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1.  Anterior Instrumentation for Correction of Adolescent Thoracic Idiopathic Scoliosis: Historic Prospective Study 
Croatian medical journal  2006;47(2):239-245.
To compare the results of anterior instrumentation and standard posterior procedure for correction of adolescent thoracic idiopathic scoliosis.
The study included 50 patients with adolescent thoracic idiopathic scoliosis who underwent corrective spinal surgery. Anterior spinal fusion by use of modified Zielke ventral derotation system (anterior approach to spine through thorax) was performed in 25 patients, whereas posterior approach was used in 25 patients. The average preoperative thoracic curve in coronal plane was 66.7 ± 9.9° and 65.0 ± 11.7° in the anterior and posterior correction groups, respectively. The median age of patients before surgery was 14 years (range, 12-18) in the anterior and 16 years (range, 13-18) in the posterior correction group. Women-to-men ratio was 22 to 3 in each group. Coronal and sagittal correction, apical vertebral body rotation, rib hump, and rib depression correction were measured before surgery and at the first (30 days after surgery) and at the second follow-up visit (at least 2 years after surgery). Posteroanterior and laterolateral radiographs of the erect spine were used (according to the method of Cobb and Nash-Moe) to assess coronal, sagittal, and horizontal plane corrections. Rib hump and rib depression were measured with Thulbourne-Gillespie measuring device. The differences in scoliosis correction parameters in the two groups were tested with Student two-tailed t test.
In the coronal plane, the thoracic curve of 66.7 ± 9.9° before surgery in the anterior correction group was reduced to 14.8 ± 8.7° after surgery (78.1 ± 12.4% relative correction), and the curve of 65.0 ± 11.7° in the posterior correction group was corrected to 29.2 ± 7.8° after surgery (55.1 ± 8.6% relative correction) (P<0.001). Apical vertebral body rotation correction according to the Nash-Moe classification from 2.0 ± 0.4° to 0.8 ± 0.6° was achieved in the anterior correction group (62.0 ± 26.6% relative correction) and from 1.7 ± 0.5° to 1.4 ± 0.5° in the posterior correction group (12.0 ± 21.8% relative correction) (P<0.001). Rib hump correction from 22.4 ± 15.5 mm to 5.4 ± 5.2 mm was found in the anterior correction group (70.9 ± 26.0% relative correction) and from 25.3 ± 7.0 mm to 13.6 ± 6.8 mm (48.4 ± 16.5% relative correction) in the posterior correction group (P = 0.084).
Compared with the standard posterior approach, the anterior approach resulted in better three-dimensional correction of idiopathic thoracic scoliosis.
PMCID: PMC2080403  PMID: 16625688
2.  Brace treatment for patients with Scheuermann's disease - a review of the literature and first experiences with a new brace design 
Scoliosis  2009;4:22.
In contemporary literature few have written in detail on the in-brace correction effects of braces used for the treatment of hyperkyphosis. Bradford et al. found their attempts effective, treating Scheuermann's kyphosis with Milwaukee braces, but their report did not specifically focus on in-brace corrections. White and Panjabi's research attempted to correct a curvature of > 50° with the help of distraction forces, but consequently led to a reduction in patient comfort in the application of the Milwaukee brace. In Germany they avoid this by utitlising braces to treat hyperkyphosis that use transverse correction forces instead of distraction forces. Further efforts to reduce brace material have resulted in a special bracing design called kyphologic™ brace. The aim of this review is to present appropriate research to collect and evaluate possible in-brace corrections which have been achieved with brace treatment for hyperkyphosis. This paper introduces new methods of bracing and compares the results of these with other successful bracing concepts.
Materials and methods
56 adolescents with the diagnosis of thoracic Scheuermann's hyperkyphosis or a thoracic idiopathic hyperkyphosis (22 girls and 34 boys) with an average age of 14 years (12-17 yrs.) were treated with the kyphologic™ brace between May 2007 and December 2008. The average Stagnara angle was 55,6° (43-80). In-brace correction was recorded and compared to the initial angle using the t-test.
The average Stagnara angle in the brace was 39°. The average in-brace correction was 16.5° (1-40°). The verage percentage of in-brace correction compared to the initial value was 36%. The differences were significant in the t-test (t = 5.31, p < 0,001). To make these results comparable to other studies, the kyphosis angle of 25° was set to 0 for our sample in order to achieve a norm value adapted (NVA) percentage of in-brace correction. By doing this a correction of 54.1% was achieved. There was no correlation between the percentage of in-brace correction and the age of the patient, but a highly significant correlation between percentage of in-brace correction and the initial Stagnara angle.
If we assume that outcome of brace treatment positively correlates with in-brace correction, the treatment should be initiated before the curvature angle exceeds 50 - 55° in a growing adolescent. In scoliosis bracing, if the average in-brace correction equals > 15°, then it is predicted that the result will lead to a final correction. Applying this to hyperkyphosis patients, the average in-brace correction with this brace was also > 15°. We therefore estimated to achieve a favourable outcome using this brace type (once compliance was attained) especially when comparing the correction effects achieved with this new approach to the correction effects reported upon using the Milwaukee brace. The latter brace has been shown to lead to beneficial outcomes in long-term studies with comparable in-brace corrections.
Conservative treatment of Scheuermann's hyperkyphosis in international literature is generally regarded as an effective treatment approach. Physiotherapy and bracing are the first-line treatments for this condition.
An average in-brace correction of > 15° as was achieved using the kyphologic™ brace predicts a favourable outcome.
The kyphologic™ brace leads to in-brace corrections comparable to those of the Milwaukee brace, which has previously been shown to provide beneficial outcome in the long-term.
A prospective follow-up study seems desirable before final conclusions can be drawn.
Future studies should focus more on thoracolumbar and lumbar curve patterns, because these patterns may predict chronic low back pain in adulthood with reduced quality of life of the patients and high costs with respect to medical care and occupational sickness leave.
Surgery according to international literature is rarely necessary in this condition.
PMCID: PMC2761858  PMID: 19788753
3.  Variability of heart rate correction methods for the QT interval 
To compare variability of heart rate-corrected QT intervals (QTc) using three different methods in a study of low-dose oral haloperidol.
In a randomized, double-blind, placebo-controlled, crossover trial, we studied QT interval pharmacodynamics of single doses of oral haloperidol (10 mg) in 16 healthy subjects. Heart rate correction of the QT interval was performed using Bazett’s, Fridericia's and subject-specific correction methods. The subject-specific correction was performed using linear mixed modelling of placebo period QT vs RR data from each study subject.
The subject-specific correction, in the form of QTc = QT/RRα, yielded a correction term α (slope of the log-transformed QT vs RR relationship) that ranged from 0.23 to 0.38 in individual subjects, i.e. the fixed correction term α = 0.5 of Bazett's correction was outside and the fixed correction term α = 0.33 of Fridericia's correction inside the range of individual values. The mean absolute slope of the QTcvs RR regression line using the subject-specific correction was significantly lower than the mean slopes obtained using either Bazett's or Fridericia's corrections. All three methods revealed a statistically significant greater mean QTc on haloperidol than on placebo at 10 h post-drug administration. The mean QT (95% CI) was 421.6 (410.8, 432.4), and 408.4 (398.6, 417.8) on haliperidol and placebo, respectively, using the subject-specific correction method (P = 0.0053). The mean QTc (95% CI) was 425.4 (414.3, 436.5) and 403.1 (394.3, 411.9) on haliperidol and placebo, respectively, using Bazett's correction (P = 1.7 × 10−5) and 423.1 (412.6, 433.6) and 408.2 (398.6, 417.8) on haliperidol and placebo, respectively, using Fridericia's correction (P = 7.7 × 10−4). Raw P-values were calculated using a paired t-test. Bonferroni-corrected P-values were calculated by multiplying the raw P-values by 13.
