University of Richmond

An increasing number of new venture firms are internationalizing their business operations early in their life cycles. Previous explanations of this trend have focused on the importance of technological knowledge, skills, and resources for new ventures' international expansion. However, little is known about how these firms use the technological learning gained through internationalization. This study examined the effects of international expansion, as measured by international diversity and mode of market entry, on a firm's technological learning and the effects of this learning on the firm's financial performance.

For the last 30 years a growing number of scholars and practitioners have been experimenting with concepts and models that facilitate our understanding of the complexities of today’s business challenges. Among these, “stakeholder theory” or “stakeholder thinking” has emerged as a new narrative to understand and remedy three interconnected business problems—the problem of understanding how value is created and traded, the problem of connecting ethics and capitalism, and the problem of helping managers think about management such that the first two problems are addressed. In this article, we review the major uses and adaptations of stakeholder theory across a broad array of disciplines such as business ethics, corporate strategy, finance, accounting, management, and marketing. We also evaluate and suggest future directions in which research on stakeholder theory can continue to provide useful insights into the practice of sustainable and ethical value creation.

In 1984, R. Edward Freeman published his landmark book, Strategic Management: A Stakeholder Approach, a work that set the agenda for what we now call stakeholder theory. In the intervening years, the literature on stakeholder theory has become vast and diverse. This book examines this body of research and assesses its relevance for our understanding of modern business. Beginning with a discussion of the origins and development of stakeholder theory, it shows how this corpus of theory has influenced a variety of different fields, including strategic management, finance, accounting, management, marketing, law, health care, public policy, and environment. It also features in-depth discussions of two important areas that stakeholder theory has helped to shape and define: business ethics and corporate social responsibility. The book concludes by arguing that we should re-frame capitalism in the terms of stakeholder theory so that we come to see business as creating value for stakeholders.

