Empirical Studies of Evolving Systems

This paper describes the results of the working group investigating the issues of empirical studies for evolving systems. The groups found that there were many issues that were central to successful evolution and this concluded that this is a very important area within software engineering. Finally nine main areas were selected for consideration. For each of these areas the central issues were identified as well as success factors. In some cases success stories were also described and the critical factors accounting for the success analysed. In some cases it was later found that a number of areas were so tightly coupled that it was important to discuss them together

Developing a new resetting tool for controlling rats

A resetting toxin device (the “Spitfire”) has been designed that delivers a toxic paste to a rat’s ventral surface when it passes through a tunnel. The rat grooms off the paste and ingests the toxin. The system was assessed in cage trials and one field trial. The purpose of the cage trials was to investigate whether a range of toxins can be delivered by the Spitfire to rats (Rattus rattus and R. norvegicus), namely 0.55% sodium fluoroacetate (1080), 0.2% brodifacoum, 15% cholecalciferol, and 12.5% zinc phosphide. The trials with 1080, brodifacoum, and zinc phosphide were successful with > 85% of rats ingesting lethal doses. The trials with cholecalciferol were less successful with only 58% of rats dying. A one-month pilot field trial was undertaken using 1080 in the Spitfires. There was a knockdown in rat (and stoat Mustela erminea) abundance, establishing proof of concept for the Spitfire delivery system with this toxin. The long-term, effective control of introduced rats will require a range of toxins with different modes of action. The Spitfire could be a useful additional control tool for rats and is currently being re-engineered to be made more reliable

Revisiting Ruddick: Feminism, pacifism and non-violence

This article explores feminist contentions over pacifism and non-violence in the contextof the Greenham Common Peace Camp in the 1980s and later developments offeminist Just War Theory. We argue that Sara Ruddick’s work puts feminist pacifism, its radical feminist critics and feminist just war theory equally into question. Although Ruddick does not resolve the contestations within feminism over peace, violence and the questions of war, she offers a productive way of holding the tension between them. In our judgment, her work is helpful not only for developing a feminist political response to the threats and temptations of violent strategies but also for thinking through the question of the relation between violence and politics as such

The C-Type Lectin of the Aggrecan G3 Domain Activates Complement

Excessive complement activation contributes to joint diseases such as rheumatoid arthritis and osteoarthritis during which cartilage proteins are fragmented and released into the synovial fluid. Some of these proteins and fragments activate complement, which may sustain inflammation. The G3 domain of large cartilage proteoglycan aggrecan interacts with other extracellular matrix proteins, fibulins and tenascins, via its C-type lectin domain (CLD) and has important functions in matrix organization. Fragments containing G3 domain are released during normal aggrecan turnover, but increasingly so in disease. We now show that the aggrecan CLD part of the G3 domain activates the classical and to a lesser extent the alternative pathway of complement, via binding of C1q and C3, respectively. The complement control protein (CCP) domain adjacent to the CLD showed no effect on complement initiation. The binding of C1q to G3 depended on ionic interactions and was decreased in D2267N mutant G3. However, the observed complement activation was attenuated due to binding of complement inhibitor factor H to CLD and CCP domains. This was most apparent at the level of deposition of terminal complement components. Taken together our observations indicate aggrecan CLD as one factor involved in the sustained inflammation of the joint

Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling

Helminth infections are accompanied by eosinophilia in parasitized tissues. Eosinophils are effectors of immunity to tissue helminths. We previously reported that in the context of experimental filarial nematode infection, optimum tissue eosinophil recruitment was coordinated by local macrophage populations following IL-4R–dependent in situ proliferation and alternative activation. However, in the current study, we identify that control of chronic adult filarial worm infection is evident in IL-4Ra–deficient (IL-4Ra2/2) mice, whereby the majority of infections do not achieve patency. An associated residual eosinophilia was apparent in infected IL-4Ra2/2 mice. By treating IL-4Ra2/2 mice serially with anti-CCR3 Ab or introducing a compound deficiency in CCR3 within IL-4Ra2/2 mice, residual eosinophilia was ablated, and susceptibility to chronic adult Brugia malayi infection was established, promoting a functional role for CCR3-dependent eosinophil influx in immune control in the absence of IL-4/IL13–dependent immune mechanisms. We investigated additional cytokine signals involved in residual eosinophilia in the absence IL-4Ra signaling and defined that IL-4Ra2/2/IL-52/2 double-knockout mice displayed significant eosinophil deficiency compared with IL-4Ra2/2 mice and were susceptible to chronic fecund adult filarial infections. Contrastingly, there was no evidence that either IL-4R–dependent or IL-4R–independent/CCR3/IL-5–dependent immunity influenced B. malayi microfilarial loads in the blood. Our data demonstrate multiplicity of Th2-cytokine control of eosinophil tissue recruitment during chronic filarial infection and that IL-4R–independent/IL-5– and CCR3-dependent pathways are sufficient to control filarial adult infection via an eosinophil-dependent effector response prior to patency

