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Purpose The water drinking test (WDT) is currently used to temporarily elevate intraocular pressure (IOP) and predict peak IOP in glaucoma. This study investigates neurovascular changes associated with WDT in normal subjects. Methods The effect of WDT (1 L in 5 min) on IOP, mean brachial blood pressure, heart rate, and pattern electroretinogram was assessed within the next hour in 16 healthy subjects (mean age: 33.5±7.9 y). As a control, testing was repeated in the same subjects without WDT 1 week later. Results Compared with control, WDT resulted in significant peak changes of the following parameters compared with baseline: IOP: +1.7±1.8 mm Hg after 30', mean brachial blood pressure: +3.9±6.3 mm Hg after 15'; heart rate: -9.2±9.8 bpm after 15', pattern electroretinogram latency: +2.1±0.9 ms after 15'. Conclusions In addition to IOP elevation, WDT was associated with significant changes of hemodynamic parameters and retinal ganglion cell function in young healthy subjects. As these represent risk factors for glaucoma, their assessment upon WDT might increase its predictive power for glaucoma development.

Background This study assessed the effect of blockading neural transmission in the ganglionated plexi by injecting lidocaine into fat pads in the vagal nerve stimulation canine model and patients with persistent atrial fibrillation (AF). Methods and Results An efficacy test of lidocaine injection was performed in 7 canines. During vagal nerve stimulation, AF was sustained for >5 minutes. The lidocaine was injected into ganglionated plexi during sinus rhythm and reinduction of AF was attempted. Six patients with persistent AF were studied at open heart surgery. Lidocaine was injected into ganglionated plexi. Atrial electrograms were recorded from 96 epicardial electrodes covering Bachmann's bundle and atrial appendages. In the canine vagal nerve stimulation AF model, AF was not inducible in 4 of 7 after lidocaine injection. In patients with persistent AF, during baseline AF, there was a left atrium (LA)‐to‐right atrium (RA) frequency gradient (LA, mean cycle length [CL] 175±17 ms; RA, mean CL 192±17 ms; P, See Editorial Hanna et al

Context Salivary gland hypofunction may affect the absorption of drugs through the oral mucosa, which in turn may affect their clinical efficacy (e.g., onset of action). Objectives The aim of this study was to assess the pharmacokinetics of a sublingual fentanyl orally disintegrating tablet (Abstral ® , Prostrakan Inc.) in a group of cancer patients with salivary gland hypofunction. Methods Nine cancer patients with salivary gland hypofunction underwent a series of three pharmacokinetic studies with the sublingual fentanyl orally disintegrating tablet. In the first phase, the patients received no pretreatment; in the second phase, the patients were allowed to moisten the oral cavity before dosing; in the third phase, the patients were given pilocarpine hydrochloride (saliva stimulant) before dosing. Fentanyl concentrations were measured using a method of high-performance liquid chromatography with validated tandem mass spectrometric detection. Results The Tmax was longer, the Cmax was lower, the AUC0-30 lower, and the AUClast lower in the phase involving no pretreatment; the Tmax/Cmax/AUC0-30/AUClast were similar in the phase involving moistening of the oral cavity and the phase involving giving pilocarpine hydrochloride. Conclusion The pharmacokinetics of the sublingual fentanyl orally disintegrating tablet appear to be negatively affected by the presence of salivary gland hypofunction, although the moistening of the oral cavity before dosing results in a pharmacokinetic profile similar to that seen with the giving of pilocarpine hydrochloride.

Objectives There is a limited understanding of paediatric medication prescribing trends and patterns, thus poorly positioning decision-makers to identify quality and safety concerns related to medication use. The objective of this study was to determine overall medication prescribing trends and patterns among children receiving Ontario Drug Benefits over a thirteen-year period in the province of Ontario, Canada. Methods Administrative health databases housed within the Institute for Clinical Evaluative Sciences (ICES), Ontario, Canada, were used to identify outpatient prescriptions dispensed from 1999 to 2012 through a publicly funded programme to children ≤18 years of age. Medications were classified according to the American Hospital Formulary Service Pharmacologic-Therapeutic Classification system. Descriptive statistics were used to summarize prescribing patterns. Key findings This study identified 457 037 children who were dispensed a new prescription between 1999 and 2012. About 56% received their first prescription before 6.5 years of age, and 85% of the children in this study were from families who received social assistance. The most commonly prescribed drugs were antiinfectives (56.1%). Prescriptions for several central nervous system agents, including antipsychotics and agents for attention-deficit/hyperactivity disorder, increased across the study period. Changes in prescribing patterns within opioids, hormones and autonomic agents were noted. The results suggest that historically, prescribing trends have shifted with public policy, pharmaceutical marketing and diagnostic patterns, thus identifying them as a possible tool to measure the impact of policydriven practice changes. Anti-infective prescribing increased markedly with the global H1N1 pandemic. Pharmaceutical marketing, formulary decisions and diagnostic trends may affect the prescribing of ADHD medications globally. The prescribing of codeine-containing products and medroxyprogesterone appeared to fluctuate in response to important publications in the medical literature, and the use of epinephrine syringes increased after public policy changes in the province of Ontario. The steady rise in the use of medications whose long-term effects in children are unknown, such as antipsychotics and proton pump inhibitors, identifies areas in need of future research. Conclusions This study presents the first overview of Canadian prescribing trends for children, the majority of which are of low socioeconomic status and represent a potentially vulnerable population. Our analysis suggests that future research is required to determine whether prescribing trends could be used as indicators of policy effectiveness, pharmacovigilance and diagnostic trends.

