Risedronate in the treatment of Paget's disease of bone: an open label, multicenter study

An open-label, multicenter study was conducted to determine the efficacy and safety of oral risedronate (a pyridinyl bisphosphonate) in 162 patients (102 men, 60 postmenopausal women; mean age, 68 years) with moderate to severe Paget's disease of bone (mean serum alkaline phosphatase [ALP] approximately seven times the upper limit of normal). Patients were treated with oral risedronate, 30 mg/day for 84 days, followed by 112 days without treatment. This 196-day cycle was repeated once if serum ALP did not normalize or increased from the nadir value by > or = 25%. At the end of the first and second cycles, the mean percentage decreases for serum ALP were 65.7% and 69.1%, and for urinary hydroxyproline/creatinine 50.4% and 66.9%, respectively. The decreases from baseline in ALP and urinary hydroxyproline/creatinine were significant (p < 0.001). Normalization of serum ALP was observed in 86 patients (53.8%): 53 during the first treatment cycle and 33 during the second. There was a significant proportion of patients reporting a decrease in the pagetic bone pain at days 84 and 196 (p < 0.001). Overall, risedronate was well tolerated. Five patients withdrew due to adverse events, none of which were considered to be drug related. In conclusion, 30 mg of oral risedronate administered daily for 84 days significantly reduced the biochemical indices of disease activity and was associated with pain reduction in patients with moderate to severe Paget's disease of bone. Normalization of ALP was observed in the majority of patients. Repeated administration of risedronate was shown to be beneficial. In general, risedronate was well tolerated and demonstrated a good safety profile.     

Interference-aware channel assignment in a metropolitan multi-radio wireless mesh network with directional antennas

We investigate the problem of channel assignment in a metropolitan multi-radio wireless mesh network with directional antennas. Our contributions include a new conflict graph model for capturing the interference between links in a mesh network with a known wireless interface communication graph, and a new channel assignment procedure which accounts for interference both between links inside the mesh network, and from external sources. Additionally, we have implemented and evaluated the proposed channel assignment procedure in an actual metropolitan mesh network with 1.6-5 km links. Key components of the channel assignment procedure are the interference model, the link ordering, and the channel selection metric. The experimental results demonstrate how link ordering and the channel selection metric affect performance, in terms of the average packet delay and http latency. The results show that the proposed channel assignment procedure achieves performance very close to a lower bound of the average packet delay, and significantly higher than the performance achieved with a simpler interference-unaware procedure, and a measurement-based scheme that has appeared in the literature, and accounts for interference only from external 802.11 sources. Moreover, we investigate the performance when a different number of channels are available, and the timescales for channel re-assignment.     

Application of the many sources asymptotic and effective bandwidths to traffic engineering

Accurate yet simple methods for traffic engineering are important for efficient management of resources in broadband networks. The goal of this paper is to apply and evaluate large deviation techniques for traffic engineering. In particular, we employ the recently developed theory of effective bandwidths, where the effective bandwidth depends not only on the statistical characteristics of the traffic stream, but also on a link’s operating point through two parameters, the space and time parameters, which can be computed using the many sources asymptotic. We show that this effective bandwidth definition can accurately quantify resource usage. Furthermore, we estimate and interpret values of the space and time parameters for various mixes of real traffic demonstrating how these values can be used to clarify the effects on the link performance of the time scales of traffic burstiness, of the link resources (capacity and buffer), and of traffic control mechanisms such as traffic shaping. Our experiments involve a large set of MPEG‐1 compressed video and Internet Wide Area Network (WAN) traces, as well as modeled voice traffic. This revised version was published online in June 2006 with corrections to the Cover Date.     

Anomaly‐based intrusion detection of jamming attacks,local versus collaborative detection

We present intrusion detection algorithms to detect physical layer jamming attacks in wireless networks. We compare the performance of local algorithms on the basis of the signal‐to‐interference‐plus‐noise ratio (SINR) executing independently at several monitors, with a collaborative detection algorithm that fuses the outputs provided by these algorithms. The local algorithms fall into two categories: simple threshold that raise an alarm if the output of the SINR‐based metrics we consider deviates from a predefined detection threshold and cumulative sum (cusum) algorithms that raise an alarm if the aggregated output exceeds the predefined threshold. For collaborative detection, we use the Dempster–Shafer theory of evidence algorithm. We collect SINR traces from a real IEEE 802.11 network, and with the use of a new evaluation method, we evaluate both the local and the Dempster–Shafer algorithms in terms of the detection probability, false alarm rate, and their robustness to different detection threshold values, under different attack intensities. The evaluation shows that the cusums achieve higher performance than the simple threshold algorithms under all attack intensities. The Dempster–Shafer algorithm when combined with the simple algorithms, it can increase their performance by more than 80%, but for the cusum algorithms it does not substantially improve their already high performance.Copyright © 2013 John Wiley & Sons, Ltd.     

