) and Kidney Disease Component Score (mean difference, 3.5; 95% CI, 1.5 to 5.5; P=0.001; Padjusted =0.005). The results did not differ among predefined subgroups or by baseline score. CONCLUSIONS:The effect of extended hours hemodialysis on patient-reported outcome measures reached statistical significance in some but not all measures. Within each measure the effect was consistent across predefined subgroups. The clinical importance of these differences is unclear.

Item does not contain fulltext Some suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75% Asians, 21% Whites, and 4% Blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, Whites, and Blacks, the adjusted hazard ratios (95% confidence interval) for eGFR 45-59 versus 90-104 ml/min per 1.73 m(2) were 1.3 (1.2-1.3), 1.1 (1.0-1.2), and 1.3 (1.1-1.7) for all-cause mortality, 1.6 (1.5-1.7), 1.4 (1.2-1.7), and 1.4 (0.7-2.9) for cardiovascular mortality, and 27.6 (11.1-68.7), 11.2 (6.0-20.9), and 4.1 (2.2-7.5) for ESRD, respectively. The corresponding hazard ratios for urine albumin-to-creatinine ratio 30-299 mg/g or dipstick 1+ versus an albumin-to-creatinine ratio under 10 or dipstick negative were 1.6 (1.4-1.8), 1.7 (1.5-1.9), and 1.8 (1.7-2.1) for all-cause mortality, 1.7 (1.4-2.0), 1.8 (1.5-2.1), and 2.8 (2.2-3.6) for cardiovascular mortality, and 7.4 (2.0-27.6), 4.0 (2.8-5.9), and 5.6 (3.4-9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races.

The evolution and utilization of estuarine and coastal regions are greatly restricted by sediment problems. This thesis aims to better understand fine sediment transport under combined action of waves and currents, especially in the wave-current bottom boundary layer (BBL). Field observations, experimental data analysis, theoretical analysis and numerical models are employed. Silt-dominated sediments are sensitive to flow dynamics and the suspended sediment concentration (SSC) increase rapidly under strong flow dynamics. This research unveils several fundamental aspects of silty sediment, i.e., the criterion of the incipient motion, the SSC profiles and their time-averaged parameterization in wave-dominated conditions. An expression for sediment incipient motion is proposed for silt-sand sediment under combined wave and current conditions. A process based intra-wave 1DV model for flow-sediment dynamics near the bed is developed in combined wave-current conditions. The high concentration layer (HCL) was simulated and sensitivity analysis was carried out by the 1DV model on factors that impact the SSC in the HCL.Finally, based on the 1DV model, the formulations of the mean SSC profile of silt-sand sediments in wave conditions were proposed. The developed approaches are expected to be applied in engineering practice and further simulation.

The evolution and utilization of estuarine and coastal regions are greatly restricted by sediment problems. Inspired by the Caofeidian sea area in Bohai Bay, China, this study aims to better understand silty sediment transport under combined action of waves and currents, especially in the wave-current bottom boundary layer (BBL), and to improve our modelling approaches in predicting estuarine and coastal sediment transport. Field observations were carried out in northwestern Caofeidian sea area of Bohai Bay and field data were collected on several other silt-dominated coasts. Analysis shows that silt-dominated sediments are sensitive to flow dynamics: the suspended sediment concentrations (SSCs) increase rapidly under strong flow dynamics (i.e., waves or strong tidal currents which can stir up sediments), and high concentrations cause heavy sudden back siltation in navigation channels. In the following, details of silty sediment transport are studied, focusing on the BBL and high concentration layer (HCL). From laboratory experiments and theoretical analysis, an expression for sediment incipient motion is proposed for silt-sand sediment under combined wave and current conditions. The Shields number was revised by adding the cohesive force and additional static pressure, leading to an extended Shields curve. To study the HCL, a process based 1DV model was developed for flow-sediment dynamics near the bed in combined wave-current conditions. Based on the physical processes, special approaches for sediment movement were introduced, including approaches for different bed forms (rippled bed and 'flat-bed'), hindered settling, stratification effects, mobile bed effects, reference concentration and critical shear stress. The HCL was simulated and sensitivity analysis was carried out by the 1DV model on factors that impact the sediment concentration in the HCL. The results show that the HCL is affected by both flow dynamics and bed forms; the thickness of the HCL is about twice the height of the wave boundary layer; bed forms determine the shape of the concentration profile near the bottom, and flow dynamics determine the magnitude. For finer sediment, stratification effects and mobile bed effects impact the sediment concentration greatly. Finally, based on the 1DV model, the formulations of the mean sediment concentration profile of silty sediments were studied. By solving the time-averaged diffusion equation for SSC and considering the effects of bed forms, stratification and hindered settling, expressions for time-averaged SSC profile under wave conditions were proposed for silt and are applicable for sand as well. Subsequently, the depth-averaged sediment concentration was yielded by integrating the SSC profile under wave conditions. In summary, this research unveils several fundamental aspects of silty sediment, i.e., criterion of the incipient motion, the SSC profiles in HCL and their time-averaged parameterization in wave-dominated conditions. A 1DV model was developed for fine sediment transport in the wave-current BBL. The developed approaches are expected to be applied in engineering practice and further simulation.

