Extramural medical education in Edinburgh
Extramural medical education in Edinburgh began over 200 years before the university medical faculty was founded in 1726 and extramural teaching continued thereafter for a further 200 years. Extramural is academic education which is conducted outside a university. In the early 16th century it was under the auspices of the Incorporation (later Royal College) of Surgeons of Edinburgh (RCSEd) and continued after the Faculty of Medicine was established by the University of Edinburgh in 1726.[1] Throughout the late 18th and 19th centuries the demand for extramural medical teaching increased as Edinburgh's reputation as a centre for medical education grew. Instruction was carried out by individual teachers, by groups of teachers and, by the end of the 19th century, by private medical schools in the city. Together these comprised the Edinburgh Extramural School of Medicine. From 1896 many of the schools were incorporated into the Medical School of the Royal Colleges of Edinburgh under the aegis of the RCSEd and the Royal College of Physicians of Edinburgh (RCPE) and based at Surgeons' Hall. Extramural undergraduate medical education in Edinburgh stopped in 1948 with the closure of the Royal Colleges' Medical School following the Goodenough Report which recommended that all undergraduate medical education in the UK should be carried out by universities.[2]
Medical teaching to 1726
editMedical education in Edinburgh is considered to have started in 1505 when the Incorporation of Barber Surgeons gained their Seal of Cause or Charter, which requested that, as was common practice elsewhere in Europe. a condemned man should be dissected each year in order that the surgical apprentices might learn anatomy.[3] The Incorporation appointed James Borthwick as a teacher of anatomy in 1647 and he, with Thomas Kincaid, instructed students in botany and pharmacy at the Incorporation's physic garden at Curryhill House.[4] A Royal Patent to teach anatomy was granted in 1694 and this led to the Incorporation building the first Surgeons Hall on the site of Curryhill House in what is now Surgeons’ Square. Opened in 1697 this included an anatomical theatre where public anatomy dissections were performed.[5] Among those participating in such dissections in the early 18th century were Archibald Pitcairne and Alexander Monteith.[5]
The Faculty of Medicine established
editThe University of Edinburgh, founded in 1582, did not begin to teach medical topics until the early 18th century, with the appointment of Robert Eliot as Professor of Anatomy.[6] John Monro, an Edinburgh surgeon, who had obtained his medical degree at Leiden University in Holland, returned to Edinburgh with a view to setting up a medical school within the university and with an associated teaching hospital on the Leiden model. With the local support of Lord Provost George Drummond, and national support from the Earl of Ilay, Monro saw his ambition fulfilled starting with the appointment of his son, Alexander Monro primus, as Professor of Anatomy in 1719. Monro at first taught extra-murally at Surgeons Hall moving his classes to the university in 1725. The appointment of Leiden medical graduates Drs John Innes, Andrew Plummer, John Rutherford and Andrew Sinclair as university professors in 1726 marked the foundation of the university medical school, which was soon teaching a broad medical curriculum and conferred medical degrees by examination. Until this time the only way to obtain a medical degree in the British Isles was from the Universities of Oxford or Cambridge. Under the terms of the Test Acts these were only open to communicant members of the Church of England. Courses could take up to 12 years and did not include hospital clinical teaching.[7] The Edinburgh medical school was open to all faiths, lectures were in English and it was cheaper than European universities or Oxford or Cambridge.[8] These combined to make Edinburgh popular for those seeking a medical degree, who came initially from within the British Isles but increasingly from the then British Empire.[8]
The associated teaching hospital, opened in 1729, was initially situated opposite the top of Robertson's Close in what is now Infirmary Street. At first this had only six beds increasing to eight. The hospital was awarded a Royal charter in 1736, the first voluntary hospital to achieve this accolade. By this time it was too small to meet the demands and a new Royal Infirmary of Edinburgh (RIE) was built next to Surgeons' Hall. This building designed by William Adam could house 228 patients and was opened in 1741.[9]
Extramural teaching in the 18th century
editEdinburgh's attraction as a medical teaching centre was further enhanced by the growing reputation of Alexander Monro primus. Yet in the first 25 years of the medical faculty an average of only three students per year opted to progress to graduate MD. Many chose to sit for the qualification of Licentiateship of the RCSEd which became available from 1770, while others went into practice with no formal institutional qualification. For all these groups the kudos of having studied at Edinburgh could enhance their status and career progress.[8]