Paget's disease of bone

Paget's disease of bone is a localized disorder of bone remodeling. Increased numbers of larger than normal osteoclasts initiate the process at affected skeletal sites, and the increase in bone resorption is followed by an increase in new bone formation, altering bone architecture. The signs and symptoms of Paget's disease are varied, depending in part on the location of the involved sites and the degree of increased bone turnover. Recent progress in Paget's disease research includes new data regarding the etiology of this disorder and the ongoing development of more effective therapies. Although the cause of Paget's disease remains unproven, the creation of pagetic osteoclasts seems ever more likely to result from both genetic and environmental factors. Many studies indicate that in patients with Paget's disease, both osteoclasts and their precursors harbor evidence of a paramyxovirus infection, although not all studies confirm this finding. Very recent genetic investigations have identified one candidate gene on chromosome 18q, although genetic heterogeneity is almost certainly present. Advances in treatment have resulted from the availability of several potent bisphosphonate compounds (e.g., pamidronate, alendronate, and risedronate) that, unlike earlier treatments, produce normal or near normal bone turnover indices in a majority of patients. New bone formation after such treatment has a more normal, lamellar pattern, and mineralization abnormalities are rare to absent with the newer compounds. The availability of such agents has prompted a more aggressive management philosophy in which both symptomatic disease and also asymptomatic disease at sites with a risk of progression and future complications are viewed as clear indications for pharmacologic intervention.     

Clinical trials and tribulations: implementation processes in schizophrenia research outcome

This article focuses on an area in clinical drug trials for new antipsychotic medications for the treatment of schizophrenia which has not received sufficient attention in the literature: the day-to-day implementation tasks performed by research staff which have potential effects on study results. Implementation tasks are viewed as dynamic processes involving interactions among research and nonresearch staff, patients, families, and pharmaceutical company staff. Research-related demands and possible sources of stress for all participants in the process, such as recruiting and maintaining patients in studies, are discussed. Suggestions are offered for increasing the ease of participation. Further investigation is called for in several areas including variability in the effectiveness of research teams and in the rarely discussed interactions between site staff and pharmaceutical company personnel, as they may affect research outcomes. It is posited that increased knowledge about implementation processes in schizophrenia drug development is needed to more fully understand study results and to enhance patients' and their families' willingness to participate.     

Integrative and sealing-over recoveries from schizophrenia: distinguishing case studies

Fast-2, a membrane mutant of Paramecium aurelia, is due to a single-gene mutation and has behavioral abnormalities. Intracellular recordings through changes of external solutions were made. The mutant membrane hyperpolarized when it encountered solutions with low K+ concentration. This hyperpolarization and other associated activities were best observed in Ca- or Na-solutions devoid of K+. Membrane potential was plotted against the concentration of K+ (0.5 to 16 mM) in solutions of fixed Na+ or Ca++ concentration. The slopes of the curves for the mutant membrane were steeper than those for the wild type at the lower concentrations of K+. Inclusion of 2 mM tetraethylammonium chloride (TEA-Cl) counteracted the mutational effects. Spontaneous action potentials in Ba-solution and the electrically evoked action potentials in various solutions are normal in this mutant. We conclude that the resting permeability to K+ relative to the permeabilities to Na+ and Ca++ has been increased by the mutation.     

A study of simple usage‐based charging schemes for broadband networks

Operators of multi‐service networks require simple charging schemes with which they can fairly recover costs from their users and effectively allocate network resources. This paper studies an approach for computing such charges from simple measurements (time and volume), and relating these to bounds of the effective bandwidth. To achieve economic efficiency, it is necessary that usage‐based charging schemes capture the relative amount of resources used by connections. Based on this criteria, we evaluate our approach for real traffic consisting of Internet Wide Area Network traces and MPEG‐1 compressed video. Its incentive compatibility is shown with an example involving deterministic multiplexing, and the effect of pricing on a network's equilibrium is investigated for deterministic and statistical multiplexing. Finally, we investigate the incentives for traffic shaping provided by the approach. This revised version was published online in June 2006 with corrections to the Cover Date.     

Resource Control for Hybrid Code and Time Division Scheduling Wireless Systems

We present a model, based on economic theory, for efficient and robust resource control in hybrid code and time division scheduling wireless systems. An important and novel feature of the model is that it captures the combined effects of the transmission rate, the signal quality, and the percentage of time slots a user can transmit in, on the overall efficiency of the wireless system. Based on this model, we propose procedures for combined rate and time slot allocation to achieve efficient utilization of wireless resources, while taking into account user requirements. These procedures can be applied using a class-based framework that allows simple implementation and requires simple communication between the network and its users, which select a service class reflecting their valuation for the average throughput and for the percentage of time slots in which they can transmit data. The work presented in this paper is a revised and extended version of the conference publication “Resource Control for Hybrid Code and Time Division Scheduling”, 15th IEEE PIMRC, Barcelona, Spain, September 2004. Vasilios A. Siris received his B.S. (1990) degree in Physics from the University of Athens, Greece, his M.S. (1992) in Computer Science from Northeastern University, Boston, USA, and his Ph.D. (1998) in Computer Science from the University of Crete, Heraklion, Greece. Since November 2002 he is an Assistant Professor at the Department of Computer Science of the University of Crete, and a Research Associate at the Institute of Computer Science of the Foundation for Research and Technologys - Hellas (FORTH), where he was a Research Assistant and then Researcher from 1993 until 2002. He serves on the management committee of the COST action 290 “WiQoST: Traffic and QoS Management on Wireless Multimedia Networks”. His current research interests include resource and QoS control in wired and wireless networks, network traffic measurement and analysis, and Denial of Service (DoS) attack detection and mitigation.