CT Grading of Otosclerosis Lee, T.C; Aviv, R.I; Chen, J.M ...
American journal of neuroradiology,
08/2009, Volume:
30, Issue:
7
Journal Article
Peer reviewed
Open access
The CT grading system for otosclerosis was proposed by Symons and Fanning in 2005. The purpose of this study was to determine if this CT grading system has high interobserver and intraobserver ...agreement.
All 997 petrous bone CTs performed between December 2000 and September 2007 were reviewed. A total of 81 subjects had CT evidence of otosclerosis on at least 1 side; 68 (84%) had bilateral disease. Because otosclerosis was clinically suspected in both ears of all 81 subjects even if CT evidence was only unilateral, both petrous bones (162 in total) were included. Two blinded neuroradiologists independently graded disease severity using the Symons/Fanning grading system: grade 1, solely fenestral; grade 2, patchy localized cochlear disease (with or without fenestral involvement) to either the basal cochlear turn (grade 2A), or the middle/apical turns (grade 2B), or both the basal turn and the middle/apical turns (grade 2C); and grade 3, diffuse confluent cochlear involvement (with or without fenestral involvement). One reviewer repeat-graded the petrous bone CTs to determine intraobserver agreement with a 7-month intervening delay to mitigate recall bias.
There were 154 agreements (95%) comparing the first grading of reviewer 1 with that of reviewer 2 (kappa = 0.93). When the repeat 7-month delayed grading of reviewer 1 was compared with that of reviewer 2, there were 151 (93%) agreements (kappa = 0.90). Therefore, mean interobserver agreement was excellent (mean kappa = 0.92). There were 155 agreements (96%) comparing the original grading of reviewer 1 with the delayed grading (kappa = 0.94), demonstrating excellent intraobserver agreement.
A recently published CT grading for otosclerosis on the basis of location of involvement yielded excellent interobserver and intraobserver agreement.
HIV reservoir quantification is essential for evaluation of HIV curative strategies and may provide valuable insights about reservoir dynamics during antiretroviral therapy. The Intact Proviral DNA ...Assay (IPDA) provides the unique opportunity to quantify the intact and defective reservoir. The current IPDA is optimized for HIV-1 subtype B, the dominant subtype in resource-rich settings. However, subtype C is dominant in Sub-Saharan Africa, jointly accounting for around 60% of the pandemic. We developed an assay capable of quantifying intact and defective proviral HIV-1 DNA of subtype B and C.
Primer and probe sequences were strategically positioned at conserved regions in psi and env and adapted to subtype B&C. In silico analysis of 752 subtype B and 697 subtype C near-full length genome sequences (nFGS) was performed to predict the specificity and sensitivity. Gblocks were used to determine the limit of blank (LoB), limit of detection (LoD), and different annealing temperatures were tested to address impact of sequence variability.
The in silico analysis showed that the HIV-1 B&C IPDA correctly identified 100% of the intact subtype B, and 86% of the subtype C sequences. In contrast, the original IPDA identified 86% and 12% of these subtype B and C sequences as intact. Furthermore, the HIV-1 B&C IPDA correctly identified hypermutated (87% and 88%) and other defective sequences (73% and 66%) for subtype B and C with comparable specificity as the original IPDA for subtype B (59% and 63%). Subtype B cis-acting sequences were more frequently identified as intact by the HIV-1 B&C IPDA compared to the original IPDA (39% and 2%). The LoB for intact proviral DNA copies was 0, and the LoD for intact proviral DNA copies was 6 (> 95% certainty) at 60 °C. Quantification of 2-6 copies can be performed with > 80% certainty. Lowering the annealing temperature to 55 °C slightly lowered the specificity but prevented exclusion of samples with single mutations in the primer/probe region.
We developed a robust and sensitive assay for the quantification of intact and defective HIV-1 subtype B and C proviral DNA, making this a suitable tool to monitor the impact of (large-scale) curative interventions.