Extramural teaching resumed in the late 18th century. James Rae, a surgeon who became president of the RCSEd lectured on anatomy, surgery and dentistry at Surgeons' Hall from 1772.[10] From 1779 John Aitken began to teach classes in anatomy, physiology, surgery and midwifery at the Anatomical Theatre in Surgeons' Square, which was probably in Old Surgeons' Hall. The surgeon John Bell taught anatomy in his house in the square from 1787 and was joined then succeeded by his brother Charles Bell, later professor of surgery at the University of London. Their classes attracted large number of students as they taught surgical anatomy in contrast to Alexander Monro secundus, the university professor of anatomy, who was not a practising surgeon.[1]
Extramural teaching of materia medica was carried out in the Royal Public Dispensary which had been established by Andrew Duncan in 1776.[11] In 1805 John Abercrombie was appointed to the staff and established a large teaching practice there.[12]
Extramural teaching in the 19th century
editIn the first part of the 19th century extramural teaching centred on Surgeons Square. This was bounded on its south side by Old Surgeons' Hall, which was sold to the university in 1832. Extramural teaching took place in the large detached houses on the east and west sides of the square. Number one Surgeons' Square on the north side was built as a teaching facility with a lecture theatre. In the latter half of the century teaching also took place in buildings near the university, chiefly in Brown Square, Argyle Square, Chambers Street and the new Surgeons' Hall. .[13] Extramural teaching expanded rapidly from 1855 when the university was forced into recognising extramural classes as counting towards its medical degrees. James Syme had written to the Town Council in 1840 requesting such recognition and when the university refused the matter was taken to court and eventually to the House of Lords who found in favour of recognition of extramural classes. This recognition was further expanded in 1858 by the Commissioners appointed as regulators of the university curriculum under the Universities (Scotland) Act,1858.[14]
From 1896 many of these small medical schools were incorporated into the Medical School of the Royal Colleges, which from 1896 became by far the largest teaching establishment in the extramural school.[3]
Many of the lecturers in the extramural school taught there in the early part of their careers. Many would go on to become well known in later life in substantive posts or academic chairs. A full list of lecturers was compiled by John Comrie and published in his History of Scottish Medicine.[15]
Surgeons' Hall
editExtramural teaching continued at Surgeons Hall throughout the century. By 1860 a broadly based curriculum of medical subjects was taught and, after the House of Lord's judgement, these were recognised by universities as counting toward the degrees of MB, CM.[16] Despite the fact that these classes took place at Surgeons' Hall, a variety of medical subjects were taught. This was by far the largest of the extramural schools of medicine in Edinburgh.[5]
In the latter half of the century lecturers included:
- William Tennant Gairdner, Daniel Rutherford Haldane, George William Balfour, James Warburton Begbie (Medicine)
- Andrew Douglas Maclagan, Robert Edmund Scoresby-Jackson (Materia medica)
- Joseph Lister, Patrick Heron Watson, John Duncan, James Dunsmure, James Spence, Joseph Bell, Thomas Annandale (Surgery)
- Thomas Grainger Stewart (Diseases of children)
- John Struthers (Anatomy)
- Diarmid Noel Paton, William Rutherford Sanders, James Bell Pettigrew, Arthur Gamgee (Physiology)
- R Haldane, Thomas Grainger Stewart, John Wylie (Pathology)
- William Walker, Douglas Argyle Robertson (Diseases of the Eye)
- Robert Spittal (Medical acoustics)
- John Smith (Dental Surgery)
- Alexander Keiller, James Mathews Duncan (Midwifery)
- David Skae (Mental Illness)
- Henry Littlejohn (Medical Jurisprudence)
John Bell's House, Surgeons' Square
editJohn Bell's house was on the south east corner of the square but did not have a number. It was built specifically for the teaching of anatomy and surgery and was thought to have been the first house in Edinburgh designed for this purpose. John Bell, had begun to lecture there in 1787 and was joined by his brother Charles Bell who succeeded him in 1799. When Charles Bell left for London in 1804 anatomy was taught by John Allan and then, from 1824 by William Cullen grand-nephew of the eminent physician William Cullen. From 1825 the house was used to store the anatomical collection of Charles Bell, which had been purchased by the RCSEd, and its final use was as a lock hospital, for the nearby Royal Infirmary.[3]
9 Surgeons' Square
editNumber nine Surgeons' Square, known as John Gordon's house, was situated on the south-west corner of the square just to the west of Old Surgeons' Hall. John Gordon, a surgeon at the Royal Infirmary, gave lecture courses here on anatomy and physiology from 1808 until his death in 1818 aged 32 years. His textbook A System of Anatomy was published in 1815. John Thomson, the extramural professor of surgery at the RCSEd, bought the house and gave lectures on surgery there from 1818 and later also lectured there on the practice of physic. His lecture course was taken over by his son William Thomson from 1830 until his appointment as Professor of Physic at the University of Glasgow in 1841.
