Safety performance evaluation of freeway merging areas under autonomous vehicles environment using a co-simulation platform.

Merging areas serve as the potential bottlenecks for continuous traffic flow on freeways. Traffic incidents in freeway merging areas are closely related to decision-making errors of human drivers, for which the autonomous vehicles (AVs) technologies are expected to help enhance the safety performance. However, evaluating the safety impact of AVs is challenging in practice due to the lack of real-world driving and incident data. Despite the increasing number of simulation-based AV studies, most relied on single traffic/vehicle driving simulators, which exhibit limitations such as inaccurate description of AV behavior using pre-defined driving models, limited testing modules, and a lack of high-fidelity traffic scenarios. To this end, this study addresses these challenges by customizing different types of car-following models for AVs on freeway and developing a software-in-the-loop co-simulation platform for safety performance evaluation. Specifically, the environmental perception module is integrated in PreScan, the decision-making and control model for AVs is designed by Matlab, and the traffic flow environment is established by Vissim. Such a co-simulation platform is supposed to be able to reproduce the mixed traffic with AVs to a large extent. By taking a real freeway merging scenario as an example, comprehensive experiments were conducted by introducing a single AV and multiple AVs on the mainline of freeway, respectively. The single AV experiment investigated the performance of different car-following models microscopically in the case of merging conflict. The safety and comfort of AVs were examined in terms of TTC and jerk, respectively. The multiple AVs experiment examined the safety impact of AVs on mixed traffic of freeway merging areas macroscopically using the developed risk assessment model. The results show that AVs could bring significant benefits to freeway safety, as traffic conflicts and risks are substantially reduced with incremental market penetration rates.

Urinary C4d and progression of kidney disease in IgA vasculitis.

BACKGROUND: IgA vasculitis nephritis is the most common secondary IgA nephropathy. Urinary C4d have been identified associated with the development and progression in primary IgA nephropathy. However, its role in kidney disease progression of IgA vasculitis nephritis is still unclear. METHODS: This study enrolled 139 patients with IgA vasculitis nephritis (IgAVN), 18 healthy subjects, 23 Focal segmental glomerulosclerosis patients and 38 IgA nephropathy (IgAN) patients. Urinary C4d levels at kidney biopsy were measured using enzyme-linked immunosorbent assay. The association between urinary C4d/creatinine and kidney disease progression event, defined as 40% eGFR decline or ESKD, was assessed using Cox proportional hazards models and restricted cubic splines. RESULTS: The levels of urinary C4d/creatinine in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/creatinine were associated with higher proteinuria and severe Oxford C lesions and glomerular C4d deposition. After a median follow-up of 52.79 months, 18 (12.95%) participants reached composite kidney disease progression event. The risk of kidney disease progression event was higher with higher levels of ln (urinary C4d/creatinine). After adjustment for clinical data, higher levels of urinary C4d/creatinine were associated with kidney disease progression in IgA vasculitis nephritis (per ln transformed urinary C4d/creatinine, hazard ratio (HR) =1.573, 95% confidence interval (CI) 1.101-2.245; P = 0.013). Compared to the lower C4d/creatinine group, hazard ratio was 5.539(95%CI, 1.135-27.035; P = 0.034) for the higher levels group. CONCLUSIONS: Higher levels of urinary C4d/creatinine were associated with kidney disease progression event in patients IgAVN.

Plasma D-dimer as a potential predictor of progression in IgA nephropathy: a cohort study.

