Modelling of aircraft manufacturing cost at the concept stage

The work presented is concerned with the estimation of manufacturing cost at the concept design stage, when little technical information is readily available. The work focuses on the nose cowl sections of a wide range of engine nacelles built at Bombardier Aerospace Shorts of Belfast. A core methodology is presented that: defines manufacturing cost elements that are prominent; utilises technical parameters that are highly influential in generating those costs; establishes the linkage between these two; and builds the associated cost estimating relations into models. The methodology is readily adapted to deal with both the early and more mature conceptual design phases, which thereby highlights the generic, flexible and fundamental nature of the method. The early concept cost model simplifies cost as a cumulative element that can be estimated using higher level complexity ratings, while the mature concept cost model breaks manufacturing cost down into a number of constituents that are each driven by their own specific drivers. Both methodologies have an average error of less that ten percent when correlated with actual findings, thus achieving an acceptable level of accuracy. By way of validity and application, the research is firmly based on industrial case studies and practice and addresses the integration of design and manufacture through cost. The main contribution of the paper is the cost modelling methodology. The elemental modelling of the cost breakdown structure through materials, part fabrication, assembly and their associated drivers is relevant to the analytical design procedure, as it utilises design definition and complexity that is understood by engineers.

A developed stage of Alfven wave phase mixing

Alfven wave phase mixing is an extensively studied mechanism for dissipating wave energy in an inhomogeneous medium. It is common in the vast majority of phase mixing papers to assume that even though short scale lengths and steep gradients develop as a result of phase mixing, nonlinear wave coupling does not occur. However, weakly nonlinear studies have shown that phase mixing generates magnetoacoustic modes. Numerical results are presented which show the nonlinear generation of magnetosonic waves by Alfven wave phase mixing. The efficiency of the effect is determined by the wave amplitude, the frequency of the Alfven waves and the gradient in the background Alfven speed. Weakly nonlinear theory has shown that the amplitude of the fast magnetosonic wave grows linearly in time. The simulations presented in this paper extend this result to later times and show saturation of the fast magnetosonic component at amplitudes much lower than that of the Alfven wave. For the case when Alfven waves are driven at the boundary, simulating photospheric footpoint motion, a clear modulation of the saturated amplitude is observed. All the results in this paper are for a low amplitude (less than or equal to 0.1), single frequency Alfven wave and a uniform background magnetic field in a two dimensional domain. For this simplified geometry, and with a monochromatic driver, we concluded that the nonlinear generation of fast modes has little effect on classical phase mixing.

Modern humans in Sarawak, Malaysian Borneo, during Oxygen Isotope Stage 3: palaeoenvironmental evidence from the Great Cave of Niah

During recent reinvestigations in the Great Cave of Niah in Borneo, the ‘Hell Trench’ sedimentary sequence seen by earlier excavators was re-exposed. Early excavations here yielded the earliest anatomically-modern human remains in island Southeast Asia. Calibrated radiocarbon dates, pollen, algal microfossils, palynofacies, granulometry and geochemistry of the ‘Hell Trench’ sequence provide information about environmental and vegetational changes, elements of geomorphic history and information about human activity. The ‘Hell’ sediments were laid down episodically in an ephemeral stream or pool. The pollen suggests cyclically changing vegetation with forest habitats alternating with more open environments; indicating that phases with both temperatures and precipitation reduced compared with the present. These events can be correlated with global climate change sequences to produce a provisional dating framework. During some forest phases, high counts of Justicia, a plant which today colonises recently burnt forest areas, point to fire in the landscape. This may be evidence for biomass burning by humans, presumably to maintain forest-edge habitats. There is evidence from palynofacies for fire on the cave floor in the ‘Hell’ area. Since the area sampled is beyond the limit of plant growth, this is evidence for human activity. The first such evidence is during an episode with significant grassland indicators, suggesting that people may have reached the site during a climatic phase characterised by relatively open habitats ~50 ka. Thereafter, people were able to maintain a relatively consistent presence at Niah. The human use of the ‘Hell’ area seems to have intensified through time, probably because changes in the local hydrological regime made the area dryer and more suitable for human use.

Cutting edge: Langerin+ dendritic cells in the mesenteric lymph node set the stage for skin and gut immune system cross-talk.

