IgA nephropathy is the most common glomerular disease worldwide, yet there is no international consensus for its pathological or clinical classification. Here a new classification for IgA nephropathy is presented by an international consensus working group. The goal of this new system was to identify specific pathological features that more accurately predict risk of progression of renal disease in IgA nephropathy, thus enabling both clinicians and pathologists to improve individual patient prognostication. In a retrospective analysis, sequential clinical data were obtained on 265 adults and children with IgA nephropathy who were followed for a median of 5 years. Renal biopsies from all patients were scored by pathologists blinded to the clinical data for pathological variables identified as reproducible by an iterative process. Four of these variables: (1) the mesangial hypercellularity score, (2) segmental glomerulosclerosis, (3) endocapillary hypercellularity, and (4) tubular atrophy/interstitial fibrosis were subsequently shown to have independent value in predicting renal outcome. These specific pathological features withstood rigorous statistical analysis even after taking into account all clinical indicators available at the time of biopsy as well as during follow-up. The features have prognostic significance and we recommended they be taken into account for predicting outcome independent of the clinical features both at the time of presentation and during follow-up. The value of crescents was not addressed due to their low prevalence in the enrolled cohort.

Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glomerular disease, IgA nephropathy, in which renal pathologists first undertook extensive iterative work to define pathologic variables with acceptable inter-observer reproducibility. Where groups of such features closely correlated, variables were further selected on the basis of least susceptibility to sampling error and ease of scoring in routine practice. This process identified six pathologic variables that could then be used to interrogate prognostic significance independent of the clinical data in IgA nephropathy (described in the accompanying article). These variables were (1) mesangial cellularity score; percentage of glomeruli showing (2) segmental sclerosis, (3) endocapillary hypercellularity, or (4) cellular/fibrocellular crescents; (5) percentage of interstitial fibrosis/tubular atrophy; and finally (6) arteriosclerosis score. Results for interobserver reproducibility of individual pathological features are likely applicable to other glomerulonephritides, but it is not known if the correlations between variables depend on the specific type of glomerular pathobiology. Variables identified in this study withstood rigorous pathology review and statistical testing and we recommend that they become a necessary part of pathology reports for IgA nephropathy. Our methodology, translating a strong evidence-based dataset into a working format, is a model for developing classifications of other types of renal disease.

Since the Oxford Classification of IgA nephropathy (IgAN)

The Oxford Classification of IgA nephropathy (IgAN) includes the following four histologic components: mesangial (M) and endocapillary (E) hypercellularity, segmental sclerosis (S) and interstitial fibrosis/tubular atrophy (T). These combine to form the MEST score and are independently associated with renal outcome. Current prediction and risk stratification in IgAN requires clinical data over 2 years of follow-up. Using modern prediction tools, we examined whether combining MEST with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than current best methods that use 2 years of follow-up data. We used a cohort of 901 adults with IgAN from the Oxford derivation and North American validation studies and the VALIGA study followed for a median of 5.6 years to analyze the primary outcome (50% decrease in eGFR or ESRD) using Cox regression models. Covariates of clinical data at biopsy (eGFR, proteinuria, MAP) with or without MEST, and then 2-year clinical data alone (2-year average of proteinuria/MAP, eGFR at biopsy) were considered. There was significant improvement in prediction by adding MEST to clinical data at biopsy. The combination predicted the outcome as well as the 2-year clinical data alone, with comparable calibration curves. This effect did not change in subgroups treated or not with RAS blockade or immunosuppression. Thus, combining the MEST score with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than our current best methods.

Ultra-wideband (UWB) communication is expected to be used for many consumer electronics products in the near future. UWB systems are capable of supporting data rates as high as several hundred Mb/s while consuming a low power. Thus, they are suitable candidates for wireless personal area networks (WPANs). Although UWB systems are allowed to utilize the 3.1-10.6GHz band, first generation UWB systems will probably use the band below 5GHz. A 3.1-5GHz CMOS UWB transceiver is presented in this paper that is based on a direct sequence spread spectrum (DSSS) method as described in reference [1], and is different from 2 merged proposals called MB-OFDM and DS-UWB in the activity of the IEEE 802.15 TG3a [2]. Figure 11.8.1 shows a block diagram of the transceiver. The 8GHz VCO output is divided by 2 to provide 4GHz I and Q signals which are fed to the transmitter block (TX) and the receiver block (RX) as local oscillator (LO) signals, and to the high-speed current-mode logic circuits of the TX pulse modulator as a clock signal.The data, which is spread with a chip rate of 1Gchip/s in the baseband block, enters TX_I and TX_Q, and then the TX pulse modulator performs pulse shaping on each bit. Figure 11.8.2 shows the circuit schematic and simplified timing chart of the TX pulse modulator. The purpose of the pulse shaping is to lower the power density at 3.1GHz, to increase the total transmit power by flattening the spectrum of the transmit signal, and to pre-equalize the waveform of the transmit signal for the RX filter characteristic.In the context of this work, pre-equalization is to perform an approximate reversed-time matched filter of the RX filter as shown in Fig. 11.8.3.The TX pulse modulator in Fig. 11.8.2 allows programmable pulse shaping. The 1GHz Johnson counter has four 1GHz outputs, Q1-4, each shifted by 250ps. Each output is multiplied by a ±1 depending on the polarity of the phase amplitude contribution and the sense of the incoming data bit. The left most multiplier provides a DC offset to the pulse shape. TX_I and TX_Q waveforms are out of alignment with each other by 1ns to perform the π/2-shift BPSK modulation [1]. Outputs Q1-4 and the DC phase are transformed into currents proportional to the signal and the programmable values in the register. The currents are summed, and mixed with LO. The LO Mixer outputs I_OUT and Q_OUT are added up and the resultant signal has an almost constant envelope.The power amplifier has differential output ports whose impedance is 100Ω, and feeds the transmit signal to the antenna through an external balun. The maximum output power is -9dBm and can be set with eight 1dB steps. Figure 11.8.3 shows a measured spectrum of the transmit signal and an analysis result for modulation using a vector signal analyzer. The measured spectrum includes the frequency response of an external balun. The spectrum shows that the transmit signal, without an external band-pass filter, meets the FCC spectrum mask and spreads flat over a wide range centering on 4GHz, although it is slightly inclined. ...