Albert Ellis Institute

A simple equilibrial model for the growth and maintenance of Phanerozoic global marine taxonomic diversity can be constructed from considerations of the behavior of origination and extinction rates with respect to diversity. An initial postulate that total rate of diversification is proportional to number of taxa extant leads to an exponential model for early phases of diversification. This model appears to describe adequately the “explosive” diversification of known metazoan orders across the Precambrian-Cambrian Boundary, suggesting that no special event, other than the initial appearance of Metazoa, is necessary to explain this phenomenon. As numbers of taxa increase, the rate of diversification should become “diversity dependent.” Ecological factors should cause the per taxon rate of origination to decline and the per taxon rate of extinction to increase. If these relationships are modeled as simple linear functions, a logistic description of the behavior of taxonomic diversity through time results. This model appears remarkably consistent with the known pattern of Phanerozoic marine ordinal diversity as a whole. Analysis of observed rates of ordinal origination also indicates these are to a large extent diversity dependent; however, diversity dependence is not immediately evident in rates of ordinal extinction. Possible explanations for this pattern are derived from considerations of the size of higher taxa and from simulations of their diversification. These suggest that both the standing diversity and the pattern of origination of orders may adequately reflect the behavior of species diversity through time; however, correspondence between rates of ordinal and species extinction may deteriorate with progressive loss of information resulting from incomplete sampling of the fossil record.

Purified PGH synthase when acting on arachidonic acid in the presence of reduced nicotinamide-adenine dinucleotide or reduced nicotinamide-adenine dinucleotide 3'-phosphate generated superoxide in burst-like fashion. In eight experiments using different batches of enzyme, the mean +/- SE rate of superoxide generation from 100 U of enzyme measured as the superoxide dismutase-inhibitable reduction of cytochrome c was 5.06 +/- 0.19 nmol/min in the first minute and 0.35 +/- 0.03 nmol/min subsequently. Optimum rates of superoxide were seen at concentrations of reduced nicotinamide-adenine dinucleotide in excess of 80 microM and reduced nicotinamide-adenine dinucleotide 3'-phosphate in excess of 100 microM. Using prostaglandin G2 or linoleic acid as substrate rather than arachidonate also resulted in superoxide generation. When prostaglandin H2 was used as substrate, no superoxide was generated. The rate of superoxide generation was markedly inhibited by cyclooxygenase inhibitors. Superoxide generation was also observed during the action of lipoxygenase on either linoleic or arachidonic acid in the presence of reduced nicotinamide-adenine dinucleotide or reduced nicotinamide-adenine dinucleotide 3'-phosphate but not in their absence. Indomethacin had no effect on superoxide generation from lipoxygenase. We conclude that PGH synthase and lipoxygenase produce superoxide via a side-chain reaction dependent on the presence of suitable reducing cosubstrate. This mechanism is analogous to that described for peroxidases in general.

The kinetic model of taxonomic diversity predicts that the long-term diversification of taxa within any large and essentially closed ecological system should approximate a logistic process controlled by changes in origination and extinction rates with changing numbers of taxa. This model is tested with a new compilation of numbers of metazoan families known from Paleozoic stages (including stage-level subdivisions of the Cambrian). These data indicate the occurrence of two intervals of logistic diversification within the Paleozoic. The first interval, spanning the Vendian and Cambrian, includes an approximately exponential increase in families across the Precambrian-Cambrian Boundary and a “pseudo-equilibrium” through the Middle and Late Cambrian, caused by diversity-dependent decrease in origination rate and increase in extinction rate. The second interval begins with a rapid re-diversification in the Ordovician, which leads to a tripling of familial diversity during a span of 50 Myr; by the end of the Ordovician diversity attains a new dynamic equilibrium that is maintained, except for several extinction events, for nearly 200 Myr until near the end of the Paleozoic. A “two-phase” kinetic model is constructed to describe this heterogeneous pattern of early Phanerozoic diversification. The model adequately describes the “multiple equilibria,” the asymmetrical history of the “Cambrian fauna,” the extremely slow initial diversification of the later “Paleozoic fauna,” and the combined patterns of origination and extinction in both faunas. It is suggested that this entire pattern of diversification reflects the early success of ecologically generalized taxa and their later replacement by more specialized taxa.

