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To mark the hundredth anniversary of the often misunderstood Allied intervention in Russia’s Civil War, The Journal of Slavic Military Studies has dedicated a section of this volume to asse...

11 All statements of fact, analysis, or opinion are the author’s own and do not reflect the official policy or position of the NIU, the Department of Defense (DoD), or the United States government.... more...

11 All statements of fact, analysis, or opinion are the author’s own and do not reflect the official policy or position of the NIU, the Department of Defense (DoD), or the United States government.... more...

The Ukrainian Orthodox Church has a chance to be an outlier in a region otherwise inhospitable to religious diversity. Less than two years after gaining autonomy in the Orthodox community, signs are promising that church elites are neither frightened by religious choice or inclined toward state sponsorship. Such a posture would contrast glaringly with the ethos of its once overseer, the Russian Orthodox Church. I argue that, although the church’s development is still embryonic, several factors suggest a more tolerant attitude toward the operations of other nontraditional may prove durable. Hopefully, the approach is not simply a matter of the church conforming to pro-democracy sentiments in Kyiv, but rather is rooted in experience and deep-seeded beliefs. If this proves to be the case, religious pluralism and constructive church-state relations has the chance to be irrevocably engrained in the country. Such a development would dispel the notion that Eastern Orthodoxy and authoritarianism are somehow inextricably connected. Even more importantly for Ukraine’s future, a modern and transparent national church may help anchor Kyiv to its current democratizing orientation, preventing a cyclical return to autocracy. more...

The West’s approach to Russian machinations in the Arctic is too often misinformed by simplistic media storylines of militarization and zero-sum competition. While Russian behavior of late in Ukraine and Syria has hardly been reassuring, Moscow’s Arctic approach stands remarkably separate from the larger tumult of relations with the West. The prevailing focus on security enhancements across Russia’s Arctic coastline risks oversimplifying Kremlin decision calculus and distorting conflict potential. Fortunately, recent trends in the region provide greater contextualization concerning Russian security. This article examines six features of Russia’s Arctic strategy that are particularly significant when considering an effective Western counter-posture in the Arctic. Three act to mitigate the risk of confrontation, while three other factors hold the potential to aggravate the security environment, After setting the geopolitical scene with these six features, this article offers five policy suggestions ... more...

The West’s habitual misunderstanding of Russia was once again on display during the recent US presidential election. Competing sides of the political divide crafted starkly different caricatures of... more...

The Arctic has reemerged as a region of geo-political consequence following rapid reduction in sea ice in the past decade. As the only non-NATO Arctic littoral state, Russia’s approaches to the many disputes in the region will undoubtedly have the greatest bearing on the future security environment. This article examines the two most threatening circumpolar disputes, sea bed delineation and navigation rights, and postulates that Russia’s policies on both issues conform to historical patterns. Recent Russian policy decisions are placed in historical context in order to gauge conflict potential in the Arctic related to these two disputes. The main finding is that the path-dependent trajectories of both issues are becoming ever more distinct as Russia articulates its Arctic policies. In particular, structural and historical factors encourage Moscow toward cooperation and compromise on sea bed negotiations but also suggest that Kremlin intransigence on navigation will continue, with potentially detrimental ef... more...

A precipitação no Nordeste brasileiro apresenta grande variabilidade, motivo pelo qual o monitoramento dos períodos secos e chuvosos se faz necessário, haja vista ser imprescindível para garantir o gerenciamento adequado dos recursos hídricos. Neste sentido foi utilizado o Índice de Anomalia de Chuva a fim de monitorar os períodos secos e chuvosos e suas intensidades. Utilizaram-se dados de 31 postos distribuídos ao longo da Bacia Hidrográfica do Rio Mamanguape com série histórica de 18 anos (de 1994 a 2011). Dentro de cada ano foram observados dois períodos distintos, um período úmido, que vai de março a agosto e um período seco, que se estende de setembro a fevereiro. Esta pesquisa apresenta a climatologia espacial da bacia, a qual evidenciou três regiões distintas, sendo a primeira a região leste, a segunda é a região central e a terceira é a região oeste. Por fim, foram efetuadas projeções de redução e aumento da precipitação em 20% sobre o valor atual obtido a partir da série histórica, como recomendado pelo IPCC (2001); foi possível, desta forma, projetar futuras variações climáticas na região da bacia as quais são passíveis de alterar, de maneira significativa, seu aporte hídrico. The rainfall in Northeast of Brazil presents great variability, thus, monitoring the dry and rainy periods is necessary, as this is essential to ensure proper management of water resources. Therefore, the Rainfall Anomaly Index was used to monitor the dry and rainy periods, as well as their intensities. Data from 31 stations distributed along the basin of the Mamanguape river with a time series of 18 years (from 1994 to 2011) was used. Within each year two distinct periods were observed, one wet season from March to August and a dry period from September to February. The study also included the weather spatial basin, which revealed three distinct regions, the first being the eastern region, the second is the central region and the third is the western region. Finally, projections were made for reduction and increase in precipitation in 20% of the current value obtained from the time series as recommended by the Intergovernmental Panel on Climate Change. Thus it was possible to project future climate changes in the watershed that may significantly alter the water intake more...