Haloperidol caused a statistically significant mean QTc prolongation using the three correction methods. The QTc intervals were less dependent on RR intervals using the subject-specific method, thus decreasing the possibility of over- or under-correction. The interindividual QTc changes from baseline varied significantly depending on the method of correction used.
PMCID: PMC1884246  PMID: 12814443
haloperidol; heart rate correction; QT interval
4.  Increase in spinal longitudinal length by correction surgery for adolescent idiopathic scoliosis 
European Spine Journal  2012;21(10):1920-1925.
One of the downsides of spinal correction surgery for adolescent idiopathic scoliosis (AIS) is the cessation of spinal longitudinal growth within the fused levels in growing children. However, the surgery itself has the potential to increase spinal longitudinal length by correcting the curvature. The purpose of this study was to evaluate the correlation between curve correction and increased spinal longitudinal length by corrective surgery for AIS.
This study included 208 consecutive patients (14 male, 194 female) with AIS who underwent posterior or anterior correction and fusion surgeries. Mean age at the time of surgery was 15.7 ± 3.3 years (range 10–20 years). Patients with hyperkyphosis of more than 40° were excluded. All patients had main curves in the thoracic spine (Lenke type 1 or 2). Forty-three patients underwent anterior spinal correction and fusion (ASF) and 164 underwent posterior spinal correction and fusion (PSF). The mean preoperative height was 154.7 ± 6.9 cm (range 133–173 cm). Pre and postoperative PA standing X-ray films were used to measure the Cobb angle and spinal length between the end vertebrae of the main thoracic curve, and between T1 and L5. The patients were divided into ASF and PSF groups, within which correlations between the Cobb angle correction and spinal length increase were evaluated.
In the ASF group, the mean preoperative Cobb angle of the main thoracic curve was 54.9 ± 8.3° (range 41–83°) and it was corrected to 19.7 ± 9.5° (range 0–47°) with a mean correction of 35.2 ± 11.1° (range 10–74°) after surgery. The mean increase in the length of the main thoracic curve was 1.5 ± 4.6 mm (range −8 to 13 mm), and the mean increase in T1–L5 length was 16.6 ± 7.7 mm (range −3 to 51 mm). Significant correlation between the correction of the Cobb angle and increase in T1–L5 length was observed, with a correlation coefficient of 0.44. In the PSF group, the mean preoperative Cobb angle of the main thoracic curve was 58.8 ± 11.6° (range 36–107°) and it was corrected to 17.1 ± 7.6° (range 10–49°), with a mean correction of 41.7 ± 10.2° (range 21–73°) after surgery. The mean increase in the length of the main thoracic curve was 14.0 ± 5.2 mm (range 0–42 mm), and the mean increase in T1–L5 length was 32.4 ± 10.8 mm (10–61 mm). Correlation between the correction of the Cobb angle and increase in T1–L5 length was high, with a correlation coefficient of 0.64. The increase in T1–L5 length could be calculated by the following formula based on linear regression analysis: increase in T1–L5 length (mm) = correction of the Cobb angle (º) × 0.77.
Spinal longitudinal length was significantly increased after surgery in both the ASF and PSF groups. Correction of the Cobb angle and increase in T1–L5 length were highly correlated with each other, especially in the PSF group.
PMCID: PMC3463697  PMID: 22310882
Adolescent idiopathic scoliosis; Posterior correction with fusion surgery; Anterior correction with fusion surgery; Spinal length
5.  Anterior instrumentation (dual screws single rod system) for the surgical treatment of idiopathic scoliosis in the lumbar area: a prospective study on 33 adolescents and young adults, based on a new system of classification 
European Spine Journal  2012;22(Suppl 2):149-163.
The choice of anterior instrumentation in the treatment of lumbar scoliosis in adolescents and young adults is not a new topic for the authors. The first results achieved using the Dwyer surgical modality were reported by one of the authors followed by the results achieved using Zielke (VDS) instrumentation. Today, new techniques and new instrumentations have been developed that challenge the instrumentation choices. Here we describe how the new system of classification of scoliotic curves we developed has been used as a basis for treating idiopathic scoliosis in lumbar area in adolescents and young adults using an anterior approach.
A prospective study was carried out between 1998 and 2010 at two hospital centers on 33 adolescents and young adult with idiopathic lumbar scoliosis involving curves of three kinds, on whom surgical treatment was performed using a single solid rod. Topography of curves: our system of classification includes curves corresponding to the following three type of scoliosis: Type K I: double thoracic and lumbar curves (lumbar predominant) scoliosis (17 cases) mean age 16 years all female patients. Mean Cobb angle of lumbar curve 41°. Mean Cobb angle of thoracic curve 28°. The lumbar curve was left hand convex in 15 cases and right hand convex in 2 cases. Horizontal tilting of L4 mean value 22°. C7 offset mean value 3 cm. Type K IV A: unbalanced thoracolumbar scoliosis (13 cases) mean age 17 years, ten female patients and three male patients. Mean Cobb angle of thoracolumbar curve 39°. The thoracolumbar curve was left hand convex 4 times and right hand convex 9 times. Horizontal tilting of L4 mean value 18°. C 7 offset mean value 2.5 cm. Type K VI A: real lumbar (three cases). Age: 17, 15 and 13 years; all female patients. Cobb angle of the lumbar curve 66°, 29° and 70° (all LH convex). Horizontal tilting of L4: 40°, 20° and 46°. C 7 offset: 7 cm, 1 cm and 4 cm.
Surgical instrumentation: We used the EUROS AZUR anterior instrumentation for all the procedures. Cages have been used on five patients at the lower stages. Number of vertebrae instrumented: mean five vertebrae. The patients did not wear postoperative orthosis. Mean duration of procedure: 3 h 50 min. Mean blood loss: 350 cm3.
Type K I scoliosis (17 cases): Mean follow-up: 6 years. Correction of the lumbar curve Cobb angle: the mean angle has been corrected from 41° to 21°. Number of vertebrae instrumented: 4:6 times and 5:11 times. Correction of the upper thoracic curve Cobb angle: mean angle corrected from 28° to 19°. Correction of L4 horizontal tilting: mean residual was 7°. Correction of C 7 offset: mean 0.7 cm. Type K IV A scoliosis (13 cases): mean follow-up: 4 years. Correction of the lumbar curve Cobb angle: the mean angle has been corrected from 39° to 16°. Mean number of instrumented vertebrae: 5 (4:4 times, 5:6 times and 6:3 times.) Correction of L4 horizontal tilting: mean residual 5°. Correction of C 7 offset: mean 0.7 cm. Type K VI A scoliosis (three cases): mean follow-up: 7, 2 and 4 years; Correction of the lumbar curve Cobb angle: the angles have been corrected from 66° to 15°, from 29° to 11° and from 70° to 28°. Number of instrumented vertebrae: 5, 4 and 6. Correction of L4 horizontal tilting: residual tilting of 8°, 7° and 17°. Correction of C 7 offset: 1 cm, 0 cm and 1 cm.
There has been no report early or late septic or vascular or neurological complications. Instrumentation failure: there were three cases of screw breakage, all occurred on the lowest implant. Revision surgery was undertaken in both cases, only the last plate needed to be replaced and the rod could be kept without any other modification of the construct. In both cases, fusion has been achieved without any loss of correction. The mean loss of correction of the main curve was 2.5° for the three series.
