Yoga Nidra: An innovative approach for management of chronic insomnia- A case report
Sleep Science and Practice volume 1, Article number: 7 (2017)
Chronic insomnia is a common sleep problem and there is a need to complement the existing treatment options. Yoga nidra practice is documented to be used for sleep by sages. Recently, yoga nidra has been used in patients of menstrual abnormalities, post- traumatic stress disorder, diabetes, anxiety and depression but little is known about its effect on sleep or sleep disorders. Although we find description of yoga nidra in literature, there is no scientific report of its application in sleep disorders. The objective of the study was to develop yoga nidra model in management of chronic insomnia patients. The model was developed using inputs from yoga school trained instructors of yoga nidra.
Patient 01: 60 years old widower with complaints of sleep maintenance insomnia since 20 years. He had worry at daytime regarding falling off to sleep which became even worse at bedtime. He had history of benign prostatic hypertrophy and had no history of any medications for sleep or any other disease. Patient 02: 78 years old male self-employed, company owner with complaints of sleep maintenance insomnia since 15 years. He felt quite energetic during the day due to the work requirement but in the evening started feeling anxious about sleep problem which worsened at bedtime. He was on tablet clonazepam 0.25 mg HS off and on since 1 year. After the baseline assessment, yoga nidra intervention was started followed by five supervised sessions after which the patients were instructed to practice yoga nidra daily on their own. Regular fortnightly follow ups were done till 4 weeks of start of yoga nidra intervention. Repeat PSG was offered in case patient volunteered. Sleep diary parameters were analysed using Friedman test and Wilcoxon Signed Ranks test. There was an improvement in sleep quality, insomnia severity, depression anxiety and stress scores after yoga nidra. The improvement remained even after 3 months of start of intervention. Repeat PSG in second patient showed an increase in N3 after 4 weeks of yoga nidra intervention.
Yoga nidra can be used as an important adjunct in management of chronic insomnia patients.
CTRI/2013/05/003682 [Registered on: 27/05/2013] Trial Registered Retrospectively.
Chronic insomnia is a common sleep problem and is associated with increased morbidity and mortality (Taylor et al. 2007). Available treatment options include pharmacological and non-pharmacological approach. Studies have shown sleeping pill users at a greater mortality risk (Kripke et al. 2002) and though drugs like zolpidem have been found to be safe for short term use (Schutte-Rodin et al. 2008) but when taken for years these medications also produce unwanted side effects like sleep related eating disorders and sleep walking (Hoque and Chesson 2009) and even increased cancer risk (Kao et al. 2012).
Non pharmacological approach using cognitive behavioral therapy for insomnia (CBTI) is considered beneficial. CBTI though remains the first line of therapy for insomnia but is often underutilized (Schutte-Rodin et al. 2008). Underutilisation of CBTI is reported because of reasons which are both patient centred and system based issues. Patient related reasons include time and cost involvement and limited availability of CBTI trained specialists being a major system based problem.
Complementary and alternative medicine in the form of Kundalini yoga (Khalsa 2004), Tai Chih Chi (Irwin et al. 2008), mindfulness meditation (Ong et al. 2014), acupuncture and Chinese herbal medicines have been tried in insomnia patients. There is a felt need to complement the existing gamut of treatment options for insomnia patients.
According to the ancient Indian scriptures, sages are known to sleep using yoga nidra. Yoga Nidra is derived from two Sanskrit words, ‘Yoga’ (‘yuj’ = yoke) meaning union or one pointed awareness and ‘nidra’ means sleep. Yoga nidra is derived from ‘pratyahara’ of raja yoga and tantric practise of ‘nyasa’. In ‘pratyahara’ mind and mental awareness are dissociated from the sensory channels. ‘Nyasa’ means ‘to place or to take the mind to that point’. Yoga nidra is documented as neither nyasa nor meditation as yoga nidra is done in supine position and unlike meditation which is an aware awake state, yoga nidra is considered as aware sleep state (Saraswati 1998). ‘Nyasa’ is practised in sitting posture and involves the recitation of mantras in Sanskrit to experience different parts of the body which increases the scope of this practise beyond different cultures.