The effects and mechanisms of tastes on labial minor salivary gland (LMSG) secretion were investigated in 59 healthy individuals. Stimulation with each of the five basic tastes (i.e., sweet, salty, sour, bitter, and umami) onto the tongue induced LMSG secretion in a dose-dependent manner. Umami and sour tastes evoked greater secretion than did the other tastes. A synergistic effect of umami on LMSG secretion was recognized: a much greater increase in secretion was observed by a mixed solution of monosodium glutamate and inosine 5′-monophosphate than by each separate stimulation. Blood flow (BF) in the nearby labial mucosa also increased following stimulation by each taste except bitter. The BF change and LMSG secretion in each participant showed a significant positive correlation with all tastes, including bitter. Administration of cevimeline hydrochloride hydrate to the labial mucosa evoked a significant increase in both LMSG secretion and BF, while adrenaline, atropine, and pirenzepine decreased LMSG secretion and BF. The change in LMSG secretion and BF induced by each autonomic agent was significantly correlated in each participant. These results indicate that basic tastes can induce the gustatory-salivary reflex in human LMSGs and that parasympathetic regulation is involved in this mechanism.

Cloud computing offers services and utilizes a lot of resources that cannot be afforded by cloud clients due to its cost overhead, which resulted in them migrating their data to the cloud. With such migration, a lot of security challenges arises threatening their data. As data being remotely stored, modifications can be applied on it; by either the untrusted service provider or unauthorized users or even a malicious party. Clients need to verify that their data wasn’t tampered with while resting in the data centers. Over the years, many data integrity schemes have been proposed. This paper providers a qualitative analysis of those schemes. It also introduces Document Integrity Processor (DIP), which is a public auditability scheme that consists of two major autonomic agents that operates on document’s content to detect any changes in the document and so enhance the data integrity level. This scheme is the first to use QR codes as metadata; which decreases its size compared to the previous schemes. It also showed 100% alteration detection accuracy.

The feasibility of large-scale decentralized networks for local computations, as an alternative to big data systems that are often privacy-intrusive, expensive and serve exclusively corporate interests, is usually questioned by network dynamics such as node leaves, failures and rejoins in the network. This is especially the case when decentralized computations performed in a network, such as the estimation of aggregation functions, e.g. summation, are linked to the actual nodes connected in the network, for instance, counting the sum using input values from only connected nodes. Reverse computations are required to maintain a high aggregation accuracy when nodes leave or fail. This paper introduces an autonomic agent-based model for highly dynamic self-corrective networks using decentralized reverse computations. The model is generic and equips the nodes with the capability to disseminate connectivity status updates in the network. Highly resilient agents to the dynamic network migrate to remote nodes and orchestrate reverse computations for each node leave or failure. In contrast to related work, no other computational resources or redundancy are introduced. The self-corrective model is experimentally evaluated using real-world data from a smart grid pilot project under highly dynamic network adjustments that correspond to catastrophic events with up to 50% of the nodes leaving the network. The model is highly agile and modular and is applied to the large-scale decentralized aggregation network of DIAS, the Dynamic Intelligent Aggregation Service, without major structural changes in its design and operations. Results confirm the outstanding improvement in the aggregation accuracy when self-corrective actions are employed with a minimal increase in communication overhead.

Single centre, single ascending dose study. To compare the pharmacokinetics and assess the safety of capromorelin, a compound that has potential to treat constipation following spinal cord injury (SCI), in groups of able-bodied and SCI volunteers. Local population from Victoria, Australia. Following initial screening and baseline blood collections, participants received ascending oral doses (20, 50 and then 100 mg at least 1-week apart) of capromorelin after pre-dose blood collection, followed by blood collections over the following 12 h for pharmacokinetic analysis and 1-week and 4-week follow-up blood collections for safety evaluations. Blood pressure and heart rate were monitored. No serious adverse events were recorded following any dose in either the able-bodied group or the SCI group. There were no abnormal blood pressure or heart rate changes. Minor adverse events resolved quickly without the need for treatment. Pharmacokinetic behaviour was broadly similar between groups, with both exhibiting dose-dependent increases in Cmax and AUC0–∞. The SCI participants showed greater variance in pharmacokinetic parameters and had a slightly delayed Tmax and half-life. Capromorelin at the doses tested was safe and well tolerated in both SCI and able-bodied participants and also showed similar pharmacokinetics with dose-dependent increases in concentration and drug exposure. Support for the study was provided by the Victorian State Government Transport Accident Commission.

Objective: To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH). Methods: Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100–600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities. Results: From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units ( p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units ( p = 0.010), with maximum change in “dizziness/lightheadedness.” Improvement in symptom-impact subscore favored droxidopa by 1.06 units ( p = 0.003), with maximum change for “standing a long time.” Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg ( p p 180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events. Conclusions: In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated. Classification of evidence: This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days.

Multiagent Systems Engineering (MaSE) Methodology is one of old object-oriented methodology which supports the development process and is established based on the development of the object-oriented software engineering methods and their adjustment with the agent view. Some characteristics of the agent like autonomy, creativity and preactivated are not paid attention. The agents are supposed as simple software processes which cooperate to obtain a certain goal. There are two basic phases in MaSE: analysis and design. The analysis phase concentrates on specializing the agent’s roles, their duties and interactions. In design phase, matters such as diagrams and conversations class are introduced. The all steps in MaSE are implemented by graphic tools, agent Tool. This tool (agent Tool) covers all the steps of MaSE methodology design and analysis. In this article, we have covered the MaSE methodology based on a practical experience. The reason of choosing the chain store system is that it has the necessary characteristics like customer and seller autonomic agent technology and it is easier to identify and understand the analysis and design steps.

The IoT systems encounter more serious issues of security, reliability and availability. In this paper, we propose an autonomic agent trust model to decrease security concerns, increase reliability and credibility and ensure information collecting, sharing and processing in dynamic IoT environments. In order to build the credibility protection model for IoT systems, agents and agent platforms have to be built on all nodes. Agent-based node in IoT systems is independent, self-governing software and hardware integrated system. Introducing the agent technology to build systems could manage resources and regulate actions of node in order to maximize the benefit of the whole IoT system. Firstly, we analyze on the credibility of IoT systems and explain why IoT systems are difficult to achieve safe and reliable computing and service quality assurance mechanisms. Secondly, we provide the architecture of trustable agent and agency. After that, we propose a novel architecture named TAEC (Trustworthy Agent Execution Chip), which is to use the high-security, cost-effective software and hardware platform for the safe operation of Agent. The proposed approach is to install TAEC on each sensor node, which provides autonomic trusted hardware execution environment for agents.

