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Almost 30 years after the detection of chronic interstitial nephritis in agricultural communities (CINAC) its etiology remains unknown. To help define this we examined 34 renal biopsies from Sri Lanka, El Salvador, India and France of patients with chronic kidney disease 2-3 and diagnosed with CINAC by light and electron microscopy. In addition to known histopathology, we identified a unique constellation of proximal tubular cell findings including large dysmorphic lysosomes with a light-medium electron-dense matrix containing dispersed dark electron-dense non-membrane bound “aggregates”. These aggregates associated with varying degrees of cellular/tubular atrophy, apparent cell fragment shedding and no-weak proximal tubular cell proliferative capacity. Identical lysosomal lesions, identifiable by electron microscopy, were observed in 9% of renal transplant implantation biopsies, but were more prevalent in six month (50%) and 12 month (67%) protocol biopsies and in indication biopsies (76%) of calcineurin inhibitor treated transplant patients. The phenotype was also found associated with nephrotoxic drugs (lomustine, clomiphene, lithium, cocaine) and in some patients with light chain tubulopathy, all conditions that can be directly or indirectly linked to calcineurin pathway inhibition or modulation. One hundred biopsies of normal kidneys, drug/toxin induced nephropathies, and overt proteinuric patients of different etiologies to some extent could demonstrate the light microscopic proximal tubular cell changes, but rarely the electron microscopic lysosomal features. Rats treated with the calcineurin inhibitor cyclosporine for four weeks developed similar proximal tubular cell lysosomal alterations, which were absent in a dehydration group. Overall, the finding of an identical proximal tubular cell (lysosomal) lesion in CINAC and calcineurin inhibitor nephrotoxicity in different geographic regions suggests a common paradigm where CINAC patients undergo a tubulotoxic mechanism similar to calcineurin inhibitor nephrotoxicity.

Higher efficacy of incretin-based therapies for type 2 diabetes mellitus has been reported from Asia. Pancreatitis and hepatitis have also been suspected to occur due to dipeptidyl peptidase-4 inhibitor (DPP4I) treatment. The present study aims at comparing selected biochemical parameters among DPP4 inhibitor users and other oral hypoglycaemic drug users. Patients were recruited from the State Pharmaceutical Corporation, Anuradhapura, Sri Lanka, for a comparative cross-sectional study. Two groups were involved: “DPP4I” user group (n= 63) and “other oral hypoglycaemic” user group (n= 126). Mann-Whitney Utest was performed to find a significant difference (p< 0.05) in the distributions of HbA1C, pancreatic amylase, serum lipase, AST and ALT levels between the two groups. Contradicting to previous Asian studies, distribution of HbA1C(p= 0.569) between anti-diabetic regimes with and without DPP4 inhibitors showed no significant difference. Also, amylase (p= 0.171), AST (p= 0.238) and ALT (p= 0.347) failed to show significance. However, lipase was significantly (p= 0.012) high in the DPP4I group. The study showed a significantly higher lipase level among the DPP4I users in comparison to other oral hypoglycaemic drug users, and possible reasons were discussed.

A novel distributed approach for searching and tracking of targets is presented for sensor network environments in which physical distance measurement using techniques such as signal strength is not feasible. The solution consists of a robust Kalman filter combined with a non‐linear least‐square method, and maximum likelihood topology maps. The primary input for estimating target location and direction of motion is provided by time stamps recorded by the sensor nodes when the target is detected within their sensing range. An autonomous robot following the target collects this information from sensors in its neighbourhood to determine its own path in search of the target. While the maximum likelihood topology coordinate space is a robust alternative to physical coordinates, it contains significant non‐linear distortions when compared with physical distances between nodes. The authors overcome this using time stamps corresponding to target detection by nodes instead of relying on distances. The performance of the proposed algorithm is compared with recently proposed pseudo gradient algorithm based on hop count and received signal strength. Even though the proposed algorithm does not depend on distance measurements, the results show that it is able to track the target effectively even when the target changes its moving pattern frequently.

Models for Internet traffic anomalies greatly benefit a range of applications including robust network design, network provisioning and performance studies. A novel approach to analyse and model network traffic anomalies is presented. The proposed approach individually characterises different aspects of anomalies, such as origin, termination, propagation and changes in duration and volume, with common random processes. These characteristics are then integrated into a single model that successfully captures the overall anomaly behaviours. Characterisation of each anomaly property requires only a few parameters, leading to a concise set of parameters for the entire model. Although the model is calibrated with local measurements made at nodes, it successfully represents the global behaviours of anomalies over the network. The proposed model is applicable both at nodal level and at subnet level. This enables hierarchically analysing large and sophisticated networks. Anomalies are analysed using a multi-scale analysis framework based on which, a real-time monitoring system that efficiently communicate ongoing anomaly information across the network is developed. The system is also used for learning regional model parameters distributively. Internet2 traffic data is analysed using the framework, and the corresponding model parameters are derived. These results provide insight on the nature of anomalies in networks.

