The Medicalization of Cannabis

Annotated and edited transcript of a Witness Seminar held on 24 March 2009. Introduction by Professor Leslie Iversen.First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2010.©The Trustee of the Wellcome Trust, London, 2010. All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/Annotated and edited transcript of a Witness Seminar held on 24 March 2009. Introduction by Professor Leslie Iversen.Annotated and edited transcript of a Witness Seminar held on 24 March 2009. Introduction by Professor Leslie Iversen.Annotated and edited transcript of a Witness Seminar held on 24 March 2009. Introduction by Professor Leslie Iversen.Annotated and edited transcript of a Witness Seminar held on 24 March 2009. Introduction by Professor Leslie Iversen.Annotated and edited transcript of a Witness Seminar held on 24 March 2009. Introduction by Professor Leslie Iversen.Annotated and edited transcript of a Witness Seminar held on 24 March 2009. Introduction by Professor Leslie Iversen.Cannabis has been considered as both an illicit drug and a medicine throughout its history. Introduced to the UK as a medicine in the nineteenth century, its medical utility was limited and it was not until tetrahydrocannabinol (THC), one of the principal active components in cannabis, was isolated in 1964 by Raphael Mechoulam and his team in Israel that scientific research on the drug expanded. Further major developments came in the 1980s, when the cannabinoid receptors in the brain were discovered. Scientists, clinicians, policy makers and patients interested in exploring and utilizing cannabis as an orthodox medication attended this seminar. Several were involved with the early elucidation of the structures of the components of the cannabis plant, or with the two MRC-funded trials in the 1990s into the therapeutic effect of cannabis on multiple sclerosis (MS) and postoperative pain. The founding director of GW Pharmaceuticals discussed the problems of growing cannabis plants and standardizing extracts to produce a medicine that could gain regulatory approval. Two MS patients related their experiences of cannabinoid medications and the significance of patient activism and self-medication in renewing research interest in the potential medical benefits of cannabis, against the backdrop of increasing recreational use, was also considered. The meeting was suggested by Professor Virginia Berridge, who chaired the meeting jointly with Professor E. M. Tansey. Contributors include: Professor David Baker, Professor Virginia Berridge Dr Vincenzo Di Marzo, Professor Griffith Edwards, Professor John Galloway, Dr Edward Gill, Dr Geoffrey Guy, Dr Clare Hodges, Dr Anita Holdcroft, Ms Victoria Hutchins, Professor Raphael Mechoulam, Professor Anthony Moffat, Dr William Notcutt, Professor Roger Pertwee, Dr Philip Robson, Dr Ethan Russo, Professor Tilli Tansey, Ms Suzanne Taylor. One appendix gives diagrams of the structures of the major plant cannabinoids and structurally-related synthetic cannabinoids. Crowther S M, Reynolds L A, Tansey E M. (eds) (2010) The Medicalization of Cannabis, Wellcome Witnesses to Twentieth Century Medicine, vol. 40. London: The Wellcome Trust Centre for the History of Medicine at UCL. ISBN 978 085484 129 5The Wellcome Trust Centre for the History of Medicine at UCL is funded by the Wellcome Trust, which is a registered charity, no. 210183

History of Dialysis in the UK: c.1950-1980

Annotated and edited transcript of a Witness Seminar held on 26 February 2008. Introduction by Professor John Pickstone.First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2009.©The Trustee of the Wellcome Trust, London, 2009.All volumes are freely available online at:www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/Annotated and edited transcript of a Witness Seminar held on 26 February 2008. Introduction by Professor John Pickstone.Annotated and edited transcript of a Witness Seminar held on 26 February 2008. Introduction by Professor John Pickstone.Annotated and edited transcript of a Witness Seminar held on 26 February 2008. Introduction by Professor John Pickstone.Annotated and edited transcript of a Witness Seminar held on 26 February 2008. Introduction by Professor John Pickstone.Dialysis, the first technological substitution for organ function, is significant not only for the numbers of patients who have benefited. It contributed to the emergence of the field of medical ethics and the development of the nurse specialist, and transformed the relationship between physicians and patients by allowing patients to control their treatment. This seminar drew on participants’ recollections of dialysis from the early, practically experimental days after the Second World War, when resources for research were scant, until the 1980s when it had become an established treatment. Pioneers from the first UK dialysis units recalled the creation of the specialty of nephrology amid discouragement from renal physicians and the MRC, which felt that the artificial kidney was a gadget that would not last. International and interdisciplinary collaborations, and interactions between with industry and clinics in developing and utilising the specialist technology were emphasized. Patients, carers, nurses, technicians and doctors reminisced about their experiences of home dialysis, its complications and impact on family life, as well as the physical effects of surviving on long-term dialysis before transplantation became routine. The meeting was suggested and chaired by Dr John Turney and witnesses include Dr Rosemarie Baillod, Professor Christopher Blagg, Professor Stewart Cameron, Mr Eric Collins, Professor Robin Eady, Mrs Diana Garratt, Professor David Kerr, Professor Sir Netar Mallick, Dr Frank Marsh, Dr Jean Northover, Dr Chisholm Ogg, Dr Margaret Platts, Dr Stanley Rosen and Professor Stanley Shaldon. Two appendices contain reminiscences from Professor Kenneth Lowe and Sir Graham Bull. Crowther S M, Reynolds L A, Tansey E M. (eds) (2009) History of dialysis in the UK: c. 1950–2000, Wellcome Witnesses to Twentieth Century Medicine, vol. 37. London: The Wellcome Trust Centre for the History of Medicine at UCL. ISBN 978 085484 1226The Wellcome Trust Centre for the History of Medicine at UCL is funded by the Wellcome Trust, which is a registered charity, no. 210183

The Resurgence of Breastfeeding, 1975-2000

Annotated and edited transcript of a Witness Seminar held on 24 April 2007. Introduction by Professor Rima Apple, University of Wisconsin-Madison.First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2009.©The Trustee of the Wellcome Trust, London, 2009.All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/Annotated and edited transcript of a Witness Seminar held on 24 April 2007. Introduction by Professor Rima Apple, University of Wisconsin-Madison.Annotated and edited transcript of a Witness Seminar held on 24 April 2007. Introduction by Professor Rima Apple, University of Wisconsin-Madison.Annotated and edited transcript of a Witness Seminar held on 24 April 2007. Introduction by Professor Rima Apple, University of Wisconsin-Madison.Annotated and edited transcript of a Witness Seminar held on 24 April 2007. Introduction by Professor Rima Apple, University of Wisconsin-Madison.As breast-milk substitutes became iAs breast-milk substitutes became increasingly sophisticated and heavily marketed in the mid-twentieth century, bottle-feeding became regarded worldwide as safe, convenient, normal and even preferable to breastfeeding. From 1975, research conducted in the developing world, particularly Gambia, began to converge with work on immunology and child psychology to reassert the value of mothers’ own milk. At the same time, growing understanding of physiology, reproductive and developmental biology shifted interest from the composition of infant formulae to the biology of infant feeding. Insights from comparative zoology, dairy science and animal husbandry, shared with research in human lactation and ‘naturalization’ of childbirth all helped to de-medicalize infant feeding. Chaired by Professor Lawrence Weaver, this Witness Seminar was attended by representatives from women’s groups, pressure groups and international organizations, including Baby Milk Action, IBFAN, La Leche League, the National Childbirth Trust, WHO and UNICEF, as well as paediatricians, obstetricians, physiologists, nutritional scientists, zoologists, psychologists and members of industry. The discussion addressed the critical events, scientific advances, and social and political steps that drove the resurgence of breastfeeding, focusing not only on the nutritional science but also on the social context in which the changes took place. Participants included: Mr James Akre, Professor Elizabeth Alder, Mrs Phyll Buchanan, Professor Forrester Cockburn, Ms Rosie Dodds, Mrs Jill Dye, Professor Fiona Dykes, Ms Hilary English, Miss Chloe Fisher, Professor Anna Glasier, Professor Lars Hanson, Dr Elisabet Helsing, Dr Edmund Hey, Professor Peter Howie, Professor Alan McNeilly, Professor Kim Michaelsen, Mrs Rachel O’Leary, Ms Gabrielle Palmer, Professor Malcolm Peaker, Dr Ann Prentice,Professor Mary Renfrew, Mrs Patti Rundall, Ms Ellena Salariya, Dr Felicity Savage, Professor Roger Short, Dr Mary Smale, Dr Alison Spiro, Dr Penny Stanway, Dr Tilli Tansey, Mrs Jenny Warren, Mr John Wells, Professor Brian Wharton, Professor Roger Whitehead, Dr Anthony Williams, Miss Carol Williams and Dr Michael Woolridge. Crowther S M, Reynolds L A, Tansey E M. (eds) (2009) The resurgence of breastfeeding, 1975–2000, Wellcome Witnesses to Twentieth Century Medicine, vol. 35. London: The Wellcome Trust Centre for the History of Medicine at UCL.The Wellcome Trust Centre for the History of Medicine at UCL is funded by the Wellcome Trust, which is a registered charity, no. 210183

Self-reported body fat change in HIV-infected men is a marker of decline in physical health-related quality of life with aging, independent of co-morbidity

Objective: Self-perception of changes in body fat among HIV+ persons is associated with decreased health related quality of life in cross-sectional studies. The longitudinal impact of body fat changes on health related quality of life, while accounting for comorbidity and anatomic location or severity of body fat changes, is unknown. Design: This was a longitudinal analysis of HIV+ and HIV- Multicenter AIDS Cohort Study (MACS) participants who completed questionnaires assessing self-perceived body fat changes (baseline visit) and a health related quality of life (Short Form-36) at baseline and then ≥5 years later. Methods: Relationships between body fat changes and change in Short Form-36 Physical and Mental Component Summary scores were investigated using mixedmodel regression. Results: We studied 270 HIV+ and 247 HIV- men. At baseline, ≥50% of HIV+ men reported body fat changes; physical component but not mental component summary scores were lower among HIV+ men who reported moderate/severe leg or abdominal fat changes (p<0.05). At follow-up, physical component summary scores were significantly lower among men with face, leg, or abdominal fat changes compared to men without perceived fat changes (p<0.05). No significant changes were seen in mental component scores by fat change location or severity. In the final model, body fat changes at any site or severity were significant predictors of a decline in physical component summary score (p<0.05), independent of demographics or comorbidities. Mental component summary score was not associated with body fat changes, but higher mental component summary score was associated with increasing age and time. Conclusions: Negative self-perceived body fat changes were associated with decline in physical health related quality of life, independent of comorbidities, and may be a marker of an increased risk for physical function decline with aging

Modeling recursive RNA interference.

An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off-switch on experiments

Virtual player design using self-learning via competitive coevolutionary algorithms

The Google Artificial Intelligence (AI) Challenge is an international contest the objective of which is to program the AI in a two-player real time strategy (RTS) game. This AI is an autonomous computer program that governs the actions that one of the two players executes during the game according to the state of play. The entries are evaluated via a competition mechanism consisting of two-player rounds where each entry is tested against others. This paper describes the use of competitive coevolutionary (CC) algorithms for the automatic generation of winning game strategies in Planet Wars, the RTS game associated with the 2010 contest. Three different versions of a prime algorithm have been tested. Their common nexus is not only the use of a Hall-of-Fame (HoF) to keep note of the winners of past coevolutions but also the employment of an archive of experienced players, termed the hall-of-celebrities (HoC), that puts pressure on the optimization process and guides the search to increase the strength of the solutions; their differences come from the periodical updating of the HoF on the basis of quality and diversity metrics. The goal is to optimize the AI by means of a self-learning process guided by coevolutionary search and competitive evaluation. An empirical study on the performance of a number of variants of the proposed algorithms is described and a statistical analysis of the results is conducted. In addition to the attainment of competitive bots we also conclude that the incorporation of the HoC inside the primary algorithm helps to reduce the effects of cycling caused by the use of HoF in CC algorithms.This work is partially supported by Spanish MICINN under Project ANYSELF (TIN2011-28627-C04-01),3 by Junta de Andalucía under Project P10-TIC-6083 (DNEMESIS) and by Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tech

Multiwavelength Observations of Pulsar Wind Nebulae

The extended nebulae formed as pulsar winds expand into their surroundings provide information about the composition of the winds, the injection history from the host pulsar, and the material into which the nebulae are expanding. Observations from across the electromagnetic spectrum provide constraints on the evolution of the nebulae, the density and composition of the surrounding ejecta, the geometry of the central engines, and the long-term fate of the energetic particles produced in these systems. Such observations reveal the presence of jets and wind termination shocks, time-varying compact emission structures, shocked supernova ejecta, and newly formed dust. Here I provide a broad overview of the structure of pulsar wind nebulae, with specific examples from observations extending from the radio band to very-high-energy gamma-rays that demonstrate our ability to constrain the history and ultimate fate of the energy released in the spin-down of young pulsars.Comment: 20 pages, 11 figures. Invited review to appear in Proc. of the inaugural ICREA Workshop on "The High-Energy Emission from Pulsars and their Systems" (2010), eds. N. Rea and D. Torres, (Springer Astrophysics and Space Science series

Association between the c.*229C>T polymorphism of the topoisomerase IIb binding protein 1 (TopBP1) gene and breast cancer

Topoisomerase IIb binding protein 1 (TopBP1) is involved in cell survival, DNA replication, DNA damage repair and cell cycle checkpoint control. The biological function of TopBP1 and its close relation with BRCA1 prompted us to investigate whether alterations in the TopBP1 gene can influence the risk of breast cancer. The aim of this study was to examine the association between five polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 30UTR region of the TopBP1 gene and breast cancer risk as well as allele-specific gene expression. Five hundred thirty-four breast cancer patients and 556 population controls were genotyped for these SNPs. Allele-specific Top- BP1 mRNA and protein expressions were determined by using real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with breast cancer. Compared to homozygous common allele carriers, heterozygous and homozygous for the T variant had significantly increased risk of breast cancer (adjusted odds ratio = 3.81, 95 % confidence interval: 1.63–8.34, p = 0.001). Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT or TT genotype. There was a significant association between the rs115160714 and tumor grade and stage. Most carriers of minor allele had a high grade (G3) tumors classified as T2-T4N1M0. Our study raises a possibility that a genetic variation of TopBP1 may be implicated in the etiology of breast cancer

3D-electrical resistivity tomography monitoring of salt transport in homogeneous and layered soil samples

Monitoring transport of dissolved substances in soil deposits is particularly relevant where safety is concerned, as in the case of geo-environmental barriers. Geophysical methods are very appealing, since they cover a wide domain, localising possible preferential flow paths and providing reliable links between geophysical quantities and hydrological variables. This paper describes a 3D laboratory application of Electrical Resistivity Tomography (ERT) used to monitor solute transport processes. Dissolution and transport tests on both homogeneous and heterogeneous samples were conducted in an instrumented oedometer cell. ERT was used to create maps of electrical conductivity of the monitored domain at different time intervals and to estimate concentration variations within the interstitial fluid. Comparisons with finite element simulations of the transport processes were performed to check the consistency of the results. Tests confirmed that the technique can monitor salt transport, infer the hydro-chemical behaviour of heterogeneous geomaterials and evaluate the performances of clay barrier

Prevention and management of excessive gestational weight gain: a survey of overweight and obese pregnant women

Background - Excessive gestational weight gain is associated with adverse infant, childhood and maternal outcomes and research to develop interventions to address this issue is ongoing. The views of women on gestational weight gain and the resources they would consider helpful in addressing this are however largely unknown. This survey aimed to determine the views of newly pregnant women, living in areas of social disadvantage, on 1) their current body weight and potential gestational weight gain and 2) the resources or interventions they would consider helpful in preventing excessive gestational weight gain. Methods - A convenience sample of overweight and obese pregnant women living in Fife, UK, were invited to complete a short anonymised questionnaire at their 12 week booking visit. Results - 428 women, BMI&#62;25 kg/m2, completed the questionnaire. Fifty-four per cent of respondents were obese (231) and 62% were living in areas of mild to moderate deprivation. Over three-quarters of participants felt dissatisfied with their current weight (81%). The majority of women (60%) expressed some concern about potential weight gain. Thirty-nine percent were unconcerned about weight gain during their pregnancy, including 34 women (19%) who reported having retained weight gained in earlier pregnancies. Amongst those concerned about weight gain advice on physical activity (41%) and access to sports/leisure facilities were favoured resources (36%). Fewer women (12%) felt that group sessions on healthy eating or attending a clinic for individualised advice (14%) would be helpful. "Getting time off work" was the most frequently cited barrier (48%) to uptake of resources other than leaflets. Conclusions- These data suggest a lack of awareness amongst overweight and obese women regarding excessive gestational weight gain. Monitoring of gestational weight gain, and approaches for its management, should be formally integrated into routine antenatal care. Barriers to the uptake of resources to address weight gain are numerous and must be considered in the design of future interventions and services