ACMS: The Akamai Configuration Management System

increasingly large distributed systems to deploy increasingly complex and mission-critical applications. In order for these systems to achieve the ultimate goal of having similar easeof-use properties as centralized systems they must allow fast, reliable, and lightweight management and synchronization of their configuration state. This goal poses numerous technical challenges in a truly Internet-scale system, including varying degrees of network connectivity, inevitable machine failures, and the need to distribute information globally in a fast and reliable fashion. In this paper we discuss the design and implementation of a configuration management system for the Akamai Network. It allows reliable yet highly asynchronous delivery of configuration information, is significantly fault-tolerant, and can scale if necessary to hundreds of thousands of servers. The system is fully functional today providing configuration management to over 15,000 servers deployed in 1200+ different networks in 60+ countries.

The evaluation and treatment of nocturia: a consensus statement

What's known on the subject? and What does the study add? Nocturia is currently defined by the International Continence Society (ICS) as the complaint that an individual has to wake at night one or more times to void. It is, however, an underreported, understudied, and infrequently recognized problem in adults. Many factors may contribute to nocturia which are treatable, yet patients do not seek care or the condition may not be identified by providers. This paper aims to help healthcare providers better serve patients who are experiencing nocturia by summarizing current research, clinical approaches, and treatment options. The results of the conference provide a balanced evaluation of the full treatment armamentarium capable of meeting the needs of patients with the manifold causes of nocturia such as nocturnal polyuria, overactive bladder, or benign prostatic hyperplasia

Nocturia think tank: Focus on nocturnal polyuria: ICI-RS 2011

The following is a report of the proceedings of the Nocturia Think Tank sessions of the annual International Consultation on Incontinence-Research Society, which took place June 1315, 2011 in Bristol, UK. The report is organized into sections pertaining to the main topics of discussions having occurred at that meeting, centering on the relationship of nocturnal polyuria (NP) and nocturia but also synthesizing more current evidence advancing our knowledge of the diagnosis and management of nocturia. This article is not meant to be a comprehensive review on the subject of nocturia, a number of which are available in the recent literature. All authors were physically present during, or in a preliminary session just prior to, the meeting in Bristol. Neurourol. Urodynam. 31:330339, 2012

Purinoceptors as therapeutic targets for lower urinary tract dysfunction

Lower urinary tract symptoms (LUTS) are present in many common urological syndromes. However, their current suboptimal management by muscarinic and α(1)-adrenoceptor antagonists leaves a significant opportunity for the discovery and development of superior medicines. As potential targets for such therapeutics, purinoceptors have emerged over the last two decades from investigations that have established a prominent role for ATP in the regulation of urinary bladder function under normal and pathophysiological conditions. In particular, evidence suggests that ATP signaling via P2X(1) receptors participates in the efferent control of detrusor smooth muscle excitability, and that this function may be heightened in disease and aging. ATP also appears to be involved in bladder sensation, via activation of P2X(3) and P2X(2/3) receptors on sensory afferent neurons, both within the bladder itself and possibly at central synapses. Such findings are based on results from classical pharmacological and localization studies in non-human and human tissues, knockout mice, and studies using recently identified pharmacological antagonists – some of which possess attributes that offer the potential for optimization into candidate drug molecules. Based on recent advances in this field, it is clearly possible that the development of selective antagonists for these receptors will occur that could lead to therapies offering better relief of sensory and motor symptoms for patients, while minimizing the systemic side effects that limit current medicines