An improved stiffness matrix model of the functional spinal unit for application to an improved understanding of pathological changes.

The stiffness matrix is a useful way to describe the mechanical behaviour of the functional spinal unit, which is defined as the superior and inferior vertebrae, capsules and ligaments. This usefulness is extended by means of the concept of the "balance point". The balance point is the load application point where the coupling coefficients of the stiffness matrix are minimized. Theoretical considerations are used to demonstrate that the stiffness matrix varies with load point location and thus a single stiffness matrix does not fully characterize the motion segment as well as to derive the stiffness matrix at any one specified point from the stiffness matrix at some other specified point. Special characteristics of the stiffness matrix obtained by loading through the "balance point" were shown. Some possible advantages derived from mechanical testing using the "balance point" concept are discussed. This study validates an improved stiffness matrix model that enhances the understanding of pathological changes by setting the gold standard of the behaviour of a normal functional spinal unit.

Muscle activity during low-speed rear impact.

PURPOSE: Whiplash associated disorders remain a major health problem in terms of impact on health care and on societal costs. Aetiology remains controversial including the old supposition that the cervical muscles do not play a significant role. This study examined the muscle activity from relevant muscles during rear-end impacts in an effort to gauge their influence on the aetiology of whiplash associated disorders. METHODS: Volunteers were subjected to a sub-injury level of rear impact. Surface electromyography (EMG) was used to record cervical muscle activity before, during and after impact. Muscle response time and EMG signal amplitude were analysed. Head, pelvis, and T1 acceleration data were recorded. RESULTS: The activities of the cervical muscles were found to be significant. The sternocleidomastoideus, trapezius and erector spinae were activated on average 59 ms, 73 ms and 84 ms after the impact stimulus, respectively, prior to peak head acceleration (113 ms). CONCLUSION: The cervical muscles reacted prior to peak head acceleration, thus in time to influence whiplash biomechanics and possibly injury mechanisms. It is recommended therefore, that muscular influences be incorporated into the development of the new rear-impact crash test dummy in order to make the dummy as biofidelic as possible.

Muscle activity during low-speed rear impact / 中华创伤杂志(英文版)

PURPOSE@#Whiplash associated disorders remain a major health problem in terms of impact on health care and on societal costs. Aetiology remains controversial including the old supposition that the cervical muscles do not play a significant role. This study examined the muscle activity from relevant muscles during rear-end impacts in an effort to gauge their influence on the aetiology of whiplash associated disorders.@*METHODS@#Volunteers were subjected to a sub-injury level of rear impact. Surface electromyography (EMG) was used to record cervical muscle activity before, during and after impact. Muscle response time and EMG signal amplitude were analysed. Head, pelvis, and T1 acceleration data were recorded.@*RESULTS@#The activities of the cervical muscles were found to be significant. The sternocleidomastoideus, trapezius and erector spinae were activated on average 59 ms, 73 ms and 84 ms after the impact stimulus, respectively, prior to peak head acceleration (113 ms).@*CONCLUSION@#The cervical muscles reacted prior to peak head acceleration, thus in time to influence whiplash biomechanics and possibly injury mechanisms. It is recommended therefore, that muscular influences be incorporated into the development of the new rear-impact crash test dummy in order to make the dummy as biofidelic as possible.

Feasibility of magnetic resonance imaging (MRI) in obtaining nucleus pulposus (NP) water content with changing postures.

Opportunities to evaluate spinal loading in vivo are limited and a large majority of studies on the mechanical functions of the spine have been in vitro cadaveric studies and/or models based on many assumptions that are difficult to validate. The purpose of this study was to investigate the feasibility of magnetic resonance imaging (MRI) in obtaining nucleus pulposus (NP) water content measurements with changing postures. MRI studies were conducted on 25 healthy males with no history of low back pain (age 20-38). The L1 to S1 intradiscal levels were imaged in supine, sitting and standing postures using an upright 0.6 Tesla magnet, where a set of H2O: D2O7 phantoms were mounted on the back of the subjects. A calibration curve, provided from these phantoms, was applied to the absolute proton density image, yielding a pixel-by-pixel map of the water content of the NP. The NP at all levels showed a highly significant water loss (p<0.001) in sitting and standing postures compared with the supine posture. A trend towards higher levels of water was observed at all levels in the standing posture relative to sitting postures, however statistically significant differences were found only at L4-L5 and L5-S1 levels. This study demonstrates that variations in water content of the NP in different postures are in agreement with those determined from published invasive disc pressure measurements. The result of study demonstrates the feasibility of using MRI to determine the water content of the NP with changing postures and to use these data to evaluate spinal loading in these postures. This measurement method of water content by quantitative MR imaging could become a powerful tool for both clinical and ergonomic applications. The proposed methodology does not require invasive pressure measurement techniques.

