Publications by authors named "Eric White"

217 Publications

Detection and Early Referral of Patients With Interstitial Lung Abnormalities: An Expert Survey Initiative.

Chest 2021 Jun 28. Epub 2021 Jun 28.

Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor MI, USA.

Background: Interstitial lung abnormalities (ILA) may represent undiagnosed early-stage or subclinical interstitial lung disease (ILD). ILA are often observed incidentally in patients who subsequently develop clinically overt ILD. There is limited information on consensus definitions for, and the appropriate evaluation of, ILA; early recognition of patients with ILD remains challenging, yet critically important. Expert consensus could inform early recognition and referral.

Research Question: Can consensus-based expert recommendations be identified to guide clinicians in the recognition, referral and follow-up of patients with, or at risk of developing, early ILDs?

Study Design And Methods: Pulmonologists and radiologists with expertise in ILD participated in two iterative rounds of surveys. Surveys aimed to establish consensus regarding ILA reporting, identification of patients with ILA, and identification of populations that might benefit from screening for ILD. Recommended referral criteria and follow-up processes were also addressed. Threshold for consensus was defined a priori as ≥ 75% agreement or disagreement.

Results: Fifty-five experts were invited and 44 participated , reaching consensus on 39/85 questions. The following clinically important statements achieved consensus: honeycombing and traction bronchiectasis or bronchiolectasis indicate potentially progressive ILD; honeycombing detected during lung cancer screening should be reported as potentially significant (e.g. with LUNG-Rads "S" modifier), recommending referral to a pulmonologist in the radiology report; high-resolution computed tomography and full pulmonary function tests should be ordered if non-dependent subpleural reticulation, traction bronchiectasis, honeycombing, centrilobular ground-glass nodules or patchy ground-glass opacity are observed on computed tomography; patients with honeycombing or traction bronchiectasis should be referred to a pulmonologist irrespective of forced vital capacity and diffusion capacity values; and patients with systemic sclerosis should be screened with pulmonary function tests for early-stage ILD.

Interpretation: Guidance for identifying clinically relevant ILA, subsequent referral and follow-up was established. These results lay foundations for developing practical guidance on managing patients with ILA.
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http://dx.doi.org/10.1016/j.chest.2021.06.035DOI Listing
June 2021

Glenoid Bone Loss in Shoulder Instability: Superiority of Three-Dimensional Computed Tomography over Two-Dimensional Magnetic Resonance Imaging Using Established Methodology.

Clin Orthop Surg 2021 Jun 9;13(2):223-228. Epub 2021 Mar 9.

USC Epstein Family Center for Sports Medicine, Keck Medicine of USC, Los Angeles, CA, USA.

Backgroud: Recent literature suggests that three-dimensional magnetic resonance imaging (3D MRI) can replace 3D computed tomography (3D CT) when evaluating glenoid bone loss in patients with shoulder instability. We aimed to examine if 2D MRI in conjunction with a validated predictive formula for assessment of glenoid height is equivalent to the gold standard 3D CT scans for patients with recurrent glenohumeral instability.

Methods: Patients with recurrent shoulder instability and available imaging were retrospectively reviewed. Glenoid height on 3D CT and 2D MRI was measured by two blinded raters. Difference and equivalence testing were performed using a paired -test and two one-sided tests, respectively. The interclass correlation coefficient (ICC) was used to test for interrater reliability, and percent agreement between the measurements of one reviewer was used to assess intrarater reliability.

Results: Using an equivalence margin of 1 mm, 3D CT and 2D MRI were found to be different ( = 0.123). The mean glenoid height was significantly different when measured on 2D MRI (39.09 ± 2.93 mm) compared to 3D CT (38.71 ± 2.89 mm) ( = 0.032). The mean glenoid width was significantly different between 3D CT (30.13 ± 2.43 mm) and 2D MRI (27.45 ± 1.72 mm) ( < 0.001). The 3D CT measurements had better interrater agreement (ICC, 0.91) than 2D MRI measurements (ICC, 0.8). intrarater agreement was also higher on CT.

Conclusions: Measurements of glenoid height using 3D CT and 2D MRI with subsequent calculation of the glenoid width using a validated methodology were not equivalent, and 3D CT was superior. Based on the validated methods for the measurement of glenoid bone loss on advanced imaging studies, 3D CT study must be preferred over 2D MRI in order to estimate the amount of glenoid bone loss in candidates for shoulder stabilization surgery and to assist in surgical decision-making.
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http://dx.doi.org/10.4055/cios20097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173237PMC
June 2021

Adoption of Anti-Fibrotic Medications: A Closer Look at the Data.

Ann Am Thorac Soc 2021 May 12. Epub 2021 May 12.

Boehringer Ingelheim Corp USA, 6893, Ridgefield, Connecticut, United States.

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http://dx.doi.org/10.1513/AnnalsATS.202103-359LEDOI Listing
May 2021

Human antigen R promotes lung fibroblast differentiation to myofibroblasts and increases extracellular matrix production.

J Cell Physiol 2021 Apr 14. Epub 2021 Apr 14.

Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive scarring caused by excessive extracellular matrix (ECM) deposition and activation of α-SMA-expressing myofibroblasts. Human antigen R (HuR) is an RNA binding protein that promotes protein translation. Upon translocation from the nucleus to the cytoplasm, HuR functions to stabilize messenger RNA (mRNA) to increase protein levels. However, the role of HuR in promoting ECM production, myofibroblast differentiation, and lung fibrosis is unknown. Human lung fibroblasts (HLFs) treated with transforming growth factor β1 (TGF-β1) showed a significant increase in translocation of HuR from the nucleus to the cytoplasm. TGF-β-treated HLFs that were transfected with HuR small interfering RNA had a significant reduction in α-SMA protein as well as the ECM proteins COL1A1, COL3A, and FN1. HuR was also bound to mRNA for ACTA2, COL1A1, COL3A1, and FN. HuR knockdown affected the mRNA stability of ACTA2 but not that of the ECM genes COL1A1, COL3A1, or FN. In mouse models of pulmonary fibrosis, there was higher cytoplasmic HuR in lung structural cells compared to control mice. In human IPF lungs, there was also more cytoplasmic HuR. This study is the first to show that HuR in lung fibroblasts controls their differentiation to myofibroblasts and consequent ECM production. Further research on HuR could assist in establishing the basis for the development of new target therapy for fibrotic diseases, such as IPF.
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http://dx.doi.org/10.1002/jcp.30380DOI Listing
April 2021

Bladder perforation: A rare complication of retention management.

Urol Case Rep 2021 Jan 8;34:101446. Epub 2020 Oct 8.

St George Hospital, South Eastern Sydney Local Health District, Gray St, Kogarah NSW, 2217, Australia.

A healthy 25 year old woman presented with acute urinary retention following alcohol ingestion. A 14 french foley catheter drained over 1 L of haematuria immediately. Due to worsening and persistent abdominal pain, CT and ultrasound imaging was performed, demonstrating only a small amount of free fluid. Diagnostic laparoscopy revealed an intraperitoneal bladder perforation with the foley catheter visible. The bladder defect was repaired and she recovered well. This is a rare case of likely iatrogenic bladder perforation from simple catheterisation without predisposing comorbidities, highlighting the importance of correct technique and awareness of potential complications.
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http://dx.doi.org/10.1016/j.eucr.2020.101446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569289PMC
January 2021

Geophysical Assessment of a Proposed Landfill Site in Fredericktown, Missouri.

FastTIMES 2020 Aug;25(2):98-106

U. S. Geological Survey, Storrs, CT 06269.

In cooperation with the U.S. Environmental Protection Agency (EPA), the U.S. Geological Survey (USGS) collected numerous types of geophysical data at a site in Fredericktown, Missouri, in June 2018. Various geophysical surveys were collectively used to help evaluate the overall suitability of the site for use as a mine waste-soil and sediment repository, and to evaluate the suite of geophysical methods for rapid collection and preliminary assessment of sites with shallow sediments. Land-based geophysical methods, which included frequency-domain electromagnetic induction (FDEM), electrical resistivity tomography (ERT), horizontal-to-vertical spectral ratio passive seismic (HVSR), and shear-wave refraction, were used to determine the depths to crystalline bedrock and characterize the overlying unconsolidated sediments (or regolith). Water-borne FDEM profiles and forward-looking infrared (FLIR) thermal image surveys were conducted along the Fredericktown City Lake shoreline to identify locations of potential interactions between groundwater and surface water. Sediment temperature profilers were installed at two locations along the shoreline to characterize shallow unconsolidated sediment thermal properties and support the interpretation of the other geophysical surveys. Geophysical reconnaissance methods including the FDEM and HVSR methods, were used to rapidly evaluate the vertical and lateral extent of overburden, or unconsolidated sediments, overlying the bedrock at the site. The results of these methods were compared to reference geophysical methods of ERT and shear-wave refraction surveys that have greater accuracy and are more labor intensive and time-consuming. A goal of the project was the evaluation of the validity and reliability of this suite of reconnaissance geophysical methods as a means by which shallow (less than 3 meters (m)) sediments can be rapidly assessed. Two orthogonal ERT survey profiles, which used 28 electrodes spaced 1 m apart in dipole-dipole and combined Wenner-Schlumberger configurations, were collected to determine the subsurface resistivity. The results were inverted to produce electrical resistivity profiles that were compared to the FDEM and HVSR survey results. The FDEM data were collected along cleared paths through the proposed disposal cell locations. The data were inverted to generate depth-dependent estimates of electrical conductivity along the transects. An analysis of the depth of investigation (DOI) indicated the FDEM imaged to depths of about 3 m below land surface. The ERT, FDEM, and HVSR indicated the depth to crystalline bedrock was approximately 1.5 m below land surface with shallower and deeper areas. Results from this investigation indicate this suite of methods will likely perform well at sites with shallow depths to bedrock and strong conductivity and acoustic impedance contrasts, where the FDEM and HVSR methods can provide estimates of the depth to bedrock, and ERT and shear-wave refraction surveys might not be worth the added time and expense.
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http://dx.doi.org/10.4133/sageep.32-031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510955PMC
August 2020

Next-generation visitation models using social media to estimate recreation on public lands.

Sci Rep 2020 09 22;10(1):15419. Epub 2020 Sep 22.

Rivers, Trails, and Conservation Assistance Program, National Park Service, Tucson, AZ, USA.

Outdoor and nature-based recreation provides countless social benefits, yet public land managers often lack information on the spatial and temporal extent of recreation activities. Social media is a promising source of data to fill information gaps because the amount of recreational use is positively correlated with social media activity. However, despite the implication that these correlations could be employed to accurately estimate visitation, there are no known transferable models parameterized for use with multiple social media data sources. This study tackles these issues by examining the relative value of multiple sources of social media in models that estimate visitation at unmonitored sites and times across multiple destinations. Using a novel dataset of over 30,000 social media posts and 286,000 observed visits from two regions in the United States, we compare multiple competing statistical models for estimating visitation. We find social media data substantially improve visitor estimates at unmonitored sites, even when a model is parameterized with data from another region. Visitation estimates are further improved when models are parameterized with on-site counts. These findings indicate that while social media do not fully substitute for on-site data, they are a powerful component of recreation research and visitor management.
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http://dx.doi.org/10.1038/s41598-020-70829-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508982PMC
September 2020

Characterizing the diverse hydrogeology underlying rivers and estuaries using new floating transient electromagnetic methodology.

