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This is a case of a two-year-old boy with a ganglion arising from the sternoclavicular joint. Ganglia are rare in the pediatric population, with less than 2% occurring under the age of 2 years old. Additionally, sternoclavicular joint ganglia are also exceedingly rare. The case illustrates the importance of keeping ganglion within the differential diagnosis for palpable subcutaneous masses, even in young children, especially when they are seen to connect to the joint.

Electric distribution systems around the world are seeing an increasing number of utility-owned and non-utility-owned (customer-owned) intelligent devices and systems being deployed. New deployments of utility-owned assets include self-healing systems, microgrids, and distribution automation. Non-utility-owned assets include solar photovoltaic generation, behind-the-meter energy storage systems, and electric vehicles. While these deployments provide potential data and control points, the existing centralized control architectures do not have the flexibility or the scalability to integrate the increasing number or variety of devices. The communication bandwidth, latency, and the scalability of a centralized control architecture limit the ability of these new devices and systems from being engaged as active resources. This paper presents a standards-based architecture for the distributed power system controls, which increases operational flexibility by coordinating centralized and distributed control systems. The system actively engages utility and non-utility assets using a distributed architecture to increase reliability during normal operations and resiliency during extreme events. Results from laboratory testing and preliminary field implementations, as well as the details of an ongoing full-scale implementation at Duke Energy, are presented.

Demand response represents a significant but largely untapped resource that can greatly enhance the flexibility and reliability of power systems. This paper proposes a hierarchical control framework to facilitate the integrated coordination between distributed energy resources and demand response. The proposed framework consists of coordination and device layers. In the coordination layer, prior to each scheduling period, each coordinator receives the aggregated utility or cost functions as well as the power operating ranges from aggregators or device controllers. Then, various resources or their aggregations are optimally coordinated in a distributed manner to achieve the system-level objectives. The obtained regulation signals are sent back to aggregators or device controllers for real-time control. In the device layer, at the scheduling stage, the controller at each device reports to coordinators (directly or through aggregators) the required information for optimal coordination, and receives the regulation signals from its commander once the coordination is completed. During the real-time operation, individual resources are controlled to follow the optimal power dispatch signals. For practical applications, a method is presented to determine the utility functions of controllable loads by accounting for the real-time load dynamics and the preferences of individual customers. The effectiveness of the proposed framework is validated by detailed simulation studies.

Restoration of end-use loads during bulk transmission system outages is a key challenge for electric utilities. During those outages, utilities often do not have enough resources to fully restore the end-use loads. System reconfiguration can provide access to non-utility assets that can enable restoration; however, not all available switching options are feasible due to voltage and load limits. Engaging non-utility assets for system restoration during system events requires commensurate compensation and incentive calculation. This paper presents a new transactive energy system framework (TESF) to incentivize distributed energy resources (DERs) to provide reactive power for supporting the self-healing functions of distribution management system (DMS). TESF engages non-utility DERs during resiliency events by incentivizing them through transactive signals computed using marginal cost of producing reactive power and marginal benefit of additional switching operations. TESF calculates additional switching options, which DMS then leverages to identify new optimal switching plans to restore additional loads. A test system consisting of multiple IEEE-13 node distribution feeders is used to demonstrate the performance of the proposed method. For the given system configuration and use-case, TESF results in 24.82% additional load restoration and one additional switching operation.

Electrical power system stability under high penetration of intermittent renewable energy generation, such as wind and solar energy, has become a high concern. It is unpredictable and hard to control due to little inertial behavior characteristic to these generation resources. To help mitigate possibly undesirable frequency excursions, demand-side frequency control presents an emerging solution. By observing the frequency deviation, devices could switch operating modes for a short time to rebalance generation. To analyze device level control algorithms, aggregate models for their behavior are needed. Refrigerators are household devices that could help with load modulation. This paper uses real measured data to analyze the refrigerator behavior, learn about its operating mode and power consumption ranges. A Markov chain process is proposed to model the transition of a refrigerator population from one operating mode to another, such that the overall load is modulated according to the control input. The Markov-chain model can be used to design control so that the overall load is modulated according to the control input.

Transactive energy is a control technique that uses market mechanisms to achieve desired control objectives. Several simulation studies and field demonstrations were carried out in recent years, but all focused on small scale systems and purpose-built simplified models which are not always capable of pointing out all the advantages and shortcomings of transactive energy methods. This work describes a co-simulation framework built on a hierarchical control architecture that allows for conducting studies on the impacts of a very large-scale deployment of transactive energy. The hierarchical transactive control architecture adopted in this work helps with alleviating computation and communication burden to facilitate a more effective large scale real-time market operation among device level resources and the system level operators. The co-simulation framework is evaluated using off-the-shelf simulators on an integrated power system model of unprecedented scale composed of the Western Electricity Coordination Council transmission system with tens of thousands of distribution systems deployed with flexible device-level distributed energy resources.

Existing approaches coordinating distributed energy resources (DERs) for grid services do not adequately evaluate the performance of such DER integration. Most studies are based on a single type of DER used for a single type of service, rather than the real-world requirements of coordinating a heterogeneous mix of DERs to provide multiple different grid services at different time-scales. Facilities also often face cybersecurity and interoperability challenges to experimenting and testing methodologies in this area. To overcome all of these challenges, Pacific Northwest National Laboratory, United Technologies Research Center, Southern California Edison, and Spirae coordinated to develop a federation between their organizations. This federation implements a cybersecure connection that facilitates near real-time communication between the four different physical sites. This not only enables control of DERs at different physical locations but also lets the software and hardware objects perform control experiments in a cybersecure environment at different time-scales. The hardware systems can consist of microgrids, building management systems, and emulated power systems objects. This paper provides a detailed overview of the federation setup and describes what this federation can be used for.

Volt/var control (VVC) of smart PV inverter is becoming one of the most popular solutions to address the voltage challenges associated with high PV penetration. This work focuses on the local droop VVC recommended by the grid integration standards IEEE1547, rule21 and addresses their major challenges i.e. appropriate parameters selection under changing conditions, and the control being vulnerable to instability (or voltage oscillations) and significant steady state error (SSE). This is achieved by proposing a two-layer local real-time adaptive VVC that has two major features i.e. a) it is able to ensure both low SSE and control stability simultaneously without compromising either, and b) it dynamically adapts its parameters to ensure good performance in a wide range of external disturbances such as sudden cloud cover, cloud intermittency, and substation voltage changes. A theoretical analysis and convergence proof of the proposed control is also discussed. The proposed control is implementation friendly as it fits well within the integration standard framework and depends only on the local bus information. The performance is compared with the existing droop VVC methods in several scenarios on a large unbalanced 3-phase feeder with detailed secondary side modeling., IEEE Transactions on Smart Grid, 2018

With an ever-evolving power grid, concerns regarding how to maintain system stability, efficiency, and reliability remain constant because of increasing uncertainties and decreasing rotating inertia. To alleviate some of these concerns, demand response represents a viable solution and is virtually an untapped resource in the current power grid. This work describes a hierarchical control framework that allows coordination between distributed energy resources and demand response. This control framework is composed of two control layers: a coordination layer that ensures aggregations of resources are coordinated to achieve system objectives and a device layer that controls individual resources to assure the predetermined power profile is tracked in real time. Large-scale simulations are executed to study the hierarchical control, requiring advancements in simulation capabilities. Technical advancements necessary to investigate and answer control interaction questions, including the Framework for Network Co-Simulation platform and Arion modeling capability, are detailed. Insights into the interdependencies of controls across a complex system and how they must be tuned, as well as validation of the effectiveness of the proposed control framework, are yielded using a large-scale integrated transmission system model coupled with multiple distribution systems.

Given that reliable markers for early ischemic brain damage are lacking, we set out to test whether pimonidazole can be used as a reliable tool in the quantification of hypoxic insults, at early time points following experimental stroke.We have used semi-quantitative Western blotting detection of pimonidazole adducts in a rat model of reversible middle cerebral artery occlusion (MCAO), treated with remote post-conditioning.First, we demonstrated that a linear relationship exist between pimonidazole binding in the ischemic hemisphere and duration of ischemia, in animals subjected to 5, 15, 30, or 60 minutes of occlusion followed by 120 minutes of reflow. Then we showed a significant reduction in pimonidazole binding in the infarcted hemisphere, when rats with 60 minutes of MCAO, immediately after establishment of cerebral reflow, had 3×15 minutes intermittent hind limb ischemia followed by 24-hour survival. We analysed the middle cerebral arteries from animals with 60 minutes of MCAO and early remote post-conditioning, followed by 30 minutes, 24, or 48 hours of reflow. At 24 hours of reflow increases in phosphorylated protein kinase C-alpha with concomitantly increased levels of p38 phosphorylation were observed.Our investigation demonstrates that pimonidazole can be used for quantifying ischemic impact in stroke, even after very short survival times. It furthermore shows that early remote post-conditioning reduces ischemic damage, probably through hyperpolarization and reduced reflow vasospasm in the conduit middle cerebral arteries.

The Grid Friendly™ Appliance (GFA) controller was proposed to autonomously switch off appliances by detecting under-frequency events. In this paper, a new frequency responsive load (FRL) controller is proposed by extending the functionality of the existing GFA controller. The proposed FRL controller can autonomously switch on (or off) end-use loads by detecting over-frequency (or under-frequency) events through local frequency measurement. Using the proposed FRL controller, a hierarchical decentralized control strategy is also developed for engaging the end-use loads to provide primary frequency response. The developed control strategy consists of two decision making layers including supervisory and device layers, and has several desirable features for primary frequency control. The FRL controller at the device layer preserves the autonomous operation of the enduse loads. The coordinator at the supervisory layer coordinates autonomous response to overcome the stability issue associated with high penetration of FRLs. The simulation results illustrate the effectiveness of the developed hierarchical decentralized control strategy in providing primary frequency response with the proposed FRL controller.