When increased prostaglandin synthesis was induced in anesthetized cats equipped with cranial windows by topical application of arachidonate (200 micrograms/ml) or bradykinin (20 micrograms/ml), there was reduction of nitroblue tetrazolium, resulting in deposition of the reduced insoluble form of this dye on the brain surface. The amount of reduced nitroblue tetrazolium deposited on the brain surface was measured spectrophotometrically after fixation of the brain by perfusion with aldehydes to eliminate interference from hemoglobin. Topical application of 56 U/ml superoxide dismutase or 20 micrograms/ml indomethacin inhibited nitroblue tetrazolium reduction by 76.5%-82.5% and by 78%-85.5%, respectively. These results show that most of the nitroblue tetrazolium reduction was accounted for by superoxide anion radical generated in the course of arachidonate metabolism via the cyclooxygenase pathway. No superoxide production could be detected in the absence of arachidonate or bradykinin. Histological examination showed no evidence of parenchymal cellular damage or vascular damage and no accumulation of leukocytes. Pronounced leukocyte accumulation occurred 24 hours after topical arachidonate in rabbits with chronically implanted cranial windows. Superoxide appearance was reduced severely by 4,4'-diisothiocyano-2,2'-stilbene disulfonate and phenylglyoxal, two specific inhibitors of the anion channel. The most likely explanation for these findings is that increased metabolism of exogenous or endogenous arachidonate via cyclooxygenase results in the appearance of superoxide anion radical in cerebral extracellular space. Superoxide crosses the membrane of undamaged cells via the anion channel.

We studied the role of prostaglandins and free radicals in the induction of the functional and morphological pial arteriolar abnormalities produced by concussive brain injury. Anesthetized cats equipped with a cranial window for the observation of the pial microcirculation were subjected to concussive brain injury using a fluid-percussion device following administration of cyclooxygenase inhibitors (indomethacin or AHR-5850) or the vehicle for the solution of these agents (NaCl or Na2CO3 solution). Pial arterioles from vehicle-treated animals displayed sustained dilation, reduced responsiveness to the vasoconstrictor effect of arterial hypocapnia, and a high density of endothelial lesions. Animals pretreated with cyclooxygenase inhibitors showed less pronounced vasodilation, normal responsiveness to hypocapnia, and a significantly reduced number of lesions. The vasodilation and reduced responsiveness to the vasoconstrictor effects of hypocapnia after brain injury also were inhibited by topical application of free radical scavengers (nitroblue tetrazolium, superoxide dismutase, or mannitol). The vessels from cats pretreated with free radical scavengers also had a lower density of endothelial lesions than controls. The results support the view that the immediate cause of cerebral arteriolar damage in concussive brain injury is the generation of free oxygen radicals associated with increased prostaglandin synthesis.

Using an absorption line from the metastable (J, K) = (3, 3) level of H3+ together with other lines of H3+ and CO observed along several sightlines, we have discovered a vast amount of high temperature (T ~ 250 K) and low density (n ~ 100 cm-3) gas with a large velocity dispersion in the Central Molecular Zone (CMZ) of the Galaxy, i.e., within 200 pc of the center. Approximately three fourths of the H3+ along the line of sight to the brightest source we observed, the Quintuplet object GCS 3-2, is inferred to be in the CMZ, with the remaining H3+ located in intervening spiral arms. About half of H3+ in the CMZ has velocities near ~ - 100 km s-1 indicating that it is associated with the 180 pc radius Expanding Molecular Ring which approximately forms outer boundary of the CMZ. The other half, with velocities of ~ - 50 km s-1 and ~ 0 km s-1, is probably closer to the center. CO is not very abundant in those clouds. Hot and diffuse gas in which the (3, 3) level is populated was not detected toward several dense clouds and diffuse clouds in the Galactic disk where large column densities of colder H3+ have been reported previously. Thus the newly discovered environment appears to be unique to the CMZ. The large observed H3+ column densities in the CMZ suggests an ionization rate much higher than in the diffuse interstellar medium in the Galactic disk. Our finding that the H3+ in the CMZ is almost entirely in diffuse clouds indicates that the reported volume filling factor (f ≥ 0.1) for n ≥ 104 cm-3 clouds in the CMZ is an overestimate by at least an order of magnitude.