The clinical picture of autonomic failure is characterized by severe and disabling orthostatic hypotension. These disorders can develop as a result of damage of central neural pathways or peripheral autonomic nerves, caused either by a primary autonomic neurodegenerative disorder or secondary to systemic illness. Treatment should be focused on decreasing pre-syncopal symptoms instead of achieving blood pressure goals. Non-pharmacologic strategies such as physical counter-maneuvers, dietary changes (i.e. high salt diet, rapid water drinking or compression garments) are the first line therapy. Affected patients should be screened for co-morbid conditions such as post-prandial hypotension and supine hypertension that can worsen orthostatic hypotension if not treated. If symptoms are not controlled with these conservative measures the next step is to start pharmacological agents; these interventions should be aimed at increasing intravascular volume either by promoting water and salt retention (fludrocortisone) or by increasing red blood cell mass when anemia is present (recombinant erythropoietin). When pressor agents are needed, direct pressor agents (midodrine) or agents that potentiate sympathetic activity (atomoxetine, yohimbine, pyridostigmine) can be used. It is preferable to use short-acting pressor agents that can be taken on as needed basis in preparation for upright activities.

We studied the effect of losartan on baroreflex sensitivity (BRS) and heart rate variability (HRV) of adult Wistar rats during acute and chronic inhibition of nitric oxide synthesis by NG-nitro-L-arginine methyl ester (L-NAME). Chronic L-NAME administration (50 mg/kg per day for 7 days, orally through gavage) increased mean arterial pressure (MAP), heart rate but significantly decreased BRS. In addition, a significant fall of standard deviation of normal RR intervals, total spectral power, high frequency spectral power and a rise of low frequency to high frequency (LF: HF) ratio was seen. Acute L-NAME administration (30 mg/kg, i.v. bolus dose) also raised MAP and impaired HRV but it was associated with augmented BRS for bradycardia reflex. Losartan treatment (10 mg/kg, i.v.) in both acute and chronic L-NAME treated rats, decreased MAP but the difference was not significant. On the other hand, losartan administration normalized depressed BRS for bradycardia reflex and significantly reduced LF to HF ratio in chronic L-NAME treated rats. But this improvement was not observed in acute L-NAME group. These results indicate importance of mechanisms other than renin-angiotensin system in the pressor response of both acute as well as chronic L-NAME. However, autonomic dysregulation especially following chronic L-NAME appears to be partly angiotensin dependent.

Background: Ozone (O3) is a well-documented respiratory oxidant, but increasing epidemiological evidence points to extrapulmonary effects, including positive associations between ambient O3 concentrations and cardiovascular morbidity and mortality. Objective: With preliminary reports linking O3 exposure with changes in heart rate (HR), we investigated the hypothesis that a single inhalation exposure to O3 will cause concentration-dependent autonomic modulation of cardiac function in rats. Methods: Rats implanted with telemeters to monitor HR and cardiac electrophysiology [electrocardiography (ECG)] were exposed once by whole-body inhalation for 4 hr to 0.2 or 0.8 ppm O3 or filtered air. A separate cohort was tested for vulnerability to aconitine-induced arrhythmia 24 hr after exposure. Results: Exposure to 0.8 ppm O3 caused bradycardia, PR prolongation, ST depression, and substantial increases in atrial premature beats, sinoatrial block, and atrioventricular block, accompanied by concurrent increases in several HR variability parameters that were suggestive of increased parasympathetic tone. Low-O3 exposure failed to elicit any overt changes in autonomic tone, heart rhythm, or ECG. However, both 0.2 and 0.8 ppm O3 increased sensitivity to aconitine-induced arrhythmia formation, suggesting a latent O3-induced alteration in myocardial excitability. Conclusions: O3 exposure causes several alterations in cardiac electrophysiology that are likely mediated by modulation of autonomic input to the heart. Moreover, exposure to low O3 concentrations may cause subclinical effects that manifest only when triggered by a stressor, suggesting that the adverse health effects of ambient levels of air pollutants may be insidious and potentially underestimated.

Vehicle swarm refers to a group of autonomous vehicles. Vehicle swarm motion coordination is a difficult problem in Intelligent Transport System. Due to similar characteristics of reactive agents and autonomous vehicles relying on self-organization principles, this paper presents reactive agent driven motion coordination for vehicle swarm that adopts large-scale independent local-reactive agents to perform a self-organized motion coordination control mechanism, which is composed of a network of swarm collaborative agents, a set of dynamic hybrid local networks of individual swarm collaborative agent and vehicle autonomic agents, and a homogenous self-organized motion coordination control protocol for individual vehicle autonomic agent’s self-adapting motion.

This article presents a way to manage and control home networking and, more specifically, a method to control the QoS within a HN. For providing this control, a new advanced platform was developed, based on a KP and unified knowledge management policies. This solution is very important for the development of mesh-networks within the home with adequate use of the combination of WiFi and PLC networks. A more extensive investigation of this technology is planned for the near future, including aspects such as congestion control and maintenance of the HN.

A new computing paradigm is currently on the spot: interaction based on series of actions. Most of autonomic agent systems (AASs) exploit this type of interaction to self-adjust their autonomous behaviors as a fundamental operational paradigm. At an interaction interface, actions evolve over time, hence series of actions occurs as a royal candidate for modeling, specifying, programming, and verifying AASs. For considering AASs, series of actions and adaptation relations; our formal approach consists, in particular, of categorical models and behaviors such that, firstly , AASs, series of actions and adaptation relations will categorically be modeled to provide algebraic frameworks for development of reasoning on their behaviors and, secondly, categorical behaviors of AASs, series of action and adaptation relations will be investigated and developed taking advantage of their categorical models.