INTRODUCTION: Coagulation disorders play a key role in chronic kidney disease, and the formation or elevation of plasma D-dimer levels reflects activation of the coagulation system. However, its relationship with the severity and progression of kidney disease in IgA nephropathy (IgAN) remains unclear. METHODS: We assessed 1818 patients with IgAN diagnosed between 2002 and 2019 at the First Affiliated Hospital, Zhejiang University School of Medicine. Plasma D-dimer levels were measured at the time of the renal biopsy. The association between plasma D-dimer levels and kidney disease progression events, defined as a 50% decline in eGFR and end-stage kidney disease (ESKD), was tested using restricted cubic splines and Cox proportional hazard models. RESULTS: The median plasma D-dimer level was 220 (170-388.5) µg/L FEU, which was significantly higher than healthy controls 170 (170-202) µg/L FEU. Plasma D-dimer levels were positively correlated with proteinuria (r = 0.211, p < 0.001) and serum galactose-deficient IgA1 (r = 0.226, p = 0.004) and negatively correlated with eGFR (r=-0.127, p < 0.001) and Oxford T (p < 0.001) and C (p = 0.004) scores. After a median follow-up of 25.67 (13.03-47.44) months, 126 (6.93%) patients experienced composite kidney disease progression events. Higher plasma D-dimer levels were associated with an increased risk of kidney disease progression events (hazard ratio, 1.73; 95% confidence interval [95% CI], 1.40-2.23) per ln-transformed plasma D-dimer (p < 0.001), after adjustment for sex, age, proteinuria, Mean arterial pressure (MAP) and Oxford classification scores. In reference to the first tertile of plasma D-dimer, hazard ratios were 1.48 (95% CI, 0.76-2.88) for the second tertile, 3.03 (95% CI, 1.58-5.82) for the third tertile. CONCLUSIONS: High plasma D-dimer levels were associated with the progression of kidney disease severity in IgA nephropathy.

Automated Tumor Count for Mitosis-Karyorrhexis Index Determination in Neuroblastoma Using Whole Slide Image and Qupath, an Image Analytic Software.

INTRODUCTION: Mitosis-karyorrhexis index (MKI) is important for risk stratification workup of neuroblastic tumors. MKI is calculated by estimating the denominator (5000 tumor cells). We hypothesized that whole slide image (WSI) with appropriate digital image analytical software could provide an objective aid to pathologist's MKI workup. MATERIALS & METHODS: With IRB approval, sixteen cases of neuroblastic tumors as convenient cases were used. H&E slides were scanned at 40X using an Aperio Scanscope AT2 scanner and stored in SVS format. Digital photos were also taken and stored in TIFF format. Qupath, an open source image analytical software, was used to annotate, define region of interest (ROI) and automatically count the cells within ROI. RESULTS: With selected parameters, Qupath was able to provide cell count using both WSI (.svs) and digital images (.TIFF). Comparison of automated count and eyeball manual count generated precision above .96, recall above .96, F1 scores above .98, with false positive rate ranging from .6 to 3.7%, and false negative rate from .6 to 3.8%. Compared to original pathological report, automated tumor cell count led to lower MKI in 3 of 16 cases (18.8%) and change of "unfavorable histology" to "favorable" in one case (1/16, 6.3%). CONCLUSION: Combination of WSI (or digital images) with Qupath is able to provide an automated, objective and consistent way for cell count to facilitate pathologist's MKI determination in neuroblastic tumors' workup and research.

Intensive Systolic Blood Pressure Lowering and Kidney Disease Progression in IgA Nephropathy: A Cohort Study.

BACKGROUND: Hypertension has been shown to be an important risk factor in IgA nephropathy (IgAN). The 2021 the Kidney Disease Improving Global Outcomes (KDIGO) Guideline proposes a target systolic blood pressure (SBP) of less than 120 mmHg in patients with Chronic Kidney Disease (CKD) not receiving dialysis. However, whether lowering SBP from <140- <120 mm Hg is renoprotective is unknown. This study aims to evaluate the association of SBP and the progression of IgAN, then explore whether lowering SBP from <140- <120 mm Hg is renoprotective. METHODS: Overall, 2,240 patients with IgAN were enrolled in this study. Cox proportional hazards models and restricted cubic splines were used to estimate the associations between SBP and kidney failure events which are defined as 50% estimated glomerular filtration rate (eGFR) decline or kidney failure. RESULTS: After a median follow-up of 30.05 months, 217 (9.69%) patients reached composite kidney failure events. The association of SBP and kidney failure events showed a linear relationship. The risk of kidney failure events was greater with higher SBP. Compared with SBP <120 mm Hg, the hazard ratio was 1.85 (1.16-2.97, p = 0.010) for SBP <140 mm Hg after adjustment for traditional risk factors. The renoprotective benefits of therapy targeting SBP <120 mm Hg from SBP <140 mm Hg was detectable within the subgroup with proteinuria >1.0 g/d, CKD 1-3a stage, but not those with proteinuria ≤ 1.0 g/d and CKD 3b-4 stage. CONCLUSIONS: In patients with IgAN, SBP was independently associated with composite kidney failure events. Lowering SBP from <140- <120 mm Hg was renoprotective.

