Local Genome Topology Can Exhibit an Incompletely Rewired 3D-Folding State during Somatic Cell Reprogramming
Pluripotent genomes are folded in a topological hierarchy that reorganizes during differentiation. The extent to which chromatin architecture is reconfigured during somatic cell reprogramming is poorly understood. Here we integrate fine-resolution architecture maps with epigenetic marks and gene expression in embryonic stem cells (ESCs), neural progenitor cells (NPCs), and NPC-derived induced pluripotent stem cells (iPSCs). We find that most pluripotency genes reconnect to target enhancers during reprogramming. Unexpectedly, some NPC interactions around pluripotency genes persist in our iPSC clone. Pluripotency genes engaged in both "fully-reprogrammed" and "persistent-NPC" interactions exhibit over/undershooting of target expression levels in iPSCs. Additionally, we identify a subset of "poorly reprogrammed" interactions that do not reconnect in iPSCs and display only partially recovered, ESC-specific CTCF occupancy. 2i/LIF can abrogate persistent-NPC interactions, recover poorly reprogrammed interactions, reinstate CTCF occupancy, and restore expression levels. Our results demonstrate that iPSC genomes can exhibit imperfectly rewired 3D-folding linked to inaccurately reprogrammed gene expression.
BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction.
METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma.
RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P < 0.001 for all comparisons). At the last spirometric measurement (mean [+/-SD] age, 26.0+/-1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P < 0.001).
CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).
Caenorhabditis elegans is a powerful model to study metabolism and how it relates to nutrition, gene expression, and life history traits. However, while numerous experimental techniques that enable perturbation of its diet and gene function are available, a high-quality metabolic network model has been lacking. Here, we reconstruct an initial version of the C. elegans metabolic network. This network model contains 1,273 genes, 623 enzymes, and 1,985 metabolic reactions and is referred to as iCEL1273. Using flux balance analysis, we show that iCEL1273 is capable of representing the conversion of bacterial biomass into C. elegans biomass during growth and enables the predictions of gene essentiality and other phenotypes. In addition, we demonstrate that gene expression data can be integrated with the model by comparing metabolic rewiring in dauer animals versus growing larvae. iCEL1273 is available at a dedicated website (wormflux.umassmed.edu) and will enable the unraveling of the mechanisms by which different macro- and micronutrients contribute to the animal's physiology.
Design of a Multi-Pinhole Collimator for I-123 DaTscan Imaging on Dual-Headed SPECT Systems in Combination with a Fan-Beam Collimator
For the 2011 FDA approved Parkinson's Disease (PD) SPECT imaging agent I-123 labeled DaTscan, the volume of interest (VOI) is the interior portion of the brain. However imaging of the occipital lobe is also required with PD for calculation of the striatal binding ratio (SBR), a parameter of significance in early diagnosis, differentiation of PD from other disorders with similar clinical presentations, and monitoring progression. Thus we propose the usage of a combination of a multi-pinhole (MPH) collimator on one head of the SPECT system and a fan-beam on the other. The MPH would be designed to provide high resolution and sensitivity for imaging of the interior portion of the brain. The fan-beam collimator would provide lower resolution but complete sampling of the brain addressing data sufficiency and allowing a volume-of-interest to be defined over the occipital lobe for calculation of SBR's. Herein we focus on the design of the MPH component of the combined system. Combined reconstruction will be addressed in a subsequent publication. An analysis of 46 clinical DaTscan studies was performed to provide information to define the VOI, and design of a MPH collimator to image this VOI. The system spatial resolution for the MPH was set to 4.7 mm, which is comparable to that of clinical PET systems, and significantly smaller than that of fan-beam collimators employed in SPECT. With this set, we compared system sensitivities for three aperture array designs, and selected the 3 x 3 array due to it being the highest of the three. The combined sensitivity of the apertures for it was similar to that of an ultra-high resolution fan-beam (LEUHRF) collimator, but smaller than that of a high-resolution fan-beam collimator (LEHRF). On the basis of these results we propose the further exploration of this design through simulations, and the development of combined MPH and fan-beam reconstruction.