Much recent research has focused on applying Autonomic Computing principles to achieve constrained self-management in adaptive systems, through self-monitoring and analysis, strategy planning, and self adjustment. However, in a highly distributed system, just monitoring current operation and context is a complex and largely unsolved problem domain. This difficulty is particularly evident in the areas of network management, pervasive computing, and autonomic communications. This paper presents a model for the filtered dissemination of semantically enriched knowledge over a large loosely coupled network of distributed heterogeneous autonomic agents, removing the need to bind explicitly to all of the potential sources of that knowledge. This paper presents an implementation of such a knowledge delivery service, which enables the efficient routing of distributed heterogeneous knowledge to, and only to, nodes that have expressed an interest in that knowledge. This gathered knowledge can then be used as the operational or context information needed to analyze to the system's behavior as part of an autonomic control loop. As a case study this paper focuses on contextual knowledge distribution for autonomic network management. A comparative evaluation of the performance of the knowledge delivery service is also provided.

Risk mitigation has gained relevance during the last years and has helped to solve risk and improve decision making among decision makers in IT Governance. However, there is still a increasing need of developing innovative tools that can help IT Practitioners to solve risk in IT Governance. Existing risk mitigation approaches or tools lacks need for adequate data which is very important in mitigating risk and there is difficulty of mitigating risk generally in IT Governance. This paper present an autonomic computing model developed to mitigate risk; mainly operational and technical in IT Governance by measuring the risk and providing risk report to the management and staffs in organisations. Autonomic Computing Systems (ACSs) are systems that manage themselves. The core of Autonomic Computing Systems are type of agent with advanced capacities for reasoning to measure the risk probability and risk impact based on available data in the knowledge base or previous experiences. The Autonomic Computing Systems provide risk advice aimed at providing decision support to management hence mitigating risk in IT Governance. Data was collected via purposely sampling using interview by case study among 13 Malaysia universities. The data was analyzed by Nvivo to get an insight on the current risk mitigation practices and process, after which a risk mitigation model has been developed using autonomic agents.

Background Murraya paniculata is traditionally used for management of gut, air way and cardiovascular disorders. The study was conducted for provision of pharmacological rationalization for folkloric uses of Murraya paniculata in gut, air way and cardiovascular problems. Methods Aqueous-ethanolic extract of Mp.Cr was tested using in vitro techniques on isolated tissue of rabbit (jejunum, trachea and aorta) to detect the possible presence of spasmolytic activity. The responses of tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system. Results Application of the extract of Mp.Cr relaxed spontaneous and high K+ (80mM)-induced contraction in rabbit jejunum preparation. Because it shifted the CRCs (Calcium response curve) towards the right side so the possible blockade was of calcium channel similar to verapamil. In rabbit trachea, extract of Mp.Cr produced relaxation of carbachol and high K+ induced contractions. When plant extract was checked further on isolated aorta for its possible vasodilator effect, it caused relaxation of phenylephrine and high K+-induced spastic contractions at different doses. Conclusion These results indicate that Murraya paniculata shows anti-spasmodic, bronchodilator and vasodilator activity facilitated through Ca++ antagonist mechanisms.

Background—The aim of this study was to investigate the feasibility of an alternative approach to electronic pacemaker by using spontaneously excitable cell grafts as a biological pacemaker in a large animal model of complete atrioventricular block. Methods and Results—Dissociated male human atrial cardiomyocytes including sinus nodal cells were grafted into the free wall of the left ventricle in five female pigs. Three weeks after the injection of cell-grafted solution/control medium the pigs underwent catheter ablation of the atrioventricular node (AV-node). After complete AV block was created, the idioventricular beat rate was more rapid in cell-grafted pigs than that in control pigs (86±21 vs. 30±10 bpm; P

Chondroitin sulfate proteoglycans are synthesized and deposited in the spinal cord following injury. These proteoglycans may restrict regeneration and plasticity and contribute to the limited recovery seen after an injury. Chondroitinase, a bacterial enzyme that catalyzes the hydrolysis of the chondroitin chains on proteoglycans, has been shown to improve motor and sensory function following partial transection lesions of the spinal cord. To assess the effects of chondroitinase in a clinically relevant model of spinal cord injury, 128 female Long-Evans rats received either a severe, moderate, or mild contusion injury at the vertebral level T9/T10 with a forceps model and were treated for 2 weeks with chondroitinase ABCI at 0.06 Units per dose, penicillinase, or vehicle control via an intrathecal catheter placed near the injury. Motor behavior was measured by open-field testing of locomotion and bladder function monitored by measuring daily residual urine volumes. Animals treated with chondroitinase showed significant improvements in open-field locomotor activity as measured by the Basso, Beattie and Bresnahan scoring system after both severe and moderate SCI (p

The parasympathetic and sympathetic divisions of the autonomic nervous system are involved in homeostatic control of a wide variety of ocular functions, including accommodation, pupillomotor control, lacrimation, eyelid position, and aqueous humor production. Familiarity with the functional anatomy of the autonomic nervous system is paramount to the understanding and application of the large number of autonomic drugs used in veterinary ophthalmology. The cholinergic and adrenergic agents discussed in this article are commonly employed to facilitate routine ophthalmic examination, in the diagnosis of autonomic dysfunction, and in the treatment of a variety of ocular diseases.