Comparison of 24-h Urine Protein, Urine Albumin-to-Creatinine Ratio, and Protein-to-Creatinine Ratio in IgA Nephropathy.

Background: Proteinuria is a strong risk factor for renal outcomes in IgA nephropathy. Random urine protein-to-creatinine ratio (PCR), random albumin-to-creatinine ratio (ACR), and 24-h urine protein excretion (24-h UP) have been widely used in clinical practice. However, the measurement which is the best predictor of long-term renal outcomes remains controversial. This study aimed to compare the three measurements in IgA nephropathy. Methods: We conducted a retrospective study of 766 patients with IgA nephropathy. The associations among baseline ACR, PCR, and 24-h UP with chronic kidney disease (CKD) progression event, defined as 50% estimated glomerular filtration rate (eGFR) decline or end stage kidney disease (ESKD), were tested and compared. Results: In this study, ACR, PCR, and 24-h UP showed high correlation (r = 0.671-0.847, P < 0.001). After a median follow-up of 29.88 (14.65-51.65) months, 51 (6.66%) patients reached the CKD progression event. In univariate analysis, ACR performed better in predicting the prognosis of IgA nephropathy, with a higher area under the receiver operating curve (ROC) curve than PCR and 24-h UP. After adjustment for traditional risk factors, ACR was most associated with composite CKD progression event [per log-transformed ACR, hazard ratio (HR): 2.82; 95% (95% CI): 1.31-6.08; P = 0.008]. Conclusions: In IgA nephropathy, ACR, PCR, and 24-h UP had a high correlation. ACR performed better in predicting the prognosis of IgA nephropathy.

Pathogenesis of IgA Vasculitis: An Up-To-Date Review.

Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schönlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune deposition at diseased vessel walls. IgAV is the most common form of vasculitis in children; typical symptoms include palpable purpura, arthritis or arthralgia, abdominal pain, and hematuria or proteinuria. Galactose-deficient IgA1 is detected in the tissues of the kidney and skin in patients with IgAV; it forms immune complexes leading to subsequent immune reactions and injuries. This report provides the recent advances in the understanding of environmental factors, genetics, abnormal innate and acquired immunity, and the role of galactose-deficient IgA1 immunocomplexes in the pathogenesis of IgAV.

Serum phosphorus and calcium levels, and kidney disease progression in immunoglobulin A nephropathy.

BACKGROUND: Disorders of calcium and phosphorus metabolism have been reported to be associated with all-cause and cardiovascular mortality in patients requiring long-term dialysis therapy. However, its role in disease progression is not well established in patients without dialysis, especially in immunoglobulin A (IgA) nephropathy. We aim to evaluate the association of serum phosphorus and calcium and progression of IgA nephropathy. METHODS: We assessed 2567 patients with IgA nephropathy at the First Affiliated Hospital, College of Medicine, Zhejiang University. Serum phosphorus and calcium were collected at the time of kidney biopsy and at each visit. The associations of serum phosphorus and serum calcium with composite kidney disease progression events, defined as 50% estimated glomerular filtration rate (eGFR) decline and kidney failure, were examined using Cox models and restricted cubic splines. RESULTS: During a median follow-up of 31.9 months, 248 (10%) patients reached composite kidney disease progression events. A linear relationship was observed between serum phosphorus and composite kidney disease progression events. With higher levels of phosphorus, the risk of kidney disease progression events increased {hazard ratio [HR] 3.54 [95% confidence interval (CI) 1.37-9.12]; P = 0.009}. Compared with the first quartile group, the HR of kidney disease progression events was 1.66 (95% CI 0.91-301) for the second quartile, 1.67 (95% CI 0.91-3.08) for the third and 2.62 (95% CI 1.44-4.77) for the fourth (P for trend = 0.002). The association between serum phosphorus and kidney disease progression was detectable [HR 8.94 (95% CI 2.33-34.21); P = 0.001] within the subgroup with eGFR <60 mL/min/1.73 m2 but not among patients with eGFR ≥60 mL/min/1.73 m2 [HR 0.87 (95% CI 0.17-4.44); P = 0.87]. After adjustment for traditional risk factors, a higher level of serum calcium was not associated with kidney disease progression events [HR 0.33 (95% CI 0.10-1.09)]. CONCLUSIONS: Higher serum phosphorus rather than serum calcium was independently associated with kidney disease progression in IgA nephropathy.