Yoga nidra was known to be practised by sages and it was passed on to their disciples traditionally. Swami Satyananda Saraswati, renowned teacher from Bihar School of Yoga, Munger, Bihar, India laid down the basics of learning yoga nidra in the form of a book. He described yoga nidra as a ‘systematic method of inducing complete physical, mental and emotional relaxation and in this state the relaxation is achieved by turning inwards, away from outer experiences’ (Saraswati 1998). It can be done following instructions from his book by a teacher or by a way of audio compact disc (CD).
Yoga nidra has been tried as a therapeutic option for many diseases. The relative ease of practise has made it an acceptable therapeutic option for many diseases. Yoga nidra has been used in patients of menstrual abnormalities (Rani et al. 2011), post- traumatic stress disorder (Stankovic 2011), diabetes (Amita et al. 2009), anxiety and depression (Rani et al. 2012) but little is known about its effect on sleep or sleep disorders.
Although we find description of yoga nidra in literature, there is no scientific report of its application in sleep disorders.
Since yoga nidra has been used as a therapeutic option with no documented side effects and it is mentioned related to sleep in scriptures, there was a felt need to develop this method as a model in management of chronic insomnia patients.
The objective of the study was to develop yoga nidra as a complementary model in management of chronic insomnia patients. Authors had asked for volunteers through advertisement placed at various OPDs. Two patients aged 60 and 78 years, who volunteered for the model of yoga nidra, are discussed. They were explained about the nature of study and informed consent was obtained. The study was approved by the Institutional ethical committee of All India Institute of Medical Sciences, New Delhi, India (reference number IESC/T-394/02.11.2012).
Diagnosed chronic insomnia patients came from sleep clinic out patients department (OPD) of MTFootnote 1, senior neurologist and certified sleep specialist. They were on treatment and were referred to KDFootnote 2 in case they volunteered to add yoga nidra intervention to the already prescribed treatment. An informed consent from the patient was taken.
Patients following usual sleep wake schedule during the study period. Patients with morning circadian preference were included. Patients who were keen to volunteer for the study were included and they had a right to withdraw anytime during the study.
Any patient who was likely to plan an intercontinental flight or was not able to follow usual sleep wake schedule during the study period. Patients with evening circadian preference were excluded from the study. Morningness Eveningness Scale (MES) (Horne and Ostberg 1976; Paine et al. 2006) was used to screen patients and only those patients with a morning preference were taken. This was done as the patients should have been most alert at the time of yoga nidra session which was in the morning from 0900 h to 1130 h making it important to exclude patients with delayed circadian rhythm. The scale also assess the time of the morning when they were most alert which helped in planning the yoga nidra sessions further. We included morning preference also because we did not want circadian rhythm as a confounding factor since the effect of yoga nidra on circadian rhythm is not known.
Two patients Patient 01 and 02 underwent the intervention using yoga nidra model.
Patient 01: 60 years old widower with complaints of not able to sleep after getting up at night since 20 years for more than 30 min and more than three times a week. Patient had worry at daytime regarding falling off to sleep which became even worse at bedtime. Patient had history of benign prostatic hypertrophy and had no history of any medications for sleep or any other disease.
Patient 02: 78 years old male self-employed, company owner with complaints of not able to sleep after getting awake at night for more than 30 min and more than three times a week since 15 years. He felt quite energetic during the day due to the work requirement but in the evening started feeling anxious about sleep problem which worsened at bedtime. He was on tablet clonazepam 0.25 mg HS off and on since 1 year.
Development of a model for using yoga nidra in insomnia patients
KD2 visited Bihar School of Yoga, Munger and attended sessions of yoga nidra taken by teachers. Permission to use yoga nidra for chronic insomnia patients was taken. She had discussions with the teachers and doctor in the school. The teachers brought out the usual problems faced during conducting and also while doing the session oneself. KD2 also did sessions herself under supervision while in ashram to get a hands-on feel of the session which would help planning for the patients subsequently. Planning of the session was done keeping the discussion in mind. The patients were taught using pre-recorded audio CD on yoga nidra© from the school which are easily available for sale.
The discussion brought out that a yoga nidra session every day for 3 to 4 days as done in short yoga programmes helps their subject to make them comfortable during the session. It was also pointed out that at times the instructions are not clear to all the subjects and might require elaboration on an individual basis. Keeping these points in mind five supervised sessions were planned continuously every day for 5 days. The method of doing yoga nidra involves seven steps namely – preparation, samkalpa (samkalpa = idea or notion formed in the heart or mind), body part awareness or rotation of consciousness, breath awareness, feeling and sensation, visualization and ending of practice (Saraswati 1998).
