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

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

Support for the U.S. Endangered Species Act over time and space: Controversial species do not weaken public support for protective legislation

© 2018 The Authors. Conservation Letters published by Wiley Periodicals, Inc. We used data from a 2014 survey (n = 1,287) of U.S. residents and recent polls to assess how public support for the U.S. Endangered Species Act (ESA) changed over time, and whether protecting controversial species affects support for the law. We assessed support for the ESA, trust in the U.S. Fish and Wildlife Service (FWS), and attitudes toward wolves across three regions with different experiences in conserving gray wolves through the ESA. We found: (a) ∼4 in 5 Americans support the ESA, whereas ∼1 in 10 oppose; (b) support for the ESA remained stable over the past two decades; (c) strong majorities (\u3e 68%) of individuals identifying with 8 special interest types support the ESA; and (d) no differences in support for the ESA, attitudes toward wolves, or trust in the FWS across regions. Results suggest that protecting species—even controversial predators—does not weaken support for protective legislation

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.

COVID-19 outcome is not affected by anti-CD20 or high-titer convalescent plasma in immunosuppressed patients

Abstract The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma in the treatment of Coronavirus Disease 2019 (COVID-19) in immunosuppressed individuals remains controversial. We describe the course of COVID-19 in patients who had received anti-CD20 therapy within the 3 years prior to infection. We compared outcomes between those treated with and those not treated with high titer SARS-CoV2 convalescent plasma. We identified 144 adults treated at Mayo clinic sites who had received anti-CD20 therapies within a median of 5.9 months prior to the COVID-19 index date. About one-third (34.7%) were hospitalized within 14 days and nearly half (47.9%) within 90 days. COVID-19 directed therapy included anti-spike monoclonal antibodies (n = 30, 20.8%), and, among those hospitalized within 14 days (n = 50), remdesivir (n = 45, 90.0%), glucocorticoids (n = 36, 72.0%) and convalescent plasma (n = 24, 48.0%). The duration from receipt of last dose of anti-CD20 therapy did not correlate with outcomes. The overall 90-day mortality rate was 14.7%. Administration of convalescent plasma within 14 days of the COVID-19 diagnosis was not significantly associated with any study outcome. Further study of COVID-19 in CD20-depleted individuals is needed focusing on the early administration of new and potentially combination antiviral agents, associated or not with vaccine-boosted convalescent plasma