Long considered a rather trivial afterthought of The Great War, the intervention by Western forces in Russia from 1918 to 1920 has recently received considerable scholarship. Yet the focus of these... more...

There is a growing tendency among many Western nations to defer to Germany the responsibility for dealing with an ever more recalcitrant Russia. Despite the perils involved, German Chancellor Angel... more...

The Arctic is beginning to test the stage-managed optics of China and Russia’s ‘strategic partnership’. Friction was most recently on display after the Arctic Council’s May 2013 decision to confer ... more...

Climate change is set to elevate the debate over maritime navigation and coastal state jurisdiction in the Arctic Ocean. Russia, with its centuries-old claim over the Northern Sea Route, is likely to increasingly clash with proponents of navigational freedoms as receding ice makes Arctic seaborne logistics viable. Moving forward, Moscow's Arctic posture may resemble its Near Abroad intransigence, particularly when dealing with foreign navies operating in Russia's self-proclaimed area of control. Lincoln E Flake reflects on how the issue of freedom of navigation could pose a greater risk to Arctic stability than the better known disputes over seabed claims and competition for hydrocarbon resources. more...

Recentemente, o conceito da pegada hídrica foi introduzido como um indicador importante de consumo de água para a humanidade. A pegada hídrica é definida como o volume total de água utilizado durante a produção de bens e serviços, bem como o consumo direto de água pelos seres humanos. A água não é consumida só diretamente mas também indiretamente, nos processos de produção. Portanto, o cálculo da pegada hídrica permite quantificar o total de água consumida ao longo da cadeia de fornecimento global. Esta revisão de literatura analisa o estado da arte da pegada hídrica desde a sua criação, no encontro internacional de especialista em comércio de água virtual realizado em dezembro de 2002 na Holanda, até os dias atuais. Os principais resultados encontrados na literatura consultada indicam consenso de que a pegada hídrica é capaz de monitorar o impacto humano sobre o meio ambiente. Além do mais, esta metodologia tem uma vasta gama de aplicações que pode ser empregada em escalas que vão desde um único produto, um processo, setor, individuo, cidades, até mesmo nações e todo o planeta.The concept of the water footprint has been recently introduced as an important indicator for human induced water consumption. The water footprint is defined as the total volume of water used during production and consumption of goods and services as well as direct water consumption by human beings. Water is not only consumed directly but also indirectly in production processes. Therefore, calculating the water footprint enables to quantify total water consumed along the whole global supply chain. This review surveys the state of the art on water footprint since the International Expert Meeting on Virtual Water Trade, held in Delft, The Netherlands, in December 2002, until current days. The major findings linked to the consulted literature indicated that the water footprint is suitable for monitoring the human impact on the environment. Furthermore, this methodology has a wide range of applications that can be used at scales ranging from a single product, process, industry, individual, cities and even nations around the globe. more...