Modeling the respiratory motion of solitary pulmonary nodules and determining the impact of respiratory motion on their detection in SPECT imaging
The objectives of this investigation were to model the respiratory motion of solitary pulmonary nodules (SPN) and then use this model to determine the impact of respiratory motion on the localization and detection of small SPN in SPECT imaging for four reconstruction strategies. The respiratory motion of SPN was based on that of normal anatomic structures in the lungs determined from breath-held CT images of a volunteer acquired at two different stages of respiration. End-expiration (EE) and time-averaged (Frame Av) non-uniform-B-spline cardiac torso (NCAT) digital-anthropomorphic phantoms were created using this information for respiratory motion within the lungs. SPN were represented as 1 cm diameter spheres which underwent linear motion during respiration between the EE and end-inspiration (EI) time points. The SIMIND Monte Carlo program was used to produce SPECT projection data simulating Tc-99m depreotide (NeoTect) imaging. The projections were reconstructed using 1) no correction (NC), 2) attenuation correction (AC), 3) resolution compensation (RC), and 4) attenuation correction, scatter correction, and resolution compensation (AC_SC_RC). A human-observer localization receiver operating characteristics (LROC) study was then performed to determine the difference in localization and detection accuracy with and without the presence of respiratory motion. The LROC comparison determined that respiratory motion degrades tumor detection for all four reconstruction strategies, thus correction for SPN motion would be expected to improve detection accuracy. The inclusion of RC in reconstruction improved detection accuracy for both EE and Frame Av over NC and AC. Also the magnitude of the impact of motion was least for AC_SC_RC.
LROC Investigation of Three Strategies for Reducing the Impact of Respiratory Motion on the Detection of Solitary Pulmonary Nodules in SPECT
The objective of this investigation was to determine the effectiveness of three motion reducing strategies in diminishing the degrading impact of respiratory motion on the detection of small solitary pulmonary nodules (SPN) in single photon emission computed tomographic (SPECT) imaging in comparison to a standard clinical acquisition and the ideal case of imaging in the absence of respiratory motion. To do this non-uniform rational B-spline cardiac-torso (NCAT) phantoms based on human-volunteer CT studies were generated spanning the respiratory cycle for a normal background distribution of Tc-99m NeoTect. Similarly, spherical phantoms of 1.0 cm diameter were generated to model small SPN for each of 150 uniquely located sites within the lungs whose respiratory motion was based on the motion of normal structures in the volunteer CT studies. The SIMIND Monte Carlo program was used to produce SPECT projection data from these. Normal and single-lesion containing SPECT projection sets with a clinically realistic Poisson noise level were created for the cases of: 1) the end-expiration (EE) frame with all counts, 2) respiration-averaged motion with all counts, 3) one-fourth of the 32 frames centered around EE (Quarter-Binning), 4) one-half of the 32 frames centered around EE (Half-Binning), and 5) eight temporally binned frames spanning the respiratory cycle. Each of the sets of combined projection data were reconstructed with RBI-EM with system spatial-resolution compensation (RC). Based on the known motion for each of the 150 different lesions, the reconstructed volumes of respiratory bins were shifted so as to superimpose the locations of the SPN onto that in the first bin (Reconstruct and Shift). Five human-observers performed localization receiver operating characteristics (LROC) studies of SPN detection. The observer results were analyzed for statistical significance differences in SPN detection accuracy among the three correction strategies, the standard acquisition, and the ideal case of the absence of respiratory motion. Our human-observer LROC determined that Quarter-Binning and Half-Binning strategies resulted in SPN detection accuracy statistically significantly below (P < 0.05) that of standard clinical acquisition, whereas the Reconstruct and Shift strategy resulted in a detection accuracy not statistically significantly different from that of the ideal case. This investigation demonstrates that tumor detection based on acquisitions associated with less than all the counts which could potentially be employed may result in poorer detection despite limiting the motion of the lesion. The Reconstruct and Shift method results in tumor detection that is equivalent to ideal motion correction.
