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Novais F.O.,University of Pennsylvania | Carvalho L.P.,Federal University of Bahia | Graff J.W.,Iowa City Medical Center | Beiting D.P.,University of Pennsylvania | And 6 more authors.
PLoS Pathogens | Year: 2013

Disease progression in response to infection can be strongly influenced by both pathogen burden and infection-induced immunopathology. While current therapeutics focus on augmenting protective immune responses, identifying therapeutics that reduce infection-induced immunopathology are clearly warranted. Despite the apparent protective role for murine CD8+ T cells following infection with the intracellular parasite Leishmania, CD8+ T cells have been paradoxically linked to immunopathological responses in human cutaneous leishmaniasis. Transcriptome analysis of lesions from Leishmania braziliensis patients revealed that genes associated with the cytolytic pathway are highly expressed and CD8+ T cells from lesions exhibited a cytolytic phenotype. To determine if CD8+ T cells play a causal role in disease, we turned to a murine model. These studies revealed that disease progression and metastasis in L. braziliensis infected mice was independent of parasite burden and was instead directly associated with the presence of CD8+ T cells. In mice with severe pathology, we visualized CD8+ T cell degranulation and lysis of L. braziliensis infected cells. Finally, in contrast to wild-type CD8+ T cells, perforin-deficient cells failed to induce disease. Thus, we show for the first time that cytolytic CD8+ T cells mediate immunopathology and drive the development of metastatic lesions in cutaneous leishmaniasis. © 2013.


Cai X.,University of Iowa | Cai X.,Iowa City Medical Center | Cram P.,University of Iowa | Cram P.,Iowa City Medical Center | And 2 more authors.
Clinical Orthopaedics and Related Research | Year: 2012

Background: Total joint arthroplasty is widely performed in patients of all races with severe osteoarthritis. Prior studies have reported that African American patients tend to receive total joint arthroplasties in low-volume hospitals compared with Caucasian patients, suggesting potential racial disparity in the quality of arthroplasty care. Questions/purposes: We asked whether (1) a hospital outcome measure of risk-adjusted mortality or complication rate within 90 days of primary TKA can be directly used to profile hospital quality of care, and (2) African Americans were more likely to receive TKAs at low-quality hospitals (or hospitals with higher risk-adjusted outcome rate) compared with Caucasian patients. Patients and Methods: We developed a risk-adjusted, 90-day postoperative outcome measure to identify high-, intermediate-, and low-quality hospitals based on patient records in the Medicare Provider Analysis and Review files between July 1, 2002, and June 30, 2005 (the first cohort). We then analyzed a second cohort of African American and Caucasian patients receiving Medicare who underwent primary TKAs between July and December 2005 to determine the independent impact of race on admissions to high-, intermediate-, and low-quality hospitals. Results: The risk-adjusted postoperative mortality/complication rate varied substantially across hospitals; hospitals can be meaningfully categorized into quality groups. In the second cohort of admissions, 8% of African American patients (n = 4894) versus 9.2% of Caucasian patients (n = 86,705) were treated in high-quality hospitals whereas 14.7% of African American patients versus 12.7% of Caucasians patients were treated in low-quality hospitals. After controlling for patient demographic, socioeconomic, geographic, and diagnostic characteristics, the odds ratio for admission to low-quality hospitals was 1.28 for African American patients compared with Caucasian patients (95% CI, 1.18-1.41). Conclusions: Among elderly Medicare beneficiaries undergoing TKA, African American patients were more likely than Caucasian patients to be admitted to hospitals with higher risk-adjusted postoperative rates of complications or mortality. Future work is needed to address the residential, social, and referring factors that underlie this disparity and implications for outcomes of care. © 2011 The Association of Bone and Joint Surgeons®.


