Modifications of Gait as Predictors of Natural Osteoarthritis Progression in STR/Ort Mice

OBJECTIVE: Osteoarthritis (OA) is a common chronic disease for which disease-modifying therapies are not currently available. Studies to seek new targets for slowing the progress of OA rely on mouse models, but these do not allow for longitudinal monitoring of disease development. This study was undertaken to determine whether gait can be used to measure disease severity in the STR/Ort mouse model of spontaneous OA and whether gait changes are related to OA joint pain. METHODS: Gait was monitored using a treadmill-based video system. Correlations between OA severity and gait at 3 treadmill speeds were assessed in STR/Ort mice. Gait and pain behaviors of STR/Ort mice and control CBA mice were analyzed longitudinally, with monthly assessments. RESULTS: The best speed to identify paw area changes associated with OA severity in STR/Ort mice was found to be 17 cm · seconds(−1). Paw area was modified with age in CBA and STR/Ort mice, but this began earlier in STR/Ort mice and correlated with the onset of OA at 20 weeks of age. In addition, task noncompliance appeared at 20 weeks. Surprisingly, STR/Ort mice did not show any signs of pain with OA development, even when treated with the opioid antagonist naloxone, but did exhibit normal pain behaviors in response to complete Freund's adjuvant–induced arthritis. CONCLUSION: The present results identify an animal model in which OA severity and OA pain can be studied in isolation from one another. The findings suggest that paw area and treadmill noncompliance may be useful tools to longitudinally monitor nonpainful OA development in STR/Ort mice. This will help in providing a noninvasive means of assessing new therapies to slow the progression of OA

Improvement of Bioenergetics Model Predictions for Fish Undergoing Compensatory Growth

A previous evaluation of a bioenergetics model applied to juvenile hybrid sunfish (F1 hybrid of female green sunfish Lepomis cyanellus × male bluegill L. macrochirus) undergoing compensatory growth (CG) indicated that the model substantially overestimated growth and underestimated cumulative consumption. This result suggested that fish bioenergetics models might not adequately account for physiological shifts that occur during CG. However, we demonstrate that application of a recently developed procedure for correcting consumption- and growth-rate-dependent systematic errors common among bioenergetics models negates much of the predictive error that had been attributed to the physiological complexities of CG. Correction equations for estimating the model-relative growth rate error (predicted less observed; g · g−1 · d−1) from the observed mean daily consumption rate (g · g−1 · d−1) and the consumption rate error (predicted less observed; g · g−1 · d−1) from the observed relative growth rate (g · g−1 · d−1) were derived by applying linear regression analysis to data from individual hybrid sunfish not undergoing CG. These independently generated correction equations significantly improved model predictions of growth and cumulative consumption for three groups of fish undergoing CG at one temperature near their growth optimum. The findings indicate that the high consumption and growth rates characteristic of fish undergoing CG merely amplify the consumption- and growth-rate-dependent errors inherent in bioenergetics models and that model predictions for fish undergoing CG can be significantly improved through application of the correction procedure

The golden circle: A way of arguing and acting about technology in the London ambulance service

This paper analyses the way in which the London Ambulance Service recovered from the events of October 1992, when it implemented a computer-aided despatch system (LASCAD) that remained in service for less than two weeks. It examines the enactment of a programme of long-term organizational change, focusing on the implementation of an alternative computer system in 1996. The analysis in this paper is informed by actor-network theory, both by an early statement of this approach developed by Callon in the sociology of translation, and also by concepts and ideas from Latour’s more recent restatement of his own position. The paper examines how alternative interests emerged and were stabilized over time, in a way of arguing and acting among key players in the change programme, christened the Golden Circle. The story traces four years in the history of the London Ambulance Service, from the aftermath of October 1992 through the birth of the Golden Circle to the achievement of National Health Service (NHS) trust status. LASCAD was the beginning of the story, this is the middle, an end lies in the future, when the remaining elements of the change programme are enacted beyond the Golden Circle

Technique for producing highly planar Si/SiO0.64Ge0.36/Si metal–oxide–semiconductor field effect transistor channels

Si/Si0.64Ge0.36/Si heterostructures have been grown at low temperature (450 °C) to avoid the strain-induced roughening observed for growth temperatures of 550 °C and above. The electrical properties of these structures are poor, and thought to be associated with grown-in point defects as indicated in positron annihilation spectroscopy. However, after an in situ annealing procedure (800 °C for 30 min) the electrical properties dramatically improve, giving an optimum 4 K mobility of 2500 cm2 V – 1 s – 1 for a sheet density of 6.2 × 1011 cm – 2. The low temperature growth yields highly planar interfaces, which are maintained after anneal as evidenced from transmission electron microscopy. This and secondary ion mass spectroscopy measurements demonstrate that the metastably strained alloy layer can endure the in situ anneal procedure necessary for enhanced electrical properties. Further studies have shown that the layers can also withstand a 120 min thermal oxidation at 800 °C, commensurate with metal–oxide–semiconductor device fabrication

Identification of shared and disease-specific host gene–microbiome associations across human diseases using multi-omic integration