Anterior instrumentation of lumbar idiopathic scoliosis gives highly satisfactory morphological and functional results, since the lumbar musculature is spared and the instrumentation placed at the apex of the curvature has selective effects. Despite our preference and that of other surgeons throughout the world for anterior instrumentation, we are still a minority in comparison with the users of posterior instrumentation. There are several reasons for this reticence, including surgeons’ training and ideas about pedicular screw fixation, but the main reason has been the lack of a sufficiently exact system of classification. Previous comparative studies between the anterior and posterior approaches have been biased by the use of an excessively restrictive mode of classification (lumbar/thoracolumbar) of the curves. Real lumbar scoliosis, unbalanced thoracolumbar scoliosis and thoracic and lumbar double curve (lumbar predominant) scoliosis should be properly defined before being compared.
PMCID: PMC3616467  PMID: 22644435
Adolescent idiopathic scoliosis; Anterior instrumentation; Trunk balance; Sagittal balance; Shoulder balance; Curve’s classification
6.  The usefulness of “corrected” body mass index vs. self-reported body mass index: comparing the population distributions, sensitivity, specificity, and predictive utility of three correction equations using Canadian population-based data 
BMC Public Health  2014;14:430.
National data on body mass index (BMI), computed from self-reported height and weight, is readily available for many populations including the Canadian population. Because self-reported weight is found to be systematically under-reported, it has been proposed that the bias in self-reported BMI can be corrected using equations derived from data sets which include both self-reported and measured height and weight. Such correction equations have been developed and adopted. We aim to evaluate the usefulness (i.e., distributional similarity; sensitivity and specificity; and predictive utility vis-à-vis disease outcomes) of existing and new correction equations in population-based research.
The Canadian Community Health Surveys from 2005 and 2008 include both measured and self-reported values of height and weight, which allows for construction and evaluation of correction equations. We focused on adults age 18–65, and compared three correction equations (two correcting weight only, and one correcting BMI) against self-reported and measured BMI. We first compared population distributions of BMI. Second, we compared the sensitivity and specificity of self-reported BMI and corrected BMI against measured BMI. Third, we compared the self-reported and corrected BMI in terms of association with health outcomes using logistic regression.
All corrections outperformed self-report when estimating the full BMI distribution; the weight-only correction outperformed the BMI-only correction for females in the 23–28 kg/m2 BMI range. In terms of sensitivity/specificity, when estimating obesity prevalence, corrected values of BMI (from any equation) were superior to self-report. In terms of modelling BMI-disease outcome associations, findings were mixed, with no correction proving consistently superior to self-report.
If researchers are interested in modelling the full population distribution of BMI, or estimating the prevalence of obesity in a population, then a correction of any kind included in this study is recommended. If the researcher is interested in using BMI as a predictor variable for modelling disease, then both self-reported and corrected BMI result in biased estimates of association.
PMCID: PMC4108015  PMID: 24885210
Body mass index; Measurement error; Obesity; Overweight; Self-report; Bias; Correction
7.  Lack of correlation between exercise and sibenadet-induced changes in heart rate corrected measurement of the QT interval 
What is already known about this subject
When this study was conducted it was already known that the ‘standard’ methods of correcting the QT interval for heart rate were not optimal and that bias could result in their use in certain circumstances, in particular when drugs or conditions also induced wide fluctuations in heart rate.The use of subject specific correction methods had been advocated and whilst these had been shown to apparently correct QT interval over usual physiological heart rates, they had not been tested under conditions where drugs could potentially increase heart rate and ‘standard’ correction methods gave apparent increases in QT interval. Furthermore, subject specific correction methods had usually been generated over a normal physiological heart rate range and made the assumption that the relationship remained linear outside of this usual range.
What this study adds
A subject specific correction factor for QT correction can be calculated from a wide range of heart rates using exercise testing and the relationships between QT and RR are unique for a given individual.The generation of subject specific correction factors from ECGs collected under resting conditions is not a robust method.That subject specific correction factors derived from exercise testing are not appropriate to apply to drugs (with no evidence to suggest effects on the QT interval) that induce increases in heart rate and that the relationship between the QT and RR interval during exercise is clearly different to the QT/RR relationship of a drug that increases heart rate.
We sought to investigate subject specific QT interval correction factors (SSCF) determined at rest and after exercise and to determine the validity of these factors after the administration of a probe drug known to increase heart rate without directly affecting cardiac repolarization.
Thirty-two healthy volunteers underwent graded exercise, multiple recordings of electrocardiogram during rest over a day and a treatment phase administering inhaled placebo or sibenadet (a β2-adrenoceptor/dopamine D2-receptor agonist) at 250, 500 or one of 750 or 1000 µg. SSCF were determined from linear regression of plots of log RR interval vs. log QT after exercise (QTcX), rest (QTcR), and combined data (QTcC). The SSCFs along with Bazett & Fridericia corrections were applied to the ECGs after inhalation of sibenadet.
SSCFs obtained from the combination of the exercise and resting day (mean QTcC = 0.41) and exercise alone (mean QTcX = 0.40) were similar with a good fit to the data (mean r2 = 0.92 and 0.93, respectively) while data at rest resulted in a less pronounced slope (mean QTcR = 0.27) and poorer fit (mean r2 = 0.52). After the administration of sibenadet, none of the SSCFs, Bazett or Fridericia corrections adequately corrected QT for heart rate induced changes.
Neither a SSCF from exercise, Bazett’s or Fridericia’s correction factors, adequately corrected the QT interval after the administration of a sympathomimetic agonist drug to increase heart rate in healthy volunteers demonstrating the potential need for QT/RR correction factors to be tailored for each drug studied.
PMCID: PMC2000729  PMID: 17380588
β-adrenoceptor agonist; exercise; heart rate; QT interval; sibenadet; subject specific correction factor
8.  Differential reinforcement of correct responses to probes and prompts in picture-name training with severely retarded children. 
A systematic sequence of prompt and probe trials was used to teach picture names to three severely retarded children. On prompt trials the experimenter presented a picture and said the picture name for the child to imitate; on probe trials the experimenter did not name the picture. A procedure whereby correct responses to prompts and probes were nondifferentially reinforced was compared with procedures whereby correct responses to prompts and probes were differentially reinforced according to separate and independent schedules of primary reinforcement. In Phase 1, correct responses to prompts and probes were reinforced nondifferentially on a fixed ratio (FR) 6 or 8 schedule; in Phase 2, correct responses to prompts were reinforced on the FR schedule and correct responses to probes were reinforced on an FR schedule of the same value; in Phase 3, correct responses to prompts were reinforced on the FR schedule and correct responses to probes were reinforced on a continuous reinforcement (CRF; every correct response reinforced) schedule; in Phase 4, correct responses to prompts were reinforced on a CRF schedule and correct responses to probes were reinforced on the FR schedule; in Phase 5, a reversal to the conditions of Phase 3 was conducted. For all three children, the FR schedule for correct responses to prompts combined with the CRF schedule for correct responses to probes (Phases 3 and 5) generated the highest number of correct responses to probes, the highest accuracy (correct responses relative to correct responses plus errors) on probe trials, and the highest rate of learning to name pictures.
PMCID: PMC1308108  PMID: 6444932
9.  Off-line motion correction methods for multi-frame PET data 
Patient motion during PET acquisition may affect measured time-activity curves, thereby reducing accuracy of tracer kinetic analyses. The aim of the present study was to evaluate different off-line frame-by-frame methods to correct patient motion, which is of particular interest when no optical motion tracking system is available or when older data sets have to be reanalysed.
Four different motion correction methods were evaluated. In the first method attenuation-corrected frames were realigned with the summed image of the first 3 min. The second method was identical, except that non-attenuation-corrected images were used. In the third and fourth methods non-attenuation-corrected images were realigned with standard and cupped transmission images, respectively. Two simulation studies were performed, based on [11C]flumazenil and (R)-[11C]PK11195 data sets, respectively. For both simulation studies different types (rotational, translational) and degrees of motion were added. Simulated PET scans were corrected for motion using all correction methods. The optimal method derived from these simulation studies was used to evaluate two (one with and one without visible movement) clinical data sets of [11C]flumazenil, (R)-[11C]PK11195 and [11C]PIB. For these clinical data sets, the volume of distribution (VT) was derived using Logan analysis and values were compared before and after motion correction.
