Scoring thermal limits in small insects using open-source, computer-assisted motion detection.

Scoring thermal tolerance traits live or with recorded video can be time consuming and susceptible to observer bias, and as with many physiological measurements, there can be trade-offs between accuracy and throughput. Recent studies show that automated particle tracking is a viable alternative to manually scoring videos, although some of the software options are proprietary and costly. In this study, we present a novel strategy for automated scoring of thermal tolerance videos by inferring motor activity with motion detection using an open-source Python command line application called DIME (detector of insect motion endpoint). We apply our strategy to both dynamic and static thermal tolerance assays, and our results indicate that DIME can accurately measure thermal acclimation responses, generally agrees with visual estimates of thermal limits, and can significantly increase throughput over manual methods.

Generation of 3D Spheroids Using a Thiol-Acrylate Hydrogel Scaffold to Study Endocrine Response in ER+ Breast Cancer.

Culturing cancer cells in a three-dimensional (3D) environment better recapitulates in vivo conditions by mimicking cell-to-cell interactions and mass transfer limitations of metabolites, oxygen, and drugs. Recent drug studies have suggested that a high rate of preclinical and clinical failures results from mass transfer limitations associated with drug entry into solid tumors that 2D model systems cannot predict. Droplet microfluidic devices offer a promising alternative to grow 3D spheroids from a small number of cells to reduce intratumor heterogeneity, which is lacking in other approaches. Spheroids were generated by encapsulating cells in novel thiol-acrylate (TA) hydrogel scaffold droplets followed by on-chip isolation of single droplets in a 990- or 450-member trapping array. The TA hydrogel rapidly (∼35 min) polymerized on-chip to provide an initial scaffold to support spheroid development followed by a time-dependent degradation. Two trapping arrays were fabricated with 150 or 300 µm diameter traps to investigate the effect of droplet size and cell seeding density on spheroid formation and growth. Both trapping arrays were capable of ∼99% droplet trapping efficiency with ∼90% and 55% cellular encapsulation in trapping arrays containing 300 and 150 µm traps, respectively. The oil phase was replaced with media ∼1 h after droplet trapping to initiate long-term spheroid culturing. The growth and viability of MCF-7 3D spheroids were confirmed for 7 days under continuous media flow using a customized gravity-driven system to eliminate the need for syringe pumps. It was found that a minimum of 10 or more encapsulated cells are needed to generate a growing spheroid while fewer than 10 parent cells produced stagnant 3D spheroids. As a proof of concept, a drug susceptibility study was performed treating the spheroids with fulvestrant followed by interrogating the spheroids for proliferation in the presence of estrogen. Following fulvestrant exposure, the spheroids showed significantly less proliferation in the presence of estrogen, confirming drug efficacy.

Exploring the effectiveness of the TSR-based protein 3-D structural comparison method for protein clustering, and structural motif identification and discovery of protein kinases, hydrolases, and SARS-CoV-2's protein via the application of amino acid grouping.

Development of protein 3-D structural comparison methods is essential for understanding protein functions. Some amino acids share structural similarities while others vary considerably. These structures determine the chemical and physical properties of amino acids. Grouping amino acids with similar structures potentially improves the ability to identify structurally conserved regions and increases the global structural similarity between proteins. We systematically studied the effects of amino acid grouping on the numbers of Specific/specific, Common/common, and statistically different keys to achieve a better understanding of protein structure relations. Common keys represent substructures found in all types of proteins and Specific keys represent substructures exclusively belonging to a certain type of proteins in a data set. Our results show that applying amino acid grouping to the Triangular Spatial Relationship (TSR)-based method, while computing structural similarity among proteins, improves the accuracy of protein clustering in certain cases. In addition, applying amino acid grouping facilitates the process of identification or discovery of conserved structural motifs. The results from the principal component analysis (PCA) demonstrate that applying amino acid grouping captures slightly more structural variation than when amino acid grouping is not used, indicating that amino acid grouping reduces structure diversity as predicted. The TSR-based method uniquely identifies and discovers binding sites for drugs or interacting proteins. The binding sites of nsp16 of SARS-CoV-2, SARS-CoV and MERS-CoV that we have defined will aid future antiviral drug design for improving therapeutic outcome. This approach for incorporating the amino acid grouping feature into our structural comparison method is promising and provides a deeper insight into understanding of structural relations of proteins.