Reality about migration of the nucleus pulposus within the intervertebral disc with changing postures.

BACKGROUND: Previous studies reported that, in non-degenerate discs, the nucleus pulposus migrates posteriorly during flexion and anteriorly during extension within the intervertebral disc. However, in these studies the differences between anterior and posterior distances have been regarded as an indicator of nucleus pulposus migration. This study investigated the reality of migration of the nucleus pulposus within the intervertebral disc with changing postures. METHOD: Magnetic resonance images were obtained of the lumbar spines of 25 asymptomatic volunteers in sitting, standing and supine postures. The anterior and posterior height of the intervertebral disc, the anterior -posterior length of the intervertebral disc and nucleus pulposus, and the positions of the anterior and posterior margins of the nucleus were measured from mid-line sagittal images. FINDINGS: Changing postures altered the anterior and posterior height of the disc and three types of morphological changes, including changes in the anterior -posterior lengths of the intervertebral disc and nucleus pulposus, together with the position of the nucleus in the disc were found. The length of the intervertebral disc and nucleus pulposus changed under the variations in spinal loading caused by posture. INTERPRETATION: The results of this study indicated that the apparent nucleus pulposus migration within intervertebral disc is actually deformation of the nucleus pulposus length which depends on posture and the magnitude of the load. In other words, adopting different postures deforms the nucleus pulposus and therefore, changes the position of the nucleus pulposus but there is no apparent nucleus pulposus migration within the intervertebral disc.

Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial.

BACKGROUND: When cure is impossible, cancer treatment should focus on both length and quality of life. Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals. The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim. METHODS: COIN was a randomised controlled trial in patients with previously untreated advanced colorectal cancer. Patients received either continuous oxaliplatin and fluoropyrimidine combination (arm A), continuous chemotherapy plus cetuximab (arm B), or intermittent (arm C) chemotherapy. In arms A and B, treatment continued until development of progressive disease, cumulative toxic effects, or the patient chose to stop. In arm C, patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression, when the same treatment was restarted. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and B is described in a companion paper. Here, we compare arms A and C, with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy, with a predefined non-inferiority boundary of 1.162. Intention-to-treat (ITT) and per-protocol analyses were done. This trial is registered, ISRCTN27286448. FINDINGS: 1630 patients were randomly assigned to treatment groups (815 to continuous and 815 to intermittent therapy). Median survival in the ITT population (n=815 in both groups) was 15.8 months (IQR 9.4-26.1) in arm A and 14.4 months (8.0-24.7) in arm C (hazard ratio [HR] 1.084, 80% CI 1.008-1.165). In the per-protocol population (arm A, n=467; arm C, n=511), median survival was 19.6 months (13.0-28.1) in arm A and 18.0 months (12.1-29.3) in arm C (HR 1.087, 0.986-1.198). The upper limits of CIs for HRs in both analyses were greater than the predefined non-inferiority boundary. Preplanned subgroup analyses in the per-protocol population showed that a raised baseline platelet count, defined as 400,000 per µL or higher (271 [28%] of 978 patients), was associated with poor survival with intermittent chemotherapy: the HR for comparison of arm C and arm A in patients with a normal platelet count was 0.96 (95% CI 0.80-1.15, p=0.66), versus 1.54 (1.17-2.03, p=0.0018) in patients with a raised platelet count (p=0.0027 for interaction). In the per-protocol population, more patients on continuous than on intermittent treatment had grade 3 or worse haematological toxic effects (72 [15%] vs 60 [12%]), whereas nausea and vomiting were more common on intermittent treatment (11 [2%] vs 43 [8%]). Grade 3 or worse peripheral neuropathy (126 [27%] vs 25 [5%]) and hand-foot syndrome (21 [4%] vs 15 [3%]) were more frequent on continuous than on intermittent treatment. INTERPRETATION: Although this trial did not show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival, chemotherapy-free intervals remain a treatment option for some patients with advanced colorectal cancer, offering reduced time on chemotherapy, reduced cumulative toxic effects, and improved quality of life. Subgroup analyses suggest that patients with normal baseline platelet counts could gain the benefits of intermittent chemotherapy without detriment in survival, whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy and should not receive a treatment break. FUNDING: Cancer Research UK.