Cathepsin K Deficiency Reduces Elastase Perfusion-Induced Abdominal Aortic Aneurysms in Mice

Objective: Cathepsin K (CatK) is one of the most potent mammalian elastases. We have previously shown increased expression of CatK in human abdominal aortic aneurysm (AAA) lesions. Whether this protease participates directly in AAA formation, however, remains unknown. Methods and Results: Mouse experimental AAA was induced with aortic perfusion of a porcine pancreatic elastase. Using this experimental model, we demonstrated that absence of CatK prevented AAA formation in mice 14 days postperfusion. CatK deficiency significantly reduced lesion CD4 T-cell content, total lesion and medial cell proliferation and apoptosis, medial smooth muscle cell (SMC) loss, elastinolytic CatL and CatS expression, and elastin fragmentation, but it did not affect AAA lesion Mac-3 macrophage accumulation or CD31 microvessel numbers. In vitro studies revealed that CatK contributed importantly to CD4 T-cell proliferation, SMC apoptosis, and other cysteinyl cathepsin and matrix metalloproteinase expression and activities in SMCs and endothelial cells but played negligible roles in microvessel growth and monocyte migration. AAA lesions from CatK-deficient mice showed reduced elastinolytic cathepsin activities compared with those from wild-type control mice. Conclusion: This study demonstrates that CatK plays an essential role in AAA formation by promoting T-cell proliferation, vascular SMC apoptosis, and elastin degradation and by affecting vascular cell protease expression and activities.Other Research Uni

Long-Term Survival Rates after Resection for Locally Advanced Kidney Cancer: Memorial Sloan Kettering Cancer Center 1989 to 2012 Experience

Purpose: We analyzed the 23-year Memorial Sloan Kettering Cancer Center experience with surgical resection, and concurrent adrenalectomy and lymphadenectomy for locally advanced nonmetastatic renal cell carcinoma. Materials and Methods: We retrospectively reviewed the records of 802 patients who underwent nephrectomy with or without concurrent adrenalectomy or lymphadenectomy for locally advanced renal cell carcinoma, defined as stage T3 or greater and M0. Patients who received adjuvant treatment within 3 months of surgery or had fewer than 3 months of followup or bilateral renal masses at presentation were excluded from analysis. Five and 10-year progression-free and overall survival was estimated by the Kaplan-Meier method. Differences between groups were analyzed by the log rank test. Results: A total of 596 (74%) and 206 patients (26%) underwent radical and partial nephrectomy, respectively. Renal cell carcinoma progressed in 189 patients and 104 died of the disease. Median followup in patients without progression was 4.6 years. Symptoms at presentation, ASA (R) classification, tumor stage, histological subtype, grade and lymph node status were significantly associated with progression-free and overall survival. On multivariate analysis adrenalectomy use decreased with time but lymphadenectomy use increased (OR 0.82 vs 1.16 per year). Larger tumors were associated with a higher likelihood of concurrent adrenalectomy and lymphadenectomy. Conclusions: In our series of patients with locally advanced nonmetastatic renal cell carcinoma survival was favorable in those in good health who were asymptomatic at presentation with T3 tumors and negative lymph nodes. Further, there has been a trend toward more selective use of adrenalectomy and increased use of lymphadenectomy

Avian Influenza Risk Perception, Europe and Asia

During autumn 2005, we conducted 3,436 interviews in European and Asian countries. We found risk perceptions of avian influenza to be at an intermediate level and beliefs of efficacy to be slightly lower. Risk perceptions were higher in Asia than Europe; efficacy beliefs were lower in Europe than Asia