O-glycoforms of polymeric immunoglobulin A1 in the plasma of patients with IgA nephropathy are associated with pathological phenotypes.

BACKGROUND: Immunoglobulin A1 (IgA1) O-glycosylation plays an important role in the pathogenesis of IgA nephropathy (IgAN). However, variations in IgA1 O-glycoforms have not been explored. We aimed to investigate the IgA1 O-glycoforms in the hinge region (HR) of polymeric IgA1 (pIgA1) and then evaluate the association between IgA1 O-glycoforms and crescent formation in IgAN. METHODS: The discovery cohort (Cohort 1) comprised 11 crescentic IgAN patients, 10 noncrescentic IgAN patients and 10 healthy controls and the validation cohort (Cohort 2) comprised 11 crescentic IgAN patients, 9 noncrescentic IgAN patients and 9 healthy controls. A total of 143 IgAN patients with different crescent percentages (Cohort 3) were also included. pIgA1 was purified from the plasma of the participants. The variation in O-glycoforms was evaluated by estimating the molecular weights of IgA1 hinge glycopeptides using reversed-phase liquid chromatography and tandem mass spectrometry under electron-transfer/higher-energy collision dissociation fragmentation mode. RESULTS: In the discovery cohort (Cohort 1), the number of N-acetylgalactosamine (GalNAc) bound to one HR was lower in IgAN patients. The proportions of GalNAc3 (defined as O-glycans bound to one HR at three sites) and GalNAc4 were highest in crescentic IgAN patients, followed by noncrescentic IgAN patients, and were lowest in healthy controls [GalNAc 3: 9.92 ± 3.37% versus 6.65 ± 1.53% versus 4.05 ± 1.24% (P < 0.001); GalNAc4: 45.91 ± 4.75% versus 41.13 ± 2.95% versus 40.98 ± 2.95% (P = 0.004), respectively]. The proportions of GalNAc5 and GalNAc6 were lowest in crescentic IgAN patients followed by noncrescentic IgAN patients and were highest in healthy controls [GalNAc5: 50.15 ± 4.27% versus 47.92 ± 4.09% versus 45.87 ± 3.79% (P = 0.028); GalNAc6: 6.58 ± 2.53% versus 6.04 ± 1.35% versus 4.65 ± 2.27% (P = 0.034), respectively]. These results were consistent in the validation cohort (Cohort 2). In another cohort with 143 patients with different crescent percentages (Cohort 3), the number of GalNAc in pIgA1 decreased with an increasing percentage of crescents. CONCLUSIONS: The number of GalNAc in IgA1 HRs was lower in IgAN patients, especially in crescentic IgAN patients, and may be associated with a severe IgAN phenotype.

Interaction between GALNT12 and C1GALT1 Associates with Galactose-Deficient IgA1 and IgA Nephropathy.

BACKGROUND: Galactose-deficient IgA1 plays a key role in the pathogenesis of IgA nephropathy, the most common primary GN worldwide. Although serum levels of galactose-deficient IgA1 have a strong genetic component, the genetic link between this molecule and IgA nephropathy has not yet been clearly established. METHODS: To identify novel loci associated with galactose-deficient IgA1, we performed a quantitative genome-wide association study for serum galactose-deficient IgA1 levels, on the basis of two different genome-wide association study panels conducted in 1127 patients with IgA nephropathy. To test genetic associations with susceptibility to IgA nephropathy, we also enrolled 2352 patients with biopsy-diagnosed IgA nephropathy and 2632 healthy controls. Peripheral blood samples from 59 patients and 27 healthy controls were also collected for gene expression analysis. RESULTS: We discovered two loci, in C1GALT1 and GALNT12, that achieved genome-wide significance, explaining about 3.7% and 3.4% of variance in serum galactose-deficient IgA1 levels, respectively. We confirmed the previously reported association of C1GALT1 with serum galactose-deficient IgA1 levels, but with a different lead single-nucleotide polymorphism (rs10238682; ß=0.26, P=1.20×10-9); the locus we identified at GALNT12 (rs7856182; ß=0.73, P=2.38×10-9) was novel. Of more interest, we found that GALNT12 exhibits genetic interactions with C1GALT1 in both galactose-deficient IgA1 levels (P=1.40×10-2) and disease risk (P=6.55×10-3). GALNT12 mRNA expression in patients with IgA nephropathy was significantly lower compared with healthy controls. CONCLUSIONS: Our data identify GALNT12 as a novel gene associated with galactose-deficient IgA1 and suggest novel genetic interactions. These findings support a key role of genetically conferred dysregulation of galactose-deficient IgA1 in the development of IgA nephropathy.