Ultrasonography is the ideal noninvasive imaging modality for evaluation of scrotal abnormalities. It is capable of differentiating the most important etiologies of acute scrotal pain and swelling, including epididymitis and testicular torsion, and is the imaging modality of choice in acute scrotal trauma. In patients presenting with palpable abnormality or scrotal swelling, ultrasonography can detect, locate, and characterize both intratesticular and extratesticular masses and other abnormalities. A 12-17 MHz high frequency linear array transducer provides excellent anatomic detail of the testicles and surrounding structures. In addition, vascular perfusion can be easily assessed using color and spectral Doppler analysis. In most cases of scrotal disease, the combination of clinical history, physical examination, and information obtained with ultrasonography is sufficient for diagnostic decision-making. This review covers the normal scrotal anatomy as well as various testicular and scrotal lesions.
Isolated middle cerebral artery dissection is a rare clinical entity, with descriptions limited to a few case reports and case series. Symptomatic dissection in the anterior circulation can present as an ischemic stroke in a young population; however, it is rarely associated with subarachnoid hemorrhage. We describe a young patient who presented with acute headache from a subarachnoid hemorrhage that was ultimately determined to be due to a vascular dissection in the middle cerebral artery. The initial angiogram showed vascular irregularities in this area with stenosis. Repeat imaging 4 days after presentation identified a pseudoaneurysm proximal to the stenosis. The patient was successfully treated with a self-expanding nitinol stent and followed up with serial angiography during postoperative recovery in the hospital; additional angiograms were performed approximately 1 and 6 months after treatment. Serial angiograms demonstrated incremental healing of the dissection. The patient was discharged and remains neurologically intact at the 6-month follow-up.
Photon-counting hexagonal pixel array CdTe detector: Spatial resolution characteristics for image-guided interventional applications
PURPOSE: High-resolution, photon-counting, energy-resolved detector with fast-framing capability can facilitate simultaneous acquisition of precontrast and postcontrast images for subtraction angiography without pixel registration artifacts and can facilitate high-resolution real-time imaging during image-guided interventions. Hence, this study was conducted to determine the spatial resolution characteristics of a hexagonal pixel array photon-counting cadmium telluride (CdTe) detector.
METHODS: A 650 mum thick CdTe Schottky photon-counting detector capable of concurrently acquiring up to two energy-windowed images was operated in a single energy-window mode to include photons of 10 keV or higher. The detector had hexagonal pixels with apothem of 30 mum resulting in pixel pitch of 60 and 51.96 mum along the two orthogonal directions. The detector was characterized at IEC-RQA5 spectral conditions. Linear response of the detector was determined over the air kerma rate relevant to image-guided interventional procedures ranging from 1.3 nGy/frame to 91.4 muGy/frame. Presampled modulation transfer was determined using a tungsten edge test device. The edge-spread function and the finely sampled line spread function accounted for hexagonal sampling, from which the presampled modulation transfer function (MTF) was determined. Since detectors with hexagonal pixels require resampling to square pixels for distortion-free display, the optimal square pixel size was determined by minimizing the root-mean-squared-error of the aperture functions for the square and hexagonal pixels up to the Nyquist limit.
RESULTS: At Nyquist frequencies of 8.33 and 9.62 cycles/mm along the apothem and orthogonal to the apothem directions, the modulation factors were 0.397 and 0.228, respectively. For the corresponding axis, the limiting resolution defined as 10% MTF occurred at 13.3 and 12 cycles/mm, respectively. Evaluation of the aperture functions yielded an optimal square pixel size of 54 mum. After resampling to 54 mum square pixels using trilinear interpolation, the presampled MTF at Nyquist frequency of 9.26 cycles/mm was 0.29 and 0.24 along the orthogonal directions and the limiting resolution (10% MTF) occurred at approximately 12 cycles/mm. Visual analysis of a bar pattern image showed the ability to resolve close to 12 line-pairs/mm and qualitative evaluation of a neurovascular nitinol-stent showed the ability to visualize its struts at clinically relevant conditions.
CONCLUSIONS: Hexagonal pixel array photon-counting CdTe detector provides high spatial resolution in single-photon counting mode. After resampling to optimal square pixel size for distortion-free display, the spatial resolution is preserved. The dual-energy capabilities of the detector could allow for artifact-free subtraction angiography and basis material decomposition. The proposed high-resolution photon-counting detector with energy-resolving capability can be of importance for several image-guided interventional procedures as well as for pediatric applications.
