945 resultados para Innocent III, Pope, 1160 or 61-1216.


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Seamless phase II/III clinical trials are conducted in two stages with treatment selection at the first stage. In the first stage, patients are randomized to a control or one of k > 1 experimental treatments. At the end of this stage, interim data are analysed, and a decision is made concerning which experimental treatment should continue to the second stage. If the primary endpoint is observable only after some period of follow-up, at the interim analysis data may be available on some early outcome on a larger number of patients than those for whom the primary endpoint is available. These early endpoint data can thus be used for treatment selection. For two previously proposed approaches, the power has been shown to be greater for one or other method depending on the true treatment effects and correlations. We propose a new approach that builds on the previously proposed approaches and uses data available at the interim analysis to estimate these parameters and then, on the basis of these estimates, chooses the treatment selection method with the highest probability of correctly selecting the most effective treatment. This method is shown to perform well compared with the two previously described methods for a wide range of true parameter values. In most cases, the performance of the new method is either similar to or, in some cases, better than either of the two previously proposed methods.

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Alterations in the gut microbiota have been recently linked to oral iron. We conducted two feeding studies including an initial diet-induced iron-depletion period followed by supplementation with nanoparticulate tartrate-modified ferrihydrite (Nano Fe(III): considered bioavailable to host but not bacteria) or soluble ferrous sulfate (FeSO4: considered bioavailable to both host and bacteria). We applied denaturing gradient gel electrophoresis and fluorescence in situ hybridization for study-1 and 454-pyrosequencing of fecal 16S rRNA in study-2. In study-1, the within-community microbial diversity increased with FeSO4 (P = 0.0009) but not with Nano Fe(III) supplementation. This was confirmed in study-2, where we also showed that iron depletion at weaning imprinted significantly lower within- and between-community microbial diversity compared to mice weaned onto the iron-sufficient reference diet (P < 0.0001). Subsequent supplementation with FeSO4 partially restored the within-community diversity (P = 0.006 in relation to the continuously iron-depleted group) but not the between-community diversity, whereas Nano Fe(III) had no effect. We conclude that (1) dietary iron depletion at weaning imprints low diversity in the microbiota that is not, subsequently, easily recovered; (2) in the absence of gastrointestinal disease iron supplementation does not negatively impact the microbiota; and (3) Nano Fe(III) is less available to the gut microbiota.

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A multidisciplinary investigation of the collective burial of Cova do Santo is presented as a novel approach to understand daily life during the Bronze Age in Northwest Iberia. The research is focused on three main aspects: i) taphonomy and patterns of disposal, ii) paleopathology and -demography as indicators of health status and lifestyle, and iii) stable isotope analysis to reconstruct paleodiet and to investigate the timing of the introduction of millet to the Iberian Peninsula. Osteological analyses were performed on 64 bones (61 human and 3 animal); additionally, bone collagen was extracted from 15 samples (13 human and 2 animal) and analyzed for its carbon and nitrogen stable isotopes composition. The radiocarbon age of the human remains is consistent with the Middle Bronze Age (c. 1890 to 1600 cal BC). The recovered remains belonged to a minimum number of 14 individuals with an estimated age at death of forty years or younger. This relatively young age is in contrast to a high prevalence of degenerative joint disease in the group. The isotopic results suggest a very homogeneous diet, which was almost exclusively based on C3 plants and terrestrial animal products. Overall, the data suggest that the studied population belonged to a period prior to the introduction of spring or summer-grown crops such as millets. The collective burial from the cave of Cova de Santo, Galicia, currently represents the largest assemblage of prehistoric human remains from Northwest Spain and the relatively good preservation of the bones offers a unique opportunity to investigate daily life in Northern Iberia during the Bronze Age.