Immune characteristics of renal allograft donors with mesangial IgA deposition.

BACKGROUND: There are few studies describing the prevalence and immune features of people with subclinical mesangial immunoglobulin A (IgA) deposition in the Chinese population. We sought to investigate the prevalence of mesangial IgA deposition among kidney donors and the immune characteristics of donors with mesangial IgA deposition. METHODS: Fifty blood-related living donors with zero-hour allograft biopsies obtained at Peking University First Hospital were enrolled. Galactose-deficient IgA1 (Gd-IgA1) in glomerular deposits was examined by double immunofluorescent staining using the specific monoclonal antibody KM55. Plasma IgA, IgA1, Gd-IgA1 and antibodies directed against Gd-IgA1 were measured using enzyme-linked immunosorbent assay. RESULTS: Thirteen of 50 (26%) donors had mesangial IgA deposition, which was confirmed by both immunofluorescence and electron microscopy. The levels of plasma IgA, IgA1 and Gd-IgA1 were all increased in donors with IgA deposition compared with those without IgA deposition (mean ± SD, 3.54 ± 0.505 versus 2.356 ± 0.265 mg/ml, p = 0.049; 3.003 ± 0.4048 versus 2.356 ± 0.265 mg/ml, p = 0.057; and 4.719 ± 0.4357 versus 3.356 ± 0.4707 ug/ml, p = 0.0440, respectively). Colocalized IgA1 and Gd-IgA1 indicated that there were galactose-deficient IgA1 deposits in the glomerular mesangium. While donors with IgA deposition showed lower levels of IgG anti-glycan antibodies than patients with IgA nephropathy (37.71 ± 8.886 versus 78.86 ± 5.155 units/ml, p = 0.001). CONCLUSIONS: The immune features of donors with IgA deposition, including IgA1 and Gd-IgA1 deposition, were similar to those of patients with IgA nephropathy, but donors with IgA deposition had lower levels of antiglycan antibodies, which may explain the subclinical status of IgA deposition in donors. Mesangial IgA deposition was common in the Chinese blood related donors cohort, further large study with both living and cadaveric donor kidneys was still needed to confirm these findings.

Associations of ABO blood type and galactose-deficient immunoglobulin A1 with adverse outcomes in patients with IgA nephropathy.

BACKGROUND: Both ABO blood group antigens and pathogenic immunoglobulin A1 (IgA1) in patients with IgA nephropathy (IgAN) are influenced by modifications of N-acetylgalactosamine and galactose. The purpose of this study was to assess whether ABO blood type is associated with galactose-deficient IgA1 (Gd-IgA1) in the progression of kidney disease in patients with IgAN. METHODS: We enrolled 1313 IgAN patients with a median of 44 months follow-up and measured the plasma Gd-IgA1 levels. Multivariate Cox regression models were used to estimate the association between all variables and adverse outcomes. Using the propensity score matching method, 718 IgAN patients with blood type either A or B were selected, and their data were used to assess the association of blood type and Gd-IgA1/serum complement 3 (sC3) with outcomes. RESULTS: We found that the risk of adverse outcomes was significantly higher in patients with blood type A than in those with type B (hazard ratio = 1.82, 95% confidence interval 1.23-2.71; P = 0.003) after multivariate adjustment. The Gd-IgA1 levels showed trends similar to the multivariate-adjusted event-free curves for the blood types. However, this higher risk of adverse outcomes in type A than in type B patients was no longer significant after the addition of Gd-IgA1/sC3 to the model. CONCLUSIONS: IgAN patients with blood type A had a higher risk of adverse outcomes than those with type B, and this risk was associated with Gd-IgA1/sC3. Thus, the ABO blood type may provide a reference for the prognostic factors for individuals with IgAN.

Urine ß2-Microglobulin and Retinol-Binding Protein and Renal Disease Progression in IgA Nephropathy.