We examine whether political corruption impedes innovation. Using a comprehensive sample of U.S. firms, we find that corruption has a substantial, negative relation with the quantity and quality of innovation. These results are robust to using various fixed effects, proxies for corruption and innovation, and subsamples. To establish causality, we employ 2 instruments for corruption: local ethnic diversity and the corruption of the state a firm’s founder grew up in. Corruption appears to reduce innovation output both on average and for the most innovative firms. Overall, this evidence is consistent with the notion that corruption reduces social welfare by impeding innovation.

The contractile effects of thromboxane A2 (TxA2), a labile arachidonic acid metabolite, were studied in arterial smooth muscle strips. TxA2 was generated upon the addition of 255 nM prostaglandin cyclic endoperoxide H2 to human platelet particles in the muscle bath. Using the isometric contaction produced by 40 mM K+ in isotonic saline as the reference contraction, bovine middle cerebral artery strips contracted to 153 +/- 14% of the reference response while bovine coronary and porcine coronary, renal and common carotid strips contracted to 47 +/- 3, 26 +/- 5, 43 +/- 2 and 2 +/- 1% of reference, respectively. The cerebral artery response to the TxA2 generating system was as great as the maximum response to prostaglandin F2alpha and two times the maximum response to 5-hydroxytryptamine. Because TxA2 is formed by brain tissue and released from aggregating platelets, it may be important in the pathogenesis of spasm associated with injured brain tissue or pathologic changes leading to platelet aggregation.

We investigate properties of the interstellar medium (ISM) in galaxies hosting long-duration gamma-ray bursts (GRBs) from an analysis of atomic species (MgI, FeI) and excited fine-structure levels of ions (e.g. SiII). Our analysis is guided primarily by echelle observations of GRB 050730 and GRB 051111. These sightlines exhibit fine-structure transitions of OI, SiII, and FeII gas that have not yet been detected in intervening quasar absorption line systems. Our results indicate that the gas with large MgI equivalent width (e.g. GRB 051111) must occur at distances >~50pc from GRB afterglows to avoid photoionization. We examine the mechanisms for fine-structure excitation and find two processes can contribute: (1) indirect UV pumping by the GRB afterglow provided a far-UV intensity in excess of 10^6 times the Galactic radiation field; and (2) collisional excitation in gas with electron density n_e>10^4 cm^-3. The observed abundances of excited ions are well explained by UV pumping with the gas at approximately a few hundred pc from the afterglow for GRB 051111 and r<100pc for GRB 050730, without invoking extreme gas density and temperature in the ISM. We show that UV pumping alone provides a simple explanation for all reported detections of excited ions in GRB afterglow spectra. The presence of strong fine-structure transitions therefore may offer little constraint for the gas density or temperature. We discuss additional implications of UV pumping including its impact on chemical abundance measurements, new prospects for observing line-strength variability, and future prospects for studying the gas density and temperature. Finally, we list a series of criteria that can distinguish between the mechanisms of UV pumping and collisional excitation.

