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In an effort to clarify and resolve conflicting views regarding heat loss in marine mammals, we compared four heat-flow models which have been used to predict the "lower critical temperature" (Tlc), below which an endotherm must increase its metabolic rate to maintain homeothermy. Although each model generated different results, all predicted Tlcs below the freezing point of seawater (-2°C) for large cetaceans. The differences between the models only became relevant when dealing with the small cetaceans and the much smaller pinnipeds. Slight changes in metabolic rate or blubber thickness substantially affected the behaviour of the models. We therefore compared the model predictions with observed Tlcs for five juvenile harbour seals (Phoca vitulina) for which metabolic rate, blubber thickness and other relevant parameters were known. The best predictions arose from a model which describes an animal as a simple cylinder; it was accurate within 6°C, although it consistently underestimated true Tlc . In contrast, the other models overestimated Tlc by 5-15°C. The "cylindrical" model proved less accurate when applied to data from a juvenile harbour porpoise (Phocoena phocoena), probably because of an unreliable parameter value describing the proportion of blabber in the body. "Cylindrical" predictions support the argument that marine mammals, for their size, do not have elevated metabolic rates relative to other mammals. We invoke this model to provide a possible explanation for "hauling out" behaviour by Pacific harbour seals (Phoca vitulina richardsi).

Peter Watts, chief executive of The Practice, talks about his organisation and where it will fit in the future landscape of primary care

Despite research efforts full potential of siRNA-based therapeutics has not yet been fully realized due to a need for suitable, effective delivery formulations. Here, we examine a potential of a new class of water-soluble chitosans as siRNA platform for pulmonary delivery. The system is based on piperazine-substituted chitosans, a material designed to integrate established, safe application of chitosan for mucosal administration with novel properties: the piperazine-substituted chitosans are freely water-soluble at physiological pH, possess low cytotoxicity (no significant reduction in cell viability up to 0.1 mg/ml), and provide efficient incorporation of siRNA into sub-300 nm colloidal complexes (at relatively low polymer/siRNA ratio of 5:1). In vitro, the complexes achieved silencing of a model gene at a level of 40–80%, when tested in a panel of lung epithelial cells. Considering the formulation ‘developability’, there were no significant changes in the complexes’ size and integrity on aerosolisation by microsprayer (PenCentury™) device. Following intratracheal aerolisation, the complexes deposited throughout the lung, although relatively inhomogeneously, as judged from IVIS imaging of the isolated mouse lung (visualizing DY647-siRNA). In vivo data illustrate absence of adverse effects on repeated administration of complexes and significant tumor reduction in atopical lung cancer model in mice. Altogether, the data illustrates potential of substituted chitosan derivatives to be utilized as a safe system for inhalation delivery of siRNA.