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1. In many fig wasp species, armoured wingless males regularly engage in lethal fights for access to females inside figs, which act as discrete mating patches. 2. Kin selection generally opposes killing brothers, because their reproductive success provides indirect genetic benefits (inclusive fitness). However, siblicide may be avoided if (i) brothers do not occur in the same figs, or (ii) males avoid fighting brothers in the same fig. Alternatively, (iii) siblicide may occur because intense mate competition between brothers at the local scale overcomes kin selection effects, or (iv) males do not recognise kin. 3. A fig may also contain wasps from other closely related species and it is not known if males also fight with these individuals. 4. Nine microsatellite loci were used in the first genetic analysis of fighting in fig wasps. We assigned species and sibling identities to males and tested alternative fighting scenarios for three Sycoscapter wasp species in figs of Ficus rubiginosa. 5. Approximately 60% of figs contained males frommore than one Sycoscapter species and approximately 80% of fights were between conspecifics, but a surprising 20% were between heterospecific males. 6.Within species, fewfigs contained brothers, suggesting that females typically lay one son per fig. Overall, most males do not compete with brothers and all fights observed were between unrelated males. Key words:Competition, fighting, genetics, kin selection, microsatellites, relatedness.

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Aim To evaluate, by scanning electron microscopy (SEM), the presence of biofilms on the external surfaces of the apical third of roots of human primary teeth with vital or necrotic pulps with and without radiographically evident periradicular pathosis. Methodology Eighteen teeth were selected: group I - normal pulp (n = 5), group II - pulp necrosis without radiographic evidence of periapical pathosis (n = 7) and group III - pulp necrosis with well-defined radiographic periapical pathosis (n = 6). After extraction, the teeth were washed with saline and immersed in 0.03 g mL(-1) trypsin solution for 20 min. The teeth were then washed in sodium cacodilate buffer and stored in receptacles containing modified Karnovsky solution. The teeth were sectioned, dehydrated in an ethanol series, critical-point dried with CO(2), sputter coated with gold and the external root surface in the apical third examined by SEM. Results In the teeth of groups I and II, the apical root surfaces were covered by collagen fibres, with no evidence of bacteria (100%). In the teeth of group III, the root apices had no collagen fibres but revealed resorptive areas containing microorganisms (cocci, bacilli, filaments and spirochetes) in all cases (100%). Conclusion Microorganisms organized as biofilms on the external root surface (extraradicular infection) were detected in primary teeth with pulp necrosis and radiographically visible periapical pathosis.

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[Ru-2(dNSAID)(4)Cl] and novel [Ru-2(dNSAID)(4)(H2O)(2)]PF6 complexes, where dNSAID = deprotonated carboxylate from the non-steroidal anti-inflammatory drugs (NSIDs), respectively: ibuprofen, Hibp (1) and aspirin, Hasp (2); naproxen, Hnpx (3) and indomethacin, Hind (4), have been prepared and characterized by optical spectroscopic methods. All of the compounds exhibit mixed valent Ru-2(II, III) cores where metal-metal bonds are stabilized by four drug-carboxylate bridging ligands in paddlewheel type structures. The diruthenium complexes and their parent NSAIDs showed no significant effects for Hep2 human larynx or T24/83 human bladder tumor. In contrast, the coordination of Ru-2(II,III) core led to synergistic effects that increased significantly the inhibition of C6 rat glioma proliferation in relation to the organic NSAIDs naproxen and ibuprofen, The possibility that the complexes Ru-2-ibp and Ru-2-npx may exert effects (anti-angiogenic and anti-matrix metalloprotease) that are similar to those exhibited by NAMI-A opens new horizons for in vivo C6 glioma model studies. (C) 2007 Elsevier Ltd. All rights reserved.

