998 resultados para 109-648A
Resumo:
Two hypotheses for how conditions for larval mosquitoes affect vectorial capacity make opposite predictions about the relationship of adult size and frequency of infection with vector-borne pathogens. Competition among larvae produces small adult females. The competition-susceptibility hypothesis postulates that small females are more susceptible to infection and predicts frequency of infection should decrease with size. The competition-longevity hypothesis postulates that small females have lower longevity and lower probability of becoming competent to transmit the pathogen and thus predicts frequency of infection should increase with size. We tested these hypotheses for Aedes aegypti in Rio de Janeiro, Brazil, during a dengue outbreak. In the laboratory, longevity increases with size, then decreases at the largest sizes. For field-collected females, generalised linear mixed model comparisons showed that a model with a linear increase of frequency of dengue with size produced the best Akaike’s information criterion with a correction for small sample sizes (AICc). Consensus prediction of three competing models indicated that frequency of infection increases monotonically with female size, consistent with the competition-longevity hypothesis. Site frequency of infection was not significantly related to site mean size of females. Thus, our data indicate that uncrowded, low competition conditions for larvae produce the females that are most likely to be important vectors of dengue. More generally, ecological conditions, particularly crowding and intraspecific competition among larvae, are likely to affect vector-borne pathogen transmission in nature, in this case via effects on longevity of resulting adults. Heterogeneity among individual vectors in likelihood of infection is a generally important outcome of ecological conditions impacting vectors as larvae.
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Giardia duodenalis (syn. lamblia; syn. intestinalis) susceptibility testing is not routinely performed because the classical culture methods are very time-consuming and laborious. We developed a novel flow cytometry (FC) assay to evaluate the susceptibility of G. duodenalis trophozoites to metronidazole (MTZ). Different concentrations of MTZ were added to cultures of trophozoites (10 5 /mL) and the cultures were incubated for different periods. The 50% inhibitory concentration was calculated and propidium iodide (PI) was used to quantify the number of dead cells. After treatment, PI-positive trophozoites increased with increasing drug concentration and exposure time. An excellent correlation was found between FC and the classical method. A novel, accurate and reliable method is now available to evaluate G. duodenalis viability.
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We present here three expression plasmids for Trypanosoma cruzi adapted to the Gateway® recombination cloning system. Two of these plasmids were designed to express trypanosomal proteins fused to a double tag for tandem affinity purification (TAPtag). The TAPtag and Gateway® cassette were introduced into an episomal (pTEX) and an integrative (pTREX) plasmid. Both plasmids were assayed by introducing green fluorescent protein (GFP) by recombination and the integrity of the double-tagged protein was determined by western blotting and immunofluorescence microscopy. The third Gateway adapted vector assayed was the inducible pTcINDEX. When tested with GFP, pTcINDEX-GW showed a good response to tetracycline, being less leaky than its precursor (pTcINDEX).
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The high occurrence of nosocomial multidrug-resistant (MDR) microorganisms is considered a global health problem. Here, we report the draft genome sequence of a MDR Pseudomonas aeruginosa strain isolated in Brazil that belongs to the endemic clone ST277. The genome encodes important resistance determinant genes and consists of 6.7 Mb with a G+C content of 66.86% and 6,347 predicted coding regions including 60 RNAs.
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Assessment of eating habits in young children from multicultural backgrounds has seldom been conducted. Our objectives were to study the reproducibility and the results of a food frequency questionnaire (FFQ) developed to assess changes in eating habits of preschool children with a high migrant population, in the context of a multidisciplinary multilevel lifestyle intervention. Three kindergarten classes (53% from migrant backgrounds) in French-speaking Switzerland were randomly selected and included 16 girls and 28 boys (mean age +/- SD, 5.4 +/- 0.7 years). The FFQ was filled out twice within a 4-week interval by the parents. Spearman rank correlations between the first and the second FFQ for the 39 items of the food questions were as follows: low (r < 0.50) for 8 (7 P < .05 and 1 nonsignificant), moderate (0.50 <or= r < 0.70) for 22 (all P < .01), and high (r >or= 0.70) for 9 (all P < .01). In addition, 28 of 39 intraclass correlation coefficients were high (>0.50, all P < .01). Eighty-six percent of the children ate breakfast at home daily, but only 67% had lunch at home. The percentages of children eating at least once a week in front of the TV were as follows: 50% for breakfast, 33% for lunch, 38% for dinner, and 48% for snacks. Forty percent of children asked their parents to buy food previously seen in advertisements and ate fast food between once a week and once a month. Children generally consumed foods with a high-energy content. The FFQ yielded good test-retest reproducibility for most items of the food questions and gave relevant findings about the eating habits of preschool children in areas with a high migrant population.