On the basis of the material discussed, our current assessments of the controversial points mentioned at the beginning of this article may be summarized as follows: Pf = 0, the minimum back pressure to coronary flow associated with a measurable conductance, is indeed greater than coronary outflow pressure (and usually left ventricular diastolic pressure, as well). Pf = 0 needs to be taken into account in attempts to determine coronary driving pressure. In maximally vasodilated beds, Pf = 0 derived from diastolic pressure-flow relationships exceeds coronary outflow pressure by at least a few mm Hg. Pf = 0 varies with coronary outflow and/or diastolic ventricular cavity pressure. When left ventricular preload is elevated, Pf = 0 exceeds outflow pressure by increasing amounts. Pf = 0 appears to be systematically higher and pressure-dependent in beds in which vasomotor tone is operative. An improved understanding of the nature of, and basis for, time-dependent changes in resistance and/or Pf = 0 during long diastoles in nonvasodilated beds is needed. The contour of pressure-flow relationships which are free of reactive effects is curvilinear rather than linear. The degree of curvilinearity is substantial and can change with interventions. Curvilinearity is accentuated at lower pressures and may reflect changes in the number of perfused vascular channels as well as the caliber of individual channels. Capacitive effects need to be dealt with quantitatively in studies of pressure-flow relationships. Values of the capacitance which is involved in these effects vary with both pressure and tone. Capacitive flow also depends upon the instantaneous rate of change of pressure, which has not usually been defined in published studies. Although intramyocardial capacitance is large and plays an important role in systolic-diastolic flow interactions, a controlling role in diastolic coronary arterial pressure-flow relationships has not been established experimentally. In vasodilated beds, in-flow remains remarkably constant for several seconds after the brief transient associated with a step-change in the level of constant pressure perfusion during a long diastole. Calculations of coronary vascular resistance (by whatever method) remain of limited value, particularly when changes in response to an intervention are modest. Because of the curvilinear diastolic pressure-flow relationship, resistance is pressure-dependent and, at any given pressure, is probably best defined by establishing the slope of a diastolic pressure-flow curve which is free of reactive effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Myocardial blood flow/unit mass (MBF) and the determinants of myocardial oxygen consumption were measured in seven control subjects (group I) and 15 patients (pts) with cardiomyopathy (CM), group II (group IIa-congestive CM: 10 pts; group IIb-hypertrophic CM: 5 pts). In group I left ventricular (LV) MBF was 64 +/- 8 (SD) ml/100g-min; it was significantly lower in IIa (45 +/- 15 ml/100g-min, P less than 0.01) and IIb (39 +/- 7 ml/100g-min, P less than 0.01). However, calculated total LV flow (LV mass X MBF) was increased in the two CM groups. In nine CM pts, LV MBF increased in response to atrial pacing from 41 +/- 7 to 63 +/- 13 ml/100g-min. In group IIa, calculated peak wall stress was normal (4.39 +/hortening (MVcf) was significantly reduced (0.53 +/- 0;18 vs 1.26 +/- 0.12 circum/sec, P less than 0.01). In IIb, MVcf was normal but peak stress was significantly reduced (2.80 +/- 0.75 vs 4.51 +/- 1.10 dynes/cm2 X 10(5), P less than 0.05). Multiple regression analysis based on all pts yielded, MBF - 16.9 MVcf + 9.30 Stress + 0.26 Heart Rate - 26.4 (r=0.79). The data indicate that MBF is reduced in CM patients and the regression analysis suggests that MBF in these 22 pts with normal coronary arteriograms was determined largely by heart rate, peak stress, and ventricular performance.

Of 145 patients with borderline hypertension, 30% had increased resting cardiac index (QI), whereas the remainder had normal values. The specific aim of this study was to investigate cardiac regulation in patients who had normal resting QI. Eighty-five control subjects were used for comparison. At rest, patients with normal QI showed evidence of decreased parasympathetic inhibition; the QI after injection of atropine increased less than in control subjects. After complete cardiac autonomic blockade with propranolol and atropine, QI and stroke volume were significantly lower in patients than in control subjects. The mechanism of this low QI was further analyzed. Central blood volume, which strongly correlates with stroke volume, was used as an estimate of the cardiac venous filling. After blockade, stroke volume was decreased in patients, but central blood volume was normal. Patients also showed a decreased heart rate and QI response to infusion of isoproterenol. It is therefore postulated that two components may be responsible for the low QI in the "denervated" heart: patients exhibit a decreased responsiveness to sympathetic stimulation, and they may also be less responsive to venous filling. Behind the facade of cardiac normality in these borderline hypertensive patients with normal cardiac output, there is evidence of altered autonomic control of the heart (decreased vagal inhibition) and of changed cardiac response to sympathetic stimulation and possibly to venous filling.