Abstract The evidentiary basis of the currently accepted classification of living amphibians is discussed and shown not to warrant the degree of authority conferred on it by use and tradition. A new taxonomy of living amphibians is proposed to correct the deficiencies of the old one. This new taxonomy is based on the largest phylogenetic analysis of living Amphibia so far accomplished. We combined the comparative anatomical character evidence of Haas (2003) with DNA sequences from the mitochondrial transcription unit H1 (12S and 16S ribosomal RNA and tRNAValine genes, ≈ 2,400 bp of mitochondrial sequences) and the nuclear genes histone H3, rhodopsin, tyrosinase, and seven in absentia, and the large ribosomal subunit 28S (≈ 2,300 bp of nuclear sequences; ca. 1.8 million base pairs; x̄ = 3.7 kb/terminal). The dataset includes 532 terminals sampled from 522 species representative of the global diversity of amphibians as well as seven of the closest living relatives of amphibians for outgroup comparisons. The primary purpose of our taxon sampling strategy was to provide strong tests of the monophyly of all “family-group” taxa. All currently recognized nominal families and subfamilies were sampled, with the exception of Protohynobiinae (Hynobiidae). Many of the currently recognized genera were also sampled. Although we discuss the monophyly of genera, and provide remedies for nonmonophyly where possible, we also make recommendations for future research. A parsimony analysis was performed under Direct Optimization, which simultaneously optimizes nucleotide homology (alignment) and tree costs, using the same set of assumptions throughout the analysis. Multiple search algorithms were run in the program POY over a period of seven months of computing time on the AMNH Parallel Computing Cluster. Results demonstrate that the following major taxonomic groups, as currently recognized, are nonmonophyletic: Ichthyophiidae (paraphyletic with respect to Uraeotyphlidae), Caeciliidae (paraphyletic with respect to Typhlonectidae and Scolecomorphidae), Salamandroidea (paraphyletic with respect to Sirenidae), Leiopelmatanura (paraphyletic with respect to Ascaphidae), Discoglossanura (paraphyletic with respect to Bombinatoridae), Mesobatrachia (paraphyletic with respect to Neobatrachia), Pipanura (paraphyletic with respect to Bombinatoridae and Discoglossidae/Alytidae), Hyloidea (in the sense of containing Heleophrynidae; paraphyletic with respect to Ranoidea), Leptodactylidae (polyphyletic, with Batrachophrynidae forming the sister taxon of Myobatrachidae + Limnodynastidae, and broadly paraphyletic with respect to Hemiphractinae, Rhinodermatidae, Hylidae, Allophrynidae, Centrolenidae, Brachycephalidae, Dendrobatidae, and Bufonidae), Microhylidae (polyphyletic, with Brevicipitinae being the sister taxon of Hemisotidae), Microhylinae (poly/paraphyletic with respect to the remaining non-brevicipitine microhylids), Hyperoliidae (para/polyphyletic, with Leptopelinae forming the sister taxon of Arthroleptidae + Astylosternidae), Astylosternidae (paraphyletic with respect to Arthroleptinae), Ranidae (paraphyletic with respect to Rhacophoridae and Mantellidae). In addition, many subsidiary taxa are demonstrated to be nonmonophyletic, such as (1) Eleutherodactylus with respect to Brachycephalus; (2) Rana (sensu Dubois, 1992), which is polyphyletic, with various elements falling far from each other on the tree; and (3) Bufo, with respect to several nominal bufonid genera. A new taxonomy of living amphibians is proposed, and the evidence for this is presented to promote further investigation and data acquisition bearing on the evolutionary history of amphibians. The taxonomy provided is consistent with the International Code of Zoological Nomenclature (ICZN, 1999). Salient features of the new taxonomy are (1) the three major groups of living amphibians, caecilians/Gymnophiona, salamanders/Caudata, and frogs/Anura, form a monophyletic group, to which we restrict the name Amphibia; (2) Gymnophiona forms the sister taxon of Batrachia (salamanders + frogs) and is composed of two groups, Rhinatrematidae and Stegokrotaphia; (3) Stegokrotaphia is composed of two families, Ichthyophiidae (including Uraeotyphlidae) and Caeciliidae (including Scolecomorphidae and Typhlonectidae, which are regarded as subfamilies); (4) Batrachia is a highly corroborated monophyletic group, composed of two taxa, Caudata (salamanders) and Anura (frogs); (5) Caudata is composed of two taxa, Cryptobranchoidei (Cryptobranchidae and Hynobiidae) and Diadectosalamandroidei new taxon (all other salamanders); (6) Diadectosalamandroidei is composed of two taxa, Hydatinosalamandroidei new taxon (composed of Perennibranchia and Treptobranchia new taxon) and Plethosalamandroidei new taxon; (7) Perennibranchia is composed of Proteidae and Sirenidae; (8) Treptobranchia new taxon is composed of two taxa, Ambystomatidae (including Dicamptodontidae) and Salamandridae; (9) Plethosalamandroidei