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Anatomical accuracy of standard-practice tractography algorithms in the motor system - A histological validation in the squirrel monkey brain.
Schilling KG, Gao Y, Stepniewska I, Janve V, Landman BA, Anderson AW
(2019) Magn Reson Imaging 55: 7-25
MeSH Terms: Algorithms, Animals, Brain, Brain Mapping, Diffusion Tensor Imaging, Image Processing, Computer-Assisted, Models, Anatomic, Motor Cortex, Probability, Reproducibility of Results, Saimiri, Sensitivity and Specificity, Software, White Matter
Show Abstract · Added March 26, 2019
For two decades diffusion fiber tractography has been used to probe both the spatial extent of white matter pathways and the region to region connectivity of the brain. In both cases, anatomical accuracy of tractography is critical for sound scientific conclusions. Here we assess and validate the algorithms and tractography implementations that have been most widely used - often because of ease of use, algorithm simplicity, or availability offered in open source software. Comparing forty tractography results to a ground truth defined by histological tracers in the primary motor cortex on the same squirrel monkey brains, we assess tract fidelity on the scale of voxels as well as over larger spatial domains or regional connectivity. No algorithms are successful in all metrics, and, in fact, some implementations fail to reconstruct large portions of pathways or identify major points of connectivity. The accuracy is most dependent on reconstruction method and tracking algorithm, as well as the seed region and how this region is utilized. We also note a tremendous variability in the results, even though the same MR images act as inputs to all algorithms. In addition, anatomical accuracy is significantly decreased at increased distances from the seed. An analysis of the spatial errors in tractography reveals that many techniques have trouble properly leaving the gray matter, and many only reveal connectivity to adjacent regions of interest. These results show that the most commonly implemented algorithms have several shortcomings and limitations, and choices in implementations lead to very different results. This study should provide guidance for algorithm choices based on study requirements for sensitivity, specificity, or the need to identify particular connections, and should serve as a heuristic for future developments in tractography.
Copyright © 2018 Elsevier Inc. All rights reserved.
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14 MeSH Terms
Validation of an algorithm to identify heart failure hospitalisations in patients with diabetes within the veterans health administration.
Presley CA, Min JY, Chipman J, Greevy RA, Grijalva CG, Griffin MR, Roumie CL
(2018) BMJ Open 8: e020455
MeSH Terms: Adult, Aged, Algorithms, Diabetes Complications, Diabetes Mellitus, Diagnosis-Related Groups, Female, Heart Failure, Hospitalization, Humans, International Classification of Diseases, Male, Middle Aged, Predictive Value of Tests, Sensitivity and Specificity, Veterans
Show Abstract · Added July 27, 2018
OBJECTIVES - We aimed to validate an algorithm using both primary discharge diagnosis (International Classification of Diseases Ninth Revision (ICD-9)) and diagnosis-related group (DRG) codes to identify hospitalisations due to decompensated heart failure (HF) in a population of patients with diabetes within the Veterans Health Administration (VHA) system.
DESIGN - Validation study.
SETTING - Veterans Health Administration-Tennessee Valley Healthcare System PARTICIPANTS: We identified and reviewed a stratified, random sample of hospitalisations between 2001 and 2012 within a single VHA healthcare system of adults who received regular VHA care and were initiated on an antidiabetic medication between 2001 and 2008. We sampled 500 hospitalisations; 400 hospitalisations that fulfilled algorithm criteria, 100 that did not. Of these, 497 had adequate information for inclusion. The mean patient age was 66.1 years (SD 11.4). Majority of patients were male (98.8%); 75% were white and 20% were black.
PRIMARY AND SECONDARY OUTCOME MEASURES - To determine if a hospitalisation was due to HF, we performed chart abstraction using Framingham criteria as the referent standard. We calculated the positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for the overall algorithm and each component (primary diagnosis code (ICD-9), DRG code or both).
RESULTS - The algorithm had a PPV of 89.7% (95% CI 86.8 to 92.7), NPV of 93.9% (89.1 to 98.6), sensitivity of 45.1% (25.1 to 65.1) and specificity of 99.4% (99.2 to 99.6). The PPV was highest for hospitalisations that fulfilled both the ICD-9 and DRG algorithm criteria (92.1% (89.1 to 95.1)) and lowest for hospitalisations that fulfilled only DRG algorithm criteria (62.5% (28.4 to 96.6)).