PURPOSE: Head motion during PET brain imaging can cause significant degradation of image quality. Several authors have proposed ways to compensate for PET brain motion to restore image quality and improve quantitation. Head restraints can reduce movement but are unreliable; thus the need for alternative strategies such as data-driven motion estimation or external motion tracking. Herein, the authors present a data-driven motion estimation method using a preprocessing technique that allows the usage of very short duration frames, thus reducing the intraframe motion problem commonly observed in the multiple frame acquisition method.
METHODS: The list mode data for PET acquisition is uniformly divided into 5-s frames and images are reconstructed without attenuation correction. Interframe motion is estimated using a 3D multiresolution registration algorithm and subsequently compensated for. For this study, the authors used 8 PET brain studies that used F-18 FDG as the tracer and contained minor or no initial motion. After reconstruction and prior to motion estimation, known motion was introduced to each frame to simulate head motion during a PET acquisition. To investigate the trade-off in motion estimation and compensation with respect to frames of different length, the authors summed 5-s frames accordingly to produce 10 and 60 s frames. Summed images generated from the motion-compensated reconstructed frames were then compared to the original PET image reconstruction without motion compensation.
RESULTS: The authors found that our method is able to compensate for both gradual and step-like motions using frame times as short as 5 s with a spatial accuracy of 0.2 mm on average. Complex volunteer motion involving all six degrees of freedom was estimated with lower accuracy (0.3 mm on average) than the other types investigated. Preprocessing of 5-s images was necessary for successful image registration. Since their method utilizes nonattenuation corrected frames, it is not susceptible to motion introduced between CT and PET acquisitions.
CONCLUSIONS: The authors have shown that they can estimate motion for frames with time intervals as short as 5 s using nonattenuation corrected reconstructed FDG PET brain images. Intraframe motion in 60-s frames causes degradation of accuracy to about 2 mm based on the motion type.
Evaluation of oxygen sensitivity of hyperpolarized helium imaging for the detection of pulmonary ischemia
PURPOSE: In this study, a new model of pulmonary embolism in rats was developed and tested, to examine if hyperpolarized (HP) (3) He MR images can measure impairment of the exchange of oxygen from the airspaces to the blood during pulmonary embolism.
METHODS: HP (3) He MRI was used to image six treatment-group rats in which a branch of the pulmonary artery was embolized, and six control-group rats. HP (3) He MR images were used to calculate the initial partial pressure of oxygen (pO ) and the rate of oxygen depletion (R) in rat lungs.
RESULTS: The pO was significantly higher in the ischemic lung than in the contralateral normal side, and pO was significantly higher in the ischemic lung than in both sides of the control lungs. Mean R in ischemic lungs was significantly lower than in the contralateral lungs, and mean R in ischemic lungs was also significantly lower than in both control lungs.
CONCLUSION: These results demonstrate that pO and R, as measured by the T1 decay of HP (3) He, are sensitive to pulmonary ischemia in rats, confirming the findings in studies performed in large animal models of pulmonary ischemia.
To review the classification of testicular tumors, describe the sonographic and pathologic features of each tumor type, and discuss the mimics, diagnostic pitfalls, and management of testicular tumors. Method consists of pictorial review. We review sonographic and pathologic findings of several testicular tumors and tumorlike entities. Although ultrasound is the first-line imaging modality to differentiate between intratesticular and extratesticular location of an intrascrotal mass, it is not specific for intratesticular lesion characterization. Therefore, correlation with histology sampling is often necessary.
Improving the Transcription of Patient Information From Image Requisitions to the Radiology Information System
PURPOSE: The purpose of this study was to improve the transcription of patient information from imaging study requisitions to the radiology information database at a single institution.
METHODS: Five hundred radiology reports from adult outpatient radiographic examinations were chosen randomly from the radiology information system (RIS) and categorized according to their degree of concordance with their corresponding clinical order indications. The number and types of grammatical errors and types of order forms were also recorded. Countermeasures centered on the education of the technical staff and referring physician offices and the implementation of a checklist. Another sample of 500 reports was taken after the implementation of the countermeasures and compared with the baseline data using a chi2 test.
