Cavity approach for the approximation of spectral density of graphs with heterogeneous structures.

Graphs have become widely used to represent and study social, biological, and technological systems. Statistical methods to analyze empirical graphs were proposed based on the graph's spectral density. However, their running time is cubic in the number of vertices, precluding direct application to large instances. Thus, efficient algorithms to calculate the spectral density become necessary. For sparse graphs, the cavity method can efficiently approximate the spectral density of locally treelike undirected and directed graphs. However, it does not apply to most empirical graphs because they have heterogeneous structures. Thus, we propose methods for undirected and directed graphs with heterogeneous structures using a new vertex's neighborhood definition and the cavity approach. Our methods' time and space complexities are O(|E|h_{max}^{3}t) and O(|E|h_{max}^{2}t), respectively, where |E| is the number of edges, h_{max} is the size of the largest local neighborhood of a vertex, and t is the number of iterations required for convergence. We demonstrate the practical efficacy by estimating the spectral density of simulated and real-world undirected and directed graphs.

Identification of alterations associated with age in the clustering structure of functional brain networks.

Initial studies using resting-state functional magnetic resonance imaging on the trajectories of the brain network from childhood to adulthood found evidence of functional integration and segregation over time. The comprehension of how healthy individuals' functional integration and segregation occur is crucial to enhance our understanding of possible deviations that may lead to brain disorders. Recent approaches have focused on the framework wherein the functional brain network is organized into spatially distributed modules that have been associated with specific cognitive functions. Here, we tested the hypothesis that the clustering structure of brain networks evolves during development. To address this hypothesis, we defined a measure of how well a brain region is clustered (network fitness index), and developed a method to evaluate its association with age. Then, we applied this method to a functional magnetic resonance imaging data set composed of 397 males under 31 years of age collected as part of the Autism Brain Imaging Data Exchange Consortium. As results, we identified two brain regions for which the clustering change over time, namely, the left middle temporal gyrus and the left putamen. Since the network fitness index is associated with both integration and segregation, our finding suggests that the identified brain region plays a role in the development of brain systems.

Safety, Tolerability and Clinical Effects of a Rapid Dose Titration of Subcutaneous Treprostinil Therapy in Pulmonary Arterial Hypertension: A Prospective Multi-Centre Trial.

BACKGROUND: Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation. OBJECTIVES: The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management. METHODS: Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study. RESULTS: Thirty-nine patients with idiopathic or heritable pulmonary arterial hypertension on stable treatment with oral pulmonary arterial hypertension-approved drugs (90% on dual combination therapy) were included. Patients achieved a median treprostinil dosage of 35.7 ng/kg/min after 16 weeks. A good overall safety profile was demonstrated with 3 patients (8%) withdrawing due to infusion site pain, which occurred in 97% of patients. After 16 weeks, median 6-min walking distance, cardiac index, pulmonary vascular resistance, and tricuspid annular plane systolic excursion improved. CONCLUSIONS: Rapid up-titration of subcutaneous treprostinil was well tolerated, achieving a clinically effective dose associated with improvement of exercise capacity and haemodynamics after 16 weeks. A rapid dose titration regimen and proactive infusion site pain management may improve the handling of this therapy and contribute to better treatment outcome.

Allelic diversity at the DLA-88 locus in Golden Retriever and Boxer breeds is limited.

In the dog, previous analyses of major histocompatibility complex class I genes suggest a single polymorphic locus, dog leukocyte antigen (DLA)-88. While 51 alleles have been reported, estimates of prevalence have not been made. We hypothesized that, within a breed, DLA-88 diversity would be restricted, and one or more dominant alleles could be identified. Accordingly, we determined allele usage in 47 Golden Retrievers and 39 Boxers. In each population, 10 alleles were found; 4 were shared. Seven novel alleles were identified. DLA-88*05101 and *50801 predominated in Golden Retrievers, while most Boxers carried *03401. In these breeds, DLA-88 polymorphisms are limited and largely non-overlapping. The finding of highly prevalent alleles fulfills an important prerequisite for studying canine CD8+ T-cell responses.

Randomised, double-blind, placebo-controlled parallel group study of P54FP for the treatment of dogs with osteoarthritis.

P54FP is an extract of Indian and Javanese turmeric, Curcuma domestica and Curcuma xanthorrhiza respectively, which contains a mixture of active ingredients including curcuminoids and essential oils. A randomised, double-blind, placebo-controlled, parallel group clinical trial of P54FP as a treatment for osteoarthritis of the canine elbow or hip was conducted to assess its efficacy and safety. Sixty-one client-owned dogs with osteoarthritis were recruited through first-opinion practices and examined at a single centre. After a two-week wash-out period, they were randomly allocated to receive P54FP or a placebo orally twice daily for eight weeks, and were re-examined after four, six and eight weeks of treatment. The effectiveness of the treatment was assessed in terms of the peak vertical force (PVz) and vertical impulse of the affected limbs, as measured with a force platform, by clinical assessments of lameness and joint pain by the investigators, and overall assessments of the response to treatment by the investigators and the owners. The results from 25 P54FP-treated dogs and 29 placebo-treated dogs showed that there was no statistically significant difference between the groups in terms of the PVz of the affected limb. The investigators' overall assessment showed a statistically significant treatment effect in favour of P54FP (P=0.012), but the owners' assessment just failed to reach statistical significance (P=0.063). No serious adverse effects were recorded, but two P54FP-treated dogs and four placebo-treated dogs were withdrawn from the study because their condition deteriorated.

Separation of amino acid enantiomers by micellar electrokinetic capillary chromatography using synthetic chiral surfactants.

A synthetic chiral surfactant was employed for the enantioselective micellar electrokinetic capillary chromatographic (MECC) separation of amino acid enantiomers derivatized with 6-aminoquinoyl-N-hydroxysuccinimidyl carbamate (AQC). The effect of surfactant concentration and buffer pH on resolution was studied, and the optimized conditions were used to evaluate the method in terms of sensitivity, reproducibility, and linearity. Resolution and alpha values for 12 ACQ-derivatized amino acids are reported. The ability to perform both achiral and chiral separations simultaneously is illustrated in a separation of a mixture of six amino acid enantiomeric pairs, all with baseline resolution. The direct reversal of enantiomer migration order, useful in quantitation and chiral identification, is also shown. Comparisons with other N-protected amino acid derivatives are made in terms of resolution and sensitivity, and the advantages of this chiral MECC technique used in conjunction with the inherent advantages of the AQC derivatizing reagent are discussed.

Novel chiral surfactant for the separation of enantiomers by micellar electrokinetic capillary chromatography.

A novel chiral surfactant was prepared as both enantiomeric forms, (R)- and (S)-N-dodecoxycarbonylvaline, and employed for the separation of enantiomeric mixtures by micellar electrokinetic capillary chromatography (MECC). The enantioselectivities (alpha) obtained for twelve typical pharmaceutical amines using the (S)-surfactant were compared to those obtained with (S)-N-dodecanoylvaline, a chiral surfactant described in the literature. Higher enantioselectivities were seen for ten of the twelve compounds using (S)-N-dodecoxycarbonylvaline. Furthermore, (S)-N-dodecoxycarbonylvaline had significantly less background absorbance in the low UV. It is shown that exact enantiomer migration order reversal can be obtained by individually employing both enantiomeric forms of the surfactant. For ionizable compounds like the amines examined here, enantioselectivity can be optimized by changing the pH of the MECC buffer. Partitioning is optimized through surfactant concentration, organic additives and pH. The ability to achieve fast chiral separations is shown. A separation of ephedrine enantiomers in urine is shown, with the only sample preparation being filtration.

Direct effects of propofol (2,6-diisopropylphenol) on canine coronary artery ring tension.

1. The direct effect of the intravenous general anesthetic propofol (2,6-diisopropylphenol) on epicardial coronary artery tone was studied in unstimulated canine coronary artery rings. 2. Rings stretched to a basal tension of 5 g and exposed to increasing concentrations of propofol generated a characteristic dose-dependent biphasic change in tension-concentrations from 10(-7) to 10(-5) M resulted in constriction (+477 +/- 118 mg) while concentrations 10(-4) and 10(-3) M resulted in relaxation (-682 +/- 75 mg). 3. The response to propofol was reversible and was not modified by the presence of endothelium, alpha 1 and beta adrenoceptor blockade or TEA sensitive potassium channel blockade. 4. The propofol induced changes in tension were altered by changes in extracellular calcium concentrations as well as by blockade of the voltage dependent calcium channel by verapamil. 5. These experiments suggest that clinical concentrations (human) of propofol may have direct vasoactive effects on epicardial coronary artery smooth muscle and that these effects may be due to actions on voltage dependent calcium channels of vascular smooth muscle.

