Predictors of yoga use among internal medicine patients
© Cramer et al.; licensee BioMed Central Ltd. 2013
Received: 9 January 2013
Accepted: 11 July 2013
Published: 13 July 2013
Yoga seems to be an effective means to cope with a variety of internalmedicine conditions. While characteristics of yoga users have beeninvestigated in the general population, little is known about predictors ofyoga use and barriers to yoga use in internal medicine patients. The aim ofthis cross-sectional analysis was to identify sociodemographic, clinical,and psychological predictors of yoga use among internal medicinepatients.
A cross-sectional analysis was conducted among all patients being referred toa Department of Internal and Integrative Medicine during a 3-year period. Itwas assessed whether patients had ever used yoga for their primary medicalcomplaint, the perceived benefit, and the perceived harm of yoga practice.Potential predictors of yoga use including sociodemographic characteristics,health behavior, internal medicine diagnosis, general health status, mentalhealth, satisfaction with health, and health locus of control were assessed;and associations with yoga use were tested using multiple logisticregression analysis. Odds ratios (OR) with 95% confidence intervals (CI)were calculated for significant predictors.
Of 2486 participants, 303 (12.19%) reported having used yoga for theirprimary medical complaint. Of those, 184 (60.73%) reported benefits and 12(3.96%) reported harms due to yoga practice. Compared to yoga non-users,yoga users were more likely to be 50–64 years old(OR = 1.45; 95%CI = 1.05-2.01;P = 0.025); female (OR = 2.45;95%CI = 1.45-4.02; P < 0.001); and collegegraduates (OR = 1.61; 95%CI = 1.14-2.27;P = 0.007); and less likely to currently smoke(OR = 0.61; 95%CI = 0.39-0.96;P = 0.031). Manifest anxiety (OR = 1.47;95%CI = 1.06-2.04; P = 0.020); and high internalhealth locus of control (OR = 1.92;95%CI = 1.38-2.67; P < 0.001) were positivelyassociated with yoga use, while high external-fatalistic health locus ofcontrol (OR = 0.66; 95%CI = 0.47-0.92;P = 0.014) was negatively associated with yoga use.
Yoga was used for their primary medical complaint by 12.19% of an internalintegrative medicine patient population and was commonly perceived asbeneficial. Yoga use was not associated with the patients’ specificdiagnosis but with sociodemographic factors, mental health, and health locusof control. To improve adherence to yoga practice, it should be consideredthat male, younger, and anxious patients and those with low internal healthlocus of control might be less intrinsically motivated to start yoga.
KeywordsYoga Complementary therapies Internal medicine
Yoga has its roots in Indian philosophy and has been a part of traditional Indianspiritual practice for around 5000 years . Yoga comprises advice for ethical lifestyle as well as spiritualpractice . While the ultimate goal of yoga has been described as uniting mind, bodyand spirit , yoga has also been used to promote physical and mental well-being. InNorth America and Europe, yoga is most often associated with physical postures(asanas), breathing techniques (pranayama), and meditation (dyana) . It differs from purely gymnastic exercises in that the practitionerfocuses his mind on the postures with inner awareness and a meditative focus of mind [3, 4]. In recent years, yoga is gaining increased popularity as a therapeuticpractice: in 2002, more than 10 million Americans practiced yoga as a means ofimproving their health, and by 2007, more than 13 million [5, 6].
Yoga has been shown to improve a variety of physical health conditions such as lowback pain , fibromyalgia , arthritis , or irritable bowel syndrome . Yoga can reduce risk factors for cardiovascular disease  and improve risk profiles in adults with type 2 diabetes mellitus . Other conditions such as asthma seem to be relatively little improved byyoga interventions .
Despite the therapeutic value of yoga for internal medicine patients, little is knownabout factors that are associated with yoga use and barriers to practice in thispatient population. Based on a representative survey, Birdee et al.  characterized yoga users as being more likely to be female, young, andwell-educated. Yoga users more often suffered from musculoskeletal disorders thannon-users; and yoga was most commonly used to treat these disorders. Higher yoga usefurther was associated with asthma, while hypertension and chronic obstructive lungdisease were associated with lower use. An earlier survey also showed an associationof yoga use with lung disease and back pain . However, while these surveys were representative for the adultpopulation, characteristics of yoga users have hardly been investigated in patientpopulations.