RESULTS: The number of RIS indications perfectly concordant with their corresponding clinical order indications increased from 232 (46.4%) to 314 (62.8%) after the implementation of the countermeasures (P < .0001). The number of partially concordant matches due to inadequate RIS indications dropped from 162 (32.4%) to 114 (22.8%) (P < .001), whereas the number of partially concordant matches due to inadequate clinical order indications increased from 22 (4.4%) to 57 (11.4%) (P < .0001). The number of discordant pairings dropped from 84 (16.8%) to 15 (3%) (P < .0001). Technologists began to input additional patient information obtained from the patients (not present in the image requisitions) in the RIS after the implementation of the countermeasures.
CONCLUSIONS: The education of technical staff members and the implementation of a checklist markedly improved the information provided to radiologists on image requisitions from referring providers.
OBJECTIVE: The longus colli muscle (LCM) forms the bulk of the deep flexor muscles of the neck. To our knowledge, very little information on the effects of trauma on this muscle group has been published. We describe MRI findings related to injury of the LCM in patients with a history of neck trauma.
MATERIAL AND METHODS: A radiology department database was searched to identify patient medical records from 2008 to 2013 that included the keywords "longus colli" and "deep flexors." Patients with fractures and ligament injuries were excluded. Patients with other obvious large soft-tissue injuries and nontraumatic conditions were also omitted. A total of 12 patients met the inclusion criterion of having an isolated or predominant injury to the LCM. Five patients had been involved in a motor vehicle accident, and seven patients had fallen. Eleven patients had undergone a CT examination before MRI was performed.
RESULTS: No fractures were noted on CT. MRI examinations of the cervical spine were obtained for the following reasons: for increased prevertebral soft-tissue swelling noted on a CT scan plus neck pain (n = 6), for neck pain only (n = 4), or as part of a routine protocol for assessment of obtunded patients (n = 2). Eight of the 12 patients had isolated injury to the LCM. The remaining four patients also had minor injuries to the other neck muscles. The MR image showed swelling and T2 hyperintensity in the LCM and revealed free fluid in the prevertebral space.
CONCLUSION: Isolated injury to the LCM may occur in neck injuries. The MRI findings indicating such injury include increased T2 signal, swelling of the muscle, and the presence of prevertebral fluid.
Stent-assisted coil embolization of aneurysms with small parent vessels: safety and efficacy analysis
BACKGROUND: Stent-assisted coil embolization (SACE) is a viable therapeutic approach for wide-neck intracranial aneurysms. However, it can be technically challenging in small cerebral vessels ( < /=2 mm).
OBJECTIVE: To present our experience with stents approved for SACE in aneurysms with small parent arteries.
METHODS: All patients who underwent stent-assisted aneurysm treatment with either a Neuroform or an Enterprise stent device at our institution between June 2006 and October 2012 were identified. Additionally, we evaluated each patient's vascular risk factors, aneurysm characteristics (ruptured vs non-ruptured, incidental finding, recanalized) and follow-up angiography data.
RESULTS: A total of 41 patients with 44 aneurysms met our criteria, including 31 women and 10 men. Most of the aneurysms were located in the anterior circulation (75%). Stent placement in vessels 1.2-2 mm in diameter was successful in 93.2%. Thromboembolic complications occurred in 6 cases and vessel straightening was seen in 1 case only. Initial nearly complete to complete aneurysm obliteration was achieved in 88.6%. Six-month follow-up angiography showed coil compaction in three cases, one asymptomatic in-stent stenosis and stent occlusion. Twelve to 20-months' follow-up showed stable coil compaction in two patients compared with previous follow-up, and aneurysm recanalization in two patients. Twenty-four to 36-months' follow-up showed further coil compaction in one of these patients and aneurysm recanalization in a previous case of stable coil compaction on mid-term follow-up.
CONCLUSIONS: Our results suggest that SACE of aneurysms with small parent vessels is feasible in selected cases and shows good long-term patency rates of parent arteries.
Successful treatment of a giant pediatric fusiform basilar trunk aneurysm with surpass flow diverter
Fusiform aneurysms present a unique challenge to traditional microsurgical and endovascular treatment because of the lack of a discernible neck and the involvement of parent vessel. Flow diversion has increasingly become the treatment of choice for fusiform aneurysms in the anterior circulation, but its results in the posterior circulation are variable. We report successful treatment of a giant fusiform upper basilar trunk aneurysm with the Surpass flow diverter in an adolescent, and discuss the potential advantages of this emerging technology in the treatment of fusiform posterior circulation aneurysms.
