Ergonomists as designers: computational modelling and simulation of complex socio-technical systems

Contemporary ergonomics problems are increasing in scale, ambition, and complexity. Understanding and creating solutions for these multi-faceted, dynamic, and systemic problems challenges traditional methods. Computational modelling approaches can help address this methodological shortfall. We illustrate this potential by describing applications of computational modelling to: (1) teamworking within a multi-team engineering environment; (2) crowd behaviour in different transport terminals; and (3) performance of engineering supply chains. Our examples highlight the benefits and challenges for multi-disciplinary approaches to computational modelling, demonstrating the need for socio-technical design principles. Our experience highlights opportunities for ergonomists as designers and users of computational models, and the instrumental role that ergonomics can play in developing and enhancing complex socio-technical systems. Recognising the challenges inherent in designing computational models, we reflect on practical issues and lessons learned so that computational modelling and simulation can become a standard and valuable technique in the ergonomists’ toolkit

Sporormiella as a tool for detecting the presence of large herbivores in the Neotropics

The reliability of using the abundance of Sporormiella spores as a proxy for the presence and abundance of megaherbivores was tested in southern Brazil. Mud-water interface samples from nine lakes, in which cattle-use was categorized as high, medium, or low, were assayed for Sporormiella representation. The sampling design allowed an analysis of both the influence of the number of animals using the shoreline and the distance of the sampling site from the nearest shoreline. Sporormiella was found to be a reliable proxy for the presence of large livestock. The concentration and abundance of spores declined from the edge of the lake toward the center, with the strongest response being in sites with high livestock use. Consistent with prior studies in temperate regions, we find that Sporormiella spores are a useful proxy to study the extinction of Pleistocene megafauna or the arrival of European livestock in Neotropical landscapes

CX3CR1 Polymorphisms are associated with atopy but not asthma in German children

Chemokines and their receptors are involved in many aspects of immunity. Chemokine CX3CL1, acting via its receptor CX3CR1, regulates monocyte migration and macrophage differentiation as well as T cell-dependent inflammation. Two common, nonsynonymous polymorphisms in CX3CR1 have previously been shown to alter the function of the CX3CL1/CX3CR1 pathway and were suggested to modify the risk for asthma. Using matrix-assisted laser desorption/ionization time-of-flight technology, we genotyped polymorphisms Val249Ile and Thr280Met in a cross-sectional population of German children from Munich (n = 1,159) and Dresden ( n = 1,940). For 249Ile an odds ratio of 0.77 (95% confidence interval 0.63-0.96; p = 0.017) and for 280Met an odds ratio of 0.71 ( 95% confidence interval 0.56-0.89; p = 0.004) were found with atopy in Dresden but not in Munich. Neither polymorphism was associated with asthma. Thus, amino acid changes in CX3CR1 may influence the development of atopy but not asthma in German children. Potentially, other factors such as environmental effects may modify the role of CX3CR1 polymorphisms. Copyright (c) 2007 S. Karger AG, Basel

Propagation of an Earth-directed coronal mass ejection in three dimensions

Solar coronal mass ejections (CMEs) are the most significant drivers of adverse space weather at Earth, but the physics governing their propagation through the heliosphere is not well understood. While stereoscopic imaging of CMEs with the Solar Terrestrial Relations Observatory (STEREO) has provided some insight into their three-dimensional (3D) propagation, the mechanisms governing their evolution remain unclear due to difficulties in reconstructing their true 3D structure. Here we use a new elliptical tie-pointing technique to reconstruct a full CME front in 3D, enabling us to quantify its deflected trajectory from high latitudes along the ecliptic, and measure its increasing angular width and propagation from 2-46 solar radii (approximately 0.2 AU). Beyond 7 solar radii, we show that its motion is determined by an aerodynamic drag in the solar wind and, using our reconstruction as input for a 3D magnetohydrodynamic simulation, we determine an accurate arrival time at the Lagrangian L1 point near Earth.Comment: 5 figures, 2 supplementary movie

Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds

Animals are frequently used as model systems for determination of safety and efficacy in pharmaceutical research and development. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this cross-species methodology by investigating species specific differences of the peroxisome proliferatoractivator receptor (PPAR) a response in rat and human

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

IL8 polymorphisms and overall survival in pazopanib- or sunitinib-treated patients with renal cell carcinoma.

BACKGROUND: We evaluated germline single nucleotide polymorphisms (SNPs) for association with overall survival (OS) in pazopanib- or sunitinib-treated patients with advanced renal cell carcinoma (aRCC). METHODS: The discovery analysis tested 27 SNPs within 13 genes from a phase III pazopanib trial (N=241, study 1). Suggestive associations were then pursued in two independent datasets: a phase III trial (COMPARZ) comparing pazopanib vs sunitinib (N=729, study 2) and an observational study of sunitinib-treated patients (N=89, study 3). RESULTS: In study 1, four SNPs showed nominally significant association (P≤0.05) with OS; two of these SNPs (rs1126647, rs4073) in IL8 were associated (P≤0.05) with OS in study 2. Because rs1126647 and rs4073 were highly correlated, only rs1126647 was evaluated in study 3, which also showed association (P≤0.05). In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P=8.8 × 10(-5); variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15-1.52), without evidence for heterogeneity of effects between studies or between pazopanib- and sunitinib-treated patients. CONCLUSIONS: Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC. These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies

Group Visits: Promoting Adherence to Diabetes Guidelines

BACKGROUND: Current diabetes management guidelines offer blueprints for providers, yet type 2 diabetes control is often poor in disadvantaged populations. The group visit is a new treatment modality originating in managed care for efficient service delivery to patients with chronic health problems. Group visits offer promise for delivering care to diabetic patients, as visits are lengthier and can be more frequent, more organized, and more educational. OBJECTIVE: To evaluate the effect of group visits on clinical outcomes, concordance with 10 American Diabetes Association (ADA) guidelines [American Diabetes Association, Diabetes Care, 28:S4–36, 2004] and 3 United States Preventive Services Task Force (USPSTF) cancer screens [U.S. Preventive Services Task Force, http://www.ahrq.gov/clinic/uspstf/resource.htm, 2003]. RESEARCH DESIGN AND METHODS: A 12-month randomized controlled trial of 186 diabetic patients comparing care in group visits with care in the traditional patient–physician dyad. Clinical outcomes (HbA1c, blood pressure [BP], lipid profiles) were assessed at 6 and 12 months and quality of care measures (adherence to 10 ADA guidelines and 3 USPSTF cancer screens) at 12 months. RESULTS: At both measurement points, HbA1c, BP, and lipid levels did not differ significantly for patients attending group visits versus those in usual care. At 12 months, however, patients receiving care in group visits exhibited greater concordance with ADA process-of-care indicators (p < .0001) and higher screening rates for cancers of the breast (80 vs. 68%, p = .006) and cervix (80 vs 68%, p = .019). CONCLUSIONS: Group visits can improve the quality of care for diabetic patients, but modifications to the content and style of group visits may be necessary to achieve improved clinical outcomes