A logical partition in an IBM pSeriesTM symmetric multiprocessor (SMP) system is a subset of the hardware of the SMP that can host an operating system (OS) instance. Dynamic reconfiguration (DR) on these logically partitioned servers enables the movement of hardware resources (such as processors, memory, and I/O slots) from one logical partition to another without requiring reboots. This capability also enables an autonomic agent to monitor usage of the partitions and automatically move hardware resources to a needy OS instance nondisruptively. Today, as SMPs and nonuniform memory access (NUMA) systems become larger and larger, the ability to run several instances of an operating system(s) on a given hardware system, so that each OS instance plus its subsystems scale or perform well, has the advantage of an optimal aggregate performance, which can translate into cost savings for customers. Though static partitioning provides a solution to this overall performance optimization problem, DR enables an improved solution by providing the capability to dynamically move hardware resources to a needy OS instance in a timely fashion to match workload demands. Hence, DR capabilities serve as key building blocks for workload managers to provide self-optimizing and self-configuring features. Besides dynamic resource balancing, DR also enables Dynamic Capacity Upgrade on Demand, and self-healing features such as Dynamic CPU Sparing, a winning solution for users in this age of rapid growth in Web servers on the Internet.

Patients with autonomic failure are characterized by orthostatic hypotension, supine hypertension, high blood pressure variability, blunted heart rate variability, and often have a "non-dipping" or "reverse dipping" pattern on 24-h ambulatory blood pressure monitoring. These alterations may lead to cardiovascular and cerebrovascular changes, similar to the target organ damage found in hypertension. Often patients with autonomic failure are on treatment with anti-hypotensive drugs, which may worsen supine hypertension. The aim of this review is to summarize the evidence for cardiac, vascular, renal, and cerebrovascular damage in patients with autonomic failure.

Autonomic networking refers to the self-managing characteristics (configuration, protection, healing, and optimization) of distributed network elements, adapting to unpredictable changes while hiding intrinsic complexity from operators and users. Autonomic Networking, which often involves closed-loop control, is applicable to the complete network (functions) lifecycle (e.g. installation, commissioning, operating, etc). An autonomic function works in a distributed way across various network elements, but allowing central guidance and reporting, and co-existence with non-autonomic methods of management. This paper will discuss some of the use cases for basics autonomic agent, which takes into consideration layer 1 (with focus on optical transport) performance for layer 3 decisions.

This paper describes a toolkit for building multiagent autonomic systems. The IBM Agent Building and Learning Environment (ABLE) provides a lightweight Java™ agent framework, a comprehensive JavaBeans™ library of intelligent software components, a set of development and test tools, and an agent platform. We describe a series of agents built using ABLE components and present three case studies of applications using the ABLE toolkit. The Autotune agent is a closed-loop controller agent that supports hierarchical distributed control. The Subsumption agent defines specific behaviors or strategies and can be plugged into a multiagent subsumption infrastructure. The Autonomic agent architecture features sensors and effectors for interacting with the external environment, layers of reflexive, reactive, and adaptive subsumption agents, components that dynamically model the autonomic system itself and its environment, and components for emotions, planning, and executive-level decision-making. By using the ABLE component library to build agents running on the ABLE distributed agent platform, we discuss how we can incrementally add new behaviors and capabilities to intelligent, autonomic systems.

Autonomic Agents in Open intelligent space face a wide diversity of Context providers and formats. With a micro approach to Context-awareness, individual Agents perform their own assessment of individual Context relevance. This assessment relies in part on the semantic proximity between requested and candidate Contexts. We present a quantitative semantic distance function that supports subjective Context relevance assessment in Agents.

The venous system contains approximately 70% of the blood volume. The sympathetic nervous system is by far the most important vasopressor system in the control of venous capacitance. The baroreflex system responds to acute hypotension by concurrently increasing sympathetic tone to resistance, as well as capacitance vessels, to increase blood pressure and venous return, respectively. Studies in experimental animals have shown that interference of sympathetic activity by an alpha1- or alpha2-adrenoceptor antagonist or a ganglionic blocker reduces mean circulatory filling pressure and venous resistance and increases unstressed volume. An alpha1- or alpha2-adrenoceptor agonist, on the other hand, increases mean circulatory filling pressure and venous resistance and reduces unstressed volume. In humans, drugs that interfere with sympathetic tone can cause the pooling of blood in limb as well as splanchnic veins; the reduction of cardiac output; and orthostatic intolerance. Other perturbations that can cause postural hypotension include autonomic failure, as in dysautonomia, diabetes mellitus, and vasovagal syncope; increased venous compliance, as in hemodialysis; and reduced blood volume, as with space flight and prolonged bed rest. Several alpha-adrenoceptor agonists are used to increase venous return in orthostatic intolerance; however, there is insufficient data to show that these drugs are more efficacious than placebo. Clearly, more basic science and clinical studies are needed to increase our knowledge and understanding of the venous system.

Recent clinical studies show that pulmonary veins (PVs) are important foci of atrial tachyarrhythmias. Autonomic nervous system was known to play a role in the genesis of atrial tachyarrhythmias. The present experiments aimed to investigate the actions of autonomic agents in dog PVs and to explore the arrhythmogenic activity in these tissues. Transmembrane action potentials were recorded with the conventional microelectrode techniques and tension was detected by a transducer. In PV driven electrically, isoproterenol (Isop, 1μM) increased while ACh (1-10μM) depressed twitch force but elevated resting tension. In PV active spontaneously, Isop increased the automatic rate and induced high frequency irregular rhythms while ACh suppressed them. The actions of Isop and ACh were antagonized by propranolol and atropine, respectively. Quite often a single microelectrode impalement recorded 2 and more types of action potentials with wide range of durations (APD), indicating presence of multiple cells with different electrophysiological properties and electrical uncoupling of neighboring cells in PV strips. Activation of β-adrenoceptor stimulated while cholinergic agonist suppressed spontaneous action potentials or high frequency irregular rhythms in PV.

