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Background: The ketogenic diet (KD) is used to treat severe childhood-onset epileptic encephalopathies, such as Infantile Spasms (IS). Unfortunately, limited resources for KD initiation result in treatment delays. We ask if earlier KD treatment of early-onset drug-resistant epilepsy results in better seizure outcomes. Methods: Children who started KD before age 4 years between 2000-present at SickKids Hospital were identified. Six-month seizure outcome was calculated as percent of pre-diet baseline seizure frequency (BSF). Results: 67 children were identified. 30 (44.8%) started KD Conclusions: KD was more effective when started before age 2 years than 2-4 years, and more effective in children with IS than in children with past history of IS. A rapid protocol for KD initiation in young infants and children may improve long-term outcomes

Background DNA interstrand cross-links (ICLs) are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma) and solid tumours (ovarian cancer) that clinical sensitivity to such agents can result from a defect in DNA ICL processing leading to their persistence. Conversely, enhanced repair can result in clinical acquired resistance following chemotherapy. The repair of ICLs is complex but it is assumed that the ‘unhooking’ step is common to all ICLs. Methods Using a modification of the single cell gel electrophoresis (Comet) assay we measured the formation and unhooking of melphalan and cisplatin-induced ICLs in cell lines and clinical samples. DNA damage response in the form of γ-H2AX foci formation and the formation of RAD51 foci as a marker of homologous recombination were also determined. Real-time PCR of 84 genes involved in DNA damage signalling pathways was also examined pre- and post-treatment. Results Plasma cells from multiple myeloma patients known to be clinically resistant to melphalan showed significant unhooking of melphalan-induced ICLs at 48 hours, but did not unhook cisplatin-induced ICLs. In ovarian cancer cells obtained from patients following platinum-based chemotherapy, unhooking of cisplatin-induced ICLs was observed at 48 hours, but no unhooking of melphalan-induced ICLs. In vitro, A549 cells were proficient at unhooking both melphalan and cisplatin-induced ICLs. γ-H2AX foci formation closely followed the formation of ICLs for both drugs, and rapidly declined following the peak of formation. RPMI8226 cells unhooked melphalan, but not cisplatin-induced ICLs. In these cells, although cross-links form with cisplatin, the γ-H2AX response is weak. In A549 cells, addition of 3nM gemcitabine resulted in complete inhibition of cisplatin-induced ICL unhooking but no effect on repair of melphalan ICLs. The RAD51 foci response was both drug and cell line specific. Real time PCR studies highlighted differences in the damage response to melphalan and cisplatin following equi-ICL forming doses. Conclusions These data suggest that the mechanisms by which melphalan and cisplatin-induced ICLs are ‘unhooked’ in vitro are distinct, and the mechanisms of clinical acquired resistance involving repair of ICLs, are drug specific.

Can the technique of proof plans, developed originally for use in theorem proving, be successfully applied outside mathematics? We look at a problem associated with the configuration of large computer systems, namely that of checking orders drawn up by sales people on behalf of customers. Strategies exist for this task which may be explicitly encoded. We discuss the formation of plans for order checking and the factors involved in determining whether such plans can be guaranteed to succeed.

Recent advances in networking technology have increased the potential for dynamic enterprise collaborations between an open set of entities on a global scale. The security of these collaborations is a major concern, and requires novel approaches suited to this new environment to be developed. Trust management appears to be a promising approach. Due to the dynamic nature of these collaborations, dynamism in the formation, evolution and exploitation of trust is essential. In this paper, we explore the properties of trust dynamics in this context. Trust is formed and evolves according to personal experience and recommendations. The properties of trust dynamics are expressed through a formal model of trust. Specific examples, based on an e-purse application scenario are used to demonstrate these properties.

A significant characteristic of global computing is the need for secure interactions between highly mobile entities and the services in their environment. Moreover, these decentralised systems are also characterised by partial views over the state of the global environment, implying that we cannot guarantee verification of the properties of the mobile entity entering an unfamiliar domain. Secure in this context encompasses both the need for cryptographic security and the need for trust, on the part of both parties, that the interaction will function as expected. In this paper, we explore an architecture for interaction/ collaboration in global computing systems. This architecture reflects the aspects of the trust lifecycle in three stages: trust formation, trust evolution and trust exploitation, forming a basis for risk assessment and interaction decisions.

A significant characteristic of pervasive computing is the need for secure interactions between highly mobile entities and the services in their environment. Moreover,these decentralised systems are also characterised by partial views over the state of the global environment, implying that we cannot guarantee verification of the properties of the mobile entity entering an unfamiliar domain. Secure in this context encompasses both the need for cryptographic security and the need for trust, on the part of both parties, that the interaction is functioning as expected. In this paper we make a broad assumption that trust and cryptographic security can be considered as orthogonal concerns (i.e. cryptographic measures do not ensure transmission of correct information). We assume the existence of reliable encryption techniques and focus on the characteristics of a model that supports the management of the trust relationships between two devices during ad-hoc interactions.

5600 Background: CTCs are prognostic and predictive markers in many solid tumours. There are no validated biomarkers to assess treatment (tx) response or molecular therapies in aEC. We conducted a ...

Existing software systems designed to support learning do not adequately provide for vicarious learning in a cross-institutional collaborative environment. We have developed an architecture based on role-based access control, which provides the necessary security, robustness, flexibility, and explicit formulation of policy. Such an architecture is general enough to be used in a variety of educational institutions and settings, yet flexible enough to allow a wide range of policies within a single system.