Path to precision: prevention of post-operative atrial fibrillation.

Development of post-operative atrial fibrillation (POAF) following open-heart surgery is a significant clinical and economic burden. Despite advancements in medical therapies, the incidence of POAF remains elevated at 25-40%. Early work focused on detecting arrhythmias from electrocardiograms as well as identifying pre-operative risk factors from medical records. However, further progress has been stagnant, and a deeper understanding of pathogenesis and significant influences is warranted. With the advent of more complex machine learning (ML) algorithms and high-throughput sequencing, we have an unprecedented ability to capture and predict POAF in real-time. Integration of multimodal heterogeneous data and application of ML can generate a paradigm shift for diagnosis and treatment. This will require a concerted effort to consolidate and streamline real-time data. Herein, we will review the current literature and emerging opportunities aimed at predictive targets and new insights into the mechanisms underlying long-term sequelae of POAF.

Automated detection of ventricular pre-excitation in pediatric 12-lead ECG.

BACKGROUND: With increased interest in screening of young people for potential causes of sudden death, accurate automated detection of ventricular pre-excitation (VPE) or Wolff-Parkinson-White syndrome (WPW) in the pediatric resting ECG is important. Several recent studies have shown interobserver variability when reading screening ECGs and thus an accurate automated reading for this potential cause of sudden death is critical. We designed and tested an automated algorithm to detect pediatric VPE optimized for low prevalence. METHODS: Digital ECGs with 12 leads or 15 leads (12-lead plus V3R, V4R and V7) were selected from multiple hospitals and separated into a testing and training database. Inclusion criterion was age less than 16 years. The reference for algorithm detection of VPE was cardiologist annotation of VPE for each ECG. The training database (n=772) consisted of VPE ECGs (n=37), normal ECGs (n=492) and a high concentration of conduction defects, RBBB (n=232) and LBBB (n=11). The testing database was a random sample (n=763). All ECGs were analyzed with the Philips DXL ECG Analysis algorithm for basic waveform measurements. Additional ECG features specific to VPE, mainly delta wave scoring, were calculated from the basic measurements and the average beat. A classifier based on decision tree bootstrap aggregation (tree bagger) was trained in multiple steps to select the number of decision trees and the 10 best features. The classifier accuracy was measured on the test database. RESULTS: The new algorithm detected pediatric VPE with a sensitivity of 78%, a specificity of 99.9%, a positive predictive value of 88% and negative predictive value of 99.7%. CONCLUSION: This new algorithm for detection of pediatric VPE performs well with a reasonable positive and negative predictive value despite the low prevalence in the general population.

Ethical Issues in Corpus Linguistics And Annotation: Pay Per Hit Does Not Affect Effective Hourly Rate For Linguistic Resource Development On Amazon Mechanical Turk.

Ethical issues reported with paid crowdsourcing include unfairly low wages. It is assumed that such issues are under the control of the task requester. Can one control the amount that a worker earns by controlling the amount that one pays? 412 linguistic data development tasks were submitted to Amazon Mechanical Turk. The pay per HIT was manipulated through a range of values. We examined the relationship between the pay that is offered per HIT and the effective pay rate. There is no such relationship. Paying more per HIT does not cause workers to earn more: the higher the pay per HIT, the more time workers spend on them (R = 0.92). So, the effective hourly rate stays roughly the same. The finding has clear implications for language resource builders who want to behave ethically: other means must be found in order to compensate workers fairly. The findings of this paper should not be taken as an endorsement of unfairly low pay rates for crowdsourcing workers. Rather, the intention is to point out that additional measures, such as pre-calculating and communicating to the workers an average hourly, rather than per-task, rate must be found in order to ensure an ethical rate of pay.

IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas.

Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients.