In addition to the impressive predictive power of machine learning (ML) models, more recently, explanation methods have emerged that enable an interpretation of complex nonlinear learning models, such as deep neural networks. Gaining a better understanding is especially important, e.g., for safety-critical ML applications or medical diagnostics and so on. Although such explainable artificial intelligence (XAI) techniques have reached significant popularity for classifiers, thus far, little attention has been devoted to XAI for regression models (XAIR). In this review, we clarify the fundamental conceptual differences of XAI for regression and classification tasks, establish novel theoretical insights and analysis for XAIR, provide demonstrations of XAIR on genuine practical regression problems, and finally, discuss challenges remaining for the field.

How much of a living marine fauna would be reflected in the fossil record? In order to answer this, I investigated the probable fate of 169 megascopic genera of the intertidal fauna of the Friday Harbor, Washington region. Three methods were used and these give very similar results. (I) From morphologic examination, 30% of the mud fauna, 32% of the sand fauna, and 29% of the rock fauna are predicted to yield many identifiable fossils; 38% of the mud fauna, 42% of the sand fauna, and 41% of the rock fauna are predicted to yield few identifiable fossils; and the remainder are predicted to yield no fossils. (II) In actual fact, 44% of the mud fauna, 32% of the sand fauna, and 39% of the rock fauna have a fossil record (data from Treatise on Invertebrate Paleontology ). (III) The 16 sediment samples which were examined yielded 29% of the total fauna. I conclude (1) that the fossilization potential for the Friday Harbor intertidal fauna is largely independent of habitat, and (2) that 40% of the present megascopic fauna would be (and has been!) preserved in the fossil record. The fossil record would accurately (and preferentially) include the herbivore and filter feeding genera. The reason which I postulate for this is based on the suitability of heavily calcified exoskeletons to an essentially sessile mode of life, and the lack of suitability of such skeletons for readily mobile forms. 67% of the genera which essentially rest in one place are known as fossils. In contrast, only 16 to 27% of the burrowing detritus eaters (e.g., polychaetes) and roving carnivores (e.g., sea stars and crabs) are known as fossils. The percentage of herbivore and filter feeding genera in rocky environments is 39%, in sand 16% and in mud 34%. In the fossil record, deposits which were originally mud are likely to be most fossiliferous because (1) that environment has a high proportion of essentially sessile genera, (2) essentially sessile genera are far more likely to have a heavily calcified skeleton, and (3) few rock intertidal regions are buried.

Several writers on religion and psychotherapy claim that people who follow a &amp;quot;loving God &amp;quot; model and who see God as a partner who works with them to resolve their problems are less emotionally disturbed and can benefit more from &amp;quot;rational &amp;quot; systems of therapy than religionists who have a more negative view of God. Some authors have specifically written that rational emotive behavior therapy (REBT) includes many religious philosophies and that the principles and practices of REBT are similar to those endorsed by certain kinds of devout religionists. In this article, the author describes the constructive philosophies of REBT and shows how they are similar to those of many religionists in regard to unconditional self-acceptance, high frustration tolerance, unconditional cceptance ofothers, the desire rather than the need for achievement and approval, and other mental health goals. It shows how REBT is compatible with some important religious views and can be used effectively with many clients who have absolutistic philosophies about God and religion. Certain rational emotive behavior therapy (REBT) practitioners have attempted to demonstrate hat REBT is compatible with many religious philosophies and that it can be used by clinicians who accept heir clients &amp;apos; religious orientations and show them how their disturbance-creating beliefs can be religiously disputed. For al-most 40 years I have known many therapists, including members of the clergy, who nicely combine REBT teachings with religious teachings and have no difficulty doing so. These recent contri-butions considerably add to other attempts (Backus, 1985;