new taxon is composed of Rhyacotritonidae and Xenosalamandroidei new taxon; (10) Xenosalamandroidei is composed of Plethodontidae and Amphiumidae; (11) Anura is monophyletic and composed of two clades, Leiopelmatidae (including Ascaphidae) and Lalagobatrachia new taxon (all other frogs); (12) Lalagobatrachia is composed of two clades, Xenoanura (Pipidae and Rhinophrynidae) and Sokolanura new taxon (all other lalagobatrachians); (13) Bombinatoridae and Alytidae (former Discoglossidae) are each others' closest relatives and in a clade called Costata, which, excluding Leiopelmatidae and Xenoanura, forms the sister taxon of all other frogs, Acosmanura; (14) Acosmanura is composed of two clades, Anomocoela (= Pelobatoidea of other authors) and Neobatrachia; (15) Anomocoela contains Pelobatoidea (Pelobatidae and Megophryidae) and Pelodytoidea (Pelodytidae and Scaphiopodidae), and forms the sister taxon of Neobatrachia, together forming Acosmanura; (16) Neobatrachia is composed of two clades, Heleophrynidae, and all other neobatrachians, Phthanobatrachia new taxon; (17) Phthanobatrachia is composed of two major units, Hyloides and Ranoides; (18) Hyloides comprises Sooglossidae (including Nasikabatrachidae) and Notogaeanura new taxon (the remaining hyloids); (19) Notogaeanura contains two taxa, Australobatrachia new taxon and Nobleobatrachia new taxon; (20) Australobatrachia is a clade composed of Batrachophrynidae and its sister taxon, Myobatrachoidea (Myobatrachidae and Limnodynastidae), which forms the sister taxon of all other hyloids, excluding sooglossids; (21) Nobleobatrachia new taxon, is dominated at its base by frogs of a treefrog morphotype, several with intercalary phalangeal cartilages—Hemiphractus (Hemiphractidae) forms the sister taxon of the remaining members of this group, here termed Meridianura new taxon; (22) Meridianura comprises Brachycephalidae (former Eleutherodactylinae + Brachycephalus) and Cladophrynia new taxon; (23) Cladophrynia is composed of two groups, Cryptobatrachidae (composed of Cryptobatrachus and Stefania, previously a fragment of the polyphyletic Hemiphractinae) and Tinctanura new taxon; (24) Tinctanura is composed of Amphignathodontidae (Gastrotheca and Flectonotus, another fragment of the polyphyletic Hemiphractinae) and Athesphatanura new taxon; (25) Athesphatanura is composed of Hylidae (Hylinae, Pelodryadinae, and Phyllomedusinae, and excluding former Hemiphractinae, whose inclusion would have rendered this taxon polyphyletic) and Leptodactyliformes new taxon; (26) Leptodactyliformes is composed of Diphyabatrachia new taxon (composed of Centrolenidae [including Allophryne] and Leptodactylidae, sensu stricto, including Leptodactylus and relatives) and Chthonobatrachia new taxon; (27) Chthonobatrachia is composed of a reformulated Ceratophryidae (which excludes such genera as Odontophrynus and Proceratophrys and includes other taxa, such as Telmatobius) and Hesticobatrachia new taxon; (28) Hesticobatrachia is composed of a reformulated Cycloramphidae (which includes Rhinoderma) and Agastorophrynia new taxon; (29) Agastorophrynia is composed of Bufonidae (which is partially revised) and Dendrobatoidea (Dendrobatidae and Thoropidae); (30) Ranoides new taxon forms the sister taxon of Hyloides and is composed of two major monophyletic components, Allodapanura new taxon (microhylids, hyperoliids, and allies) and Natatanura new taxon (ranids and allies); (31) Allodapanura is composed of Microhylidae (which is partially revised) and Afrobatrachia new taxon; (32) Afrobatrachia is composed of Xenosyneunitanura new taxon (the “strange-bedfellows” Brevicipitidae [formerly in Microhylidae] and Hemisotidae) and a more normal-looking group of frogs, Laurentobatrachia new taxon (Hyperoliidae and Arthroleptidae, which includes Leptopelinae and former Astylosternidae); (33) Natatanura new taxon is composed of two taxa, the African Ptychadenidae and the worldwide Victoranura new taxon; (34) Victoranura is composed of Ceratobatrachidae and Telmatobatrachia new taxon; (35) Telmatobatrachia is composed of Micrixalidae and a worldwide group of ranoids, Ametrobatrachia new taxon; (36) Ametrobatrachia is composed of Africanura new taxon and Saukrobatrachia new taxon; (37) Africanura is composed of two taxa: Phrynobatrachidae (Phrynobatrachus, including Dimorphognathus and Phrynodon as synonyms) and Pyxicephaloidea; (38) Pyxicephaloidea is composed of Petropedetidae (Conraua, Indirana, Arthroleptides, and Petropedetes), and Pyxicephalidae (including a number of African genera, e.g. Amietia [including Afrana], Arthroleptella, Pyxicephalus, Strongylopus, and Tomopterna); and (39) Saukrobatrachia new taxon is the sister taxon of Africanura and is composed of Dicroglossidae and Aglaioanura new taxon, which is, in turn, composed of Rhacophoroidea (Mantellidae and Rhacophoridae) and Ranoidea (Nyctibatrachidae and Ranidae, sensu stricto). Many generic revisions are made either to render a monophyle

