Prognostic value of TP53, KRAS and EGFR mutations in nonsmall cell lung cancer : the EUELC cohort

Nonsmall cell lung cancer samples from the European Early Lung Cancer biobank were analysed to assess the prognostic significance of mutations in the TP53, KRAS and EGFR genes. The series included 11 never-smokers, 86 former smokers, 152 current smokers and one patient without informed smoking status. There were 110 squamous cell carcinomas (SCCs), 133 adenocarcinomas (ADCs) and seven large cell carcinomas or mixed histologies. Expression of p53 was analysed by immunohistochemistry. DNA was extracted from frozen tumour tissues. TP53 mutations were detected in 48.8% of cases and were more frequent among SCCs than ADCs (p<0.0001). TP53 mutation status was not associated with prognosis. G to T transversions, known to be associated with smoking, were marginally more common among patients who developed a second primary lung cancer or recurrence/metastasis (progressive disease). EGFR mutations were almost exclusively found in never-smoking females (p=0.0067). KRAS mutations were detected in 18.5% of cases, mainly ADC (p<0.0001), and showed a tendency toward association with progressive disease status. These results suggest that mutations are good markers of different aetiologies and histopathological forms of lung cancers but have little prognostic value, with the exception of KRAS mutation, which may have a prognostic value in ADC. Copyright©ERS 2012.

Where are all the female participants in sports and exercise medicine research?

The aim of this study is to estimate the ratio of male and female participants in Sports and Exercise Medicine research. Original research articles published in three major Sports and Exercise Medicine journals (Medicine and Science in Sport and Exercise, British Journal of Sports Medicine and American Journal of Sports Medicine) over a three year period were examined. Each article was screened to determine the following: total number of participants, the number of female participants and the number of male participants. The percentage of females and males per article in each of the journals was also calculated. Cross tabulations and Chi square analysis were used to compare the gender representation of participants within each of the journals. Data were extracted from 1, 382 articles involving a total of 6, 076, 705 participants. 2, 366, 998 (39%) participants were female and 3, 709, 707 (61%) male. The average percentage of female participants per article across the journals ranged from 35-37%. Females were significantly under-represented across all of the journals (X2 =23566, df=2, p<0.00001). There were no significant differences between the three journals. In conclusion, Sports and Exercise Medicine practitioners should be cognisant of sexual dimorphism and gender disparity in the current literature.

Rodent Scope: A User-Configurable Digital Wireless Telemetry System for Freely Behaving Animals

This paper describes the design and implementation of a wireless neural telemetry system that enables new experimental paradigms, such as neural recordings during rodent navigation in large outdoor environments. RoSco, short for Rodent Scope, is a small lightweight user-configurable module suitable for digital wireless recording from freely behaving small animals. Due to the digital transmission technology, RoSco has advantages over most other wireless modules of noise immunity and online user-configurable settings. RoSco digitally transmits entire neural waveforms for 14 of 16 channels at 20 kHz with 8-bit encoding which are streamed to the PC as standard USB audio packets. Up to 31 RoSco wireless modules can coexist in the same environment on non-overlapping independent channels. The design has spatial diversity reception via two antennas, which makes wireless communication resilient to fading and obstacles. In comparison with most existing wireless systems, this system has online user-selectable independent gain control of each channel in 8 factors from 500 to 32,000 times, two selectable ground references from a subset of channels, selectable channel grounding to disable noisy electrodes, and selectable bandwidth suitable for action potentials (300 Hz–3 kHz) and low frequency field potentials (4 Hz–3 kHz). Indoor and outdoor recordings taken from freely behaving rodents are shown to be comparable to a commercial wired system in sorting for neural populations. The module has low input referred noise, battery life of 1.5 hours and transmission losses of 0.1% up to a range of 10 m.

Ability of recombinant human bone morphogenetic protein 2 to enhance bone healing in the presence of tobramycin : evaluation in a rat segmental defect model