Hu Z.,University of Iowa | Abramoff M.D.,University of Iowa | Abramoff M.D.,Iowa City Medical Center | Kwon Y.H.,University of Iowa | And 2 more authors.
Investigative Ophthalmology and Visual Science | Year: 2010

PURPOSE. To develop an automated approach for segmenting the neural canal opening (NCO) and cup at the level of the retinal pigment epithelium (RPE)/Bruch's membrane (BM) complex in spectral-domain optical coherence tomography (SD-OCT) volumes. To investigate the correspondence and discrepancy between the NCO-based metrics and the clinical disc margin on fundus photographs of glaucoma subjects. METHODS. SD-OCT scans and corresponding stereo fundus photographs of the optic nerve head were obtained from 68 eyes of 34 patients with glaucoma or glaucoma suspicion. Manual planimetry was performed by three glaucoma experts to delineate a reference standard (RS) for cup and disc margins from the images. An automated graph-theoretic approach was used to identify the NCO and cup. NCO-based metrics were compared with the RS. RESULTS. Compared with the RS disc margin, the authors found mean unsigned and signed border differences of 2.81 ± 1.48 pixels (0.084 ± 0.044 mm) and -0.99 ± 2.02 pixels (-0.030 ± 0.061 mm), respectively, for NCO segmentation. The correlations of the linear cup-to-disc (NCO) area ratio, disc (NCO) area, rim area, and cup area of the algorithm with the RS were 0.85, 0.77, 0.69, and 0.83, respectively. CONCLUSIONS. In most eyes, the NCO-based 2D metrics, as estimated by the novel automated graph-theoretic approach to segment the NCO and cup at the level of the RPE/BM complex in SD-OCT volumes, correlate well with RS. However, a small discrepancy exists in NCO-based anatomic structures and the clinical disc margin of the RS in some eyes. © Association for Research in Vision and Ophthalmology.


Kumar N.,University of Miami | Liang D.,University of Iowa | Comellas A.,University of Iowa | Chu A.D.,NASA | Abrams T.,Iowa City Medical Center
Journal of Exposure Science and Environmental Epidemiology | Year: 2013

A hybrid approach is proposed to estimate exposure to fine particulate matter (PM 2.5) at a given location and time. This approach builds on satellite-based aerosol optical depth (AOD), air pollution data from sparsely distributed Environmental Protection Agency (EPA) sites and local time-space Kriging, an optimal interpolation technique. Given the daily global coverage of AOD data, we can develop daily estimate of air quality at any given location and time. This can assure unprecedented spatial coverage, needed for air quality surveillance and management and epidemiological studies. In this paper, we developed an empirical relationship between the 2 km AOD and PM 2.5 data from EPA sites. Extrapolating this relationship to the study domain resulted in 2.3 million predictions of PM 2.5 between 2000 and 2009 in Cleveland Metropolitan Statistical Area (MSA). We have developed local time-space Kriging to compute exposure at a given location and time using the predicted PM 2.5. Daily estimates of PM 2.5 were developed for Cleveland MSA between 2000 and 2009 at 2.5 km spatial resolution; 1.7 million (∼79.8%) of 2.13 million predictions required for multiyear and geographic domain were robust. In the epidemiological application of the hybrid approach, admissions for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was examined with respect to time-space lagged PM 2.5 exposure. Our analysis suggests that the risk of AECOPD increases 2.3% with a unit increase in PM 2.5 exposure within 9 days and 0.05° (∼5 km) distance lags. In the aggregated analysis, the exposed groups (who experienced exposure to PM 2.5 >15.4 μg/m 3) were 54% more likely to be admitted for AECOPD than the reference group. The hybrid approach offers greater spatiotemporal coverage and reliable characterization of ambient concentration than conventional in situ monitoring-based approaches. Thus, this approach can potentially reduce exposure misclassification errors in the conventional air pollution epidemiology studies. © 2013 Nature America, Inc.


Acion L.,University of Iowa | Ramirez M.R.,University of Iowa | Jorge R.E.,University of Iowa | Jorge R.E.,Iowa City Medical Center | Arndt S.,University of Iowa
Addiction | Year: 2013