Planning of the Model included three basic parts
Assessment for readiness and voluntary participation
Discussion with yoga teachers and doctor at the school brought out that the subject has to be ready for taking a session as it included voluntarily following the instructions without sleeping. It was suggested by the Bihar school of yoga teachers that the session should be carried out when the person is most alert to avoid sleep during the session. Since the sessions were done in the morning hours, we excluded patients with an evening circadian preference in the study.
The patient was verbally informed that this method was novel and though has been tried in other diseases with no reported side effects but it was essential to follow up closely for initial days requiring the patient to report daily for a minimum of 5 days initially and subsequently for follow ups. Since it required time, volunteering was an indirect measure of the commitment of the patient towards the management. The patient was free to withdraw from the study at any time of the intervention.
The patient was then briefed about yoga nidra, its philosophy and available reports of its use as a therapeutic option. Then baseline assessment was completed and documented.
Initial five daily supervised sessions at the time when they are most alert during daytime was planned. Each session takes approximately 30 min. Before the start of the session, the patient was instructed to make himself comfortable. Since, insomnia patients are sensitive to changes in their daily routine on sleep (basic premise for use of principles of sleep hygiene and education), intervention like yoga nidra is likely to affect sleep and hence the patients were kept under direct supervision of a certified sleep specialist. The constant supervision was maintained by KD at all times, initially by planning daily supervised sessions and the monitoring using sleep diary/development of any new symptoms specifically for potential side effects (Edinger et al. 2015) and informing about regular follow ups.
What to do during the session for the observer
The patient was not interrupted during the session. Signs of restlessness e.g. tossing and turning, moving hands, shutting eyes too tightly, not looking relaxed etc. were observed. Cues of whether the patient was following instructions were carefully noted e.g. When the instructor asked the subject to take a deep breath, or look down while keeping eyes closed, the observer made a note of whether the patient followed. In case the patient was found not following instructions or appeared restless, time of the practise was noted from the player and subsequently discussed after the session.
Discussion by the observer with the patient after the session
The patient was asked of the various phases of yoga nidra (as mentioned in ‘Additional file 1’) he felt he went through. This is extremely important as yoga nidra is considered very relaxing and might put an insomnia patient to sleep despite being the most alert time of the day for him. According to the experienced teachers usually there is 50% retention of the basic various phases by the second day of practise. The practising subjects on an average start remembering all the different phases by the end of the fourth day. We gave 5 days considering some insomnia patients might fall sleepy during the sessions. Then the patients were asked to practise the session at home every day.
Patients were now asked about the problem faced during the session. The noted time points by the observer where he felt the patient was not following were also discussed. In case any clarifications regarding the instructions were required they were provided so as to better the next session.
The patient was also encouraged to listen to the tape at home after the first supervised session and was instructed to write down instructions which were not clear to the patient. This was done to increase his compliance during the subsequent sessions. These points of the patient were discussed the next day before starting the next day session as advised by yoga school since it relieves anxiety of the patient.
The entire session was then discussed with the patient as to how he feels it went, the patient was assured and instructed to follow the instructions as they were and not analyse or worry about them.
Yoga nidra intervention was done using a copyrighted pre-recorded Yoga Nidra audio CD approximately 27.2 min from Bihar School of Yoga, Munger, Bihar, India. Conduct of yoga nidra session was done in a sound proof room, with minimal ambient lighting during daytime. The subject was made to lie in the supine posture on a comfortable mattress. The entire session was done in shavasana (shava means “corpse” and asana means “posture”). The posture used for this asana is lying on the back, the arms and legs are kept at about 45° with the palms facing upwards. A soft pillow is optional to give maximum comfort to the patient while the entire session. This posture minimises the contact points especially between the limbs of the body. Brief outline of practise of doing yoga nidra and general instructions given to subjects is attached in ‘Additional file 1’ (Saraswati 1998).
Sleep diary– Sleep diary was used by the patients to mark the daily activities. This could be filled on paper or on an excel sheet according to the patients choice.