The aim of this analysis was to identify sociodemographic, clinical, andpsychological predictors of yoga use for the patient’s primary medicalcomplaint among internal medicine patients. The analysis was based onsociodemographic variables, medical diagnosis, mental health, satisfaction, andhealth locus of control  that describes health behavior as a function of control beliefs : an individual’s belief about control of health outcomes can beclassified as either internal (health depends on the individual’s attributesor behavior) or external (health depends on the behavior of other people, fate orluck) [16, 17]. It has been shown that an internal health locus of control is associatedwith carrying out recommended health behaviors such as exercise behavior [18, 19] or weight management .
To identify predictors for therapeutic yoga use, a cross-sectional analysis wasconducted in a mixed internal medicine population. Based on the findings in the USgeneral population, it was hypothesized that yoga use for the patient’sprimary medical complaint would be higher in female, young, and well-educatedpatients. Associations of yoga use were further expected for patients with specificmedical conditions such as musculoskeletal conditions and lung diseases. Based onthe findings on other categories of health behavior, it was further hypothesizedthat higher yoga use would be found in patients with higher internal health locus ofcontrol.
The survey was part of the internal quality assurance of the Department forInternal and Integrative Medicine, Essen, Germany. All data were assessed aspaper-based self-rated questionnaires except for main diagnosis, age, and genderthat were taken from the patient’s medical record. Questionnaires werehanded out at admission and collected in by the receptionist. The information onmedical diagnosis and prior complementary therapies use were also used fordeveloping the individual treatment plan.
The survey was conducted in compliance with the Helsinki Declaration. No approvalwas required from an ethics committee according to the Germanlawa.
All patients being referred to a Department for Internal and Integrative Medicinebetween January 2001 and January 2004 were asked to complete the surveyimmediately upon admission. All patients were diagnosed with an internalmedicine condition . All included patients gave written informed consent. All data werede-identified and analyzed anonymously.
Using the Freiburg Questionnaire on Attitudes on Naturopathy it was assessedwhich complementary therapies patients had used before to treat their primarymedical complaint . For this analysis, only the question on yoga use was evaluated: Haveyou ever used yoga for your primary medical complaint? (response choice:yes/no). Those patients that reported to have used yoga for their primarymedical complaint were queried about helpfulness: How helpful was yoga for yourprimary medical complaint? (response choices: helpful/not helpful/harmful).Answers were categorized as helpful (yes, no) and harmful (yes, no).
Potential predictors of yoga use
Linear sociodemographic variables were categorized in order to be able tocompute odds ratios between yoga-users and non-users. Age (18–29,30–39, 40–49, 50–64, ≥65 years), sex, education(less than college, college graduate), employment (full-time, part-time,unemployed), and family status (in relationship, not in relationship), wereused as possible predictors together with health behaviors including smokingstatus (current smokers, past smoker, non-smokers), alcohol intake(abstainers, less than twice weekly, at least twice weekly), fast foodintake (abstainers, less than twice weekly, at least twice weekly).
The patients’ main diagnosis was assessed by the transferring doctoraccording to ICD-10 . For this analysis, diagnoses were categorized as a)osteoarthritis, b) arthritis, c) fibromyalgia, d) spinal pain, e) headache,f) other pain, g) hypertension, h) ischemic cardiac disease, i) irritablebowel syndrome, j) inflammatory bowel disease, k) lung diseases, l) other,more rare conditions.
General health status was assessed on a 5 point scale and categorized asgood, very good or excellent versus poor or fair.
Anxiety and depression were assessed using the Hospital Anxiety andDepression Scale (HADS) . Scores ranging from 8 to 10 were defined as subthreshold anxietyor depression while scores > 10 were defined as thresholdanxiety or depression . In this sample, Cronbach’s α was 0.81 for the anxietysubscale and 0.84 for the depression subscale.
Satisfaction with health and life in general (FLZ)
Satisfaction with health and life in general were assessed using one 5-pointLikert item each from the questionnaire for life satisfaction (FLZ) . The endpoints were 1 = very unsatisfied and5 = very satisfied. The higher the score the more satisfied thepatient was with health and life in general. Every patient was categorizedas having either high (i.e. above median) or low (i.e. below median)satisfaction with health and satisfaction with life in general.