Aims: To examine the association between military deployment of a parent and use of alcohol and drugs among children of deployed military personnel. Design: Observational and cross-sectional study. Setting: Data from the USA 2010 Iowa Youth Survey, a statewide survey of 6th, 8th and 11th graders, were analyzed during 2011. Participants: Of all 6th-, 8th- and 11th-grade students enrolled in Iowa in 2010, 69% (n=78240) completed the survey. Measurements: Ever drink more than a few sips of alcohol and past 30-day: binge drinking, marijuana consumption, other illegal drug use and prescription drug misuse. Findings: The rates of alcohol use [risk difference (RD)=7.85, 99.91% confidence interval (CI)=4.44-11.26], binge drinking (RD=8.02, 99.91% CI=4.91-11.13), marijuana use (RD=5.30, 99.91% CI=2.83-7.77), other illegal drug use (RD=7.10, 99.91% CI=4.63-9.56) and prescription drug misuse (RD=8.58, 99.91% CI=5.64-11.51) are greater for children of currently or recently deployed parents than for children of parents who are not in the military. The magnitude of the effects is consistent across 6th, 8th and 11th grades. Disrupted living arrangements further accentuate increased substance use, with the largest effect seen in children with a deployed parent who was not living with a parent or relative. Conclusions: Children of deployed military personnel should be considered at higher risk for substance use than children of non-military citizens. © 2013 Society for the Study of Addiction.


Booth B.M.,University of Arkansas for Medical Sciences | Mengeling M.,University of Iowa | Torner J.,University of Iowa | Sadler A.G.,Iowa City Medical Center
Journal of Traumatic Stress | Year: 2011

The association of rape history and sexual partnership with alcohol and drug use consequences in women veterans is unknown. Midwestern women veterans (N = 1,004) completed a retrospective telephone interview assessing demographics, rape history, substance abuse and dependence, depression, and posttraumatic stress disorder (PTSD). One third met lifetime criteria for substance use disorder (SUD), half reported lifetime completed rape, a third childhood rape, one quarter in-military rape, 11% sex with women. Lifetime SUD was higher for women with rape history (64% vs. 44%). Women with women as sex partners had significantly higher rates of all measures of rape, and also lifetime substance use disorder. Postmilitary rape, sex partnership, and current depression were significantly associated with lifetime SUD in multivariate models (odds ratio = 2.3, 3.6, 2.1, respectively). Many women veterans have a high need for comprehensive mental health services. Published 2011. This article is a US Government work and is in the public domain in the USA.


Zhang L.,University of Iowa | Sonka M.,University of Iowa | Folk J.C.,University of Iowa | Russell S.R.,University of Iowa | And 2 more authors.
Investigative Ophthalmology and Visual Science | Year: 2014

Purpose. We reported a fully automated method to identify and quantify the thickness of the outer retinal-subretinal (ORSR) layer from clinical spectral-domain optical coherence tomography (SD-OCT) scans of choroidal neovascularization (CNV) due to exudative age-related macular degeneration (eAMD). Methods. A total of 23 subjects with CNV met eligibility. Volumetric SD-OCT scans of 23 eyes were obtained (Zeiss Cirrus, 200 × 200 × 1024 voxels). In a subset of eyes, scans were repeated. The OCT volumes were analyzed using our standard parameters and using a 3-dimensional (3D) graph-search approach with an adaptive cost function. A retinal specialist graded the segmentation as generally accurate, local segmentation inaccuracies, or failure. Reproducibility on repeat scans was analyzed using root mean square coefficient of variation (RMS CV) of the average ORSR thickness. Results. Using a standard segmentation approach, 1/23 OCT segmentations was graded generally accurate and 22/23 were failure(s). With the adaptive method 21/23 segmentations were graded generally accurate; 2/23 were local segmentation inaccuracies and none was a failure. The intermethod quality of segmentation was significantly different (P << 0.001). The average ORSR thickness measured on CNV patients (78.0 μm; 95% confidence interval [CI], 72.5-83.4 μm) is significantly larger (P << 0.001) than normal average ORSR layer thickness (51.5 ± 3.3 μm). The RMS CV was 8.1%. Conclusions. We have developed a fully automated 3D method for segmenting the ORSR layer in SD-OCT of patients with CNV from eAMD. Our method can quantify the ORSR layer thickness in the presence of fluid, which has the potential to augment management accuracy and efficiency of anti-VEGF treatment. © 2014 The Association for Research in Vision and Ophthalmology, Inc.