Objective To determine whether locally applied tobramycin influences the ability of recombinant human bone morphogenetic protein 2 (rhBMP-2) to heal a segmental defect in the rat femur. Methods The influence of tobramycin on the osteogenic differentiation of mesenchymal stem cells was first evaluated in vitro. For the subsequent, in vivo experiments, a 5-mm segmental defect was created in the right femur of each of 25 Sprague-Dawley rats and stabilized with an external fixator and four Kirschner wires. Rats were divided in four groups: empty control, tobramycin (11 mg)/absorbable collagen sponge, rhBMP-2 (11 μg)/absorbable collagen sponge, and rhBMP-2/absorbable collagen sponge with tobramycin. Bone healing was monitored by radiography at 3 and 8 weeks. Animals were euthanized at 8 weeks and the properties of the defect were compared with the intact contralateral femur. Bone formation in the defect region was assessed by dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing. Results Tobramycin exerted a dose-dependent inhibition of alkaline phosphatase induction and calcium deposition by mesenchymal stem cells cultured under osteogenic conditions. The inhibition was reversed in the presence of 500 ng/mL of rhBMP-2. Segmental defects in the rat femora failed to heal in the absence of rhBMP-2. Tobramycin exerted no inhibitory effects on the ability of rhBMP-2 to heal these defects and increased the bone area of the defects treated with rhBMP-2. Data obtained from all other parameters of healing, including dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing, were unaffected by tobramycin. Conclusions Although our in vitro results suggested that tobramycin inhibits the osteogenic differentiation of mesenchymal stem cells, this could be overcome by rhBMP-2. Tobramycin did not impair the ability of rhBMP-2 to heal critical-sized femoral defects in rats. Indeed, bone area was increased by nearly 20% in the rhBMP-2 group treated with tobramycin. This study shows that locally applied tobramycin can be used in conjunction with rhBMP-2 to enhance bone formation at fracture sites.

Determinants of second row passenger comfort

China is becoming an increasingly important automotive market. Customer’s vehicle usage, preferences and requirements differ from traditional western markets in a number of aspects – rear seat usage rates are higher, vehicles are used for business purposes as well as for private transport and rear seat usage is generally more important to Chinese customers compared to their western counterparts. The purpose of this project is to dimension and investigate these differences from an ergonomics perspective and use these results to guide the design of future products. The focus for this project will be specific to vehicles in the CD segment. More specifically, this project focuses on the second row ‘ambience’. Ambience refers to the global feeling perceived by second row passengers, and the main factors contributing to ambience are: ingress and egress comfort, seat comfort, roominess, and ease of use of the controls. In order to investigate the aforementioned parameters, an experimental study has been conducted in Shanghai, China. This experiment involved 80 healthy Chinese CD- and D-car customers. These subjects were asked to evaluate different features present in the second row environment of three different cars: A Ford Mondeo, Toyota Camry and Mercedes S-class. Various data has been collected during this experiment: First, the anthropometric dimensions of the subjects have been measured. The subjects were also asked to fill a questionnaire about demographics, their own car usage, and their perception of a various number of features present in the three tested cars. A great amount of technical data was also collected. The first part of this report presents the results given by the questionnaires. It includes Chinese demographics, vehicle usage habits, and the subjective perception of the features present in the tested cars. It also presents the results of the anthropometric measurements. This gives a first insight into Chinese customers’ habits and preferences. The second part deals with the technical data recorded during the experiment: second row seat adjustment ranges, roominess, optimal location of controls, and pressure mapping analysis. Analysis of technical data allows a deeper understanding of the factors contributing to comfort and ambience perception. Using the technical data together with the comfort ratings given by the subjects in the questionnaire, recommendations on several design parameters were provided. Finally, an experimental study of car ingress-egress has been conducted in a University laboratory controlled environment. During this study, the ingress and egress motion of 20 customers from Chinese origin was recorded using a motion capture system. The last part of this report presents the protocol and data processing that led to building an ingress-egress motion database that was provided to Ford.

Recovering Functional Integrity in Pastures Dominated by an Invasive Grass Species

