From bedside to bench: Comroe and dripps revisited

Twenty-five years ago a paper published in Science by Julius Comroe and Robert Dripps purported to demonstrate that 41 per cent of all articles judged to be essential for later clinical advances were not clinically oriented at the time of the study and 62 per cent of key articles were the result of basic research. Since that analysis, support for basic research has increased in the G7 countries. In the UK, Research Council expenditure on basic research has increased from a low of £444 million (or 42 per cent of total civil R&D) in 1991/92 to £769 million (or 61 per cent of total civil R&D) in 1998/99. Although it would be difficult to argue that Comroe and Dripps were directly responsible for a strategic shift (or drift) in the type of science supported by research funders, their arguments are often cited (albeit at times implicitly) in support of the increased funding for basic biomedical research. In 1987 Richard Smith wrote a critical paper reassessing Comroe and Dripps. His main argument was that the original study was in itself ‘unscientific’ and that it should be “followed by bigger and better studies”. This study is, in part, an answer to that challenge. Given the increased support for basic research, and the apparent importance based on the work of Comroe and Dripps, we felt it was important to investigate Smith’s comments by replicating Comroe and Dripps’s study and at the same time try to improve upon the methodology. The current project had two objectives: 1. To see if the original Comroe and Dripps’s methodology was ‘replicable’. 2. To validate the key findings of Comroe and Dripps. By looking at neonatal intensive care (NIC), we concluded that Comroe and Dripps’ study – as reported – is not repeatable, reliable or valid, and thus is an insufficient evidence base for increased expenditure on basic biomedical research. We did, however, develop an alternative methodology which used bibliographic databases and bibliometric techniques to describe the research underpinning five of the most important clinical advances in NIC, as identified through a Delphi survey. Using the revised bibliometric protocol, we demonstrated that after a time-lag of about 17 years, between 2 and 21 per cent of research underpinning the clinical advances could be described as basic. This observation is at odds with Comroe and Dripps’s finding that 62 per cent of key research articles judged to be essential for latter clinical advance were the result of basic research. In reaching this conclusion we are acutely aware of the significant limitations to the revised methodology and, therefore, we caution against the over-interpretation of our results. However, we would argue that there needs to be a greater understanding of how basic research supports healthcare and hope this report will inform part of this wider debate.R&D Directorate of the NHS Executive London; Wellcome Trus

Einstein-Weyl geometry, the dKP equation and twistor theory

It is shown that Einstein-Weyl (EW) equations in 2+1 dimensions contain the dispersionless Kadomtsev-Petviashvili (dKP) equation as a special case: If an EW structure admits a constant weighted vector then it is locally given by $h=d y^2-4d xd t-4ud t^2, \nu=-4u_xd t$, where $u=u(x, y, t)$ satisfies the dKP equation $(u_t-uu_x)_x=u_{yy}$. Linearised solutions to the dKP equation are shown to give rise to four-dimensional anti-self-dual conformal structures with symmetries. All four-dimensional hyper-K\"ahler metrics in signature $(++--)$ for which the self-dual part of the derivative of a Killing vector is null arise by this construction. Two new classes of examples of EW metrics which depend on one arbitrary function of one variable are given, and characterised. A Lax representation of the EW condition is found and used to show that all EW spaces arise as symmetry reductions of hyper-Hermitian metrics in four dimensions. The EW equations are reformulated in terms of a simple and closed two-form on the \CP^1-bundle over a Weyl space. It is proved that complex solutions to the dKP equations, modulo a certain coordinate freedom, are in a one-to-one correspondence with minitwistor spaces (two-dimensional complex manifolds ${\cal Z}$ containing a rational curve with normal bundle \O(2)) that admit a section of $\kappa^{-1/4}$, where $\kappa$ is the canonical bundle of ${\cal Z}$. Real solutions are obtained if the minitwistor space also admits an anti-holomorphic involution with fixed points together with a rational curve and section of $\kappa^{-1/4}$ that are invariant under the involution.Comment: 22 pages, 1 figur

Hypercomplex Integrable Systems

In this paper we study hypercomplex manifolds in four dimensions. Rather than using an approach based on differential forms, we develop a dual approach using vector fields. The condition on these vector fields may then be interpreted as Lax equations, exhibiting the integrability properties of such manifolds. A number of different field equations for such hypercomplex manifolds are derived, one of which is in Cauchy-Kovaleskaya form which enables a formal general solution to be given. Various other properties of the field equations and their solutions are studied, such as their symmetry properties and the associated hierarchy of conservation laws.Comment: Latex file, 19 page

MendelianRandomization v0.5.0: updates to an R package for performing Mendelian randomization analyses using summarized data.

