ObjectSecurity (United Kingdom)

PurposeTo evaluate single dose pharmacokinetics (PK) of novel reduced-dose film coated Danziten™ (nilotinib tablets) using a population PK approach, establish bioequivalence vs. Tasigna® (nilotinib capsules) and investigate food effects on PK of both formulations.MethodsA population PK model evaluating nilotinib capsules (300 or 400 mg) or tablets (142 or 190 mg) was developed using data from 14 single dose studies and > 30,000 plasma samples from healthy men and women. Steady-state nilotinib concentration–time profiles following twice daily dosing with various treatment and food conditions were simulated using a randomly sampled dataset of 50 subjects.ResultsPK was characterized by a 2-compartment model with linear elimination and zero-order absorption with lag time. Bioequivalence was met for all steady state exposure metrics for both doses under fasted conditions. A milligram strength for nilotinib tablets ~ 50% lower than that for capsules resulted in bioequivalent nilotinib exposures. Administration with a low-fat meal under modified fasting conditions increased the bioavailability (BA) of 142 mg and 190 mg nilotinib tablets by 26.0% and 29.3%, respectively, vs. fasting; values for 300 mg and 400 mg capsules were 56.8% and 60.7%. Administration with a high-fat meal under modified fasting conditions increased the BA of 142 and 190 mg nilotinib tablets by 48.6% and 52.2%, respectively; values for 300 and 400 mg capsules were 180.6% and 183.3%.ConclusionNilotinib tablets 142 and 190 mg provide bioequivalent exposures to 300 mg and 400 mg capsules under fasted conditions and substantially smaller effects of food on exposure.

To restore, recover and resume operations in the wake of a major interruption to business requires clearly defined goals and the existence of a roadmap to achieve, if not exceed, established expectations. This paper proposes that the use of a qualitative approach to measuring business continuity maturity provides the ideal lens through which to gauge an organisation's current state, identify the gaps that need to be closed, and create that roadmap to resilience. Specifically, the paper argues that looking at how well something is completed or understood provides significantly more value than a yes/no quantitative approach that looks only at if something meets expectations. As any successful programme requires ongoing refinement, this paper is intended both to encourage and challenge practitioners to understand better why - and how - to measure their business continuity programme, as well as provide a foundation for development, with a view to unlocking the opportunity for continued resiliency.

2.AbstractHealthcare-associated wastewater reservoirs and asymptomatic gastrointestinal patient colonisation by carbapenemase-producing Enterobacterales (CPE) contribute to nosocomial CPE dissemination. We systematically sampled wastewater sites (n=4488 sampling events; 349 sites) and patients (n=1247) across six wards over 6-12 months in 2016 to better understand blaKPC-associated CPE (KPC-E) diversity within these niches and transmission potential in an endemic healthcare setting. Up to five isolates in KPC-E-positive samples were sequenced (Illumina). Recombination-adjusted phylogenies were used to define genetically related strains; assembly and mapping-based typing approaches were used to characterise antimicrobial resistance genes, insertion sequences, and Tn4401 types/target site sequences. The wider accessory genome was evaluated in a subset of the largest clusters, and those crossing niches.Wastewater site KPC-E-positivity was substantial (101/349 sites [28.9%] positive); 228/5,601 (4.1%) patients cultured were CPE culture-positive over the same timeframe. At a genomic-level, 13 KPC-E species and 109 strains were identified, and 24% of wastewater and 26% of patient KPC-E-positive samples harboured ≥1 strain. Most diversity was explained by the individual niche, suggesting localised factors are important in selection and spread. Tn4401+target site sequence diversity was greater in wastewater sites (p<0.001), which might favour Tn4401-associated transposition/evolution. Shower/bath and sluice/mop-associated sites were more likely to be KPC-E-positive (Adjusted Odds Ratio [95% CI]: 2.69 [1.44-5.01], p=0.0019 and 2.60 [1.04-6.52], p=0.0410, respectively). Different strains had different transmission and blaKPCdissemination dynamics.There may be substantial KPC-E colonisation of wastewater sites and patients in KPC-E-endemic healthcare settings. Niche-specific factors (e.g. microbial interactions, selection pressure) likely affect carbapenemase gene persistence and evolution, and different strains and mobile genetic elements with different transmission dynamics influence carbapenemase gene dissemination; these factors should be considered in surveillance and control strategies.

Abstract Establishing and managing a “good” set of requirements is one of the critical success factors for any space system project, and for the development of any complex product in general. The NextGenRE project sponsored by the European Space Agency has developed an innovative approach featuring the use of semantic wiki technology to enable users to specify structured, semantically‐rich requirements associated with canonical system designs in OMG SysML. Reuse of requirements through templates is supported, as well as semantic reasoning to check properties such as consistency and coherence among requirements. The approach is entirely model‐based, allowing tight integration of the requirements engineering and design processes and opening the way to the application of model checking and simulation techniques. The new approach is being validated alongside an existing space project.

The past decade has seen significant changes in systems development with many organizations adopting agile methodologies as a viable methodology for developing systems. An increasing number of research studies reveal the growing popularity and acceptance of agile methodologies. While most academic research has focused on adoption and adaptation of agile methods, there is very limited understanding of their post-adoption usage and incorporation within organizations. What factors explain the effective usage of agile methodologies? A synthesis of past research in Systems Development Methodologies, Information Systems implementation, Diffusion of Innovations, and Agile Methodologies was conducted to develop a research model that identifies the main factors pertinent to the propagation and effective usage of agile methodologies in organizations. The model is tested by applying it to the usage of Kanban for Software Engineering practices at BBC Worldwide, London. Insights gained from the case study are discussed.

Overall, transport layer security with session-aware user authentication offers a promising approach to solving man-in-the-middle attack problems by leveraging the legacy authentication mechanisms and systems that the general public has become accustomed to using.

In the past, it was very common to develop middleware without consideration of security from the very beginning. To integrate security, the middleware that should be protected has to provide appropriate hooks and interfaces, and has to meet the requirements of security. In most cases it is not possible to develop a new, secure middleware from scratch. It is only possible to make minor modification to existing systems. In this paper we describe the successful integration of a CORBA Component based middleware and a policy management framework for the definition, management and enforcement of security policies. Integration is achieved by defining Container Portable Interceptors and QoS Enablers which provide the necessary hooks for interception and provision of context interfaces to integrate the security framework.

This paper discusses the difficulties of describing an appropriate notion of the security attributes and in object-oriented middleware systems such as CORBA. Middleware security needs such security attributes in order to be able to express middleware layer security policies. Our analysis points out that, whilst there is no information available on the ORB layer to describe the caller and target, it is possible in practice to use descriptors from other layers. In CORBA security, the mechanism-specific identifiers on the caller side and the information from the object reference on the target side turn out to be most appropriate and trustworthy for describing caller and target application objects at the right granularity. As a proof of concept we mention our MICOSec CORBA security implementation which demonstrates the feasibility of our approach. Our paper shows that it is unrealistic to expect a security service layer to be able to abstract fully from the underlying security mechanisms without implications on granularity and semantic mismatches.