For both [11C]flumazenil and (R)-[11C]PK11195 simulation studies, optimal results were obtained when realignment was based on non-attenuation-corrected images. For the clinical data sets motion disappeared visually after motion correction. Regional differences of up to 433% in VT before and after motion correction were found for scans with visible movement. On the other hand, when no visual motion was present in the original data set, overall differences in VT before and after motion correction were <1.5 ± 1.3%.
Frame-by-frame motion correction using non-attenuation-corrected images improves the accuracy of tracer kinetic analysis compared to non-motion-corrected data.
Electronic supplementary material
The online version of this article (doi:10.1007/s00259-009-1193-y) contains supplementary material, which is available to authorised users.
PMCID: PMC2779434  PMID: 19585116
PET; Motion correction; Kinetic modelling; Volume of distribution
10.  Comparison of ring artifact removal methods using flat panel detector based CT images 
Ring artifacts are the concentric rings superimposed on the tomographic images often caused by the defective and insufficient calibrated detector elements as well as by the damaged scintillator crystals of the flat panel detector. It may be also generated by objects attenuating X-rays very differently in different projection direction. Ring artifact reduction techniques so far reported in the literature can be broadly classified into two groups. One category of the approaches is based on the sinogram processing also known as the pre-processing techniques and the other category of techniques perform processing on the 2-D reconstructed images, recognized as the post-processing techniques in the literature. The strength and weakness of these categories of approaches are yet to be explored from a common platform.
In this paper, a comparative study of the two categories of ring artifact reduction techniques basically designed for the multi-slice CT instruments is presented from a common platform. For comparison, two representative algorithms from each of the two categories are selected from the published literature. A very recently reported state-of-the-art sinogram domain ring artifact correction method that classifies the ring artifacts according to their strength and then corrects the artifacts using class adaptive correction schemes is also included in this comparative study. The first sinogram domain correction method uses a wavelet based technique to detect the corrupted pixels and then using a simple linear interpolation technique estimates the responses of the bad pixels. The second sinogram based correction method performs all the filtering operations in the transform domain, i.e., in the wavelet and Fourier domain. On the other hand, the two post-processing based correction techniques actually operate on the polar transform domain of the reconstructed CT images. The first method extracts the ring artifact template vector using a homogeneity test and then corrects the CT images by subtracting the artifact template vector from the uncorrected images. The second post-processing based correction technique performs median and mean filtering on the reconstructed images to produce the corrected images.
The performances of the comparing algorithms have been tested by using both quantitative and perceptual measures. For quantitative analysis, two different numerical performance indices are chosen. On the other hand, different types of artifact patterns, e.g., single/band ring, artifacts from defective and mis-calibrated detector elements, rings in highly structural object and also in hard object, rings from different flat-panel detectors are analyzed to perceptually investigate the strength and weakness of the five methods. An investigation has been also carried out to compare the efficacy of these algorithms in correcting the volume images from a cone beam CT with the parameters determined from one particular slice. Finally, the capability of each correction technique in retaining the image information (e.g., small object at the iso-center) accurately in the corrected CT image has been also tested.
The results show that the performances of the algorithms are limited and none is fully suitable for correcting different types of ring artifacts without introducing processing distortion to the image structure. To achieve the diagnostic quality of the corrected slices a combination of the two approaches (sinogram- and post-processing) can be used. Also the comparing methods are not suitable for correcting the volume images from a cone beam flat-panel detector based CT.
PMCID: PMC3201024  PMID: 21846411
11.  caCORRECT2: Improving the accuracy and reliability of microarray data in the presence of artifacts 
BMC Bioinformatics  2011;12:383.
In previous work, we reported the development of caCORRECT, a novel microarray quality control system built to identify and correct spatial artifacts commonly found on Affymetrix arrays. We have made recent improvements to caCORRECT, including the development of a model-based data-replacement strategy and integration with typical microarray workflows via caCORRECT's web portal and caBIG grid services. In this report, we demonstrate that caCORRECT improves the reproducibility and reliability of experimental results across several common Affymetrix microarray platforms. caCORRECT represents an advance over state-of-art quality control methods such as Harshlighting, and acts to improve gene expression calculation techniques such as PLIER, RMA and MAS5.0, because it incorporates spatial information into outlier detection as well as outlier information into probe normalization. The ability of caCORRECT to recover accurate gene expressions from low quality probe intensity data is assessed using a combination of real and synthetic artifacts with PCR follow-up confirmation and the affycomp spike in data. The caCORRECT tool can be accessed at the website:
We demonstrate that (1) caCORRECT's artifact-aware normalization avoids the undesirable global data warping that happens when any damaged chips are processed without caCORRECT; (2) When used upstream of RMA, PLIER, or MAS5.0, the data imputation of caCORRECT generally improves the accuracy of microarray gene expression in the presence of artifacts more than using Harshlighting or not using any quality control; (3) Biomarkers selected from artifactual microarray data which have undergone the quality control procedures of caCORRECT are more likely to be reliable, as shown by both spike in and PCR validation experiments. Finally, we present a case study of the use of caCORRECT to reliably identify biomarkers for renal cell carcinoma, yielding two diagnostic biomarkers with potential clinical utility, PRKAB1 and NNMT.
caCORRECT is shown to improve the accuracy of gene expression, and the reproducibility of experimental results in clinical application. This study suggests that caCORRECT will be useful to clean up possible artifacts in new as well as archived microarray data.
PMCID: PMC3230913  PMID: 21957981
12.  Spontaneous lumbar curve correction in selective anterior instrumentation and fusion of idiopathic thoracic scoliosis of Lenke type C 
European Spine Journal  2012;22(Suppl 2):138-148.
Posterior pedicle screw instrumented correction and fusion have become the gold standard in the surgical treatment of thoracic scoliosis. However, in thoracic Lenke type C curves selective posterior fusion of the thoracic curve may lead to spinal imbalance. The aim of the study was to analyse the radiological results of selective anterior thoracic fusion using a standard open dual rod technique with special respect to spontaneous lumbar curve correction (SLCC).
Twenty-eight patients (26 patients with Lenke 1C and 2 patients with Lenke 2C curves) with an average age of 15 years were surgically treated with an anterior dual rod system through a standard open double thoracotomy approach. Average clinical and radiological follow-up was 4 years (24–84 months).
Fusion was carried out mostly from end-to-end vertebra. The primary curve was corrected from 61.6° (average correction on reverse bending films 42.9 %) to 27.1° (56.0 % correction) with an average loss of correction of 2.2°. The secondary lumbar curve measured 47.7° preoperatively (40–56°, average correction on reverse bending films 66.2 %) and corrected spontaneously to 30.1° (36 % SLCC) and remained stable without any cases of deterioration or decompensation during follow-up. Lumbar apical vertebral translation increased minimally by an average of 4 mm directly, postoperatively, and returned to an average of preoperative values during follow-up. All but two curves remained as type C lumbar modifier at follow-up. Preoperatively, three patients showed a marked coronal imbalance of more than 3 cm (all left, average 4.0 cm); at follow-up, two patients were still out of balance by more than 3 cm (all to the left, average 3.4 cm). Preoperatively, a marked shoulder imbalance of more than 1.0 cm was found in 11 patients; this was corrected in all patients to <1.0 cm at follow-up. The apical vertebral rotation measured according to Perdriolle was corrected from 23.5° to 15.0° in the thoracic spine (36.2 % correction) with an average clinical reduction of the rib hump of 63.2 %. In the lumbar spine, there was no relevant radiological derotation; however, clinically, the lumbar hump corrected spontaneously by 44.3 %. Thoracic kyphosis measured 28.5° preoperatively and 32.3° at follow-up. All six patients with a preoperative hypokyphosis (<20°) of an average of 9.5° were successfully corrected to an average thoracic kyphosis of 23.8° at follow-up. There were no cases of junctional thoracolumbar kyphosis. There were neither reoperations nor implant failures with pseudarthrosis.