The diary was to be filled twice a day, once in the morning on getting up and then again at night just before bedtime. The individual fills in the details of time of lying in bed, approximate time required to fall asleep, wake up time, number of breaks in sleep and the approximate time that the individual feels that he was awake before falling off to sleep. Sleep quality on a scale of 10 was also reported in the diary along with other details of time of meals, exercise and time of yoga nidra. Parameters calculated using 2 weeks sleep diary were- Time in Bed (TIB): the total time the individual was lying in the bed i.e. the number of hours from the time of lying in bed to time of finally waking up; Sleep Onset Latency (SOL): the time initially spent in bed trying to sleep after lying in bed to sleep; Wake After Sleep Onset (WASO): time spent awake in bed after initially sleeping and before finally waking up; Total Sleep Time (TST): TST can be calculated by subtracting the SOL and WASO from TIB; Sleep Efficiency: calculated by the formula- (TST/TIB) x100; Total Wake Duration (TWD): SOL + total time of sleep breaks. These parameters were calculated for each night for the patient. Day 01st to 14th represent baseline, 15th day represents the first day of yoga nidra intervention, 28th -41st was used for the data analysis i.e. when the patient came for fourth week follow up. Baseline sleep diary was a mandatory requirement as is considered an important tool in assessing sleep in an insomnia patient.
Sleep questionnaires- Pittsburgh Sleep Quality Index (PSQI) (Buysse et al. 1989), Insomnia Severity Index (ISI) (Morin et al. 2011), Depression Anxiety Stress Scale (DASS) (Lovibond and Lovibond 1995; Brown et al. 1997) Epworth Sleepiness Scale (“ESS © MW JOHNS 1990–1997. USED UNDER LICENSE”) (Johns 1991) Pre Sleep Arousal Scale (PSAS) (Nicassio et al. 1985).
Digital polysomnography (PSG) - Overnight PSG was done using Somnomedics© PSG system, Germany with the standard montage. Electroencephalography (EEG), Electro-oculography (EOG) and Electromyography (EMG) were sampled at 256 Hz. The low frequency and high frequency filter setting were EEG-0.3,35 Hz; EOG-0.3,35 Hz; EMG- 10,256 Hz; EEG, EOG and EMG channels were placed along with pulse oximeter, RIP belts for thoracic and abdominal movements, Electrocardiography (ECG), oronasal pressure cannula and thermistor sensors according to American Association of Sleep Medicine (AASM) guidelines (Berry et al. 2014). Notch filter at 50 Hz was put and simultaneous video monitoring was done with the PSG device during the entire night. This was done in MT1 sleep lab by technicians. The staging of the sleep was done using AASM criteria and relative percentages of various sleep stages were calculated. Parameters like TIB, TST, WASO, SPT, Sleep Period Time (TST+ WASO), SOL: Time from start of recording to first epoch of sleep and, REM Latency, SE = TSTx100/TBT were calculated. Various stages of rapid eye movement sleep (REM) and Non REM sleep (N1, N2, N3) were scored and calculated as percentage of TST and TIB.
Two fortnightly follow ups were considered mandatory for the patients after the start of yoga nidra intervention. During this study, patients were also instructed to meet MT1 at least at the end of the month and at any time when the patient felt he deteriorated during this intervention.
Assessment of outcome measures
Primary outcome measures which were considered for improvement of patients were related to sleep and also improvement in daytime functioning (Edinger et al. 2015). These were sleep diary parameters -total sleep time, total wake duration, overall rating of sleep quality and Insomnia Severity Index for assessment of sleep. Day time functioning was evaluated by depression anxiety and stress scores during daytime using DASS and sleepiness during the day using “ESS © MW JOHNS 1990–1997 (Johns 1991). USED UNDER LICENSE”. Pre sleep arousal scale was also used. From this scale a total score, somatic and cognitive score of pre sleep arousal were calculated. A reduction in these scores occurs with reduction in pre sleep arousal. An increase in insomnia severity index, ESS©MW JOHNS 1990–1997 (Johns 1991) and DASS shows increase in severity in insomnia, increase in daytime sleepiness and increase in depression, anxiety and stress scores respectively.
Study design consisting of first 2 weeks of baseline followed by intervention using supervised yoga nidra training is shown in timeline in Fig. 1.