The wholesale power markets have undergone substantial change over the past few years to deal with increasing penetrations of variable energy resources. The market design and processes have become more complex because of introduction of new products and services to deal with the variability and intermittency of renewable resources. Additionally, the increasing adoption of distributed energy resources presents new challenges for the power grid operations, requiring additional flexibility to ensure stable, reliable, and resilient grid operations. The current market designs, however, do not explicitly value flexibility from resources. This paper presents a novel unit commitment/economic dispatch problem formulation that explicitly values the flexibility offered by resources. The market design is based on the concept of two-part pricing where resources are first paid to make their capacities available, including the flexibility, in the day-ahead markets and subsequently paid performance payments based on real-time dispatch.

The most formidable challenge in assembling a smart grid is the integration of a high penetration of renewables. Demand response (DR), a largely promising concept, is increasingly discussed as a means to cope with the intermittent and uncertain renewables. In this paper, we propose a dynamic market mechanism (DMM) that reaches the market equilibrium through continuous negotiations between key market players. In addition to incorporating renewables, this market mechanism also incorporates a quantitative taxonomy of DR devices, based on the inherent magnitude, runtime, and integral constraints of demands. The DMM is evaluated on an IEEE 118 bus system, a high-fidelity simulation model of the midwestern U.S. power grid. The results show how the proposed mechanism can be utilized to determine combinations of DR devices in the presence of intermittent and uncertain renewables with varying levels of penetration so as to result in a desired level of social welfare.

The inflammatory response plays a pivotal role in propagating injury of intracerebral hemorrhage (ICH). Glucagon-like-peptide-1 (GLP-1) is a hormone with antidiabetic effect and may also have antiinflammatory properties. Despite consensus that the glucoregulatory action is mediated by the GLP-1 receptor (GLP-1R), mechanisms in the brain remain unclear. We investigated the effect of a long-acting GLP-1 analog, liraglutide, and its truncated metabolite, GLP-1(9–36)a from dipeptidyl peptidase-4 (DPP-4) cleavage in ICH-induced brain injury. Primary outcomes were cerebral edema formation, neurobehavior, and inflammatory parameters. GLP-1(9–36)a, GLP-1R inhibitor, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation inhibitor and DPP-4 inhibitor were administered to examine the mechanisms of action. Liraglutide suppressed neuroinflammation, prevented brain edema and neurologic deficit following ICH, which were partially reversed by GLP-1R inhibitor and AMPK phosphorylation inhibitor. Liraglutide-mediated AMPK phosphorylation was unaffected by GLP-1R inhibitor, and was found to be induced by GLP-1(9–36)a. GLP-1(9–36)a showed salutary effects on primary outcomes that were reversed by AMPK phosphorylation inhibitor but not by GLP-1R inhibitor. Liraglutide and DPP-4 inhibitor co-administration reversed liraglutide-mediated AMPK phosphorylation and antiinflammatory effects. Liraglutide exerted duals actions and the antiinflammatory effects are partially mediated by its metabolite in a phosphorylated AMPK-dependent manner. Therapies that inhibit GLP-1 degradation may weaken the metabolite-mediated effects.

Aneurysmal rebleeding poses a serious risk in patients with subarachnoid hemorrhage (SAH). Studies have shown that antifibrinolytic therapy with tranexamic acid has a dramatic effect on the rate of rebleeding. Therefore, changes in the fibrinolytic system could be hypothesized. We have used an experimental SAH rat model to demonstrate serial changes in the haemostatic system as evaluated by Thromboelastography® (TEG). In the SAH group, a shorter reaction time (R-time) and higher maximum amplitude (MA) were observed. In the saline group, only a shorter R-time was observed. The study has shown that a hypercoagulable state is present immediately after experimental SAH is induced as determined by TEG. The reduction in R-time and rise in MA observed in the SAH group indicate that blood in the subarachnoid space is necessary to accomplish a full systemic coagulation response. This abnormality in coagulation profile seems to be a response to the acute traumatic event caused by induction of SAH.