Strategic entrepreneurship (SE) involves simultaneous opportunity-seeking and advantage-seeking behaviors and results in superior firm performance. On a relative basis, small, entrepreneurial ventures are effective in identifying opportunities but are less successful in developing competitive advantages needed to appropriate value from those opportunities. In contrast, large, established firms often are relatively more effective in establishing competitive advantages but are less able to identify new opportunities. We argue that SE is a unique, distinctive construct through which firms are able to create wealth. An entrepreneurial mindset, an entrepreneurial culture and entrepreneurial leadership, the strategic management of resources and applying creativity to develop innovations are important dimensions of SE. Herein we develop a model of SE that explains how these dimensions are integrated to create wealth.

Abstract Entrepreneurship involves identifying and exploiting entrepreneurial opportunities. However, to create the most value entrepreneurial firms also need to act strategically. This calls for an integration of entrepreneurial and strategic thinking. We explore this strategic entrepreneurship in several important organizational domains to include external networks and alliances, resources and organizational learning, innovation and internationalization. The research in this special issue examines both traditional (e.g., contingency theory, strategic fit) and new theory (e.g., cultural entrepreneurship, business model drivers). The research also integrates, extends, and tests theory and research from entrepreneurship and strategic management in new ways such as creative destruction (discontinuities), resource‐based view, organizational learning, network theory, transaction costs and institutional theory. The research presented herein provides a basis for future research on strategic entrepreneurship for wealth creation. Copyright © 2001 John Wiley & Sons, Ltd.

Strategic alliances are an important source of resources, learning, and thereby competitive advantage. Few firms have all of the resources needed to compete effectively in the current dynamic landscape. Thus, firms seek access to the necessary resources through alliances. We examine the management of strategic alliances using the theoretical frames of transactions cost, social network theory and the resource-based view. Alliances must be effectively managed for their benefits to be realized. Effective alliance management begins with selecting the right partner. Furthermore, alliances must be managed to build social capital and knowledge. To maximize cooperation among the partners, a trust-based relationship must be developed. Therefore, we conclude that managing alliances is crucial for firms to gain competitive advantage and create value with strategic alliances.

Psychology can be distinguished from other behavioral sciences by its emphasis on the behavior of the individual person. Behavior, in turn, is influenced by the way in which the external world is represented in the mind, and by the individual's exercise of choice. The article examines the possibility that relatively enduring attributes of the person might affect entrepreneurial activity, describes the social cognitive processes Involved in constructing representations of the external environment, and suggests which motivational variables affect behavioral choices. Although past research on “the psychology of the entrepreneur” has not been productive, a psychological approach based on persons, process, and choice holds promise for the future.

This review builds on self-control theory (Carver & Scheier, 1998) to develop a theoretical framework for investigating associations of implicit theories with self-regulation. This framework conceptualizes self-regulation in terms of 3 crucial processes: goal setting, goal operating, and goal monitoring. In this meta-analysis, we included articles that reported a quantifiable assessment of implicit theories and at least 1 self-regulatory process or outcome. With a random effects approach used, meta-analytic results (total unique N = 28,217; k = 113) across diverse achievement domains (68% academic) and populations (age range = 5-42; 10 different nationalities; 58% from United States; 44% female) demonstrated that implicit theories predict distinct self-regulatory processes, which, in turn, predict goal achievement. Incremental theories, which, in contrast to entity theories, are characterized by the belief that human attributes are malleable rather than fixed, significantly predicted goal setting (performance goals, r = -.151; learning goals, r = .187), goal operating (helpless-oriented strategies, r = -.238; mastery-oriented strategies, r = .227), and goal monitoring (negative emotions, r = -.233; expectations, r = .157). The effects for goal setting and goal operating were stronger in the presence (vs. absence) of ego threats such as failure feedback. Discussion emphasizes how the present theoretical analysis merges an implicit theory perspective with self-control theory to advance scholarship and unlock major new directions for basic and applied research.

Two-dimensional sociometric models have had a critical role in the investigation of children's peer relations in the past decade. In a meta-analysis, fitting categorical models (Hedges, 1982), sociometric group differences on behavioral and information source typologies were assessed. The broad-band behavioral analysis showed that popular children's array of competencies makes them likely recipients of positive peer nominations, whereas high levels of aggression and withdrawal and low levels of sociability and cognitive abilities are associated with rejected peer status. A consistent profile marked by less sociability and aggression emerged for neglected status. Controversial children had higher aggressive behavior than rejected children but compensated for it with significantly better cognitive and social abilities. The moderator effects of narrow-band behavioral categories and information source were also examined.

BACKGROUND AND METHODS: Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled. RESULTS: Three hundred eighty-four patients had a verified diagnosis of overt generalized convulsive status epilepticus. In this group, lorazepam was successful in 64.9 percent of those assigned to receive it, phenobarbital in 58.2 percent, diazepam plus phenytoin in 55.8 percent, and phenytoin in 43.6 percent (P=0.02 for the overall comparison among the four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verified diagnosis of subtle generalized convulsive status epilepticus, no significant differences among the treatments were detected (range of success rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, the differences among treatment groups were not significant, either among the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences among the treatments with respect to recurrence during the 12-hour study period, the incidence of adverse reactions, or the outcome at 30 days. CONCLUSIONS: As initial intravenous treatment for overt generalized convulsive status epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbital or diazepam plus phenytoin, it is easier to use.

