Si le renouveau de la paix royale au XIIème siècle est un phénomène bien connu, son essor aux XIIIème et XIVème siècles l’est beaucoup moins. La période qui sépare les règnes de Philippe Auguste à ...celui de Charles IV – 1180-1328 – est pourtant décisive. Durant celle-Ci, à la faveur d’un contexte très favorable à sa cause, la royauté parvient à s’ériger en éminente pacificatrice de son royaume, achevant de substituer la paix du roi à l’ancienne paix de Dieu. Le défi est pourtant immense. Plus que tout, trois méfaits ne cessent de menacer la paix, contre lesquels la couronne s’efforce de lutter : les violences sur les chemins, les associations illicites, et les guerres qui surviennent entre les sujets. Dans le combat résolu qu’ils engagent, les rois sont portés par la pensée des ecclésiastiques. Ces derniers, s’appuyant sur l’antique tradition carolingienne, ne cessent de rappeler aux rois que leur devoir est d’œuvrer pour la tranquillité du royaume. La renaissance aristotélicienne renforce considérablement cette rhétorique : à la lumière d’Aristote, les théologiens soulignent que la paix est la fin même de l’office princier. Galvanisés par ces discours édifiants, les Capétiens s’efforcent de réfréner les tumultes provoqués par les agresseurs de chemins, les fauteurs de guerre, et les sujets qui se liguent. À cette fin, ils n’hésitent pas à agir en législateurs : ils édictent de nombreuses lois, tantôt locales et tantôt générales, qui condamnent avec fermeté ces dangereux malfaiteurs. L’application de ces préceptes se heurte à de fortes résistances, et la politique royale connaît de réelles vicissitudes. Néanmoins, l’action menée par la royauté renforce sa vocation souveraine et porte des fruits concrets. Les actes de la pratique montrent que les serviteurs de la couronne entreprennent de nombreuses actions visant à sanctionner les fauteurs de troubles violant la légalité royale. Le volontarisme de la couronne est tout particulièrement évident à l’encontre de ceux qui livrent des guerres, régulièrement condamnés pour leurs entreprises devant la justice royale. En définitive, en déployant ainsi tous leurs efforts, les Capétiens parviennent à instaurer un ordre pacifique sur lequel peuvent ensuite s’appuyer leurs successeurs Valois.
If the renewal of king's peace in the XIIth century is a well-Known phenomenon, its blossoming in the XIIIth and XIVth centuries is less-Known. The period which separates the reigns of Philippe Auguste and Charles le Bel – 1180-1328 – is none-The-Less decisive. During this period, thanks to a very favourable context, kingship succeeded in setting itself up as an eminent peacemaker of its kingdom, finally replacing God's ancient peace by king's peace. The challenge is however immense. More than anything, three ravages which the crown strives to fight, keep on threatening the peace : violence on public roads, illicit associations, and wars arising between subjects. In their resolute fight, kings are prompted by the thought of the ecclesiastics who, referring to the antique carolingian tradition, insist on reminding the kings that their duty is to work for their kingdom tranquillity. The Aristotelian rebirth reinforces this rhetoric : in the light of Aristote, theologians emphasize that peace is the ultimate aim of a king's duty. Stimulated by those enlightened discourses, Capetians try to refrain the disorders generated by highwaymen, warmongers and subjects who join together. To achieve their goal they choose to act as legislators : they enact numerous laws, some local some general, which firmly condemn those dangerous criminals. Enforcing these precepts meets with strong resistances and king's policy goes through real vicissitudes. However, king's policy reinforces its sovereignty and achieves concrete results. Sources attest that the crown servants undertake numerous actions aiming at punishing troublemakers who violate the king's law. The crown determination is particularly obvious against those who take part in wars and are regularly sentenced for their wrongdoing by the king's justice. Hence by expending all their efforts and energy, Capetians succeed in establishing some peaceful order on which their successors the Valois will lean.
Objectives
Effect of 3 different dairy protein sources on the recovery of muscle function after limb immobilization in old rats.
Design
Longitudinal animal study.
Setting
Institut National de la ...Recherche Agronomique (INRA). The study took part in a laboratory setting.
Intervention
Old rats were subjected to unilateral hindlimb immobilization for 8 days and then allowed to recover with 3 different dietary proteins: casein, soluble milk proteins or whey proteins for 49 days.