Health locus of control
Health locus of control was assessed using the GKÜ , a 9-item German modified short-form of the multidimensionalhealth locus of control scale, the most commonly used scale to assess healthlocus of control . Response choices ranged from “strongly disagree” to“strongly agree”. The instrument assesses 3 dimensions of healthlocus of control beliefs (3 items each): internal (high perceived owninfluence on health status), external-social (health status perceived ascontrolled by others) and external-fatalistic (health status perceived asdepending on luck or destiny). Cronbach’s α was 0.74 forinternal, 0.46 for external-social, and 0.53 for external-fatalistic healthlocus of control. For every patient, each dimension was categorized aseither high (i.e. above median) or low (i.e. below median).
Chi square tests were used to compare sociodemographic, clinical, andpsychological characteristics between patients who ever used yoga for theirprimary medical complaint and those who did not. A p-value of ≤0.05was considered statistically significant. Independent predictors oftherapeutic yoga use were identified using multiple logistic regressionanalysis. A backward stepwise procedure with a Wald statistic p-value of≤0.05 was used. In order to be able to compare the individualinfluence the different variables had on yoga use, continuous variables werecategorized and adjusted odds raios with 95% confidence intervals werecalculated. Among the potential factors that were entered in the initialregression model, only factors were selected that were associated with yogause at a p-value of ≤0.10 in univariate analysis. Statistical analysiswas performed using IBM SPSS® software (release 20.0, IBM, USA).
Of the 2804 patients being referred during the 3-year study period, 2486 agreed toparticipate in the survey (response rate 88.66%). Of the respondents, 325 patients(13.07%) did not answer the question on yoga use. Therefore, the analysis was basedon a sample of 2161 patients. In this sample, the amount of missing values rangedfrom 0.0% for diagnosis, age, and gender to 4.8% for one item of the GKÜ.Overall, 1.8% of the values were missing. Out of 2161 patients, 1715 (79.4%) werefemale, mean age was 52.9 ± 14.1. Most patients were diagnosed withchronic pain; the most commonly diagnosed conditions were spinal pain(n = 412; 19.1%), headache (n = 257; 11.9%), andfibromyalgia (n = 249; 11.5%). Five hundred eighty-one patients (29.9%)were high school graduates; 569 (26.3%) were full-time employed; and 341 (15.8%)were part-time employed. One thousand two hundred sixty-two patients (58.4%) were ina relationship. Regarding health behavior, 1834 (84.9%) regularly consumed fastfood; 357 (16.5%) regularly consumed alcoholic beverages; and 299 (13.8%) currentlysmoked.
Three hundred and three patients (12.19%) reported having used yoga for their primarymedical complaint. Of those, 184 (60.73%) reported that yoga had been helpful and 12(3.96%) reported that yoga had been harmful.
Sociodemographic, clinical, and psychologicalcharacteristics of patients who used yoga for their primary medicalcomplaint (yoga users) and those who did not (yoganon-users)
Yoga non-users (n = 1858)
Yoga users (n = 303)
Less than 30
30 to 39
40 to 49
50 to 64
65 or greater
High school graduate
Alcohol at least twice weekly
Fast food abstainer
Fast food at least twice weekly
Ischemic cardiac disease
Irritable bowel syndrome
Inflammatory bowel disease
Good, very good or excellent
High satisfaction with health
High satisfaction in general
Health locus of control
Independent predictors of yoga use for the patient’s primarymedical complaint
Adjusted odds ratio
95% confidence interval
Education: College graduate
Internal health locus of control
External-fatalistic health locus of control
In this survey, 12.19% of internal medicine patients reported having used yoga fortheir primary medical complaint. The majority of patients found yoga to be helpfulin dealing with their complaints and only a small minority reported harms associatedwith yoga practice. Yoga users were more likely to be female, in their fifties tomid-sixties and well educated. They smoked less than non-users. Yoga use wasassociated with above-threshold levels of anxiety but not with internal medicinediagnosis. Patients who used yoga for their primary medical complaint tended to havehigh internal health locus of control and low external-fatalistic health locus ofcontrol.