Exotic grasses have been introduced in countries worldwide for pasture improvement, soil stabilisation and ornamental purposes. Some of these introductions have proven successful, but many have not (Cook & Dias 2006). In Australia, the Commonwealth Plant Introduction Scheme was initiated in 1929, and over-time introduced more than 5000 species of grasses, legumes and other forage and browse plants (Cook & Dias 2006). Lonsdale (1994) suggested that, in tropical Australia, 13% of introductions have become a problem, with only 5% being considered useful for agriculture. Low (1997) suggested that 5 out of 18 of Australia's worst tropical environmental weeds were intentionally introduced as pasture grasses. The spread and dominance of invasive grass species that degrade the quality of pastures for production can impact significantly on the livelihoods of small proprietors. Although Livestock grazing contributes only a small percentage to the world's GDP (1.5%), maintaining the long-term stability of this industry is crucial because of the high social and environmental consequence of a collapse. One billion of the world's poor are dependent on livestock grazing for food and income with this industry occupying more than 25% of the world's land base (Steinfeld et al. 2006). The ling-term sustainability of livestock grazing is also crucial for the environment. A recent FAO report attributed livestock production as a major cause of five of the most serious environmental problems: global warming, land degredation, air and water pollution, and the loss of biodiversity (Steinfeld et al. 2006). For these reasons, finding more effective approaches that guide the sustainable management of pastures is urgently needed. In Australia more than 55% of land use is for livestock grazing by sheelp and/or cattle. This land use dominate in the semi-arid and arid regions where rainfall and soil conditions are marginal for production (Commonwealth of Australia 2004). Although the level of agriculture production by conglomerates is increasing, the majority of livestock grazing within Australia remains family owned and operated (Commonwealth of Australia 2004). The sustainability of production from a grazed pasture is dependent on its botanical composition (Kemp & Dowling 1991, Kemp et al. 1996). In a grazed pasture, the dominance of an invasive grass species can impact on the functional integrity of the ecosystem, including production and nutrient cycling; wwhich will in turn, affect the income of proprietors and the ability of the system to recover from disturbance and environmental change. In Australia, $0.3 billion is spent on weed control in livestock production, but despite this substantial investment $1.9 billion is still lost in yield as a result of weeds (Sinden et al. 2004). In this paper, we adaprt a framework proposed for the restoration of degraded rainforest communities (Lamb & Gilmour 2003, Lamb et al. 2005) to compare and contrast options for recovering function integrity (i.e. a diverse set of desirable plant species that maintain key ecological processes necessary for sustainable production and nutrient cycling) within pasture communities dominated by an invasive grass species. To do this, we uase a case-study of the invasion of Eragrostis curvula (Africal lovegrss; hereafter, Lovegrass), a serious concern in Australian agricultural communities (Parsons and Cuthbertson 1992). The spread and dominance of Lovegrass is a problem because its low palatability, low nutritional content and competitiveness affect the livelihood of graziers by reducing the diversity of other plant species. We conclude by suggesting modifications to this framework for pasture ecosystems to help increase the effiency of strategies to protect functional integrity and balance social/economic and biodiversity values.

A comparative analysis of relevant crop carbon footprint calculators, with reference to cotton production in Australia

An increasing concern over the sustainability credentials of food and fiber crops require that farmers and their supply chain partners have access to appropriate and industry-friendly tools to be able to measure and improve the outcomes. This article focuses on one of the sustainability indicators, namely, greenhouse gas (GHG) emissions, and nine internationally accredited carbon footprint calculators were identified and compared on an outcomes basis against the same cropping data from a case study cotton farm. The purpose of this article is to identify the most “appropriate” methodology to be applied by cotton suppliers in this regard. From the analysis of the results, we subsequently propose a new integrated model as the basis for an internationally accredited carbon footprint tool for cotton and show how the model can be applied to evaluate the emission outcomes of different farming practices.

Computational micromodel for epigenetic mechanisms

Characterization of the epigenetic profile of humans since the initial breakthrough on the human genome project has strongly established the key role of histone modifications and DNA methylation. These dynamic elements interact to determine the normal level of expression or methylation status of the constituent genes in the genome. Recently, considerable evidence has been put forward to demonstrate that environmental stress implicitly alters epigenetic patterns causing imbalance that can lead to cancer initiation. This chain of consequences has motivated attempts to computationally model the influence of histone modification and DNA methylation in gene expression and investigate their intrinsic interdependency. In this paper, we explore the relation between DNA methylation and transcription and characterize in detail the histone modifications for specific DNA methylation levels using a stochastic approach.

