Segmental torso masses in adolescent idiopathic scoliosis

Background Adolescent Idiopathic Scoliosis is the most common type of spinal deformity whose aetiology remains unclear. Studies suggest that gravitational forces in the standing position play an important role in scoliosis progression, therefore anthropometric data are required to develop biomechanical models of the deformity. Few studies have analysed the trunk by vertebral level and none have performed investigations of the scoliotic trunk. The aim of this study was to determine the centroid, thickness, volume and estimated mass, for sections of the trunk in Adolescent Idiopathic Scoliosis patients. Methods Existing low-dose Computed Tomography scans were used to estimate vertebral level-by-level torso masses for 20 female Adolescent Idiopathic Scoliosis patients. ImageJ processing software was used to analyse the Computed Tomography images and enable estimation of the segmental torso mass corresponding to each vertebral level. Findings The patients’ mean age was 15.0 (SD 2.7) years with mean major Cobb Angle of 52° (SD 5.9) and mean patient weight of 58.2 (SD 11.6) kg. The magnitude of torso segment mass corresponding to each vertebral level increased by 150% from 0.6kg at T1 to 1.5kg at L5. Similarly, the segmental thickness corresponding to each vertebral level from T1-L5 increased inferiorly from a mean 18.5 (SD 2.2) mm at T1 to 32.8 (SD 3.4) mm at L5. The mean total trunk mass, as a percentage of total body mass, was 27.8 (SD 0.5) % which was close to values reported in previous literature. Interpretation This study provides new anthropometric reference data on segmental (vertebral level-by-level) torso mass in Adolescent Idiopathic Scoliosis patients, useful for biomechanical models of scoliosis progression and treatment.

Supine to standing Cobb Angle change in idiopathic scoliosis: The effect of endplate preselection

Introduction Standing radiographs are the ‘gold standard’ for clinical assessment of adolescent idiopathic scoliosis (AIS), with the Cobb Angle used to measure the severity and progression of the scoliotic curve. Supine imaging modalities can provide valuable 3D information on scoliotic anatomy, however, due to changes in gravitational loading direction, the geometry of the spine alters between the supine and standing position which in turn affects the Cobb Angle measurement. Previous studies have consistently reported a 7-10° [1-3] Cobb Angle increase from supine to standing, however, none have reported the effect of endplate pre-selection and which (if any) curve parameters affect the supine to standing Cobb Angle difference. Methods Female AIS patients with right-sided thoracic major curves were included in the retrospective study. Clinically measured Cobb Angles from existing standing coronal radiographs and fulcrum bending radiographs [4] were compared to existing low-dose supine CT scans taken within 3 months of the reference radiograph. Reformatted coronal CT images were used to measure Cobb Angle variability with and without endplate pre-selection (end-plates selected on the radiographs used on the CT images). Inter and intra-observer measurement variability was assessed. Multi-linear regression was used to investigate whether there was a relationship between supine to standing Cobb Angle change and patient characteristics (SPSS, v.21, IBM, USA). Results Fifty-two patients were included, with mean age of 14.6 (SD 1.8) years; all curves were Lenke Type 1 with mean Cobb Angle on supine CT of 42° (SD 6.4°) and 52° (SD 6.7°) on standing radiographs. The mean fulcrum bending Cobb Angle for the group was 22.6° (SD 7.5°). The 10° increase from supine to standing is consistent with existing literature. Pre-selecting vertebral endplates was found to increase the Cobb Angle difference by a mean 2° (range 0-9°). Multi-linear regression revealed a statistically significant relationship between supine to standing Cobb Angle change with: fulcrum flexibility (p=0.001), age (p=0.027) and standing Cobb Angle (p<0.001). In patients with high fulcrum flexibility scores, the supine to standing Cobb Angle change was as great as 20°.The 95% confidence intervals for intra-observer and inter-observer measurement variability were 3.1° and 3.6°, respectively. Conclusion There is a statistically significant relationship between supine to standing Cobb Angle change and fulcrum flexibility. Therefore, this difference can be considered a measure of spinal flexibility. Pre-selecting vertebral endplates causes only minor changes.