AIM: To re-examine whether hepatic vein thrombosis (HVT) (classical Budd-Chiari syndrome) and hepatic vena cava-Budd Chiari syndrome (HVC-BCS) are the same disorder.
METHODS: A systematic review of observational studies conducted in adult subjects with primary BCS, hepatic vein outflow tract obstruction, membranous obstruction of the inferior vena cava (IVC), obliterative hepatocavopathy, or HVT during the period of January 2000 until February 2015 was conducted using the following databases: Cochrane Library, CINAHL, MEDLINE, PubMed and Scopus.
RESULTS: Of 1299 articles identified, 26 were included in this study. Classical BCS is more common in women with a pure hepatic vein obstruction (49%-74%). HVC-BCS is more common in men with the obstruction often located in both the inferior vena cava and hepatic veins (14%-84%). Classical BCS presents with acute abdominal pain, ascites, and hepatomegaly. HVC-BCS presents with chronic abdominal pain and abdominal wall varices. Myeloproliferative neoplasms (MPN) are the most common etiology of classical BCS (16%-62%) with the JAK2V617-F mutation found in 26%-52%. In HVC-BCS, MPN are found in 4%-5%, and the JAK2V617-F mutation in 2%-5%. Classical BCS responds well to medical management alone and 1(st) line management of HVC-BCS involves percutaneous recanalization, with few managed with medical management alone.
CONCLUSION: Systematic review of recent data suggests that classical BCS and HVC-BCS may be two clinically different disorders that involve the disruption of hepatic venous outflow.
Academic-industry collaborations are an emerging format of translational stroke research. Next to classic contract research models, a multitude of collaboration models has been developed, some of which even allowing for multinational or intercontinental research programs. This development has recently been paralleled by first successful attempts to overcome the translational stroke research road block, such as the unprecedented success of novel endovascular approaches or the advent of the multicenter preclinical trial concept. While the first underlines the role of the industry as a major innovation driver in stroke research, the latter will require enrollment of industrial partners for optimal output. Moreover, academic-industry partnerships are invaluable to bridge the translational "valley of death" as well as funding gaps in times of dwindling public funding and declining high risk capital investments. However, these collaborations are also subject to relevant challenges because interests, values, and aims often significantly differ between cademia and industry. Here, we describe common academic-industry collaboration models as well as associated benefits and challenges in the stroke research arena. We also suggest strategies for improved planning, implementation, guidance, and utilization of academic-industry collaborations to the maximum mutual benefit.
Patient delay in seeking care for heart attack symptoms: findings from focus groups conducted in five U.S. regions
BACKGROUND: Patient delay in seeking health care for heart attack symptoms is a continuuing problem in the United States.
METHODS: Investigators conducted focus groups (N = 34; 207 participants) in major U.S. regions (NE, NW, SE, SW, MW) as formative evaluation to develop a multi-center randomized community trial (the REACT Project). Target groups included adults with previous heart attacks, those at higher risk for heart attack, and bystanders to heart attacks. There were also subgroups reflecting gender and ethnicity (African-American, Hispanic-American, White).
FINDINGS: Patients, bystanders, and those at higher risk expected heart attack symptoms to present as often portrayed in the movies, that is, as sharp, crushing chest pain rather than the more common onset of initially ambiguous but gradually increasing discomfort. Patients and those at higher risk also unrealistically judge their personal risk as low, understand little about the benefits of rapid action, are generally unaware of the benefits of using EMS/9-1-1 over alternative transport, and appear to need the "permission" of health care providers or family to act. Moreover, participants reported rarely discussing heart attack symptoms and appropriate responses in advance with health care providers, spouses, or family members. Women often described heart attack as a "male problem," an important aspect of their underestimation of personal risk. African-American participants were more likely to describe negative feelings about EMS/9-1-1, particularly whether they would be transported to their hospital of choice.
CONCLUSIONS: Interventions to reduce patient delay need to address expectations about heart attack symptoms, educate about benefits and appropriate actions, and provide legitimacy for taking specific health care-seeking actions. In addition, strategy development must emphasize the role of health care providers in legitimizing the need and importance of taking rapid action in the first place.