Many advances in medical therapy for chronic glaucoma have taken place in the past few years that have altered previous concepts of stepwise medical therapy for glaucoma. beta-adrenergic blockers are still the most common medicine prescribed as monotherapy. However, latanoprost and brimonidine are often given as monotherapy as well as early adjunctive therapy. In addition, newer treatments that are used as early adjunctive therapy are dorzolamide, brinzolamide, apraclonidine, and the combination products, consisting of dorzolamide/timolol maleate and pilocarpine/timolol maleate. Older adjunctive treatments are now often prescribed as late adjunctive therapy including pilocarpine, epinephrine compounds, and acetazolamide. The extent of maximum tolerated medical therapy and the decision to perform either laser or conventional filtration surgery depend on the physician's judgment and on the patient's needs and preferences. In the future, newer medical therapies that may protect the health of the optic nerve directly could be developed including blood flow-based, neuroprotective, and genetically based agents.

Postural (orthostatic) hypotension is defined as a fall in blood pressure of over 20 mm Hg systolic, (or 10 mm Hg diastolic), on standing or during head-up tilt to at least 60°.1 In neurological practice, it may result from diseases or drugs that impair the activity of sympathetic vasoconstrictor nerves. Postural hypotension may be a presenting feature in certain autonomic disorders (such as pure autonomic failure), it may be a pointer towards an alternative diagnosis (as in multiple system atrophy presenting with parkinsonian features), and it may complicate drug therapy (as with levodopa). Postural hypotension is associated with increased morbidity and also mortality, especially in elderly people, in whom falls result in injuries. Advances have resulted in a better understanding of the pathophysiological processes, and in the treatment of postural hypotension. Postural hypotension usually is considered when there are characteristic features resulting from cerebral ischaemia such as loss of consciousness (fainting, syncope). Other symptoms may occur (table1).2 Measuring blood pressure while lying and after 2 minutes of standing often confirms a postural fall. However, the lack of a fall, in the presence of suggestive symptoms, should warrant further investigation. There are various disorders, including the chronic fatigue syndrome and the postural tachycardia syndrome, in which postural intolerance may not be accompanied by hypotension. Additional factors may be needed to unmask postural hypotension (table2), especially in mild to moderate autonomic failure. View this table: Table 1 Some of the symptoms resulting from postural hypotension, and impaired perfusion of various organs View this table: Table 2 Factors that may influence postural hypotension Further evaluation is best undertaken in an autonomic laboratory. Studies ideally should utilise a tilt table, as patients with neurological disabilities or a profound fall in blood pressure can rapidly and safely be returned to the horizontal position. Additional screening tests (the Valsalva manoeuvre, pressor …

INTRODUCTION Clozapine, an atypical antipsychotic with documented efficacy in the management of treatment-resistant schizophrenia, is associated with the risk of adverse hematological outcomes. Of particular concern are reductions in white blood cells (WBC) and absolute neutrophil counts (ANC). Individuals who display moderate leukopenia (3000/mm(3) > WBC ≥ 2000/mm) upon initiation of clozapine therapy are at increased risk of developing agranulocytosis, defined as an ANC less than 500/mm. Complications of agranulocytosis can be severe and include increased risk of infection and mortality. OBJECTIVES The primary objective of this study was to examine data on clozapine recipients who experienced adverse drug reactions (ADRs) related to decreases in WBC or ANC and ascertain whether other drugs and/or drug interactions had played a role. The analysis included multiple classes of medications. METHODS A retrospective chart review was performed of open and closed medical records of all inpatient recipients of clozapine at a state psychiatric center between January 1, 2004 and June 30, 2011. Laboratory records of patients prescribed clozapine were examined for abnormal WBC counts or ANC. A hematological ADR was considered to have occurred if there was a substantial drop in either WBC or ANC or mild or moderate leukopenia or granulocytopenia. Each episode was analyzed for medications that might have contributed to the ADR. Data were collected for all scheduled and STAT medications started at any point during the clozapine patient's hospitalization. The following seven medication groups, based on the Therapeutic Classification System of the American Hospital Formulary System (AHFS), were chosen for analysis because they were consistently used in the majority of the patient population: antihistamines, anti-infectives, autonomic agents, cardiovascular agents, antipsychotics, vitamins, and gastrointestinal agents. Pearson correlation coefficients were calculated to identify associations between the presence of hematological ADRs and medications administered concomitantly with clozapine. RESULTS The following significant correlation coefficients were found between the use of a class of medications and the occurrence of a hematological ADR: antiinfective agents 0.409 (p < 0.01), gastrointestinal agents 0.329 (p < 0.01), and autonomic agents 0.309 (p < 0.01). In the subset of patients who were prescribed a proton-pump inhibitor or ranitidine concomitantly with clozapine, 24/26 (96%) experienced a hematological ADR. CONCLUSIONS Autonomic agents, anti-infective agents, and proton pump inhibitors and other gastrointestinal agents were all associated with hematological ADRs when co-prescribed with clozapine. Medications from these classes should be initiated cautiously in patients being treated with clozapine to avoid precipitous drops in ANC or WBC that may increase the risk of agranulocytosis.

The idea of autonomic computing, and accordingly autonomic networking, has drawn the attention of industry and academia during the past years. An autonomic behavior is widely understood as a control loop which is realized by an autonomic entity/agent that manages some resources, in order to improve the performance and regulate diverse operational aspects of the managed network or IT infrastructure. Self-management, realized through autonomic behaviors, is an appealing and dangerous vision at the same time. On one hand, it promises to reduce the need for human involvement in the network and system management processes. On the other hand, it bears a number of potential pitfalls that could be even dangerous to the network, the IT infrastructure, and the corresponding services. One of these pitfalls is constituted by the stability of the control loops, and correspondingly by the interference among multiple autonomic agents operating in parallel. In this paper, a novel approach to ensuring runtime synchronization and stability of multiple parallel autonomic control loops is presented. We formally model the problem of runtime action synchronization, propose different possible solutions, and provide a case study, as well as different performance measurements based on a prototype that implements our approach.

