Increased therapeutic efficiency of a lipid-soluble alkylating agent incorporated in liposomes.

A highly hydrophobic alkylating agent, 1-N,N-bis(beta-bromoethyl) amino-3-methylnaphthalene, given as the free drug in oil, cured a substantial proportion of mice bearing the PC6 myeloma in the dose range 2-7 mg/kg. However, these doses were toxic, and the LD50 was 6-7 mg/kg. When incorporated in liposomes, similar curative effects were obtained at doses of 10-41 mg/kg without material toxicity, even at the highest dose. Liposome entrapment therefore greatly increases the therapeutic efficiency of this agent

Modeling software design diversity

Design diversity has been used for many years now as a means of achieving a degree of fault tolerance in software-based systems. Whilst there is clear evidence that the approach can be expected to deliver some increase in reliability compared with a single version, there is not agreement about the extent of this. More importantly, it remains difficult to evaluate exactly how reliable a particular diverse fault-tolerant system is. This difficulty arises because assumptions of independence of failures between different versions have been shown not to be tenable: assessment of the actual level of dependence present is therefore needed, and this is hard. In this tutorial we survey the modelling issues here, with an emphasis upon the impact these have upon the problem of assessing the reliability of fault tolerant systems. The intended audience is one of designers, assessors and project managers with only a basic knowledge of probabilities, as well as reliability experts without detailed knowledge of software, who seek an introduction to the probabilistic issues in decisions about design diversity

A Grassmann integral equation

The present study introduces and investigates a new type of equation which is called Grassmann integral equation in analogy to integral equations studied in real analysis. A Grassmann integral equation is an equation which involves Grassmann integrations and which is to be obeyed by an unknown function over a (finite-dimensional) Grassmann algebra G_m. A particular type of Grassmann integral equations is explicitly studied for certain low-dimensional Grassmann algebras. The choice of the equation under investigation is motivated by the effective action formalism of (lattice) quantum field theory. In a very general setting, for the Grassmann algebras G_2n, n = 2,3,4, the finite-dimensional analogues of the generating functionals of the Green functions are worked out explicitly by solving a coupled system of nonlinear matrix equations. Finally, by imposing the condition G[{\bar\Psi},{\Psi}] = G_0[{\lambda\bar\Psi}, {\lambda\Psi}] + const., 0<\lambda\in R (\bar\Psi_k, \Psi_k, k=1,...,n, are the generators of the Grassmann algebra G_2n), between the finite-dimensional analogues G_0 and G of the (``classical'') action and effective action functionals, respectively, a special Grassmann integral equation is being established and solved which also is equivalent to a coupled system of nonlinear matrix equations. If \lambda \not= 1, solutions to this Grassmann integral equation exist for n=2 (and consequently, also for any even value of n, specifically, for n=4) but not for n=3. If \lambda=1, the considered Grassmann integral equation has always a solution which corresponds to a Gaussian integral, but remarkably in the case n=4 a further solution is found which corresponds to a non-Gaussian integral. The investigation sheds light on the structures to be met for Grassmann algebras G_2n with arbitrarily chosen n.Comment: 58 pages LaTeX (v2: mainly, minor updates and corrections to the reference section; v3: references [4], [17]-[21], [39], [46], [49]-[54], [61], [64], [139] added

Future Logistics: What to Expect, How to Adapt

As a result of global societal and economic as well as technological developments logistics and supply chains face unprecedented challenges. Climate change, the need for more sustainable products and processes, major political changes, the advance of “Industry 4.0” and cyber-physical system are some of the challenges that require radical solutions, but also present major opportunities. The authors argue that logistics has to reinvent itself, not only to address these chal-lenges but also to cope with mass individualization on the one hand while exploit-ing broad-fielded business applications of artificial intelligence on the other hand. An essential challenge will be to find a compromise between these two develop-ments – in line and in combination with the known triple-bottom line for sustaina-bility – that will define supply chains and logistics concepts of the future

Precision computerised cognitive behavioural therapy (cCBT) for adolescents with depression: a pilot and feasibility randomised controlled trial protocol for SPARX-UK

Background A serious game called SPARX (Smart, Positive, Active, Realistic, X-factor thoughts), originally developed in New Zealand and incorporating cognitive behavioural therapy (CBT) principles, has been shown to help reduce symptoms of depression and anxiety in adolescents with mild to moderate depression in studies undertaken in Australasia. However, SPARX has never been trialled in the United Kingdom (UK), and there have been issues relating to low engagement when it has been used in a real-world context. Aims To conduct the first pilot and feasibility randomised controlled trial (RCT) in England to explore the use of SPARX in different settings. The trial will explore whether SPARX supported by an e-coach (assistant psychologists) improves adherence and engagement compared with self-directed (i.e. self-help) use. The trial results will be used to inform the optimal mode of delivery (SPARX supported vs. SPARX self-directed), to calculate an appropriate sample size for a full RCT, and to decide which setting is most suitable. Methods Following consultation with young people to ensure study suitability/appropriateness, a total of 120 adolescents (11–19 years) will be recruited for this three-arm study. Adolescents recruited for the study across England will be randomised to receive either SPARX with human support (from an e-coach), self-directed SPARX, or a waitlist control group. Assessments will be conducted online at baseline, week 4, and 8–10-week post-randomisation. The assessments will include measures which capture demographic, depression (Patient Health Questionnaire modified for adolescents [PHQ-A]) and anxiety (Revised Child Anxiety and Depression Scale [RCADS]) symptomatology, and health-related quality-of-life data (EQ-5D-Y and proxy version). Analyses will be primarily descriptive. Qualitative interviews will be undertaken with a proportion of the participants and clinical staff as part of a process evaluation, and the qualitative data gathered will be thematically analysed. Finally, feasibility data will be collected on recruitment details, overall study uptake and engagement with SPARX, participant retention, and youth-reported acceptability of the intervention. Discussion The findings will inform the design of a future definitive RCT of SPARX in the UK. If the subsequent definitive RCT demonstrates that SPARX is effective, then an online serious game utilising CBT principles ultimately has the potential to improve the provision of care within the UK’s health services if delivered en masse

New Treatment of the BSW Sampling and Its Applications to Stream Ciphers

By combining the time-memory-data tradeoff (TMDTO) attack independently proposed by Babbage and Golic (BG) with the BSW sampling technique, this paper explores to mount a new TMDTO attack on stream ciphers. The new attack gives a wider variety of trade-offs, compared with original BG-TMDTO attack. It is efficient when multiple data is allowed for the attacker from the same key with different IVs, even though the internal state size is twice the key size. We apply the new attack to MICKEY and Grain stream ciphers, and improves the existing TMDTO attacks on them. Our attacks on Grain v1 and Grain-128 stream ciphers are rather attractive in the respect that the online time, offline time and memory complexities are all better than an exhaustive key search, and the amount of keystream needed are completely valid. Finally, we generalize the new attack to a Guess and Determine-TMDTO attack on stream ciphers, and mount a Guess and Determine-TMDTO attack on SOSEMANUK stream cipher with the online time and offline time complexities both equal to 2128, which achieves the best time com-plexity level compared with all existing attacks on SOSEMANUK so far

Internal accounting practices at Whitbread & Company c.1890-1925

This paper examines internal accounting practices at Whitbread & Company from c. 1890 to 1925. At this time, there was an increasing interest in cost accounting, but there is little detailed extant research on general internal accounting practices of firms. The brewing sector, we suggest, is a potentially fruitful realm to further our knowledge of this time. Drawing on the Whitbread brewery archival records, we chart the internal accounting practices of the company. Our findings reveal a stable set of accounting practices, focused mainly on bookkeeping, although the firm’s auditor produced some reports which may have been useful for management decision-making. We argue these practices were highly institutionalised, and seemingly resistant to external forces present in the company’s environment