Transcriptional profiles and host response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole blood mRNA signatures, local and systemic immune mediator concentrations in 131 adults hospitalised with influenza from which extensive clinical and investigational data were obtained by the MOSAIC consortium. Signatures reflecting interferon-related antiviral pathways were common up to day 4 of symptoms in cases not requiring mechanical ventilatory support; in those needing mechanical ventilation an inflammatory, activated neutrophil and cell stress/death (‘bacterial’) pattern was seen, even early in disease. Identifiable bacterial co-infection was not necessary for this ‘bacterial’ signature but could enhance its development, while attenuating the early ‘viral’ signature. Our findings emphasise the importance of timing and severity in the interpretation of host responses to acute viral infection, and identify specific patterns of immune activation that may enable the development of novel diagnostic and therapeutic tools for severe influenza.

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Infrared-ultraviolet double resonance (IRUVDR) experiments have been implemented in the ultra-cold environment provided by a CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme) apparatus. With this technique rate coefficients of two kinds have been measured for rotational energy transfer in collisions between NO and He, Ar and N2: (a) rate coefficients for total removal from specific states of NO(X 2Π1/2; v=3; J=0.5, 3.5 or 6.5) and (b) state-to-state rate coefficients for rotational energy transfer from these levels to specific final states. Using different Laval nozzles, results have been obtained at several different temperatures: for He as collision partner, 295, 149, 63, 27, 15 and 7 K; for Ar, 139, 53, 44 and 27 K; and for N2, 86 and 47 K. The thermally averaged cross-sections for total removal show remarkably little variation, either with temperature or with initial rotational state. The variation of state-to-state rate coefficients with ΔJ shows three general features: (i) a decrease with increasing ΔJ; (ii) a propensity to favor even ΔJ transitions over odd ΔJ changes; and (iii) at lower temperatures, decreases in J are increasingly favored over increases in J and the distribution of rate coefficients against ΔJ becomes narrower. The experimental rate coefficients for collisions with He and Ar are compared with those from both close coupled and coupled states calculations based on potential energy surfaces determined within the coupled electron pair approximation (CEPA) with a large atomic orbital basis set. The agreement between theory and experiment of both the total and the state-to-state rate coefficients is excellent over the complete range of temperatures covered in the experiments.

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