Background: Tubulointerstitial involvement has been reported to have a decisive influence on the progression of IgA nephropathy (IgAN). High levels of urine ß2-microglobulin (ß2-MG) and retinol-binding protein (RBP) were observed in patients with IgAN with tubulointerstitial lesions. However, their roles in disease progression remain unclear. This study aimed to evaluate the associations of urine ß2-MG and RBP with the progression of IgAN. Methods: We retrospectively investigated a cohort of 2,153 patients with IgAN. Clinical and pathological features, outcomes, and urine ß2-MG, and RBP at the time of biopsy were collected. The associations, of urine ß2-MG and RBP with the composite renal outcome, defined as a decline in estimated glomerular filtration rate (eGFR) of ≥50% from baseline or end-stage renal disease (ESRD), were examined using restricted cubic splines and the Cox proportional hazards models. Results: During a median follow-up of 20.40 months, 140 (6.50%) patients reached the composite renal outcomes. Restricted cubic splines showed that patients with higher urinary ß2-MG and RBP levels had worse renal outcomes. The Cox regression analysis revealed that urine ß2-MG and RBP were associated with a risk of the composite renal outcome in the multivariate adjusted model [+1 SD for log ß2-MG, hazard ratio (HR) = 1.462, 95% CI: 1.136-1.882, p = 0.003; +1 SD for log RBP, HR = 1.972, 95% CI: 1.486-2.617, p = 0.001]. The associations were detectable within patients with baseline eGFR <90 ml/min/1.73 m2 (+1 SD for log ß2-MG, HR = 1.657, 95% CI: 1.260-2.180, p < 0.001; +1 SD for log RBP, HR = 1.618, 95% CI: 1.199-2.183, p = 0.002), but not among patients with eGFR ≥90 ml/min/1.73 m2. Conclusion: Higher levels of urine ß2-MG and RBP were independent risk factors for renal disease progression in IgAN.

A Novel MEMS Gyroscope In-Self Calibration Approach.

This paper presents a novel approach for hand-held low-cost MEMS (micro-electro-mechanical system) gyroscope in-self calibration. This method does not need the support of external high-precision equipment compared with traditional calibration scheme and can be accomplished by user hand rotation. In this approach, Kalman filter is designed to perform the calibration procedure and estimate gyroscope bias error, scale factor error and non-orthogonal error. The system observability is analyzed and the dynamic rotating conditions under which the sensor errors become observable are derived. The design principles of optimal calibration procedure are provided as well. Both simulated and practical experiments are carried out to test the validation of the proposed calibration algorithm. The achieved results demonstrate that the introduced approach can provide promising calibration scheme for the low-cost MEMS gyroscope.

Persistent Hematuria and Kidney Disease Progression in IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Hematuria is the most typical presentation of immunoglobulin A nephropathy (IgAN); however, its role in disease progression is still controversial. This study aimed to evaluate the association of hematuria and progression of IgAN. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A cohort of 1,333 patients with IgAN treated at a Chinese referral hospital with a median follow-up of 45 months. PREDICTORS: Microhematuria was evaluated in fresh urine using a fully automated urine particle analyzer (automated method) and urine sediment examination by a skilled examiner (manual method). Hematuria was characterized as a time-varying attribute; namely, average hematuria level was calculated for every 6-month period for each patient during follow-up. Remission was defined as average red blood cell count ≤5/high-power field (manual method) or ≤28 red blood cells/µL (automated method) during the first 6 months of follow-up. OUTCOMES: Composite event of 50% decline in estimated glomerular filtration rate or development of kidney failure. ANALYTICAL APPROACH: Multivariable cause-specific hazards models to analyze the relationship between hematuria and the composite kidney disease progression event. RESULTS: Time-varying hematuria during follow-up was an independent risk factor for the composite kidney disease progression event (HR, 1.46; 95% CI, 1.13-1.87; P = 0.003). Hematuria remission during the 6 months after diagnosis was associated with a significantly lower rate of the composite kidney disease progression event (HR, 0.41; 95% CI, 0.28-0.61; P < 0.001). A significant interaction was detected between remission of proteinuria and remission of hematuria during the first 6 months (P < 0.001). The association between remission of hematuria and kidney disease progression was detectable (HR, 0.46; 95% CI, 0.32-0.68) within the subpopulation with persistent proteinuria (protein excretion > 1.0 g/d during the first 6 months), but not among patients whose proteinuria had remitted (HR, 0.64; 95% CI, 0.31-1.29; P = 0.2). The 2 techniques for hematuria evaluation were strongly and significantly linearly correlated (r = 0.948; P < 0.001), and results using these 2 methods were consistent. LIMITATIONS: A single-center retrospective study. Proportional hazards regression incorporating time-varying covariates may create time-varying confounding. The predictive value of reductions in hematuria was not directly evaluated. CONCLUSIONS: Level of hematuria was independently associated with kidney disease progression, whereas hematuria remission was associated with improved kidney outcomes in IgAN among patients with persistent proteinuria. Additionally, to monitor IgAN progression, automated methods to evaluate hematuria hold promise as a replacement for manual evaluation of urinary sediment.