Whole body hematocrit/large vessel hematocrit (WBH/LVH ratio) has been examined in 21 normotensive and 35 hypertensive subjects and found to be the same, presumably as an expression of a uniform distribution of the blood volume in the two groups. Moderate renal impairment, the degree of the retinopathy, or the height of the diastolic blood pressure do not seem to influence the ratio figures. The WBH/LVH ratio was examined during treatment with various hypotensive drugs. A significant increase in the ratio was demonstrated during the influence of a single effective intravenous dose of pentolinium. Similar results were obtained during short-term treatment with guanethidine alone and during long-term treatment with guanethidine and hydrochlorothiazide. Treatment with hydrochlorothiazide alone caused an increase in ratio after one week and after three months, but these increases were not significant. The possible causes of these alterations in the WBH/LVH ratio are discussed. The advantage of employing a double isotope technique in preference to a quicker single isotope technique has been analyzed in relation to the determination of the total blood volume in patients during treatment with hypotensive drugs.

Short-term exercise produced a decrease in plasma volume and a rise in B.P. in normotensives and untreated hypertensive patients. The decrease in plasma volume is presumably due to an increased intra-capillary pressure in the contracting muscles. In guanethidine-treated patients there was no change in plasma volume during exercise, probably because of vasodilatation and decreased intra-capillary pressure in the contracting muscles. In several of the guanethidine-treated patients B.P. fell during and after exercise, in some cases so markedly that symptoms of cerebral ischemia developed.

Eleven patients with essential hypertension were treated with hydrochlorothiazide/KCl for three months. A significant fall in total blood volume, exchangeable sodium and blood pressure could be demonstrated both after one to two weeks and after three months of treatment, while a fall in serum sodium and body weight was only significant after one to two weeks of treatment. Thus, hypovolemia may, perhaps, be the explanation for the antipressor effect of thiazide even after three months of treatment.

Thirty-one multiple sclerosis patients in a stable phase were given intensive symptomatic therapy. Isometric and isokinetic measurements of voluntary power were used to assess the effect of the treatment. Twenty-one of the patients were improved, six unchanged and four aggravated. The relative improvement was on the average 35%, best in the weakest patients. Isokinetic measurements revealed a particularly good progress for the fastest movements, probably reflecting reduction of spasticity. The optimum effect of treatment was found on an average after three weeks. Such tests seem to be useful in following and analysing the training and possibly in establishing treatment models.

With the shale gas revolution, coal retirements, environmental regulations, and increasing renewable energy resources, the interdependency of natural gas and electricity has grown significantly. Interdependency challenges, such as mismatched market schedules and disparate market operations, require quantitative modeling in order to garner insights into the effectiveness of various solutions. In this paper, a quantitative model with a dynamic market mechanism is proposed to evaluate the effects of the fuel uncertainty of natural gas-fired power plants on Social Welfare. The results of the model show that as fuel uncertainty increases, Social Welfare decreases in a nonlinear manner, with an increasing slope at higher levels of uncertainty. The model also shows that the effect of market mismatch can be mitigated with increase in the level of Demand Response.

The pathogenesis of cerebral ischaemia after subarachnoid haemorrhage (SAH) still remains elusive. The purpose of the present study was to examine whether specific protein kinas C (PKC) inhibition in rats could alter the transcriptional SAH induced Endothelin (ET) type B and 5-hydroxytryptamine type 1B (5-HT1B) receptor upregulation and prevent the associated cerebral blood flow (CBF) reduction. The PKC inhibitor RO-31-7549 or vehicle was injected intracisternally after the induced SAH in rats ( n = 3 to 10 in each groups for each method). The involvement of the PKC isoforms was investigated with Western blot; only PKCδ and PKCα subtypes were increased after SAH RO-31-7549 treatment abolished this. At 2 days after the SAH basilar and middle cerebral arteries were harvested and the contractile response to endothelin-1 (ET-1; ETA and ETB receptor agonist) and 5-carboxamidotryptamine (5-CT; 5-HT1 receptor agonist) were investigated with a myograph. The contractile responses to ET-1 and 5-CT were increased ( P < 0.05) after SAH compared with sham operated rats. In parallel, the ETB and 5-HT1B receptor mRNA and protein expression were significantly elevated after SAH, as analysed by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Administration of RO-31-7549 prevented the upregulated contraction elicited by application of ET-1 and 5-CT in cerebral arteries and kept the ETB and 5-HT1B receptor mRNA and protein levels at pre-SAH levels. Regional and global CBF evaluated by an autoradiographic technique were reduced by 60%±4% after SAH ( P < 0.05) and prevented by treatment with rO-31-7549. Our study suggests that PKC plays an important role in the pathogenesis of cerebral ischaemia after SAH.

