Oncogenic variants of the cellular Ras protein are often associated with different types of human cancers. However, the mechanisms by which oncogenic Ras induces transformation are not fully established. Expression of the transcriptional repressor Par-4 was down-regulated by oncogenic Ras via the Raf-MEK-ERK pathway. Restoration of Par-4 levels by abrogation of the Raf-MEK-ERK pathway with the MEK-inhibitor PD98059 or by ectopic Par-4, that acted to inhibit ERK expression and activation, was sufficient to suppress oncogenic Ras-induced transformation. These findings identify Par-4 as a novel target that has to be down-modulated by oncogenic Ras for successful transformation.

Background Serum cryoglobulins (SC) may be found in many diseases (1), and the presence of serum cryoglobulins is a known risk factor for lymphoma evolution in some non malignant diseases.Objectives The aim of this study was to distiguish the role of cryoglobulinemic vasculitis (CV), classified according to the recent validated criteria (1,2), and primary Sjögren's syndrome (pSS) as risk factors of lymphoma in patients positive serum cryoglobulins. Importantly, SC, CV and pSS may occur together.Methods 950 charts from consecutive patients with positive SC were evaluated. Patients carrying both pSS and HCV infection, as well as incomplete charts, were excluded.Results 657 patients with SC were selected, 374 with CV and 283 without CV, according to the published criteria (2,3). PSS, classified according to the American-European Group Criteria was present in 96 patients (44 with CV, 52 without). Lymphoma was reported in 61/657 (9.8%) patients with SC. Among them, CV was present in 44/61 (72,1%; 14 also with pSS), and pSS in 17/61 (27,9%; and 14/17 had CV). Patients with SC with CV showed an higher prevalence of lymphoma than patients with SC without CV (44/374, 11.5% vs.17/283, 6.3%; p=0.025, OR=1.93 [95%IC: 1.08-3.39]. Patients with pSS, SC and CV also showed a higher prevalence of lymphoma than patients with pSS, SC but without CV (14/44, 31.8% vs. 3/52, 7.4%; p=0.001, OR=7.62 [95%CI 2.02-28.74]. CV and pSS were confirmed as independent risk factor for lymphoma by multivariate analysis (OR 2,18 95%CI 1,18-3,83, p=0,012; OR 2,65 95%CI 1,04-6,76, p=0,042, respectively). Infection by the hepatitis C virus (HCV) was detected in 467/561 (83,2%) patients with SC without pSS, and did not statistically predispose to lymphoma when associated with CV in this subset (p=1,0).Conclusions Cryoglobulinemic vasculitis and pSS are independent risk factors for lymphoma in patients with evidence of SC. Patients with both the conditions (CV and pSS) have the highest risk. In the follow-up of SC positive patients, a very high attention should be deserved to pSS, in particular when CV is present.ReferencesDe Vita S, et al. Ann Rheum Dis. 2011; 2) Quartuccio L, et al. Rheumatology (Oxford). 2014Disclosure of Interest None declared

OBJECTIVE: The aim of this study was to validate the classification criteria for cryoglobulinaemic vasculitis (CV).

METHODS: Twenty-three centres were involved. New patients with CV (group A) and controls, i.e. subjects with serum cryoglobulins but lacking CV based on the gold standard of clinical judgment (group B) and subjects without cryoglobulins but with clinical features that can be observed in the course of CV (group C), were studied. Positivity of serum cryoglobulins was necessary for CV classification. Sensitivity and specificity of the criteria were calculated by comparing group A vs group B. The group A vs group C comparison was done to demonstrate the possible diagnostic utility of the criteria.

RESULTS: The study included 268 patients in group A, 182 controls in group B and 193 controls in group C (small vessel vasculitis, 51.8%). The questionnaire (at least 2/3 positive answers) showed 89.0% sensitivity and 93.4% specificity; the clinical item (at least 3/4 clinical involvement) showed 75.7% sensitivity and 89.0% specificity and the laboratory item (at least 2/3 laboratory data) showed 80.2% sensitivity and 62.4% specificity. The sensitivity and specificity of the classification criteria (at least 2/3 positive items) were 89.9% and 93.5%, respectively. The comparison of group A with group C demonstrated the clinical utility of the criteria in differentiating CV from CV mimickers.

CONCLUSION: Classification criteria for CV were validated in a second, large, international study confirming good sensitivity and specificity in a complex systemic disease.

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Bandwidth constriction and datagram loss are prominent issues that affect the perceived quality of streaming video over lossy networks, such as wireless. The use of layered video coding seems attractive as a means to alleviate these issues, but its adoption has been held back in large part by the inherent priority assigned to the critical lower layers and the consequences for quality that result from their loss. The proposed use of forward error correction (FEC) as a solution only further burdens the bandwidth availability and can negate the perceived benefits of increased stream quality. In this paper, we propose Adaptive Layer Distribution (ALD) as a novel scalable media delivery technique that optimises the tradeoff between the streaming bandwidth and error resiliency. ALD is based on the principle of layer distribution, in which the critical stream data is spread amongst all datagrams thus lessening the impact on quality due to network losses. Additionally, ALD provides a parameterised mechanism for dynamic adaptation of the scalable video, while providing increased resilience to the highest quality layers. Our experimental results show that ALD improves the perceived quality and also reduces the bandwidth demand by up to 36% in comparison to the well-known Multiple Description Coding (MDC) technique.