Agreement between cardiologists and fellows in interpretation of ischemic electrocardiographic changes in acute myocardial infarction.

BACKGROUND: Time from symptom onset may not be the best indicator for choosing reperfusion therapy for patients presenting with acute ST-elevation myocardial infarction (STEMI); consequently ECG-based methods have been developed. METHODS: This study evaluated the inter-observer agreement between experienced cardiologists and junior doctors in identifying the ECG findings of the pre-infarction syndrome (PIS) and evolving myocardial infarction (EMI). The ECGs of 353 STEMI patients were independently analyzed by two cardiologists, one fellow in cardiology, one fellow in internal medicine and a medical student. The last two were given a half-hour introduction of the PIS/EMI-algorithm. RESULTS: The inter-observer reliability between all the investigators was found to be good according to kappa statistics (κ 0.632-0.790) for the whole study population. When divided into different subgroups, the inter-observer agreements were from good to very good between the cardiologists and the fellow in cardiology (κ 0.652 -0.813) and from moderate to good (κ 0.464-0.784) between the fellow in internal medicine, medical student and the others. CONCLUSIONS: The PIS and EMI ECG patterns are reliably identified by experienced cardiologists and can be easily adopted by junior doctors.

Normal standards for computer-ECG programs for prognostically and diagnostically important ECG variables derived from a large ethnically diverse female cohort: the Women's Health Initiative (WHI).

BACKGROUND: Substantial new information has emerged recently about the prognostic value for a variety of new ECG variables. The objective of the present study was to establish reference standards for these novel risk predictors in a large, ethnically diverse cohort of healthy women from the Women's Health Initiative (WHI) study. METHODS AND RESULTS: The study population consisted of 36,299 healthy women. Racial differences in rate-adjusted QT end (QT(ea)) and QT peak (QT(pa)) intervals as linear functions of RR were small, leading to the conclusion that 450 and 390 ms are applicable as thresholds for prolonged and shortened QT(ea) and similarly, 365 and 295 ms for prolonged and shortened QT(pa), respectively. As a threshold for increased dispersion of global repolarization (T(peak)T(end) interval), 110 ms was established for white and Hispanic women and 120 ms for African-American and Asian women. ST elevation and depression values for the monitoring leads of each person with limb electrodes at Mason-Likar positions and chest leads at level of V1 and V2 were first computed from standard leads using lead transformation coefficients derived from 892 body surface maps, and subsequently normal standards were determined for the monitoring leads, including vessel-specific bipolar left anterior descending, left circumflex artery and right coronary artery leads. The results support the choice 150 µV as a tentative threshold for abnormal ST-onset elevation for all monitoring leads. Body mass index (BMI) had a profound effect on Cornell voltage and Sokolow-Lyon voltage in all racial groups and their utility for left ventricular hypertrophy classification remains open. CONCLUSIONS: Common thresholds for all racial groups are applicable for QT(ea), and QT(pa) intervals and ST elevation. Race-specific normal standards are required for many other ECG parameters.

Bispecific and trispecific killer cell engagers directly activate human NK cells through CD16 signaling and induce cytotoxicity and cytokine production.

This study evaluates the mechanism by which bispecific and trispecific killer cell engagers (BiKEs and TriKEs) act to trigger human natural killer (NK) cell effector function and investigates their ability to induce NK cell cytokine and chemokine production against human B-cell leukemia. We examined the ability of BiKEs and TriKEs to trigger NK cell activation through direct CD16 signaling, measuring intracellular Ca²âº mobilization, secretion of lytic granules, induction of target cell apoptosis, and production of cytokine and chemokines in response to the Raji cell line and primary leukemia targets. Resting NK cells triggered by the recombinant reagents led to intracellular Ca²âº mobilization through direct CD16 signaling. Coculture of reagent-treated resting NK cells with Raji targets resulted in significant increases in NK cell degranulation and target cell death. BiKEs and TriKEs effectively mediated NK cytotoxicity of Raji targets at high and low effector-to-target ratios and maintained functional stability after 24 and 48 hours of culture in human serum. NK cell production of IFN-γ, TNF-α, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, macrophage inflammatory protein (MIP)-1α, and regulated and normal T cell expressed and secreted (RANTES) was differentially induced in the presence of recombinant reagents and Raji targets. Moreover, significant increases in NK cell degranulation and enhancement of IFN-γ production against primary acute lymphoblastic leukemia and chronic lymphocytic leukemia targets were induced with reagent treatment of resting NK cells. In conclusion, BiKEs and TriKEs directly trigger NK cell activation through CD16, significantly increasing NK cell cytolytic activity and cytokine production against tumor targets, showing their therapeutic potential for enhancing NK cell immunotherapies for leukemias and lymphomas.