Sci Total Environ 2020 Oct 9;740:140074. Epub 2020 Jun 9.

U.S. Geological Survey, Hydrogeophysics Branch, 11 Sherman Place, Storrs, CT 06238, USA.

The hydrogeology below large surface water features such as rivers and estuaries is universally under-informed at the long reach to basin scales (tens of km+). This challenge inhibits the accurate modeling of fresh/saline groundwater interfaces and groundwater/surface water exchange patterns at management-relevant spatial extents. Here we introduce a towed, floating transient electromagnetic (TEM) system (i.e. FloaTEM) for rapid (up to 15 km/h) high resolution electrical mapping of the subsurface below large water bodies to depths often a factor of 10 greater than other towed instruments. The novel FloaTEM system is demonstrated at a range of diverse 4th through 6th-order riverine settings across the United States including 1) the Farmington River, near Hartford, Connecticut; 2) the Upper Delaware River near Barryville, New York; 3) the Tallahatchie River near Shellmound, Mississippi; and, 4) the Eel River estuary, on Cape Cod, near Falmouth, Massachusetts. Airborne frequency-domain electromagnetic and land-based towed TEM data are also compared at the Tallahatchie River site, and streambed geologic scenarios are explored with forward modeling. A range of geologic structures and pore water salinity interfaces were identified. Process-based interpretation of the case study data indicated FloaTEM can resolve varied sediment-water interface materials, such as the accumulation of fines at the bottom of a reservoir and permeable sand/gravel riverbed sediments that focus groundwater discharge. Bedrock layers were mapped at several sites, and aquifer confining units were defined at comparable resolution to airborne methods. Terrestrial fresh groundwater discharge with flowpaths extending hundreds of meters from shore was also imaged below the Eel River estuary, improving on previous hydrogeological characterizations of that nutrient-rich coastal exchange zone. In summary, the novel FloaTEM system fills a critical gap in our ability to characterize the hydrogeology below surface water features and will support more accurate prediction of groundwater/surface water exchange dynamics and fresh-saline groundwater interfaces.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140074DOI Listing
October 2020

Standard Versus Low-Dose Computed Tomography for Assessment of Acetabular Fracture Reduction.

J Orthop Trauma 2020 09;34(9):462-468

Department of Orthopaedic Surgery, University of Southern California, Keck School of Medicine, Los Angeles, CA.

Objective: First, to assess the impact of varying computed tomography (CT) radiation dose on surgeon assessment of postfixation acetabular fracture reduction and malpositioned implants. Second, to quantify the accuracy of CT assessments compared with the experimentally set displacement in cadaver specimens. We hypothesized that a CT dose would not affect the assessments and that CT assessments would show a high concordance with known displacement.

Methods: We created posterior wall acetabular fractures in 8 fresh-frozen cadaver hips and reduced them with varying combinations of step and gap displacement. The insertion of an intra-articular screw was randomized. Each specimen had a CT with standard (120 kV), intermediate (100 kV), and low-dose (80 kV) protocols, with and without metal artifact reduction postprocessing. Reviewers quantified gap and step displacement, overall reduction, quality of the scan, and identified intra-articular implants.

Results: There were no significant differences between the CT dose protocols for assessment of gap, step, overall displacement, or the presence of intra-articular screws. Reviewers correctly categorized displacement as anatomic (0-1 mm), imperfect (2-3 mm), or poor (>3 mm) in 27.5%-57.5% of specimens. When the anatomic and imperfect categories were condensed into a single category, these scores improved to 52.5%-82.5%. Intra-articular screws were correctly identified in 56.3% of cases. Interobserver reliability was poor or moderate for all items. Reviewers rated the quality of most scans as "sufficient" (60.0%-72.5%); reviewers more frequently rated the low-dose CT as "inferior" (30.0%) and the standard dose CT as "excellent" (25%).

Conclusion: A CT dose did not affect assessment of displacement, intra-articular screw penetration, or subjective rating of scan quality in the setting of a fixed posterior wall fracture.
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http://dx.doi.org/10.1097/BOT.0000000000001778DOI Listing
September 2020

Medial Femoral Trochlea Osteochondral Graft: A Quantitative Anatomic Comparison to the Proximal Pole of the Scaphoid.

J Wrist Surg 2020 Aug 17;9(4):283-288. Epub 2020 Apr 17.

Department of Integrative Anatomical Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, California.

 Treatment of scaphoid proximal pole (SPP) nonunion with a vascularized osteochondral graft from the medial femoral trochlea (MFT) has been described, with positive outcomes thus far. However, our understanding of the congruency between the articular surfaces of these structures is incomplete.  Our purpose was to evaluate the congruency of the MFT and SPP using a quantitative anatomical approach.  The distal femur and ipsilateral scaphoid were dissected from 12 cadavers and scanned with computerized tomography. Three-dimensional models were created and articular surfaces were digitally "dissected." The radius of curvature (RoC) of the radioulnar (RU) and proximodistal (PD) axes of the SPP and MFT, respectively, as well as the orthogonal axes (SPP, anteroposterior [AP]; MFT, mediolateral [ML]) were calculated. The RoC values were compared using the Wilcoxon signed-rank test.  The RoC values for the SPP and MFT were not significantly different in the RU-PD plane (  = 0.064). However, RoC values for the SPP and MFT were significantly different in the AP-ML plane (  = 0.001).  For most individuals, the RU curvature of the SPP was similar to the PD curvature of the MFT. For nearly all individuals, the AP curvature of the SPP and the ML curvature of the MFT shared less congruence.  Articular surface congruity may not be a critical factor associated with improvements in wrist function following this procedure.
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http://dx.doi.org/10.1055/s-0040-1708862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395846PMC
August 2020

Identification of a unique temporal signature in blood and BAL associated with IPF progression.