Section I. Introduction, Rationale, and Basic Issues: Chapter 1. Rational Emotive Behavioral Approaches to Childhood Disorders: History, Theory, Practice and Research, Michael E. Bernard, Albert Ellis and Mark Terjesen. Chapter 2. REBT Assessment and Treatment with Children, Raymond DiGiuseppe and Michael E. Bernard. Chapter 3. REBT Assessment and Treatment with Adolescents, Howard Young. Chapter 4. Frustration Tolerance Training for Children and Adolescents, William J. Knaus. Chapter 5. Emotional Resilience Training for Children and Adolescents, Michael E. Bernard and Daniela Pires. Section II. Disorders Of Childhood: Chapter 6. A Developmental, Rational Emotive Behavioral Approach for Working with Parents, Marie Joyce. Chapter 7. Depression in Children and Adolescents: REBT Approaches to Assessment and Treatment, Ann Vernon. Chapter 8. Childhood Anxieties, Fears, and Phobias: A Cognitive-Behavioral, Psychosituational Approach, Russell Grieger and John Boyd. Chapter 9. Treating Aggressive Children: A Rational-Emotive Behavior Systems Approach, Raymond DiGiuseppe and Jill Kelter. Chapter 10. Rational Emotive Behavior Therapy and Attention Deficit Disorders, Kristene Doyle and Mark Terjesen. Chapter 11. Working with the Educational Underachiever: A Social and Emotional Developmental Approach, Michael E. Bernard. Section III. Applications: Chapter 12. Working with the Parents and Teachers of Exceptional Children, John McInerney and Bridget McInerney. Chapter 13. Rational Emotive Behavior Group Therapy with Children and Adolescents, MarkTerjesen and Maria A. Esposito. Chapter 14. Applications of REBT in Schools: Prevention, Promotion, Intervention, Ann Vernon and Michael Bernard.

Myocardial blood flow (MBF) per unit mass was measured in 10 patients (pts) with severe aortic stenosis (AS) and no significant aortic insufficiency, normal ejection fractions, and normal coronary arteriograms, using xenon-133 and a multiple crystal scintillation camera. MBF per unit mass was reduced in AS (53 +/- 13 mg/100g.min) in comparison to a group of seven normal control patients (69 +/- 12 ml/100g.min) (P less than 0.05). When normalized for heart rate. MBF remained depressed in aortic stenosis (0.65 +/- 0.11 ml/100 g.beat). MBF/beat was strongly related to peak left ventricular wall stress in both groups (r = 0.97). Individual values of MBF/beat were normalized for peak stress using an analysis of covarience; the adjusted mean values were 0.62 +/- 0.03 ml/100g.beat for the AS patients and 0.84 +/- 0.03 ml/100 g.beat for the control patients. There was no overlap between groups in adjusted MBF per beat. Values of MBF per beat and peak stress for a group of ten cardiomyopathy patients with depressed contractility were observed to fall close to the regression line for AS patients. The results suggest that variability in resting MBF in these AS patients is due primarily to differences in LV stress and that reduction in MBF per beat in this group may be due to reduced contractility.

Previous studies have shown that there is both a significant shortening in platelet survival and a measured hyperactivity to platelet-aggregating agents in patients with documented coronary artery disease compared with control groups. We used a recently described radioimmunoassay for the platelet-secreted protein platelet factor 4 (PF4) to study 162 patients with documented coronary artery disease. There was a significant increase in plasma PF4 concentrations in patients with documented coronary artery disease compared with angiographically normal patients (8.7 vs 16 ng/ml, respectively, n = 121), but as in previous studies of platelet survival, we could not correlate elevated plasma PF4 concentration and the severity or site of the coronary artery disease. In addition, there was no correlation with left ventricular function, serum cholesterol or the type of angina. Patients with confirmed acute myocardial infarction had no significant difference in mean plasma PF4 concentrations compared with similar groups of coronary disease patients who had prolonged chest pain or chronic stable angina. Coronary artery bypass grafting in a subgroup of patients did not affect the mean plasma PF4 concentration during 1 year of follow-up after bypass surgery, but medical therapy for angina with increasing doses of propranolol and nitrates significantly reduced PF4 concentration in another subgroup of patients who were not considered to be candidates for surgical therapy.