Automated discrimination of proximal right coronary artery occlusion from middle-to-distal right coronary artery occlusion and left circumflex occlusion in ST-elevation myocardial infarction.

BACKGROUND: Classifying the location of an occlusion in the culprit artery during ST-elevation myocardial infarction (STEMI) is important for risk stratification to optimize treatment. We developed a new logistic regression (LR) algorithm for 3-group classification of occlusion location as proximal right coronary artery (RCA), middle-to-distal RCA or left circumflex (LCx) coronary artery with inferior myocardial infarction. We compared the performance of the new LR algorithm with the recently introduced decision tree classifier of Fiol et al (Ann Noninvasive Electrocardiol. 2004;4:383-388) in the classification of the same 3 categories. METHODS: The new algorithm was developed on a set of electrocardiograms from an emergency department setting (n = 64) and tested on a different set from a prehospital setting (n = 68). All patients met the current STEMI criteria with angiographic confirmation of culprit artery and occlusion location. Using LR, 4 ST-segment deviation features were chosen by forward stepwise selection. Final LR coefficients were obtained by averaging more than 200 bootstrap iterations on the training set. In addition, a separate 4-feature classifier was designed adding ST features of V4R and V8, only available in the training set. RESULTS: The LR algorithm classified proximal RCA occlusion vs combined LCx occlusion and middle-to-distal RCA occlusion, with a sensitivity of 76% and specificity of 81% as compared with 71% and 62% for the Fiol classifier. The difference in specificity was statistically significant. The LR classifier trained with additional ST features of V4R and V8, but still limited to 4, improved the overall agreement in the training set from 65% to 70%. CONCLUSION: Discrimination of proximal RCA lesion location from LCx or middle-to-distal RCA using the new LR classifier shows improvement over decision tree­type classification criteria. Automated identification of proximal RCA occlusion could speed up the risk stratification of patients with STEMI. The addition of leads V4R and V8 should further improve the automated classification of the occlusion site in RCA and LCx.

Automated discrimination of proximal right coronary artery occlusion from middle-to-distal right coronary artery occlusion and left circumflex occlusion in ST-elevation myocardial infarction.

BACKGROUND: Classifying the location of an occlusion in the culprit artery during ST-elevation myocardial infarction (STEMI) is important for risk stratification to optimize treatment. We developed a new logistic regression (LR) algorithm for 3-group classification of occlusion location as proximal right coronary artery (RCA), middle-to-distal RCA or left circumflex (LCx) coronary artery with inferior myocardial infarction. We compared the performance of the new LR algorithm with the recently introduced decision tree classifier of Fiol et al (Ann Noninvasive Electrocardiol. 2004;4:383-388) in the classification of the same 3 categories. METHODS: The new algorithm was developed on a set of electrocardiograms from an emergency department setting (n = 64) and tested on a different set from a prehospital setting (n = 68). All patients met the current STEMI criteria with angiographic confirmation of culprit artery and occlusion location. Using LR, 4 ST-segment deviation features were chosen by forward stepwise selection. Final LR coefficients were obtained by averaging more than 200 bootstrap iterations on the training set. In addition, a separate 4-feature classifier was designed adding ST features of V4R and V8, only available in the training set. RESULTS: The LR algorithm classified proximal RCA occlusion vs combined LCx occlusion and middle-to-distal RCA occlusion, with a sensitivity of 76% and specificity of 81% as compared with 71% and 62% for the Fiol classifier. The difference in specificity was statistically significant. The LR classifier trained with additional ST features of V4R and V8, but still limited to 4, improved the overall agreement in the training set from 65% to 70%. CONCLUSION: Discrimination of proximal RCA lesion location from LCx or middle-to-distal RCA using the new LR classifier shows improvement over decision tree-type classification criteria. Automated identification of proximal RCA occlusion could speed up the risk stratification of patients with STEMI. The addition of leads V4R and V8 should further improve the automated classification of the occlusion site in RCA and LCx.

