Experiences of Establishing an Academic Early Phase Clinical Trials Unit

Background: Early phase trials are essential in drug development, determining appropriate dose levels and assessing preliminary activity. These trials are undertaken by industry and academia, with increasing collaborations between the two. There is pressure to perform these trials quickly, safely and robustly. However, there are inherent differences between developing and managing early phase, compared to late phase, drug trials. This paper describes an approach to establishing an academically-led early phase trial portfolio, highlighting lessons learned and sharing experiences. Methods: In 2009 the University of Leeds Clinical Trials Research Unit became the Clinical Trials Coordinating Office for Myeloma UK’s phase I and II trials. We embarked on a transition from working extensively in phase III to early phase trials development and conduct. This involved evaluating and revising our well-established standard operating procedures, visiting other academic early phase units, and developing essential new documentation and processes. Results: A core team of trial and data managers and statisticians was established to facilitate expertise and knowledge retention. A detailed training plan was implemented focusing on essential standard practices for early phase. These included pharmacovigilance, recruitment, trial design and set-up, data and site monitoring, and oversight committees. Training in statistical methods for early phase trials was incorporated. Conclusion: Initial scoping of early phase trial management and conduct was essential in establishing this early phase portfolio. Many of the processes developed were successful. However, regular review and evaluation were implemented to enable changes and ensure efficiencies. It is recommended that others embarking on this venture build on the experiences described in this article

Shroud boundary condition characterization experiments at the Radiant Heat Facility.

A series of experiments was performed to better characterize the boundary conditions from an inconel heat source ('shroud') painted with Pyromark black paint. Quantifying uncertainties in this type of experimental setup is crucial to providing information for comparisons with code predictions. The characterization of this boundary condition has applications in many scenarios related to fire simulation experiments performed at Sandia National Laboratories Radiant Heat Facility (RHF). Four phases of experiments were performed. Phase 1 results showed that a nominal 1000 C shroud temperature is repeatable to about 2 C. Repeatability of temperatures at individual points on the shroud show that temperatures do not vary more than 10 C from experiment to experiment. This variation results in a 6% difference in heat flux to a target 4 inches away. IR camera images showed the shroud was not at a uniform temperature, although the control temperature was constant to about {+-}2 C during a test. These images showed that a circular shaped, flat shroud with its edges supported by an insulated plate has a temperature distribution with higher temperatures at the edges and lower temperatures in the center. Differences between the center and edge temperatures were up to 75 C. Phase 3 results showed that thermocouple (TC) bias errors are affected by coupling with the surrounding environment. The magnitude of TC error depends on the environment facing the TC. Phase 4 results were used to estimate correction factors for specific applications (40 and 63-mil diameter, ungrounded junction, mineral insulated, metal-sheathed TCs facing a cold surface). Correction factors of about 3.0-4.5% are recommended for 40 mil diameter TCs and 5.5-7.0% for 63 mil diameter TCs. When mounted on the cold side of the shroud, TCs read lower than the 'true' shroud temperature, and the TC reads high when on the hot side. An alternate method uses the average of a cold side and hot side TC of the same size to estimate the true shroud temperature. Phase 2 results compared IR camera measurements with TC measurements and measured values of Pyromark emissivity. Agreement was within measured uncertainties of the Pyromark paint emissivity and IR camera temperatures

Numerical predictions and experimental results of a dry bay fire environment.

The primary objective of the Safety and Survivability of Aircraft Initiative is to improve the safety and survivability of systems by using validated computational models to predict the hazard posed by a fire. To meet this need, computational model predictions and experimental data have been obtained to provide insight into the thermal environment inside an aircraft dry bay. The calculations were performed using the Vulcan fire code, and the experiments were completed using a specially designed full-scale fixture. The focus of this report is to present comparisons of the Vulcan results with experimental data for a selected test scenario and to assess the capability of the Vulcan fire field model to accurately predict dry bay fire scenarios. Also included is an assessment of the sensitivity of the fire model predictions to boundary condition distribution and grid resolution. To facilitate the comparison with experimental results, a brief description of the dry bay fire test fixture and a detailed specification of the geometry and boundary conditions are included. Overall, the Vulcan fire field model has shown the capability to predict the thermal hazard posed by a sustained pool fire within a dry bay compartment of an aircraft; although, more extensive experimental data and rigorous comparison are required for model validation

Sexed up: theorizing the sexualization of culture

This paper reviews and examines emerging academic approaches to the study of ‘sexualized culture’; an examination made necessary by contemporary preoccupations with sexual values, practices and identities, the emergence of new forms of sexual experience and the apparent breakdown of rules, categories and regulations designed to keep the obscene at bay. The paper maps out some key themes and preoccupations in recent academic writing on sex and sexuality, especially those relating to the contemporary or emerging characteristics of sexual discourse. The key issues of pornographication and democratization, taste formations, postmodern sex and intimacy, and sexual citizenship are explored in detail. </p

Letters to Andrew Inglis Clark, Tasmania from Walter Gill, Melbourne dated July 10 1882

The pressure of work has delayed his move to Sydney. He has already secured and is paying for lodgings in Darlinghurst. Time spent in Melbourne although strengthened legal knowledge and made many friends, has not got me any closer to the goal of my ambition. Hoping for better prospects in NSW. How fortunate he is to have such a sincere, warm-hearted and purest of friends in Andrew, and will forever be obligated. Sorry that he lost his seat in the last election and is surprised at Witton's silence. C4/C13

The basic ingredients of the North Atlantic storm track. Part I: land-sea contrast and orography

Understanding and predicting changes in storm tracks over longer time scales is a challenging problem, particularly in the North Atlantic. This is due in part to the complex range of forcings (land–sea contrast, orography, sea surface temperatures, etc.) that combine to produce the structure of the storm track. The impact of land–sea contrast and midlatitude orography on the North Atlantic storm track is investigated through a hierarchy of GCM simulations using idealized and “semirealistic” boundary conditions in a high-resolution version of the Hadley Centre atmosphere model (HadAM3). This framework captures the large-scale essence of features such as the North and South American continents, Eurasia, and the Rocky Mountains, enabling the results to be applied more directly to realistic modeling situations than was possible with previous idealized studies. The physical processes by which the forcing mechanisms impact the large-scale flow and the midlatitude storm tracks are discussed. The characteristics of the North American continent are found to be very important in generating the structure of the North Atlantic storm track. In particular, the southwest–northeast tilt in the upper tropospheric jet produced by southward deflection of the westerly flow incident on the Rocky Mountains leads to enhanced storm development along an axis close to that of the continent’s eastern coastline. The approximately triangular shape of North America also enables a cold pool of air to develop in the northeast, intensifying the surface temperature contrast across the eastern coastline, consistent with further enhancements of baroclinicity and storm growth along the same axis