Background Transthoracic echocardiography ( TTE ) is often considered for risk stratification of patients with acute pulmonary embolism ( PE ). We sought to determine the contemporary utilization of early TTE (within 72 hours of PE diagnosis) and explored the association between TTE findings and PE -related mortality. Methods and Results Data from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry, a multicenter registry of consecutive patients with acute PE , were used (2001-July 2017). We used a generalized linear mixed model to determine predictors of early TTE performance. Moreover, the association between 3 TTE variables (right atrial enlargement, right ventricular hypokinesis, and presence of right heart thrombi) and 30-day PE -related mortality was assessed in generalized linear mixed models adjusted for PE severity index, and other comorbidities. Among 35 935 enrollees with acute PE , 15 375 (42.8%) underwent early TTE . There was an increase in early TTE utilization rate over time ( P<0.001 for trend). Younger age, female sex, enrollment in countries other than Spain, history of coronary disease, heart failure, atrial fibrillation, tachycardia, and hypotension were the main predictors of early TTE ( P<0.01 for all). In multivariable analyses, right atrial enlargement (adjusted odds ratio: 3.74; 95% confidence interval, 2.10-6.66), right ventricular hypokinesis (adjusted odds ratio: 3.11, 95% confidence interval: 1.85-5.21) and right heart thrombi (adjusted odds ratio: 4.39, 95% confidence interval, 1.99-9.71) were associated with increased odds for PE -related mortality. Conclusions Early TTE is commonly performed for acute PE and utilization rates have increased over time. Right atrial enlargement, right ventricular hypokinesis, and right heart thrombi are predictive of worse outcomes. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02832245.

Calcium channel blockers suppress early ischemic arrhythmias, possibly by diminishing intracellular calcium overload and its effect on the ventricular action potential. To explore this, we compared the effects of diltiazem on ischemic "injury" potentials and ventricular fibrillation during serial coronary artery occlusions in dogs. Injury potentials and ventricular fibrillation were elicited every 15-25 minutes by simultaneous occlusion of the left anterior descending and circumflex arteries during rapid atrial pacing. DC epicardial electrograms were recorded differentially between the ischemic region and a small nonischemic region supplied by a proximal branch of the left anterior descending artery. Injury potentials developed with a uniform time course during five control occlusions, but were reduced by diltiazem infusion (0.5 mg/kg over 25 minutes) in each of eight dogs. The mean diastolic injury potential (T-Q depression) at 150 seconds of ischemia was 9.1 +/- 2.7 mV before diltiazem and 6.1 +/- 1.6 mV afterward (P less than 0.001). Diltiazem increased the mean time between coronary occlusion and ventricular fibrillation from 186 to 366 seconds (P less than 10(-5), but did not change the magnitude of the diastolic injury potential at onset of ventricular fibrillation. Diltiazem also delayed ischemia-induced conduction impairment to the same extent that it delayed injury potential development. In five dogs, the effect of diltiazem on regional blood flow near the epicardial electrodes was measured by infusion of radionuclide-labeled microspheres. Coronary occlusion reduced flow to the ischemic zone from 0.86 to 0.05 ml/min per g (P = 0.001). Diltiazem increased preocclusion flow by 11% (P = 0.03), but did not significantly alter flow during occlusion. Hemodynamic measurements show that diltiazem did not diminish cardiac work. Diltiazem therefore produced a flow-independent reduction of cellular depolarization during ischemia, which may be due to relief of calcium overload, and which may explain the antifibrillatory effect.