Electrocardiographic estimates of regional action potential durations and repolarization time subintervals reveal ischemia-induced abnormalities in acute coronary syndrome not evident from global QT.

We evaluated electrocardiogram estimates of repolarization times (RTs) and action potential durations (APD) separately for initial and terminal repolarization periods in a reference group of 5376 healthy men and women and in 125 acute coronary syndrome patients with and 657 without diagnostic ST elevation (ST-elevation myocardial infarction [STEMI] and non-STEMI [NSTEMI], respectively). Two key covariates in the model are the rate-adjusted QT peak interval (QT(pa)), assigned to earliest epicardial RT (RT(epi)), and (T(p)-T(xd)), the rate-invariant interval from T(p) to the inflection point (T(xd)) at T wave downstroke. (T(p)-T(xd)) defines the crossmural RT gradient (XMRT(grad)). Transmural RT(grad) (TMRT(grad)) is obtained as CosΘ(R(max)|T(max))*XMRT(grad), where Θ is the spatial angle between the maximal QRS and T vectors. Derived endocardial variables are the XMRT(endo), equal to QT(pa) + XMRT(grad) and TMRT(endo), equal to QT(pa) + TMRT(grad). Noting that excitation time (ET) and RT define APD, APD(epi) = RT(epi) - QR(p) in V6 and TMAPD(endo) = TMRT(endo)--10 milliseconds. Compared to the reference group, the estimates for APD(epi) and TMAPD(endo) were shortened in STEMI by 20 and 31 milliseconds, respectively, (p < 0.001 for both) signifying transmural ischemia. In contrast, in NSTEMI, TMAPD(endo) was shortened by 28 milliseconds (P < 0.001) with a lesser, 5 millisecond shortening of APD(epi), signifying subendocardial ischemia. QT was prolonged by 6 milliseconds in STEMI (P < 0.05) and by 8 milliseconds in NSTEMI (P < 0.001). Prolonged QT with shortened APD(epi) suggests that prolonged repolarization in terminal possibly non-ischemic regions accounts for QT prolongation in both myocardial infarction groups. These substantial differences in ischemia-induced regional manifestations of repolarization abnormalities revealed by the repolarization model were not evident from evaluation of the global QT.

Electrocardiogram-derived respiration in screening of sleep-disordered breathing.

Methods for assessment of sleep-disordered breathing (SDB), including sleep apnea, range from a simple questionnaire to complex multichannel polysomnography. Inexpensive and efficient electrocardiogram (ECG)-based solutions could potentially fill the gap and provide a new SDB screening tool. In addition to the heart rate variability (HRV)-based SDB screening method that we reported a year ago, we have developed a novel method based on ECG-derived respiration (EDR). This method derives the respiratory waveform by (a) measuring peak-to-trough QRS amplitude in a single-channel ECG, (b) removing outlier introduced by noise and artifacts, (c) interpolating the derived values, and (d) filtering values within the respiration rates of 5 and 25 cycles per minute. Each 30 seconds of the respiratory waveform is then classified as normal, SDB, or indeterminate epoch. The previously reported HRV-based method, applied at the same time, is based on power spectrum of heart rate over a sliding 6-minute time window to classify the middle 30-second epoch. We then combined the EDR- and HRV-based techniques to optimize the classification of each epoch. The combined method further improved the accuracy of SDB screening in an independent test database with annotated SDB epochs. The development database was from PhysioNet (n = 25 polysomnograms). The test database was from Sleep Health Centers in Boston (n = 1907 polysomnogram) where the SDB epochs (n = 1,538,222 epochs) were scored using American Academy of Sleep Medicine criteria. The first test was to classify every epoch in the evaluation data set. The combined EDR and HRV method classified 78% of the epochs as either normal or SDB and 22% as indeterminate, with a total accuracy of 88% for scored epochs (not indeterminate). The second test was to evaluate the SDB status for each patient. The algorithm correctly classified 71% of patients with either moderate-to-severe SDB or mild-to-no SDB. We believe that the ECG-based methods provide an efficient and inexpensive tool for SDB screening in both home and hospital settings and make SDB screening feasible in large populations.