William Sharpey taught anatomy in the house from 1831 until he was appointed Professor of Anatomy and Physiology at the University of London. He was assisted as a lecturer by Allen Thomson until the latter's appointment to the Chair of Physiology at the University of Edinburgh. Others who lectured here in the 1830s included John William Turner and, who lectured on anatomy and James Young Simpson who lectured on midwifery.[5]
10 Surgeons' Square
editNumber ten, in the south-west corner of Surgeons' Square, had been built for use as a lecture theatre for the physician Andrew Duncan senior. The anatomist John Barclay bought the building in 1800 and began to teach anatomy. The house also contained a dissection room. His classes proved extremely popular and by the time he retired in 1825 he was teaching some 300 students per year. After Charles Bell left Edinburgh in 1808 and Alexander Monro secundus retired from anatomy teaching at the university the same year, Barclay became the most popular anatomy teacher in Edinburgh. His popularity was further enhanced by the unpopularity of Alexander Monro tertius, who had succeeded his father in the university chair. Barclay had amassed a large collection of comparative anatomy specimens used for teaching and this collection was bought by the RCSEd to form the Barclay collection in their museum. Barclay was succeeded in his anatomy school by Robert Knox. Knox catalogued the Barclay collection and the Charles Bell collection as curator of the Surgeons' Hall museum. The greatly enlarged collection was housed from 1832 in the new Surgeons' Hall which had been built to accommodate it. Knox was also a gifted anatomy teacher in marked contrast to Alexander Monro tertius at the university. Knox's classes were made more attractive by offering anatomical dissection under his supervision. As the demand for bodies for dissection exceeded supply, the serial killers William Burke and William Hare sold the bodies of their victims to Knox's anatomy school. After Burke was hanged for these crimes Knox was exonerated by a committee of 'distinguished citizens' and continued to teach at 10 Surgeons' Square until 1833. At the height of his popularity as a teacher in 1826, Knox attracted over 500 students to his anatomy classes, the largest number ever seen in the British Isles. William Fergusson assisted Knox with anatomy teaching until 1840 when he was appointed professor of surgery at King's College London and later became sergeant-surgeon to Queen Victoria.[14]
1 Surgeons' Square
editThe land at the north side of Surgeons' Square was owned by the engraver William Home Lizars who in 1825 built an anatomy school with a lecture theatre for his brother John Lizars a local surgeon. John Lizars taught anatomy and surgery and was succeeded by Peter David Handyside, Henry Lonsdale and James Spence. The building was later used as a museum, as a school, as part of the University Settlement and latterly as a nursery school. It is one of only three buildings still standing in the square in 2020.[3]
3 Surgeons' Square
editDavid Craigie taught anatomy from 1818 and later taught clinical medicine and practice of medicine. He later became president of the RCPE. From 1835 chemistry was taught by Andrew Fyfe who later went on to become professor of chemistry at the University of Aberdeen. From 1845 chemistry was taught here by Thomas Anderson, who went on to lecture in Glasgow where he drew the attention of Joseph Lister to the works of Louis Pasteur and supplied Lister with his first sample of carbolic acid, from which Lister developed antiseptic theory.[17]
Brown Square
editBrown Square was built as a residential development in 1763 and demolished in the late nineteenth century.[18] The Brown Square School of Medicine was established by James Syme, later Professor of Surgery in the university. Syme taught anatomy and surgery and was joined in the school by John Macintosh who taught medicine and midwifery and John Argyll Robertson who taught materia medica. When Syme resigned from the school his anatomy class was continued by Alexander Jardine Lizars, later professor of anatomy in the University of Aberdeen. The school closed in 1836 when the teaching was transferred to 11 Argyle Square.[3]
11 Argyle Square
editThe Argyll Square school was active early in the 1830s and expanded when teaching activity from Brown Square was transferred. It was known mainly as an anatomy school where the subject was taught by Peter Handyside, Alexander Keiller, Alexander Jardine Lizars and John Struthers, both of whom later became professors of anatomy at the University of Aberdeen.