Analysis of prospective follow-up data usually includes a Cox regression model. When a hazard rate ratio, obtained as the exponential of an estimated regression coefficient from the Cox model, is ...greater than 1.0, it consistently exceeds relative risk, and is exceeded by the odds ratio. The divergence of these distinct epidemiologic measures increases with the product of three factors: (1) the length of follow-up, (2) the average rate of the end point occurence over the follow-up period, and (3) the magnitude of risk, either above or below 1. Cornfield's rare disease assumption is basically the product of the first two of these factors. However, risks in excess of 2.5 have a powerful effect on the divergence of these measures, and this point has received less emphasis. Conversely, and as seen frequently in applications, relative risk, hazard rate ratio, and odds ratio numerically approximate one another with shorter follow-up, rarer end points, and risks closer to 1. Although the hazard rate ratio is not always distinguished from relative risk, it is commonly close to, and is always between, relative risk and the odds ratio. Consistent and accurate terminology would have us use hazard rate ratio with Cox regression and odds ratio with logistic regression. The term “relative risk” seems to be a default choice, regardless of the model being used. However, when relative risk is the object of the model chosen, as in a Poisson regression approximation of two binomial proportions or an equivalent weighted least squares, then for us, relative risk is the accurate terminology.
With increasing evidence of adverse health effects associated with particulate matter (PM), the exposure impact of natural sources, such as forest fires, has substantial public health relevance. In ...addition to the threat to nearby communities, pollutants released from forest fires can travel thousands of kilometers to heavily populated urban areas. There was a dramatic increase in forest fire activity in the province of Quebec, Canada, during July 2002. The transport of PM released from these forest fires was examined using a combination of a moderate-resolution imaging spectroradiometer satellite image, back-trajectories using a hybrid single-particle Lagrangian integrated trajectory, and local light detection and ranging measurements. Time- and size-resolved PM was evaluated at three ambient and four indoor measurement sites using a combination of direct reading instruments (laser, time-of-flight aerosol spectrometer, nephelometer, and an oscillating microbalance). The transport and monitoring results consistently identified a forest fire related PM episode in Baltimore that occurred the first weekend of July 2002 and resulted in as much as a 30-fold increase in ambient fine PM. On the basis of tapered element oscillating microbalance measurements, the 24 h PM2.5 concentration reached 86 μg/m3 on July 7, 2002, exceeding the 24 h national ambient air quality standard. The episode was primarily comprised of particles less than 2.5 μm in aerodynamic diameter, highlighting the preferential transport of the fraction of PM that is of greatest health concern. Penetration of the ambient episode indoors was efficient (median indoor-to-outdoor ratio 0.91) such that the high ambient levels were similarly experienced indoors. These results are significant in demonstrating the impact of a natural source thousands of kilometers away on ambient levels of and potential exposures to air pollution within an urban center. This research highlights the significance of transboundary air pollution and the need for studies that assess the public health impacts associated with such sources and transport processes.
(
) has recently been legalized in multiple countries globally for either its recreational or medicinal use. This, in turn, has led to a marked increase in the number of
varieties available for use ...in either market. However, little information currently exists on the genetic distinction between adopted varieties. Such fundamental knowledge is of considerable value and underpins the accelerated development of both a nascent pharmaceutical industry and the commercial recreational market. Therefore, in this study, we sought to assess genetic diversity across 10
varieties by undertaking a reduced representation shotgun sequencing approach on 83 individual plants to identify variations which could be used to resolve the genetic structure of the assessed population. Such an approach also allowed for the identification of the genetic features putatively associated with the production of secondary metabolites in
. Initial analysis identified 3608 variants across the assessed population with phylogenetic analysis of this data subsequently enabling the confident grouping of each variety into distinct subpopulations. Within our dataset, the most diagnostically informative single nucleotide polymorphisms (SNPs) were determined to be associated with the long-terminal repeat (LTRs) class of retroelements, with 172 such SNPs used to fully resolve the genetic structure of the assessed population. These 172 SNPs could be used to design a targeted resequencing panel, which we propose could be used to rapidly screen different
plants to determine genetic relationships, as well as to provide a more robust, scientific classification of
varieties as the field moves into the pharmaceutical sphere.