Sci Rep 2020 07 21;10(1):12049. Epub 2020 Jul 21.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109 , USA.

Idiopathic pulmonary fibrosis (IPF) is a progressive and heterogeneous interstitial lung disease of unknown origin with a low survival rate. There are few treatment options available due to the fact that mechanisms underlying disease progression are not well understood, likely because they arise from dysregulation of complex signaling networks spanning multiple tissue compartments. To better characterize these networks, we used systems-focused data-driven modeling approaches to identify cross-tissue compartment (blood and bronchoalveolar lavage) and temporal proteomic signatures that differentiated IPF progressors and non-progressors. Partial least squares discriminant analysis identified a signature of 54 baseline (week 0) blood and lung proteins that differentiated IPF progression status by the end of 80 weeks of follow-up with 100% cross-validation accuracy. Overall we observed heterogeneous protein expression patterns in progressors compared to more homogenous signatures in non-progressors, and found that non-progressors were enriched for proteomic processes involving regulation of the immune/defense response. We also identified a temporal signature of blood proteins that was significantly different at early and late progressor time points (p < 0.0001), but not present in non-progressors. Overall, this approach can be used to generate new hypothesis for mechanisms associated with IPF progression and could readily be translated to other complex and heterogeneous diseases.
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http://dx.doi.org/10.1038/s41598-020-67956-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374599PMC
July 2020

Type I Collagen Signaling Regulates Opposing Fibrotic Pathways through αβ Integrin.

Am J Respir Cell Mol Biol 2020 11;63(5):613-622

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.

Fibrosis is characterized by fibroblast activation, leading to matrix remodeling culminating in a stiff, type I collagen-rich fibrotic matrix. Alveolar epithelial cell (AEC) apoptosis is also a major feature of fibrogenesis, and AEC apoptosis is sufficient to initiate a robust lung fibrotic response. TGF-β (transforming growth factor-β) is a major driver of fibrosis and can induce both AEC apoptosis and fibroblast activation. We and others have previously shown that changes in extracellular matrix stiffness and composition can regulate the cellular response to TGF-β. In the present study, we find that type I collagen signaling promotes TGF-β-mediated fibroblast activation and inhibits TGF-β-induced AEC death. Fibroblasts cultured on type I collagen or fibrotic decellularized lung matrix had augmented activation in response to TGF-β, whereas AECs on cultured on type I collagen or fibrotic lung matrix were more resistant to TGF-β-induced apoptosis. Both of these responses were mediated by integrin αβ, a major collagen receptor. AECs treated with an α integrin inhibitor or with deletion of α integrin had loss of collagen-mediated protection from apoptosis. We found that mice with fibroblast-specific deletion of α integrin were protected from fibrosis whereas mice with AEC-specific deletion of α integrin had more lung injury and a greater fibrotic response to bleomycin. Intrapulmonary delivery of an α integrin-activating collagen peptide inhibited AEC apoptosis and and attenuated the fibrotic response. These studies underscore the need for a thorough understanding of the divergent response to matrix signaling.
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http://dx.doi.org/10.1165/rcmb.2020-0150OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605165PMC
November 2020

Predicting flood insurance claims with hydrologic and socioeconomic demographics via machine learning: Exploring the roles of topography, minority populations, and political dissimilarity.

J Environ Manage 2020 Oct 15;272:111051. Epub 2020 Jul 15.

Water Resources Institute of New York, NY, USA. Electronic address:

Current research on flooding risk often focuses on understanding hazards, de-emphasizing the complex pathways of exposure and vulnerability. We investigated the use of both hydrologic and social demographic data for flood exposure mapping with Random Forest (RF) regression and classification algorithms trained to predict both parcel- and tract-level flood insurance claims within New York State, US. Topographic characteristics best described flood claim frequency, but RF prediction skill was improved at both spatial scales when socioeconomic data was incorporated. Substantial improvements occurred at the tract-level when the percentage of minority residents, housing stock value and age, and the political dissimilarity index of voting precincts were used to predict insurance claims. Census tracts with higher numbers of claims and greater densities of low-lying tax parcels tended to have low proportions of minority residents, newer houses, and less political similarity to state level government. We compared this data-driven approach and a physically-based pluvial flood routing model for prediction of the spatial extents of flooding claims in two nearby catchments of differing land use. The floodplain we defined with physically based modeling agreed well with existing federal flood insurance rate maps, but underestimated the spatial extents of historical claim generating areas. In contrast, RF classification incorporating hydrologic and socioeconomic demographic data likely overestimated the flood-exposed areas. Our research indicates that quantitative incorporation of social data can improve flooding exposure estimates.
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http://dx.doi.org/10.1016/j.jenvman.2020.111051DOI Listing
October 2020

Illustrative review of knee meniscal tear patterns, repair and replacement options, and imaging evaluation.

Clin Imaging 2021 Jan 2;69:4-16. Epub 2020 Jul 2.

Department of Radiology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address:

This review article aims to reinforce anatomical concepts about meniscal tears while linking associated treatment options. The main teaching points start with the basic meniscal anatomy and key differences between the medial and lateral menisci. Subsequently, various meniscal tear patterns along with their associated history and physical exam findings will be discussed with corresponding illustrations and MR images. Additional discussion will involve the different surgical repair techniques (with arthroscopic correlates), their indications with pertinent imaging findings, imaging related to previous meniscal tear repairs, and novel surgical techniques. Lastly, keys to evaluating for retear with an emphasis on MRI arthrogram findings will be reviewed. While each of these topics is not discussed in totality, the key points of the review article will enforce key concepts and help radiologists evaluate the menisci on imaging.
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http://dx.doi.org/10.1016/j.clinimag.2020.06.045DOI Listing
January 2021

Development and Initial Validation Analyses of the Living with Idiopathic Pulmonary Fibrosis Questionnaire.