CONCLUSIONS - Our algorithm, which included primary discharge diagnosis and DRG codes, demonstrated excellent PPV for identification of hospitalisations due to decompensated HF among patients with diabetes in the VHA system.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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16 MeSH Terms
In vitro feasibility of next generation non-linear beamforming ultrasound methods to characterize and size kidney stones.
Tierney JE, Schlunk SG, Jones R, George M, Karve P, Duddu R, Byram BC, Hsi RS
(2019) Urolithiasis 47: 181-188
MeSH Terms: Algorithms, Feasibility Studies, Humans, Image Processing, Computer-Assisted, Kidney, Kidney Calculi, Sensitivity and Specificity, Ultrasonography
Show Abstract · Added April 3, 2018
Ultrasound imaging for kidney stones suffers from poorer sensitivity, diminished specificity, and overestimation of stone size compared to computed tomography (CT). The purpose of this study was to demonstrate in vitro feasibility of novel ultrasound imaging methods comparing traditional B-mode to advanced beamforming techniques including plane wave synthetic focusing (PWSF), short-lag spatial coherence (SLSC) imaging, mid-lag spatial coherence (MLSC) imaging with incoherent compounding, and aperture domain model image reconstruction (ADMIRE). The ultrasound techniques were evaluated using a research-based ultrasound system applied to an in vitro kidney stone model at 4 and 8 cm depths. Stone diameter sizing and stone contrast were compared among the different techniques. Analysis of variance was used to analyze the differences among group means, with p < 0.05 considered significant, and a Student's t test was used to compare each method with B-mode, with p < 0.0025 considered significant. All stones were detectable with each method. MLSC performed best with stone sizing and stone contrast compared to B-mode. On average, B-mode sizing error ± SD was > 1 mm (1.2 ± 1.1 mm), while those for PWSF, ADMIRE, and MLSC were < 1 mm (- 0.3 ± 2.9 mm, 0.6 ± 0.8, 0.8 ± 0.8, respectively). Subjectively, MLSC appeared to suppress the entire background thus highlighting only the stone. The ADMIRE and SLSC techniques appeared to highlight the stone shadow relative to the background. The detection and sizing of stones in vitro are feasible with advanced beamforming methods with ultrasound. Future work will include imaging stones at greater depths and evaluating the performance of these methods in human stone formers.
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8 MeSH Terms
Exact Topological Inference for Paired Brain Networks Persistent Homology.
Chung MK, Vilalta-Gil V, Lee H, Rathouz PJ, Lahey BB, Zald DH
(2017) Inf Process Med Imaging 2017: 299-310
MeSH Terms: Algorithms, Brain, Brain Mapping, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Pattern Recognition, Automated, Reproducibility of Results, Sensitivity and Specificity
Show Abstract · Added March 21, 2018
We present a novel framework for characterizing paired brain networks using techniques in hyper-networks, sparse learning and persistent homology. The framework is general enough for dealing with any type of paired images such as twins, multimodal and longitudinal images. The exact nonparametric statistical inference procedure is derived on testing monotonic graph theory features that do not rely on time consuming permutation tests. The proposed method computes the exact probability in quadratic time while the permutation tests require exponential time. As illustrations, we apply the method to simulated networks and a twin fMRI study. In case of the latter, we determine the statistical significance of the heritability index of the large-scale reward network where every voxel is a network node.
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9 MeSH Terms
Human papillomavirus 16 E6 antibodies are sensitive for human papillomavirus-driven oropharyngeal cancer and are associated with recurrence.
Lang Kuhs KA, Kreimer AR, Trivedi S, Holzinger D, Pawlita M, Pfeiffer RM, Gibson SP, Schmitt NC, Hildesheim A, Waterboer T, Ferris RL
(2017) Cancer 123: 4382-4390
MeSH Terms: Antibodies, Viral, Cell Transformation, Viral, Female, Human papillomavirus 16, Humans, Immunohistochemistry, Male, Middle Aged, Oncogene Proteins, Viral, Oropharyngeal Neoplasms, Papillomavirus Infections, Predictive Value of Tests, Prognosis, Recurrence, Repressor Proteins, Sensitivity and Specificity
Show Abstract · Added October 23, 2017
BACKGROUND - Human papillomavirus 16 (HPV16) E6 antibodies may be an early marker of the diagnosis and recurrence of human papillomavirus-driven oropharyngeal cancer (HPV-OPC).