In-vitro kinematic testing of porcine cervical spine: a rotational manipulation model.

Although spinal manipulation is widely used in the management of neck and pain, its exact mechanisms and biomechancial effects are not clear. A porcine model was used to study the relative movements of intervertebral joints under spinal rotation maneuvers with different input angular displacements and thrust velocities. Ten porcine spines (C2/4) were fixed and mounted in a material testing machine. Rotational maneuvers with different input angular displacements (0.8, 1.5, 2 and 3 degrees) and thrust velocities (0.1 - 200 degrees/s) were applied to C2 with C4 fixed. Angular displacement induced at the adjacent level was measured and expressed as percentage of the applied angular displacement. For all the tested conditions, angular deformation at the adjacent level could not be avoided when an angular thrust was applied to the target level. The percentage of the angular displacement induced at the adjacent level was found to be dependent on both the input angular displacement and thrust velocity. If rapid thurst of manipulation is used to direct the input energy and motion at the target level with minimal interference at the adjacent levels, the applied angular displacement should not be too large and the thrust velocity should be within a medium velocity range.

Effects of static compression with different loading magnitudes and durations on the intervertebral disc: an in vivo rat-tail study.

STUDY DESIGN: An in vivo rat-tail model was used to study the effects of static compression with different loading magnitudes and durations on the intervertebral disc. OBJECTIVE: To investigate the effects of static compression with different loading magnitudes and durations on the intervertebral disc over a period of time. SUMMARY OF BACKGROUND DATA: A disc degeneration model is essential for studying therapeutic effects on degenerated disc. Static compression can induce degenerative-like changes in the intervertebral disc. However, the consequences of the simulation model over a period of resting have not been clearly documented, which may have confounding effects on the experimental outcome. METHODS: Thirty-five rats were used. Static compressions with different loads (11 or 17 N) and durations (1 hour daily or continuous) were applied to the rat-tail caudal 8-9 disc for 2 weeks, and followed with 3 weeks of rest. The disc height was quantified in vivo on days 4, 18, and 39. The rats were killed and the discs were harvested for morphologic examination on day 39 after the disc height measurement. RESULTS: Significant decrease in disc height was observed after continuous static compression for both 11 and 17 N, and continued during the resting period. The morphologic evaluation of the continuous compressed disc showed a decreased nuclear size, reduced number of nuclear cells, and irregular nuclear shape with inward bulging of disorganized annular collagen lamellas. Daily compression of 1 hour was found to induce a transient increase in disc height, but restored after the 3-week resting period. Favorable morphologic changes, including vacuolated nuclear cells and oval nuclear shape with well-organized annular collagen lamellas, were seen in the rat disc specimens with daily compression of 1 hour. CONCLUSION: Disc degenerative-like changes without recovery were demonstrated in the rat caudal disc after continuous compression. The changes in disc height and disc morphology were found to be dependent on the duration of load application and may have clinical implication.

Early physiotherapy intervention in an Accident and Emergency Department reduces pain and improves satisfaction for patients with acute low back pain: a randomised trial.