Electrocardiographic estimates of action potential durations and transmural repolarization time gradients in healthy subjects and in acute coronary syndrome patients--profound differences by sex and by presence vs absence of diagnostic ST elevation.

Action potential duration (APD) changes increasing repolarization time (RT) dispersion are potentially arrhythmogenic. A repolarization model developed from electrocardiographic data of 5376 healthy men and women was used to derive parameter estimates for APD and RT and their transmural gradients (RT(grad) and APD(grad), respectively) in myocardial infarction patients, 126 with and 658 without diagnostic ST elevation (STEMI and NSTEMI, respectively). The model uses, as covariates, rate-adjusted QT and QT peak intervals (QT(a) and QT(pa), respectively) and diagonal crossmural RT(grad) derived as T(p)-T(xd), the interval from T(p) to the inflection point at descending limb of global T wave. An additional parameter is Θ(T|T(ref)), the spatial angle between a subject's T vector and the average T vector of the normal reference group. If Θ(T|T(ref)) >0, QT(pa) is assigned to RT(epi) and QT(pa) + RT(grad) to RT(endo), with RT(epi) and RT(endo) assignments reversed if Θ(T|T(ref)) ≤0. Parameter estimates for APD(epi) and APD(endo) were shorter in men than in women (by 17 ms and 14 ms, respectively, P < .001 for both). Compared to the reference group, RT(epi) in the STEMI group was shortened by 14 ms in men and by 18 ms in women (P < .001 for both) with a lesser decrease in RT(endo) suggesting predominantly subepicardial ischemia. In NSTEMI only RT(endo) was shortened, by 6 ms in males (P < .01) and 10 ms in females (P < .001), suggesting subendocardial ischemia. RT(grad) signifying local crossmural RT dispersion was prolonged in STEMI by 8 ms in men and by 11 ms in men (P < .001 for both). RT(grad) was not changed significantly in NSTEMI. Rate-adjusted T(p)-T(e) interval signifying global RT dispersion was increased in both MI and in both sex groups (P <.001 for all). In conclusion, QT prolongation observed in NSTEMI without prolongation of RT(grad) and APD(epi) suggests a delay during terminal repolarization, and in contrast, in STEMI, QT is not changed significantly in spite of prolonged RT(grad) because of shortened APD(epi) and RT(epi). These repolarization abnormalities are not revealed by QT alone but readily by the repolarization model.

Heart rate, gender differences, and presence versus absence of diagnostic ST elevation as determinants of spatial QRS|T angle widening in acute coronary syndrome.

We explored the directions of the repolarization sequence (RS) and excitation sequence (ES) as determinants of QRS|T angle widening in 126 patients with acute coronary syndrome (ACS) with and 658 patients without diagnostic ST-segment elevation myocardial infarction and in a reference group of 5,376 normal subjects. The initial and terminal RS and ES directions were derived from the initial and terminal T and QRS vectors from quintiles 1 to 3 and 5 of time-normalized QRS and T. In addition to the QRS|T angle, we evaluated the RS and ES deviation angles from the normal RS and ES directions. The normal zones for the ES and RS directions in the reference group were used to classify the ES and RS in the group with and without ST-segment myocardial infarction as normal or deviant. The initial and terminal QRS|T angles were rate invariant in the normal group but correlated with the heart rate (r = 0.33) in the ACS group. Adjusted for a heart rate of 70 beats/min, the initial QRS|T angle increased progressively in the ACS group from 41° among those with normal RS and ES directions to 121° when both were deviant. This apparently ischemia-induced initial QRS|T angle increase was associated with an initial RS direction from the anterior-right to the posterior-left producing a progressively greater peak TV1 amplitude. The terminal ES orientation in the ACS group was toward the right ventricular outflow tract with a QRS|T angle of 124° in 48% and leftward and posterior, with the QRS|T angle decreasing to 59°, in the remaining 52%. In conclusion, the initial and terminal RS and ES orientations differ drastically and their deviant orientation accounts for the widened QRS|T angle in patients with ACS, differences not revealed by evaluation of the mean QRS|T angle.