Plasma Galactose-Deficient IgA1 and C3 and CKD Progression in IgA Nephropathy.

BACKGROUND AND OBJECTIVES: Increased circulating galactose-deficient IgA1 and subsequently complement activation both play important roles in the pathophysiology of IgA nephropathy. However, their relationship to disease severity and progression remains unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We assessed 1210 participants in a cohort study of biopsy-proven IgA nephropathy at Peking University First Hospital. Plasma concentrations of galactose-deficient IgA1 and complement component C3 were measured at the time of biopsy. We tested associations of galactose-deficient IgA1 and galactose-deficient IgA1/C3 ratio with CKD progression event, defined as ESKD or 50% decline in eGFR, using Cox proportional hazards models and restricted cubic splines. RESULTS: After a median follow-up of 43 months (interquartile range, 24-76 months), 172 (14%) participants reached the CKD progression event. The association of galactose-deficient IgA1 levels and CKD progression event showed a nonlinear relationship. The risk of CKD progression events was greater with higher plasma galactose-deficient IgA1 levels but reached a plateau when galactose-deficient IgA1>325 U/ml, whereas the risk of CKD progression events monotonically increased with higher galactose-deficient IgA1/C3 ratio. After adjustment for traditional risk factors (demographics, eGFR, proteinuria, hypertension, Oxford pathologic score, and corticosteroids/immunosuppressive therapy), higher levels of galactose-deficient IgA1/C3 ratio were independently associated with CKD progression event (per natural log-transformed [galactose-deficient IgA1/C3], hazard ratio, 2.03; 95% confidence interval [95% CI], 1.25 to 3.29; P=0.004). In reference to the first quartile of the galactose-deficient IgA1/C3 ratio, hazard ratios were 1.71 (95% CI, 1.01 to 2.89) for the second quartile, 1.55 (95% CI, 0.91 to 2.63) for the third quartile, and 2.17 (95% CI, 1.33 to 3.56) for the fourth quartile. CONCLUSIONS: In IgA nephropathy, plasma galactose-deficient IgA1/C3 ratio was associated with CKD progression event independent of clinical and biopsy characteristics.

Assessing right-turning vehicle-pedestrian conflicts at intersections using an integrated microscopic simulation model.

Frequent vehicle-pedestrian conflicts deserve special attention for safety assessment at intersections. This study helps verify how the simulation as an innovative approach can be utilized for right-turning vehicle-pedestrian conflict assessment at intersection crosswalks prior to implementation. Various behavior models such as vehicle turning path, turning speed, gap acceptance model and pedestrian behavior model, have been established. Through integrating the calibrated models into one simulation platform, the stochastic behavior of vehicles and pedestrians under different geometric layouts and operational conditions can be reproduced. Based on the field data collected by an unmanned aerial vehicle (UAV) at two urban intersections in Beijing, China, it was demonstrated through validation of surrogate safety measures (SSMs), i.e., Post Encroachment Time (PET) and vehicle passing speed at conflict points, that the simulation model can reasonably represent the frequency and severity of conflict occurrence at signalized crosswalks. The sensitivity analysis results indicated that large dimensions and turning angles of intersections tend to result in undesirable safety performance.

[Establishment of a plant phosphorus utilization and weed control system based on phosphite and its dehydrogenase].