We reviewed studies of the Dark Triad (DT) personality traits--Machiavellianism, narcissism, and psychopathy-and meta-analytically examined their implications for job performance and counterproductive work behavior (CWB). Relations among the DT traits and behaviors were extracted from original reports published between 1951 and 2011 of 245 independent samples (N = 43,907). We found that reductions in the quality of job performance were consistently associated with increases in Machiavellianism and psychopathy and that CWB was associated with increases in all 3 components of the DT, but that these associations were moderated by such contextual factors as authority and culture. Multivariate analyses demonstrated that the DT explains moderate amounts of the variance in counterproductivity, but not job performance. The results showed that the 3 traits are positively related to one another but are sufficiently distinctive to warrant theoretical and empirical partitioning.

Abstract This meta‐analysis builds upon a previous meta‐analysis by (1) including 65 per cent more studies that have over twice the sample size to estimate the relationships between emotional intelligence (EI) and job performance; (2) using more current meta‐analytical studies for estimates of relationships among personality variables and for cognitive ability and job performance; (3) using the three‐stream approach for classifying EI research; (4) performing tests for differences among streams of EI research and their relationships with personality and cognitive intelligence; (5) using latest statistical procedures such as dominance analysis; and (6) testing for publication bias. We classified EI studies into three streams: (1) ability‐based models that use objective test items; (2) self‐report or peer‐report measures based on the four‐branch model of EI; and (3) “mixed models” of emotional competencies. The three streams have corrected correlations ranging from 0.24 to 0.30 with job performance. The three streams correlated differently with cognitive ability and with neuroticism, extraversion, openness, agreeableness, and conscientiousness. Streams 2 and 3 have the largest incremental validity beyond cognitive ability and the Five Factor Model (FFM). Dominance analysis demonstrated that all three streams of EI exhibited substantial relative importance in the presence of FFM and intelligence when predicting job performance. Publication bias had negligible influence on observed effect sizes. The results support the overall validity of EI. Copyright © 2010 John Wiley & Sons, Ltd. Note: Correction added on 22 July 2010 after first publication online on 29 June 2010. The affiliations for Ronald H. Humphrey and Thomas H. Hawver have been corrected in this version of the article.

ABSTRACT: This paper argues that the notion of value has been overly simplified and narrowed to focus on economic returns. Stakeholder theory provides an appropriate lens for considering a more complex perspective of the value that stakeholders seek as well as new ways to measure it. We develop a four-factor perspective for defining value that includes, but extends beyond, the economic value stakeholders seek. To highlight its distinctiveness, we compare this perspective to three other popular performance perspectives. Recommendations are made regarding performance measurement for both academic researchers and practitioners. The stakeholder perspective on value offered in this paper draws attention to those factors that are most closely associated with building more value for stakeholders, and in so doing, allows academics to better measure it and enhances managerial ability to create it.

We present a range of coding schemes for OFDM transmission using binary, quaternary, octary, and higher order modulation that give high code rates for moderate numbers of carriers. These schemes have tightly bounded peak-to-mean envelope power ratio (PMEPR) and simultaneously have good error correction capability. The key theoretical result is a previously unrecognized connection between Golay complementary sequences and second-order Reed-Muller codes over alphabets Z/sub 2/h. We obtain additional flexibility in trading off code rate, PMEPR, and error correction capability by partitioning the second-order Reed-Muller code into cosets such that codewords with large values of PMEPR are isolated. For all the proposed schemes we show that encoding is straightforward and give an efficient decoding algorithm involving multiple fast Hadamard transforms. Since the coding schemes are all based on the same formal generator matrix we can deal adaptively with varying channel constraints and evolving system requirements.

In this article, we present ppmlhdfe, a new command for estimation of (pseudo-)Poisson regression models with multiple high-dimensional fixed effects (HDFE). Estimation is implemented using a modified version of the iteratively reweighted least-squares algorithm that allows for fast estimation in the presence of HDFE. Because the code is built around the reghdfe package ( Correia, 2014 , Statistical Software Components S457874, Department of Economics, Boston College), it has similar syntax, supports many of the same functionalities, and benefits from reghdfe‘s fast convergence properties for computing high-dimensional leastsquares problems. Performance is further enhanced by some new techniques we introduce for accelerating HDFE iteratively reweighted least-squares estimation specifically. ppmlhdfe also implements a novel and more robust approach to check for the existence of (pseudo)maximum likelihood estimates.