Topical transcutaneous immunization (TCI) presents many clinical advantages, but its underlying mechanism remains unknown. TCI induced Ag-specific IgA Ab-secreting cells expressing CCR9 and CCR10 in the small intestine in a retinoic acid-dependent manner. These intestinal IgA Abs were maintained in Peyer\'s patch-null mice but abolished in the Peyer\'s patch- and lymph node-null mice. The mesenteric lymph node (MLN) was shown to be the site of IgA isotype class switching after TCI. Unexpectedly, langerin(+)CD8alpha(-) dendritic cells emerged in the MLN after TCI; they did not migrate from the skin but rather differentiated rapidly from bone marrow precursors. Depletion of langerin(+) cells impaired intestinal IgA Ab responses after TCI. Taken together, these findings suggest that MLN is indispensable for the induction of intestinal IgA Abs following skin immunization and that cross-talk between the skin and gut immune systems might be mediated by langerin(+) dendritic cells in the MLN.

Modelling the MAPK signalling pathway using a two-stage identification algorithm

Signal transduction pathways describe the dynamics of cellular response to input signalling molecules at receptors on the cell membrane. The Mitogen-Activated Protein Kinase (MAPK) cascade is one of such pathways that are involved in many important cellular processes including cell growth and proliferation. This paper describes a black-box model of this pathway created using an advanced two-stage identification algorithm. Identification allows us to capture the unique features and dynamics of the pathway and also opens up the possibility of regulatory control design. In the approach described, an optimal model is obtained by performing model subset selection in two stages, where the terms are first determined by a forward selection method and then modified using a backward selection model refinement. The simulation results demonstrate that the model selected using the two-stage algorithm performs better than with the forward selection method alone.

Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis - Proteomic patterns of joint inflammation in early stage disease

Synovial fluid is a potential source of novel biomarkers for many arthritic disorders involving joint inflammation, including juvenile idiopathic arthritis. We first compared the distinctive protein ‘fingerprints’ of local inflammation in synovial fluid with systemic profiles within matched plasma samples. The synovial fluid proteome at the time of joint inflammation was then evaluated across clinical subgroups to identify early disease associated proteins. We measured the synovial fluid and plasma proteomes using the two-dimensional fluorescence difference gel electrophoresis approach. Image analysis software was used to highlight the expression levels of joint and subgroup associated proteins across the study cohort (n = 32). A defined subset of 30 proteins had statistically significant differences (p < 0.05) between sample types such that synovial fluid could be differentiated from plasma. Furthermore distinctive synovial proteome expression patterns segregate patient subgroups. Protein expression patterns localized in the chronically inflamed joint therefore have the potential to identify patients more likely to suffer disease which will spread from a single joint to multiple joints. The proteins identified could act as criteria to prevent disease extension by more aggressive therapeutic intervention directed at an earlier stage than is currently possible.

The Impact of Admissions for the Management of End-stage renal disease on hospital bed occupancy

BACKGROUND:

End-stage renal disease (ESRD) is increasingly prevalent but the inpatient costs associated with this condition are poorly defined due to limitations with data extraction and failure to differentiate between hospitalisation for renal and non-renal disease reasons. The impact of admissions primarily for the management of ESRD on hospital bed utilisation was assessed over a 5-year period in a large teaching hospital.

METHODS:

All admission episodes were reviewed and the ESRD group was identified by a primary International Classification of Diseases code for ESRD or a non-specific primary renal failure code with a secondary code for ESRD. The frequency and duration of hospitalisation and contribution to bed day occupancy of this group with ESRD was determined.

RESULTS:

There were 70,808 patients responsible for a total of 116,915 admissions and 919,212 bed days over the study period. Of these, 988 (1.4%) patients were admitted for the management of ESRD, accounting for 2,387 (2.0%) of admissions and utilisation of 23,011 (2.5%) bed days. After adjustment for age and gender, those admitted for ESRD management were significantly more likely to have a prolonged admission exceeding 30 days (odds ratio 1.46, 95% confidence interval 1.23-1.72, p < 0.001). When the admission was an emergency rather than an elective event, the patient was 4.6 times more likely to be hospitalised for over 30 days.

CONCLUSIONS:

Persons admitted for ESRD management are hospitalised more frequently and for longer than the overall inpatient population, occupying a substantial number of bed days.