Conscription has been employed for more than a century. To evaluate the course and fate of conscripts deemed mentally unfit for immediate continued service, a prospective questionnaire study of conscripts referred for mental evaluation was conducted. Questionnaires were completed at the time of enrollment, time of admittance for evaluation, time of discharge from their evaluation and at 1-year follow-up. Out of a class of 6949 conscripts, 93 were referred for psychiatric evaluation and 69 of those referred decided to enter the study (60 of these were in time deemed unfit for further military service). At the time of admittance, on average after 79 days of service, there was a significant 36%, 34%, 20% and 20% increase in depression, sleep, somatization and interpersonality scores, respectively. At the time of discharge 14 days after admittance, the symptom scores had dropped to a level comparable to scores at the time of enrollment. At 1-year follow-up, the descending trend in scores was maintained, though not reaching statistical significance compared with scores at time of discharge. The scores at 1-year follow-up were also, except for a higher depression score, comparable with the scores of a control group of conscripts evaluated 1 year after service. The psychological profile of conscripts referred for evaluation was different at the time of enrollment compared with conscripts in general, the scores being between 9% (interpersonality) and 29% (depression) higher. They also had a higher prevalence of adverse family events in their history. The course observed is indifferent from other situations of enforced stress.

The cellular mechanisms responsible for cerebral vasospasm (CVS) occurring after subarachnoid hemorrhage (SAH) have been of major interest over the past 50 years. The present review describes how each of the discrete anatomic components that comprise the cerebral artery may contribute to the pathology of CVS. The blood extravasated after SAH is hemolyzed and undergoes degradation with resultant production of free radicals, known to be powerful initiators of vascular damage. An inflammatory response is generated activating both leukocytes and platelets with subsequent release of inflammatory agents. The cerebral artery affected by CVS undergoes phenotypic change involving both the endothelial and smooth muscle cells. In the endothelium the production of nitric oxide and prostacyclin is affected. In the smooth muscle cells signal transduction pathways that enhance the function of the contractile proteins and induce the upregulation of contractile receptors are activated. In parallel, there is evidence that nervous reflex pathways involving the trigeminal ganglion and the hypothalamus are activated. However, the relative contributions of each of the systems are speculative. Therapy may be directed at disrupting the cascade leading from the SAH insult to CVS or at overcoming the dysfunction incurred by CVS; possible therapeutical interventions are considered.

Overall the aim has been to characterise the in vitro upregulation of the 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) and endothelin (ET) receptors in the cerebral circulation as well as demonstrating phenotypic changes in a pathophysiological model mimicking subarachnoid haemorrhage. The first part describes receptor upregulation using organ culture of whole vessel segments from both rat and man. The upregulation is dependent on gene transcription and translation; thus, an active signalling pathway is involved. Further analysis of this pathway revealed that protein kinase C is especially important in the upregulation process of the ET(B) receptor. The second part attempts to take the concept of receptor upregulation into the pathophysiological realm, especially focusing on experimental subarachnoid haemorrhage. Changes similar to those observed using the in vitro organ culture technique were observed in vivo. Especially the ET(B) receptor upregulates and perhaps more importantly, this appears to be associated with a generally increased sensitivity towards ET-1. Now, even at physiological concentrations of ET-1 were appreciable contraction observed. Similar results were obtained when studying the upregulation of the 5-HT(1B) receptor; the upregulation imparts increased sensitivity of the cerebral arteries towards serotonin. The increased functional responses represent a significant contribution towards the understanding of cerebral vasospasm after subarachnoid haemorrhage. Finally, it is revealed that the ET(B) receptor is more frequently present in human arteries from patients with cerebrovascular disease thus substantiating the idea of receptor upregulation as part of human cerebrovascular pathology.

The vasomotor effects of triptans in the middle cerebral artery (MCA) of rats were studied using the pressurised arteriography method and in vitro vessel baths. Using the arteriograph, MCAs from Sprague-Dawley rats were mounted on two glass micropipettes, pressurised to 85 mm Hg and luminally perfused. Luminally added 5- hydroxytryptamine (5-HT), sumatriptan and rizatriptan induced maximal dilatations of 22 ± 4, 10 ± 2 and 13 ± 5%, respectively, compared to the resting diameter. The relaxant effect of sumatriptan was blocked by the 5- HT1B/1D receptor selective antagonist GR 55562 (10–6M). The use of Nω-nitro-L-arginine and charybdotoxin revealed that the dilatation involved both nitric oxide and endothelially derived hyperpolarising factor. Thus, the earlier demonstrated expression of 5-HT1B/1D immunoreactivity in the endothelium may well translate into a relaxant response to 5-HT and triptans. Using the vessel bath technique, MCA segments were mounted on two metal wires. The relaxant responses to sumatriptan could not be reproduced using this model; instead, weak contractile responses (6 ± 3% of submaximal contractile capacity) were observed. The difference in observations between the experimental models may be related to the maintenance of shear stress in the arteriograph.

Summary: This pilot study looks at the frequency of suicide among Danish soldiers who took part in the UN mandated forces (UNMF) during the 1990's. In a contingent of nearly 4000 Danish UN soldiers four suicides were documented, two of whom committed suicide less than one month before deployment and two who committed suicide within a year after discharge from mission. Contributing factors, prevention strategies, and implications for future research are discussed.

In recent decades, moves toward higher integration of Renewable Energy Resources have called for fundamental changes in both the planning and operation of the overall power grid. One such change is the incorporation of Demand Response (DR), the process by which consumers can adjust their demand in a flexible manner. This paper presents a survey of various aspects of DR including the different types of participants, as well as the underlying challenges and the overall potential of DR when it comes to large-scale implementations. Benefits of DR as reported in the literature for performance metrics such as frequency control and price control, as well as methods for ensuring privacy are discussed. A quantitative taxonomy of DR recently proposed in the literature based on the inherent magnitude, run-time, and integral constraints is discussed and its integration with economic dispatch is explored.

5-hydroxytryptamine (5-HT) is thought to be involved in migraine headache and the pathophysiology of cerebrovascular diseases. Previous data show that organ culture induces a phenotypic change in cerebral vessels. Therefore we investigated if these changes also applied for the vasoconstrictive 5-HT receptors. Rat cerebral arteries express 5-HT 2 receptors. Using organ culture we observed a phenotypic change with a selective up-regulation of 5-HT IB/ID receptors. This was revealed by an increased sensitivity to the selective 5-HT IB/ID agonist 5-CT after organ culture (pEC 50(fresh) 5.6±0.2 and pEC 50(cultured) 6.8 ± 0.4). The response was inhibited by the 5-HT IB/ID selective antagonist GR55562 (pEC 50(fresh) 5.1 ± 0.2 and pEC 50(cultured) 6.0 ± 0.3). The organ model might mimic the phenotypic changes during cerebrovascular diseases.

Background Criteria for Systemic Inflammatory Response Syndrome (SIRS) are recognized as operational criteria for detecting a possible bacteriaemia. Given the sensitivity and specificity of the criteria, clinical judgment is crucial in detecting the condition. The aim of the study was retrospectively to identify clinical characteristics of patients not primarily thought of as having bacteriaemia, yet harboring the condition.

Objectives: Hypothermia is still unproven as beneficial treatment in human stroke, although in animal models, conditioning the brain with hypothermia has induced tolerance to insults. Here, we delineate the feasibility of drug-induced mild hypothermia in reducing ischemic brain damage when conditioning before (preconditioning) and after (postconditioning) experimental stroke. Methods: Hypothermia was induced in rats with a bolus of 6 mg/kg talipexole followed by 20 h continuous talipexole infusion of 6 mg/kg in total. Controls received similar treatment with saline. The core body temperature was continuously monitored. In preconditioning, hypothermia was terminated before either reversible occlusion of the middle cerebral artery (MCAO) for 60 min or global ischemia for 10 min with 2-vessel occlusion and hypotension. In postconditioning, rats experienced 60 min of MCAO before hypothermia was induced either immediately or with 3 h delay. Rats survived ischemia for 2, 7 or 90 days. Infarct volumes were quantified by stereology. Additional experiments of methodological relevance were included in the study. Results: Talipexole induced mild hypothermia (35.1 ± 1.1 to 36.0 ± 0.5°C) for Conclusion: Talipexole is registered for use as a dopamine substitute in humans with Parkinson's disease. Although dosages cannot be directly translated to patients, our study exemplifies in an animal model that drug-induced hypothermia in a clinical setting might reduce cerebral ischemic damage before neuro- and cardiac surgical procedures and after stroke.

Intraventricular hemorrhage (IVH) subsequent to intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) is associated with high mortality and morbidity. The use of fibrinolytic agents to treat this condition has previously been reported in small clinical trials with limited numbers of patients. Variability regarding inclusion criteria, method of administration and outcome have made it difficult to draw firm conclusions regarding the efficacy of antifibrinolytic therapy. Nine patients with CT-diagnosed IVH were treated with Alteplase intrathecally for 3 to 5 days according to the CT-verified clearance of IVH. After the treatment period, a repeat CT scan was performed to evaluate treatment effect.

Canine coagulation factor VII (FVII) deficiency can be hereditary or acquired and may cause life threatening bleeding episodes if untreated. FVII procoagulant activity can be measured by FVII activity (FVII:C), but assays for measurement of canine specific FVII antigen (FVII:Ag) have not been available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable in the diagnosis of hereditary canine FVII deficiency.

Objective: Delayed cerebral vasospasm has long been recognized as an important cause of poor outcome after an otherwise successful treatment of a ruptured intracranial aneurysm, but it remains a pathophysiological enigma despite intensive research for more than half a century. Method: Summarized in this review are highlights of research from North America, Europe and Asia reflecting recent advances in the understanding of delayed ischemic deficit. Result: It will focus on current accepted mechanisms and on new frontiers in vasospasm research. Conclusion: A key issue is the recognition of events other than arterial narrowing such as early brain injury and cortical spreading depression and of their contribution to overall mortality and morbidity.

Thirteen pregnancies in ten women on oxcarbazepine (OXC) monotherapy and one pregnancy in a woman on OXC and topiramate therapy were retrospectively analyzed. A significant decrease of ratio plasma concentration of 10-monohydroxy derivate (MHD) of oxcarbazepine to dosage was found by 26.2% during first trimester, by 36.5% during second trimester and by 38.2% during third trimester when compared to pre-pregnant levels. Eight patients experienced seizure deterioration during the pregnancy, five of which had been seizure-free before the pregnancy. In seven pregnancies (50%) the seizure frequency was at least doubled during pregnancy compared to a pre-pregnancy baseline. There was a trend toward a correlation between seizure deterioration and decrease in plasma concentration of MHD.

Cerebral vasospasm is an important syndrome that afflicts 30% of patients in the aftermath of, and secondary to, subarachnoid hemorrhage. Starting approximately one week after the hemorrhage, the condition worsens the prognosis of the hemorrhage significantly. Apart from general supportive care, no treatment exists for cerebral vasospasm. During the past 50 years, it was thought that the ischemia that signifies poor outcome is more or less exclusively caused by arterial narrowing. However, this idea has recently been challenged by the failure of the drug clazosentan to improve patient outcome, despite reversing vasoconstriction. In this article, we discuss the opinion that factors other than vasoconstriction are important in the pathophysiology and prognosis of cerebral vasospasm. Such factors include global ischemia, disruption of the blood-brain barrier, activation of apoptotic and inflammatory pathways, and cortical spreading depression.

Upregulation of endothelin B (ETB) and 5-hydroxytryptamine 1B (5-HT1B) receptors via transcription has been found after experimental subarachnoid hemorrhage (SAH), and this is associated with enhanced phosphorylation of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK1/2). In the present study, we hypothesized that inhibition of ERK1/2 alters the ETB and 5-HT1B receptor upregulation and at the same time prevents the sustained cerebral blood flow (CBF) reduction associated with SAH. The ERK1/2 inhibitor SB386023-b was injected intracisternally in conjunction with and after the induced SAH in rats. At 2 days after the SAH, cerebral arteries were harvested for quantitative real-time polymerase chain reaction, immunohistochemistry and analysis of contractile responses to endothelin-1 (ET-1; ETA and ETB receptor agonist) and 5-carboxamidotryptamine (5-CT; 5-HT1 receptor agonist) in a sensitive myograph. To investigate if ERK1/2 inhibition had an influence on the local and global CBF after SAH, an autoradiographic technique was used. At 48 h after induced SAH, global and regional CBF were reduced by 50%. This reduction was prevented by treatment with SB386023-b. The ERK1/2 inhibition also decreased the maximum contraction elicited by application of ET-1 and 5-CT in cerebral arteries compared with SAH. In parallel, ERK1/2 inhibition downregulated ETB and 5-HT1B receptor messenger ribonucleic acid and protein levels compared with the SAH. Cerebral ischemia after SAH involves vasoconstriction and subsequent reduction in the CBF. The results suggest that ERK1/2 inhibition might be a potential treatment for the prevention of cerebral vasospasm and ischemia associated with SAH.

Misalignment and instability after cervical laminectomy, performed to treat spondylotic myelopathy, has been described as possible adverse effects. Forty-six consecutively patients on whom laminectomy had been performed in a 4-year period were identified; 7.7 +/- 0.6 years after operation, 11 patients had died and 27 patients were available for follow-up. Postoperative static subluxation was observed in 26% of the patients with an average slip of 3.7 +/- 3.1 mm; 7% had abnormal intervertebral movement displaying 1-2 mm movement from full flexion to full extension. Seventy-four per cent of the patients showed abnormal spinal curvature as judged from radiographs. However, no correlation with outcome was observed. Seventy-four per cent of the patients thought of the result of the operation as either good or fair; objectively, the best long-term effect of the operation was upon arm function. Although some patients develop postural anomaly, laminectomy remains, in terms of instability, a justifiable procedure in the elderly patient with spondylosis.

Object. Cerebral vasospasm following subarachnoid hemorrhage (SAH) leads to reduced blood flow in the brain. Inspired by organ culture—induced changes in the receptor phenotype of cerebral arteries, the authors investigated possible changes in the 5-hydroxytryptamine (HT) receptor phenotype after experimental SAH. Methods. Experimental SAH was induced in rats by using an autologous prechiasmatic injection of arterial blood. Two days later, the middle cerebral artery (MCA), posterior communicating artery (PCoA), and basilar artery (BA) were harvested and examined functionally with the aid of a sensitive in vitro pharmacological method and molecularly by performing quantitative real-time reverse transcription—polymerase chain reaction (PCR). In the MCA and BA the 5-HT1B receptor was upregulated, as determined through both functional and molecular analysis. In response to selective 5-HT1 receptor agonists both the negative logarithm of the 50% effective concentration was increased (one log unit in the MCA and one half unit in the BA), as was the agonist's potency (increased by 50% in the MCA and doubled in the BA). In addition, the authors found an approximately fourfold increase in the number of copies of messenger RNA coding for the 5-HT1B receptor as determined by quantitative real-time PCR. In the PCoA no upregulation of the 5-HT1B receptor was observed. Conclusions. Changes in the receptor phenotype in favor of contractile receptors may well represent the end stage in a sequence of events leading from SAH to the actual development of cerebral vasospasm. Insight into the mechanism of upregulation may provide new targets for developing specific treatment against cerebral vasospasm.

The vascular effects of endothelins (ET) are in mammals mediated via two receptor subtypes, endothelin A (ET(A), mainly constrictive) and endothelin B (ET(B), mainly dilating) receptors. We have examined the presence of ET(A) and ET(B) receptor mRNA using the reverse transcription polymerase chain reaction (RT-PCR) in both normal human cerebral arteries and cerebral arteries from patients with cerebrovascular disease. Two vessel preparations were studied: macroscopic arteries and microvessels, the latter obtained through a sensitive separation method. In endothelial cells both ET(A) and ET(B) receptor mRNA was detected. In almost all samples from normal cerebral arteries only ET(A) receptor mRNA was detected, whereas in vessel samples from patients with cerebrovascular disease as well as cerebral neoplasms, additional ET(B) receptor mRNA was detected significantly more frequently. The pathophysiological significance of this difference is at present speculative, but does point to a vascular involvement of this receptor in cerebrovascular disease.

Brain Natriuretic Peptide (BNP) belongs to the family of natriuretic peptides, the other members being Atrial Natriuretic Peptide (ANP) and C-type Natriuretic Peptide (CNP); each type also existing in iso-forms. The average peptide length is 30 amino acid residues ranging from 20 to 54 [14]. Their systemic effects are hypotension, natriuresis and hyponatraemia, acting via specific natriuretic peptide receptors characterized on the basis of pharmacology and molecular biology [5].

Background and novelty Coagulation Factor VIII (FVIII) is an essential cofactor in the blood coagulation cascade. Inability to produce functional FVIII results in haemophilia A which can be treated with recombinant FVIII [1]. Chinese Hamster Ovary (CHO) cells are the most used cell line for producing complex biopharmaceuticals due to its ability to perform complex post-translational modifications. When mammalian cells overexpress a protein like FVIII they will adapt by regulating various proteins and pathways to support synthesis/production of this protein. Yields of FVIII produced in CHO are low and for this reason a greater understanding of what constitute a high producing cell line is desired. In this study a full transcriptome analysis was undertaken in order to analyze the differences between high and low producers of FVIII

Stroke gives rise to an immediately infarcted area surrounded by an area of critically perfused neural tissue ('area at risk'); the fate of this tissue being dependent on increased perfusion subacutely. Using experimental temporary occlusion of the middle cerebral artery (MCA) in the rat we studied the possible upregulation of the 5-HT(1) receptor in the MCA.Experimental stroke: The MCA of an anaesthetised rat was exposed and temporarily occluded with a hook for 120 mins. Afterwards the rat was revitalised.In vitro pharmacological examination: After two days the rat was killed and the MCA's were harvested and suspended on wires for measurement of contractile properties. Selective 5-HT(1) agonists and antagonists were used to study contractile responses.Contractile responses to 5-HT(1) stimulation were clearly enhanced after stroke (compared to the contralateral MCA). This receptor upregulation implies an increased sensitivity towards the endogenous agonist 5-hydroxytryptamine. It has earlier been shown that temporary occlusion leads to upregulation of a contractile ET(B) receptor. The combined upregulation of contractile receptors may further reduce the blood supply to the area at risk, thus, increasing the infarct size with subsequent increased neurological disability.

Intestinal intubation was performed with a tri-bore tubing in ten subjects without signs of gastrointestinal disease. After administration of a test meal containing Co58-labeled vitamin B12 and with polyethylene glycol as a marker substance, samples of intestinal juice were collected from the upper, middle and anal thirds of the small intestine. During the passage of the test dose from the upper to the middle third of the gut a modest, but significant, absorption of about 6 per cent was discovered. During the passage from the middle to the anal third of the intestine a considerably larger absorption took place, on an average of about 25 per cent of the oral dose. These results agree entirely with those obtained from experiments performed in animals and with clinical observations in man after operations on the small intestine. The most outstanding feature was that, contrary to the generally accepted view, our study seems to indicate that in certain cases the absorption of B12 begins far up in the jejunum. This seemed to be the case in 3 out of 9 experiments. The study throws no light on the cause of this.