METHODS - This study identified 161 incident oropharyngeal cancer (OPC) cases diagnosed at the University of Pittsburgh (2003-2013) with pretreatment serum. One hundred twelve had preexisting clinical HPV testing with p16 immunohistochemistry and HPV in situ hybridization (87 were dual-positive [HPV-OPC], and 25 were dual-negative [HPV-negative]); 62 had at least 1 posttreatment serum sample. Eighty-six of the 161 tumors were available for additional HPV16 DNA/RNA testing (45 were dual-positive [HPV16-OPC], and 19 were dual-negative [HPV16-negative). HPV16 E6 antibody testing was conducted with multiplex serology. The following were evaluated: 1) the sensitivity and specificity of HPV16 E6 serology for distinguishing HPV-OPC and HPV16-OPC from HPV-negative OPC, 2) HPV16 E6 antibody decay after treatment with linear models accommodating correlations in variance estimates, and 3) pre- and posttreatment HPV16 E6 levels and the risk of recurrence with Cox proportional hazards models.
RESULTS - Seventy-eight of 87 HPV-OPCs were HPV16 E6-seropositive (sensitivity, 89.7%; 95% confidence interval [CI], 81.3%-95.2%), and 24 of 25 HPV-negative OPCs were HPV16 E6-seronegative (specificity, 96.0%; 95% CI, 79.6%-99.9%). Forty-two of 45 HPV16-OPCs were HPV16 E6-seropositive (sensitivity, 93.3%; 95% CI, 81.7%-98.6%), and 18 of 19 HPV16-negative OPCs were HPV16 E6-seronegative (specificity, 94.7%; 95% CI, 74.0%-99.9%). Posttreatment HPV16 E6 antibody levels did not decrease significantly from the baseline (P = .575; median follow-up, 307 days) and were not associated with the risk of recurrence. However, pretreatment HPV16 E6 seropositivity was associated with an 86% reduced risk of local/regional recurrence (hazard ratio, 0.14; 95% CI, 0.03-0.68; P = .015).
CONCLUSIONS - HPV16 E6 antibodies may have potential clinical utility for the diagnosis and/or prognosis of HPV-OPC. Cancer 2017;123:4382-90. © 2017 American Cancer Society.
© 2017 American Cancer Society.
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16 MeSH Terms
A novel real-time RT-PCR assay for influenza C tested in Peruvian children.
Howard LM, Johnson M, Gil AI, Pekosz A, Griffin MR, Edwards KM, Lanata CF, Grijalva CG, Williams JV, RESPIRA-PERU Group
(2017) J Clin Virol 96: 12-16
MeSH Terms: Child, Preschool, Female, Humans, Infant, Influenza, Human, Influenzavirus C, Male, Molecular Diagnostic Techniques, Peru, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity
Show Abstract · Added July 27, 2018
BACKGROUND - Influenza C virus (ICV) is associated with acute respiratory illness. Yet ICV remains under recognized, with most previous studies using only culture to identify cases.
OBJECTIVES - To develop a sensitive and specific real-time RT-PCR assay for ICV that allows for rapid and accurate detection in a clinical or research setting.
STUDY DESIGN - Multiple ICV sequences obtained from GenBank were analyzed, including 141 hemagglutinin-esterase (HE), 106 matrix (M), and 97 nucleoprotein (NP) sequences. Primers and probes were designed based on conserved regions. Multiple primer-probe sets were tested against multiple ICV strains.
RESULTS - The ICV M and NP genes offered the most conserved sequence regions. Primers and probes based on newer sequence data offered enhanced detection of ICV, especially for low titer specimens. An NP-targeted assay yielded the best performance and was capable of detecting 10-100 RNA copies per reaction. The NP assay detected multiple clinical isolates of ICV collected in a field epidemiology study conducted in Peru.
CONCLUSIONS - We report a new real-time RT-PCR assay for ICV with high sensitivity and specificity.