In this study, cDNA for a somatostatin receptor variant (somatostatin receptor subtype 2, SSTR 2) was isolated, cloned, and sequenced from rainbow trout. A 1821-nt cDNA was isolated and found to contain a single initiation site 387-nt from the most 5' end, an open reading frame of 1116-nt, and a single putative polyadenylation site 189-nt from the most 3' end. The encoded protein contains 372 amino acids and contains seven membrane-spanning domains. Based on structural analysis, the protein was identified as a subtype 2 SSTR. These data support the emergence of a multigenic SSTR family early in the course of vertebrate evolution, concomitant with or perhaps prior to the divergence of boney fish. The distribution of SSTR 2 mRNA in tissues was determined by quantitative real time-PCR (QRT-PCR). SSTR 2 was most abundant in the brain (where it was detected in the telencephalon, optic tectum, and hypothalamus), skeletal muscle, and liver, but it also was present in the endocrine pancreas (Brockmann body) and various regions of the gastrointestinal tract (esophagus, stomach, intestine). SSTR 2 mRNA was most abundant in the brain, muscle, and liver. In vitro the Brockmann body and liver with increasing concentrations of glucose (1, 4, 10mM) resulted in increased expression of SSTR 2 mRNA. These findings contribute to the understanding of the evolution of the SSTR family and provide insight into the roles of SSTR 2 in fish. more...

Although acute hypertensive pulmonary edema is sometimes regarded as the most severe form of heart failure, at the peak of symptoms, hearts perform well above resting levels and cannot be said to be failing. Another characteristic of the condition, the rapidity of its onset and reversal when properly treated, suggests positive feedback as a causal mechanism. It is proposed that the syndrome results from a feedback loop with increased sympathetic tone as the efferent output, increased pulmonary vascular pressure as the stimulus to increased sympathetic tone, and positive feedback occurring because elevated sympathetic tone constricts systemic veins, thereby transferring blood from peripheral veins to the pulmonary vasculature. Evidence for the proposed mechanism derives from all the empirical treatments that have evolved. All remove blood from the pulmonary circuit, and all but the oldest, bloodletting, do so by transferring blood from the pulmonary circuit to the peripheral veins. more...

Postnatal decreases in vascular reactivity involve decreases in the thick filament component of myofilament calcium sensitivity, which is measured as the relationship between cytosolic calcium concentration and myosin light chain (MLC20) phosphorylation. The present study tests the hypothesis that downregulation of thick filament reactivity is due to downregulation of myosin light chain kinase (MLCK) activity in adult compared with fetal arteries. Total MLCK activity, calculated as %MLC20phosphorylated per second in intact arteries during optimal inhibition of myosin light chain phosphatase activity, was significantly less in adult (6.56 ± 0.29%) than in fetal preparations (7.39 ± 0.53%). In situ MLC20concentrations (μM) in adult (198 ± 28) and fetal arteries (236 ± 44) did not differ significantly. In situ MLCK concentrations (μM), however, were significantly greater in adult (8.21 ± 0.59) than in fetal arteries (1.83 ± 0.13). In situ MLCK activities (ng MLC20phosphorylated·s−1·ng MLCK−1) were significantly less in adult (0.26 ± 0.01) than in fetal arteries (1.52 ± 0.11). In contrast, MLCK activities in adult (15.8 ± 1.5) and fetal artery homogenates (17.3 ± 1.3) were not significantly different. When in situ fractional activation was calculated, adult values (1.72 ± 0.17%) were significantly less than fetal values (9.08 ± 0.83%). Together, these results indicate that decreased thick filament reactivity in adult compared with fetal ovine carotid arteries is due at least in part to greater MLCK activity in fetal arteries, which in turn cannot be explained by differences in MLCK, MLC20, or calmodulin concentrations. Instead, this difference appears to involve age-related differences in fractional activation of the MLCK enzyme. more...

Background ERCP is usually performed with the patient in the prone position. Little data exist on ERCP in the supine position, which is considered unsafe in nonintubated patients. Objective Our purpose was to compare outcomes of ERCP in the prone and supine positions. Design Retrospective study. Setting Tertiary care medical center. Patients All patients undergoing ERCP by one endoscopist over an 18-month period. Main Outcome Measurements American Society of Anesthesiologists (ASA) score, procedural degree of difficulty, procedural time, success rates, complication rates, effects on oxygen desaturation and hemodynamics, amount of sedation, need for precut sphincterotomy. Results A total of 649 patients were evaluated, of whom 506 patients were prone and 143 were supine. There were no differences between the groups with regard to sex, procedural time, ASA scores, need for precut sphincterotomy, adverse cardiovascular events, episodes of oxygen desaturation, dose of meperidine or midazolam, or oxygen supplementation. Complete success and complication rates were similar for both groups (90.2% and 11.2% for supine and 92.5% and 9.1% for prone, respectively). Procedural degree of difficulty was significantly higher in the supine group ( P Limitations Retrospective study, one endoscopist. Conclusions ERCP performed in nonintubated patients placed supine is often more difficult and may lead to more mild adverse respiratory events than when performed with the patient prone. Supine ERCP is appropriate in certain patients who cannot lie prone (abdominal pain, abdominal distention, ascites, recent abdominal or neck surgery, indwelling percutaneous tubes and need for access during the procedure to indwelling internal/external percutaneous biliary catheters, and in the morbidly obese) with more intensive monitoring in those who are not intubated. more...