Lecturers in other subjects included:
Thomas Wood (practice of medicine); John Lizars (surgery); Dr Marr (midwifery); David Skae (medical jurisprudence); J A Robertson (materia medica).[5]
Marshall Street
editThe School of Medicine and Pharmacy was located her in the latter years of the century. Lecturers included:
Alexander Johnstone (botany); J R Paterson (chemistry); E Urquhart (materia medica and pharmacy); Dr Matheson (midwifery); Dr Matheson and Alexander Keiller (medicine).[19]
Minto House, Chambers Street
editMinto House, a large town house owned by the Elliot family was bought by James Syme in 1829 and converted into a small surgical teaching hospital with an operating theatre and lecture room. There Syme taught surgery as did his assistants Alexander Peddie, later President of the Royal College of Physicians of Edinburgh and John Brown, whose account of the work of the hospital is described in his novel Rab and his Friends.[20] The hospital closed in 1852. Minto House was demolished in 1873 and 'new' Minto house was built on the site, becoming numbers 18-20 Chambers Street. Number 20 Chambers Chambers Street also housed a medical school.[3]
New Minto House, 20 Chambers Street.
editIn 1878 a medical school was opened with the anatomical teaching done by James Cossar Ewart, later Professor of Natural History at the University of Aberdeen. He was succeeded as anatomy lecturer by Johnston Symington later Professor of Anatomy at Queen's College, Belfast, and he in turn was succeeded by the surgeon Alexander Miles. In 1895 the anatomy dissecting room was taken over by the Edinburgh School of Medicine for Women, New Minto House was subsequently bought by the University of Edinburgh.[21]
Edinburgh School of Medicine for Women, Surgeons' Square
editSophia Jex-Blake, a pioneer of medical education for women, founded the school in 1886. Most of its teaching took place in Surgeons' Square, with clinical teaching at Leith Hospital.as the RIE still continued to refuse access to women students. With competition from the College of Medicine for Women and beset with financial problems, the school closed in 1898.[21]
Edinburgh College of Medicine for Women, 30 Chambers Street
editThe Edinburgh College of Medicine for Women was founded by Elsie Inglis and her father John Inglis in 1889 at a time when women were not admitted to university medical schools in the UK. Clinical teaching was initially at Glasgow Royal Infirmary as the RIE still did not accept women for clinical teaching i its wards. By July 1892 the college had sufficient funds and sufficient influence to have two wards in the RIE opened to the women medical students. The college merged with the School of Medicine of the Royal Colleges in 1916.[1]
Lecturers included:
- John W Ballantyne (Midwifery and gynaecology)
- William Craig - (Materia medica)
- James Hodsdon - (Surgery) went on to be knighted and elected president of the RCSEd.