Copyright © 2017 Elsevier B.V. All rights reserved.
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MeSH Terms
Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach.
Choi E, Lantz TL, Vlacich G, Keeley TM, Samuelson LC, Coffey RJ, Goldenring JR, Powell AE
(2018) Gut 67: 1595-1605
MeSH Terms: Animals, Biomarkers, Cell Lineage, Disease Models, Animal, Gastric Mucosa, Membrane Glycoproteins, Mice, Mice, Knockout, Nerve Tissue Proteins, Predictive Value of Tests, Sensitivity and Specificity, Stem Cells, Stomach Ulcer, Wound Healing
Show Abstract · Added September 27, 2017
OBJECTIVE - Lrig1 is a marker of proliferative and quiescent stem cells in the skin and intestine. We examined whether Lrig1-expressing cells are long-lived gastric progenitors in gastric glands in the mouse stomach. We also investigated how the Lrig1-expressing progenitor cells contribute to the regeneration of normal gastric mucosa by lineage commitment to parietal cells after acute gastric injury in mice.
DESIGN - We performed lineage labelling using (Lrig1/YFP) or (Lrig1/LacZ) mice to examine whether the Lrig1-YFP-marked cells are gastric progenitor cells. We studied whether Lrig1-YFP-marked cells give rise to normal gastric lineage cells in damaged mucosa using Lrig1/YFP mice after treatment with DMP-777 to induce acute injury. We also studied Lrig1- (Lrig1 knockout) mice to examine whether the Lrig1 protein is required for regeneration of gastric corpus mucosa after acute injury.
RESULTS - Lrig1-YFP-marked cells give rise to gastric lineage epithelial cells both in the gastric corpus and antrum, in contrast to published results that Lgr5 only marks progenitor cells within the gastric antrum. Lrig1-YFP-marked cells contribute to replacement of damaged gastric oxyntic glands during the recovery phase after acute oxyntic atrophy in the gastric corpus. Lrig1 null mice recovered normally from acute gastric mucosal injury indicating that Lrig1 protein is not required for lineage differentiation. Lrig1+ isthmal progenitor cells did not contribute to transdifferentiating chief cell lineages after acute oxyntic atrophy.
CONCLUSIONS - Lrig1 marks gastric corpus epithelial progenitor cells capable of repopulating the damaged oxyntic mucosa by differentiating into normal gastric lineage cells in mouse stomach.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
1 Communities
3 Members
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14 MeSH Terms
Subject-specific regional measures of water diffusion are associated with impairment in chronic spinal cord injury.
Choe AS, Sadowsky CL, Smith SA, van Zijl PCM, Pekar JJ, Belegu V
(2017) Neuroradiology 59: 747-758
MeSH Terms: Adult, Aged, Anisotropy, Biomarkers, Body Water, Chronic Disease, Female, Humans, Image Interpretation, Computer-Assisted, Injury Severity Score, Male, Middle Aged, Sensitivity and Specificity, Spinal Cord Injuries
Show Abstract · Added April 10, 2019
PURPOSE - We aimed to identify non-invasive imaging parameters that can serve as biomarkers for the integrity of the spinal cord, which is paramount to neurological function. Diffusion tensor imaging (DTI) indices are sensitive to axonal and myelin damage, and have strong potential to serve as such biomarkers. However, averaging DTI indices over large regions of interest (ROIs), a common approach to analyzing the images of injured spinal cord, leads to loss of subject-specific information. We investigated if DTI-tractography-driven, subject-specific demarcation approach can yield measures that are more specific to impairment.
METHODS - In 18 individuals with chronic spinal cord injury (SCI), subject-specific demarcation of the injury region was performed using DTI tractography, which yielded three regions relative to injury (RRI; regions superior to, at, and below injury epicenter). DTI indices averaged over each RRI were correlated with measures of residual motor and sensory function, obtained using the International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI).
RESULTS - Total ISNCSCI score (ISNCSCI-tot; sum of ISNCSCI motor and sensory scores) was significantly (p < 0.05) correlated with fractional anisotropy and axial and radial diffusivities. ISNCSCI-tot showed strongest correlation with indices measured from the region inferior to the injury epicenter (IRRI), the degree of which exceeded that of those measured from the entire cervical cord-suggesting contribution from Wallerian degeneration.