It has been reported that sensitization of animals to allergens increases both early shortening velocity and myosin light-chain kinase of their airway smooth muscle without increasing force generated by these muscles. Since early shortening sets muscle length for the duration of a contraction, these responses might be expected to produce greater airway obstruction. Here, it is explained how the more rapid early shortening without increased force production is predicted by the 2-stage process of activation followed by contraction posited by the crossbridge theory of contraction when the rate, but not the extent, of activation is increased. The experimental results are reproduced by a simple model in which activation rate is increased 1.6-fold without any other changes in contractile parameters. These results reinforce suggestions that sensitized animals are a model for reactive airway disease. more...

The full functional length range of trachealis muscle was measured to identify a precise reference length and to assess the length changes that the myofilament lattice can accommodate. The initial reference length ( L10%) was that where rest tension equaled 10% of total force (passive tension plus active force). Total force at this length served as a force reference (Fref = 219 ± 12 kPa, N = 7). Muscles initially adapted at L10% for 30–60 min had no rest tension when shortened to 10%. Passive tension rose steeply and linearly with slope 11.2 Fref/ L10% at lengths >1.04 L10%. Rest tension at 1.1 L10% declined by 10% and declined steeply at lengths between 0.1 and 0.2 L10%, extrapolating to zero at 0.076 L10%. Muscles visibly reextended during relaxation at lengths 10%. At long lengths, force extrapolated to zero at 1.175 L10%. The >15-fold length range (0.076–1.175 L10%) for force generation and nearly constant force over a greater than threefold length range is likely produced by several structural accommodations, including filament sliding, an increased number of sliding filaments in series, and increased length of passive structures in series with the sliding filaments. Visible reextension during relaxation suggests that the lattice does not undergo plastic adaptations at lengths 10% and that lattice plasticity is limited to a three- to fourfold length range. more...

Muscle birefringence, caused mainly by parallel thick filaments, increases in smooth muscle during stimulation, signalling thick filament formation upon activation. The reverse occurs in skeletal muscle, where a decrease in birefringence has been correlated with crossbridge movement away from the thick filaments. When force generation by trachealis muscle was inhibited with wortmannin, which inhibits myosin light-chain phosphorylation and thick-filament formation, but not the calcium increase caused by stimulation, the birefringence response inverted, suggesting crossbridge movement similar to that of skeletal muscle. Resistance to quick stretches was much greater in stimulated muscle than in unstimulated muscle before wortmannin treatment and no different in stimulated and unstimulated muscle after force inhibition by wortmannin. Before wortmannin treatment, stimulation reduced thick-filament cross-sectional areas in electron micrographs by 44%. After force inhibition by wortmannin, filament areas were not significantly different in stimulated and unstimulated muscle and not significantly different from those of relaxed muscle without wortmannin treatment. These results suggest that myofibrillar-space calcium causes crossbridges to move away from the thick filaments without firmly attaching to thin filaments. more...

asthma affects 17.7 million Americans, 5 million of them children ([41][1]). Its incidence has more than doubled in the general population since 1980, with a disproportionate increase in children under the age of 4 ([41][1]). Measures of the yearly burden of this disease, 5,500 deaths ([31][2]) more...

Birefringence and force produced by pig tracheal smooth muscles were recorded every 100 ms during electrically stimulated tetani at muscle lengths that varied 1.5-fold and at the peak of acetylcholine contractures at the same lengths. Isometric force was nearly the same at all lengths. Resting birefringence at the longest length was 30% greater than that at the shortest length. During tetani, birefringence increased with approximately the same time course as force, rising by 20% at the shortest length and 9% at the longest length, and continued to increase by an additional 0.5–1.5% of the resting value for 2–8 s after stimulation ended and force began to fall. This late increase was greatest and more sustained at longer lengths. During contractures, birefringence increased by 25 and 18% at the shortest and longest lengths, respectively. Comparison of these results with our published thick-filament densities suggests that thick-filament density increased by about 80, 72 and 50% during contractures at the short, intermediate and long lengths, and that ∼35% of birefringence in the resting muscle at the longest length was not due to thick filaments. These findings support the hypotheses that tracheal smooth muscle adapts to longer lengths by increasing thick-filament mass and that myosin thick filaments are evanescent, dissociating partially during relaxation and reforming upon activation. The results further suggest that thick-filament formation is sufficiently rapid to account for the velocity slowing and some of the force increase observed during the rise of activation of tracheal smooth muscle. more...

