Feasibility study to inform the design of a UK multi-centre randomised controlled trial of prophylactic antibiotics for the prevention of recurrent cellulitis of the leg

Background: This paper describes the results of a feasibility study for a randomised controlled trial (RCT). Methods: Twenty-nine members of the UK Dermatology Clinical Trials Network (UK DCTN) expressed an interest in recruiting for this study. Of these, 17 obtained full ethics and Research & Development (R&D) approval, and 15 successfully recruited patients into the study. A total of 70 participants with a diagnosis of cellulitis of the leg were enrolled over a 5-month period. These participants were largely recruited from medical admissions wards, although some were identified from dermatology, orthopaedic, geriatric and general surgery wards. Data were collected on patient demographics, clinical features and willingness to take part in a future RCT. Results: Despite being a relatively common condition, cellulitis patients were difficult to locate through our network of UK DCTN clinicians. This was largely because patients were rarely seen by dermatologists, and admissions were not co-ordinated centrally. In addition, the impact of the proposed exclusion criteria was high; only 26 (37%) of those enrolled in the study fulfilled all of the inclusion criteria for the subsequent RCT, and were willing to be randomised to treatment. Of the 70 participants identified during the study as having cellulitis of the leg (as confirmed by a dermatologist), only 59 (84%) had all 3 of the defining features of: i) erythema, ii) oedema, and iii) warmth with acute pain/tenderness upon examination. Twenty-two (32%) patients experienced a previous episode of cellulitis within the last 3 years. The median time to recurrence (estimated as the time since the most recent previous attack) was 205 days (95% CI 102 to 308). Service users were generally supportive of the trial, although several expressed concerns about taking antibiotics for lengthy periods, and felt that multiple morbidity/old age would limit entry into a 3-year study. Conclusion: This pilot study has been crucial in highlighting some key issues for the conduct of a future RCT. As a result of these findings, changes have been made to i) the planned recruitment strategy, ii) the proposed inclusion criteria and ii) the definition of cellulitis for use in the future trial.

New Directions in Commercial Secrecy and Encryption Protocols

Secure transmission of bulk data is of interest to many content providers. A commercially-viable distribution of content requires technology to prevent unauthorised access. Encryption tools are powerful, but have a performance cost. Without encryption, intercepted data may be illicitly duplicated and re-sold, or its commercial value diminished because its secrecy is lost. Two technical solutions make it possible to perform bulk transmissions while retaining security without too high a performance overhead. These are: 1. a) hierarchical encryption - the stronger the encryption, the harder it is to break but also the more computationally expensive it is. A hierarchical approach to key exchange means that simple and relatively weak encryption and keys are used to encrypt small chunks of data, for example 10 seconds of video. Each chunk has its own key. New keys for this bottom-level encryption are exchanged using a slightly stronger encryption, for example a whole-video key could govern the exchange of the 10-second chunk keys. At a higher level again, there could be daily or weekly keys, securing the exchange of whole-video keys, and at a yet higher level, a subscriber key could govern the exchange of weekly keys. At higher levels, the encryption becomes stronger but is used less frequently, so that the overall computational cost is minimal. The main observation is that the value of each encrypted item determines the strength of the key used to secure it. 2. b) non-symbolic fragmentation with signal diversity - communications are usually assumed to be sent over a single communications medium, and the data to have been encrypted and/or partitioned in whole-symbol packets. Network and path diversity break up a file or data stream into fragments which are then sent over many different channels, either in the same network or different networks. For example, a message could be transmitted partly over the phone network and partly via satellite. While TCP/IP does a similar thing in sending different packets over different paths, this is done for load-balancing purposes and is invisible to the end application. Network and path diversity deliberately introduce the same principle as a secure communications mechanism - an eavesdropper would need to intercept not just one transmission path but all paths used. Non-symbolic fragmentation of data is also introduced to further confuse any intercepted stream of data. This involves breaking up data into bit strings which are subsequently disordered prior to transmission. Even if all transmissions were intercepted, the cryptanalyst still needs to determine fragment boundaries and correctly order them. These two solutions depart from the usual idea of data encryption. Hierarchical encryption is an extension of the combined encryption of systems such as PGP but with the distinction that the strength of encryption at each level is determined by the "value" of the data being transmitted. Non- symbolic fragmentation suppresses or destroys bit patterns in the transmitted data in what is essentially a bit-level transposition cipher but with unpredictable irregularly-sized fragments. Both technologies have applications outside the commercial and can be used in conjunction with other forms of encryption, being functionally orthogonal.

Delays in activity based neural networks

In this paper we study the effect of two distinct discrete delays on the dynamics of a Wilson-Cowan neural network. This activity based model describes the dynamics of synaptically interacting excitatory and inhibitory neuronal populations. We discuss the interpretation of the delays in the language of neurobiology and show how they can contribute to the generation of network rhythms. First we focus on the use of linear stability theory to show how to destabilise a fixed point, leading to the onset of oscillatory behaviour. Next we show for the choice of a Heaviside nonlinearity for the firing rate that such emergent oscillations can be either synchronous or anti-synchronous depending on whether inhibition or excitation dominates the network architecture. To probe the behaviour of smooth (sigmoidal) nonlinear firing rates we use a mixture of numerical bifurcation analysis and direct simulations, and uncover parameter windows that support chaotic behaviour. Finally we comment on the role of delays in the generation of bursting oscillations, and discuss natural extensions of the work in this paper.