Phase III study of nilotinib versus best supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinib

Background This phase III open-label trial investigated the efficacy of nilotinib in patients with advanced gastrointestinal stromal tumors following prior imatinib and sunitinib failure. Patients and methods Patients were randomized 2:1 to nilotinib 400 mg b.i.d. or best supportive care (BSC; BSC without tyrosine kinase inhibitor, BSC+imatinib, or BSC+sunitinib). Primary efficacy end point was progression-free survival (PFS) based on blinded central radiology review (CRR). Patients progressing on BSC could cross over to nilotinib. Results Two hundred and forty-eight patients enrolled. Median PFS was similar between arms (nilotinib 109 days, BSC 111 days; P=0.56). Local investigator-based intent-to-treat (ITT) analysis showed a significantly longer median PFS with nilotinib (119 versus 70 days; P=0.0007). A trend in longer median overall survival (OS) was noted with nilotinib (332 versus 280 days; P=0.29). Post hoc subset analyses in patients with progression and only one prior regimen each of imatinib and sunitinib revealed a significant difference in median OS of >4 months in favor of nilotinib (405 versus 280 days; P=0.02). Nilotinib was well tolerated. Conclusion In the ITT analysis, no significant difference in PFS was observed between treatment arms based on CRR. In the post hoc subset analyses, nilotinib provided significantly longer median O

Continuous and transparent multimodal authentication: reviewing the state of the art

Individuals, businesses and governments undertake an ever-growing range of activities online and via various Internet-enabled digital devices. Unfortunately, these activities, services, information and devices are the targets of cybercrimes. Verifying the user legitimacy to use/access a digital device or service has become of the utmost importance. Authentication is the frontline countermeasure of ensuring only the authorized user is granted access; however, it has historically suffered from a range of issues related to the security and usability of the approaches. They are also still mostly functioning at the point of entry and those performing sort of re-authentication executing it in an intrusive manner. Thus, it is apparent that a more innovative, convenient and secure user authentication solution is vital. This paper reviews the authentication methods along with the current use of authentication technologies, aiming at developing a current state-of-the-art and identifying the open problems to be tackled and available solutions to be adopted. It also investigates whether these authentication technologies have the capability to fill the gap between high security and user satisfaction. This is followed by a literature review of the existing research on continuous and transparent multimodal authentication. It concludes that providing users with adequate protection and convenience requires innovative robust authentication mechanisms to be utilized in a universal level. Ultimately, a potential federated biometric authentication solution is presented; however it needs to be developed and extensively evaluated, thus operating in a transparent, continuous and user-friendly manner

The EPA Cancer Risk Assessment Default Model Proposal: Moving Away From the LNT

This article strongly supports the Environmental Protection Agency proposal to make significant changes in their cancer risk assessment principles and practices by moving away from the use of the linear nonthreshold (LNT) dose–response as the default model. An alternate approach is proposed based on model uncertainty which integrates the most scientifically supportable features of the threshold, hormesis, and LNT models to identify the doses that optimize population-based responses (ie, maximize health benefits/minimize health harm). This novel approach for cancer risk assessment represents a significant improvement to the current LNT default method from scientific and public health perspectives

Misuse detection in a simulated IaaS environment

Cloud computing is an emerging technology paradigm by offering elastic computing resources for individuals and organisations with low cost. However, security is still the most sensitive issue in cloud computing services as the service remains accessible to anyone after initial simple authentication login for significant periods. This has led to increase vulnerability to potential attacks and sensitive customer information being misused. To be able to detect this misuse, an additional intelligent security measures are arguably required. Tracking user’s activity by building user behaviour profiles is one technique that has been successfully applied in a variety of applications such as telecommunication misuse and credit card fraud. This paper presents an investigation into applying behavioural profiling in a simulated IaaS-based infrastructure for the purposes of misuse detection by verifying the active user continuously and transparently. In order to examine the feasibility of this approach within cloud infrastructure services, a private dataset was collected containing real interactions of 60 users over a three-week period (totalling 1,048,195 log entries). A series of experiments were conducted using supervised machine learning algorithms to examine the ability of detecting abnormal usage. The best experimental result of 0.32% Equal Error Rate is encouraging and indicates the ability of identifying misuse within cloud computing services via the behavioural profiling technique

Valence band splitting in wurtzite InGaAs nanoneedles studied by photoluminescence excitation spectroscopy

We use low-temperature microphotoluminescence and photoluminescence excitation spectroscopy to measure the valence band parameters of single wurtzite InGaAs nanoneedles. The effective indium composition is measured by means of polarization-dependent Raman spectroscopy. We find that the heavy-hole and light-hole splitting is ∼95 meV at 10 K and the Stokes shift is in the range of 35–55 meV. These findings provide important insight in the band structure of wurtzite InGaAs that could be used for future bandgap engineering

Comparison of the Effects of Incomplete Revascularization on 12-month Mortality in Patients <80 compared to ≥80 Years of Age Undergoing Percutaneous Coronary Intervention

Although randomized trial data suggest that complete revascularization improves outcomes after percutaneous coronary intervention (PCI), the impact of differing revascularization strategies in octogenarians is not well defined. We performed a retrospective analysis, which was conducted of 9,628 consecutive patients who underwent PCI at a large UK center. Octogenarians were more likely to have significant co-morbidity, a higher Mehran bleed risk score (24.5 ± 6.8 vs 13.3 ± 7.4, p <0.0001), and more complex disease (baseline SYNTAX score 18.7 ± 11.0 vs 13.1 ± 8.9, p = 0.002) than younger patients. During PCI, octogenarians were more likely to undergo left main or proximal LAD intervention, but despite this, significantly less likely to receive drug-eluting stents (66.5% vs 80.1%, p <0.001). Postprocedurally, octogenarians had greater residual disease burden (residual SYNTAX score 10.1 ± 8.7 vs 1.6 ± 3.3, p <0.0001). At 12 months, adverse outcomes (definite stent thrombosis 3.3% vs 1.1%, p <0.001, clinically driven in-stent restenosis PCI 3.7% vs 2.6%, p = 0.005, and 12-month mortality 12.8% vs 4.2%, p <0.0001) were all more frequent in octogenarians. Although age, shock, diabetes, and BMS use were independently predictive of increased 12-month mortality, incomplete revascularization was not. In conclusion, octogenarians are a complex group to treat balancing high-risk bleeding profile and complex coronary disease. However, in multivariate analysis, incomplete revascularization was not independently predictive of adverse outcomes. These data support a conservative target lesion—only DES-driven revascularization strategy