Clinical relevance of glomerular IgM deposition in patients with lupus nephritis.

BACKGROUND: The aim of the study was to investigate the clinical relevance of IgM deposition in patients with lupus nephritis (LN) in a large cohort. RESULTS: 217 patients with renal biopsy-proven active LN were enrolled. The associations between glomerular IgM deposition and clinicopathological parameters were further analyzed. IgM deposition was positively correlated with glomerular C1q and C3 deposition moderately (r = 0.436, P < 0.001; r = 0.408, P < 0.001, respectively), and inversely correlated with plasma levels of C3 and CFH mildly (r = - 0.138, P = 0.043; r = - 0.147, P = 0.037, respectively). By multivariate analysis, we found that glomerular IgM deposition independently contributed to glomerular C3 deposition in patients with LN (OR = 2.002, 95% CI 1.295-3.094, P = 0.002). In addition, we also found that patients with IgM 0-2+ had similar plasma CFH levels, but in patients with IgM3+-4+, plasma CFH levels were significantly lower (300.4 ± 155.8 µg/mL vs. 429.9 ± 187.5 µg/mL, P < 0.001). Furthermore, patients with high density of glomerular IgM and low levels of CFH had heavier proteinuria, higher serum creatinine and lower plasma C3 levels (5.7 ± 3.1 g/d vs. 4.7 ± 3.5 g/d, P = 0.037; 150.1 ± 121.0 µmol/L vs. 105.6 ± 97.1 µmol/L, P = 0.005; 0.3 ± 0.2 µg/L vs. 0.4 ± 0.2 µg/L, P = 0.04, respectively), comparing with those with low density of glomerular IgM and low levels of CFH. CONCLUSIONS: Our results suggested the involvement of glomerular deposited IgM in complement activation and renal injury in LN.

Fibroblast growth factor 21 (FGF21) is a sensitive marker of osteoporosis in haemodialysis patients: a cross-sectional observational study.

INTRODUCTION: Osteoporosis is one of the important bone abnormalities in chronic kidney disease-mineral and bone disorder (CKD-MBD) and still lacks a sensitive biomarker to diagnose. Fibroblast growth factor 21 (FGF21) can stimulate bone loss in patients with diabetes and increase in CKD patients. In this study, we investigated whether FGF21 could serve as a biomarker to predict osteoporosis in a haemodialysis cohort. METHODS: We recorded demographic information, biochemical data, and serum FGF21 and FGF23 levels and measured the CT attenuation values of 339 haemodialysis patients from two large medical centres. We assessed the correlation of CT attenuation values with serum FGF21 and FGF23 levels and tested whether they were independent factors for osteoporosis. ROC curves were constructed to compare the prognostic value of FGF21 and FGF23 for osteoporosis. RESULTS: Based on the CT attenuation value, serum FGF21 levels were higher in our osteoporosis group (median 640.86 pg/ml vs. 245.46 pg/ml, P ˂ 0.01). Meanwhile, FGF21 (r = -0.136, P < 0.05) and FGF23 (r = -0.151, P < 0.05) were both negatively associated with osteoporosis. Moreover, FGF21 (ß = -0.067, P < 0.05) was an independent factor for osteoporosis. Furthermore, FGF21 combined with age yielded a marked specificity (90.5 %) and sensitivity (61.8 %) in predicting osteoporosis of haemodialysis patients with less residual renal function. CONCLUSIONS: FGF21 has a positive relationship with the incidence of osteoporosis in patients on haemodialysis. FGF21 combined with age is a good predictive biomarker for osteoporosis in patients on haemodialysis, especially those with less residual renal function.

CD62P and P10 as predictive markers for assessing the efficacy of hemodialysis in treating end-stage renal disease.