Am J Respir Crit Care Med 2020 12;202(12):1689-1697

Endpoint Outcomes, Boston, Massachusetts.

Several new drugs for idiopathic pulmonary fibrosis (IPF) are in development. Tools are needed to assess whether these drugs benefit patients on outcomes that matter most to them. Health-related quality of life (HRQL) is one such outcome. It is influenced by many factors, but symptoms and their impacts are two strong drivers. To develop a questionnaire to assess symptoms, disease impacts, and HRQL specifically for patients with IPF. Working with the U.S. Food and Drug Administration through the Drug Development Tool Qualification process, focus groups, concept elicitation, and cognitive debriefing interviews were conducted to inform the development of a 44-item pilot questionnaire. The pilot paper-and-pen questionnaire was migrated to an equivalent electronic version and field-tested in a 14-day study. Response data were subjected to psychometric testing, including exploratory factor analysis, item calibration using item response theory models, test-retest reliability, and validity testing. A total of 125 patients with IPF (62.4% men) completed the longitudinal study. The mean ± SD age of the cohort was 69 ± 7.60 years, and the mean FVC% predicted was 71 ± 20.0. After factor and item analyses, 35 items were retained, and these comprise the two modules (symptoms and impacts) of the Living with IPF (L-IPF) questionnaire. The L-IPF yields five scales demonstrating good psychometric properties, including correlation with concurrently collected FVC% predicted and the ability to discriminate between patients with differing levels of IPF severity. The L-IPF is a new questionnaire that assesses symptoms, disease impacts, and HRQL in patients with IPF.
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http://dx.doi.org/10.1164/rccm.202002-0415OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737580PMC
December 2020

Imaging Coccygeal Trauma and Coccydynia.

Radiographics 2020 Jul-Aug;40(4):1090-1106

From the Department of Radiology, Palmer College of Chiropractic-West Campus, 90 E Tasman Dr, San Jose, CA 95134 (M.R.S.); Department of Radiology, Cedars-Sinai Medical Center, Los Angeles, Calif (G.R.M.); and Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, Calif (D.B.P., A.T., E.A.W., J.S.G.).

The coccygeal region has complex anatomy, much of which may contribute to or be the cause of coccyx region pain (coccydynia). This anatomy is well depicted at imaging, and management is often dictated by what structures are involved. Coccydynia is a common condition that is known to be difficult to evaluate and treat. However, imaging can aid in determining potential causes of pain to help guide management. Commonly, coccydynia (coccygodynia) occurs after trauma and appears with normal imaging features at static neutral radiography, but dynamic imaging with standing and seated lateral radiography may reveal pathologic coccygeal motion that is predictive of pain. In addition, several findings seen at cross-sectional imaging in patients with coccydynia can point to a source of pain that may be subtle and easily overlooked. Radiology can also offer a role in management of coccygeal region pain with image-guided pain management procedures such as ganglion impar block. In addition to mechanical coccyx pain, a host of other conditions involving the sacrococcygeal region may cause coccydynia, which are well depicted at imaging. These include neoplasm, infection, crystal deposition, and cystic formations such as pilonidal cyst. The authors review a variety of coccydynia causes, their respective imaging features, and common management strategies.RSNA, 2020.
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http://dx.doi.org/10.1148/rg.2020190132DOI Listing
June 2021

Intrathecal delivery of nusinersen in individuals with complicated spines.

Muscle Nerve 2020 07 30;62(1):114-118. Epub 2020 Apr 30.

Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: The treatment of spinal muscular atrophy (SMA) with nusinersen requires intrathecal medication administration, which can be challenging in individuals with complicated spines. This retrospective case series reviews the nusinersen treatment experience at one academic medical center with children and adults with SMA and complicated spines.

Methods: Twenty medical records of individuals receiving nusinersen were reviewed and administration methods summarized and assessed.

Results: Ten children and 10 adults were treated, and 55% had complicated spines. In total, 163 treatments were given, 91 in those with complicated spines. In the complicated spines, 74% of treatments were done by means of fluoroscopic lumbar puncture, 22% by means of intrathecal Ommaya reservoir, 3% by means of palpation, and < 1% by means of computed tomography-guided transforaminal approach.

Conclusions: A large majority of individuals with complicated spines can receive intrathecal nusinersen using fluoroscopic guidance in the lumbar region. Other delivery methods are available but less frequently used.
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http://dx.doi.org/10.1002/mus.26899DOI Listing
July 2020

A Precise and Reliable Method of Determining Lesion Size in Osteonecrosis of the Femoral Head Using Volumes.

J Arthroplasty 2020 01 24;35(1):285-290. Epub 2019 Jul 24.

Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA.

Background: To ascertain whether volumetric measurements to characterize lesion size in osteonecrosis of the femoral head using magnetic resonance imaging (MRI) and 3D software are more precise than other previously described methods.

Methods: Twenty-four patients were included in the study. Two musculoskeletal radiologists independently analyzed radiographs and MRIs using the methods described by Kerboul et al [9], Koo and Kim [10], and Cherian et al [11]. Volumetric measurements were calculated from the MRIs using 3D imaging software. Inter-rater reliability was calculated for all 4 methods using the interclass correlation coefficient (ICC). Levene's test was used to compare the variance across methods, serving as a measure of precision of each method.

Results: An ICC value of 0.81 was calculated for the volumetric measurements. The ICC values of the Kerboul et al, Koo and Kim, and Cherian et al methods were 0.94, 0.61, and 0.49, respectively. Levene's test for homogeneity of variance using absolute deviations showed the variance was not equal across methods (P < .01). The variance and the corresponding 95% confidence interval were calculated showing that the variance for the volumetric measurements was the smallest among the 4 methods examined, indicating that the volumetric measurements are more precise in characterizing lesion size as compared to the other methods.