Selective anterior correction and fusion in primary thoracic curves with lumbar modifier type Lenke C resulted in a reliable and satisfactory SLCC. Advantages of anterior versus posterior techniques are the true segmental derotation with excellent rib hump correction and a superior restoration of thoracic kyphosis.
PMCID: PMC3616460  PMID: 22531898
Spontaneous lumbar curve correction; Selective thoracic fusion; Adolescent idiopathic scoliosis; Anterior fusion; Anterior dual rod instrumentation
13.  Accuracy Improvement Capability of Advanced Projectile Based on Course Correction Fuze Concept 
The Scientific World Journal  2014;2014:273450.
Improvement in terminal accuracy is an important objective for future artillery projectiles. Generally it is often associated with range extension. Various concepts and modifications are proposed to correct the range and drift of artillery projectile like course correction fuze. The course correction fuze concepts could provide an attractive and cost-effective solution for munitions accuracy improvement. In this paper, the trajectory correction has been obtained using two kinds of course correction modules, one is devoted to range correction (drag ring brake) and the second is devoted to drift correction (canard based-correction fuze). The course correction modules have been characterized by aerodynamic computations and flight dynamic investigations in order to analyze the effects on deflection of the projectile aerodynamic parameters. The simulation results show that the impact accuracy of a conventional projectile using these course correction modules can be improved. The drag ring brake is found to be highly capable for range correction. The deploying of the drag brake in early stage of trajectory results in large range correction. The correction occasion time can be predefined depending on required correction of range. On the other hand, the canard based-correction fuze is found to have a higher effect on the projectile drift by modifying its roll rate. In addition, the canard extension induces a high-frequency incidence angle as canards reciprocate at the roll motion.
PMCID: PMC4109594  PMID: 25097873
14.  Ensuring precision in lower limb deformity correction through a combination of temporary external fixation followed by internal fixation: Results of a retrospective study 
Indian Journal of Orthopaedics  2014;48(5):495-500.
It is important to plan preoperatively when contemplating internal fixation following deformity correction. Surgeons often find it difficult to retain the achieved correction till the end of internal fixation. To maintain precise correction we used hybrid technique which uses both external and internal fixation. The objective of the study was to evaluate the effectiveness of this hybrid technique in achieving and retaining desired correction.
Materials and Methods:
In this retrospective study, we evaluated the magnitude of deformity with radiological parameters. We compared correction which was planned and correction which was achieved. The technique was used during surgery for corrective osteotomies. Before carrying out the osteotomy, rail fixator with two swivel clamps was applied. After osteotomy swivel clamps were loosened. Desired correction was achieved. While fixator held the fragments in corrected position, definitive internal fixation was carried out. External fixator was removed after completion of internal fixation. Position of mechanical axis ratio, mechanical lateral distal femoral angle and mechanical medial proximal tibial angle were measured before and 12 weeks after surgery. Student t-test was used to analyze the difference between correction which was planned and correction which was achieved.
There was no statistical difference between the desired correction and the correction achieved.
Temporary use of external fixator while correcting angular deformities of lower limb allows to achieve accurate correction.
PMCID: PMC4175864  PMID: 25298557
Deformity correction; osteotomy; external fixation; internal fixation; hybrid fixation; Fixation; osteotomy; knee joint; techniques
15.  Comparative analysis of pedicle screw versus hybrid instrumentation in adolescent idiopathic scoliosis surgery 
International Orthopaedics  2007;32(4):523-528.
The expectations of both the patient and surgeon have been greatly revised in the last 10 years with the introduction of pedicle screws (PS) in spinal surgery. In this study, we have retrospectively evaluated and compared the results of PS instrumentation and the Hybrid System (HS), the latter consists of pedicle screws, sublaminar wire and hooks. The mean follow-up period was 60.1 months (range: 49–94 months) for the patients of the HS group and 29.3 months (range: 24–35 months) for those of the PS group. In the HS group, pedicle screws were used at the thoracolumbar junction and lumbar vertebra, the bilateral pediculotransverse claw hook configuration was used at the cranial end of the instrumentation, sublaminar wire was used on the concave side of the apical region and the compressive hook was used on the convex side. In the PS group, PS were used on the concave sides at all levels and on the convex side of the cranial and caudal end of instrumentation, in the transition zone and at the apex. The two groups were comparable for variables such as mean age, preoperative Cobb angle, thoracic kyphosis angle, lordosis angle, coronal balance, flexibility of the curve, apical vertebra rotation (AVR), apical vertebra rotation (AVT) and the number of vertebrae included in the fusion (p > 0.05). The parameters of values of correction, ratio of correction loss, AV derotation, AVT correction ratio, amount of blood loss, operation time, postoperative global coronal and sagittal balance, thoracic kyphosis angle and lumbar lordosis angle were measured at the last follow-up and used for comparing the HS and PS groups. There was no statistically significant difference between the groups for correction ratio, postoperative coronal balance, postoperative thoracic kyphosis and lumbar lordosis angle, operation time, amount of blood loss and number of fixation points (p > 0.05) The difference for the ratio of correction loss, AV derotation angle and the AVT correction ratio at the last follow-up visit and for the total follow-up period between the groups was found to be statistically significant (p < 0.05). Although it is possible to obtain a similar amount of correction by either instrumentation system, the loss of correction seems to be lower with the more rigid PS construction. The PS system also has a stronger effect on vertebral bodies, thereby providing better AV de-rotation. There was no significant difference (p > 0.05) between the groups in terms of correction rate, postoperative coronal and sagittal balance, operation time, blood loss and number of fixation points. This may indicate that anchor points are more important than the use – or not – of screws. Correction durability and AV de-rotation was better with PS instrumentation, while AVT was better corrected by HS instrumentation (p < 0.05). We propose that the reason for the better correction of AVT with HS instrumentation is the forceful translation offered by the sublaminar wire at the apical region, while the reason for the better correction durability of the PS instrumentation may be due to the fact that multiple pedicle screws which afford three-column control are better at maintaining the correction and preventing late deterioration.
PMCID: PMC2532282  PMID: 17437110
16.  Validation of computerized diagnostic information in a clinical database from a national equine clinic network 
Computerized diagnostic information offers potential for epidemiological research; however data accuracy must be addressed. The principal aim of this study was to evaluate the completeness and correctness of diagnostic information in a computerized equine clinical database compared to corresponding hand written veterinary clinical records, used as gold standard, and to assess factors related to correctness. Further, the aim was to investigate completeness (epidemiologic sensitivity), correctness (positive predictive value), specificity and prevalence for diagnoses for four body systems and correctness for affected limb information for four joint diseases.
A random sample of 450 visits over the year 2002 (nvisits = 49,591) was taken from 18 nation wide clinics headed under one company. Computerized information for the visits selected and copies of the corresponding veterinary clinical records were retrieved. Completeness and correctness were determined using semi-subjective criteria. Logistic regression was used to examine factors associated with correctness for diagnosis.