While no data on the rate of yoga use in the European population is available, theprevalence of yoga use found in this survey is higher than that found in the generalpopulation where prevalence ranged from 5.1% [5, 14] to 7.5% . A recent survey in breast cancer patients however reported even higherprevalence of yoga use after cancer diagnosis . While differences between settings limit the comparability of theseresults, this might indicate that specific patient groups tend to try yoga moreoften than the general population. The finding that yoga use is higher amongwell-educated non-smoking persons is in line with prior surveys in the generaleducation [14, 15] and in breast cancer patients . Female gender also has commonly been associated with higher yoga use [14, 15]. While no association with age was found in breast cancer patients, yogausers in the general population tended to be younger than non-users, a finding thatcontradicts the results of the present survey: in the 2002 National Health InterviewSurvey, age of 40 years or higher was significantly associated with lower yoga usecompared to the age group of 30 years or lower . Comparably, an earlier survey found significantly higher rates of yogause in the age group of 34–53 years when compared to those aged 54 years orhigher .
Yoga use has been associated with a variety of health conditions in the generalpopulation, mainly musculoskeletal or mental disorders , and lung disease . Interestingly, in the current survey, that focused specifically oninternal medicine patients, yoga use was associated with anxiety but not withinternal medicine diagnosis. Yoga has been shown to have beneficial effects on avariety of internal medicine conditions including spinal pain [7, 29], fibromyalgia , and arthritis . While the prior surveys suggest that these are the most commonconditions for which yoga is used [14, 15], this is not reflected in the current patient-based survey. As otherconditions such as asthma  are less likely to benefit from yoga use, internal medicinepatients’ decision to try yoga to cope with their conditions does not seem tobe evidence-based. Providing more detailed information about evidence ofeffectiveness of yoga for specific health conditions could improve patients’possibility for informed decision making.
Health locus of control was a strong predictor of yoga use for the patients’primary medical complaints. Yoga use was higher in patients who had high internalhealth locus of control, that is the belief that health depends on the persons ownbehavior; and low external-fatalistic health locus of control, that is the beliefthat health depends on fate on luck [16, 17]. As yoga is an active coping strategy that depends on the patients’motivations and actions, this association is reasonable. It is in line with priorstudies that found associations of exercise behavior with higher internal and lowerexternal health locus of control [18, 19]. General use of complementary therapies has also been found to beassociated with high internal health locus of control . It should be noted that internal and external health locus of controlare generally uncorrelated with each other or only slightly negativelyintercorrelated . Therefore one patient could theoretically have both high internal andhigh external health locus of control.
The results of this study are limited by the single-center setting that might limitgeneralizability of the results. The results might therefore only apply to Germaninternal medicine patients that have a general interest in integrative medicine. TheDepartment of Internal and Integrative Medicine Essen, Germany, is a modelinstitution that treats patients with internal diseases using a combination ofconventional and evidence-based complementary therapies . While the department might specifically attract patients who aregenerally interested in internal medicine, patients have to be referred to thedepartment by their general practitioners and costs are covered by the Germanstatutory and many private health insurances. A further limitation is that the datahas been collected several years ago. As the rate of yoga use has been shown tosteadily increase in the USA [5,6,], a comparable development might be considerablefor Germany. While no data on yoga use in Germany are available, it seems likelythat this analysis underestimates the total rate of actual yoga use. The survey didnot assess reasons for yoga use, attitudes towards yoga, specific yoga style, orfrequency of yoga use. Subjective efficacy and safety of yoga use were assessed butthe perceived benefits or harms were not investigated in depths.Moreover, due to thedesign of the questionnaire, patients were unable to rate yoga as both helpful andharmful. Internal consistency of the instruments was good for the HADS, acceptablefor the internal scale of the GKÜ, but poor for the external-fatalistic scale.Therefore, external-fatalistic health locus of control as a predictor of yoga usehas to be interpreted with care. As single items from the FLZ were used instead ofthe complete instrument, psychometric properties are unclear for satisfaction. Race,religion, body mass index, and other factors that have been shown to be associatedwith yoga use in earlier studies were not assessed in the current survey. Despitethese limitations, the current study can enrich earlier findings on predictors ofyoga use in other populations [14, 15, 28].
Future research should investigate predictors of yoga use for the patient’sprimary medical complaint in a more representative patient sample and focus onreasons for use and barriers to use. Investigation of knowledge about evidence ofeffectiveness for yoga and on yoga in general in this patient population couldimprove informed decision making about use or non-use of yoga as a copingstrategy.