Recently, the SEC has called for research regarding the relationship between audit tenure and audit failures. In this study, we address this issue by examining prior audit reports for a sample of companies entering into bankruptcy during the period 1996–1998. We use a multivariate analysis to test for the association between the type of audit opinion issued on the financial statements immediately prior to bankruptcy and the length of auditor tenure. Our results indicate that there were significantly more audit reporting failures in the earlier years of the auditor/client relationship than when auditors had served these clients for longer tenures. The results do not support the arguments of those who propose mandatory auditor rotation and suggest that, contrary to the concerns expressed by the SEC, there is an inverse relationship between auditor tenure and audit reporting failures.

Organizations are combining resources through acquisitions and alliances in record numbers. Since publication of our original study in 1991, research has confirmed that resource complementarity creates the potential for greater synergy from acquisitions and alliances, leading to higher long-term firm performance as an end result. The valuable, unique, and inimitable synergy that can be realized by integrating complementary resources provides an opportunity for the firm to create competitive advantages that can be sustained for a period of time. In addition, complementary resources present opportunities for enhanced learning as well as the development of new capabilities. However, we also suggest that the existence of complementary resources is a necessary but insufficient condition to achieve synergy. The resources must be effectively integrated and managed to realize the synergy.

The intracellular sensing protein termed NLRP3 (for NACHT, LRR, and PYD domains-containing protein 3) forms a macromolecular structure called the NLRP3 inflammasome. The NLRP3 inflammasome plays a major role in inflammation, particularly in the production of IL (interleukin)-1β. IL-1β is the most studied of the IL-1 family of cytokines, including 11 members, among which are IL-1α and IL-18. Here, we summarize preclinical and clinical findings supporting the key pathogenetic role of the NLRP3 inflammasome and IL-1 cytokines in the formation, progression, and complications of atherosclerosis, in ischemic (acute myocardial infarction), and nonischemic injury to the myocardium (myocarditis) and the progression to heart failure. We also review the clinically available IL-1 inhibitors, although not currently approved for cardiovascular indications, and discuss other IL-1 inhibitors, not currently approved, as well as oral NLRP3 inflammasome inhibitors currently in clinical development. Canakinumab, IL-1β antibody, prevented the recurrence of ischemic events in patients with prior acute myocardial infarction in a large phase III clinical trial, including 10 061 patients world-wide. Phase II clinical trials show promising data with anakinra, recombinant IL-1 receptor antagonist, in patients with ST-segment-elevation acute myocardial infarction or heart failure with reduced ejection fraction. Anakinra also improved outcomes in patients with pericarditis, and it is now considered standard of care as second-line treatment for patients with recurrent/refractory pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing IL-1α and IL-1β, has also shown promising results in a phase II study in recurrent/refractory pericarditis. In conclusion, there is overwhelming evidence linking the NLRP3 inflammasome and the IL-1 cytokines with the pathogenesis of cardiovascular diseases. The future will likely include targeted inhibitors to block the IL-1 isoforms, and possibly oral NLRP3 inflammasome inhibitors, across a wide spectrum of cardiovascular diseases.

The results contained herein pertain to the problem of determining the equilibrium distribution of customers in closed queuing systems composed of M interconnected stages of service. The number of customers, N, in a closed queuing system is fixed since customers pass repeatedly through the M stages with neither entrances nor exits permitted. At the ith stage there are r i parallel exponential servers all of which have the same mean service rate μ i . When service is completed at stage i, a customer proceeds directly to stage j with probability p ıj . Such closed systems are shown to be stochastically equivalent to open systems in which the number of customers cannot exceed N. The equilibrium equations for the joint probability distribution of customers are solved by a separation of variables technique. In the limit of N → ∞ it is found that the distribution of customers in the system is regulated by the stage (or stages) with the slowest effective service rate. Asymptotic expressions are given for the marginal distributions of customers in such systems. Then, an asymptotic analysis is carried out for systems with a large number of stages (i.e., M ≫ 1) all of which have comparable effective service rates. Approximate expressions are obtained for the marginal probability distributions. The details of the analysis are illustrated by an example.