Measurements
Body weight, muscle mass, muscle fibre size, isometric, isokinetic torque, muscle fatigability and muscle oxidative status were measured before and at the end of the immobilization period and during the recovery period i.e 7, 21, 35 and 49 days post immobilization.
Results
In contrast to the casein diet, soluble milk proteins and whey proteins were efficient to favor muscle mass recovery after cast immobilization during aging. By contrast, none of the 3 diary proteins was able to improve muscle strength, power and fatigability showing a discrepancy between the recovery of muscle mass and function. However, the soluble milk proteins allowed a better oxidative capacity in skeletal muscle during the rehabilitation period.
Conclusion
Whey proteins and soluble milk proteins improve muscle mass recovery after immobilization-induced muscle atrophy in old rats but do not allow muscle functional property restoration.
(Headache 2011;51:533‐543)
Objective.— To evaluate the efficacy and tolerability of telcagepant when co‐administered with ibuprofen or acetaminophen for the acute treatment of migraine.
Background.— ...Telcagepant is an oral calcitonin gene‐related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. Combining telcagepant with analgesics that have a different mechanism of action could produce greater efficacy.
Methods.— Randomized, double‐blind, placebo‐controlled study. Patients were randomized to treat a moderate or severe migraine headache with either telcagepant 280 mg + ibuprofen 400 mg (N = 171), telcagepant 280 mg + acetaminophen 1000 mg (N = 171), telcagepant 280 mg (N = 170), or placebo (N = 171). The primary efficacy endpoint was 2‐hour pain freedom. The study had approximately 88% power to detect an additive effect of at least 15 percentage points (telcagepant combination vs telcagepant monotherapy) and 48% power to detect an additive effect of at least 10 percentage points. Safety and tolerability were assessed by adverse events and laboratory tests.
Results.— The percentages of patients with 2‐hour pain freedom were greater in each active treatment group compared to placebo (P < .001): telcagepant + ibuprofen = 35.2%, telcagepant + acetaminophen = 38.3%, telcagepant = 31.2%, placebo = 10.9%. No significant differences were seen for either of the combination groups vs telcagepant monotherapy, but both were numerically larger than telcagepant monotherapy. All the active treatments were generally well tolerated. The percentage of patients reporting any adverse event within 48 hours was higher in the active treatment groups than placebo: telcagepant + ibuprofen = 30.3%, telcagepant + acetaminophen = 31.6%, telcagepant = 24.8%, placebo = 18.2%. The most common adverse events reported by ≥4 patients in one or more of the treatment groups that included telcagepant were fatigue, nausea, dizziness, somnolence, dry mouth, and tremor.
Conclusions.— The combination of telcagepant 280 mg with either ibuprofen 400 mg or acetaminophen 1000 mg did not show a statistically significant difference from telcagepant alone. Numerically greater treatment effects in the combination treatment groups over the telcagepant 280 mg monotherapy suggest that telcagepant combination treatments may merit further evaluation in studies powered to detect smaller additive benefits. (Clinicaltrials.gov; NCT00758836).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Centrifugal microfluidics has received much attention in the last decade for the automation of blood testing at the point-of-care, specifically for the detection of chemistries, proteins, and nucleic ...acids. However, the detection of common blood cells on-disc, particularly leukocytes, remains a challenge. In this paper, we present two analytical methods for enumerating leukocytes on a centrifugal platform using a custom-built fluorescent microscope, acridine orange nuclear staining, and image processing techniques. In the first method, cell analysis is performed in glass capillary tubes; in the second, acrylic chips are used. A bulk-cell analysis approach is implemented in both cases where the pixel areas of fractionated lymphocyte/monocyte and granulocyte layers are correlated with cell counts. Generating standard curves using porcine blood sample controls, we observed strong linear fits to measured cell counts using both methods. Analyzing the pixel intensities of the fluorescing white cell region, we are able to differentiate lymphocytes from monocytes via pixel clustering, demonstrating the capacity to perform a 3-part differential. Finally, a discussion of pros and cons of the bulk-cell analysis approach concludes the paper.