Three hundred and ninety six visits had veterinary clinical notes that were retrievable. The overall completeness and correctness were 91% and 92%, respectively; both values considered high. Descriptive analyses showed significantly higher degree of correctness for first visits compared to follow up visits and for cases with a diagnostic code recorded in the veterinary records compared to those with no code noted. The correctness was similar regardless of usage category (leisure/sport horse, racing trotter and racing thoroughbred) or gender.
For the four body systems selected (joints, skin and hooves, respiratory, skeletal) the completeness varied between 71% (respiration) and 91% (joints) and the correctness ranged from 87% (skin and hooves) to 96% (respiration), whereas the specificity was >95% for all systems. Logistic regression showed that correctness was associated with type of visit, whether an explicit diagnostic code was present in the veterinary clinical record, and body system. Correctness for information on affected limb was 95% and varied with joint.
Based on the overall high level of correctness and completeness the database was considered useful for research purposes. For the body systems investigated the highest level of completeness and correctness was seen for joints and respiration, respectively.
PMCID: PMC2801496  PMID: 20003256
17.  Prevalence and Distribution of Corrective Lenses among School-Age Children 
No population-based data are available regarding the proportion of school-age children who have corrective lenses in the U.S. The objective of this study was to quantify the proportion of children who have corrective lenses (glasses or contact lenses) and to evaluate the association of corrective lenses with age, gender, race/ethnicity, health insurance status, and family income.
Children 6 to 18 years of age were identified in the 1998 Medical Expenditure Panel Survey. National estimates were made of the proportion with corrective lenses. Logistic regression modeling was used to assess factors that were associated with corrective lenses.
Based on the 5,141 children in the 1988 Medical Expenditure Panel Survey, an estimated 25.4% of the 52.6 million children between 6 and 18 years had corrective lenses. Girls had greater odds than boys of having corrective lenses (odds ratio, 1.41; p < 0.001). Insured children, regardless of race/ethnicity, and uninsured nonblack/non-Hispanic children had similar odds of having corrective lenses. Compared with uninsured black or Hispanic children (odds ratio, 1), greater odds of corrective lens use was found among uninsured nonblack/non-Hispanic children (odds ratio, 2.29; p = 0.002) and black or Hispanic children with public (odds ratio, 1.67; p = 0.005) or private health insurance (odds ratio,1.77; p = 0.004). Among families with an income ≥200% of the federal poverty level, the odds of having corrective lenses increased with age (p ≤ 0.04). In contrast, among those families <200% of the federal poverty level, the odds of having corrective lenses at 12 to 14 years was similar to 15- to 18-year olds (p = 0.93).
The use of corrective lenses suggests that correctable visual impairment is the most common treatable chronic condition of childhood. Income, gender, and race/ethnicity, depending on insurance status, are associated with having corrective lenses. The underlying causes and the impacts of these differences must be understood to ensure optimal delivery of eye care.
PMCID: PMC2562227  PMID: 14747754
eyeglasses; health services research; socioeconomic factors; child; adolescent
18.  Optimizing wavefront-guided corrections for highly aberrated eyes in the presence of registration uncertainty 
Journal of Vision  2013;13(7):8.
Dynamic registration uncertainty of a wavefront-guided correction with respect to underlying wavefront error (WFE) inevitably decreases retinal image quality. A partial correction may improve average retinal image quality and visual acuity in the presence of registration uncertainties. The purpose of this paper is to (a) develop an algorithm to optimize wavefront-guided correction that improves visual acuity given registration uncertainty and (b) test the hypothesis that these corrections provide improved visual performance in the presence of these uncertainties as compared to a full-magnitude correction or a correction by Guirao, Cox, and Williams (2002). A stochastic parallel gradient descent (SPGD) algorithm was used to optimize the partial-magnitude correction for three keratoconic eyes based on measured scleral contact lens movement. Given its high correlation with logMAR acuity, the retinal image quality metric log visual Strehl was used as a predictor of visual acuity. Predicted values of visual acuity with the optimized corrections were validated by regressing measured acuity loss against predicted loss. Measured loss was obtained from normal subjects viewing acuity charts that were degraded by the residual aberrations generated by the movement of the full-magnitude correction, the correction by Guirao, and optimized SPGD correction. Partial-magnitude corrections optimized with an SPGD algorithm provide at least one line improvement of average visual acuity over the full magnitude and the correction by Guirao given the registration uncertainty. This study demonstrates that it is possible to improve the average visual acuity by optimizing wavefront-guided correction in the presence of registration uncertainty.
PMCID: PMC3680305  PMID: 23757512
optical design; wavefront-guided correction; stochastic parallel gradient descent; keratoconus; registration uncertainty
19.  Use of Corrective Lenses among Adolescents: Findings from the National Health and Nutrition Examination Survey 
To evaluate demographic variations in the use of corrective lenses among adolescent children.
Cross-sectional analysis of 3,916 children 12-18 years who participated in the 1999-2002 National Health and Nutrition Examination Survey (NHANES) vision examination component, which included: questions regarding use of corrective lenses; distance visual acuity, with corrective lenses if available; and non-cycloplegic autorefraction. Results reflect population-level estimates.
Overall, 32.2% (95% confidence interval [CI]: 29.5%-35.0%) reported wearing corrective lenses. Girls and those with any private insurance had greater adjusted odds of reporting wearing corrective lenses. In contrast, children aged 15 through 18 years versus those 12 through 14 years, and white children compared to Black or Hispanic children had greater adjusted odds of actually having them available at the time of NHANES participation. Although 12.6% (95% CI: 8.8%-16.3%) of those who did not have their previously prescribed corrective lenses available had 20/25 or better distance visual acuity in both eyes without correction, 26.9% (95% CI:21.6%-32.1%) with their corrective lenses had distance visual acuity of 20/40 or worse in at least one eye when using their corrective lenses.
Near visual acuity was not measured and children with corrective lenses available only had their corrected distance visual acuity measured. No data regarding the accuracy of the NHANES assessment of distance visual acuity are available. Autorefraction was performed without cycloplegia.
Many adolescent children report wearing corrective lenses. Variations across demographic characteristics appear to be due to a combination of undertreatment, overtreatment, and compliance with previously recommended corrective lenses.
PMCID: PMC2132442  PMID: 18062494
refractive errors; adolescent health services; eyeglasses
20.  Correcting Mortality for Loss to Follow-Up: A Nomogram Applied to Antiretroviral Treatment Programmes in Sub-Saharan Africa 
PLoS Medicine  2011;8(1):e1000390.
Matthias Egger and colleagues present a nomogram and a web-based calculator to correct estimates of program-level mortality for loss to follow-up, for use in antiretroviral treatment programs.
The World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART.
Methods and Findings
We developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in a treatment programme is a weighted average of mortality among patients lost to follow-up and patients remaining in care. The nomogram gives a correction factor based on the percentage of patients lost to follow-up at a given point in time, and the estimated ratio of mortality between patients lost and not lost to follow-up. The mortality observed among patients retained in care is then multiplied by the correction factor to obtain an estimate of programme-level mortality that takes all deaths into account. A web calculator directly calculates the corrected, programme-level mortality with 95% confidence intervals (CIs). We applied the method to 11 ART programmes in sub-Saharan Africa. Patients retained in care had a mortality at 1 year of 1.4% to 12.0%; loss to follow-up ranged from 2.8% to 28.7%; and the correction factor from 1.2 to 8.0. The absolute difference between uncorrected and corrected mortality at 1 year ranged from 1.6% to 9.8%, and was above 5% in four programmes. The largest difference in mortality was in a programme with 28.7% of patients lost to follow-up at 1 year.
The amount of bias in mortality estimates can be large in ART programmes with substantial loss to follow-up. Programmes should routinely report mortality among patients retained in care and the proportion of patients lost. A simple nomogram can then be used to estimate mortality among all patients who started ART, for a range of plausible mortality rates among patients lost to follow-up.