- William Keiller (Anatomy) became Professor of Anatomy at the University of Texas at Galveston.[16]
- Harvey Littlejohn (Public Health) became professor of Forensic Medicine at the University of Edinburgh
- William Ivison Macadam (Chemistry)
- Robert Philip (Medicine) later a pioneer in the treatment of tuberculosis and president of the RCPE
- William Russell (Pathology) later Professor of Medicine at the University of Edinburgh and president of the RCPE
Queens' College
editQueen's College was the first association of extramural lecturers and schools. It was known to be active from 1841 to 1842. Classes were held at several different locations, with most at Brown Square and Argyle Square. From 1841 the lectures were recognised by the Universities of London, Oxford, Cambridge, St Andrews and Aberdeen, the Royal Colleges of Surgeons of England, Edinburgh and Ireland, the Apothecaries Hall, London and the Faculty of Physicians and Surgeons of Glasgow.[5] Lecturers included Robert Knox (11 Argyle Square) - anatomy and surgery; William Campbell (11 Argyle Square) -midwifery; James Marr (3 Surgeons' Square) - midwifery David Skae (11 Argyle Square) -medical jurisprudence; George Atkin (23 Brown Square) - botany.[5]
Extramural teaching in the 20th century
editThe School of Medicine of the Royal Colleges of Edinburgh
editIn the last decade of the nineteenth century an Association of Extramural Teachers was formed with a view to consolidating most of the smaller schools into a single institution under the aegis of the two medical Royal Colleges in Edinburgh. Dr (later Sir) Henry Littlejohn was chairman of the association and a leading figure in the formation of this new school. In 1894 the Scottish universities agreed that university students could attend half of their classes in the new school as counting towards a degree. From 1896 many of the small medical schools were incorporated into the School of Medicine of the Royal Colleges, which from 1896 became by far the largest teaching establishment in the extramural school. While most of the classes were held in Surgeons' Hall, there was teaching on smaller sites including The New School in Bristo Street, Park Place School. and 27 Nicolson Square.[3] Clinical teaching was provided at the Royal Infirmary of Edinburgh, Leith Hospital and the Sick Children's Hospital.[1] Clinical teaching continued in local dispensaries enabling students to learn about community care and experience in dispensary practice became part of the medical curriculum in 1890.[11] The Royal Public Dispensary had been founded in 1776, the New Town Dispensary in 1815 and there was also clinical teaching at the Provident Dispensary and the Livingstone Memorial Dispensary.[11]
In session 1896-97 there were 931 students, rising to 1317 the following year and remaining over 100 until World War I.[5] At the time of its closure in 1948, about 350 students were enrolled.[5] The School attracted many students drawn from marginal groups or those facing educational barriers, initially women and in later years students from the then British Empire and pollical refugees.[1] Many of the students who attended the classes were also registered with the University of Edinburgh and went on to graduate with the degree of MB ChB. The remainder aimed to sit the Triple Qualification, an examination held by the medical Royal Colleges and recognised by the General Medical Council.[22]
The Goodenough Report published in 1944 recommended that all undergraduate medical education in the UK should be carried out by universities.[2] In the face of this the school closed in 1948.[1]
Lecturers included:
- Joseph Ryland Whittaker, Richard James Arthur Berry (Anatomy)
- Agnes Rose MacGregor, Peter MacCallum, Robert Muir (Pathology)
- A Nimmo Smith (Bacteriology)
- James Ormiston Affleck, Byrom Bramwell, William Russel, George Alexander Gibson, Robert William Philip, John Comrie, Douglas Chalmers Watson, Andrew Rae Gilchrist, T R R Todd, David Murray Lyon (Medicine)
- Alexander Pirie Watson, Montagu Cotterill, Charles Walker Cathcart, William James Stuart, John William Struthers, Henry Wade, G L Chiene, James Methuen Graham, Walter Quarry Wood, Walter Mercer (Surgery)
- Robert Johnstone, Benjamin Philip Watson, James Haig Fergusson, Douglas Miller, Clifford Kennedy, Ernest Fahmy (Midwifery/Gynaecology)
- Arthur H H Sinclair, Harry Moss Traquair (Ophthalmology)
- Douglas Guthrie, Ion Simson Hall, G Ewart Martin (Diseases of Ear, Nose and Throat)
- Dawson Turner (Radiology)
Further reading
edit- Kaufman, Matthew H. (2003). Medical teaching in Edinburgh during the 18th and 19th centuries. Royal College of Surgeons of Edinburgh. Edinburgh: Royal College of Surgeons of Edinburgh. ISBN 978-0-9503620-8-3. OCLC 54786390.
- Comrie, John D.; Wellcome Historical Medical Museum (1927). History of Scottish medicine to 1860 [electronic resource]. Wellcome Library. London : Published for the Wellcome Historical Medical Museum by Baillière, Tindall & Cox.
- Guthrie, Douglas (1965). Extramural Medical Education in Edinburgh. Edinburgh: E & S Livingstone.
References
edit- ^ a b c d e f "The Archive of the Extramural School of Medicine of the Royal Colleges of Edinburgh". The Royal College of Surgeons of Edinburgh (RCSEd) Library and Archive. 17 February 2015. Retrieved 10 September 2020.
- ^ a b "Training of Doctors: the Goodenough Committee's Report". Br Med J. 2 (4359): 121–123. 1944. doi:10.1136/bmj.2.4359.121. ISSN 0007-1447. S2CID 220183532.