Conclusion: Volumetric measurements of lesion size using 3D MRI imaging software to assess osteonecrosis of the femoral head are more precise than previously described methods and have excellent interobserver reliability. A 3D MRI assessment of volume of osteonecrosis in the femoral head may be useful in clinical decision-making.
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http://dx.doi.org/10.1016/j.arth.2019.05.039DOI Listing
January 2020

Reliability, construct validity and responsiveness to change of the PROMIS-29 in systemic sclerosis-associated interstitial lung disease.

Clin Exp Rheumatol 2019 Jul-Aug;37 Suppl 119(4):49-56. Epub 2019 Sep 4.

University of Michigan Scleroderma Program, Division of Rheumatology Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.

Objectives: PROMIS-29 is a generic health-related quality of life instrument. Our objective was to assess the reliability, construct validity, and responsiveness to change of PROMIS-29 in systemic sclerosis-associated interstitial lung disease (SSc-ILD).

Methods: Seventy-three participants with SSc-ILD were administered patient reported outcomes (PROs) at baseline and follow-up visits which included PROMIS-29 and other measures of generic health, dyspnea, and cough instruments. We assessed internal consistency reliability using Cronbach's α, an alpha of ≥ 0.70 was considered satisfactory. We assessed the responsiveness to change using linear regression models.

Results: Mean age of the participants was 51.9 years and the mean disease duration was 7.9 years after first non-Raynaud's symptom. Of the 73 participants, 56.2% were classified as diffuse SSc and 26% limited SSc. The baseline (mean ± SD) FVC % predicted was 73.9±15.5 with a DLCO % predicted of 57.7±21.1; 95.9% had fibrotic NSIP pattern on HRCT. PROMIS-29 scores were 0.2 to 0.9 SD below the US population. Cronbach's α reliability was acceptable for all domains (ranged from 0.77 to 0.98). All scales showed statistically significant correlations with hypothesised PROMIS-29 domains (p≤0.05 for all comparisons). PROMIS-29 showed none-to-small discriminatory ability in comparison with physiologic measures (FVC and DLCO). There was no significant relationship between the change in FVC versus the change in PROMIS-29 measures over time.

Conclusions: PROMIS-29 has adequate reliability and construct validity for evaluation in SSc-ILD. It has moderate-to-large correlations with other PROs. The PROMIS-29 domains were not found to change over time in this cohort, likely due to stable nature of the observational cohort.
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October 2019

Biomarkers of extracellular matrix turnover in patients with idiopathic pulmonary fibrosis given nintedanib (INMARK study): a randomised, placebo-controlled study.

Lancet Respir Med 2019 09 17;7(9):771-779. Epub 2019 Jul 17.

National Institute for Health Research Respiratory Biomedical Research Centre, City Campus, Nottingham University Hospital, Nottingham, UK.

Background: A hallmark of idiopathic pulmonary fibrosis is the excess accumulation of extracellular matrix in the lungs. Degradation of extracellular matrix generates free-circulating protein fragments called neoepitopes. The aim of the INMARK trial was to investigate changes in neoepitopes as predictors of disease progression in patients with idiopathic pulmonary fibrosis and the effect of nintedanib on these biomarkers.

Methods: In this randomised, double-blind, placebo-controlled trial, patients with a diagnosis of idiopathic pulmonary fibrosis within the past 3 years and forced vital capacity (FVC) of 80% predicted or higher were eligible to participate. Patients were recruited from hospitals, private practices, clinical research units, and academic medical centres. Patients were randomly assigned (1:2) with the use of a pseudo-random number generator to receive oral nintedanib 150 mg twice a day or placebo for 12 weeks in a double-blind fashion, followed by open-label nintedanib for 40 weeks. The primary endpoint was the rate of change in C-reactive protein (CRP) degraded by matrix metalloproteinases 1 and 8 (CRPM) from baseline to week 12 in the intention-to-treat population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT02788474, and with the European Clinical Trials Database, number 2015-003148-38.

Findings: Between June 27, 2016, and May 15, 2017, 347 patients were randomly assigned to the nintedanib group (n=116) or to the placebo group (n=231). One patient from the placebo group was not treated owing to a randomisation error. At baseline, mean FVC was 97·5% (SD 13·5) predicted. In the double-blind period, 116 patients received nintedanib and 230 patients received placebo. The rate of change in CRPM from baseline to week 12 was -2·57 × 10 ng/mL/month in the nintedanib group and -1·90 × 10 ng/mL/month in the placebo group (between-group difference -0·66 × 10 ng/mL/month [95% CI -6·21 × 10 to 4·88 × 10]; p=0·8146). The adjusted rate of change in FVC over 12 weeks was 5·9 mL in the nintedanib group and -70·2 mL in the placebo group (difference 76·1 mL/12 weeks [31·7 to 120·4]). In patients who received placebo for 12 weeks followed by open-label nintedanib, rising concentrations of CRPM over 12 weeks were associated with disease progression (absolute decline in FVC ≥10% predicted or death) over 52 weeks. In the double-blind period, serious adverse events were reported in eight (7%) patients given nintedanib and 18 (8%) patients given placebo. Grade 3 diarrhoea was reported in two (2%) patients in the nintedanib group and two (1%) patients in the placebo group. No patients had grade 4 diarrhoea.

Interpretation: In patients with idiopathic pulmonary fibrosis and preserved lung function, treatment with nintedanib versus placebo for 12 weeks did not affect the rate of change in CRPM but was associated with a reduced rate of decline in FVC. These results suggest that change in CRPM is not a marker of response to nintedanib in patients with idiopathic pulmonary fibrosis.