The observation that the length-force relationship in airway smooth muscle can be shifted along the length axis by accommodating the muscle at different lengths has stimulated great interest. In light of the recent understanding of the dynamic nature of length-force relationship, many of our concepts regarding smooth muscle mechanical properties, including the notion that the muscle possesses a unique optimal length that correlates to maximal force generation, are likely to be incorrect. To facilitate accurate and efficient communication among scientists interested in the function of airway smooth muscle, a revised and collectively accepted nomenclature describing the adaptive and dynamic nature of the length-force relationship will be invaluable. Setting aside the issue of underlying mechanism, the purpose of this article is to define terminology that will aid investigators in describing observed phenomena. In particular, we recommend that the term “optimal length” (or any other term implying a unique length that correlates with maximal force generation) for airway smooth muscle be avoided. Instead, the in situ length or an arbitrary but clearly defined reference length should be used. We propose the usage of “length adaptation” to describe the phenomenon whereby the length-force curve of a muscle shifts along the length axis due to accommodation of the muscle at different lengths. We also discuss frequently used terms that do not have commonly accepted definitions that should be used cautiously. more...

Background A rapid change in length of cardiac muscle during isometric contraction is followed by developed force that is less than appropriate for the new length because of deactivation of the contractile system. Length change deactivation may have favorable or unfavorable effects on cardiac function, depending on the circumstances under which it is produced. Methods Left ventricular papillary muscles from male Sprague-Dawley rats were arranged for recording of isometric force. After each control or reference isometric contraction, a quick release-quick stretch V-step was applied to the following contraction. For each repetition of control and experimental contractions, the time of application of V-steps was increased by 20 ms until peak force was reached. Effects of these V-steps were assessed from ratios of peak redeveloped force to peak force in an isometric reference contraction. Slopes of plots of these ratios versus time after the onset of the contraction were used to quantify the effects of inotropic agents on deactivation. Results Increasing calcium from 2.5 to 5.0 or 7.5 mM increased force by 12±4% (mean±SEM), did not change time to peak, and did not significantly alter the deactivation slope. Adding 5 mM epinephrine increased force by 16±5%, decreased time to peak by 34±3%, and increased the deactivation slope by 106±9% ( PConclusions The quantitatively different effects of the three agents on length change deactivation slopes and time to peak force suggest a common mechanism, probably involving thin-filament cooperativity. more...

We consider methods for assessing agreement or disagreement between the results of a meta-analysis of small studies addressing a clinical question and the result of a large clinical trial (LCT) addressing the same clinical question. We recommend basing conclusions about agreement upon the difference between the two results (relative risk, log-odds ratio or similar summary statistic), in the light of the estimated standard error of that difference. To estimate the standard error of the meta-analytic result we recommend a random effects analysis, and where a between-studies variance component is found, that component of variance should be used twice: once in the estimated standard error for the meta-analytic result and again in the standard error of the LCT result (augmenting the internal standard error of that statistic). Such broadening of the standard error reduces the appearance of disagreement. We also offer a critique of a different published approach, which is based on consistency of findings of statistical significance, a matter of how the two results regard zero, which is a poor measure of how closely they agree with each other. more...

This is a method of comparing the size of observations in two groups by ranking all the observations and comparing the average ranks of the two groups. The distribution theory is described. The test has high efficiency for the comparison of two normal distributions with the same variance, and is much better than the t test for some nonnormal distributions. Topics discussed include adjustment for tied data and the calculation of confidence limits for a difference in translation between the two distributions. Keywords: rank; ARE ; tied data; two-sample t test more...