Please see later in the article for the Editors' Summary
Editors' Summary
AIDS has killed more than 25 million people since 1981 and about 33 million people (30 million of them in low- and middle-income countries) are now infected with HIV, which causes AIDS. HIV destroys immune system cells, leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (ART) became available. For people living in affluent, developed countries, HIV/AIDS became a chronic condition, but for people living in low- and middle-income countries, ART was prohibitively expensive and HIV/AIDS remained a fatal illness. In 2003, this situation was declared a global health emergency and governments, international agencies, and funding bodies began to implement plans to increase ART coverage in developing countries. By the end of 2009, 5.25 million of the 14.6 million people in low- and middle-income countries who needed ART (36%) were receiving it.
Why Was This Study Done?
ART program managers in developing countries need to monitor the effectiveness of their programs to ensure that their limited resources are used wisely. In particular, they need accurate records of the death (mortality) rates in their programs. However, in resource-limited countries, many patients drop out of ART programs. In sub-Saharan Africa, for example, only about 60% of patients are retained in ART programs 2 years after starting therapy. In many programs, it is not known how many of the patients lost to follow-up subsequently die, but it is known that mortality is higher among these patients than among those who remain in care. Thus, in programs with high dropout rates and poor ascertainment of death in patients lost to follow-up, estimates of the mortality of all patients starting ART are underestimates. In this study, the researchers develop a simple nomogram (a graphical method for finding the value of a third variable from the values of two other variables) to correct estimates of program-level mortality for loss to follow-up.
What Did the Researchers Do and Find?
The researchers' nomogram uses the percentage of patients lost to follow and the estimated ratio of mortality between patients lost and not lost to follow-up to provide a correction factor that converts mortality among patients remaining in care to mortality among all the patients in a program. The researchers first applied their nomogram to the Academic Model Providing Access to Healthcare (AMPATH), a large ART program in Kenya. They used data collected by outreach teams to estimate mortality among the 40.5% of patients lost to follow-up at two AMPATH sites between 1 January 2005 and 31 January 2007. The uncorrected estimate of mortality over this period was 2.8%, whereas the corrected estimate obtained using the nomogram was 9.4%. The researchers then applied their nomogram to 11 other African ART programs. This time, the researchers used a statistical model to provide estimates of mortality among patients lost to follow-up. Mortality among patients retained in care was 1.4% to 12.0% at 1 year; loss to follow-up ranged from 2.8% to 28.7%. The nomogram provided a correction value for mortality among all patients in the ART program of 1.2 to 8.0, which resulted in absolute differences between uncorrected and corrected mortality of 1.6% to 9.8%. The largest absolute difference was in the program with the largest percentage of patients lost to follow-up.
What Do These Findings Mean?
These findings indicate that, in ART programs where a large percentage of patients are lost to follow-up, program-level mortality estimates based on the mortality among patients retained in the program can be substantial underestimates. This bias needs to be taken into account when comparing the effectiveness of different programs, so the researchers recommend that all programs routinely report mortality among patients retained in care and the proportion of patients lost to follow-up. The nomogram developed by the researchers can then be used to estimate mortality among all patients who started ART using a range of plausible mortality rates among patients lost to follow-up. To help program managers make use of the nomogram, the researchers provide a user-friendly web calculator based on the nomogram on the International epidemiologic Databases to Evaluate AIDS (IeDEA) Southern Africa website.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Gregory Bisson
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the HIV and AIDS in Africa, and on universal access to AIDS treatment (in English and Spanish)
The World Health Organization provides information about universal access to AIDS treatment, including the 2010 progress report (in English, French and Spanish)
The International epidemiologic Databases to Evaluate Aids (IeDEA) Southern Africa website provides access to a calculator for correcting overall program-specific mortality for loss to follow-up
PMCID: PMC3022522  PMID: 21267057
21.  Dynamics May Significantly Influence the Estimation of Interatomic Distances in Biomolecular X-ray Structures 
Journal of Molecular Biology  2011;411(1):286-297.
Atomic positions obtained by X-ray crystallography are time and space averages over many molecules in the crystal. Importantly, interatomic distances, calculated between such average positions and frequently used in structural and mechanistic analyses, can be substantially different from the more appropriate time-average and ensemble-average interatomic distances. Using crystallographic B-factors, one can deduce corrections, which have so far been applied exclusively to small molecules, to obtain correct average distances as a function of the type of atomic motion. Here, using 4774 high-quality protein X-ray structures, we study the significance of such corrections for different types of atomic motion. Importantly, we show that for distances shorter than 5 Å, corrections greater than 0.5 Å may apply, especially for noncorrelated or anticorrelated motion. For example, 14% of the studied structures have at least one pair of atoms with a correction of ≥ 0.5 Å in the case of noncorrelated motion. Using molecular dynamics simulations of villin headpiece, ubiquitin, and SH3 domain unit cells, we demonstrate that the majority of average interatomic distances in these proteins agree with noncorrelated corrections, suggesting that such deviations may be truly relevant. Importantly, we demonstrate that the corrections do not significantly affect stereochemistry and the overall quality of final refined X-ray structures, but can provide marked improvements in starting unrefined models obtained from low-resolution X-ray data. Finally, we illustrate the potential mechanistic and biological significance of the calculated corrections for KcsA ion channel and show that they provide indirect evidence that motions in its selectivity filter are highly correlated.
Graphical Abstract
Research Highlights
► We obtain corrected interatomic distances from static X-ray structures and B-factors. ► For a large set of protein structures, we show that corrections may exceed 0.5 Å. ► Molecular dynamics simulations agree best with noncorrelated corrections. ► Use of corrected distances in refinement frequently lowers the Rfree factor. ► Corrections give indirect evidence of correlated motions in KcsA selectivity filter.
PMCID: PMC3171141  PMID: 21645520
PDB, Protein Data Bank; MD, molecular dynamics; RMSF, root-mean-square fluctuation; molecular dynamics; B-factors; averaging; molecular replacement; refinement
22.  Visual performance in cataract patients with low levels of postoperative astigmatism: full correction versus spherical equivalent correction 
To evaluate whether visual performance could be improved in pseudophakic subjects by correcting low levels of postoperative astigmatism.
An exploratory, noninterventional study was conducted using subjects who had been implanted with an aspheric intraocular lens and had 0.5–0.75 diopter postoperative astigmatism. Monocular visual performance using full correction was compared with visual performance using spherical equivalent correction. Testing consisted of high- and low-contrast visual acuity, contrast sensitivity, and reading acuity and speed using the Radner Reading Charts.
Thirty-eight of 40 subjects completed testing. Visual acuities at three contrast levels (100%, 25%, and 9%) were significantly better using full correction than when using spherical equivalent correction (all P < 0.001). For contrast sensitivity testing under photopic, mesopic, and mesopic with glare conditions, only one out of twelve outcomes demonstrated a significant improvement with full correction compared with spherical equivalent correction (at six cycles per degree under mesopic without glare conditions, P = 0.046). Mean reading speed was numerically faster with full correction across all print sizes, reaching statistical significance at logarithm of the reading acuity determination (logRAD) 0.2, 0.7, and 1.1 (P < 0.05). Statistically significant differences also favored full correction in logRAD score (P = 0.0376), corrected maximum reading speed (P < 0.001), and logarithm of the minimum angle of resolution/logRAD ratio (P < 0.001).
In this study of pseudophakic subjects with low levels of postoperative astigmatism, full correction yielded significantly better reading performance and high- and low-contrast visual acuity than spherical equivalent correction, suggesting that cataractous patients may benefit from surgical correction of low levels of preoperative corneal astigmatism.
