Updating outdated predictive accident models for modern rural roads [forthcoming]

Reliable predictive accident models (PAMs) are essential to design and maintain safe road networks however, ongoing changes in road and vehicle design coupled with road safety initiatives, mean that these models can quickly become dated. Unfortunately, because the fitting of sophisticated PAMs including a wide range of explanatory variables is not a trivial task, available models tend to be based on data collected many years ago and seem unlikely to give reliable estimates of current accidents. Large, expensive studies to produce new models are likely to be, at best, only a temporary solution. This paper thus seeks to develop a practical and efficient methodology to allow currently available PAMs to be updated to give unbiased estimates of accident frequencies at any point in time. Two principal issues are examined: the extent to which the temporal transferability of predictive accident models varies with model complexity; and the practicality and efficiency of two alternative updating strategies. The models used to illustrate these issues are the suites of models developed for rural dual and single carriageway roads in the UK. These are widely used in several software packages in spite of being based on data collected during the 1980s. It was found that increased model complexity by no means ensures better temporal transferability and that calibration of the models using a scale factor can be a practical alternative to fitting new models

Methodology for fitting and updating predictive accident models with trend [forthcoming]

Reliable predictive accident models (PAMs) have a variety of important uses in traffic safety research and practice. They are used to help identify sites in need of remedial treatment, in the design of transport schemes to assess safety implications, and to estimate the effectiveness of remedial treatments. The PAMs currently in use in the UK are now quite old; the data used in their development was gathered up to 30 years ago. Many changes have occurred over that period in road and vehicle design, in road safety campaigns and legislation, and the national accident rate has fallen substantially. It seems unlikely that these aging models can be relied upon to provide accurate and reliable predictions of accident frequencies on the roads today. This paper addresses a number of methodological issues that arise in seeking practical and efficient ways to update PAMs. Models for accidents on rural single carriageway roads have been chosen to illustrate these issues, including the choice of distributional assumption for overdispersion, the choice of goodness of fit measures, questions of independence between observations in different years, and between links on the same scheme, the estimation of trends in the models, the uncertainty of predictions, as well as considerations about the most efficient and convenient ways to fit the required models, given the considerable advances that have been seen in statistical computing software in recent years

Upwelling on the continental slope of the Alaskan Beaufort Sea : storms, ice, and oceanographic response

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C00A13, doi:10.1029/2008JC005009.The characteristics of Pacific-born storms that cause upwelling along the Beaufort Sea continental slope, the oceanographic response, and the modulation of the response due to sea ice are investigated. In fall 2002 a mooring array located near 152°W measured 11 significant upwelling events that brought warm and salty Atlantic water to shallow depths. When comparing the storms that caused these events to other Aleutian lows that did not induce upwelling, interesting trends emerged. Upwelling occurred most frequently when storms were located in a region near the eastern end of the Aleutian Island Arc and Alaskan Peninsula. Not only were these storms deep but they generally had northward-tending trajectories. While the steering flow aloft aided this northward progression, the occurrence of lee cyclogenesis due to the orography of Alaska seems to play a role as well in expanding the meridional influence of the storms. In late fall and early winter both the intensity and frequency of the upwelling diminished significantly at the array site. It is argued that the reduction in amplitude was due to the onset of heavy pack ice, while the decreased frequency was due to two different upper-level atmospheric blocking patterns inhibiting the far field influence of the storms.The following grants provided support for this study: National Science Foundation grants OPP-0731928 (R.S.P.) and OPP-0713250 (R.S.P. and P.S.F.), Office of Naval Research grant N00014-07-1-1040 (D.J.T. and R.A.G.), Natural Sciences and Engineering Research Council of Canada (G.W.K.M.), Woods Hole Oceanographic Institution Arctic Initiative (J.Y.)

