Comparison of a reduced carbohydrate and reduced fat diet for LDL, HDL, and VLDL subclasses during 9-months of weight maintenance subsequent to weight loss.

OBJECTIVES: This study compared LDL, HDL, and VLDL subclasses in overweight or obese adults consuming either a reduced carbohydrate (RC) or reduced fat (RF) weight maintenance diet for 9 months following significant weight loss. METHODS: Thirty-five (21 RC; 14 RF) overweight or obese middle-aged adults completed a 1-year weight management clinic. Participants met weekly for the first six months and bi-weekly thereafter. Meetings included instruction for diet, physical activity, and behavior change related to weight management. Additionally, participants followed a liquid very low-energy diet of approximately 2092 kJ per day for the first three months of the study. Subsequently, participants followed a dietary plan for nine months that targeted a reduced percentage of carbohydrate (approximately 20%) or fat (approximately 30%) intake and an energy intake level calculated to maintain weight loss. Lipid subclasses using NMR spectroscopy were analyzed prior to weight loss and at multiple intervals during weight maintenance. RESULTS: Body weight change was not significantly different within or between groups during weight maintenance (p>0.05). The RC group showed significant increases in mean LDL size, large LDL, total HDL, large and small HDL, mean VLDL size, and large VLDL during weight maintenance while the RF group showed increases in total HDL, large and small HDL, total VLDL, and large, medium, and small VLDL (p<0.05). Group*time interactions were significant for large and medium VLDL (p>0.05). CONCLUSION: Some individual lipid subclasses improved in both dietary groups. Large and medium VLDL subclasses increased to a greater extent across weight maintenance in the RF group.

c-Myc is required for maintenance of glioma cancer stem cells.

BACKGROUND: Malignant gliomas rank among the most lethal cancers. Gliomas display a striking cellular heterogeneity with a hierarchy of differentiation states. Recent studies support the existence of cancer stem cells in gliomas that are functionally defined by their capacity for extensive self-renewal and formation of secondary tumors that phenocopy the original tumors. As the c-Myc oncoprotein has recognized roles in normal stem cell biology, we hypothesized that c-Myc may contribute to cancer stem cell biology as these cells share characteristics with normal stem cells. METHODOLOGY/PRINCIPAL FINDINGS: Based on previous methods that we and others have employed, tumor cell populations were enriched or depleted for cancer stem cells using the stem cell marker CD133 (Prominin-1). We characterized c-Myc expression in matched tumor cell populations using real time PCR, immunoblotting, immunofluorescence and flow cytometry. Here we report that c-Myc is highly expressed in glioma cancer stem cells relative to non-stem glioma cells. To interrogate the significance of c-Myc expression in glioma cancer stem cells, we targeted its expression using lentivirally transduced short hairpin RNA (shRNA). Knockdown of c-Myc in glioma cancer stem cells reduced proliferation with concomitant cell cycle arrest in the G(0)/G(1) phase and increased apoptosis. Non-stem glioma cells displayed limited dependence on c-Myc expression for survival and proliferation. Further, glioma cancer stem cells with decreased c-Myc levels failed to form neurospheres in vitro or tumors when xenotransplanted into the brains of immunocompromised mice. CONCLUSIONS/SIGNIFICANCE: These findings support a central role of c-Myc in regulating proliferation and survival of glioma cancer stem cells. Targeting core stem cell pathways may offer improved therapeutic approaches for advanced cancers.

The price of innovation: new estimates of drug development costs.

The research and development costs of 68 randomly selected new drugs were obtained from a survey of 10 pharmaceutical firms. These data were used to estimate the average pre-tax cost of new drug development. The costs of compounds abandoned during testing were linked to the costs of compounds that obtained marketing approval. The estimated average out-of-pocket cost per new drug is 403 million US dollars (2000 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a real discount rate of 11% yields a total pre-approval cost estimate of 802 million US dollars (2000 dollars). When compared to the results of an earlier study with a similar methodology, total capitalized costs were shown to have increased at an annual rate of 7.4% above general price inflation.

Maintenance of a case-base for the retrieval of rotationally symmetric shapes for the design of metal castings

In this paper, we discuss the problem of maintenance of a CBR system for retrieval of rotationally symmetric shapes. The special feature of this system is that similarity is derived primarily from graph matching algorithms. The special problem of such a system is that it does not operate on search indices that may be derived from single cases and then used for visualisation and principle component analyses. Rather, the system is built on a similarity metric defined directly over pairs of cases. The problems of efficiency, consistency, redundancy, completeness and correctness are discussed for such a system. Performance measures for the CBR system are given, and the results for trials of the system are presented. The competence of the current case-base is discussed, with reference to a representation of cases as points in an n-dimensional feature space, and a Gramian visualisation. A refinement of the case base is performed as a result of the competence analysis and the performance of the case-base before and after refinement is compared.

