Intravenous injection of leconotide, an omega conotoxin : synergistic antihyperalgesic effects with morphine in a rat model of bone cancer pain

Objective.  Leconotide (CVID, AM336, CNSB004) is an omega conopeptide similar to ziconotide, which blocks voltage sensitive calcium channels. However, unlike ziconotide, which must be administered intrathecally, leconotide can be given intravenously because it is less toxic. This study investigated the antihyperalgesic potency of leconotide given intravenously alone and in combinations with morphine-administered intraperitoneally, in a rat model of bone cancer pain. Design.  Syngeneic rat prostate cancer cells AT3B-1 were injected into one tibia of male Wistar rats. The tumor expanded within the bone causing hyperalgesia to heat applied to the ipsilateral hind paw. Measurements were made of the maximum dose (MD) of morphine and leconotide given alone and in combinations that caused no effect in an open-field activity monitor, rotarod, and blood pressure and heart rate measurements. Paw withdrawal thresholds from noxious heat were measured. Dose response curves for morphine (0.312–5.0 mg/kg intraperitoneal) and leconotide (0.002–200 µg/kg intravenous) given alone were plotted and responses compared with those caused by morphine and leconotide in combinations. Results.  Leconotide caused minimal antihyperalgesic effects when administered alone. Morphine given alone intraperitoneally caused dose-related antihyperalgesic effects (ED50 = 2.40 ± 1.24 mg/kg), which were increased by coadministration of leconotide 20 µg/kg (morphine ED50 = 0.16 ± 1.30 mg/kg); 0.2 µg/kg (morphine ED50 = 0.39 ± 1.27 mg/kg); and 0.02 µg/kg (morphine ED50 = 1.24 ± 1.30 mg/kg). Conclusions.  Leconotide caused a significant increase in reversal by morphine of the bone cancer-induced hyperalgesia without increasing the side effect profile of either drug. Clinical Implication.  Translation into clinical practice of the method of analgesia described here will improve the quantity and quality of analgesia in patients with bone metastases. The use of an ordinary parenteral route for administration of the calcium channel blocker (leconotide) at low dose opens up the technique to large numbers of patients who could not have an intrathecal catheter for drug administration. Furthermore, the potentiating synergistic effect with morphine on hyperalgesia without increased side effects will lead to greater analgesia with improved quality of life.

Running shoes increase Achilles tendon load in walking : an acoustic propagation study

Background: Footwear remains a prime candidate for the prevention and rehabilitation of Achilles tendinopathy as it is thought to decrease tension in the tendon through elevation of the heel. However, evidence for this effect is equivocal. Purpose: This study used an acoustic transmission technique to investigate the effect of running shoes on Achilles tendon loading during barefoot and shod walking. Methods: Acoustic velocity was measured in the Achilles tendon of twelve recreationally–active males (age, 31±9 years; height, 1.78±0.06 m; weight, 81.0±16.9 kg) during barefoot and shod walking at matched self–selected speed (3.4±0.7 km/h). Standard running shoes incorporating a 10– mm heel offset were used. Vertical ground reaction force and spatiotemporal parameters were determined with an instrumented treadmill. Axial acoustic velocity in the Achilles tendon was measured using a custom built ultrasonic device. All data were acquired at a rate of 100 Hz during 10s of steady–state walking. Statistical comparisons between barefoot and shod conditions were made using paired t–tests and repeated measure ANOVAs. Results: Acoustic velocity in the Achilles tendon was highly reproducible and was typified by two maxima (P1, P2) and minima (M1, M2) during walking. Footwear resulted in a significant increase in step length, stance duration and peak vertical ground reaction force compared to barefoot walking. Peak acoustic velocity in the Achilles tendon (P1, P2) was significantly higher with running shoes. Conclusions: Peak acoustic velocity in the Achilles tendon was higher with footwear, suggesting that standard running shoes with a 10–mm heel offset increase tensile load in the Achilles tendon. Although further research is required, these findings question the therapeutic role of standard running shoes in Achilles tendinopathy.