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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.
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BACKGROUND & AIMS Hy's Law, which states that hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure (ALF). We aimed to optimize the definition of Hy's Law and to develop a model for predicting ALF in patients with DILI. METHODS We collected data from 771 patients with DILI (805 episodes) from the Spanish DILI registry, from April 1994 through August 2012. We analyzed data collected at DILI recognition and at the time of peak levels of alanine aminotransferase (ALT) and total bilirubin (TBL). RESULTS Of the 771 patients with DILI, 32 developed ALF. Hepatocellular injury, female sex, high levels of TBL, and a high ratio of aspartate aminotransferase (AST):ALT were independent risk factors for ALF. We compared 3 ways to use Hy's Law to predict which patients would develop ALF; all included TBL greater than 2-fold the upper limit of normal (×ULN) and either ALT level greater than 3 × ULN, a ratio (R) value (ALT × ULN/alkaline phosphatase × ULN) of 5 or greater, or a new ratio (nR) value (ALT or AST, whichever produced the highest ×ULN/ alkaline phosphatase × ULN value) of 5 or greater. At recognition of DILI, the R- and nR-based models identified patients who developed ALF with 67% and 63% specificity, respectively, whereas use of only ALT level identified them with 44% specificity. However, the level of ALT and the nR model each identified patients who developed ALF with 90% sensitivity, whereas the R criteria identified them with 83% sensitivity. An equal number of patients who did and did not develop ALF had alkaline phosphatase levels greater than 2 × ULN. An algorithm based on AST level greater than 17.3 × ULN, TBL greater than 6.6 × ULN, and AST:ALT greater than 1.5 identified patients who developed ALF with 82% specificity and 80% sensitivity. CONCLUSIONS When applied at DILI recognition, the nR criteria for Hy's Law provides the best balance of sensitivity and specificity whereas our new composite algorithm provides additional specificity in predicting the ultimate development of ALF.
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Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)a blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNFa blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNFa therapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNFa blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI.
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A partir d'un terrain ethnographique réalisé dans une unité d'urgences psychiatriques, cet article s'intéresse en particulier à la prise de décision concernant le suivi des patients ayant des comportements ou des idées suicidaires. Face à l'imprévisibilité du suicide, l'évaluation du potentiel suicidaire permet de donner une assise formelle et scientifique au travail thérapeutique des soignants. Le choix du suivi (hospitalisation ou accompagnement ambulatoire) dépend toutefois de deux dimensions moins explicites : l'autonomie du patient et son adhésion au dispositif psychiatrique. L'analyse des discours des soignants permet ainsi de relever les logiques contradictoires qui sous-tendent cette décision : d'une part la nécessité de garder le lien avec le patient (en privilégiant un accompagnement) et d'autre part l'exigence de protéger sa vie (en optant pour une hospitalisation).
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BACKGROUND: An accurate, noninvasive technique for the diagnosis of coronary disease would be an important advance. We investigated the accuracy of coronary magnetic resonance angiography among patients with suspected coronary disease in a prospective, multicenter study. METHODS: Coronary magnetic resonance angiography was performed during free breathing in 109 patients before elective x-ray coronary angiography, and the results of the two diagnostic procedures were compared. RESULTS: A total of 636 of 759 proximal and middle segments of coronary arteries (84 percent) were interpretable on magnetic resonance angiography. In these segments, 78 (83 percent) of 94 clinically significant lesions (those with a > or = 50 percent reduction in diameter on x-ray angiography) were also detected by magnetic resonance angiography. Overall, coronary magnetic resonance angiography had an accuracy of 72 percent (95 percent confidence interval, 63 to 81 percent) in diagnosing coronary artery disease. The sensitivity, specificity, and accuracy for patients with disease of the left main coronary artery or three-vessel disease were 100 percent (95 percent confidence interval, 97 to 100 percent), 85 percent (95 percent confidence interval, 78 to 92 percent), and 87 percent (95 percent confidence interval, 81 to 93 percent), respectively. The negative predictive values for any coronary artery disease and for left main artery or three-vessel disease were 81 percent (95 percent confidence interval, 73 to 89 percent) and 100 percent (95 percent confidence interval, 97 to 100 percent), respectively. CONCLUSIONS: Among patients referred for their first x-ray coronary angiogram, three-dimensional coronary magnetic resonance angiography allows for the accurate detection of coronary artery disease of the proximal and middle segments. This noninvasive approach reliably identifies (or rules out) left main coronary artery or three-vessel disease.