QUESTION: What is the effect of early physiotherapy intervention on pain and patient satisfaction in acute low back pain? DESIGN: Randomised trial with concealed allocation, assessor blinding, and intention-to-treat analysis. PARTICIPANTS: 110 patients attending the Accident and Emergency Department of a local acute hospital. INTERVENTION: The experimental group received early physiotherapy intervention which consisted of education, reassurance, pain management, mobility training, interferential therapy, walking training, and walking aids as indicated. The control group received only walking training and walking aids as indicated. All participants received conventional medical intervention and outpatient physiotherapy intervention. OUTCOME MEASURES: Pain was measured using the Numeric Pain Rating Scale and satisfaction was measured using the Numeric Global Rating of Change Scale at baseline, discharge from the Accident and Emergency Department, admission to the Physiotherapy Outpatient Department, 1 month, 3 months, and 6 months. RESULTS: Participants in the experimental group had 1.6 out of 10 points (97.5% CI 0.8 to 2.3) less pain than the control group on discharge from the Accident and Emergency Department and still had 0.9 points (97.5% CI 0.1 to 1.6) less pain on admission to the Physiotherapy Outpatient Department. Participants in the experimental group were 2.1 out of 20 points (97.5% CI 1.2 to 2.9) more satisfied than the control group on discharge from the Accident and Emergency Department. CONCLUSION: Early physiotherapy intervention was effective in reducing pain and increasing satisfaction for patients with acute low back pain in an Accident and Emergency Department but the effect tailed off.

The effect of body position and axial load on spinal canal morphology: an MRI study of central spinal stenosis.

STUDY DESIGN: A method comparison study. OBJECTIVE: To investigate the effect of body position and axial load of the lumbar spine on disc height, lumbar lordosis, and dural sac cross-sectional area (DCSA). SUMMARY OF BACKGROUND DATA.: The effects of flexion and extension on spinal canal diameters and DCSA are well documented. However, the effects of axial loading, achieved by upright standing or by a compression device, are still unclear. METHODS: Patients with lumbar spinal stenosis were examined in 2 separate studies, including 16 and 20 patients, respectively. In section 1, magnetic resonance imaging (MRI) scans were performed during upright standing and supine positions with and without axial load. In section 2, MRI scans were performed exclusively in supine positions, one with flexion of the lumbar spine (psoas-relaxed position), an extended position (legs straight), and an extended position with applied axial loading. Disc height, lumbar lordosis, and DCSA were measured and the different positions were compared. RESULTS: In section 1, the only significant difference between positions was a reduced lumbar lordosis during standing when compared with lying (P = 0.04), most probably a consequence of precautions taken to secure immobility during the vertical scans. This seemingly makes our standing posture less valuable as a standard of reference. In section 2, DCSA was reduced at all 5 lumbar levels after extension, and further reduced at 2 levels after adding compression (P < 0.05). Significant reductions of disc height were found at 3 motion segments and of DCSA at 11 segments after compression, but these changes were never seen in the same motion segment. CONCLUSION: Horizontal MRI with the patient supine and the legs straightened was comparable to vertical MRI whether axial compression was added or not. Extensionwas the dominant cause rather than compression in reducing DCSA. Axial load was not considered to have a clinically relevant effect on spinal canal diameters.

Postural changes of the dural sac in the lumbar spines of asymptomatic individuals using positional stand-up magnetic resonance imaging.

STUDY DESIGN: Positional magnetic resonance imaging (MRI) study of control subjects. OBJECTIVES: To determine dimensional changes in the lumbar dural sac as a function of posture, and to establish changes between the supine, erect and seated positions. SUMMARY OF BACKGROUND DATA: Studies using computerized tomography and MRI were done to determine the mechanical effects on the lumbar spinal canal in the different positions. There has been no consecutive study, however, in which normal individuals were investigated for positional changes of the dural sac, including true standing position. METHODS: Thirty-two male asymptomatic volunteers were recruited. The examination was performed using a new MRI system. All subjects were examined with sagittal T2 and axial T1-weighted spin-echo images. The subjects were studied in the supine, standing, and sitting positions. The measurements were made using OSIRIS software (Digital Imaging Unit University Hospital of Geneva, Geneva, Switzerland). On axial images, dural sac cross-sectional area and anteroposterior (AP) dural sac diameter were measured at the level of the L3/4, L4/5, and L5/S1 discs. On midsagittal images, AP dural sac diameter and the upper-endplate angles of L1 and S1 were measured. RESULTS: We found a disc degeneration or disc protrusion in 41% (12/29) of the subjects, but there was no obvious compression of the dural sac. Depending on the postures, the mean dural sac cross-sectional area and AP dural sac diameter changed. At all levels, mean dural sac cross-sectional area in the supine position was significantly smaller than in other postures. The dural area decreased most at the L5/S1 level due to positional change from standing to supine. The largest dural area at the L5/S1 level was in sitting extended. AP dural sac diameter on axial and midsagittal images showed a similar tendency. CONCLUSIONS: A significant posture-dependent difference of the dural sac cross-sectional area at the level of intervertebral disc in asymptomatic volunteers has been demonstrated. When the posture changed from supine to standing position, lumbar dural sac volume expanded by the increased pressure of cerebrospinal fluid, and the dural sac cross-sectional area increased. The smallest values were found in the supine position.