Mediastinal lymph node metastasis model by orthotopic intrapulmonary implantation of Lewis lung carcinoma cells in mice

This study is designed to establish a pulmonary tumour model to investigate the biology and therapy of lung cancer in mice. Current methods for forming a solitary intrapulmonary nodule and subsequent metastasis to mediastinal lymph nodes are not well defined. Lewis lung carcinoma (LLC) cell suspensions were orthotopically introduced into the lung parenchyma of C57/BL6 mice via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. The implantation process was performed within approximately 50 s per mouse, and the operative mortality was less than 5%. Single pulmonary nodules developed at the implanted site in 93% of animals and subsequent mediastinal lymph node metastasis was observed in all mice that formed a lung nodule after intrapulmonary implantation. The size of tumour nodule and the weight of mediastinal lymph node increased in a time-dependent manner. The mean survival time of mice implanted successfully with LLC cells was 21 ± 2 days (range 19–24 days). Histopathological analysis revealed that no metastatic tumour was detectable in the mediastinal lymph nodes on day 11, but metastatic foci at mediastinal lymph nodes were clearly observed on days 17 and 21 after implantation. Other metastases in distant organs or lymph nodes were not observed at 21 days after the implantation. Comparative studies with intrapleural and intravenous injections of LLC cells suggest that the mediastinal lymph node metastasis by intrapulmonary impantation is due to the release of tumour cells from the primary nodule, and not due to extrapulmonary leakage of cells. An intravenous administration of cis-diamine dichrolo platinum on day 1 after tumour implantation tended to suppress the primary tumour nodule and significantly inhibited lymph node metastasis. Thus, a solitary pulmonary tumour nodule model with lymph node metastasis approximates clinical lung cancer and may provide a useful basis for lung cancer research. © 1999 Cancer Research Campaig

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Modeling Electrically Active Viscoelastic Membranes

The membrane protein prestin is native to the cochlear outer hair cell that is crucial to the ear's amplification and frequency selectivity throughout the whole acoustic frequency range. The outer hair cell exhibits interrelated dimensional changes, force generation, and electric charge transfer. Cells transfected with prestin acquire unique active properties similar to those in the native cell that have also been useful in understanding the process. Here we propose a model describing the major electromechanical features of such active membranes. The model derived from thermodynamic principles is in the form of integral relationships between the history of voltage and membrane resultants as independent variables and the charge density and strains as dependent variables. The proposed model is applied to the analysis of an active force produced by the outer hair cell in response to a harmonic electric field. Our analysis reveals the mechanism of the outer hair cell active (isometric) force having an almost constant amplitude and phase up to 80 kHz. We found that the frequency-invariance of the force is a result of interplay between the electrical filtering associated with prestin and power law viscoelasticity of the surrounding membrane. Paradoxically, the membrane viscoelasticity boosts the force balancing the electrical filtering effect. We also consider various modes of electromechanical coupling in membrane with prestin associated with mechanical perturbations in the cell. We consider pressure or strains applied step-wise or at a constant rate and compute the time course of the resulting electric charge. The results obtained here are important for the analysis of electromechanical properties of membranes, cells, and biological materials as well as for a better understanding of the mechanism of hearing and the role of the protein prestin in this mechanism

Power efficiency of outer hair cell somatic electromotility

© 2009 Rabbitt et al. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS Computational Biology 5 (2009): e1000444, doi:10.1371/journal.pcbi.1000444.Cochlear outer hair cells (OHCs) are fast biological motors that serve to enhance the vibration of the organ of Corti and increase the sensitivity of the inner ear to sound. Exactly how OHCs produce useful mechanical power at auditory frequencies, given their intrinsic biophysical properties, has been a subject of considerable debate. To address this we formulated a mathematical model of the OHC based on first principles and analyzed the power conversion efficiency in the frequency domain. The model includes a mixture-composite constitutive model of the active lateral wall and spatially distributed electro-mechanical fields. The analysis predicts that: 1) the peak power efficiency is likely to be tuned to a specific frequency, dependent upon OHC length, and this tuning may contribute to the place principle and frequency selectivity in the cochlea; 2) the OHC power output can be detuned and attenuated by increasing the basal conductance of the cell, a parameter likely controlled by the brain via the efferent system; and 3) power output efficiency is limited by mechanical properties of the load, thus suggesting that impedance of the organ of Corti may be matched regionally to the OHC. The high power efficiency, tuning, and efferent control of outer hair cells are the direct result of biophysical properties of the cells, thus providing the physical basis for the remarkable sensitivity and selectivity of hearing.This work was supported by NIDCD R01 DC04928 (Rabbitt), NIDCD R01 DC00384 (Brownell) and NASA Ames GSRA56000135 (Breneman)