Weekly reports of the abundance of the Argentine ant, Linepithema humile, in 69 households for 18 mo (1/98–7/99) in the San Francisco Bay Area in northern California were compared with weather data. Ant abundance inside homes was highest in cold rainy weather, and there was a second smaller peak of ant abundance in hot dry weather. Pesticide use in the home decreased ant abundance, from one week to the next, only when ant abundance was extremely high. more...

A method is described for freezing thin strips of smooth muscle by replacing physiological saline in the muscle chamber with cold organic solvent in100 ms. Calculations suggest that, with a perfectly stirred boundary at the tissue surface, freezing could occur within approximately 15 ms at the center of a 200-microm-thick piece of tissue by use of acetone coolant at -78.5 degrees C and in approximately half the time with either isopentane at its freezing point (-160 degrees C) or aluminum chilled with liquid nitrogen. Myosin light chain phosphorylation in muscles frozen with cold acetone began to rise approximately 200 ms earlier than force and increased at a much more rapid rate. The difference in onsets of the two processes reflects the delay in arresting phosphorylation plus two lags associated with force generation, attachment of phosphorylated bridges followed by force generating movements of the attached bridges. The much more rapid rise of phosphorylation, once it began, suggests that most of this delay is due to physiological lags and not to slow arrest of metabolism. more...

To better understand excitation-contraction coupling in smooth muscle, myosin phosphorylation and force-velocity properties of canine tracheal muscle were compared during the rise and early plateau of force in electrically stimulated tetani. Velocity reached a peak of approximately 1.5 times plateau value when force had risen to approximately 45% of its maximum value and then declined progressively. Except early in the tetanus, when phosphorylation rose rapidly, maximum power and phosphorylation had nearly parallel time courses, reaching peaks of 1.2-1.3 times reference at 6-8 s before declining to the plateau level at approximately 12 s. Force, velocity, maximum power, and phosphorylation fell somewhat during the plateau, with the closest correlation between phosphorylation and power. These results suggest that 1) early velocity slowing is not associated with light chain dephosphorylation and 2) maximum power, which we use to signal changes in activation, is closely correlated with the degree of light chain phosphorylation, at least when phosphorylation level is not changing rapidly. Dissociation of these two properties would be expected early in the tetanus if phosphorylation precedes mechanical activity. more...

Force-velocity curves measured at different times during tetani of sheep trachealis muscle were analyzed to assess whether velocity slowing could be explained by thick-filament lengthening. Such lengthening increases force by placing more cross bridges in parallel on longer filaments and decreases velocity by reducing the number of filaments spanning muscle length. From 2 s after the onset of stimulation, when force had achieved 42% of it final value, to 28 s, when force had been at its tetanic plateau for ∼15 s, velocity decreases were exactly matched by force increases when force was adjusted for changes in activation, as assessed from the maximum power value in the force-velocity curves. A twofold change in velocity could be quantitatively explained by a series-to-parallel change in the filament lattice without any need to postulate a change in cross-bridge cycling rate. more...

A force transducer with variable sensitivity and speed is described. Its moving element is a cantilever beam that projects vertically into a muscle bath. A brace constrains bending of the beam to a short, proximal “hinge.” Rotation of the beam about the hinge is amplified 30-fold by an optical lever consisting of a laser diode beam reflected from a mirror on the cantilever to a photodiode pair. This design places the electrical components at a distance from the damp environment of the muscle bath. Large changes in sensitivity and speed can be obtained by substituting different cantilevers. Smaller changes can be made by varying the length of the hinge. A transducer with a 6-mm cantilever optimized for the study of single, skinned skeletal muscle fibers is described in detail. This device had a resonant frequency of 22 kHz and sensitivity such that the total root-mean-square noise in the circuit was more than 500-fold smaller than the expected maximum force. Variations of this device with orders of magnitude different sensitivities are also described. more...

The outpatient treatment of heart failure can be divided into 2 broad categories: older therapies, which improve hemodynamics, and newer therapies, which increase survival and improve function. Hemodynamic "triple" therapy includes digoxin to increase cardiac inotropy, antihypertensives to lower systolic pressure, and diuretics to remove fluid and decrease filling pressures. Disease-modifying therapy requires the use of specific agents to lower blood pressure (angiotensin-converting enzyme inhibitors, angiotensin II blockers, spironolactone, or hydralazine and nitrates) and beta-adrenergic blockade with carvedilol. The success of these newer therapies suggests that the standard triple therapy for heart failure should be expanded to "quadruple" therapy that includes carvedilol. more...