The MendelianRandomization package is a software package written for the R software environment that implements methods for Mendelian randomization based on summarized data. In this manuscript, we describe functions that have been added to the package or updated in recent years. These features can be divided into four categories: robust methods for Mendelian randomization, methods for multivariable Mendelian randomization, functions for data visualization, and the ability to load data into the package seamlessly from the PhenoScanner web-resource. We provide examples of the graphical output produced by the data visualization commands, as well as syntax for obtaining suitable data and performing a Mendelian randomization analysis in a single line of code

Building better Sex Robots: Lessons from Feminist Pornography

How should we react to the development of sexbot technology? Taking their cue from anti-porn feminism, several academic critics lament the development of sexbot technology, arguing that it objectifies and subordinates women, is likely to promote misogynistic attitudes toward sex, and may need to be banned or restricted. In this chapter I argue for an alternative response. Taking my cue from the sex positive ‘feminist porn’ movement, I argue that the best response to the development of ‘bad’ sexbots is to make better ones. This will require changes to the content, process and context of sexbot development. Doing so will acknowledge the valuable role that technology can play in human sexuality, and allow us to challenge gendered norms and assumptions about male and female sexual desire. This will not be a panacea to the social problems that could arise from sexbot development, but it offers a more realistic and hopeful vision for the future of this technology in a pluralistic and progressive society

On Self-Dual Gravity I

(One typo corrected and one incorrect statement removed. Extra details on conserved quantities and symmetry algebras added).Comment: 17 pages, Latex, DAMTP-R92/4

Speckle from phase ordering systems

The statistical properties of coherent radiation scattered from phase-ordering materials are studied in detail using large-scale computer simulations and analytic arguments. Specifically, we consider a two-dimensional model with a nonconserved, scalar order parameter (Model A), quenched through an order-disorder transition into the two-phase regime. For such systems it is well established that the standard scaling hypothesis applies, consequently the average scattering intensity at wavevector _k and time t' is proportional to a scaling function which depends only on a rescaled time, t ~ |_k|^2 t'. We find that the simulated intensities are exponentially distributed, with the time-dependent average well approximated using a scaling function due to Ohta, Jasnow, and Kawasaki. Considering fluctuations around the average behavior, we find that the covariance of the scattering intensity for a single wavevector at two different times is proportional to a scaling function with natural variables mt = |t_1 - t_2| and pt = (t_1 + t_2)/2. In the asymptotic large-pt limit this scaling function depends only on z = mt / pt^(1/2). For small values of z, the scaling function is quadratic, corresponding to highly persistent behavior of the intensity fluctuations. We empirically establish a connection between the intensity covariance and the two-time, two-point correlation function of the order parameter. This connection allows sensitive testing, either experimental or numerical, of existing theories for two-time correlations in systems undergoing order-disorder phase transitions. Comparison between theory and our numerical results requires no adjustable parameters.Comment: 18 pgs RevTeX, to appear in PR

Who will use pre-exposure prophylaxis (PrEP) and why?: Understanding PrEP awareness and acceptability amongst men who have sex with men in the UK – a mixed methods study

Background: Recent clinical trials suggest that pre-exposure prophylaxis (PrEP) may reduce HIV transmission by up to 86% for men who have sex with men (MSM), whilst relatively high levels of PrEP acceptability have been reported to date. This study examines PrEP awareness amongst sub-groups of MSM communities and acceptability amongst MSM in a low prevalence region (Scotland, UK), using a mixed methods design. Methods: Quantitative surveys of n = 690 MSM recruited online via social and sociosexual media were analysed using descriptive statistics and multivariate logistic regression. In addition, n = 10 in-depth qualitative interviews with MSM were analysed thematically. Results: Under one third (29.7%) of MSM had heard of PrEP, with awareness related to living in large cities, degree level education, commercial gay scene use and reporting an HIV test in the last year. Just under half of participants (47.8%) were likely to use PrEP if it were available but there was no relationship between PrEP acceptability and previous PrEP awareness. Younger men (18–25 years) and those who report higher risk UAI were significantly more likely to say they would use PrEP. Qualitative data described specific PrEP scenarios, illustrating how risk, patterns of sexual practice and social relationships could affect motivation for and nature of PrEP use. Conclusion: These findings suggest substantial interest PrEP amongst MSM reporting HIV risk behaviours in Scotland. Given the Proud results, there is a strong case to investigate PrEP implementation within the UK. However, it appears that disparities in awareness have already emerged along traditional indicators of inequality. Our research identifies the need for comprehensive support when PrEP is introduced, including a key online component, to ensure equity of awareness across diverse MSM communities (e.g. by geography, education, gay scene use and HIV proximity), as well as to responding to the diverse informational and sexual health needs of all MSM communities

Work‒family interface in the context of career success: A qualitative inquiry

Work–family researchers are increasingly recognizing the need to expand their focus to advance the field. One population largely neglected by work‒family researchers is individuals who have been extremely successful in their careers. In addition, organizational career scholars have largely neglected the interplay between employees’ work and family lives. This study contributes to the work‒family literature by studying work‒family interface (WFI) in the context of career success. We sought to explore the lived experiences of 28 distinguished professors who are among the top 2‒5% scholars in their field, to provide an in-depth understanding of their WFI and the prominent factors affecting it over their careers. Our findings have theoretical implications for both work‒family and career success literature

The local economic development processes in low-income countries: the case of the metropolis of Chegutu in Zimbabwe

Local authorities are widely regarded as catalysts accelerating localised processes of economic development in industrialised countries but in low-income countries they are perceived as dysfunctional, inefficient and ineffective in meeting and addressing societal demands. This abstract view is however, not grounded in empirical research. As such, utilising the case of the metropolis of Chegutu a survey was designed to empirically explicate the economic processes militating its economic development. The findings are useful to policy-makers, local government authorities and management scholars. The study's unique contribution lies in its examination of the processes of local economic development in a low-income country