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Purple acid phosphatases (PAPs) are a group of metallohydrolases that contain a dinuclear Fe(II)M(II) center (M(II) = Fe, Mn, Zn) in the active site and are able to catalyze the hydrolysis of a variety of phosphoric acid esters. The dinuclear complex [(H(2)O)Fe(III)(mu-OH)Zn(II)(L-H)](CIO(4))(2) (2) with the ligand 2-[N-bis(2-pyridylmethyl)aminomethyl]-4-methyl-6-[N-(2-pyridylmethyl)(2-hydroxybenzyl) aminomethyl]phenol (H(2)L-H) has recently been prepared and is found to closely mimic the coordination environment of the Fe(III)Zn(II) active site found in red kidney bean PAP (Neves et al. J. Am. Chem. Soc. 2007, 129, 7486). The biomimetic shows significant catalytic activity in hydrolytic reactions. By using a variety of structural, spectroscopic, and computational techniques the electronic structure of the Fe(III) center of this biomimetic complex was determined. In the solid state the electronic ground state reflects the rhombically distorted Fe(III)N(2)O(4) octahedron with a dominant tetragonal compression align ad along the mu-OH-Fe-O(phenolate) direction. To probe the role of the Fe-O(phenolate) bond, the phenolate moiety was modified to contain electron-donating or -withdrawing groups (-CH(3), -H, -Br, -NO(2)) in the 5-position. Tie effects of the substituents on the electronic properties of the biomimetic complexes were studied with a range of experimental and computational techniques. This study establishes benchmarks against accurate crystallographic struck ral information using spectroscopic techniques that are not restricted to single crystals. Kinetic studies on the hydrolysis reaction revealed that the phosphodiesterase activity increases in the order -NO(2)<- Br <- H <- CH(3) when 2,4-bis(dinitrophenyl)phosphate (2,4-bdnpp) was used as substrate, and a linear free energy relationship is found when log(k(cat)/k(0)) is plotted against the Hammett parameter a. However, nuclease activity measurements in the cleavage of double stranded DNA showed that the complexes containing the electron-withdrawing -NO(2) and electron-donating CH3 groups are the most active while the cytotoxic activity of the biomimetics on leukemia and lung tumoral cells is highest for complexes with electron-donating groups.

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The first one-pot synthesis of neutral and electron-rich [hydroxy(tosyloxy)iodo]arenes (HTIBs) from iodine and arenes is presented, thereby avoiding the need for expensive iodine(III) precursors. A large set of including a polyfluorinated analogue, can be obtained from the corresponding aryl iodide under the same conditions. The reaction proceeds under mild conditions, without excess reagents, and is fast and high-yielding. Together, the two presented routes give access to a wide range of HTIBs, which are useful reagents in a variety of synthetic transformations.

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The study on reactivity of several -substituted -sulfonyl malonates toward 1,4-diazabicyclo[2.2.2]octane (DABCO) and Bu3N is described. The reactivity with DABCO revealed the possible competition between decarbalkoxylation and unexpected desulfonylation, depending on the -substituent, because of sterical hindrance around the electrophilic centers (SO2 and CO2R). The derivatives with crowded -substituents suffer selective desulfonylation, and a novel and efficient desulfonylation method can be proposed. The dependence of the reactivity of -sulfonyl malonates on the sterical hindrance around the electrophilic centers is confirmed by conformational analysis (Macromodel/MM2* and Mopac/MP3). The carbanionic mechanism is proved because the corresponding protonated, deuterated, and sulfenylated products were obtained by addition of the corresponding electrophilic agents. Bu3N showed itself to be a novel selective decarbalkoxylation agent for any -substituted -sulfonyl malonate.

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The synthesis and characterization of lanthanide(III) citrates with stoichiometries 1:1 and 2:3; [LnL center dot xH(2)O] and [Ln(2)(LH)(3)center dot 2H(2)O], Ln=La, Ce, Pr, Nd, Sm and Eu are reported. L stands for (C6O7H5)(3-) and LH for (C6O7H6)(2-). Infrared absorption spectra of both series evidence coordination of carboxylate groups through symmetric bridges or chelation. X-ray powder patterns show the amorphous character of [LnL center dot xH(2)O]. The compounds [Ln(2)LH(3)center dot 2H(2)O] are crystalline and isomorphous. Emission spectra of Eu compounds suggest C-2v symmetry for the coordination polyhedron of [LnL center dot xH(2)O] and C-4v for [Ln(2)(LH)(3)center dot 2H(2)O]. Thermal analyses (TG-DTG-DTA) were carried out for both series. The thermal analysis patterns of the two series are quite different and both fit in a 4-step model of thermal decomposition, with lanthanide oxides as final products.

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A versatile and metal-free approach for the synthesis of molecules bearing seven- and eight-membered rings is described. The strategy is based on the ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or methyl ether) mediated by the hypervalent iodine reagent HTIB (Phl(OH)OTs). The reaction condition can be easily adjusted to give seven-membered rings bearing different functional groups. A route to medium-ring lactones was also developed.