Injury to peripheral or central primary afferent neurons can produce severe and chronic neuropathic or deafferentation pain. This type of pain responds poorly, if at all, to nonsteroidal anti-inflammatory drugs and often is relatively opioid resistant. Several classes of drugs have been used with varying effectiveness to treat neuropathic pain. None are effective for all patients. Tricyclic antidepressants (TCAs) are often considered the drugs of choice at doses that are only one third to one half of the antidepressant doses. Available TCAs are contrasted by their side-effect profiles and pharmacokinetic characteristics. Amitryptyline is the most commonly used drug, but desipramine may be the TCA of choice for this indication. When the TCA alone is not sufficient an anticonvulsant can be added. Recent experience suggests that gabapentin may be the anticonvulsant of choice for this purpose. The used of systemic local anesthetics and topical capsaicin to deplete substance P is also described. Other classes of medications that have been used with varying results are discussed and include autonomic agents, depleting agents, andN-methyl-D-aspartate receptor antagonists. Methods of obtaining complete medication histories and of stopping ineffective drugs are described. The importance of an interdisciplinary, multimodel approach to the management of neuropathic pain is discussed.

We studied hemodynamic responses to alpha- and beta-receptor agonists in eight healthy men before and after 14 days of 6 degrees head-down tilt (HDT) to test the hypothesis that increased adrenoreceptor responsiveness is induced by prolonged exposure to simulated microgravity. Steady-state infusions of isoproterenol (Iso) at rates of 0.005, 0.01, and 0.02 microgram.kg-1.min-1 were used to assess beta 1- and beta 2-adrenoreceptor responsiveness. Infusions of phenylephrine (PE) at rates of 0.25, 0.50, and 1.00 microgram.kg-1.min-1 were used to assess responsiveness of alpha 1-vascular adrenoreceptors. Slopes calculated from linear regressions between Iso and PE doses and changes in beat-to-beat heart rate, blood pressure, and leg vascular resistance (occlusion plethysmography) for each subject were used as an index of alpha- and beta-adrenoreceptor responsiveness. HDT increased the slopes of heart rate (1,056 +/- 107 to 1,553 +/- 83 beats micrograms-1.kg-1.min-1; P = 0.014) and vasodilation (-469 +/- 111 to -1,446 +/- 309 peripheral resistance units.microgram-1.kg-1.min-1; P = 0.0224) to Iso infusion. There was no alteration in blood pressure or vascular resistance responses to PE infusion after HDT. Our results provide evidence that simulated microgravity causes selective increases in beta 1- and beta 2-adrenoreceptor responsiveness without affecting alpha 1-vascular adrenoreceptor responses.

1. Positive inotropic responses to calcitonin gene-related peptide (CGRP) were evaluated in atria isolated from in vivo rat models of hyper-sensory-motor innervation (following neonatal guanethidine treatment) and hypo-sensory-motor innervation (following neonatal capsaicin treatment), to explore the hypothesis that functional responsiveness of atrial myocardium to CGRP may correlate with tissue levels of the sensory-motor neurotransmitters. Comparative of inotropic responses to CGRP following in vitro treatment of atria with guanethidine was also performed. 2. Following long-term guanethidine treatment, positive inotropic responses to CGRP were significantly attenuated, while supersensitivity to the sympathetic transmitter noradrenaline was shown. Maximal inotropic responses to CGRP (30 nM) were 214.0 +/- 28.1 (n = 8) and 146.8 +/- 21.7 mg (n = 8; P < 0.01) increase of the basal contractile tension in control and treated preparations, respectively. The pD2 values for noradrenaline were 6.71 +/- 0.12 (n = 8) and 7.26 +/- 0.13 (n = 6; P < 0.01) in control and treated atria, respectively. Acute application of guanethidine in vitro did not modify the positive inotropism by CGRP or the beta-adrenoceptor agonist isoprenaline. 3. Sensory-motor hypoinnervation following chronic treatment with capsaicin did not affect the inotropic responses to CGRP. Neither guanethidine nor capsaicin treatment affected the contractile apparatus of myocytes, as demonstrated by similar basal contractile tension as well as calcium-evoked inotropic responses in control and treated preparations. 4. In summary, increased sensory-motor innervation, following long-term sympathectomy with guanethidine, resulted in attenuation of the inotropic responses of the rat atrium to CGRP, while no changes in the inotropic responses were seen following sensory-motor denervation with capsaicin. Down-regulation of CGRP receptors or altered post-receptor signalling may be involved in the reduced responsiveness to CGRP.

This paper investigates agent-based modelling and design of a real time mission planning module for an Unmanned Aerial Vehicle (UAV). Agents can act on behalf of remote human operators, who impose mission objectives, performing autonomous or supervised behaviours. The planning module is in charge to deliberate the strategic tasks to achieve mission objectives and to satisfy environment constraints (area of operations, aircraft performances, etc.). We define a multi-objective model for implementing a goal-directed decision making support to the planning module. A formal model is used to infer from requirements real time constraints, by which mission planning is dynamically scheduled. Preliminary development and performance evaluation using embedded devices are discussed.

To explore the association of autonomic agents with the development and severity of retinopathy of prematurity (ROP).The medical records of all preterm infants screened for ROP were retrospective reviewed. The association between development and severity of ROP and the use and dose(s) of autonomic agents was analyzed, after adjustment for the covariates gestational age, weight, development of septicemia, intraventricular hemorrhage, and respiratory distress syndrome.A total of 350 infants were screened. Caffeine was used in 338 infants; dopamine in 98 infants. There was a significant association between the use of dopamine and development of ROP (P0.001; relative risk [RR] = 1.6 [95% CI, 1.23-2.06]) and the need for ROP treatment (P = 0.001; RR = 4.63 [95% CI, 1.82-11.79]). The number of dopamine doses was significantly associated with the development of any ROP (P0.001; RR = 1.07 [95% CI, 1.03-1.1]), the severity of ROP (P0.001; RR = 1.09 [95% CI, 1.05-1.14]), and the need for treatment (P0.001; RR = 1.09 [95% CI, 1.05-1.14]). The total dose of caffeine was significantly associated with the development of any ROP (P = 0.003; RR = 1.03 [95% CI, 1.01-1.05]) and the need for treatment (P = 0.006, RR = 1.073 [95% CI; 1.021-1.13]).Although a causal relationship was not identified, the use of the autonomic agents caffeine and dopamine was associated with the development and severity of retinopathy of prematurity in this cohort.

Electronic contracts are crucial for future e-Business models due to the increasing importance of Web services and the cloud as a reliable commodity enabling service-based value chains. Negotiation is the prerequisite for establishing a contract between two or more partners. These contracts are usually based on Service Level Agreements (SLAs). In this paper we present the framework of a smart Web service marketplace, which allows for automatic, autonomous, and adaptive negotiation and re-negotiation of Web services based on economic principles. Our approach enables market based service trading following a bazaar style and extends the classical supermarket approach typical for service negotiation today. We extend the WS-Agreement standard by feasible workflows to support auctioning for negotiation and re-negotiation. A specific highlight of our framework is the mapping of business strategies defined by economic goals of the respective organization into an ICT enabled framework. It facilitates autonomic agents acting as organizational representatives stipulating SLAs without human interaction. This allows for business transactions transparently to the environment but adhering to business objectives of the originating organization.

The design and development of autonomous software agents is still a challenging task and needs further investigation. Giving an agent the maximum autonomous capabilities may not necessarily produce satisfactory agent behavior. Consequently, adjustable autonomy has become the hallmark of autonomous systems development that influences an agent to exhibit satisfactory behavior. To perform such influences, however, a dynamic adjustment mechanism is needed to be configured. The influences are costly in time and implementation especially for systems with time-critical domain. They might negatively influence agent decisions and cause system disturbance. In this paper, we propose a framework to govern an agent autonomy adjustment and minimize system disturbance. The main components of the proposed framework are the Planner, Scheduler and Controller (PSC) that conform to the current trends in automated systems. Two modules are also suggested which are Autonomy Analysis Module (AAM) and Situation Awareness Module (SAM). They are accordingly used to distribute the autonomy and provide balance to the system so that it’s local and global desires do not conflict.

Two types of Ca2+ currents with characteristics of T- and L-type Ca2+ currents were recorded in ventricular myocytes of dogfish (Squalus acanthias). The T-type Ca2+ current activated near -70 mV and had a peak current density of 9.8 pA/pF at -34 mV. The L-type Ca2+ current activated near -50 mV and had a peak current density of 10.6 pA/pF near 0 mV. The threshold for activation of the T-type Ca2+ current was 20 mV negative to that of the tetrodotoxin-sensitive Na+ current. Inactivation of the T-type Ca2+ current was rapid with a limiting time constant of 5 ms at positive potentials. The T-type Ca2+ current was not modulated by isoproterenol or acetylcholine. In dogfish the T-type Ca2+ channel has current densities equivalent to the L-type channel and is likely to activate before the Na+ channel, contributing significantly to generation of the foot of the action potential.

Background The presence of atrioventricular nodal dual-pathway physiology in patients with atrioventricular nodal reentrant tachycardia (AVNRT) provides an opportunity to characterize the effect of a selective slow-pathway ablation on the ventricular rate during atrial fibrillation (AF). This may have important clinical implications for the nonpharmacological management of AF with a rapid ventricular rate. Methods and Results Selective radiofrequency catheter ablation of the atrioventricular nodal slow pathway was performed with a stepwise approach in patients with documented sustained AVNRT. The AV nodal conduction properties and refractoriness and the ventricular rate during induced AF were assessed at baseline and under autonomic blockade before and after a selective slow-pathway ablation in 18 patients (mean age, 34±8 years). Sustained AVNRT was induced with a mean cycle length of 339±58 ms. A slow-pathway ablation was successfully achieved with 5±4 applications of radiofrequency energy. The shortest cycle length of 1:1 AV conduction and the AV nodal effective refractory period significantly prolonged after ablation (367±53 versus 403±55 ms, P P P P P Conclusions In patients undergoing a slow-pathway ablation for control of AVNRT, selective slow-pathway ablation may cause a significant decrease in the ventricular rate during AF. These effects are primarily due to the prolongation of AV nodal conduction properties and refractory period of the residual AV nodal transmission system. These findings may have important therapeutic implications for the nonpharmacological treatment of AF, particularly in patients with underlying dual AV nodal physiology.

Previous studies including ours showed that cyclosporine (CSA) causes baroreflex dysfunction and hypertension. Here we tested the hypothesis that oxidative damage in central and peripheral tissues underlies the hypertensive, baroreflex and autonomic actions elicited by CSA in rats. We investigated the effects of individual and combined 7-day treatments with CSA (25 mg/kg/day, n=7) and 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol, superoxide dismutase mimetic, 100 mg/kg/day, n=7) on blood pressure, reflex heart rate responses to peripherally mediated pressor and depressor responses, and biomarkers of oxidative stress. CSA elevated blood pressure and reduced reflex bradycardic (phenylephrine) and tachycardic (sodium nitroptrusside) responses. The ability of muscarinic (atropine, 1 mg/kg i.v.) or β-adrenoceptor blockade (propranolol, 1 mg/kg i.v.) to reduce reflex heart rate responses was reduced in CSA-treated rats, suggesting the impairment by CSA of reflex cardiac autonomic control. Concurrent administration of tempol abolished CSA-induced hypertension and normalized the associated impairment in baroreflex gain and cardiac autonomic control. Tempol also reversed the CSA-induced increases in aortic and brainstem nitrite/nitrate and malondialdehyde (MDA) and decreases in aortic superoxide dismutase (SOD). These findings implicate oxidative stress in peripheral and central cardiovascular sites in the deleterious actions of CSA on blood pressure and baroreceptor control of heart rate.