Executive function and postural instability in people with Parkinson’s disease

The specific aspects of cognition contributing to balance and gait have not been clarified in people with Parkinson’s disease (PD). Twenty PD participants and twenty age- and gender-matched healthy controls were assessed on cognition and clinical mobility tests. General cognition was assessed with the Mini Mental State Exam and the Addenbrooke’s Cognitive Exam. Executive function was evaluated using the Trail Making Tests (TMT-A and TMT-B) and a computerized cognitive battery which included a series of choice reaction time (CRT) tests. Clinical gait and balance measures included the Tinetti, Timed Up & Go, Berg Balance and Functional Reach tests. PD participants performed significantly worse than the controls on the tests of cognitive and executive function, balance and gait. PD participants took longer on Trail Making Tests, CRT-Location and CRT-Colour (inhibition response). Furthermore, executive function, particularly longer times on CRT-Distracter and greater errors on the TMT-B were associated with worse balance and gait performance in the PD group. Measures of general cognition were not associated with balance and gait measures in either group. For PD participants, attention and executive function were impaired. Components of executive function, particularly those involving inhibition response and distracters, were associated with poorer balance and gait performance in PD.

iNOS expression and osteocyte apoptosis in idiopathic, non- traumatic osteonecrosis

Background and purpose Non-traumatic osteonecrosis is a progressive disease with multiple etiologies. It affects younger individuals more and more, often leading to total hip arthroplasty. We investigated whether there is a correlation between inducible nitric oxide synthase (iNOS) expression and osteocyte apoptosis in non-traumatic osteonecrosis. Patients and methods We collected and studied 20 human idiopathic, non-traumatic osteonecrosis femoral heads. Subchondral bone samples in the non-sclerotic region (n = 30), collected from osteoarthritis patients, were used as controls. Spontaneously hypertensive rats were used as a model for osteonecrosis in the study. We used scanning electron microscopy, TUNEL assay, and immunohistochemical staining to study osteocyte changes and apoptosis. Results The morphology of osteocytes in the areas close to the necrotic region changed and the number of apoptotic osteocytes increased in comparison with the same region in control groups. The expression of iNOS and cytochrome C in osteocytes increased while Bax expression was not detectable in osteonecrosis samples. Using spontaneously hypertensive rats, we found a positive correlation between iNOS expression and osteocyte apoptosis in the osteonecrotic region. iNOS inhibitor (aminoguanidine) added to the drinking water for 5 weeks reduced the production of iNOS and osteonecrosis compared to a control group without aminoguanidine. Interpretation Our findings show that increased iNOS expression can lead to osteocyte apopotosis in idiopathic, non-traumatic osteonecrosis and that an iNOS inhibitor may prevent the progression of the disease.

On the realization of the current-driven dust ion-acoustic instability

The current-driven dust ion-acoustic instability in a collisional dusty plasma is studied. The effects of dust-charge variation, electron and ion capture by the dust grains, as well as various dissipative mechanisms leading to the changes of the particles momenta, are taken into account. It is shown that the threshold for the excitation of the dust ion-acoustic waves can be high because of the large dissipation rate induced by the dusts. © 1999 American Institute of Physics.

A loop cancellation based active damping solution for constant power instability in vehicular power systems

In recent years, electric propulsion systems have increasingly been used in land, sea and air vehicles. The vehicular power systems are usually loaded with tightly regulated power electronic converters which tend to draw constant power. Since the constant power loads (CPLs) impose negative incremental resistance characteristics on the feeder system, they pose a potential threat to the stability of vehicular power systems. This effect becomes more significant in the presence of distribution lines between source and load in large vehicular power systems such as electric ships and more electric aircrafts. System transients such as sudden drop of converter side loads or increase of constant power requirement can cause complete system instability. Most of the existing research work focuses on the modeling and stabilization of DC vehicular power systems with CPLs. Only a few solutions are proposed to stabilize AC vehicular power systems with non-negligible distribution lines and CPLs. Therefore, this paper proposes a novel loop cancellation technique to eliminate constant power instability in AC vehicular power systems with a theoretically unbounded system stability region. Analysis is carried out on system stability with the proposed method and simulation results are presented to validate its effectiveness.