In this paper we describe an approach for the detection and classication of weak, distributed patterns in sensor networks. Of course, before one can begin development of a pattern detection algorithm, one must rst dene the term "pattern", which by nature is a broad and inclusive term. One of the key aspects of our work is a denition of pattern that has already proven eective in detecting anomalies in real world data. While designing detection algorithms for all classes of patterns in all types of networks sounds appealing, this approach would almost certainly require heuristic methods and only cursory statements of performance. Rather, we have specically studied the problem of intrusion detection in computer networks in which a pattern is an abnormal or unexpected spatio-temporal dependence in the data collected across the nodes. We do not attempt to match an a priori template, but instead have developed algorithms that allow the pattern to reveal itself in the data by way of dependence or independence of observed time series. Although the problem is complex and challenging, recent advances in 1techniques for robust matrix completion, compressed sensing, and correlation detection provide promising opportunities for progress. Our key contribution to this body of work is the development of methods that make an accounting of uncertainty in the measurements on which the inferences are based. The performance of our methods will be demonstrated on real world data, including measured data from the Abilene Internet2 network.

The effects of different wavelength conversion ranging configurations on the performance of Wavelength Division Multiplexing (WDM) optical switches are investigated. Any-to-Any, Any-to-Range, Range-to-Any, and Range-to-Rangeconversion ranging configurations are considered. These mechanisms provide important design alternatives for optical switches due to technological limitations in the implementation of full range wavelength conversion in an all-optical wavelength converter device. Limited-range wavelength converter (LRWC) is a more economical and practical solution for WDM based optical networks. Differences among the input and output side ranging mechanisms and their effects on conversion resource sharing, and consequently on performance, are investigated. Any- to-Rangeranging configuration is the most efficient mechanism and it operates comparably to Any-to-Any, reducing the need for complex control algorithms. The results help determine the most efficient ranging configuration for all-optical crossconnect.The effects of different wavelength conversion ranging configurations on the performance of Wavelength Division Multiplexing (WDM) optical switches are investigated. Any-to-Any, Any-to-Range, Range-to-Any, and Range-to-Rangeconversion ranging configurations are considered. These mechanisms provide important design alternatives for optical switches due to technological limitations in the implementation of full range wavelength conversion in an all-optical wavelength converter device. Limited-range wavelength converter (LRWC) is a more economical and practical solution for WDM based optical networks. Differences among the input and output side ranging mechanisms and their effects on conversion resource sharing, and consequently on performance, are investigated. Any- to-Rangeranging configuration is the most efficient mechanism and it operates comparably to Any-to-Any, reducing the need for complex control algorithms. The results help determine the most efficient ranging configuration for all-optical crossconnect.

Network Survivability is defined as the ability of a network to support the committed Quality of Services (QoS) continuously in the presence of different failure scenarios. Both availability and performance degradation of a system in presence of failure are integral components of survivability evaluation. Therefore, a composite model is presented for network survivability that includes system availability analysis to find out the cost due to system downtime, and system failure impact analysis to find out the transient performance degradation when failure occurs. A new analytical technique is presented to evaluate the excess loss due to failure (ELF) as the transient performance degradation when the system is operating in gracefully degraded states. Single and multiple link failures as well as node failures are considered. An algorithm is proposed to carry out the steady state availability analysis of a network even when the available paths between a pair of nodes are non-disjoint. A recursive generalized form of the availability algorithm when there are multiple paths available between a pair of nodes is presented. The availability model and the performance model are combined to construct a hierarchical model to evaluate the network survivability performance. Simulation results are used to validate the proposed model. A WDM network with wavelength conversion is considered as an example for this evaluation.

All-optical multihop networks, where the data portion of a packet is maintained in an optically encoded format from the source to the destination, can be achieved by augmenting optical switching nodes with optical buffering. Topologically, the ShuffleNet network is a strong contender for implementing such networks ranging from cluster networks to metropolitan area networks. The performance of a regular multihop network whose nodes are augmented with optical buffering and use deflection routing is evaluated. Using the ShuffleNet network as an example, we show that performance, in terms of throughput, average delay, and loss probability, can be improved as multiple fiber delay loops are added for a large range of network parameters. We then compare the performance of ShuffleNet with the Manhattan Street networks with similar features.