Quellec G.,University of Iowa | Russell S.R.,University of Iowa | Russell S.R.,Iowa City Medical Center | Abramoff M.D.,University of Iowa | Abramoff M.D.,Iowa City Medical Center
IEEE Transactions on Medical Imaging | Year: 2011

Automated detection of lesions in retinal images is a crucial step towards efficient early detection, or screening, of large at-risk populations. In particular, the detection of microaneurysms, usually the first sign of diabetic retinopathy (DR), and the detection of drusen, the hallmark of age-related macular degeneration (AMD), are of primary importance. In spite of substantial progress made, detection algorithms still produce 1) false positivestarget lesions are mixed up with other normal or abnormal structures in the eye, and 2) false negativesthe large variability in the appearance of the lesions causes a subset of these target lesions to be missed. We propose a general framework for detecting and characterizing target lesions almost instantaneously. This framework relies on a feature space automatically derived from a set of reference image samples representing target lesions, including atypical target lesions, and those eye structures that are similar looking but are not target lesions. The reference image samples are obtained either from an expert- or a data-driven approach. Factor analysis is used to derive the filters generating this feature space from reference samples. Previously unseen image samples are then classified in this feature space. We tested this approach by training it to detect microaneurysms. On a set of images from 2739 patients including 67 with referable DR, DR detection area under the receiver-operating characteristic curve (AUC) was comparable (rm AUC=0.927)to our previously published red lesion detection algorithm (rm AUC=0.929). We also tested the approach on the detection of AMD, by training it to differentiate drusen from Stargardt's disease lesions, and achieved an (rm AUC=0.850 on a set of 300 manually detected drusen and 300 manually detected flecks. The entire image processing sequence takes less than a second on a standard PC compared to minutes in our previous approach, allowing instantaneous detection. Free-response receiver-operating characteristic analysis showed the superiority of this approach over a framework where false positives and the atypical lesions are not explicitly modeled. A greater performance was achieved by the expert-driven approach for DR detection, where the designer had sound expert knowledge. However, for both problems, a comparable performance was obtained for both expert- and data-driven approaches. This indicates that annotation of a limited number of lesions suffices for building a detection system for any type of lesion in retinal images, if no expert-knowledge is available. We are studying whether the optimal filter framework also generalizes to the detection of any structure in other domains. © 2010 IEEE.


Tang L.,University of Iowa | Niemeijer M.,University of Iowa | Reinhardt J.M.,University of Iowa | Garvin M.K.,University of Iowa | And 3 more authors.
IEEE Transactions on Medical Imaging | Year: 2013

A novel splat feature classification method is presented with application to retinal hemorrhage detection in fundus images. Reliable detection of retinal hemorrhages is important in the development of automated screening systems which can be translated into practice. Under our supervised approach, retinal color images are partitioned into nonoverlapping segments covering the entire image. Each segment, i.e., splat, contains pixels with similar color and spatial location. A set of features is extracted from each splat to describe its characteristics relative to its surroundings, employing responses from a variety of filter bank, interactions with neighboring splats, and shape and texture information. An optimal subset of splat features is selected by a filter approach followed by a wrapper approach. A classifier is trained with splat-based expert annotations and evaluated on the publicly available Messidor dataset. An area under the receiver operating characteristic curve of 0.96 is achieved at the splat level and 0.87 at the image level. While we are focused on retinal hemorrhage detection, our approach has potential to be applied to other object detection tasks. © 2012 IEEE.


Wakefield B.J.,Iowa City Medical Center
Telemedicine journal and e-health : the official journal of the American Telemedicine Association | Year: 2013

The use of telemonitoring of patients with chronic illness in their homes is growing. Current literature does not describe what types of patient problems are addressed by nurses in these programs and what actions are taken in response to identified problems. This study defined and analyzed patient problems and nursing actions delivered in a telemonitoring program focused on chronic disease management. Data were drawn from a clinical trial that evaluated telemonitoring in patients with comorbid diabetes and hypertension. Using study patient records, patient problems and nursing actions were coded using an inductive approach. In total, 2,336 actions were coded for 68 and 65 participants in two intervention groups. The most frequent reasons for contact were reporting information to the primary care provider and lifestyle information related to diabetes and hypertension (e.g., diet, smoking cessation, foot care, and social contacts). The most frequent mode of contact was the study sending a letter to a participant. Detailed descriptions of interventions delivered facilitate analysis of the unique contributions of nurses in the expanding market of telemonitoring, enable identification of the appropriate number and combination of interventions needed to improve outcomes, and make possible more systematic translation of findings to practice. Furthermore, this information can inform calculation of appropriate panel sizes for care managers and the competencies needed to provide this care.

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