BACKGROUND: CD62P is a platelet α-granule membrane protein, and P10 is a platelet membrane glycoprotein thrombospondin. To better understand the effects of hemodialysis (HD), we have conducted this study to investigate CD62P and P10 in assessing the efficacy of HD in treating patients with end-stage renal disease (ESRD). METHODS: The case group consisted of 111 patients suffering ESRD treated with regular HD and the control group enrolled 117 healthy subjects. Before and after HD treatment, a series of parameters were observed, based on which, CD62P and P10 levels were detected in the patients in two groups before and after HD therapy. The correlation analysis analyzed the correlations of CD62P and P10 markers with serum creatinine (Scr), blood urea nitrogen (BUN), and subjective score; and logistic regression analysis was performed to reveal factors affecting the efficacy of HD. RESULTS: BUN, Scr, serum phosphorus, intact parathyroid hormone (iPTH), fibrinogen, and ß2-microglobulin (ß2-MG) decreased while hemoglobin, albumin, and activated partial thromboplastin time increased in the patients suffering ESRD; patients presented with improvements in subjective symptoms and an increase in dry weight. CD62P and P10 levels were lower in post-treatment patients. CD62P and P10 positively correlated with Scr, BUN and subjective score; post-treatment CD62P and P10 levels, BUN, hemoglobin, albumin, triglyceride, iPTH, ß2-MG, and fibrinogen were correlated with the efficacy of HD. CONCLUSION: CD62P and P10 might be correlated to the efficacy of HD in treating ESRD, in turn providing predictive markers for assessing the ability of HD in treating ESRD.

Double-pulse 2-µm integrated path differential absorption lidar airborne validation for atmospheric carbon dioxide measurement.

Field experiments were conducted to test and evaluate the initial atmospheric carbon dioxide (CO2) measurement capability of airborne, high-energy, double-pulsed, 2-µm integrated path differential absorption (IPDA) lidar. This IPDA was designed, integrated, and operated at the NASA Langley Research Center on-board the NASA B-200 aircraft. The IPDA was tuned to the CO2 strong absorption line at 2050.9670 nm, which is the optimum for lower tropospheric weighted column measurements. Flights were conducted over land and ocean under different conditions. The first validation experiments of the IPDA for atmospheric CO2 remote sensing, focusing on low surface reflectivity oceanic surface returns during full day background conditions, are presented. In these experiments, the IPDA measurements were validated by comparison to airborne flask air-sampling measurements conducted by the NOAA Earth System Research Laboratory. IPDA performance modeling was conducted to evaluate measurement sensitivity and bias errors. The IPDA signals and their variation with altitude compare well with predicted model results. In addition, off-off-line testing was conducted, with fixed instrument settings, to evaluate the IPDA systematic and random errors. Analysis shows an altitude-independent differential optical depth offset of 0.0769. Optical depth measurement uncertainty of 0.0918 compares well with the predicted value of 0.0761. IPDA CO2 column measurement compares well with model-driven, near-simultaneous air-sampling measurements from the NOAA aircraft at different altitudes. With a 10-s shot average, CO2 differential optical depth measurement of 1.0054±0.0103 was retrieved from a 6-km altitude and a 4-GHz on-line operation. As compared to CO2 weighted-average column dry-air volume mixing ratio of 404.08 ppm, derived from air sampling, IPDA measurement resulted in a value of 405.22±4.15 ppm with 1.02% uncertainty and 0.28% additional bias. Sensitivity analysis of environmental systematic errors correlates the additional bias to water vapor. IPDA ranging resulted in a measurement uncertainty of <3 m.

Self-calibration and laser energy monitor validations for a double-pulsed 2-µm CO2 integrated path differential absorption lidar application.