Development of a serial comparison program for conduction defects, acute myocardial infarction, and the use of additional leads.

Serial comparison of electrocardiograms (ECGs) is a useful tool in clinical diagnostic ECG and an enhancement to computer ECG analysis. When an analysis algorithm is modified, the corresponding serial comparison program needs to be updated accordingly. The new Philips diagnostic algorithm increased the number of leads in the ECG from the traditional 12 leads to 16, making it possible to diagnose right ventricular infarct/injury based on right-sided lead V4R. To keep pace with the widespread reperfusion therapy for acute myocardial infarct, the serial comparison program was revised to recognize the rapid ECG changes in patients with ST-elevation myocardial infarct following successful reperfusion therapies. The serial comparison program was also enhanced to split "combined" statements in the category of ventricular conduction delay (includes incomplete ventricular conduction delay and bundle-branch blocks) and compare each of the statements separately.

Computerized classification of proximal occlusion in the left anterior descending coronary artery.

Proximal occlusion within the left anterior descending (LAD) coronary artery in patients with acute myocardial infarction leads to higher mortality than does nonproximal occlusion. We evaluated an automated program to detect proximal LAD occlusion. All patients with suspected acute coronary syndrome (n = 7,710) presenting consecutively to the emergency department of a local hospital with a coronary angiogram­confirmed flow-limiting lesion and notation of occlusion site were included in the study (n = 711). Electrocardiograms (ECGs) that met ST-segment elevation myocardial infarction (STEMI) criteria were included in the training set (n = 183). Paired angiographic location of proximal LAD and ECGs with ST elevation in the anterolateral region were used for the computer program development (n = 36). The test set was based on ECG criteria for anterolateral STEMI only without angiographic reports (n = 162). Tested against 2 expert cardiologists' agreed reading of proximal LAD occlusion, the algorithm has a sensitivity of 95% and a specificity of 82%. The algorithm is designed to have high sensitivity rather than high specificity for the purpose of not missing any proximal LAD in the STEMI population. Our preliminary evaluation suggests that the algorithm can detect proximal LAD occlusion as an additional interpretation to STEMI detection with similar accuracy as cardiologist readers.

Automatic detection and quantification of sleep apnea using heart rate variability.

Detection of sleep apnea using electrocardiographic (ECG) parameters is noninvasive and inexpensive. Our approach is based on the hypothesis that the patient's sleep-wake cycle during episodes of sleep apnea modulates heart rate (HR) oscillations. These HR oscillations appear as low-frequency fluctuations of instantaneous HR (IHR) and can be detected using HR variability analysis in the frequency domain. The purpose of this study was to evaluate the efficacy of our ECG-based algorithm for sleep apnea detection and quantification. The algorithm first detects normal QRS complexes and R-R intervals used to derive IHR and to estimate its spectral power in several frequency ranges. A quadratic classifier, trained on the learning set, uses 2 parameters to classify the 1-minute epoch in the middle of each 6-minute window as either apneic or normal. The windows are advanced by 1-minute steps, and the classification process is repeated. As a measure of quantification, the algorithm correctly classified 84.7% of all the 1-minute epochs in the evaluation database; and as a measure of the accuracy of apnea classification, the algorithm correctly classified all 30 test recordings in the evaluation database either as apneic or normal. Our sleep apnea detection algorithm based on analysis of a single-lead ECG provides accurate apnea detection and quantification. Because of its noninvasive and low-cost nature, this algorithm has the potential for numerous applications in sleep medicine.