Background: Desensitization and blockade of 5-HT sub(2C) receptors (5-HT sub(2C)R) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral ...pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT sub(2C)R desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT super(-/-)) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT sub(2C)R was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT sub(2C)R-induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos-induced expression) levels. Results: Although 5-HTT super(-/-) mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT sub(2C)R-mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT sub(2C)R-mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT super(-/-) mutants. These indices of tolerance to 5-HT sub(2C)R stimulation were associated neither with altered levels of 5-HT sub(2C)R protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT sub(2C)R was higher in 5-HTT super(-/-) mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT sub(2C)R-like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT sub(2C)R agonist RO-60,0175 was absent in 5-HTT super(-/-) mutants. Conclusions: Such blunted responsiveness of the 5-HT sub(2C)R system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT super(-/-) mice.
How the spatial expansion of a species changes at a human time scale is a process difficult to determine. We studied the dispersal pattern of the French white stork population, using a 21-year ...ringing/resighting dataset. We used the graph-theory to investigate the strength of links between 5 populations (North-East, North-West, Centre, West, and South) and to determine factors important for the birds' movements. Two clusters of populations were identified within the metapopulation, with most frequent movements of individuals between North-Eastern and Centre populations, and between North-Western and Western populations. Exchanges of individuals between populations were asymmetrical, where North-Eastern and North-Western populations provided more emigrants than they received immigrants. Neither the geographical distance between populations, nor the difference in densities influenced the number of individuals exchanging between populations. The graph-theory approach provides a dynamic view of individual movements within a metapopulation and might be useful for future population studies in the context of conservation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology ...studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT-/-) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR–induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos–induced expression) levels. Results: Although 5-HTT-/- mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR–mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR–mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT-/- mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT-/- mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR–like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT-/- mutants. Conclusions: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT-/- mice.
This work was supported by grants from INSERM, UPMC, the European Community (FP7, “Devanx” consortium, F2-2007–201714), and ANR (Sercedit 2008–2010, contract ANR-06-Neuro-045-01). Dr CBP Martin was recipient of a fellowship from the French Ministère de la Recherche during performance of this work. Dr Trigo was supported by Fundacion Alicia Koplowitz. Dr Fink (DA07287, DA034488) and Dr Cunningham (DA024157, DA020087) were supported by the National Institute on Drug Abuse grants.
The often-cited means to reduce poverty in rural areas is to push the sustainable intensification of the agricultural sector or to favor a livelihood diversification strategy. However, rural ...households that invest their resources in multiple domains can achieve contrasting livelihood returns and benefits. The present paper explores the contribution of livestock activities, especially dairy, in the various livelihood strategies of rural households, based on an evaluation of revenue repartition, poverty level, and nutrient input in the diverse households, using a simulation tool at the farm household level. Our research was carried out in a case study on the viability of rural households in the governorate of Beni Suef (Middle Egypt). The results show that the diversification of activities towards cropping activities and off-farm jobs in the household contributed more to poverty reduction than dairy activities. Householders with small herds and land access benefited weakly from milk price increases and more generally, from a specialization of dairy activities due to structural constraints. This calls for identifying new rural policies for small-scale (less than 2.5ha) units that represent more than 90 percent of family farms in Egypt. Notably, new job opportunities and diversification should be developed along the agro-food value chain process.
Centrifugal microfluidics has received much attention in the last decade for the automation of blood testing at the point-of-care, specifically for the detection of chemistries, proteins, and nucleic ...acids. However, the detection of common blood cells on-disc, particularly leukocytes, remains a challenge. In this paper, we present two methods for enumerating leukocytes on a centrifugal platform using a custom-built fluorescent microscope, nuclear staining, and image processing. In the first method, cell analysis is performed in glass capillary tubes; in the second, acrylic chips are used. A bulk-cell analysis approach is implemented in both cases where the pixel areas of fractionated lymphocyte/monocyte and granulocyte layers are correlated with cell counts. Generating standard curves using porcine blood sample controls, we observed strong linear fits to measured cell counts using both methods. Analyzing the pixel intensities of the fluorescing white cell region, we are able to differentiate lymphocytes from monocytes
via
pixel clustering, demonstrating the capacity to perform a 3-part differential. Finally, a discussion of pros and cons of the bulk-cell analysis approach concludes the paper.
Methods for enumerating leukocytes on a centrifugal platform using a custom built fluorescent microscope, nuclear stain, and image processing techniques.