CONCLUSION - DTI tractography-driven, subject-specific injury demarcation approach provided measures that were more specific to impairment. Notably, DTI indices obtained from the IRRI region showed the highest specificity to impairment, demonstrating their strong potential as biomarkers for the SCI severity.
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MeSH Terms
Chemical exchange rotation transfer imaging of intermediate-exchanging amines at 2 ppm.
Zu Z, Louie EA, Lin EC, Jiang X, Does MD, Gore JC, Gochberg DF
(2017) NMR Biomed 30:
MeSH Terms: Amines, Animals, Brain, Computer Simulation, Creatine, Magnetic Resonance Imaging, Neoplasms, Rats, Rotation, Sensitivity and Specificity
Show Abstract · Added March 19, 2018
Chemical exchange saturation transfer (CEST) imaging of amine protons exchanging at intermediate rates and whose chemical shift is around 2 ppm may provide a means of mapping creatine. However, the quantification of this effect may be compromised by the influence of overlapping CEST signals from fast-exchanging amines and hydroxyls. We aimed to investigate the exchange rate filtering effect of a variation of CEST, named chemical exchange rotation transfer (CERT), as a means of isolating creatine contributions at around 2 ppm from other overlapping signals. Simulations were performed to study the filtering effects of CERT for the selection of transfer effects from protons of specific exchange rates. Control samples containing the main metabolites in brain, bovine serum albumin (BSA) and egg white albumen (EWA) at their physiological concentrations and pH were used to study the ability of CERT to isolate molecules with amines at 2 ppm that exchange at intermediate rates, and corresponding methods were used for in vivo rat brain imaging. Simulations showed that exchange rate filtering can be combined with conventional filtering based on chemical shift. Studies on samples showed that signal contributions from creatine can be separated from those of other metabolites using this combined filter, but contributions from protein amines may still be significant. This exchange filtering can also be used for in vivo imaging. CERT provides more specific quantification of amines at 2 ppm that exchange at intermediate rates compared with conventional CEST imaging.
Copyright © 2017 John Wiley & Sons, Ltd.
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10 MeSH Terms
Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial).
Galadanci NA, Umar Abdullahi S, Vance LD, Musa Tabari A, Ali S, Belonwu R, Salihu A, Amal Galadanci A, Wudil Jibir B, Bello-Manga H, Neville K, Kirkham FJ, Shyr Y, Phillips S, Covert BV, Kassim AA, Jordan LC, Aliyu MH, DeBaun MR
(2017) Am J Hematol 92: 780-788
MeSH Terms: Anemia, Sickle Cell, Antisickling Agents, Child, Child, Preschool, Female, Follow-Up Studies, Hospitalization, Humans, Hydroxyurea, Incidence, Male, Medication Adherence, Nigeria, Reproducibility of Results, Sensitivity and Specificity, Stroke, Treatment Outcome, Ultrasonography, Doppler, Transcranial
Show Abstract · Added April 27, 2017
The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non-imaging TCD measurements (≥200 cm/s) received moderate fixed-dose hydroxyurea therapy (∼20 mg/kg/day). A comparison group of children with TCD measurements <200 cm/s was followed prospectively. Approximately 88% (330 of 375) of families agreed to be screened, while 87% (29 of 33) of those with abnormal TCD measurements, enrolled in the trial. No participant elected to withdraw from the trial. The average mean corpuscular volume increased from 85.7 fl at baseline to 95.5 fl at 24 months (not all of the children who crossed over had a 24 month visit), demonstrating adherence to hydroxyurea. The comparison group consisted of initially 210 children, of which four developed abnormal TCD measurements, and were started on hydroxyurea. None of the monthly research visits were missed (n = total 603 visits). Two and 10 deaths occurred in the treatment and comparison groups, with mortality rates of 2.69 and 1.81 per 100 patient-years, respectively (P = .67). Our results provide strong evidence, for high family recruitment, retention, and adherence rates, to undertake the first randomized controlled trial with hydroxyurea therapy for primary stroke prevention in children with SCA living in Africa.
© 2017 Wiley Periodicals, Inc.
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18 MeSH Terms