Robust-WDM is a technique to realize wavelength division multiplexed (WDM) local area networks (LANs) in the presence of laser wavelength drifts. Various medium access control (MAC) protocols have been proposed for Robust-WDM LANs. Among these protocols, the one with Aperiodic Reservation and Lenient Token-Passing control channel (the AR/LTP protocol) is the most promising. We discuss three internetworking strategies for AR/LTP Robust-WDM LANs. The aim is to explore the possibility to scale the AR/LTP Robust-WDM concepts to the metropolitan domain by looking at some basic medium-access arrangements and specifying the advantages and limitations of each. Special Remote Access Nodes (RANs) are proposed to facilitate interconnection. It is shown that by some modifications in the basic AR/LTP local area protocol and by parallel processing of connection requests, commands and control signals, the waiting time performance of a Robust-WDM interconnection can be improved. The improvement would be accomplished at the expense of some control sophistication. Further improvement can be achieved by designing a set of point-to-point links among the RANs of different Robust-WDM stars. In this case, control is relatively simplified, but the design of a RAN is made more complex and expensive.

Multihop networks are strong candidates for the implementation of high-speed networks, ranging from back-plane networks for cluster computing to metropolitan-area networks. Besides using deflection routing for contention resolution, optical buffering may be used to enhance the performance of optical multihop networks and to reduce or even eliminate the need for optical-electrical conversions. The enhancements obtained by augmenting traditional MSN (Manhattan Street Networks) with optical buffering are evaluated. The MSN considered here is based on a novel 6 × 6 optical switching node with up to two fiber delay loops. Impact of the parameters associated with optical buttering, such as the number of delay loops and the loop length, are discussed in detail.

The wavelength division multiplexing (WDM) network architectures, in general, are based on transmitters and/or receivers that can be precisely and speedily tuned to predetermined, fixed wavelengths. These requirements are not easy to meet in practice. Robust WDM, the subject of this paper, has been introduced as a technique to implement WDM in the local area. The strength of this novel approach is that it does not rely on wavelength-sensitive devices that are required to perform with extreme stability. This paper describes the basis of this approach and presents two types of medium access control (MAC) protocols that are suitable for Robust WDM local area networks (LANs). The performance of networks based on these protocols is discussed in detail. It is shown that the new approach has considerable promise for WDM networks in the local area.

Logic behaviour of an ECL OR/NOR gate under different physical faults is examined. It is shown that the conventional stuck-at fault modelling may be inadequate for obtaining a sufficiently high fault coverage. A new augmented stuck-at fault model is presented which provides a better coverage of physical failures.

Simulators are valuable tools; they help in understanding how complex systems will operate and perform without actually having to build a physical model to test. However, they often require extensive development and run times. This is especially true for many networks such as FDDI, where a large number of nodes and priority classes are involved. A high-level algorithm is presented to evaluate the performance characteristics of a token LAN. The goal of the research was to find a method for obtaining an estimate of the average access delay, and the average end-to-end delay of advanced token-ring networks. The FDDI (fibre distributed data interface) standards were used as the basis of a FFOL (FDDI follow-on LAN) solution. A method was developed that will generate exact results for such networks at low- to medium-load network environments. As the load level increases, the error rate of the estimate also increases; this however is monitored and can be used as a confidence measure for the results obtained. A symmetric multimedia environment is used in the model, with bimodal traffic consisting of short data packets, and longer video packets. A short introduction to the network setup and the examination of the method developed is presented in single and multinetwork environments. Specific network parameters were chosen for these experiments, but the method is easy to customise to other network parameters.

Combining the inherent advantages of bipolar and CMOS, BiCMOS is emerging as a major technology for high speed, high performance, digital and mixed signal applications. Logic behaviour of single- and double-BJT BiCMOS devices under transistor level shorts and opens is examined. In addition to sequential behaviour, some stuck open faults exhibit increased delay. While most stuck on faults can be detected by logic level testing, some of them can only be detected by monitoring the power supply current (IDDQ monitoring). A stuck open fault in double-BJT BiCMOS device manifesting as enhanced dynamic IDD current is shown. The faulty behaviour of bipolar (TTL) and CMOS logic families is compared with BiCMOS. Testability of both single- and double-BJT BiCMOS devices are discussed, along with a design for testability approach for detecting stuck open faults in S-BJT BiCMOS devices.