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Host-cell factor 1 (HCF-1) is an unusual transcriptional regulator that undergoes a process of proteolytic maturation to generate N- (HCF-1(N)) and C- (HCF-1(C)) terminal subunits noncovalently associated via self-association sequence elements. Here, we present the crystal structure of the self-association sequence 1 (SAS1) including the adjacent C-terminal HCF-1 nuclear localization signal (NLS). SAS1 elements from each of the HCF-1(N) and HCF-1(C) subunits form an interdigitated fibronectin type 3 (Fn3) tandem repeat structure. We show that the C-terminal NLS recruited by the interdigitated SAS1 structure is required for effective formation of a transcriptional regulatory complex: the herpes simplex virus VP16-induced complex. Thus, HCF-1(N)-HCF-1(C) association via an integrated Fn3 structure permits an NLS to facilitate formation of a transcriptional regulatory complex.
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Cet exemplaire de la Lectura d’Henri de Suso sur les Décrétales, dont il ne reste que le premier volume, présente la particularité de contenir aussi le texte des Décrétales, chacune d’elles étant suivie par le commentaire correspondant. Certaines anomalies de la copie permettent de préciser que les copistes avaient comme modèle deux manuscrits différents, un pour la Lectura et l’autre pour les Décrétales dans une édition augmentée des Novelles d'Innocent IV, qui devaient être insérées à la suite des titres correspondants, selon la prescription pontificale de 1245. Le texte même des Novelles qui n’était pas commenté dans la Lectura n’a pas été repris dans la copie, sauf l’Extravagante Quia frequenter, au f. 37v, et Sext. I, 13, 1, au f. 133. F. 1-360v. F. 1-177v. "Apparatus [HENRICI de SEGUSIO cardinalis] Ostiensis super textum Decretalium". [Prooemium:] "[A]d Dei omnipotentis gloriam et universalis ecclesie decus et decorem necnon rei publice et maxime scolasticorum utilitatem... - ...emendate"; — [In epistola dedicatoria Gregorii IX:] "Vicarius regis pacifici ad communem utilitatem et maxime studencium quinque compilationes... - ...et punit" (éd.Venise, I, 3-3v). — "Incipit liber primus Decretalium". [GREGORIUS IX papa, Epistola dedicatoria, salutatio] ; suivi de [HENRICUS DE SEGUSIO, Lectura :] "Gregorius episcopus. Omnes sunt episcopi licet vocentur archiepiscopi, primates vel patriarche... de manu apud eum"; — [GREGORIUS IX papa, Epistola dedicatoria] terminée par l'inscription rubriquée de la première Décrétale; suivi de: [HENRICUS DE SEGUSIO, Lectura in epistola dedicatoria :] "Rex. Regum et omnium potestatum. VIII di. que contra mores... - ...super verbo hac tantum"; et de [ID., Lectura in prima rubrica : ]"Quoniam omne quod non est in fine... - ...de fide catholica" (éd.Venise, I, 3v-5) (1-2v). — Extra 1, 1, 1 ; suivi de [ID., Lectura : ] "Firmiter credimus. Bene dicit nam dubius in fine... - ...Extra 1, 37, 1 ; suivi de [ID., Lectura : ] "Clerici... Et si beneficio etc. careant... de foro compe.", incomplet de la fin par lacune matérielle (éd.Venise, I, 5-182, § 10) (2v-177v). A noter: var. de plusieurs lignes à l'explicit des commentaires sur Extra 1, 1, 2 et 1, 3, 11. A noter les anomalies suivantes :L’inscription de chaque Décrétale, à quelques exceptions près, a été inscrite à la fin du texte de la Décrétale précédente. Le libellé: "Innocentius IIIIus" ou bien "Innocentius IIIIus in concil. Lugdun", qui a été inscrit à la fin des titres I, 3 (25v), 6, (85), 10 (103), 28 (132v), 29 (153), 30 (155v), 31 (164) correspond, en fait, à l'inscription des Novelles d'Innocent IV éditées dans le Sexte, livre I, en tête des titres 3, 6, 8, 13, 14, 15, 16.Au f. 37v, à la suite d'Extra 1, 6, 6, le texte de la constitution d'Innocent IV Quia frequenter a été copié, puis exponctué en marge par un correcteur avec la mention "vacat": "Quia frequenter in electione summorum