After obtaining informed consent from the patient, as a baseline assessment apart from the 2 weeks sleep diary the patients had to fill sleep questionnaires ISI, “ESS (Johns 1991) © MW JOHNS 1990–1997. USED UNDER LICENSE”, PSQI and pre sleep arousal scale. Patients also filled MES which was used to screen subjects and only those with morning preference were used for the study. Baseline PSG was done. This was done not only to assess insomnia but also to document presence of other sleep disorders.
Yoga nidra supervised sessions
Yoga nidra training was done using copyrighted CD. After 05 days of yoga nidra training under supervision, the patients were instructed to practice yoga nidra at home daily at a time when he was alert.
Assessment at the end of two weeks
PSQI, “ESS (Johns 1991) © MW JOHNS 1990–1997. USED UNDER LICENSE”, ISI, and PSAS and patient were instructed to fill sleep diary for the next 14 days.
Assessment at the end of four weeks
Questionnaires like PSQI, “ESS (Johns 1991) © MW JOHNS 1990–1997. USED UNDER LICENSE”, ISI, and PSAS were completed by the patient and 2 weeks sleep diary of the past 2 weeks was collected as assessed.
Sleep diaries for both the patients were analysed. Patient 01 filled the diary continuously till 93rd day i.e. 79th day after intervention (93-14 = 79) and patient 02 till 46th day i.e. 32nd day after starting intervention. Analysis of sleep diary was done as: baseline1-14; at 1 month- 28–41 day and for patient 01 at 3 months as 79–93 day. Various sleep diary parameters are shown schematically for patient 01 and 02 in Fig. 2.
Sleep diary parameters of patient 01 showed significant changes in sleep onset latency (Friedman χ2 (2) = 12.606, p < .005), WASO (Friedman χ2 (2) = 7.370, p < .05), TWD (Friedman χ2 (2) = 16.618, p < .005) and rating of sleep on a scale of 0 to 10 (Friedman χ2 (2) = 23.192, p < .0005). Results of post hoc tests are shown in Fig. 3. Sleep diary parameters of patient 02 are shown in Fig. 4. Significant improvement was found in SOL and TST as shown in the figure.
On regular visits patients were asked about the anxiety and worry regarding falling asleep. They reported an improvement in the problem. Our patients did not report any headaches, drowsiness, or any daytime symptom of excessive sleepiness. The ISI, DASS and PSAS scores were also noted. Questionnaireresults for both patients are shown in Tables 1 and 2. BaselinePSG data of both patients did not show association of any other sleep problem. The latencies and percentage of different stages is shown in Table 3 along with repeat PSG of Patient 01 who volunteered to undergo repeat PSG after 04 weeks of intervention.
Discussion and Conclusions
After yoga nidra intervention, we found significant changes in sleep parameters. In the first patient total sleep time did not change significantly though sleep onset latency and WASO improved significantly. In our study patients were instructed about sleep hygiene principles as a result of which excessive lying in bed was reduced. That may explain improvement in sleep onset latency in this patient. In the second patient both total sleep time and sleep onset latency showed improvement with no significant changes in WASO. Yoga nidra has been found to be associated with shift towards parasympathetic dominance (Markil et al. 2012). High cardiac vagal control is related to better subjective and objective sleep quality (Werner et al. 2015). Yoga practise in the morning has been found to increase parasympathetic drive at night (Patra and Telles 2010) causing sleep to be more restorative which may explain significant improvement in sleep quality ratings and WASO.N3% TST improved with intervention which is a reliable indicator in PSG in insomnia (Israel et al. 2012). This increase in slow wave sleep may be responsible for the improved sleep quality. The probable mechanisms which might affect sleep quality and subjectively feeling better may be linked to cognitive structuring effects of these practices which make the mental processing of external inputs more relaxed (Deepak 2002). Though probable mechanisms involved with yoga nidra are not clear at present but mindfulness meditation is known to target deficits in executive attention which characterise mood and anxiety (Ainsworth et al. 2013) and psychological symptoms (Smernoff et al. 2015). Reduction in sympathetic arousal and reduced emotional states are the probable reasons for improvement in insomnia patients with mindfulness meditation (Ong et al. 2014; Morin et al. 1992; Ong et al. 2008; Ong et al. 2009; Martires and Zeidler 2015).