Clothing Cultures, Volume 3, Issue 3

Tiziana Ferrero-Regis, guest editor of Vol. 1, issue 3, of Intellect journal Clothing Cultures. "Welcome to the third issue of Clothing Cultures. We are honoured to have served as the guest editors for this issue. The authors in this issue explore three intersecting themes in using various methods: identity, cross-cultural encounters and everyday practices related to designing, branding and wearing clothing. These themes are at the core of fashion and dress: as an everyday individual and social project, and as a system in which people and objects (clothing) globally circulate. The performance of identity (Goffman 1979; Butler 1990), social practices and the movement of people and commodities (Appadurai 1986, 1996) create and transfer cultural meanings..."

Gray matter deficits, mismatch negativity, and outcomes in schizophrenia

Reduced mismatch negativity (MMN) in response to auditory change is a well-established finding in schizophrenia and has been shown to be correlated with impaired daily functioning, rather than with hallmark signs and symptoms of the disorder. In this study, we investigated (1) whether the relationship between reduced MMN and impaired daily functioning is mediated by cortical volume loss in temporal and frontal brain regions in schizophrenia and (2) whether this relationship varies with the type of auditory deviant generating MMN. MMN in response to duration, frequency, and intensity deviants was recorded from 18 schizophrenia subjects and 18 pairwise age- and gender-matched healthy subjects. Patients’ levels of global functioning were rated on the Social and Occupational Functioning Assessment Scale. High-resolution structural magnetic resonance scans were acquired to generate average cerebral cortex and temporal lobe models using cortical pattern matching. This technique allows accurate statistical comparison and averaging of cortical measures across subjects, despite wide variations in gyral patterns. MMN amplitude was reduced in schizophrenia patients and correlated with their impaired day-to-day function level. Only in patients, bilateral gray matter reduction in Heschl’s gyrus, as well as motor and executive regions of the frontal cortex, correlated with reduced MMN amplitude in response to frequency deviants, while reduced gray matter in right Heschl’s gyrus also correlated with reduced MMN to duration deviants. Our findings further support the importance of MMN reduction in schizophrenia by linking frontotemporal cerebral gray matter pathology to an automatically generated event-related potential index of daily functioning.

Numerical studies on CFRP strengthened steel columns under transverse impact

Strengthening of metallic structures using carbon fibre reinforced polymer (CFRP) has become a smart strengthening option over the conventional strengthening method. Transverse impact loading due to accidental vehicular collision can lead to the failure of existing steel hollow tubular columns. However, knowledge is very limited on the behaviour of CFRP strengthened steel members under dynamic impact loading condition. This paper deals with the numerical simulation of CFRP strengthened square hollow section (SHS) steel columns under transverse impact loading to predict the behaviour and failure modes. The transverse impact loading is simulated using finite element (FE) analysis based on numerical approach. The accuracy of the FE modelling is ensured by comparing the predicted results with available experimental tests. The effects of impact velocity, impact mass, support condition, axial loading and CFRP thickness are examined through detail parametric study. The impact simulation results indicate that the strengthening technique shows an improved impact resistance capacity by reducing lateral displacement of the strengthened column about 58% compared to the bare steel column. Axial loading plays an important role on the failure behaviour of tubular column.

Emerging Planning Frameworks for Climate Adaptation

This chapter focuses on the more strategic activities that lead people in the regional community to decide how they want to respond to climate change. Such strategic activities include analysing, prioritising and deciding upon the best course of action. Planning for climate adaptation (usually seen to include the setting of visions and objectives, the determination of key strategies and the monitoring of broad outcomes) encompasses the strategic activities involved in the system of governance for climate adaptation. Planning occurs at all scales from global to the business, property, family and even individual scales. Applying a rapid appraisal technique, this chapter analyses the system of planning for climate adaptation as it relates to the achievement of adaptation outcomes within the Wet Tropics Cluster. It finds that some aspects of the system are healthier than others, and identifies several actions that regional NRM bodies may consider (either collectively or individually) to enhance adaptation outcomes by improving the planning system within the cluster.