Yoga was practiced for the patients’ primary medical complaints by 12.09% of aninternal medicine patient population and was commonly perceived as beneficial. Yogause was not associated with the patients’ specific diagnosis but withsociodemographic factors, mental health, and health locus of control. To improveadherence to yoga practice in research and clinical practice, it should beconsidered that males, younger patients, smokers, anxious patients, and those withlow internal health locus of control might be less intrinsically motivated to startyoga and might need additional information.
aIn Germany, the need for ethical approval is only statutorily regulatedfor clinical trials on drugs and medical devices, and for stem cell research.
http://www.gesetze-im-internet.de/amg_1976/__40.html [German only].
The Medical Association's Professional Code of Conduct (Berufsordnung für die inDeutschland tätigen Ärztinnen und Ärzte der Bundesärztekammer)regulates the need for further ethical approval of other research conducted byphysicians and states that research projects that interfere with a human’sphysical or psychological integrity or uses bodily materials or data that arerelatable to a specific human need to be approved by an ethics committee. This wasnot the case in this survey as all data were de-identified and analyzedanonymously.
The authors thank all physicians, nurses, staff members and patients for theirhelp in data collection. This study was part of a quality assurance program andsupported by a research grant from the Karl and Veronica Carstens Foundation,Essen, Germany.
- Feuerstein G: The yoga tradition. 1998, Prescott: Hohm PressGoogle Scholar
- Iyengar BKS: Light on yoga. 1966, New York: Schocken BooksGoogle Scholar
- Büssing A, Edelhäuser F, Weisskircher A, Fouladbakhsh JM, Heusser P: Inner correspondence and peacefulness with practices among participants ineurythmy therapy and yoga: a validation study. Evid Based Complement Alternat Med. 2011, 2011: 329023-View ArticlePubMedGoogle Scholar
- Cramer H, Lauche R, Haller H, Langhorst J, Dobos G, Berger B: A qualitative study of yoga for patients with chronic neck pain. J Altern Complement Med. 2013, 19: 536-542. 10.1089/acm.2011.0885.View ArticlePubMedGoogle Scholar
- Barnes PM, Powell-Griner E, McFann K, Nahin RL: Complementary and alternative medicine use among adults: United States,2002. Advance Data. 2004, 27: 1-19.Google Scholar
- Barnes PM, Nahin R: Complementary and alternative medicine use among adults and children: UnitedStates, 2007. Natl Health Stat Report. 2008, 10: 1-23.Google Scholar
- Cramer H, Lauche R, Haller H, Dobos G: A systematic review and meta-analysis of yoga for low back pain. Clin J Pain. 2013, 29: 450-460. 10.1097/AJP.0b013e31825e1492.View ArticlePubMedGoogle Scholar
- Langhorst J, Klose P, Dobos GJ, Bernardy K, Häuser W: Effficacy and safety of meditative movement therapies in fibromyalgiasyndrome: a systematic review and meta-analysis of randomized controlledtrials. Rheumatol Int. 2013, 33: 193-207. 10.1007/s00296-012-2360-1.View ArticlePubMedGoogle Scholar
- Haaz S, Bartlett SJ: Yoga for arthritis: a scoping review. Rheum Dis Clin North Am. 2001, 37: 33-46.View ArticleGoogle Scholar
- Kuttner L, Chambers CT, Hardial J, Israel DM, Jacobson K, Evans K: A randomized trial of yoga for adolescents with irritable bowel syndrome. Pain Res Manag. 2006, 11: 217-223.View ArticlePubMedPubMed CentralGoogle Scholar
- Innes KE, Bourguignon C, Taylor AG: Risk indices associated with the insulin resistance syndrome, cardiovasculardisease, and possible protection with yoga: a systematic review. J Am Board Fam Pract. 2005, 18: 491-519. 10.3122/jabfm.18.6.491.View ArticlePubMedGoogle Scholar
- Innes KE, Vincent HK: The influence of yoga-based programs on risk profiles in adults with type 2diabetes mellitus: a systematic review. Evid Based Complement Alternat Med. 2007, 4: 469-486. 10.1093/ecam/nel103.View ArticlePubMedGoogle Scholar