Virtual resistance based active damping solution for constant power instability in AC microgrids

With ever-increasing share of power electronic loads constant power instability is becoming a significant issue in microgrids, especially when they operate in the islanding mode. Transient conditions like resistive load-shedding or sudden increase of constant power loads (CPL) might destabilize the whole system. Modeling and stability analysis of AC microgrids with CPLs have already been discussed in literature. However, no effective solutions are provided to stabilize this kind of system. Therefore, this paper proposes a virtual resistance based active damping method to eliminate constant power instability in AC microgrids. Advantages and limitations of the proposed method are also discussed in detail. Simulation results are presented to validate the proposed active damping solution.

Supine to standing Cobb angle change in idiopathic scoliosis : the effect of endplate pre-selection

Background Supine imaging modalities provide valuable 3D information on scoliotic anatomy, but the altered spine geometry between the supine and standing positions affects the Cobb angle measurement. Previous studies report a mean 7°-10° Cobb angle increase from supine to standing, but none have reported the effect of endplate pre-selection or whether other parameters affect this Cobb angle difference. Methods Cobb angles from existing coronal radiographs were compared to those on existing low-dose CT scans taken within three months of the reference radiograph for a group of females with adolescent idiopathic scoliosis. Reformatted coronal CT images were used to measure supine Cobb angles with and without endplate pre-selection (end-plates selected from the radiographs) by two observers on three separate occasions. Inter and intra-observer measurement variability were assessed. Multi-linear regression was used to investigate whether there was a relationship between supine to standing Cobb angle change and eight variables: patient age, mass, standing Cobb angle, Risser sign, ligament laxity, Lenke type, fulcrum flexibility and time delay between radiograph and CT scan. Results Fifty-two patients with right thoracic Lenke Type 1 curves and mean age 14.6 years (SD 1.8) were included. The mean Cobb angle on standing radiographs was 51.9° (SD 6.7). The mean Cobb angle on supine CT images without pre-selection of endplates was 41.1° (SD 6.4). The mean Cobb angle on supine CT images with endplate pre-selection was 40.5° (SD 6.6). Pre-selecting vertebral endplates increased the mean Cobb change by 0.6° (SD 2.3, range −9° to 6°). When free to do so, observers chose different levels for the end vertebrae in 39% of cases. Multi-linear regression revealed a statistically significant relationship between supine to standing Cobb change and fulcrum flexibility (p = 0.001), age (p = 0.027) and standing Cobb angle (p < 0.001). The 95% confidence intervals for intra-observer and inter-observer measurement variability were 3.1° and 3.6°, respectively. Conclusions Pre-selecting vertebral endplates causes minor changes to the mean supine to standing Cobb change. There is a statistically significant relationship between supine to standing Cobb change and fulcrum flexibility such that this difference can be considered a potential alternative measure of spinal flexibility.

The effect of endplate preselection when measuring supine versus standing cobb angle change in idiopathic scoliosis

The primary aim of this study was to determine whether endplate pre-selection makes a difference to the Cobb Angle change between supine and standing which is known to occur in idiopathic scoliosis. A secondary aim of this study was to identify which (if any) patient characteristics were correlated with supine versus standing Cobb change. The study found that pre-selecting vertebral endplates causes only has a minor effect on supine to standing Cobb change in scoliosis. There is a statistically significant relationship between supine to standing Cobb Angle change and fulcrum flexibility. Therefore, supine to standing Cobb Angle change can be considered as a measure of spinal flexibility when both standing and supine images are clinically available.