Double-pulsed 2-µm integrated path differential absorption (IPDA) lidar is well suited for atmospheric CO2 remote sensing. The IPDA lidar technique relies on wavelength differentiation between strong and weak absorbing features of the gas normalized to the transmitted energy. In the double-pulse case, each shot of the transmitter produces two successive laser pulses separated by a short interval. Calibration of the transmitted pulse energies is required for accurate CO2 measurement. Design and calibration of a 2-µm double-pulse laser energy monitor is presented. The design is based on an InGaAs pin quantum detector. A high-speed photoelectromagnetic quantum detector was used for laser-pulse profile verification. Both quantum detectors were calibrated using a reference pyroelectric thermal detector. Calibration included comparing the three detection technologies in the single-pulsed mode, then comparing the quantum detectors in the double-pulsed mode. In addition, a self-calibration feature of the 2-µm IPDA lidar is presented. This feature allows one to monitor the transmitted laser energy, through residual scattering, with a single detection channel. This reduces the CO2 measurement uncertainty. IPDA lidar ground validation for CO2 measurement is presented for both calibrated energy monitor and self-calibration options. The calibrated energy monitor resulted in a lower CO2 measurement bias, while self-calibration resulted in a better CO2 temporal profiling when compared to the in situ sensor.

Evaluation of an airborne triple-pulsed 2 µm IPDA lidar for simultaneous and independent atmospheric water vapor and carbon dioxide measurements.

Water vapor and carbon dioxide are the most dominant greenhouse gases directly contributing to the Earth's radiation budget and global warming. A performance evaluation of an airborne triple-pulsed integrated path differential absorption (IPDA) lidar system for simultaneous and independent monitoring of atmospheric water vapor and carbon dioxide column amounts is presented. This system leverages a state-of-the-art Ho:Tm:YLF triple-pulse laser transmitter operating at 2.05 µm wavelength. The transmitter provides wavelength tuning and locking capabilities for each pulse. The IPDA lidar system leverages a low risk and technologically mature receiver system based on InGaAs pin detectors. Measurement methodology and wavelength setting are discussed. The IPDA lidar return signals and error budget are analyzed for airborne operation on-board the NASA B-200. Results indicate that the IPDA lidar system is capable of measuring water vapor and carbon dioxide differential optical depth with 0.5% and 0.2% accuracy, respectively, from an altitude of 8 km to the surface and with 10 s averaging. Provided availability of meteorological data, in terms of temperature, pressure, and relative humidity vertical profiles, the differential optical depth conversion into weighted-average column dry-air volume-mixing ratio is also presented.

Single-frequency gain-switched Ho-doped fiber laser.

We demonstrate a single-frequency gain-switched Ho-doped fiber laser based on heavily doped silicate glass fiber fabricated in-house. A Q-switched Tm-doped fiber laser at 1.95 µm was used to gain-switch the Ho-doped fiber laser via in-band pumping. Output power of the single-frequency gain-switched pulses has been amplified in a cladding-pumped Tm-Ho-codoped fiber amplifier with 1.2 m active fiber pumped at 803 nm. Two different nonlinear effects, i.e., modulation instability and stimulated Brillouin scattering, could be seen in the 10 µm-core fiber amplifier when the peak power exceeds 3 kW. The single-frequency gain-switched fiber laser was operated at 2.05 µm, a popular laser wavelength for Doppler lidar application. This is the first demonstration of this kind of fiber laser.

Fully conductively cooled, diode-pumped Ho:Tm:LuLiF4 laser oscillator/amplifier.

A fully conductively cooled and diode-pumped linear Ho:Tm:LuLiF laser oscillator can generate more than 1 J normal mode pulses at a 10 Hz pulse repetition rate where heat pipes are used for cooling pump diodes and laser crystal. As an amplifier, it can amplify the 80 mJ/180 ns pulses into 400 mJ pulses before the appearance of amplified spontaneous emission (ASE). The ASE threshold is about 5.6 J with a 40 mm long and side-polished laser crystal. For a 5 mJ input pulse and 5.6 J pump pulse, the double-pass gain exceeds 22.5. If the lateral surface of the laser crystal is fine ground, the ASE threshold can rise to higher than 8 J, but the efficiency will be lower due to large pump diffusion.

220 µJ monolithic single-frequency Q-switched fiber laser at 2 µm by using highly Tm-doped germanate fibers.