Background: Treatment plans fail if patients have poor medication adherence. Our aim was to compare medication adherence, reasons for non-adherence, and satisfaction with community support among type 2 diabetes mellitus patients who pay for their medications and those who receive it free. Methods: A descriptive cross-sectional study was conducted at Anuradhapura, Sri Lanka, among patients who were on oral anti-diabetic drugs for at least 3 months. They were grouped into two: universal-free group and fee-paying group. Three different scales were used to score medication adherence, reasons for non-adherence, and satisfaction with community support. Fisher’s exact test was performed to determine if there was a significant difference between the two groups (p&lt; 0.05) concerning medication adherence and satisfaction with community support. Results: The median (IQR) medication adherence scores for fee-paying group and universal-free group were 3 (2-3) and 3 (3-3), respectively; the median (IQR) scores for satisfaction with community support were 5 (2–6) and 4 (4–6), respectively. Both the adherence and the satisfaction failed to show a significant difference between the two groups. Forgetfulness, being away from home, complex drug regime, and willingness to avoid side effects were common reasons of non-adherence for both the groups. Conclusions: There was no significant difference in medication adherence between the universal-free group and fee-paying group, despite of having a significantly different income. The universal-free health service would be a probable reason.

A protocol for fibre optic local area networks, the register insertion bus (RIB), is proposed. RIB uses a folded-bus topology with an access scheme which includes the existence of two buffers in each station to hold packets that would conflict. Simulations have shown the access scheme to efficiently utilise the network with a minimum of overhead. RIB implements a fair access scheme at normal network loads but at high loads a priority scheme is implemented. An enhancement technique is discussed that will implement a fair access scheme by altering the time between transmissions based on the measured network load.

A systematic scheme for testing NMOS complex gates is presented. A minimal complete test set for all single and multiple detectable s-open, s-on and bridging faults is obtained. The scheme can easily be extended to test any general NMOS complex gate.

Some faults in storage elements (SEs) do not manifest as stuck-at-0/1 faults. These include data-feedthrough faults that cause the SE cell to exhibit combinational behaviour. The authors investigate the implications of such faults on the behaviour of circuits using unclocked SEs. It is shown that effects of data-feedthrough faults at the behavioural level are different from those due to stuck-at faults, and therefore tests generated for the latter may be inadequate.

We present a theory and algorithm for detecting and classifying weak, distributed patterns in network data that provide actionable information with quantiable measures of uncertainty. Our work demonstrates the eectiveness of space-time inference on graphs, robust matrix completion, and second order analysis for the detection of distributed patterns that are not discernible at the level of individual nodes. Motivated by the importance of the problem, we are specically interested in detecting weak patterns in computer networks related to Cyber Situational Awareness. Our focus is on scenarios where the nodes (terminals, routers, servers, etc.) are sensors that provide measurements (of packet rates, user activity, central processing unit usage, etc.) that, when viewed independently, cannot provide a denitive determination of the underlying pattern, but when fused with data from across the network both spatially and temporally, the relevant patterns emerge. The approach is applicable to many types of sensor networks including computer networks, wireless networks, mobile sensor networks, and social networks, as well as in contexts such as databases and disease outbreaks.

The high degree of parallelism in the simulation of digital VLSI systems can be utilized by a data flow architecture to reduce the enormous simulation times. The existing logic simulation accelerators based on the data flow principle use a static data flow architecture along with a timing wheel mechanism to implement the event driven simulation algorithm. The drawback in this approach is that the timing wheel becomes a bottleneck to high simulation throughput. Other shortcomings of the existing architecture are the high communication overhead in the arbitration and distribution networks, and reduced pipelining due to a static data flow architecture. To overcome these, three major improvements are made to the design of a classical data flow based logic simulation accelerator. These include:

Bipolar Emitter Coupled Logic (ECL) devices can now be fabricated at higher densities and consumes much lower power. Behaviour of simple and complex ECL gates are examined in the presence of physical faults. The effectiveness of the classical stuck-at model in representing physical failures in ECL gates is examined. It is shown that the conventional stuck-at fault model cannot represent a majority of circuit level faults. A new augmented stuck-at fault model is presented which provides a significantly higher coverage of physical failures. The model may be applicable to other logic families that use logic gates with both true and complementary outputs. A design for testability approach is suggested for on-line detection of certain error conditions occurring in gates with true and complementary outputs which is a normal implementation for ECL devices.

The effects of Built-In Current Sensors (BICS) on IDDQ measurements as well as on the performance of the circuit under test are considered. Most of the Built-In Current Sensor designs transform the ground terminal of the circuit under test into a virtual ground. This causes increases in both propagation delay and IDDQ sampling time with the increase in the number of gates, affecting both test as well as operational performance. The effects that current sensors have on the operational and test performance of a circuit are considered. Circuit partitioning may be used for overcoming the effects of BICS on IDDQ measurements as well as on the performance of the circuit under test.

Current drawn by a static CMOS VLSI integrated circuit during quiescent periods is extremely small and is normally of the order of nanoamperes. However, it is remarkably susceptible to a number of failure modes. Many faults present in such ICs cause the quiescent power-supply current (IDDQ) to increase by several orders of magnitude. Some of these faults may not manifest themselves as logical faults, and would not be detected by traditional IC test techniques.