BRCA1 deficiency exacerbates estrogen-induced DNA damage and genomic instability

Germline mutations in BRCA1 predispose carriers to a high incidence of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through critical roles in DNA repair, cell cycle arrest and transcriptional control. A major question has been why BRCA1 loss or mutation leads to tumors mainly in estrogen-regulated tissues, given that BRCA1 has essential functions in all cell types. Here we report that estrogen and estrogen metabolites can cause DNA double strand breaks (DSB) in estrogen receptor-α negative breast cells and that BRCA1 is required to repair these DSBs to prevent metabolite-induced genomic instability. We found that BRCA1 also regulates estrogen metabolism and metabolite-mediated DNA damage by repressing the transcription of estrogen-metabolising enzymes, such as CYP1A1, in breast cells. Lastly, we used a knock-in human cell model with a heterozygous BRCA1 pathogenic mutation to show how BRCA1 haploinsufficiency affects these processes. Our findings provide pivotal new insights into why BRCA1 mutation drives the formation of tumours in estrogen-regulated tissues, despite the general role of BRCA1 in DNA repair in all cell types.

Evaluation of a patient-specific finite-element model to simulate conservative treatment in adolescent idiopathic scoliosis

Study design Retrospective validation study. Objectives To propose a method to evaluate, from a clinical standpoint, the ability of a finite-element model (FEM) of the trunk to simulate orthotic correction of spinal deformity and to apply it to validate a previously described FEM. Summary of background data Several FEMs of the scoliotic spine have been described in the literature. These models can prove useful in understanding the mechanisms of scoliosis progression and in optimizing its treatment, but their validation has often been lacking or incomplete. Methods Three-dimensional (3D) geometries of 10 patients before and during conservative treatment were reconstructed from biplanar radiographs. The effect of bracing was simulated by modeling displacements induced by the brace pads. Simulated clinical indices (Cobb angle, T1–T12 and T4–T12 kyphosis, L1–L5 lordosis, apical vertebral rotation, torsion, rib hump) and vertebral orientations and positions were compared to those measured in the patients' 3D geometries. Results Errors in clinical indices were of the same order of magnitude as the uncertainties due to 3D reconstruction; for instance, Cobb angle was simulated with a root mean square error of 5.7°, and rib hump error was 5.6°. Vertebral orientation was simulated with a root mean square error of 4.8° and vertebral position with an error of 2.5 mm. Conclusions The methodology proposed here allowed in-depth evaluation of subject-specific simulations, confirming that FEMs of the trunk have the potential to accurately simulate brace action. These promising results provide a basis for ongoing 3D model development, toward the design of more efficient orthoses.

Morphometric analysis of the thoracic intervertebral foramen osseous anatomy in adolescent idiopathic scoliosis using low dose computerized tomography

Introduction. The dimensions of the thoracic intervertebral foramen in adolescent idiopathic scoliosis (AIS) have not previously been quantified. During posterior approach scoliosis correction surgery pedicle screws may occasionally breach into the foramen. Better understanding of the dimensions of the foramen may be useful in surgical planning. This study describes a reproducible method for measurement of the thoracic foramen in AIS using computerized tomography (CT). Methods. In 23 pre-operative female patients with Lenke 1 type AIS with right side convexity major curves confined to the thoracic spine the foraminal height (FH), foraminal width (FW), pedicle to superior articular process distance (P-SAP) and cross sectional foraminal area (FA) were measured using multiplanar reconstructed CT. Measurements were made at entrance, midpoint and exit of the thoracic foramina from T1/T2 to T11/T12. Results were correlated with potential dependent variables of major curve Cobb Angle measured on X-ray and CT, Age, Weight, Lenke classification subtype, Risser Grade and number of spinal levels in the major curve. Results. The FH, FW, P-SAP and FA dimensions and ratios are all significantly larger on the convexity of the major curve and maximal at or close to the apex. Mean thoracic foraminal dimensions change in a predictable manner relative to position on the major thoracic curve. There was no significant correlation with the measured foraminal dimensions or ratios and the potential dependent variables. The average ratio of convexity to concavity dimensions at the apex foramina for entrance, midpoint and exit respectively are FH (1.50, 1.38, 1.25), FW (1.28, 1.30, 0.98), FA (2.06, 1.84, 1.32), P-SAP (1.61, 1.47, 1.30). Conclusion. Foraminal dimensions of the thoracic spine are significantly affected by AIS. Foraminal dimensions have a predictable convexity to concavity ratio relative to the proximity to the major curve apex. Surgeons should be aware of these anatomical differences during scoliosis correction surgery.