Nowadays, available phosphorus (P) deficiency in soil and weed resistance to herbicides have emerged as two severe limiting factors for sustainable agriculture. Therefore, it is of urgent needs to improve plant absorption/utilization ability of the soil P, seek phosphate (Pi)-alternative P fertilizers, and develop new forms of weed control systems. Phosphite (Phi), as a P resource of relatively high amount only less than Pi in Earth, can be converted to utilizable Pi uniquely in some bacterial species by oxidization via its specific dehydrogenase (PTDH), but inhibits plant growth and development. This implies that Phi might rather become a suitable P fertilizer for plants if introducing a PTDH detoxifier from bacteria. Herein, we created the transgenic tobaccos harboring a Pseudomonas PTDH gene (PsPtx) amplified from the soil metagenome previously. RT-PCR showed that the exotic PsPtx gene could express similarly in root, stem and leaf tissues of all transgenic lines. PsPtx transgenic tobaccos could utilize Phi by oxidization as the sole Pi supply, and also outperformed wild-type tobacco with a remarkably dominant growth under Phi stress conditions. Moreover, the PsPtx gene was preliminarily evaluated with a notable quality as a potential candidate of the selection marker in plant genetic transformation. Conclusively, PsPtx and its encoded phosphite dehydrogenase might be applicable for developing a dual system of plant phosphorus utilization and weed control using Phi as P fertilizer and herbicide, and provide an effectual solution to some obstacles in the current crop transgenic studies.

Dividing CKD stage 3 into G3a and G3b could better predict the prognosis of IgA nephropathy.

Chronic kidney disease (CKD) stage 3 was divided into stage G3a and stage G3b in the 2013 Kidney Disease Improving Global Outcomes guidelines. Whether it is appropriate to regard 45 mL/min/per 1.73 m2 as the threshold value of G3a/G3b staging and whether dividing CKD stage 3 into G3a/G3b plays a useful role in assessing the prognosis of patients with IgA nephropathy (IgAN) remain unknown. Three hundred and ninety patients from the First Affiliated Hospital of Zhengzhou University and Peking University First Hospital diagnosed with IgAN in CKD stage 3 were enrolled and successfully followed up. Cox proportional hazards model was used to analyze hazard ratios of reaching the composite endpoints (doubling of serum creatinine, end-stage renal disease: estimated glomerular filtration rate (eGFR) <15 ml/min/per 1.73 m2 or renal replacement therapy, or death) for patients with different eGFR and risk factors affecting composite endpoints. The Kaplan-Meier method was used to calculate the cumulative renal survival rate of patients. When eGFR was lower than 45 ml/min/per 1.73 m2, the hazard ratio increased sharply for patients in CKD stage 3 who reached the composite endpoints. Renal injury and prognosis were significantly different between patients in the G3a and G3b groups. Stage G3b was a major risk factor affecting prognosis. A threshold value of 45 ml/min/per 1.73 m2 appears appropriate to assess the prognosis of IgAN patients with CKD stage 3. Dividing IgAN patients with CKD stage 3 into G3a and G3b is very useful to help understand disease conditions and for predicting the risk for disease progression.

Estimation of red-light running frequency using high-resolution traffic and signal data.

Red-light-running (RLR) emerges as a major cause that may lead to intersection-related crashes and endanger intersection safety. To reduce RLR violations, it's critical to identify the influential factors associated with RLR and estimate RLR frequency. Without resorting to video camera recordings, this study investigates this important issue by utilizing high-resolution traffic and signal event data collected from loop detectors at five intersections on Trunk Highway 55, Minneapolis, MN. First, a simple method is proposed to identify RLR by fully utilizing the information obtained from stop bar detectors, downstream entrance detectors and advance detectors. Using 12 months of event data, a total of 6550 RLR cases were identified. According to a definition of RLR frequency as the conditional probability of RLR on a certain traffic or signal condition (veh/1000veh), the relationships between RLR frequency and some influential factors including arriving time at advance detector, approaching speed, headway, gap to the preceding vehicle on adjacent lane, cycle length, geometric characteristics and even snowing weather were empirically investigated. Statistical analysis shows good agreement with the traffic engineering practice, e.g., RLR is most likely to occur on weekdays during peak periods under large traffic demands and longer signal cycles, and a total of 95.24% RLR events occurred within the first 1.5s after the onset of red phase. The findings confirmed that vehicles tend to run the red light when they are close to intersection during phase transition, and the vehicles following the leading vehicle with short headways also likely run the red light. Last, a simplified nonlinear regression model is proposed to estimate RLR frequency based on the data from advance detector. The study is expected to helpbetter understand RLR occurrence and further contribute to the future improvement of intersection safety.