We report a unique all fiber-based single-frequency Q-switched laser in a monolithic master oscillator power amplifier configuration at ~1920 nm by using highly Tm-doped germanate fibers for the first time. The actively Q-switched fiber laser seed was achieved by using a piezo to press the fiber in the fiber Bragg grating cavity and modulate the fiber birefringence, enabling Q-switching with pulse width and repetition rate tunability. A single-mode polarization maintaining large core 25 µm highly Tm-doped germanate fiber was used in the power amplifier stage. For 80 ns pulses with 20 kHz repetition rate, we achieved 220 µJ pulse energy, which corresponds to a peak power of 2.75 kW with transform-limited linewidth.

Microinflammation is involved in the dysfunction of arteriovenous fistula in patients with maintenance hemodialysis.

BACKGROUND: Vascular access (VA) dysfunction is a major clinical complication in the hemodialysis population and has a direct effect on dialysis outcome. This study was conducted to explore the role of microinflammation in the VA dysfunction in maintenance hemodialysis patients. METHODS: Forty-seven patients (male 35 and female 12) receiving maintenance hemodialysis were included for this study. They were divided into three groups: group 1 (n = 15), patients with initial hemodialysis and new arteriovenous fistula (AVF); group 2 (n = 18), patients treated with hemodialysis for long term with well-functional VA; group 3 (n = 14), maintenance hemodialysis patients with VA dysfunction. Biochemical parameters and serum tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) were determined. High-sensitivity C-reactive protein (hs-CRP) was determined by latex-enhanced immuno-nephelometric method. Tissues of radial artery were taken from group 1 and group 3 for the histological study. Expression of CD68 and MCP-1 in the radial artery was determined by immunohistochemistry. RESULTS: Serum hs-CRP in group 3 was significantly higher than those in group 1 and group 2 ((7.40 +/- 2.42) mg/L vs (4.21 +/- 1.62) mg/L and (5.04 +/- 3.65) mg/L, P < 0.01 and P < 0.05, respectively). Serum TNF-alpha in group 3 was significantly higher than those in group 1 and group 2 ((64.03 +/- 9.29) pg/ml vs (54.69 +/- 12.39) pg/ml and (54.05 +/- 7.68) pg/ml, P < 0.05 and P < 0.01, respectively). Serum IL-6 in group 3 was also significantly higher than those in group 1 and group 2 ((70.09 +/- 14.53) pg/ml vs (56.43 +/- 10.11) pg/ml and (60.77 +/- 9.70) pg/ml, P < 0.01 and P < 0.05, respectively). Patients in group 3 had a thicker internal layer of vessels than in group 1 ((0.356 +/- 0.056) mm vs (0.111 +/- 0.021) mm, P < 0.01). Expression of CD68 and MCP-1 in the fistula vessel walls in group 3 were much higher than those in group 1 (P < 0.01). Moreover, serum hs-CRP level was positively correlated with the neointimal hyperplasia, the expression of CD68 and MCP-1 in fistula vessel (P < 0.01, respectively). CONCLUSION: Microinflammation might be involved in the dysfunction of AVF in patients with maintenance hemodialysis.

Side-line tunable laser transmitter for differential absorption lidar measurements of CO2: design and application to atmospheric measurements.

A 2 microm wavelength, 90 mJ, 5 Hz pulsed Ho laser is described with wavelength control to precisely tune and lock the wavelength at a desired offset up to 2.9 GHz from the center of a CO(2) absorption line. Once detuned from the line center the laser wavelength is actively locked to keep the wavelength within 1.9 MHz standard deviation about the setpoint. This wavelength control allows optimization of the optical depth for a differential absorption lidar (DIAL) measuring atmospheric CO(2) concentrations. The laser transmitter has been coupled with a coherent heterodyne receiver for measurements of CO(2) concentration using aerosol backscatter; wind and aerosols are also measured with the same lidar and provide useful additional information on atmospheric structure. Range-resolved CO(2) measurements were made with <2.4% standard deviation using 500 m range bins and 6.7 min? (1000 pulse pairs) integration time. Measurement of a horizontal column showed a precision of the CO(2) concentration to <0.7% standard deviation using a 30 min? (4500 pulse pairs) integration time, and comparison with a collocated in situ sensor showed the DIAL to measure the same trend of a diurnal variation and to detect shorter time scale CO(2) perturbations. For vertical column measurements the lidar was setup at the WLEF tall tower site in Wisconsin to provide meteorological profiles and to compare the DIAL measurements with the in situ sensors distributed on the tower up to 396 m height. Assuming the DIAL column measurement extending from 153 m altitude to 1353 m altitude should agree with the tower in situ sensor at 396 m altitude, there was a 7.9 ppm rms difference between the DIAL and the in situ sensor using a 30 min? rolling average on the DIAL measurement.