City bus driving and low back pain: a study of the exposures to posture demands, manual materials handling and whole-body vibration.

A cross-sectional study was conducted to investigate worker exposure to posture demands, manual materials handling (MMH) and whole body vibration as risks for low back pain (LBP). Using validated questionnaire, information about driving experience, driving (sitting) posture MMH, and health history was obtained from 80 city bus drivers. Twelve drivers were observed during their service route driving (at least one complete round trip) and vibration measurements were obtained at the seat and according to the recommendations of ISO 2631 (1997), for three models of bus (a mini-bus, a single-decker bus, a double-decker bus). The results showed that city bus drivers spend about 60% of the daily work time actually driving, often with the torso straight or unsupported, perform occasional and light MMH, and experience discomforting shock/jerking vibration events. Transient and mild LBP (not likely to interfere with work or customary levels of activity) was found to be prevalent among the drivers and a need for ergonomic evaluation of the drivers' seat was suggested.

The length of the cervical cord: effects of postural changes in healthy volunteers using positional magnetic resonance imaging.

STUDY DESIGN: The length of the cervical cord in healthy volunteers was measured in the supine and erect position using positional magnetic resonance imaging (MRI). OBJECTIVE: To assess the relationship between the length of the cervical cord and cervical posture in healthy volunteers. SUMMARY OF BACKGROUND DATA: A number of detailed descriptions of the normal morphologic features of the cervical cord have been published. However, to our knowledge, there is no report to compare the relationship between the length of the cervical cord and cervical posture in healthy volunteers using positional MRI. METHODS: This study was performed on 20 healthy volunteers using positional MRI. The subjects were studied in the supine and erect positions. The recumbent series consisted of 3 positions: neutral, flexion, and extension. The erect series consisted of 3 positions: neutral, flexion, and extension. On the midsagittal image, the length of the cervical cord from C1 to C7 was measured at the anterior, middle, and posterior line. The angle of the lower-endplate of C2 and C7 was measured. The results were compared with each series. RESULTS: In the recumbent and erect series, the mean length of the cervical cord in flexion was longer than in neutral and extension at the anterior, middle, and posterior line. There were significant differences between the length of the cervical cord in flexion, neutral, and extension. The mean length of the cervical cord in extension was shorter than in neutral and flexion at the anterior, middle, and posterior line. There were significant differences between length of the cervical cord in extension, neutral, and flexion. CONCLUSIONS: We found posture-dependent differences of the length of the cervical cord in the recumbent and erect series. These results may be important when assessing the dynamic factor in cervical spondylotic myelopathy.

Biomechanical aspects of the cervical cord: effects of postural changes in healthy volunteers using positional magnetic resonance imaging.

STUDY DESIGN: The area in cross-sectional view of the cervical cord (ACSCC) at each disc levels was measured in supine and erect positions using positional magnetic resonance imaging (pMRI). OBJECTIVES: To assess the relationship between ACSCC and cervical posture in healthy volunteers using pMRI. SUMMARY OF BACKGROUND DATA: There have been few detailed descriptions of the normal morphologic features of the cervical cord. However, there is no report to compare the relationship between ACSCC and cervical posture in healthy volunteers. METHODS: The study was performed on 20 healthy volunteers. The subjects were studied with pMRI in the supine and erect positions. The recumbent series and the erect series consist of 3 positions each: neutral, flexion and extension. On axial images, ACSCC was measured at the C2/3, C3/4, C4/5, C5/6, and C6/7 disc levels. On midsagittal image, the angle of the lower-endplate of C2 and C7 was measured. The results were compared between each series. RESULTS: In the recumbent and erect series, ACSCC was larger in extension than in neutral and flexion at all levels. There were significant differences between ACSCC in extension, neutral and flexion. ACSCC was smaller in flexion than in neutral and extension at all levels. There were significant differences between ACSCC in flexion, neutral and extension. CONCLUSIONS: We found posture-dependent differences of ACSCC in the recumbent and erect series. These results may be valuable for identifying a dynamic factor in patients with cervical spondylotic myelopathy.

