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.

Designing Climate Mitigation Policy

This paper provides an exhaustive review of critical issues in the design of climate mitigation policy by pulling together key findings and controversies from diverse literatures on mitigation costs, damage valuation, policy instrument choice, technological innovation, and international climate policy. We begin with the broadest issue of how high assessments suggest the near and medium term price on greenhouse gases would need to be, both under cost-effective stabilization of global climate and under net benefit maximization or Pigouvian emissions pricing. The remainder of the paper focuses on the appropriate scope of regulation, issues in policy instrument choice, complementary technology policy, and international policy architectures.

Flow stabilization with active hydrodynamic cloaks

We demonstrate that fluid flow cloaking solutions, based on active hydrodynamic metamaterials, exist for two-dimensional flows past a cylinder in a wide range of Reynolds numbers (Re's), up to approximately 200. Within the framework of the classical Brinkman equation for homogenized porous flow, we demonstrate using two different methods that such cloaked flows can be dynamically stable for Re's in the range of 5-119. The first highly efficient method is based on a linearization of the Brinkman-Navier-Stokes equation and finding the eigenfrequencies of the least stable eigenperturbations; the second method is a direct numerical integration in the time domain. We show that, by suppressing the von Kármán vortex street in the weakly turbulent wake, porous flow cloaks can raise the critical Reynolds number up to about 120 or five times greater than for a bare uncloaked cylinder. © 2012 American Physical Society.

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.

Application of accelerated carbonation with a combination of Na2CO3 and CO2 in cement-based solidification/stabilization of heavy metal-bearing sediment

The efficient remediation of heavy metal-bearing sediment has been one of top priorities of ecosystem protection. Cement-based solidification/stabilization (s/s) is an option for reducing the mobility of heavy metals in the sediment and the subsequent hazard for human beings and animals. This work uses sodium carbonate as an internal carbon source of accelerated carbonation and gaseous CO2 as an external carbon source to overcome deleterious effects of heavy metals on strength development and improve the effectiveness of s/s of heavy metal-bearing sediment. In addition to the compressive strength and porosity measurements, leaching tests followed the Chinese solid waste extraction procedure for leaching toxicity - sulfuric acid and nitric acid method (HJ/T299-2007), German leaching procedure (DIN38414-S4) and US toxicity characteristic leaching procedures (TCLP) have been conducted. The experimental results indicated that the solidified sediment by accelerated carbonation was capable of reaching all performance criteria for the disposal at a Portland cement dosage of 10 wt.% and a solid/water ratio of 1: 1. The concentrations of mercury and other heavy metals in the leachates were below 0.10 mg/L and 5 mg/L, respectively, complying with Chinese regulatory level (GB5085-2007). Compared to the hydration, accelerated carbonation improved the compressive strength of the solidified sediment by more than 100% and reduced leaching concentrations of heavy metals significantly. It is considered that accelerated carbonation technology with a combination of Na2CO3 and CO2 may practically apply to cement-based s/s of heavy metal-bearing sediment. (C) 2008 Elsevier B.V. All rights reserved.

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.

The effects of cadence and power output upon physiological and biomechanical responses to incremental arm-crank ergometry

The aim of this study was to examine the effects of cadence and power output on physiological and biomechanical responses to incremental arm-crank ergometry (ACE). Ten male subjects (mean +/- SD age, 30.4 +/-5.4 y; height, 1.78 +/-0.07 m; mass, 86.1 +/-14.2 kg) undertook 3 incremental ACE protocols to determine peak oxygen uptake (VO2 peak; mean of 3 tests: 3.07 +/- 0.17 L.min-1) at randomly assigned cadences of 50, 70, or 90 r.min-1. Heart rate and expired air were continually monitored. Central (RPE-C) and local (RPE-L) ratings of perceived exertion were recorded at volitional exhaustion. Joint angles and trunk rotation were analysed during each exercise stage. During submaximal power outputs of 50, 70, and 90 W, oxygen consumption (VO2) was lowest for 50 r.min-1 and highest for 90 r.min-1 (p < 0.01). VO2 peak was lowest during 50 r.min-1 (2.79 +/-0.45 L.min-1; p < 0.05) when compared with both 70 r.min-1 and 90 r.min-1 (3.16 +/-0.58, 3.24 +/-0.49 L.min-1, respectively; p > 0.05). The difference between RPE-L and RPE-C at volitional exhaustion was greatest during 50 r.min-1 (2.9 +/- 1.6) when compared with 90 r.min-1 (0.9 +/- 1.9, p < 0.05). At VO2 peak, shoulder range of motion (ROM) and trunk rotation were greater for 50 and 70 r.min-1 when compared with 90 r.min-1 (p < 0.05). During submaximal power outputs, shoulder angle and trunk rotation were greatest at 50 r.min-1 when compared with 90 r.min-1 (p < 0.05). VO2 was inversely related to both trunk rotation and shoulder ROM during submaximal power outputs. The results of this study suggest that the greater forces required at lower cadences to produce a given power output resulted in greater joint angles and range of shoulder and trunk movement. Greater isometric contractions for torso stabilization and increased cost of breathing possibly from respiratory-locomotor coupling may have contributed increased oxygen consumption at higher cadences.

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]

What price harmony? Teachers' methods of delivering an ethos of tolerance and respect for diversity in an integrated school in Northern Ireland

The aim of the paper is to explore teachers’ methods of delivering an ethos of tolerance, respect
and mutual understanding in one integrated secondary school in Northern Ireland. Drawing on
interviews with teachers in the school, it is argued that most teachers make ‘critical choices’
which both reflect and reinforce a ‘culture of avoidance’, whereby politically or religiously contentious
issues are avoided rather than explored. Although teachers are well-intentioned in making
these choices, it is shown that they have the potential to create the conditions that maintain or even
harden psychological boundaries between Catholics and Protestants rather than dilute them.

A stabilization mechanism of zirconia based on oxygen vacancies only

The microscopic mechanism leading to stabilization of cubic and tetragonal forms of zirconia (ZrO2) is analyzed by means of a self-consistent tight-binding model. Using this model, energies and structures of zirconia containing different vacancy concentrations are calculated, equivalent in concentration to the charge compensating vacancies associated with dissolved yttria (Y2O3) in the tetragonal and cubic phase fields (3.2 and 14.4% mol, respectively). The model is shown to predict the large relaxations around an oxygen vacancy, and the clustering of vacancies along the 111 directions, in good agreement with experiments and first principles calculations. The vacancies alone are shown to explain the stabilization of cubic zirconia, and the mechanism is analyzed. (C) 2002 Acta Materialia Inc. Published by Elsevier Science Ltd. All rights reserved.