We investigated whether computed tomography (CT) perfusion-derived cerebral blood flow (CBF) and cerebral blood volume (CBV) could be used to differentiate between penumbra and infarcted gray matter ...in a limited, exploratory sample of acute stroke patients.
Thirty patients underwent a noncontrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) scan within 7 hours of stroke onset, NCCT and CTA at 24 hours, and NCCT at 5 to 7 days. Twenty-five patients met the criteria for inclusion and were subsequently divided into 2 groups: those with recanalization at 24 hours (n=16) and those without (n=9). Penumbra was operationally defined as tissue with an admission CBF <25 mL x 100 g(-1) x min(-1) that was not infarcted on the 5- to 7-day NCCT. Logistic regression was applied to differentiate between infarct and penumbra data points.
For recanalized patients, CBF was significantly lower (P<0.05) for infarct (13.3+/-3.75 mL x 100 g(-1) x min(-1)) than penumbra (25.0+/-3.82 mL x 100 g(-1) x min(-1)). CBV in the penumbra (2.15+/-0.43 mL x 100 g(-1)) was significantly higher than contralateral (1.78+/-0.30 mL x 100 g(-1)) and infarcted tissue (1.12+/-0.37 mL x 100 g(-1)). Logistic regression using an interaction term (CBFxCBV) resulted in sensitivity, specificity, and accuracy of 97.0%, 97.2%, and 97.1%, respectively. The interaction term resulted in a significantly better (P<0.05) fit than CBF or CBV alone, suggesting that the CBV threshold for infarction varies with CBF. For patients without recanalization, CBF and CBV for infarcted regions were 15.1+/-5.67 mL x 100 g(-1) x min(-1) and 1.17+/-0.41 mL x 100 g(-1), respectively.
We have shown in a limited sample of patients that CBF and CBV obtained from CTP can be sensitive and specific for infarction and should be investigated further in a prospective trial to assess their utility for differentiating between infarct and penumbra.
Nephrotic syndrome in childhood Eddy, Allison A; Symons, Jordan M
The Lancet (British edition),
08/2003, Volume:
362, Issue:
9384
Journal Article
Peer reviewed
Childhood nephrotic syndromes are most commonly caused by one of two idiopathic diseases: minimal-change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS). A third distinct ...type, membranous nephropathy, is rare in children. Other causes of isolated nephrotic syndrome can be subdivided into two major categories: rare genetic disorders, and secondary diseases associated with drugs, infections, or neoplasia. The cause of idiopathic nephrotic syndrome remains unknown, but evidence suggests it may be a primary T-cell disorder that leads to glomerular podocyte dysfunction. Genetic studies in children with familial nephrotic syndrome have identified mutations in genes that encode important podocyte proteins. Patients with idiopathic nephrotic syndrome are initially treated with corticosteroids. Steroid-responsiveness is of greater prognostic use than renal histology. Several secondline drugs, including alkylating agents, ciclosporin, and levamisole, may be effective for complicated and steroid-unresponsive MCNS and FSGS patients. Nephrotic syndrome is associated with several medical complications, the most severe and potentially fatal being bacterial infections and thromboembolism. Idiopathic nephrotic syndrome is a chronic relapsing disease for most steroid-responsive patients, whereas most children with refractory FSGS ultimately develop end-stage renal disease. Research is being done to further elucidate the disorder's molecular pathogenesis, identify new prognostic indicators, and to develop better approaches to treatment.
