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

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

Discrete Mutations in Colorectal Cancer Correlate with Defined Microbial Communities in the Tumor Microenvironment

Variation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetics. However, we do not know whether genetic mutations in CRC tumors interact with the structure and composition of the microbial communities surrounding the tumors, and if so, whether changes in the microbiome can be used as a predictor for tumor mutational status. Here, we characterized the association between CRC tumor mutational landscape and its proximal microbial communities by performing whole exome sequencing and microbiome profiling in tumors and normal colorectal tissue samples from the same patient. We find a significant association between loss of function mutations in relevant tumor genes and pathways and shifts in the abundances of specific sets of bacterial taxa. In addition, by constructing a risk index classifier from these sets of microbes, we accurately predict the existence of loss of function mutations in cancer related genes and pathways, including MAPK and Wnt signaling, solely based on the composition of the microbiota. These results can serve as a starting point for understanding the interactions between host genetic alterations and proximal microbial communities in CRC, as well as for the development of individualized microbiota targeted therapies

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

Electron and hole mobility reduction and Hall factor in phosphorus-compensated p-type silicon

The conductivity mobility for majority carrier holes in compensated p-type silicon is determined by combined measurement of the resistivity and the net doping, the latter via electrochemical capacitance-voltage measurements. The minority electron mobility was also measured with a technique based on measurements of surface-limited effective carrier lifetimes. While both minority and majority carrier mobilities are found to be significantly reduced by compensation, the impact is greater on the minority electron mobility. The Hall factor, which relates the Hall mobility to the conductivity mobility, has also been determined using the Hall method combined with the capacitance-voltage measurements. Our results indicate a similar Hall factor in both compensated and noncompensated samples.This work was supported by the Australian Research Council ARC and by the DAAD/Go8 researcher exchange funding scheme

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

Temporal Relationships Exist Between Cecum, Ileum, and Litter Bacterial Microbiomes in a Commercial Turkey Flock, and Subtherapeutic Penicillin Treatment Impacts Ileum Bacterial Community Establishment

Gut health is paramount for commercial poultry production, and improved methods to assess gut health are critically needed to better understand how the avian gastrointestinal tract matures over time. One important aspect of gut health is the totality of bacterial populations inhabiting different sites of the avian gastrointestinal tract, and associations of these populations with the poultry farm environment, since these bacteria are thought to drive metabolism and prime the developing host immune system. In this study, a single flock of commercial turkeys was followed over the course of twelve weeks to examine bacterial microbiome inhabiting the ceca, ileum, and corresponding poultry litter. Furthermore, the effects of low-dose, growth-promoting penicillin treatment (50 g/ton) in feed on the ileum bacterial microbiome were also examined during the early brood period. The cecum and ileum bacterial communities of turkeys were distinct, yet shifted in parallel to one another over time during bird maturation. Corresponding poultry litter was also distinct yet more closely represented the ileal bacterial populations than cecal bacterial populations, and also changed parallel to ileum bacterial populations over time. Penicillin applied at low dose in feed significantly enhanced early weight gain in commercial poults, and this correlated with predictable shifts in the ileum bacterial populations in control versus treatment groups. Overall, this study identified the dynamics of the turkey gastrointestinal microbiome during development, correlations between bacterial populations in the gastrointestinal tract and the litter environment, and the impact of low-dose penicillin on modulation of bacterial communities in the ileum. Such modulations provide a target for alternatives to low-dose antibiotics