Head-of-bed elevation improves end-expiratory lung volumes in mechanically ventilated subjects : a prospective observational study

BACKGROUND: Head-of-bed elevation (HOBE) has been shown to assist in reducing respiratory complications associated with mechanical ventilation; however, there is minimal research describing changes in end-expiratory lung volume. This study aims to investigate changes in end-expiratory lung volume in a supine position and 2 levels of HOBE. METHODS: Twenty postoperative cardiac surgery subjects were examined using electrical impedance tomography. End-expiratory lung impedance (EELI) was recorded as a surrogate measurement of end-expiratory lung volume in a supine position and at 20° and then 30°. RESULTS: Significant increases in end-expiratory lung volume were seen at both 20° and 30° HOBE in all lung regions, except the anterior, with the largest changes from baseline (supine) seen at 30°. From baseline to 30° HOBE, global EELI increased by 1,327 impedance units (95% CI 1,080–1,573, P < .001). EELI increased by 1,007 units (95% CI 880–1,134, P < .001) in the left lung region and by 320 impedance units (95% CI 188–451, P < .001) in the right lung. Posterior increases of 1,544 impedance units (95% CI 1,405–1,682, P < .001) were also seen. EELI decreased anteriorly, with the largest decreases occurring at 30° (−335 impedance units, 95% CI −486 to −183, P < .001). CONCLUSIONS: HOBE significantly increases global and regional end-expiratory lung volume; therefore, unless contraindicated, all mechanically ventilated patients should be positioned with HOBE.

Calibration of treatment time intensity modulated EPID images for anatomical imaging

Intensity Modulated Radiotherapy (IMRT) is a well established technique for delivering highly conformal radiation dose distributions. The complexity of the delivery techniques and high dose gradients around the target volume make verification of the patient treatment crucial to the success of the treatment. Conventional treatment protocols involve imaging the patient prior to treatment, comparing the patient set-up to the planned set-up and then making any necessary shifts in the patient position to ensure target volume coverage. This paper presents a method for calibrating electronic portal imaging device (EPID) images acquired during IMRT delivery so that they can be used for verifying the patient set-up.

Urban Form at the Edge : Proceedings from ISUF 2013 [Volume 1]

Urban morphology as a field of study has developed primarily in Europe and North America, and more recently emerging as a recurrent topic in China and South America. As a counterpoint to this centric view, the ISUF 2013 conference explored aspects of ‘urban form at the edge’. In particular the conference examined ‘off centre areas’ such as India, Africa, Middle East, Central Asia and Australasia which require innovative approaches to the study of traditional, as well as post-colonial and contemporary, morphologies. Broader interpretations of urban form at the edge focus on minor centres and suburbia, with their developing and transilient character; edge cities and regional centres; and new technologies and approaches that are developing alongside established methods, tools and theories of urban morphology...

Magnetic resonance imaging: An accurate, radiation-free, alternative to computed tomography for the primary imaging and three-dimensional reconstruction of the bony orbit

Purpose: To determine the extent to which the accuracy of magnetic resonance imaging (MRI) based virtual 3-dimensional (3D) models of the intact orbit can approach that of the gold standard, computed tomography (CT) based models. The goal was to determine whether MRI is a viable alternative to CT scans in patients with isolated orbital fractures and penetrating eye injuries, pediatric patients, and patients requiring multiple scans in whom radiation exposure is ideally limited. Materials and Methods: Patients who presented with unilateral orbital fractures to the Royal Brisbane and Women’s Hospital from March 2011 to March 2012 were recruited to participate in this cross-sectional study. The primary predictor variable was the imaging technique (MRI vs CT). The outcome measurements were orbital volume (primary outcome) and geometric intraorbital surface deviations (secondary outcome)between the MRI- and CT-based 3D models. Results: Eleven subjects (9 male) were enrolled. The patients’ mean age was 30 years. On average, the MRI models underestimated the orbital volume of the CT models by 0.50 0.19 cm3 . The average intraorbital surface deviation between the MRI and CT models was 0.34 0.32 mm, with 78 2.7% of the surface within a tolerance of 0.5 mm. Conclusions: The volumetric differences of the MRI models are comparable to reported results from CT models. The intraorbital MRI surface deviations are smaller than the accepted tolerance for orbital surgical reconstructions. Therefore, the authors believe that MRI is an accurate radiation-free alternative to CT for the primary imaging and 3D reconstruction of the bony orbit. �