A statistical evaluation of the effects of gender differences in assessment of acute inhalation toxicity

Acute inhalation toxicity of chemicals has conventionally been assessed by the median lethal concentration (LC50) test (organisation for economic co-operation and development (OECD) TG 403). Two new methods, the recently adopted acute toxic class method (ATC; OECD TG 436) and a proposed fixed concentration procedure (FCP), have recently been considered, but statistical evaluations of these methods did not investigate the influence of differential sensitivity between male and female rats on the outcomes. This paper presents an analysis of data from the assessment of acute inhalation toxicity for 56 substances. Statistically significant differences between the LC50 for males and females were found for 16 substances, with greater than 10-fold differences in the LC50 for two substances. The paper also reports a statistical evaluation of the three test methods in the presence of unanticipated gender differences. With TG 403, a gender difference leads to a slightly greater chance of under-classification. This is also the case for the ATC method, but more pronounced than for TG 403, with misclassification of nearly all substances from Globally Harmonised System (GHS) class 3 into class 4. As the FCP uses females only, if females are more sensitive, the classification is unchanged. If males are more sensitive, the procedure may lead to under-classification. Additional research on modification of the FCP is thus proposed

A cluster randomised controlled trial of the efficacy of a brief walking intervention delivered in primary care : study protocol

Background: The aim of the present research is to conduct a fully powered explanatory trial to evaluate the efficacy of a brief self-regulation intervention to increase walking. The intervention will be delivered in primary care by practice nurses (PNs) and Healthcare Assistants (HCAs) to patients for whom increasing physical activity is a particular priority. The intervention has previously demonstrated efficacy with a volunteer population, and subsequently went through an iterative process of refinement in primary care, to maximise acceptability to both providers and recipients. Methods/ Design: This two arm cluster randomised controlled trial set in UK general practices will compare two strategies for increasing walking, assessed by pedometer, over six months. Patients attending practices randomised to the self-regulation intervention arm will receive an intervention consisting of behaviour change techniques designed to increase walking self-efficacy (confidence in ability to perform the behaviour), and to help people translate their “good” intentions into behaviour change by making plans. Patients attending practices randomised to the information provision arm will receive written materials promoting walking, and a short unstructured discussion about increasing their walking. The trial will recruit 20 PN/HCAs (10 per arm), who will be trained by the research team to deliver the selfregulation intervention or information provision control intervention, to 400 patients registered at their practices (20 patients per PN/HCA). This will provide 85% power to detect a mean difference of five minutes/day walking between the self-regulation intervention group and the information provision control group. Secondary outcomes include health services costs, and intervention effects in sub-groups defined by age, ethnicity, gender, socioeconomic status, and clinical condition. A mediation analysis will investigate the extent to which changes in constructs specified by the Theory of Planned Behaviour lead to changes in objectively assessed walking behaviour. Discussion: This trial addresses the current lack of evidence for interventions that are effective at increasing walking and that can be offered to patients in primary care. The intervention being evaluated has demonstrated efficacy, and has been through an extensive process of adaptation to ensure acceptability to both provider and recipient, thus optimising fidelity of intervention delivery and treatment receipt. It therefore provides a strong test of the hypothesis that a self-regulation intervention can help primary care patients increase their walking

A new sighting study for the fixed concentration procedure to allow for gender differences

The fixed concentration procedure (FCP) has been proposed as an alternative to the median lethal concentration (LC50) test (organisation for economic co-operation and development (OECD) test guideline [TG] 403) for the assessment of acute inhalation toxicity. The FCP tests animals of a single gender (usually females) at a number of fixed concentration levels in a sequential fashion. It begins with a sighting study that precedes the main FCP study and is used to determine the main study starting concentration. In this paper, we propose a modification to the sighting study and suggest that it should be conducted using both male and female animals, rather than just animals of a single gender. Statistical analysis demonstrates that, when females are more sensitive, the new procedure is likely to give the same classification as the original FCP, whereas, if males are more sensitive, the new procedure is much less likely to lead to incorrect classification into a less toxic category. If there is no difference in the LC50 for females and males, the new procedure is slightly more likely to classify into a more stringent class than the original FCP. Overall, these results show that the revised sighting study ensures gender differences in sensitivity do not significantly impact on the performance of the FCP, supporting its use as an alternative test method for assessing acute inhalation toxicity