While gut microbiome and host gene regulation independently contribute to gastrointestinal disorders, it is unclear how the two may interact to influence host pathophysiology. Here we developed a machine learning-based framework to jointly analyse paired host transcriptomic (n = 208) and gut microbiome (n = 208) profiles from colonic mucosal samples of patients with colorectal cancer, inflammatory bowel disease and irritable bowel syndrome. We identified associations between gut microbes and host genes that depict shared as well as disease-specific patterns. We found that a common set of host genes and pathways implicated in gastrointestinal inflammation, gut barrier protection and energy metabolism are associated with disease-specific gut microbes. Additionally, we also found that mucosal gut microbes that have been implicated in all three diseases, such as Streptococcus, are associated with different host pathways in each disease, suggesting that similar microbes can affect host pathophysiology in a disease-specific manner through regulation of different host genes. Our framework can be applied to other diseases for the identification of host gene–microbiome associations that may influence disease outcomes

Preparing to work: dramaturgy, cynicism and normative ‘remote’ control in the socialization of graduate recruits in management consulting

online) This paper examines the socialization of graduate recruits into a knowledge intensive labour process and organizational culture. Theoretically the paper draws upon the idea of ‘preparing for work’ to position this early socialization as a crucial moment in the production of subjectivities suited (and booted) for the labour process of management consulting. Empirically the paper reports on a two-day induction session for new graduate recruits joining a global management consultancy and their responses to this training. Particular attention is given to the use of role-play and a dramaturgical workshop used in part of the training process. The paper argues that the utilization of dramaturgy in training is consistent with the overall approach to control developed in the firm in response to the fact that the labour process of consulting is often conducted on client sites, away from any direct supervisory gaze. As such, the consultants were subjected to a form of cultural control that was designed to function independently of direct supervision. This control did not operate directly upon the new employees professed values, however, but at one step removed so that a ‘cynical distance’ from the content of the organization’s culture was accepted so long as a professional ‘ethic of behaviour’ was established. By focusing on an ‘ethic of behaviour’ these young professionals were encouraged to internalize a self-control akin to that of an actor, rather than internalizing the corporate values entirely

Greening of grey infrastructure should not be used as a Trojan horse to facilitate coastal development

Climate change and coastal urbanization are driving the replacement of natural habitats with artificial structures and reclaimed land globally. These novel habitats are often poor surrogates for natural habitats. The application of integrated greening of grey infrastructure (IGGI) to artificial shorelines demonstrates how multifunctional structures can provide biodiversity benefits whilst simultaneously serving their primary engineering function. IGGI is being embraced globally, despite many knowledge gaps and limitations. It is a management tool to compensate anthropogenic impacts as part of the Mitigation Hierarchy. There is considerable scope for misuse and ‘greenwashing’ however, by making new developments appear more acceptable, thus facilitating the regulatory process. We encourage researchers to exercise caution when reporting on small-scale experimental trials. We advocate that greater attention is paid to when experiments ‘fail’ or yield unintended outcomes. We advise revisiting, repeating and expanding on experiments to test responses over broader spatio-temporal scales to improve the evidence base. Synthesis and applications. Where societal and economic demand makes development inevitable, particular attention should be paid to avoiding, minimizing and rehabilitating environmental impacts. Integrated greening of grey infrastructure (IGGI) should be implemented as partial compensation for environmental damage. Mutual benefits for both humans and nature can be achieved when IGGI is implemented retrospectively in previously developed or degraded environments. We caution, however, that any promise of net biodiversity gain from new developments should be scrutinized and any local ecological benefits set in the context of the wider environmental impacts. A ‘greened’ development will always impinge on natural systems, a reality that is much less recognized in the sea than on land.</p

Creative writing in A level English literature

This is an Author's Accepted Manuscript of an article published in New Writing: The International Journal for the Practice and Theory of Creative Writing, 6(3), 187 - 195, 2009, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/14790720903556155.This is a time of change and real development for creative writing at A level. Whilst it has been an important part of English Language and English Language & Literature A level specifications for some time, its presence within English Literature has been marginal, and is an option that has rarely been adopted by teachers of the subject. Recent changes to English Literature specifications, however, mean that creative writing (along with recreative and transformative writing) now exists in a much more formalised way on all A level English Literature specifications. As the largest of the three A level Englishes, this is a significant development. The advent of creative writing in English Literature makes this an important issue in teachers' Continuing Professional Development (Green, 2008) and raises important questions for the teaching body in schools and lecturers in further education. What is the role of creative writing in teaching literature? How do creative and analytical writing relate to each other? What is the relationship between creative writing and reading? This paper offers an initial response to these and other issues, and suggests some of the ways in which creative writing can be used both in its own right and to enhance the study of English Literature at A level

Experimental determination of proton hardness factors at several irradiation facilities

The effort to characterise detector sensors and components for the High Luminosity upgrade of the CERN Large Hadron Collider requires collaboration between irradiation facilities around the world. By convention, the radiation damage following irradiation with particle beams is reported as the 1 MeV neutron equivalent fluence, obtained using the corresponding hardness factor. Measurements of proton hardness factors at three different kinetic energies are presented, by characterisation of commercially available diodes before and after irradiation, using irradiations at the University of Birmingham, the Karlsruhe Institute of Technology, and CERN. Possible future improvements to these measurements are also discussed