Paying the price for loss of light

Considers the Court of Appeal ruling in Forsyth-Grant v Allen on the principles to be applied in assessing damages for the loss of light. Outlines the method for calculating damages for loss of right to light, the type of amenity which will be included in calculations for loss of amenity and the process applied in this case for assessing damages arising from the loss of profits that would have been made by the owner of the right to light if they had negotiated to relax the covenant, with reference to case law. Notes the limits to damages available for hypothetical loss and the difference between this award of profits and an account of profits.

A price worth paying?: Women and work – choice, constraint or satisficing

Purpose – Are women held back or holding back? Do women choose their jobs/careers or are they structurally or normatively constrained? The purpose of this paper is to shed fresh light on these questions and contribute to an on-going debate that has essentially focused on the extent to which part-time work is women’s choice, the role of structural and organisational constraints and the role of men in excluding women. Design/methodology/approach – The paper uses data from interviews with 80 working women – both full-time and part-time – performing diverse work roles in a range of organisations in the south east of England. Findings – It was found that many women do not make strategic job choices, rather they often ‘‘fall into’’ jobs that happen to be available to them. Some would not have aspired to their present jobs without male encouragement; many report incidents of male exclusion; and virtually all either know or suspect that they are paid less than comparable men. Those working reduced hours enjoy that facility, yet they are aware that reduced hours and senior roles are seen as incompatible. In short, they recognise both the positive and negative aspects of their jobs, whether they work full or part-time, whether they work in male-dominated or female-dominated occupations, and whatever their position in the organisational hierarchy. Accordingly, the paper argues that the concept of ‘‘satisficing’’, i.e. a decision which is good enough but not optimal, is a more appropriate way to view women’s working lives than are either choice or constraint theories. Originality/value – There is an ongoing, and often polarised, debate between those who maintain that women choose whether to give preference to work or home/family and others who maintain that women, far from being self-determining actors, are constrained structurally and normatively. Rather than supporting these choice or constraint theories, this paper argues that ‘‘satisficing’’ is a more appropriate and nuanced concept to explain women’s working lives.

Memorandum submitted by the University of Greenwich: are the consumer price increases for electricity imposed in January 2008 justified?

This paper examines whether increases to published wholesale prices justify the retail electricity price increases imposed on residential consumers in January 2008. The study is based on analysis of two questions: Is the reported wholesale price a reliable indicator of the cost electricity retailers are paying to buy power; and is the corporate structure of the British electricity sector competitive? [Taken from first paragraph of summary]

Routine maintenance and sustainability of existing social housing

Improving the sustainability of the housing stock is a major challenge facing the UK social housing sector. UK social housing accounts for approximately 18% of total UK housing and generates maintenance costs in the region of 1.25 billion pounds per annum. The extent to which routine maintenance can be used as a vehicle to improve the overall sustainability (social, environmental and economic) of existing social housing is one focus of a 5 year EPSRC funded research programme. This paper reports the findings of a questionnaire survey examining current social housing maintenance practices and attitudes towards sustainability. The research found that, whilst the stock condition survey is the favoured format for determining maintenance need and economics the basis for priority setting; neither systematically addresses wider sustainability issues; and, whilst cost is a major barrier to more sustainable solutions being adopted, landlords are able and have the desire to improve their practices.

Routine maintenance and sustainability of existing social housing

Presently the UK social housing stock accounts for approximately 18% of the total UK housing with maintenance costs in the region of £1.25 billion per annum. In terms of its impact on the environment, housing is generally responsible for approximately 27% of the UK’s CO2 emissions. The extent to which routine maintenance (planned preventative and responsive) can be used as a vehicle to improve the overall sustainability (social, environmental and economic) of existing social housing is one focus of a 5 year EPSRC funded research programme. This paper reports on the findings of a series of in-depth interviews with social housing providers examining current social housing maintenance practices and attitudes towards sustainability. This paper will report the initial findings of interviews and outline a new performance based multi-criteria maintenance model from which an AHP hierarchy will be presented, integrating the principles of sustainability into maintenance strategies