Wave energy extraction from device arrays : experimental investigation in a large wave facility

Multiple wave energy devices supported by a common structure represent one possible method of efficiently converting ocean wave energy into electricity. In this study, experimental measurements of multiple small-scale wave energy devices are reported to assist the development and validation of numerical models. Through observation and measurement, the response of two float geometries subjected to a range of wave conditions and device settings were determined. A range of regular wave conditions were identified that caused a linear relationship to occur between the heave displacement amplitude of the float and the incident wave amplitude. These test cases will enable comparisons to be made with linear simulations of response. Tests conducted in various wave conditions have highlighted the capability of altering the device response by changing the equilibrium draft of one float geometry. Additional damping on the upper surface of the float, due to wave overtopping, could be exploited as a method of limiting the heave response of the device in large amplitude waves. The influence of hydrodynamic interactions on arrays of closely spaced devices has been experimentally investigated for devices subjected to regular and irregular wave conditions. The magnitude and occurrence of interactions and their affect on the individual device response is demonstrably dependent on the incident wave frequency and device separation distance. Compared to an isolated device, positive interactions result in higher average power outputs for an array of devices at certain wave frequencies. Positive interactions occuring at particular wave frequencies are balanced by negative interactions at other wave frequencies, in agreement with published numerical studies of array performance. Varying the level of mechanical damping applied to the float through the power take-off system results in a frequency shift of the calculated power transfer function and alters the motion path of the float. This finding implies that the level of generator torque could be used as an alternative method to tune the response of the device based on the measured incident wave-field. Several time-averaged and time-varying approaches to simulating the response of a wave energy device subjected to wave-field forcing and undergoing free response have been studied. By comparing the simulated and measured responses, the feasibility of using linear and non-linear force terms in a time-varying model has been assessed. In general, single degree-of-freedom simulations based on linear hydrodynamic parameters tend to over-predict device response amplitudes, requiring the application of additional damping. The simulation approach which resulted in the closest agreement with measured responses required the combination of linear diffraction force and radiation added mass terms with non-linear drag and buoyancy force terms, as well as body inertia and gravity forces. This approach goes part way to simulating the complex time-varying hydrodynamics associated with a wave energy device subjected to wave-field forcing.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Novel Missions for Next Generation Microsatellites: The Results of a Joint AFRL/JPL Study

The development of technologies for miniature, low-mass, high density components and of systems that efficiently utilize these teclmologies has enabled a path to the next generation of highly capable microsatellites in the range of 10 - 100-kg. The characteristics and capabilities of this emerging class of satellites are briefly described. These satellites have the potential for revolutionizing space missions owing to their small size, low cost, significant capability, and good return on investment. This paper documents conceptual microsatellite mission scenarios examined in a collaborative effort between the Air Force Research Laboratory (AFRL) and the Jet Propulsion Laboratory of the California Institute of Technology (JPL). Six areas of mutual interest were selected from an initial set of about 30 microsatellite mission areas. Each of the selected areas was examined in more depth. The concepts explored include a remote sensing microsatellite, an on-orbit servicing microsatellite, a micronavigation and communication system, an adjunct microsatellite, and two distributed microsatellite systems; one for surveillance and one for space weather and physics observations. These missions are described briefly. A unique characteristic of these microsatellites, exploited in some of the mission scenarios, is the potential for low cost and rapid launch using non-traditional methods. One method examined involves using air-to-space missile technology

An evaluation of the fixed concentration procedure for assessment of acute inhalation toxicity

Acute inhalation studies are conducted in animals as part of chemical hazard identification and for classification and labelling. Current methods employ death as an endpoint (OECD TG403 and TG436) while the recently approved fixed concentration procedure (FCP) (OECD TG433) uses fewer animals and replaces lethality as an endpoint with evident toxicity. Evident toxicity is the presence of clinical signs that predict that exposure to the next highest concentration will cause severe toxicity or death in most animals. Approval of TG433 was the result of an international initiative, led by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), which collected data from six laboratories on clinical signs recorded for inhalation studies on 172 substances. This paper summarises previously published data and describes the additional analyses of the dataset that were essential for approval of the TG