PMCID: PMC3295631  PMID: 22399846
aspheric intraocular lens; astigmatism; cataract surgery; contrast sensitivity; reading acuity; visual acuity
23.  Automated patient motion detection and correction in dynamic renal scintigraphy 
Kidney motion during dynamic renal scintigraphy can cause errors in calculated renal function parameters. Our goal was to develop and validate algorithms to detect and correct patient motion.
We retrospectively collected dynamic images from 86 clinical renal studies (42 females, 44 males), acquired using the following protocol for 99m Tc Mertiatide (MAG3) imaging: 80 128×128 image frames (24 2-second frames, 16 15-second frames, 40 30-second frames, 128×128, 3.2 mm/pixel). We simulated ten types of vertical motion in each patient study, resulting in 860 image sets. Motion consisted of up or down shifts of magnitude 0.25 pixels to 4 pixels per frame, and were either A) gradual shift additive over multiple frames or B) abrupt shift of one or more consecutive frames, with a later return to the start position. Additional horizontal motion was added to test its effect on detection of vertical motion. Original and shifted files were submitted to a motion detection algorithm. Corrective shifts were applied, and corrected and original, unshifted images were compared on a pixel by pixel basis. Motion detected in the shifted data was also tabulated before and after correcting for motion detected in the original unshifted data. A detected shift was considered correct if it was within 0.25 pixel of the simulated magnitude. Software was developed to facilitate visual review of all images, and to summarize kidney motion and motion correction using linograms.
Overall detection of simulated shifts was 99% (3068/3096 frames) when the existing motion in the original images was first corrected. When the original motion was not corrected, overall shift detection was 76% (2345/3096 frames). For image frames in which no shift was added, (and original motion was not corrected) 87% (27142/31132 frames) were correctly detected as having no shift. When corrected images were compared to original, calculated count recovery was 100% for all shifts that were whole pixel magnitudes. For fractional pixel shifts, percent count recovery varied from 52–73%. Visual review suggested that some original, unshifted frames exhibited true patient motion.
The algorithm accurately detected motion as small as 0.25 pixels. Whole pixel motion can be detected and corrected with high accuracy. Fractional pixel motion can be detected and corrected but with less accuracy. Importantly, the algorithm accurately identified unshifted frames, which helps to prevent the introduction of errors during motion correction.
PMCID: PMC3104056  PMID: 21565959
motion correction; renal scintigraphy; cross-correlation
24.  The results of anterior fusion and Cotrel-Dubousset-Hopf instrumentation in idiopathic scoliosis 
European Spine Journal  2000;9(6):505-515.
Anterior instrumentation for the correction of scoliotic curves has recently been gaining in popularity. The problems of high mortality and morbidity that were associated with the employment of anterior instrumentation in the first years it was used have now been overcome. Efforts are now being concentrated on increasing the correction rates in the frontal plane and decreasing the kyphotic effect in the sagittal plane. The anterior Cotrel-Dubousset-Hopf (CDH) system is a recently developed instrumentation that has been claimed to decrease the kyphotic effect through the use of double rods. This study aimed to investigate the impact of the anterior CDH system on idiopathic scoliotic curves in frontal and sagittal planes. To this end, 26 idiopathic scoliosis patients treated with the CDH system were followed for a mean period of 32.8 ± 5.3 months. In the frontal plane, Cobb angles of major and secondary curves were measured, and postoperative and final correction rates determined. In the sagittal plane, sagittal contours of both the instrumented region and the thoracic and lumbar regions were measured, and their preoperative, postoperative and final control values were determined. In addition to clinical examination, lateral trunk shift (LT), shift of head (SH) and shift of stable vertebra (SS) were measured in vertebral units (VU), on the preoperative and postoperative radiographs in order to evaluate the effect of the system on trunk balance. It was established that in patients with single flexible thoracolumbar and lumbar curves and those with rigid thoracic curves, the correction rates obtained in the frontal plane were respectively 79.4 ± 14.8%, 68.0 ± 9.4% and 61.5 ± 8.0%, with statistical significance. Their final corrections at the last control were 76.3 ± 17.4%, 56.9 ± 9.1% and 52.3 ± 8.3%, respectively. Although the corrections in the lumbar rigid curves were relatively low, they were still statistically significant. Taking all the patients together, the mean preoperative Cobb angle of the major curves of 67.2°± 20.2° improved to a mean of 28.6°± 21.0°, which was a statistically significant difference (P < 0.05), giving a mean correction rate of 61.2 ± 20.3%. The mean correction loss of major curves in the frontal plane in all patients was 6.0°± 3.8° and the mean final correction rate was 52.6 ± 23.2%. In the sagittal plane, there was a favorable kyphotic effect on the thoracic region of patients with hypokyphosis and lordosis pattern, whilst in patients with kyphotic pattern, this effect was minimal. In patients with a single flexible lumbar curve, kyphotic effect was not observed except in two patients. In these two patients, it was thought that excessive compression force may have been used. As to the patients with a rigid lumbar curve, there was a slight decrease in lumbar lordosis. No postoperative complaints were made about imbalance, and the mean overall correction in LT values was 60.1 ± 21.7%. While preoperatively, the SH and SS values of all patients were over 0.5 VU, postoperatively, 12 patients (46.2%) were completely balanced (SH = 0 VU, SS = 0 VU) and 8 patients (30.8%) were balanced (0 VU < SH and SS < 0.5 VU). The remaining six patients, whose balance values were corrected with statistical significance but were still over 0.5 VU, were found to be the ones with rigid lumbar curves. Implant failure and systemic complications were not noted in the follow-up period. In view of these findings, it was determined that CDH instrumentation achieves significant correction rates in the frontal and sagittal planes, particularly in single flexible lumbar, thoracolumbar and thoracic rigid curves. It was found that the kyphotic effect was minimized with a double rod system. Significant clinical and radiological corrections were achieved in balance values, without any imbalance and decompensation problems.
PMCID: PMC3611411  PMID: 11189919
Key words Idiopathic scoliosis; Anterior instrumentation; Surgical treatment; Complications
25.  Racial Disparities in Uncorrected and Undercorrected Refractive Error in the United States 
To identify risk factors for inadequately corrected refractive error in the United States.
This cross-sectional study included 12,758 participants 12 years of age and older from the 2005 to 2008 National Health and Nutrition Examination Survey. The primary outcome was the proportion of individuals with inadequate refractive correction for whom refractive correction would result in a visual acuity of 20/40 or better. The primary predictor was race/ethnicity. Secondary predictors included age, sex, annual household income, education, insurance, type of refractive error, current corrective lens use, presenting and best corrected visual acuity, cataract surgery, glaucoma, and age-related macular degeneration.
Overall, 50.6% of subjects had a refractive error which was correctable to 20/40 or better with refraction. The percentage of subjects with correctable refractive error who were inadequately corrected was 11.7%. Odds of inadequate refractive correction were significantly greater in Mexican Americans and non-Hispanic blacks than in their non-Hispanic white counterparts in all age groups, with the greatest disparity in the 12- to 19-year-old group. Other risk factors associated with inadequate refractive correction in adults but not in teenagers included low annual household income, low education, and lack of health insurance.
Racial disparities in refractive error correction were most pronounced in those under 20 years of age, as well as in adults with low annual household income, low education level, and lack of health insurance. Targeted efforts to provide culturally appropriate education, accessible vision screening, appropriate refractive correction, and routine follow-up to these medically underserved groups should be pursued as a public health strategy.
This US population-based study found Non-Caucasian race to be associated with inadequately corrected refractive error. The racial disparities were most pronounced in subjects under 20 years as well as in adults with low annual household income, low education level and lack of health insurance.
PMCID: PMC4215743  PMID: 25249602
ethnic disparities; healthcare access; NHANES; racial disparities; refractive error

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