A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to he stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase H and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright (C) 2008 John Wiley & Sons, Ltd.

Liposomes and skin: From drug delivery to model membranes

The early eighties saw the introduction of liposomes as skin drug delivery systems, initially promoted primarily for localised effects with minimal systemic delivery. Subsequently, a novel ultradeformable vesicular system (termed "Transfersomes" by the inventors) was reported for transdermal delivery with an efficiency similar to subcutaneous injection. Further research illustrated that the mechanisms of liposome action depended on the application regime and the vesicle composition and morphology. Ethical, health and supply problems with human skin have encouraged researchers to use skin models. 'IYaditional models involved polymer membranes and animal tissue, but whilst of value for release studies, such models are not always good mimics for the complex human skin barrier, particularly with respect to the stratum corneal intercellular lipid domains. These lipids have a multiply bilayered organization, a composition and organization somewhat similar to liposomes, Consequently researchers have used vesicles as skin model membranes. Early work first employed phospholipid liposomes and tested their interactions with skin penetration enhancers, typically using thermal analysis and spectroscopic analyses. Another approach probed how incorporation of compounds into liposomes led to the loss of entrapped markers, analogous to "fluidization" of stratum corneum lipids on treatment with a penetration enhancer. Subsequently scientists employed liposomes formulated with skin lipids in these types of studies. Following a brief description of the nature of the skin barrier to transdermal drug delivery and the use of liposomes in drug delivery through skin, this article critically reviews the relevance of using different types of vesicles as a model for human skin in permeation enhancement studies, concentrating primarily on liposomes after briefly surveying older models. The validity of different types of liposome is considered and traditional skin models are compared to vesicular model membranes for their precision and accuracy as skin membrane mimics. (c) 2008 Elsevier B.V. All rights reserved.

'In practice it doesn't always work out like that.' Undergraduate experiences in a research community of practice

This paper examines the extent to which a structured undergraduate research intervention, UROP, permits undergraduate students early access to legitimate peripheral participation (LPP) in a research community of practice. Accounts of placement experiences suggest that UROP affords rich possibilities for engagement with research practice. Undergraduates tread a path of gaining access to mature practice while also building their own independence, participating in work that they see matters to the community and making gains in use of a shared research repertoire. Students place UROP experiences in a contrasting frame to research exercises experienced during degree programmes; their sense of the authenticity of the research experienced through UROP emerges as a key element of these accounts. The data generate the interesting question that the degree of engagement with mature practice may account for more of the gain from UROP than simply the quantity of contact other researchers.

Geoarchaeological investigations of midden-formation processes in the early to late Neolithic levels at Catalhoyuk, Turkey ca. 8550-8370 cal BP.

Anthropogenic midden deposits are remarkably well preserved at the Neolithic settlement of atalhöyük and provide significant archaeological information on the types and nature of activities occurring at the site. To decipher their complex stratigraphy and to investigate formation processes, a combination of geoarchaeological techniques was used. Deposits were investigated from the early ceramic to late Neolithic levels, targeting continuous sequences to examine high resolution and broader scale changes in deposition. Thin-section micromorphology combined with targeted phytolith and geochemical analyses indicates they are composed of a diverse range of ashes and other charred and siliceous plant materials, with inputs of decayed plants and organic matter, fecal waste, and sedimentary aggregates, each with diverse depositional pathways. Activities identified include in situ burning, with a range of different fuel types that may be associated with different activities. The complexity and heterogeneity of the midden deposits, and thus the necessity of employing an integrated microstratigraphic approach is demonstrated, as a prerequisite for cultural and palaeoenvironmental reconstructions.

Predicting early data revisions to US GDP and the effects of releases on equity markets

The effects of data uncertainty on real-time decision-making can be reduced by predicting early revisions to US GDP growth. We show that survey forecasts efficiently anticipate the first-revised estimate of GDP, but that forecasting models incorporating monthly economic indicators and daily equity returns provide superior forecasts of the second-revised estimate. We consider the implications of these findings for analyses of the impact of surprises in GDP revision announcements on equity markets, and for analyses of the impact of anticipated future revisions on announcement-day returns.