Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis

Background & Aims: Prognostic biomarkers are lacking in primary sclerosing cholangitis, hampering patient care and the development of therapy. We aimed to identify novel protein biomarkers of disease severity and prognosis in primary sclerosing cholangitis (PSC). Methods: Using a bead-based array targeting 63 proteins, we profiled a derivation panel of Norwegian endoscopic retrograde cholangiography bile samples (55 PSC, 20 disease controls) and a Finnish validation panel (34 PSC, 10 disease controls). Selected identified proteins were measured in serum from two Norwegian PSC cohorts (n = 167 [1992-2006] and n = 138 [2008-2012]), inflammatory bowel disease (n = 96) and healthy controls (n = 100). Results: In the bile derivation panel, the levels of 14 proteins were different between PSC patients and controls (p <0.05); all were confirmed in the validation panel. Twenty-four proteins in the bile derivation panel were significantly (p <0.05) different between PSC patients with mild compared to severe cholangiographic changes (modified Amsterdam criteria); this was replicated for 18 proteins in the validation panel. Interleukin (IL)-8, matrix metallopeptidase (MMP)9/lipocalin (LCN)2-complex, S100A8/9, S100A12 and tryptophan hydroxylase (TPH)2 in the bile were associated with both a PSC diagnosis and grade of cholangiographic changes. Stratifying PSC patients according to tertiles of serum IL-8, but not MMP9/LCN2 and S100A12, provided excellent discrimination for transplant-free survival both in the serum derivation and validation cohort. Furthermore, IL-8 was associated with transplant-free survival in multivariable analyses in both serum panels independently of age and disease duration, indicating an independent influence on PSC progression. However, the Enhanced Liver Fibrosis (ELF (R)) test and Mayo risk score proved to be stronger predictors of transplant-free survival. Conclusions: Based on assaying of biliary proteins, we have identified novel biliary and serum biomarkers as indicators of severity and prognosis in PSC. Lay summary: Prognostic biomarkers are lacking in primary sclerosing cholangitis, hampering patient care and the development of therapy. We have identified inflammatory proteins including calprotectin and IL-8 as important indicators of disease severity and prognosis in bile and serum from patients with primary sclerosing cholangitis. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.Peer reviewe

Radio frequency ranging for wireless sensor network localization

Wireless sensor networks (WSNs) have a diverse range of industrial, scientific and medical applications where the sensor nodes are of low cost, standard with respect to hardware architecture, processing abilities and communicate using low-power narrow-band radios. Position information of the sensing nodes within those applications is often a requirement in order to make use of the data recorded by the sensors themselves. On deployment, sensing nodes normally have no prior knowledge of their position and thus a localization mechanism is often a requirement. The process of localizing a 'blind' device consists of ranging estimates or angle measurements to a set of references with a prior knowledge of their position relative to a co-ordinate system and the position computation of the blind device in relation to the fixed references. This research focuses on the process of ranging to enable two-dimensional localization of sensing nodes within WSNs. Alternative ranging methods for the specified application field have not demonstrated their ability to meet the resolution and accuracy (resolution 0.3 m with accuracy better than ± 1.0 m line-of-sight) required. A novel radio frequency (RF) time-of-flight (TOF) ranging system is presented in this work to mitigate those problems. The system has been prototyped using a TI CC2431 development platform with ranging and data packet transfer performed on a single channel in the 2.4 GHz ISM frequency band. The frequency difference between the two transceivers involved with ranging is used to obtain sub-clock TOF phase offset measurement in order to achieve high resolution TOF measurements. Performance results have been obtained for the line-of-sight (LOS), non-line-of-sight (NLOS) and indoor conditions. Accuracy is typically better than 7.0m RMS for the LOS condition over 250.0m and 15.8m RMS for the NLOS condition over 120.0m using a sample average of one-hundred two-way ranging transactions. Indoors accuracy is measured to 1.7m RMS using a 1000 sample average over 8.0m. Corresponding results are also presented for the algorithms suitability for localizing sensor nodes in two-dimensions. Ranging performance is bound by the signal-to-noise ratio (SNR), signal bandwidth, synchronization and frequency difference between devices. This ranging algorithm demonstrates a novel method where resolution and accuracy are improved time dependent in comparison to frequency dependent methods using narrow-band RF

Gözetim Toplumunda Sosyal Medya ve Mahremiyetin Dönüşümü

Relative ranging between Wireless Sensor Network (WSN) nodes is considered to be an important requirement for a number of distributed applications. This paper focuses on a two-way, time of flight (ToF) technique which achieves good accuracy in estimating the point-to-point distance between two wireless nodes. The underlying idea is to utilize a two-way time transfer approach in order to avoid the need for clock synchronization between the participating wireless nodes. Moreover, by employing multiple ToF measurements, sub-clock resolution is achieved. A calibration stage is used to estimate the various delays that occur during a message exchange and require subtraction from the initial timed value. The calculation of the range between the nodes takes place on-node making the proposed scheme suitable for distributed systems. Care has been taken to exclude the erroneous readings from the set of measurements that are used in the estimation of the desired range. The two-way ToF technique has been implemented on commercial off-the-self (COTS) devices without the need for additional hardware. The system has been deployed in various experimental locations both indoors and outdoors and the obtained results reveal that accuracy between 1 m RMS and 2.5 m RMS in line-of-sight conditions over a 42 m range can be achieved