Funding: Boehringer Ingelheim.
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http://dx.doi.org/10.1016/S2213-2600(19)30255-3DOI Listing
September 2019

MR imaging of cartilage repair surgery of the knee.

Clin Imaging 2019 Nov - Dec;58:129-139. Epub 2019 Jul 11.

Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address:

Articular cartilage is a complex tissue with unique properties that are essential for normal joint function. Many processes can result in cartilage injury, ranging from acute trauma to degenerative processes. Articular cartilage lacks vascularity, and therefore most chondral defects do not heal spontaneously and may require surgical repair. A variety of cartilage repair techniques have been developed and include bone marrow stimulation (microfracture), osteochondral autograft transfer system (OATS) or osteochondral allograft transplantation, autologous chondrocyte implantation (ACI), matrix-assisted chondrocyte implantation (MACI), and other newer processed allograft cartilage techniques. Although arthroscopy has long been considered as the gold standard for evaluation of cartilage after cartilage repair, magnetic resonance (MR) imaging is a non-invasive method to assess the repair site and can be scored using Magnetic resonance Observation of Cartilage Repair Tissue (MOCART). MR also provides additional evaluation of the subchondral bone and for other potential causes of knee pain or internal derangement. Conventional MR can be used to evaluate the status of cartilage repair and potential complications. Compositional MR sequences can provide supplementary information about the biochemical contents of the reparative tissue. This article reviews the various types of cartilage repair surgeries and their postoperative MR imaging appearances.
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http://dx.doi.org/10.1016/j.clinimag.2019.07.004DOI Listing
March 2020

Routine Chest Radiography for the Evaluation of Pneumothorax Following Bronchoscopy.

Acad Radiol 2019 05;26(5):585-590

Department of Radiology, Michigan Medicine, Ann Arbor, Michigan; Michigan Radiology Quality Collaborative, Ann Arbor, Michigan.

Rationale And Objectives: To determine the utility of routine postbronchoscopy chest radiography to detect pneumothorax.

Materials And Methods: This retrospective quality improvement cohort study was approved by the Institutional Review Board. All outpatients (n = 1443) who underwent protocol-driven postbronchoscopy chest radiography in one health system from January 2010 to July 2017 were identified by electronic medical record query. The prevalence of pneumothorax (with 95% confidence intervals [CI]) and clinical outcome were determined following coded review of chest radiography reports and review of the electronic medical record. The effect of smoking and lung disease on risk of pneumothorax was determined with Chi Square tests.

Results: Of 1443 subjects undergoing interventional bronchoscopy, 6% (93/1443) were current smokers, 35% (505/1442) were former smokers, and 35% (540/1443) had known lung disease. Pneumothorax prevalence was 3.4% (49/1443; 95% CI: 2.6%-4.5%) following any intervention and 4.1% (42/1032; 95% CI: 3.9%-5.5%) following transbronchial intervention. In those without known pre-existing pneumothorax or a confirmed false positive diagnosis, the real overall pneumothorax rate was 2.9% (42/1443; 95% CI: 2.1%-3.9%). The risk of pneumothorax did not differ based on smoking history (p = 0.99) or history of lung disease (p = 0.19). Of 49 subjects with pneumothorax, 13 were symptomatic, and 10 had a change in management including chest tube placement (N = 2), inpatient admission (N = 3), and/or observation (N = 7). No pneumothorax-related intervention was performed in asymptomatic patients.

Conclusion: Pneumothorax following interventional outpatient bronchoscopy is uncommon, usually asymptomatic, and often clinically insignificant. Asymptomatic postbronchoscopy patients are very low risk and may not need routine imaging.
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http://dx.doi.org/10.1016/j.acra.2018.11.025DOI Listing
May 2019

Coracoid process fractures: anatomy, injury patterns, multimodality imaging, and approach to management.

Emerg Radiol 2019 Aug 25;26(4):449-458. Epub 2019 Mar 25.

Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

The coracoid process of the scapula is in close proximity to major neurovascular structures, including the brachial plexus and the axillary artery and vein. In addition, it serves as a major site of attachment for multiple tendons and ligaments about the shoulder. Isolated coracoid fractures are rare; however, they can be easily overlooked on routine shoulder radiographs. Importantly, when these fractures go undiagnosed, they are at high risk for nonunion. In this paper, we will review the relevant anatomy of the coracoid process, classification schemes for coracoid fractures, mechanisms of injury how these fractures typically present, multimodality imaging findings, and associated injuries. Finally, we will briefly discuss the clinical management of these fractures.
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http://dx.doi.org/10.1007/s10140-019-01683-2DOI Listing
August 2019

Frailty and geriatric conditions in older patients with idiopathic pulmonary fibrosis.

Respir Med 2019 03 24;148:6-12. Epub 2019 Jan 24.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Health System, Ann Arbor, MI, USA.

Background: Functional status, an important predictor of health outcomes in older patients, has not been studied in an IPF population. This study aimed to determine the prevalence of frailty and geriatric conditions in older patients with IPF.

Methods: IPF patients age ≥65 years were identified prospectively at the University of Michigan. Frailty was assessed using the Fried frailty phenotype. Questionnaires addressing functional status, geriatric conditions and symptoms were administered. Quantitative measurement of pectoralis muscle area was performed. Patient variables were compared among different frailty groups.

Results: Of the 50 participants, 48% were found to be frail and 40% had ≥2 geriatric conditions. Frailty was associated with increased age, lower lung function, shorter 6-min walk distance, higher symptom scores and a greater number of comorbidities, geriatric conditions and functional limitations (p < 0.05). Pectoralis muscle area was nearly significant (p = 0.08). Self-reported fatigue score (odds ratio [OR] = 2.13, confidence interval [CI] 95% 1.23-3.70, p = 0.0068) and diffusion capacity (OR = 0.54 CI 95% 0.35-0.85, p = 0.0071) were independent predictors of frailty.