In our patients yoga nidra did not reduce total sleep time unlike a study on meditators where a reduced sleep need due to meditation was proposed (Kaul et al. 2010). Yoga nidra has been used in diseases and has been found to reduce perceived stress and anxiety (Rani et al. 2011; Stankovic 2011; Amita et al. 2009; Rani et al. 2012). In our patient we found improvement in depression and anxiety scores at 3 months of intervention. At 2 weeks patient 02 showed increased anxiety and stress and that may be attributable to his personal commitment of a business trip and his apprehension of doing yoga nidra which became better in subsequent trips. This is important to understand while planning this model that initial support is important during initial 3 to 4 weeks of intervention. Following the yoga nidra model planned for the patients there was no adverse effect reported but it is important that the intervention be given under supervision of a sleep practitioner because the changes seen in the patients need to be assessed and monitored specially when an increased association to have anxiety, other somatic complaints like headaches, nausea is likely to be more in insomnia patients with mind body therapies including meditation (Jacobsen and Edinger 1982; Carlson and Nitz 1991).
This highlights the differences between patients and meditators and hence the medical supervision of these patients is extremely important.
Yoga nidra is easy to administer, relatively safe and does improve sleep in chronic insomnia. Another advantage of yoga nidra model is, that after the first five supervised sessions the patient is not dependant on the therapist, on the contrary he can do it all by himself in the comfort of his own house. This also gives confidence to the patient and alleviates his anxiety as seen in one of our patient. This may be one of the important factors for sustained improvement in anxiety and stress in both patients at 3 months of intervention.
The model developed for yoga nidra intervention can be used in chronic insomnia patients as an adjunct in management of chronic insomnia. Initial monitoring by a sleep physician should be done during 3 to 4 weeks of intervention. Though there are potential benefits of yoga nidra in insomnia patients, exact mechanism of yoga nidra is not yet clear. In our study both the volunteers were of elderly age group. Another limitation of our study is that in this case report there is a limited sample size (2 cases), so no firm conclusions can be drawn yet, until further studies are done on a larger number of patients. The efficacy of yoga nidra can be better understood in a randomised controlled trial in comparison to CBTI preferably in a younger age group.
Second author: Dr Manjari Tripathi- MT
First author: Dr Karuna Datta- KD
American association of sleep medicine
Cognitive behavioural therapy for insomnia
Depression anxiety and stress scale
- ESS © MW JOHNS 1990–1997. USED UNDER LICENSE:
Epworth sleepiness scale
Insomnia severity index
Morningness eveningness scale
- N1, 2, 3:
Non REM stages as per AASM scoring criteria
Out patients department
Pre sleep arousal scale
Pittsburgh sleep quality index
Rapid eye movement
Sleep onset latency
Sleep period time
Time in bed
Total sleep time
Total wake duration
Wake after sleep onset
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The authors acknowledge the support of Bihar School of Yoga Munger, Bihar, India for providing valuable inputs, books, literature and blessings in designing and completing the study. Authors are also thankful to the sleep technicians of MT sleep lab who conducted overnight polysomnography for the study. Authors thank MAPI trust for granting permission to use ESS “ESS contact information and permission to use: MAPIResearch Trust, Lyon, France. E-mail: PROinformation@mapi-trust.org – Internet: www.mapi-trust.org”.
Funding for the study was provided from the department and Institute (All India Institute of Medical Sciences New Delhi, India) funds and resources. No separate funding agency was involved in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Availability of data and materials
The datasets during and/or analysed during the current study available from the corresponding author on reasonable request.
HM and MT helped KD design the study. Data collection was done by KD under guidance of MT. Analysis and interpretation of results and writing the manuscript was done by KD with guidance of HM and MT. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
A statement on ethics approval and consent provided in the methods section along with the reference number. The Institute Ethics Committee of All India Institute of Medical Sciences New Delhi, India approved the study and the reference number isIESC/T-394/02.11.2012.
‘All the patients were explained about the nature of study and informed consent obtained. The study was approved by the Institutional ethical committee of All India Institute of Medical Sciences, New Delhi, India (reference number IESC/T-394/02.11.2012).’
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Datta, K., Tripathi, M. & Mallick, H.N. Yoga Nidra: An innovative approach for management of chronic insomnia- A case report. Sleep Science Practice 1, 7 (2017). https://doi.org/10.1186/s41606-017-0009-4