- Posadzki P, Ernst E: Yoga for asthma? A systematic review of randomized clinical trials. J Asthma. 2011, 48: 632-639. 10.3109/02770903.2011.584358.View ArticlePubMedGoogle Scholar
- Birdee GS, Legedza AT, Saper RB, Bertisch SM, Eisenberg DM: Characteristics of yoga users: results of a national survey. J Gen Intern Med. 2008, 23: 1653-1658. 10.1007/s11606-008-0735-5.View ArticlePubMedPubMed CentralGoogle Scholar
- Saper RB, Eisenberg DM, Davis RB, Culpepper L, Phillips RS: Prevalence and patterns of adult yoga use in the United States: results of anational survey. Altern Ther Health Med. 2004, 10: 44-49.PubMedGoogle Scholar
- Wallston KA: Control and Health. Encyclopedia of Health & Behavior. Edited by: Anderson N. 2004, Thousand Oaks: Sage, 217-220.Google Scholar
- Wallston KA: Multidimensional Health Locus of Control Scale. Encyclopedia of Health Psychology. Edited by: Christensen AJ, Martin R, Smyth J. 2004, New York: Kluwer Academic/Plenum, 171-172.Google Scholar
- Slenker SE, Price JH, O'Connell JK: Health locus of control of joggers and nonexercisers. Percept Mot Skills. 1985, 61: 323-328. 10.2466/pms.19188.8.131.523.View ArticlePubMedGoogle Scholar
- Norman P, Bennett P, Smith C, Murphy S: Health locus of control and leisure-time exercise. Pers Individ Dif. 1997, 23: 769-774. 10.1016/S0191-8869(97)00106-2.View ArticleGoogle Scholar
- Saltzer EB: The Weight Locus of Control (WLOC) Scale specific measure for obesityresearch. J Pers Assess. 1982, 46: 620-628. 10.1207/s15327752jpa4606_11.View ArticlePubMedGoogle Scholar
- Lauche R, Cramer H, Moebus S, Paul A, Michalsen A, Langhorst J, Dobos G: Results of a 2-week inpatient stay at the department for internal andintegrative medicine: an observational study. Evid Based Complement Alternat Med. 2012, 2012: 875874-PubMedPubMed CentralGoogle Scholar
- Huber R, Koch D, Beiser I, Zschocke I, Luedtke R: Experience and attitudes towards CAM-a survey of internal and psychosomaticpatients in a German university hospital. Altern Ther Health Med. 2004, 10: 32-36.PubMedGoogle Scholar
- World Health Organization: International Statistical Classification of Diseases and Related HealthProblems. 10th revision.http://apps.who.int/classifications/icd10/browse/2010/en,
- Herrmann C, Buss U, Snaith RP: Hospital Anxiety and Depression Scale - Deutsche Version (HADS-D).Manual. 1995, Bern, Switzerland: Hans Huber,Google Scholar
- Snaith RP: The Hospital Anxiety And Depression Scale. Health Qual Life Outcomes. 2003, 1: 29-10.1186/1477-7525-1-29.View ArticlePubMedPubMed CentralGoogle Scholar
- Fahrenberg J, Myrtek M, Schumacher J, Brähler E: Fragebogen zur Lebenszufriedenheit (FLZ). Handanweisung. 2000, Göttingen, Germany: HogrefeGoogle Scholar
- Westhoff G: Handbuch psychosozialer Messinstrumente. 1993, Göttingen, Germany: HogrefeGoogle Scholar
- Desai K, Bowman MA, Galantino ML, Hughes-Halbert C, Vapiwala N, Demichele A, Mao JJ: Predictors of yoga use among patients with breast cancer. Explore (NY). 2010, 6: 359-363. 10.1016/j.explore.2010.08.002.View ArticleGoogle Scholar
- Cramer H, Lauche R, Hohmann C, Lüdtke R, Haller H, Michalsen A, Langhorst J, Dobos G: Randomized controlled trial comparing yoga and home-based exercise forchronic neck pain. Clin J Pain. 2013, 29: 216-223. 10.1097/AJP.0b013e318251026c.View ArticlePubMedGoogle Scholar
- McFadden KL, Hernández TD, Ito TA: Attitudes toward complementary and alternative medicine influence its use. Explore (NY). 2010, 6: 380-388. 10.1016/j.explore.2010.08.004.View ArticlePubMed CentralGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6882/13/172/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), whichpermits unrestricted use, distribution, and reproduction in any medium, provided theoriginal work is properly cited.