Yongxin Luan,1 Shuyan Zhang,1 Ling Zuo,2 Lixiang Zhou1 1Department of Neurosurgery, First Bethune Hospital of Jilin University, 2Department of Ophthalmology, Second Bethune Hospital of Jilin University, Changchun, People’s Republic of China Background: Glioblastoma multiforme is one of the most deadly forms of brain cancer. We investigated the regulatory effects of microRNA-100 (miR-100) on cell proliferation, migration, and chemosensitivity in human glioblastoma. Methods: miR-100 expression was assessed by quantitative real-time polymerase chain reaction in both glioblastoma cells and human tumors. Lentiviruses of miR-100 mimics and inhibitors were transfected into U251 and T98G cells. The regulatory effects of either overexpressing or downregulating miR-100 on glioblastoma were evaluated by a viability assay, growth assay, migration assay, chemosensitivity assay, and an in vivo tumor transplantation assay. Expression of fibroblast growth factor receptor 3 (FGFR3), the bioinformatically predicted target of miR-100, was examined by Western blot in glioblastoma. FGFR3 was then ectopically overexpressed in U251 and T98G cells, and its effects on miR-100-mediated cancer regulation were evaluated by growth, migration, and chemosensitivity assays. Results: MiR-100 was markedly downregulated in both glioblastoma cell lines and human tumors. Overexpressing miR-100 through lentiviral transfection in U251 and T98G cells significantly inhibited cancer growth (both in vitro and in vivo) and migration and increased chemosensitivity to cisplatin and 1, 3-bis (2-chloroethyl)-l-nitrosourea, whereas downregulation of miR-100 had no effects on development of cancer. FGFR3 was directly regulated by miR-100 in glioblastoma. Ectopically overexpressing FGFR3 was able to ameliorate the anticancer effects of upregulation of miR-100 on glioblastoma growth, migration, and chemosensitivity. Conclusion: MiR-100 was generally downregulated in glioblastoma. Overexpressing miR-100 had anticancer effects on glioblastoma, likely through regulation of FGFR3. The MiR-100/FGFR3 signaling pathway might be a biochemical target for treatment in patients with glioblastoma. Keywords: glioblastoma, miR-100, fibroblast growth factor receptor 3, cisplatin

Context Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial.Objective To evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks.Design, Setting, and Participants Individual-level meta-analysis including 2 051 244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years).Main Outcome Measures Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates.Results Mortality (112 325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m(2) vs 80 mL/min/1.73 m(2) were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and >= 75 years, respectively (P Conclusions Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.

Item does not contain fulltext BACKGROUND: Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown. METHODS: We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes. FINDINGS: We analysed data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75,306 deaths occurred during a mean follow-up of 8.5 years (SD 5.0). In the 23 studies with data for cardiovascular mortality, 21,237 deaths occurred from cardiovascular disease during a mean follow-up of 9.2 years (SD 4.9). In the general and high-risk cohorts, mortality risks were 1.2-1.9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1.73 m(2) [vs 95 mL/min per 1.73 m(2)], HR 1.35; 95% CI 1.18-1.55; vs 1.33; 1.19-1.48 and at ACR 30 mg/g [vs 5 mg/g], 1.50; 1.35-1.65 vs 1.52; 1.38-1.67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts. INTERPRETATION: Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes. FUNDING: US National Kidney Foundation.

Contains fulltext : 110640.pdf (Publisher’s version ) (Closed access) CONTEXT: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking. OBJECTIVE: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics. DESIGN, SETTING, AND PARTICIPANTS: A meta-analysis of data from 1.1 million adults (aged >/= 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012. MAIN OUTCOME MEASURES: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years). RESULTS: Estimated GFR was classified into 6 categories (>/=90, 60-89, 45-59, 30-44, 15-29, and /=65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts. CONCLUSION: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines recommended the Modification of Diet in Renal Disease study (MDRD) equation for estimating glomerular filtration rate (GFR) for the classification of chronic kidney disease (CKD), but its accuracy was limited to North-American patients with estimated GFR The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) developed another equation for estimating GFR, derived from a population that included both participants without kidney disease and with CKD. But many ethnicities were inadequately represented. The International Society of Nephrology, Kidney Disease Improving Global Outcomes committee promulgated clinical practice guidelines, which recommended the CKD-EPI equation. Investigators in Asia subsequently assessed the performance of these GFR estimating equations - the MDRD study equation, the CKD-EPI equation (creatinine only), and the CKD-EPI equations (creatinine and cystatin C). In this review, we summarize the studies performed in Asia on validating or establishing new Asian-ethnicity GFR estimating equations. We included both prospective and retrospective studies which used serum markers traceable to reference materials, and focused the review of the performance of GFR estimation by comparisons with the GFR estimations obtained from the CKD-EPI equations.