Cracking the BAFF code.

The tumour necrosis factor (TNF) family members B cell activating factor (BAFF) and APRIL (a proliferation-inducing ligand) are crucial survival factors for peripheral B cells. An excess of BAFF leads to the development of autoimmune disorders in animal models, and high levels of BAFF have been detected in the serum of patients with various autoimmune conditions. In this Review, we consider the possibility that in mice autoimmunity induced by BAFF is linked to T cell-independent B cell activation rather than to a severe breakdown of B cell tolerance. We also outline the mechanisms of BAFF signalling, the impact of ligand oligomerization on receptor activation and the progress of BAFF-depleting agents in the clinical setting

Inflammation and breast cancer. Metalloproteinases as common effectors of inflammation and extracellular matrix breakdown in breast cancer

Two rapidly evolving fields are converging to impact breast cancer: one has identified novel substrates of metalloproteinases that alter immune cell function, and the other has revealed a role for inflammation in human cancers. Evidence now shows that the mechanisms underlying these two fields interact in the context of breast cancer, providing new opportunities to understand this disease and uncover novel therapeutic strategies. The metalloproteinase class of enzymes is well studied in mammary gland development and physiology, but mostly in the context of extracellular matrix modification. Aberrant metalloproteinase expression has also been implicated in breast cancer progression, where these genes act as tumor modifiers. Here, we review how the metalloproteinase axis impacts mammary physiology and tumorigenesis and is associated with inflammatory cell influx in human breast cancer, and evaluate its potential as a regulator of inflammation in the mammary gland

The influence of gender on the outcome of arterial procedures in the lower extremity

OBJECTIVES: To determine the outcome of arterial reconstructive procedures, we audited retrospectively peripheral bypass grafts and endarterectomies performed between 1982 and 1990. MATERIALS AND METHODS: 1005 peripheral arterial procedures were performed in 862 lower limbs in 782 patients. 62% of the limbs were critically ischaemic. The procedures include 565 bypasses, 346 endarterectomies and 94 combinations of both. 30% of the patients were women. Follow-up information was obtained from practitioners in charge of post-hospital care by questionnaires. Factors potentially affecting patency were investigated by multivariate analysis and patency rates were calculated by life-tables. MAIN RESULTS: Overall secondary patency was 61% at one year and 35% at 5 years. Bypasses and endarterectomies in women yielded lower patency rates than in men (49% vs. 67% at 1 year, p < 0.001). The relative risk of failure in women as compared to men was 1.30. The risk of failure was further increased by "redo" surgery (relative risk 1.51), diabetes (1.40), critical ischaemia (1.34) and crural procedures (1.34). CONCLUSIONS: Secondary patency rates were significantly lower in women than in men. This is in agreement with some other studies, although gender has gained little attention as a risk factor in vascular surgery

Treatment of varicose veins with minimally invasive methods: is conventional surgery still a "gold standard"?

AIM: To assess the current role of thermal ablation in the treatment of saphenous reflux in comparison to more conventional methods. METHOD: Some pertinent publications are presented as well as the author's experience with thermal ablation using ClosureFast. RESULTS: Over the last decade several techniques for thermal ablation of saphenous reflux have been developed. There is some evidence--although scarce--that thermal ablation was from the start not inferior to standard surgery (high ligation and stripping). In addition, more recent thermal ablation techniques appear to have milder side effects than the pioneers. CONCLUSION: Thermal ablation of saphenous reflux has quickly assumed an important role in the treatment of varicose veins and the parameters of thermal ablation may further be optimised. Therefore, we believe that high ligation and stripping of refluxing saphenous veins will widely be displaced by thermal ablation

System-level performance evaluation of reconfigurable processors

Reconfigurable architectures that tightly integrate a standard CPU core with a field-programmable hardware structure have recently been receiving increased attention. The design of such a hybrid reconfigurable processor involves a multitude of design decisions regarding the field-programmable structure as well as its system integration with the CPU core. Determining the impact of these design decisions on the overall system performance is a challenging task. In this paper, we first present a framework for the cycle-accurate performance evaluation of hybrid reconfigurable processors on the system level. Then, we discuss a reconfigurable processor for data-streaming applications, which attaches a coarse-grained reconfigurable unit to the coprocessor interface of a standard embedded CPU core. By means of a case study we evaluate the system-level impact of certain design features for the reconfigurable unit, such as multiple contexts, register replication, and hardware context scheduling. The results illustrate that a system-level evaluation framework is of paramount importance for studying the architectural trade-offs and optimizing design parameters for reconfigurable processors. q 2004 Elsevier B.V. All rights reserved

Swiss Army Survey in Switzerland to determine the prevalence of Francisella tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu lato, and tick-borne encephalitis virus in ticks

A total of 6071 Ixodes ricinus ticks were collected on Swiss Army training grounds in five regions of Switzerland. The aim of the survey was to assess the prevalence of ticks infected with the human pathogens Francisella tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu lato, and the European tick-borne encephalitis virus. TaqMan PCR (PE Biosystems, USA) and TaqMan RT-PCR (PE Biosystems) analyses were performed on DNA and RNA extracted from pools of ten ticks grouped by gender. Here, for the first time, it is shown that ticks may harbor Francisella tularensis in Switzerland, at a rate of 0.12%. Furthermore, 26.54% of the ticks investigated harbored Borrelia burgdorferi sensu lato, 1.18% harbored members of the Ehrlichia phagocytophila genogroup, and 0.32% harbored the European tick-borne encephalitis virus. A new instrumentation was applied in this study to carry out and analyze more than 2300 PCR reactions in only 5 days. Furthermore, the results reveal that people working in outdoor areas, including army personnel on certain training grounds contaminated with ticks containing tick-borne pathogens, are at risk for different tick-borne diseases

G. Székely Ch. Brechbühler J. Dual

Virtual reality (VR)-based surgical simulator systems offer a very elegant approach to enriching and enhancing traditional training in endoscopic surgery. However, while a number of VR simulator systems have been proposed and realized in the past few years, most of these systems are far from being able to provide a reasonably realistic surgical environment. We explore the current limits for realism and the approaches to reaching and surpassing those limits by describing and analyzing the most important components of VR-based endoscopic simulators. The feasibility of the proposed techniques is demonstrated on a modular prototype system that implements the basic algorithms for VR training in gynaecologic laparoscopy.