The processing of brain diffusion tensor imaging (DTI) data for large cohort studies requires fully automatic pipelines to perform quality control (QC) and artifact/outlier removal procedures on the ...raw DTI data prior to calculation of diffusion parameters. In this study, three automatic DTI processing pipelines, each complying with the general ENIGMA framework, were designed by uniquely combining multiple image processing software tools. Different QC procedures based on the RESTORE algorithm, the DTIPrep protocol, and a combination of both methods were compared using simulated ground truth and artifact containing DTI datasets modeling eddy current induced distortions, various levels of motion artifacts, and thermal noise. Variability was also examined in 20 DTI datasets acquired in subjects with vascular cognitive impairment (VCI) from the multi-site Ontario Neurodegenerative Disease Research Initiative (ONDRI). The mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated in global brain grey matter (GM) and white matter (WM) regions. For the simulated DTI datasets, the measure used to evaluate the performance of the pipelines was the normalized difference between the mean DTI metrics measured in GM and WM regions and the corresponding ground truth DTI value. The performance of the proposed pipelines was very similar, particularly in FA measurements. However, the pipeline based on the RESTORE algorithm was the most accurate when analyzing the artifact containing DTI datasets. The pipeline that combined the DTIPrep protocol and the RESTORE algorithm produced the lowest standard deviation in FA measurements in normal appearing WM across subjects. We concluded that this pipeline was the most robust and is preferred for automated analysis of multisite brain DTI data.
Objectives/Hypothesis: The objective was to correlate implant performance in cochlear otosclerosis to 1) matched control samples, 2) severity of otic capsule involvement, 3) prior ipsilateral ...surgery, and 4) programming issues.
Study Design: Retrospective case controlled study
Methods: Study cohort comprised 30 individuals. Diagnosis was based on prior ear surgery (stapedectomy n = 18 or fenestration n = 2) and/or pathognomonic radiological findings. High‐resolution computed tomography images of the temporal bones were assessed by two radiologists and graded (range, 0–3) for the extent of otosclerosis. Operative records were reviewed. Performance, programming visits, and the number of electrode deactivations at 6 months and at 1 year after implantation were determined for the individuals with otosclerosis and compared with a group of matched control subjects. A within‐group comparison correlating severity of otosclerosis to the above was carried out.
Results: Implant performance in individuals with cochlear otosclerosis was not significantly different from those without. Previous surgery on the side of implantation did not alter performance. Programming difficulty as reflected in the number of visits and electrode deactivation for sound quality reasons were comparable. Deactivation for facial nerve stimulation occurred exclusively in otosclerotics with the most severe radiological disease (grade 3) and was only with non‐modiolar hugging electrodes (n = 5). There was no observed difference between the radiological extent of otosclerosis and implant performance.
Conclusion: Individuals with severe otosclerosis considering cochlear implantation can be counseled to expect similar benefit to those without, regardless of whether prior surgery occurred on the side of implantation or of severity of otic capsule involvement. There is a significant risk of facial nerve stimulation in otosclerotics with grade 3 disease.
The suitability of barley ( Hordeum vulgare L.) grain for malting depends on many criteria, including the size, shape and uniformity of the kernels. Here, image analysis was used to measure kernel ...size and shape attributes (area, perimeter, length, width, F-circle and F-shape) in grain samples of 140 doubled-haploid lines from a two-rowed (cv Harrington) by six-rowed (cv Morex) barley cross. Interval mapping was used to map quantitative trait loci (QTLs) affecting the means and within-sample standard deviations of these attributes using a 107-marker genome map. Regions affecting one or more kernel size and shape traits were detected on all seven chromosomes. These included one near the vrs1 locus on chromosome 2 and one near the int-c locus on chromosome 4. Some, but not all, of the QTLs exhibited interactions with the environment and some QTLs affected the within-sample variability of kernel size and shape without affecting average kernel size and shape. When QTL analysis was conducted using data from only the two-rowed lines, the region on chromosome 2 was not detected but QTLs were detected elsewhere in the genome, including some that had not been detected in the analysis of the whole population. Analysis of only the six-rowed lines did not detect any QTLs affecting kernel size and shape attributes. QTL alleles that made kernels larger and/or rounder also tended to improve malt quality and QTL alleles that increased the variability of kernel size were associated with poor malt quality.
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