Efficient operation of diode-pumped single-frequency thulium-doped fiber lasers near 2 micro m.

Efficient operation of diode-pumped single-frequency fiber lasers at wavelengths from 1740 to 2017 nm has been demonstrated by using a very short piece of newly developed single-mode active fiber, i.e., heavily thulium-doped germanate glass fiber. At 1893 nm, the single-frequency fiber laser has a pump threshold of 30 mW, a slope efficiency of 35%, and maximum output power of 50 mW with respect to the launched power of single-mode pump diodes at 805 nm. To the best of our knowledge, this is the highest lasing efficiency achieved in single-frequency fiber lasers operating near 2 micro m. Frequency noise of the single-frequency fiber laser at 1893 nm has been characterized and compared with that of single-frequency fiber lasers at 1 and 1.55 micro m.

1 J/pulse Q-switched 2 microm solid-state laser.

Q-switched output of 1.1 J/pulse at a 2.053 microm wavelength has been achieved in a diode-pumped Ho: Tm: LuLF laser with a side-pumped rod configuration in a master-oscillator-power-amplifier (MOPA) architecture. This is the first time to our knowledge that a 2 microm laser has broken the joule per pulse barrier for Q-switched operation. The total system efficiency reaches 5% and 6.2% for single- and double-pulse operation, respectively. The system produces an excellent 1.4 times transform-limited beam quality.

Coherent differential absorption lidar measurements of CO2.

A differential absorption lidar has been built to measure CO2 concentration in the atmosphere. The transmitter is a pulsed single-frequency Ho:Tm:YLF laser at a 2.05-microm wavelength. A coherent heterodyne receiver was used to achieve sensitive detection, with the additional capability for wind profiling by a Doppler technique. Signal processing includes an algorithm for power measurement of a heterodyne signal. Results show a precision of the CO2 concentration measurement of 1%-2% 1sigma standard deviation over column lengths ranging from 1.2 to 2.8 km by an average of 1000 pulse pairs. A preliminary assessment of instrument sensitivity was made with an 8-h-long measurement set, along with correlative measurements with an in situ sensor, to determine that a CO2 trend could be detected.

600-mJ, double-pulse 2-microm laser.

An efficient double-pulse Ho:Tm:YLF 2-microm laser with total Q-switched output energy of 600 mJ has been demonstrated. A double-pulse pair is obtained per pump pulse. By operation of the laser in a double-pulse format, the residual energy stored among the Tm ions is transferred to the Ho atoms that were de-excited by the extraction of the first Q-switched pulse. Thus, the overall laser efficiency is increased by 61%.

Precise wavelength control of a single-frequency pulsed Ho:Tm:YLF laser.

We demonstrate wavelength control of a single-frequency diode-pumped Ho:Tm:YLF laser by referencing its wavelength to an absorption line of carbon dioxide. We accomplish this wavelength control by injection seeding with a cw Ho:Tm:YLF laser that can be tuned over or stabilized to carbon dioxide or water vapor lines. We show that the pulsed laser can be scanned precisely over an absorption line of carbon dioxide by scanning the injection seed laser wavelength. We locked the pulsed laser to within 18.5 MHz of the absorption line center by stabilizing the injection seed on the line center. The single-frequency pulsed output, intended for use as a transmitter for differential absorption lidar detection of atmospheric carbon dioxide and water vapor and for coherent detection of wind, is 100 mJ per pulse at a 5-Hz repetition rate.