Patient-controlled analgesia. A serious incident.

A patient received a massive overdose of papaveretum intravenously (estimated to be 180 mg) when the glass syringe of a patient-controlled analgesia machine disengaged from the drive mechanism. She was successfully resuscitated. The pump, on loan from the supplier, had passed a brief evaluation by the infusion pump test house designated by the Medical Devices Directorate of the Department of Health; it has since been withdrawn. It is recommended that patient-controlled analgesia equipment should be placed at or below patient heart level. The Department of Health is called on to institute a full, independent evaluation scheme for patient-controlled analgesia equipment.

Alprazolam but not diazepam protects hamsters with heart disease from the medical consequences of stress.

We have previously shown that subjecting cardiomyopathic hamsters in the lesion-developing period of their heart disease to cold-immobilization stress had lethal consequences which could be blocked by alprazolam treatment. This experiment replicated that finding and also examined the efficacy of diazepam in this paradigm. In contrast to alprazolam, diazepam did not prevent the cardiomyopathic subjects from succumbing to the stressor. Thus, the effect of alprazolam in reducing stress-induced mortality did not reflect a generic benzodiazepine action.

Learned fear: a cause of arrhythmia onset in the presence of digitalis.

In earlier studies we have shown that guinea pigs exposed to signal-shock pairs develop digitalis toxicity earlier than control pigs on a test day when shocks are not delivered. Presenting subjects with signal-shock pairs is known to produce learned changes in autonomic tone thought to reflect fear. However, we were unable to find evidence of such changes in that model. A recent report extended our work on psychosomatic digitalis toxicity to the rabbit. Although that animal has been extensively used in studies of visceral learning, that study did not provide sufficient data to rigorously conclude that visceral learning had taken place. In this report, we show that rabbits which have learned that a signal accurately predicts the occurrence of shock develop digitalis-toxic arrhythmias more often during the signal and significantly earlier than other rabbits given prior exposure to equal numbers of signals and shocks, never explicitly paired. The use of this latter control group indicates that rabbits exposed to signal-shock pairs have learned to associate the signal with its consequences; independent evidence of learning exists in the fact that these rabbits showed a signal-locked bradycardia on their training day. However, bradycardia did not appear to be the mechanism for the early elicitation of digitalis toxicity on the test day when ouabain was infused during probes with the signal alone. These data may have clinical significance in their indication that factors in the external milieu can precipitate digitalis-toxic arrhythmias in individuals that would otherwise have no evidence of digitalis toxicity.

Fluid retention and relative hypoventilation in acute mountain sickness.

The presence of pulmonary, cerebral, and/or peripheral edema in acute mountain sickness (AMS) implies a derangement in the body's handling of water. Previously, we demonstrated water retention and increased symptoms of AMS when hypocapnia was prevented in subjects exposed to simulated high altitude. This led us to the hypothesis that upon ascent to high altitude, those persons who fail to increase their ventilation adequately and hence do not become hypocapnic will retain water reflected as weight gain and will develop AMS. To test this hypothesis, we studied in Kathmandu, Nepal (1,377 m) 42 healthy western tourists; all were restudied in Pheriche (4,243 m) within 6 days of exposure to high altitude. Symptoms of AMS were highly correlated (p less than 0.001) with weight change, suggesting that persons becoming symptomatic retained fluid. On going from low to high altitude, those persons who lost weight and remained well increased their resting ventilation, whereas those who gained weight did not (p = 0.03). This relative hypoventilation in the latter group was confirmed by higher values of Pco2 (heated hand vein blood) and lower values of arterial saturation (ear oximeter) at Pheriche. Vital capacity measured in Kathmandu was correlated with arterial saturation at Pheriche (p = 0.02); persons with low vital capacity were more hypoxemic with more symptoms of AMS. We conclude that relative hypoventilation and weight gain appear early in the development of AMS suggesting links between altitude hypoxia, hyperventilation, hypocapnia, and the body's handling of water.

Estudio del sector textil en Bolivia

Contenido: 1.Introduccion. 2.Definicion de objetivos. 3.Metodologia.4.Situacion actual del sector. 5.Marco de desenvolvimiento operativo. 6.Diagnostico del sector. 7.Planta tipo de hilado y tejido de algodon.Esquemas. 8.Pronostico de posibilidades del sector. 9.Conclusiones finales. Anexos.