Polar or Apolar—The Role of Polarity for Urea-Induced Protein Denaturation

Urea-induced protein denaturation is widely used to study protein folding and stability; however, the molecular mechanism and driving forces of this process are not yet fully understood. In particular, it is unclear whether either hydrophobic or polar interactions between urea molecules and residues at the protein surface drive denaturation. To address this question, here, many molecular dynamics simulations totalling ca. 7 µs of the CI2 protein in aqueous solution served to perform a computational thought experiment, in which we varied the polarity of urea. For apolar driving forces, hypopolar urea should show increased denaturation power; for polar driving forces, hyperpolar urea should be the stronger denaturant. Indeed, protein unfolding was observed in all simulations with decreased urea polarity. Hyperpolar urea, in contrast, turned out to stabilize the native state. Moreover, the differential interaction preferences between urea and the 20 amino acids turned out to be enhanced for hypopolar urea and suppressed (or even inverted) for hyperpolar urea. These results strongly suggest that apolar urea–protein interactions, and not polar interactions, are the dominant driving force for denaturation. Further, the observed interactions provide a detailed picture of the underlying molecular driving forces. Our simulations finally allowed characterization of CI2 unfolding pathways. Unfolding proceeds sequentially with alternating loss of secondary or tertiary structure. After the transition state, unfolding pathways show large structural heterogeneity

Stroke patients' utilisation of extrinsic feedback from computer-based technology in the home: a multiple case study realistic evaluation

Background Evidence indicates that post − stroke rehabilitation improves function, independence and quality of life. A key aspect of rehabilitation is the provision of appropriate information and feedback to the learner. Advances in information and communications technology (ICT) have allowed for the development of various systems to complement stroke rehabilitation that could be used in the home setting. These systems may increase the provision of rehabilitation a stroke survivor receives and carries out, as well as providing a learning platform that facilitates long-term self-managed rehabilitation and behaviour change. This paper describes the application of an innovative evaluative methodology to explore the utilisation of feedback for post-stroke upper-limb rehabilitation in the home. Methods Using the principles of realistic evaluation, this study aimed to test and refine intervention theories by exploring the complex interactions of contexts, mechanisms and outcomes that arise from technology deployment in the home. Methods included focus groups followed by multi-method case studies (n = 5) before, during and after the use of computer-based equipment. Data were analysed in relation to the context-mechanism-outcome hypotheses case by case. This was followed by a synthesis of the findings to answer the question, ‘what works for whom and in what circumstances and respects?’ Results Data analysis reveals that to achieve desired outcomes through the use of ICT, key elements of computer feedback, such as accuracy, measurability, rewarding feedback, adaptability, and knowledge of results feedback, are required to trigger the theory-driven mechanisms underpinning the intervention. In addition, the pre-existing context and the personal and environmental contexts, such as previous experience of service delivery, personal goals, trust in the technology, and social circumstances may also enable or constrain the underpinning theory-driven mechanisms. Conclusions Findings suggest that the theory-driven mechanisms underpinning the utilisation of feedback from computer-based technology for home-based upper-limb post-stroke rehabilitation are dependent on key elements of computer feedback and the personal and environmental context. The identification of these elements may therefore inform the development of technology; therapy education and the subsequent adoption of technology and a self-management paradigm; long-term self-managed rehabilitation; and importantly, improvements in the physical and psychosocial aspects of recovery

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure