Full label space reduction in MPLS networks: asymmetric merged tunneling

Traffic Engineering objective is to optimize network resource utilization. Although several works have been published about minimizing network resource utilization in MPLS networks, few of them have been focused in LSR label space reduction. This letter studies Asymmetric Merged Tunneling (AMT) as a new method for reducing the label space in MPLS network. The proposed method may be regarded as a combination of label merging (proposed in the MPLS architecture) and asymmetric tunneling (proposed recently in our previous works). Finally, simulation results are performed by comparing AMT with both ancestors. They show a great improvement in the label space reduction factor

Label Space Reduction in MPLS Networks: How Much Can A Single Stacked Label Do?

Most network operators have considered reducing LSR label spaces (number of labels used) as a way of simplifying management of underlaying virtual private networks (VPNs) and therefore reducing operational expenditure (OPEX). The IETF outlined the label merging feature in MPLS-allowing the configuration of multipoint-to-point connections (MP2P)-as a means of reducing label space in LSRs. We found two main drawbacks in this label space reduction a)it should be separately applied to a set of LSPs with the same egress LSR-which decreases the options for better reductions, and b)LSRs close to the edge of the network experience a greater label space reduction than those close to the core. The later implies that MP2P connections reduce the number of labels asymmetrically

Emerging pharmacotherapies for alcohol dependence: a systematic review focusing on reduction in consumption.

BACKGROUND: European Medicines Agency guidelines recognize two different treatment goals for alcohol dependence: abstinence and reduction in alcohol consumption. All currently approved agents are indicated for abstinence. This systematic review aimed to identify drugs in development for alcohol dependence treatment and to establish, based upon trial design, if any are seeking market authorization for reduction in consumption. METHODS: We searched PubMed and Embase (December 2001-November 2011) to identify agents in development for alcohol dependence treatment. Additional studies were identified by searching ClinicalTrials.gov and the R&D Insight and Clinical Trials Insight databases. Studies in which the primary focus was treatment of comorbidity, or n≤20, were excluded. Studies were then classified as 'abstinence' if they: described a detoxification/alcohol withdrawal period; enrolled patients who had undergone detoxification previously; or presented relapse/abstinence rates as the primary outcome. Studies in patients actively drinking at baseline were classified as 'reduction in consumption'. RESULTS: Of 602 abstracts identified, 45 full-text articles were eligible. Five monotherapies were in development for alcohol dependence treatment: topiramate, fluvoxamine, aripiprazole, flupenthixol and nalmefene. Nalmefene was the only agent whose sponsor was clearly seeking definitive approval for reduction in consumption. Development status was unclear for topiramate, fluvoxamine, aripiprazole and flupenthixol. Fifteen agents were examined in published exploratory investigator-initiated trials; the majority focused on abstinence. Ongoing (unpublished) trials tended to focus on reduction in consumption. CONCLUSIONS: While published studies generally focused on abstinence, ongoing trials focused on reduction in consumption, suggesting a change in emphasis in the approach to treating alcohol dependence.

Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fluvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report

BACKGROUND Mixed hyperlipidemia is common in patients with diabetes. Statins, the choice drugs, are effective at reducing lipoproteins that contain apolipoprotein B100, but they fail to exert good control over intestinal lipoproteins, which have an atherogenic potential. We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day. METHODS Patients with type 2 diabetes and mixed hyperlipidemia were recruited. Fasting lipid profile was taken when patients were treated with diet, diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids. The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA. RESULTS The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides, VLDL triglycerides and the triglyceride/HDL cholesterol ratio, and an increase in HDL cholesterol (P < 0.05). Fluvastatin induced a reduction of 26% in B100 (P < 0.05) and 14% in B48 (NS). However, the addition of omega 3 fatty acids enhanced this reduction to 32% in B100 (NS) and up to 36% in B48 (P < 0.05). CONCLUSION Our preliminary findings therefore suggest an additional benefit on postprandial atherogenic particles when omega 3 fatty acids are added to standard treatment with fluvastatin.

Regional consumption of antibiotics : a demand system approach

Through this paper. we have attempted to model the demand for different classes of antibiotics used for respiratory infections in outpatient care in Switzerland using a spatial version of the linear approximate Almost Ideal Demand System (AIDS) model. This model takes spatial dependency into account by means of spatial lags of antibiotic budget shares. We control for the health status of patients and the potential harmful effects of antibiotic use in terms of bacterial resistance. Elasticities to socioeconomic determinants of consumption and own- and cross-price elasticities between different groups of antibiotic have also been computed in this paper. Significant cross-price elasticities are found between newer or more expensive generations and older or less expensive generations of antibiotics. (C) 2009 Elsevier B.V. All rights reserved.

Reduction in morbidity and mortality from childhood diarrhoeal disease after species A rotavirus vaccine introduction in Latin America : a review

Countries in Latin America were among the first to implement routine vaccination against species A rotavirus (RVA). We evaluate data from Latin America on reductions in gastroenteritis and RVA disease burden following the introduction of RVA vaccine. Published literature was reviewed to identify case-control studies of vaccine effectiveness and population-based studies examining longitudinal trends of diarrhoeal disease reduction after RVA vaccine introduction in Latin American countries. RVA vaccine effectiveness and impact on gastroenteritis mortality and hospitalization rates and RVA hospitalization rates are described. Among middle-income Latin American countries with published data (Mexico, Brazil, El Salvador and Panama), RVA vaccine contributed to a gastroenteritis-associated mortality reduction of 22-41%, a gastroenteritis-associated hospitalization reduction of 17-51% and a RVA hospitalization reduction of 59-81% among children younger than five years of age. In Brazil and El Salvador, case-control studies demonstrated that a full RVA vaccination schedule was 76-85% effective against RVA hospitalization; a lower effectiveness of 46% was seen in Nicaragua, the only low-income country with available data. A growing body of literature offers convincing evidence of "real world" vaccine program successes in Latin American settings, which may be expanded as more countries in the region include RVA vaccine in their immunization programs.

Comparative evaluation under routine conditions of the nitrate reduction assay, the proportion assay and the MGIT 960 assay for drug susceptibility testing of clinical isolates of Mycobacterium tuberculosis

The performance of the nitrate reductase assay (NRA) was compared with the proportion method (PM) on Lowenstein-Jensen medium and the BACTEC MGIT960 assay under routine conditions using 160 clinical isolates of Mycobacterium tuberculosis with a high proportion of resistant strains. The mean time to obtain results was 8.8 days and the overall agreements between NRA and PM and NRA and M960 were 95% and 94%, respectively. NRA was easy to perform and represents a useful tool for the rapid screening of drug-resistant M. tuberculosis strains in low-resource countries.

Glucose control after severe brain injury.

PURPOSE OF REVIEW: A substantial body of evidence supports the use of intensive insulin therapy in general critical care practice, particularly in surgical intensive care unit patients. The impact of intensive insulin therapy on the outcome of critically ill neurological patients, however, is still controversial. While avoidance of hyperglycemia is recommended in neurointensive care, no recommendations exist regarding the optimal target for systemic glucose control after severe brain injury. RECENT FINDINGS: An increase in brain metabolic demand leading to a deficiency in cerebral extracellular glucose has been observed in critically ill neurological patients and correlates with poor outcome. In this setting, a reduction of systemic glucose below 6 mmol/l with exogenous insulin has been found to exacerbate brain metabolic distress. Recent studies have confirmed these findings while showing intensive insulin therapy to have no substantial benefit on the outcome of critically ill neurological patients. SUMMARY: Questions persist regarding the optimal target for glucose control after severe brain injury. Further studies are needed to analyze the impact of intensive insulin therapy on brain glucose metabolism and outcome of critically ill neurological patients. According to the available evidence, a less restrictive target for systemic glucose control (6-10 mmol/l) may be more appropriate.

Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat.

Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2'-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned locomotion but not with the prevention of cocaine-induced sensitization.

Spinal cord stimulation treatment for angina pectoris: more than a placebo?

BACKGROUND: The effects of thoracolumbal spinal cord stimulation (SCS) are confined to restricted microcirculatory areas. This limitation is generally attributed to a predominantly segmental mode of action on the autonomic nervous system. The goal of this study was to determine whether SCS applied close to supraspinal autonomic centers would induce generalized hemodynamic changes that could explain its alleged antianginal properties. METHODS: Invasive hemodynamic tests were performed in 15 anesthetized Göttingen minipigs submitted to iterative cervical SCS of various duration and intensity. RESULTS: Hemodynamic changes exceeding 10% were observed in 59 of 68 SCS sessions (87%). Their extent and time to peak varied with SCS intensity. At 2, 5, and 10 V, significant (t test p < 0.05) peak changes occurred in cardiac output (+34%, +29%, and +28%, respectively), stroke volume (+19%, +16%, +15%), mean pressure (+9%, +27%, +40%), heart rate (+14%, +23%, +14%), systemic (-17%, NS, NS), and pulmonary vascular (25%, NS, NS) resistances. Strikingly, at 2 V, the increase in cardiac output (+34%) was higher than the synchronous rise in rate pressure product (+22%), indicating efficient cardiac work. At 10 V, however, the cardiac work was inefficient (rate pressure product + 53%/cardiac output + 28%). CONCLUSIONS: Low-voltage cervical neuromodulation reduces the postcharge and improves cardiac work efficiency. The resulting reduction in oxygen myocardial demand may account for decreased anginal pain.

Asymmetric tunnels in P2MP LSPs as a label space reduction method

The objective of traffic engineering is to optimize network resource utilization. Although several works have been published about minimizing network resource utilization, few works have focused on LSR (label switched router) label space. This paper proposes an algorithm that takes advantage of the MPLS label stack features in order to reduce the number of labels used in LSPs. Some tunnelling methods and their MPLS implementation drawbacks are also discussed. The described algorithm sets up NHLFE (next hop label forwarding entry) tables in each LSR, creating asymmetric tunnels when possible. Experimental results show that the described algorithm achieves a great reduction factor in the label space. The presented works apply for both types of connections: P2MP (point-to-multipoint) and P2P (point-to-point)

A Label space reduction algorithm for P2MP LSPs using asymmetric tunnels

The aim of traffic engineering is to optimise network resource utilization. Although several works on minimizing network resource utilization have been published, few works have focused on LSR label space. This paper proposes an algorithm that uses MPLS label stack features in order to reduce the number of labels used in LSPs forwarding. Some tunnelling methods and their MPLS implementation drawbacks are also discussed. The algorithm described sets up the NHLFE tables in each LSR, creating asymmetric tunnels when possible. Experimental results show that the algorithm achieves a large reduction factor in the label space. The work presented here applies for both types of connections: P2MP and P2P

The neurobiological basis of prefrontal cortex impairment in the phencyclidine model of schizophrenia : convergent reduction of synaptic glutamate release, energy metabolism and cognitive performance

RÉSUMÉ : Le traitement répété à la phencyclidine (PCP), un bloqueur du récepteur NMDA (NMDAR), reproduit chez les rongeurs une partie de la symptomatologie typique de la schizophrénie. Le blocage prolongé du NMDAR par la PCP mime une hypofunction du NMDAR, une des principales altérations supposées exister dans les cerveaux des patients schizophréniques. Le but de notre étude était d'examiner les conséquences neurochimiques, métaboliques et fonctionnelles du traitement répété à la phencyclidine in vivo, au niveau du cortex préfrontal (cpf), une région cérébrale qui joue un rôle dans les déficits cognitifs observés chez les patients schizophréniques. Pour répondre à cette question, les rats ou les souris ont reçu chaque jour une injection soit de PCP (5 mg/kg), soit de solution saline, pendant 7 ou 14 jours. Les animaux ont ensuite été sacrifiés au moins 24 heures après le dernier traitement. Des tranches aiguës du cpf ont été préparées rapidement, puis stimulées avec une concentration élevée de KCI, de manière à induire une libération de glutamate à partir des terminaisons synaptiques excitatrices. Les résultats montrent que les tranches du cpf des animaux traités à la PCP ont libéré une quantité de glutamate significativement inférieure par rapport à celles des animaux contrôle. Ce déficit de libération a persisté 72 heures après la fin du traitement, tandis qu'il n'était pas observé dans le cortex visuel primaire, une autre région corticale. En outre, le traitement avec des antipsychotiques, l'halopéridol ou l'olanzapine, a supprimé le déficit induit par la PCP. Le même déficit de libération a été remarqué sur des synaptosomes obtenus à partir du cpf des animaux traités à la phenryclidine. Cette observation indique que la PCP induit une modification plastique adaptative du mécanisme qui contrôle la libération du glutamate dans les terminaisons synaptiques. Nous avons découvert que cette modification implique la sous-régulation d'un NMDAR présynaptique, qui serait doué d'un rôle d'autorécepteur stimulateur de la libération du glutamate. Grâce à des tests comportementaux conduits en parallèle et réalisés pour évaluer la fonctionnalité du cpf, nous avons observé chez les souris traitées à la PCP une flexibilité comportementale réduite lors d'un test de discrimination de stimuli visuels/tactiles. Le déficit cognitif était encore présent 4 jours après la dernière administration de PCP. La technique de l'autoradiographie quantitative du [14C]2-deoxyglucose a permis d'associer ce déficit à une réduction de l'activité métabolique cérébrale pendant le déroulement du test, particulièrement au niveau du cpf. Dans l'ensemble, nos résultats suggèrent que le blocage prolongé du NMDAR lors de l'administration répétée de PCP produit un déficit de libération du glutamate au niveau des terminaisons synaptiques excitatrices du cpf. Un tel déficit pourrait être provoqué par la sousrégulation d'un NMDAR présynaptique, qui aurait une fonction de stimulateur de libération; la transmission excitatrice du cpf s'en trouverait dans ce cas réduite. Ce résultat est en ligne avec l'activité métabolique et fonctionnelle réduite du cpf et l'observation de déficits cognitifs induits lors de l'administration de la PCP. ABSTRACT : Sub-chronic treatment with phencyclidine (PCP), an NMDA receptor (NMDAR) channel blocker, reproduces in rodents part of the symptomatology associated to schizophrenia in humans. Prolonged pharmacological blockade of NMDAR with PCP mimics NMDAR hypofunction, one of the main alterations thought to take place in the brains of schizophrenics. Our study was aimed at investigating the neurochemical, metabolic and behavioral consequences of repeated PCP administration in vivo, focusing on the functioning of the prefrontal cortex (pfc), a brain region highly relevant for the cognitive deficits observed in schizophrenic patients. Rats or mice received a daily administration of either PCP (5 mg/kg) or saline for 7 or 14 days. At least 24 hours after the last treatment the animals were sacrificed. Acute slices of the pfc were quickly prepared and challenged with high KCl to induce synaptic glutamate release. Pfc slices from PCP-treated animals released significantly less glutamate than slices from salinetreated animals. The deficit persisted 72 hours after the end of the treatment, while it was not observed in another cortical region: the primary visual cortex. Interestingly, treatment with antipsychotic drugs, either haloperidol or olanzapine, reverted the glutamate release defect induced by PCP treatment. The same release defect was observed in synaptosomes prepared from the pfc of PCP-treated animals, indicating that PCP induces a plastic adaptive change in the mechanism controlling glutamate release in the glutamatergic terminals. We discovered that such change most likely involves the down-regulation of a newly identified, pre-synaptic NMDAR with stimulatory auto-receptor function on glutamate release. In parallel sets of behavioral experiments challenging pfc function, mice sub-chronically treated with PCP displayed reduced behavioral flexibility (reversal learning) in a visual/tactile-cued discrimination task. The cognitive deficit was still evident 4 days after the last PCP administration and was associated to reduced brain metabolic activity during the performance of the behavioral task, notably in the pfc, as determined by [14C]2-deoxyglucose quantitative autoradiography. Clverall, our findings suggest that prolonged NMDAR blockade by repeated PCP administration results in a defect of glutamate release from excitatory afferents in the pfc, possibly ascribed to down-regulation of apre-synaptic stimulatory NMDAR. Deficient excitatory neurotransmission in the pfc is consistent with the reduced metabolic and functional activation of this area and the observed PCP-induced cognitive deficits.

QFT control for vibration reduction in structures equipped with MR dampers

This short paper addresses the problem of designing a QFT (quantitative feedback theory) based controllers for the vibration reduction in a 6-story building structure equipped with shear-mode magnetorheological dampers. A new methodology is proposed for characterizing the nonlinear hysteretic behavior of the MR damper through the uncertainty template in the Nichols chart. The design procedure for QFT control design is briefly presented