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

Isolating and Reconstructing Key Components of North Atlantic Ocean Variability From a Sclerochronological Spatial Network

This is the final version. Available from AGU via the DOI in this record.Our understanding of North Atlantic Ocean variability within the coupled climate system is limited by the brevity of instrumental records and a deficiency of absolutely dated marine proxies. Here we demonstrate that a spatial network of marine stable oxygen isotope series derived from molluscan sclerochronologies (δ18Oshell) can provide skillful annually resolved reconstructions of key components of North Atlantic Ocean variability with absolute dating precision. Analyses of the common δ18Oshell variability, using principal component analysis, highlight strong connections with tropical North Atlantic and subpolar gyre (SPG) sea surface temperatures and sea surface salinity in the North Atlantic Current (NAC) region. These analyses suggest that low-frequency variability is dominated by the tropical Atlantic signal while decadal variability is dominated by variability in the SPG and salinity transport in the NAC. Split calibration and verification statistics indicate that the composite series produced using the principal component analysis can provide skillful quantitative reconstructions of tropical North Atlantic and SPG sea surface temperatures and NAC sea surface salinities over the industrial period (1864–2000). The application of these techniques with extended individual δ18Oshell series provides powerful baseline records of past North Atlantic variability into the unobserved preindustrial period. Such records are essential for developing our understanding of natural climate variability in the North Atlantic Ocean and the role it plays in the wider climate system, especially on multidecadal to centennial time scales, potentially enabling reduction of uncertainties in future climate predictions

Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle

Brain cells continuously produce and release protons into the extracellular space, with the rate of acid production corresponding to the levels of neuronal activity and metabolism. Efficient buffering and removal of excess H+ is essential for brain function, not least because all the electrogenic and biochemical machinery of synaptic transmission is highly sensitive to changes in pH. Here, we describe an astroglial mechanism that contributes to the protection of the brain milieu from acidification. In vivo and in vitro experiments conducted in rodent models show that at least one third of all astrocytes release bicarbonate to buffer extracellular H+ loads associated with increases in neuronal activity. The underlying signalling mechanism involves activity-dependent release of ATP triggering bicarbonate secretion by astrocytes via activation of metabotropic P2Y1 receptors, recruitment of phospholipase C, release of Ca2+ from the internal stores, and facilitated outward HCO3− transport by the electrogenic sodium bicarbonate cotransporter 1, NBCe1. These results show that astrocytes maintain local brain extracellular pH homeostasis via a neuronal activity-dependent release of bicarbonate. The data provide evidence of another important metabolic housekeeping function of these glial cells

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

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

Organizational factors and depression management in community-based primary care settings

Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe