Congenital afibrinogenemia, the most severe form of fibrinogen deficiency, is characterized by the complete absence of fibrinogen. The disease is caused by mutations in 1 of the 3 fibrinogen genes FGG, FGA, and FGB, clustered on the long arm of human chromosome 4. The majority of cases are due to null mutations in the FGA gene although one would expect the 3 genes to be equally implicated. However, most patients studied so far are white, and therefore the identification of causative mutations in non-European families is necessary to establish if this finding holds true in all ethnic groups. In this study, we report the identification of a novel nonsense mutation (Arg134Xaa) in the FGG gene responsible for congenital afibrinogenemia in 10 patients from Lebanon. Expression studies in COS-7 cells demonstrated that the Arg134Xaa codon, which is encoded by adjacent exons (TG-intron 4-A) affected neither mRNA splicing nor stability, but led to the production of an unstable, severely truncated fibrinogen ␥ chain that is not incorporated into a functional fibrinogen hexamer. ( IntroductionInherited disorders of fibrinogen are rare and affect either the quantity (hypofibrinogenemia and afibrinogenemia) or the quality (dysfibrinogenemia) of circulating fibrinogen. Fibrinogen is produced in the liver from 3 homologous polypeptide chains, A␣, B␤, and ␥, which assemble to form a hexamer containing 2 copies of each chain. Fibrinogen is the precursor of fibrin, the major protein constituent of the blood clot. Congenital afibrinogenemia (OMIM: online Mendelian Inheritance in Man; no. 202400), 1 the most severe form of fibrinogen deficiency, is characterized by the complete absence of fibrinogen. The disease was originally described in 1920; 2 it has an estimated prevalence of around 1 to 2 in 1 000 000. Umbilical cord hemorrhage is often the first sign of the disorder; gum bleeding, epistaxis, menorrhagia, gastrointestinal bleeding, and hemarthrosis occur with varying intensity, and spontaneous intracerebral bleeding and splenic rupture can occur throughout life. 3,4 Congenital afibrinogenemia is inherited in an autosomal recessive manner: the condition exists only when both alleles are mutated, in homozygosity or compound heterozygosity; both sexes are affected. Although the disease was first described in 1920, the genetic locus responsible for the disorder was only recently determined. We identified the first causative mutations for this disorder in a nonconsanguineous Swiss family. The genetic defect was an apparently recurrent deletion of approximately 11 kb of DNA that eliminates the majority of the FGA gene and so leads to a complete absence of functional fibrinogen. 5 The deletions were all identical to the base pair and probably resulted from nonhomologous (illegitimate) recombination, mediated by a direct 7 bp repeat, AACTTTT, and perhaps also by indirect repeats in the breakpoint region. Many families with this disorder have been studied since then, allowing the identification of numerous causative mutations (reviewe...

INTRODUCTIONThe otorhinolaryngology department at Northwick Park Hospital uses the Tristel wipes system for cleaning nasendoscopes in the outpatient clinics. This system uses chlorine dioxide as its only disinfectant. The manufacturer claims the system provides safe sterilisation of nasendoscopes. However, there appear to be no reports in the literature to date that evaluate the efficacy of this system in a clinical setting. The aim of this study was to evaluate the 'in use' efficacy of Tristel wipes in decontaminating nasendoscopes and to identify any significant contamination between cleaning and usage. METHODS A total of 31 cleaning episodes were performed. Each cleaning episode included two swabs after cleaning the scopes, one from the tip and the other from the handle. Another two swabs from the same areas were also taken before application to the patient. The microbiology unit evaluated all swabs for bacterial, fungal and mycobacterial growth. RESULTS Overall, 123 swabs from 31 cleaning episodes were tested. None of the swabs taken from the tips (n=31) or handles (n=31) after cleaning with Tristel wipes developed any organism growth. Furthermore, none of the swabs taken from the tip of the scopes before using on patients (n=31) developed any growth. Of the 31 swabs taken from the handle before use, 3 developed significant staphylococcal growth. CONCLUSIONS In our study, the 'in use' efficacy of Tristel wipes in cleaning the scopes of bacteria, fungi and mycobacteria was 100%. Attention to hand hygiene and the use of gloves should be considered when handling the cleaned scopes to minimise the risk of contamination between cleaning and application to patients.

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This paper presents an integrated methodology for the comprehensive assessment of com bined rotorcraft-powerplant systems at mission level. Analytical evaluation of existing and conceptual designs is carried out in terms of operational performance and environ mental impact. The proposed approach comprises a wide-range of individual modeling theories applicable to rotorcraft flight dynamics and gas turbine engine performance. A novel, physics-based, stirred reactor model is employed for the rapid estimation of nitro gen oxides (NOx) emissions. The individual mathematical models are implemented within an elaborate numerical procedure, solving for total mission fuel consumption and associ ated pollutant emissions. The combined approach is applied to the comprehensive analy sis of a reference twin-engine light (TEL) aircraft modeled after the Eurocopter Bo 105 helicopter, operating on representative mission scenarios. Extensive comparisons with flight test data are carried out and presented in terms of main rotor trim control angles and power requirements, along with general flight performance charts including payload-range diagrams. Predictions of total mission fuel consumption and NOx emis sions are compared with estimated values provided by the Swiss Federal Office of Civil Aviation (FOCA). Good agreement is exhibited between predictions made with the physics-based stirred reactor model and experimentally measured values ofNOx emission indices. The obtained results suggest that the production rates of NOx pollutant emissions are predominantly influenced by the behavior of total air inlet pressure upstream of the combustion chamber, which is affected by the employed operational procedures and the time-dependent all-up mass (AUM) of the aircraft.It is demonstrated that accurate esti mation of on-board fuel supplies ahead offlight is key to improving fuel economy as well as reducing environmental impact. The proposed methodology essentially constitutes an enabling technology for the comprehensive assessment of existing and conceptual rotor craft-powerplant systems, in terms of operational performance and environmental impact.

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This paper aims to present an integrated rotorcraft conceptual design and analysis framework, deployed for the multidisciplinary design and optimization of regenerative powerplant configurations in terms of rotorcraft operational and environmental performance. The proposed framework comprises a wide-range of individual modeling theories applicable to rotorcraft flight dynamics, gas turbine engine performance, and weight estimation as well as a novel physics-based, stirred reactor model for the rapid estimation of gas turbine gaseous emissions. A multi-objective particle swarm optimizer (mPSO) is coupled with the aforementioned integrated rotorcraft multidisciplinary design framework. The combined approach is applied to conduct multidisciplinary design and optimization of a reference twin engine light civil rotorcraft modeled after the Airbus-Helicopters Bo105 helicopter, operating on representative mission scenario. Through the implementation of a multi-objective optimization study, Pareto front models have been acquired, quantifying the optimum interrelationship between the mission fuel consumption and gaseous emissions for the representative rotorcraft and a variety of engine configurations. The acquired optimum engine configurations are subsequently deployed for the design of conceptual rotorcraft regenerative engines, targeting improved mission fuel economy, enhanced payload range capability, as well as improvements in the rotorcraft overall environmental impact. The proposed methodology essentially constitutes an enabler in terms of focusing the multidisciplinary design and optimization of rotorcraft powerplants within realistic, three-dimensional operations and toward the realization of their associated design trade-offs at mission level.

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