Conclusions: Frailty and geriatric conditions are common in older patients with IPF. The presence of frailty was associated with objective (diffusion capacity) and subjective (self-reported fatigue score) data. Longitudinal evaluation is necessary to determine impact of frailty on disease-related outcomes in IPF.
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http://dx.doi.org/10.1016/j.rmed.2019.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690058PMC
March 2019

Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in Pulmonary Fibrosis.

Am J Respir Crit Care Med 2019 05;199(9):1127-1138

1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, and.

Idiopathic pulmonary fibrosis (IPF) causes considerable global morbidity and mortality, and its mechanisms of disease progression are poorly understood. Recent observational studies have reported associations between lung dysbiosis, mortality, and altered host defense gene expression, supporting a role for lung microbiota in IPF. However, the causal significance of altered lung microbiota in disease progression is undetermined. To examine the effect of microbiota on local alveolar inflammation and disease progression using both animal models and human subjects with IPF. For human studies, we characterized lung microbiota in BAL fluid from 68 patients with IPF. For animal modeling, we used a murine model of pulmonary fibrosis in conventional and germ-free mice. Lung bacteria were characterized using 16S rRNA gene sequencing with novel techniques optimized for low-biomass sample load. Microbiota were correlated with alveolar inflammation, measures of pulmonary fibrosis, and disease progression. Disruption of the lung microbiome predicts disease progression, correlates with local host inflammation, and participates in disease progression. In patients with IPF, lung bacterial burden predicts fibrosis progression, and microbiota diversity and composition correlate with increased alveolar profibrotic cytokines. In murine models of fibrosis, lung dysbiosis precedes peak lung injury and is persistent. In germ-free animals, the absence of a microbiome protects against mortality. Our results demonstrate that lung microbiota contribute to the progression of IPF. We provide biological plausibility for the hypothesis that lung dysbiosis promotes alveolar inflammation and aberrant repair. Manipulation of lung microbiota may represent a novel target for the treatment of IPF.
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http://dx.doi.org/10.1164/rccm.201809-1650OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515865PMC
May 2019

Prevalence, Treatment, and Outcomes of Coexistent Pulmonary Hypertension and Interstitial Lung Disease in Systemic Sclerosis.

Arthritis Rheumatol 2019 08 18;71(8):1339-1349. Epub 2019 Jun 18.

University of Michigan, CiviBioPharma, Chevy Chase, Maryland, Ann Arbor.

Objective: Systemic sclerosis (SSc) is associated with interstitial lung disease (ILD) and pulmonary hypertension (PH). This study was undertaken to determine the prevalence, characteristics, treatment, and outcomes of PH in a cohort of patients with SSc-associated ILD.

Methods: Patients with SSc-associated ILD on high-resolution computed tomography (HRCT) were included in a prospective observational cohort. Patients were screened for PH based on a standardized screening algorithm and underwent right-sided heart catheterization (RHC) if indicated. PH classification was based on hemodynamic findings and the extent of ILD on HRCT. Summary statistics and survival using the Kaplan-Meier method were calculated.

Results: Of the 93 patients with SSc-associated ILD included in the study, 76% were women and 65.6% had diffuse cutaneous SSc. The mean age was 54.9 years, and the mean SSc disease duration was 8 years. Twenty-nine patients (31.2%) had RHC-proven PH; of those 29 patients, 24.1% had PAH, 55.2% had World Health Organization (WHO) Group III PH, 34.5% had WHO Group III PH with pulmonary vascular resistance >3.0 Wood units, 48.3% had a PH diagnosis within 7 years of SSc onset, 82.8% received therapy for ILD, and 82.8% received therapy for PAH. The survival rate 3 years after SSc-associated ILD diagnosis for all patients was 97%. The survival rate 3 years after PH diagnosis for those with SSc-associated ILD and PH was 91%.

Conclusion: In a large cohort of patients with SSc-associated ILD, a significant proportion of patients had coexisting PH, which often occurs early after SSc diagnosis. Most patients were treated with ILD and PAH therapies, and survival was good. Patients with SSc-associated ILD should be evaluated for coexisting PH.
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http://dx.doi.org/10.1002/art.40862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663644PMC
August 2019

Adhesive capsulitis: review of imaging findings, pathophysiology, clinical presentation, and treatment options.

Skeletal Radiol 2019 Aug 3;48(8):1171-1184. Epub 2019 Jan 3.

Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.

Adhesive capsulitis, commonly referred to as "frozen shoulder," is a debilitating condition characterized by progressive pain and limited range of motion about the glenohumeral joint. It is a condition that typically affects middle-aged women, with some evidence for an association with endocrinological, rheumatological, and autoimmune disease states. Management tends to be conservative, as most cases resolve spontaneously, although a subset of patients progress to permanent disability. Conventional arthrographic findings include decreased capsular distension and volume of the axillary recess when compared with the normal glenohumeral joint, in spite of the fact that fluoroscopic visualization alone is rarely carried out today in favor of magnetic resonance imaging (MRI). MRI and MR arthrography (MRA) have, in recent years, allowed for the visualization of several characteristic signs seen with this condition, including thickening of the coracohumeral ligament, axillary pouch and rotator interval joint capsule, in addition to the obliteration of the subcoracoid fat triangle. Additional findings include T2 signal hyperintensity and post-contrast enhancement of the joint capsule. Similar changes are observable on ultrasound. However, the use of ultrasound is most clearly established for image-guided injection therapy. More aggressive therapies, including arthroscopic release and open capsulotomy, may be indicated for refractory disease, with arthroscopic procedures favored because of their less invasive nature and relatively high success rate.
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http://dx.doi.org/10.1007/s00256-018-3139-6DOI Listing
August 2019
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