- ^ a b c d e f g Kaufman, Matthew H. (2003). Medical teaching in Edinburgh during the 18th and 19th centuries. Royal College of Surgeons of Edinburgh. Edinburgh: Royal College of Surgeons of Edinburgh. ISBN 978-0-9503620-8-3. OCLC 54786390.
- ^ Macintyre, IMC. and MacLaren IF. Surgeons Lives The Royal College of Surgeons of Edinburgh. Edinburgh 2005 p.28
- ^ a b c d e f g h i Guthrie, Douglas (1965). Extramural Medical Education in Edinburgh. Edinburgh: E & S Livingstone. p. 9.
- ^ Comrie, John D.; Wellcome Historical Medical Museum (1927). History of Scottish medicine to 1860 [electronic resource]. Wellcome Library. London : Published for the Wellcome Historical Medical Museum by Baillière, Tindall & Cox.
- ^ Barry, Jonathan (2019). "Educating physicians in seventeenth-century England". Science in Context. 32 (2): 137–154. doi:10.1017/S0269889719000188. ISSN 0269-8897. PMC 7254574.
- ^ a b c Lawrence, Christopher (2006). "The shaping of things to come: Scottish medical education 1700–1939". Medical Education. 40 (3): 212–218. doi:10.1111/j.1365-2929.2006.02393.x. ISSN 1365-2923. PMID 16483323. S2CID 23168665.
- ^ Arthur Logan Turner (1937). Story of a Great Hospital: The Royal Infirmary of Edinburgh, 1729-1929. Oliver and Boyd.
- ^ Boyes, John (1953). "James Rae 1716–1791". Proceedings of the Royal Society of Medicine. 46 (6): 457–460. doi:10.1177/003591575304600612. ISSN 0035-9157. PMC 1918565. PMID 13074190. S2CID 43776949.
- ^ a b c Thomson, D. M. (1984). "General practice and the Edinburgh Medical School: 200 years of teaching, care and research". The Journal of the Royal College of General Practitioners. 34 (258): 9–12. ISSN 0035-8797. PMC 1959640. PMID 6363687.
- ^ Macintyre, Iain (2012). "John Abercrombie (1780–1844)" (PDF). The Journal of the Royal College of Physicians of Edinburgh. 42 (3): 285. doi:10.4997/JRCPE.2012.320. PMID 23113324.
- ^ "Edinburgh, Argyle Square, General | Canmore". canmore.org.uk. Retrieved 24 July 2020.
- ^ a b Comrie, John (1932). "History of Scottish medicine". Wellcome Collection. Balliere, Tindall & Cox. Retrieved 15 August 2020.
- ^ "History of Scottish medicine". Wellcome Collection. Retrieved 15 August 2020.
- ^ "Medical Schools of Scotland, 1860-61". Edinburgh Medical Journal. 6 (4): 352–353. 1860. ISSN 0367-1038. PMC 5310441. PMID 29646881.
- ^ Rodwell, G. F. (2004). "Anderson, Thomas (1819–1874), chemist". In Anderson, T. B. (ed.). Oxford Dictionary of National Biography. Vol. 1 (online ed.). Oxford University Press. doi:10.1093/ref:odnb/500. (Subscription or UK public library membership required.)
- ^ "Engraving of Brown Square, Edinburgh by W. Forrest after D. Wilson". www.europeana.eu. Retrieved 2 August 2020.
- ^ "(676) - Towns > Edinburgh > 1846-1975 - Post Office Edinburgh and Leith directory > 1889-1890 - Scottish Directories - National Library of Scotland". digital.nls.uk. Retrieved 15 August 2020.
- ^ Brown, John (1861). Rab and His Friends. Edinburgh: Edmonston and Douglas.
- ^ a b Somerville, J. M. (2005). "Dr Sophia Jex-Blake and the Edinburgh School of Medicine for Women, 1886-1898". The Journal of the Royal College of Physicians of Edinburgh. 35 (3): 261–267. ISSN 1478-2715. PMID 16402502.
- ^ Dingwall, H. M. (2010). "The Triple Qualification examination of the Scottish medical and surgical colleges, 1884-1993". The Journal of the Royal College of Physicians of Edinburgh. 40 (3): 269–276. doi:10.4997/jrcpe.2010.317. ISSN 1478-2715. PMID 20973439.