pontificum colupna Dei... - ...minime computato" avec l'inscription: "Idem" écrite à la fin de la Décrétale précédente qui renvoie à Alexandre III. Sur ce texte qui n’a pas été repris dans le Sexte ; cf. H. Singer, Zeitschrift der Savigny-Stiftung für Rechtesgeschichte, Kan. Abt., VI (1916), 1-140 (éd. Friedberg, 946, Sext. 1, 6, 3, note c). Autres manuscrits recensés : Londres, B.L. ms. Add. 18368, f. 8v ; Paris, BNF ms. latin 14324, f. 234 ; Paris, Bibl. Sainte-Geneviève ms. 339, f. 90 ; Prague, I-B4, f. ? (renseignement aimablement communiqué par Michèle Bégou-Davia).Au f. 133, le titre I, 28 est suivi du texte de Sext. I, 13, 1.Au f.114v, le texte d’Extra 1, 15, 1 §1-6 a été copié une première fois dans le module de la glose à la fin d'un cahier, puis exponctué en marge avec la mention "vacat" et recopié dans le gros module habituel sur un feuillet additionnel (115).Aux ff. 133v-134, les Décrétales 1, 29, 3 et 4, suivies de leurs commentaires, ont été interverties ; de même que les Décrétales 1, 29, 42 et 43, aux ff. 152v-153v. F. 178-360v. "Incipit liber secundus". Extra 2, 1, 1 ; suivi de [HENRICUS DE SEGUSIO, Lectura:] "[D]e Quovultdeo etc. Supple ita statutum est d. n. sed propter hoc plene non subvenitur constronccioni [sic].." - ... Extra 2, 30, 6 "... archid. c. fi. § fi". "Explicit liber secundus. Benedictus sit Deus." (éd.Venise, II, 2-209v). Comme dans le livre I, le libellé inscrit à la fin des titres II, 1 (187), 2 (196v), 5 (202), 13 (240), 14 (247), 15 (249), 18 (252v), 25 (312v), 27 (329v), 28 (357v) correspond à l'inscription des Novelles d'Innocent IV éditées dans le Sexte, livre II, en tête des titres 1-3, 5-7, 9, 12, 14, 15.Au f. 196v, le copiste a copié à la suite les commentaire sur Extra 2, 2, 19 et 20, omettant le texte de Extra 2, 20 qu'il a dû ajouter ensuite dans la marge. Au f. 205, le copiste a mal apprécié l’espace réservé pour Extra 6, 2, le texte commencé normalement en gros module d'écriture, se poursuit en petit module et se termine dans la marge inférieure. De même, au f. 227, les dernières lignes d’ Extra 12, 7 ont dû être écrites dans la marge, avec un signe de renvoi. F. 360v-362. Commentaire anonyme sur Extra 2, 28, 59 De appellationibus: "Ut debitus honor etc. More solito dominus Innocencius premittit causam constitutionis exprimens duas causas motivas: qualiter hec constitutio promulgatur antipophornando... - ... se scit et c. arguta". A noter, f. 1-72v, en marge. PETRUS DE SAMPSONA, Distinctiones super Decretalibus 1, 1, 1-1, 6, 44, excerpta; cf. M. Bertram, "Pierre de Sampson et Bernard de Montmirat...", dans L'Eglise et le droit dans le Midi (XIIIe-XIVe s.) (Cahiers de Fanjeaux, 29), Toulouse, 1994, 37-74 et part. 66, parmi les mss recensés. En marge de l'inscription de l'épitre de Grégoire IX: "Greg. ep. etc. Dominus papa Christi universitatis vicarius set episcopus dicitur singularis quare dominus papa dicatur servus... - ...a papa"; en marge de l'épitre dédicatoire: "Rex pacificus quarum alique propter nimiam similitudinem quedam propter contrarietatem sed numquid in hac compilacione... - ...per totum", incipit A de M. Bertram, art. cit., 64 (1) ; — en marge de la Lectura sur l'épitre dédicatoire: Rex pacificus dicitur esse pacificus et Christus pacem diligit temporalem... - ...approbatur" (1v). — Dernière glose en marge d'Extra 1, 6, 44: "Itaque interim etc. Hii etiam qui pape... - ... et similibus" (72v). A noter, au f. 55v, à la fin de la glose, la signature "P. Sampsone" et au f. 67, "P. Samp.". F. 1-69v, passim et 124v-125. Gloses marginales ajoutées par une main cursive anglaise, contemporaine de la copie. « Doctoribus. Qui faciunt universitatem... - ...dilectus. [signé] Abb(at)is" (Bernardus de Montmirat, Lectura in Decretales, ed. Venise, 1588, I, 2) (1). —En marge de la Lecture sur Extra 1, 6, 42: "B. in apostillis suis dicit quod si aliquis potestatem... - ...commento Hostiensis" (69v).