The ADMIN-ICU survey: A survey on antimicrobial dosing and monitoring in ICUs

Objectives: There is little evidence and few guidelines to inform the most appropriate dosing and monitoring for antimicrobials in the ICU. We aimed to survey current practices around the world. Methods: An online structured questionnaire was developed and sent by e-mail to obtain information on local antimicrobial prescribing practices for glycopeptides, piperacillin/tazobactam, carbapenems, aminoglycosides and colistin. Results: A total of 402 professionals from 328 hospitals in 53 countries responded, of whom 78% were specialists in intensive care medicine (41% intensive care, 30% anaesthesiology, 14% internal medicine) and 12% were pharmacists. Vancomycin was used as a continuous infusion in 31% of units at a median (IQR) daily dose of 25 (25–30) mg/kg. Piperacillin/tazobactam was used as an extended infusion by 22% and as a continuous infusion by 7%. An extended infusion of carbapenem (meropenem or imipenem) was used by 27% and a continuous infusion by 5%. Colistin was used at a daily dose of 7.5 (3.9–9) million IU (MIU)/day, predominantly as a short infusion. The most commonly used aminoglycosides were gentamicin (55%) followed by amikacin (40%), with administration as a single daily dose reported in 94% of the cases. Gentamicin was used at a daily dose of 5 (5–6) mg/day and amikacin at a daily dose of 15 (15–20) mg/day. Therapeutic drug monitoring of vancomycin, piperacillin/tazobactam and meropenem was used by 74%, 1% and 2% of the respondents, respectively. Peak aminoglycoside concentrations were sampled daily by 28% and trough concentrations in all patients by 61% of the respondents. Conclusions: We found wide variability in reported practices for antibiotic dosing and monitoring. Research is required to develop evidence-based guidelines to standardize practices.

Diet-induced hypercholesterolemia promotes androgen-independent prostate cancer metastasis via IQGAP1 and caveolin-1

Obesity and metabolic syndrome are associated with several cancers, however, the molecular mechanisms remain to be fully elucidated. Recent studies suggest that hypercholesterolemia increases intratumoral androgen signaling in prostate cancer, but it is unclear whether androgenindependent mechanisms also exist. Since hypercholesterolemia is associated with advanced, castrate-resistant prostate cancer, in this study, we aimed to determine whether and how hypercholesterolemia affects prostate cancer progression in the absence of androgen signaling. We demonstrate that diet-induced hypercholesterolemia promotes orthotopic xenograft PC-3 cell metastasis, concomitant with elevated expression of caveolin-1 and IQGAP1 in xenograft tumor tissues. In vitro cholesterol treatment of PC-3 cells stimulated migration and increased IQGAP1 and caveolin-1 protein level and localization to a detergent-resistant fraction. Down-regulation of caveolin-1 or IQGAP1 in PC-3 cells reduced migration and invasion in vitro, and hypercholesterolemia-induced metastasis in vivo. Double knock-down of caveolin-1 and IQGAP1 showed no additive effect, suggesting that caveolin-1 and IQGAP1 act via the same pathway. Taken together, our data show that hypercholesterolemia promotes prostate cancer metastasis independent of the androgen pathway, in part by increasing IQGAP1 and caveolin-1. These results have broader implications for managing metastasis of cancers in general as IQGAP1 and hypercholesterolemia are implicated in the progression of several cancers.

General properties of electrochemical capacitors

The use of capacitors for electrical energy storage actually predates the invention of the battery. Alessandro Volta is attributed with the invention of the battery in 1800, where he first describes a battery as an assembly of plates of two different materials (such as copper and zinc) placed in an alternating stack and separated by paper soaked in brine or vinegar [1]. Accordingly, this device was referred to as Volta’s pile and formed the basis of subsequent revolutionary research and discoveries on the chemical origin of electricity. Before the advent of Volta’s pile, however, eighteenth century researchers relied on the use of Leyden jars as a source of electrical energy. Built in the mid-1700s at the University of Leyden in Holland, a Leyden jar is an early capacitor consisting of a glass jar coated inside and outside with a thin layer of silver foil [2, 3]. With the outer foil being grounded, the inner foil could be charged with an electrostatic generator, or a source of static electricity, and could produce a strong electrical discharge from a small and comparatively simple device.

Heat acclimation for protection from exertional heat stress (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of heat acclimation interventions aimed at protecting health and performance from exertional heat stress.

Cochrane review: Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults

Delayed-onset muscle soreness, or ‘DOMS’, affects many people after exercise and can impair future performance. It usually peaks one to four days after exercise and several strategies are used to overcome it. The effectiveness and safety of many of these strategies applied and promoted is unknown.

Rigorous scaling law for the heat current in disordered harmonic chain

We study the energy current in a model of heat conduction, first considered in detail by Casher and Lebowitz. The model consists of a one-dimensional disordered harmonic chain of n i.i.d. random masses, connected to their nearest neighbors via identical springs, and coupled at the boundaries to Langevin heat baths, with respective temperatures T_1 and T_n. Let EJ_n be the steady-state energy current across the chain, averaged over the masses. We prove that EJ_n \sim (T_1 - T_n)n^{-3/2} in the limit n \to \infty, as has been conjectured by various authors over the time. The proof relies on a new explicit representation for the elements of the product of associated transfer matrices.