Using axially loaded MRI to investigate the biomechanics of adolescent idiopathic scoliosis

Introduction. Spinal flexibility measurement is an important aspect of pre-operative clinical assessment in the treatment of Adolescent Idiopathic Scoliosis (AIS). Clinically, curve flexibility is a combined measure for all vertebral levels. We propose that in vivo flexibility for individual spinal joints could provide valuable additional information in planning treatment for scoliosis. Methods. Individual spinal joint flexibility in the coronal plane was measured for a series of AIS patients using axially loaded magnetic resonance imaging. Each patient underwent magnetic resonance imaging in the supine position, with no axial load, and then following application of an axial compressive load equal to half the patient’s bodyweight. Coronal plane disc wedge angles in the unloaded and loaded configurations were measured. Joint moments exerted by the axial compressive load were used to derive estimates of individual joint compliance. Results. Fifteen AIS patients were included in the study (mean clinical Cobb angle 46 degrees, mean age 15.3 years). Mean intra-observer measurement error for endplate inclination was 1.6˚. The mean increase in measured major Cobb angle between unloaded and loaded scans was 7.6˚. For certain spinal levels (+2,+1,-2 relative to the apex) there was a statistically significant relationship between change in wedge angle under load and initial wedge angle, such that initially highly wedged discs demonstrated a smaller change in wedge angle than less wedged discs. Highly wedged discs were observed near the apex of the curve, which corresponded to lower joint compliance in the apical region. Conclusion. Approaches such as this can provide valuable biomechanical data on in vivo spinal biomechanics in AIS. Knowledge of individual joint flexibility may assist surgeons to determine which spinal procedure is most appropriate for a patient, which levels should be included in a spinal fusion and the relative mobility of individual joints in the deformed region of the spine.

Using low dose computerized tomography to morphometrically analyse the thoracic intervertebral foramen osseous anatomy in adolescent idiopathic scoliosis

INTRODUCTION The dimensions of the thoracic intervertebral foramen in adolescent idiopathic scoliosis (AIS) have not previously been quantified. During posterior approach scoliosis correction surgery pedicle screws may occasionally breach into the foramen. Better understanding of the dimensions of the foramen may be useful in surgical planning. This study describes a reproducible method for measurement of the thoracic foramen in AIS using computerized tomography (CT). METHODS In 23 pre-operative female patients with Lenke 1 type AIS with right side convexity major curves confined to the thoracic spine the foraminal height (FH), foraminal width (FW), pedicle to superior articular process distance (P-SAP) and cross sectional foraminal area (FA) were measured using multiplanar reconstructed CT. Measurements were made at entrance, midpoint and exit of the thoracic foramina from T1/T2 to T11/T12. Results were correlated with potential dependent variables of major curve Cobb Angle measured on X-ray and CT, Age, Weight, Lenke classification subtype, Risser Grade and number of spinal levels in the major curve. RESULTS The FH, FW, P-SAP and FA dimensions and ratios are all significantly larger on the convexity of the major curve and maximal at or close to the apex. Mean thoracic foraminal dimensions change in a predictable manner relative to position on the major thoracic curve. There was no significant correlation with the measured foraminal dimensions or ratios and the potential dependent variables. The average ratio of convexity to concavity dimensions at the apex foramina for entrance, midpoint and exit respectively are FH (1.50, 1.38, 1.25), FW (1.28, 1.30, 0.98), FA (2.06, 1.84, 1.32), P-SAP (1.61, 1.47, 1.30). CONCLUSION Foraminal dimensions of the thoracic spine are significantly affected by AIS. Foraminal dimensions have a predictable convexity to concavity ratio relative to the proximity to the major curve apex. Surgeons should be aware of these anatomical differences during scoliosis correction surgery.