Giovanni Alfonso Borelli--the father of biomechanics.

Giovanni Alfonso Borelli is often described as the father of biomechanics. He was born in Naples in 1608. His De Motu Animalium, published in 1680, extended to biology the rigorous analytical methods developed by Galileo in the field of mechanics. Borelli calculated the forces required for equilibrium in various joints of the human body well before Newton published The Laws of Motion Borelli was the first to understand that the levers of the musculoskeletal system magnify motion rather than force, so that muscles must produce much larger forces than those resisting the motion. Borelli died in Rome on December 31, 1679, but his impressive body of original work helped inspire a great number of future scientists, microscopists, and inventors. The highest honor bestowed by the American Society of Biomechanics is the Giovanni Borelli Award.

Sagittal plane moment arms of the female lumbar region rectus abdominis in an upright neutral torso posture.

BACKGROUND: Prior imaging studies of torso muscle moment arms for use as inputs into biomechanical models have been derived from subjects lying supine. Recent research suggests moment arms of the rectus abdominis are larger when standing versus lying supine. METHODS: Axial MRI images, through and parallel to the intervertebral discs were obtained from five females in a standing upright neutral posture. Digitizing software was utilized to quantify the distance in the sagittal plane between the centroids of the intervertebral disc and the rectus abdominis muscle, and converted to the transverse plane to allow comparisons with studies with subjects in a supine posture. FINDINGS: The mean sagittal plane moment arms in the transverse plane were 9.7, 9.1, 8.5, 8.5 and 9.8 cm at the L(1)/L(2), L(2)/L(3), L(3)/L(4), L(4)/L(5) and L(5)/S(1) intervertebral levels, respectively. Compared with a study on females of a similar age group, the moment arms from this study were larger at each level, increasing from 7.3% larger at L(1)/L(2) to 43.7% larger at L(5)/S(1). INTERPRETATION: Accurate anatomical geometrical representation in biomechanical models is necessary for valid estimates of internal loading. Sagittal plane rectus abdominis moment arms were larger from the upright neutral torso posture in this study compared to studies with subjects lying supine. This suggests the torso internal moment generating capability would be represented differently in biomechanical models that use data from studies where subjects were upright, which is more reflective of the postures biomechanical models are utilized for, than when using anatomical geometry derived from supine postures.

The accuracy of surface measurement for motion analysis of osteoporotic thoracolumbar spine.

The surface method of measuring the movements of lower thoracic and lumbar spine with osteoporosis using Fastrak® was examined for validity. There is an increasing awareness of the health risks of exposure to radiation associated with repeated radiographic assessment of spinal curvature and spinal movements. As a skin-surface measurement device, Fastrak® was employed to study the effect of low bone mineral density on spine motion. However, the reliability and validity of data recorded has not been established. The purpose of this study was to develop a methodology to determine the accuracy of the surface measurement device when it is applied to the motion analysis of osteoporotic spine. The results obtained indicated that the rotation angle of lumbar and lower thoracic spine could be predicted with acceptable accuracy from the data collected from skin-mounted sensors, while the prediction error of translational movements were not acceptable.

Bernardino Ramazzini: the father of occupational medicine.

Bernardino Ramazzini was born on October 4, 1633, in the small town of Capri located in the duchy of Modula, Italy. He is credited with establishing the field of occupational medicine during his lifetime. His major contributions came after 1682, when Duke Francesco II of Modena assigned him to establish a medical department at the University of Modena. He was installed in the title of professor "Medicinae Theoricae." In 1700, Ramazzini was appointed chair of practical medicine in Padua, Republic of Venice, the premier medical faculty in Italy. In 1700, he wrote the seminal book on occupational diseases and industrial hygiene, De Morbis Artificum Diatriba (Diseases of Workers). Although Ramazzini is perhaps most well known for his work on exposure to toxic materials, he wrote extensively about diseases of the musculoskeletal system. In particular, he warned of the problems of inactivity and poor postures inherent in some jobs.