DOMINO-AD protocol:donepezil and memantine in moderate to severe Alzheimer's disease - a multicentre RCT

Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil.

1.° Anonymi glossae in totum jus civile. — 2.° Innocentii IV. Papae, tractatus exceptionum. — 3.° Domini Dyni de Mugilo, sive potius de Mugello, legum Doctoris, tractatus de praescriptionibus. — 4.° Poggii, Florentini, invectiva in Laurentium Vallam. — 5.° Differentiae legum et canonum : authore domino Galvano de Bononia

Colbertinus, antea Jacobi Augusti Thuani

1.° Fratris Martini Poloni, de ordine Praedicatorum ac domini Papae Poenitentiarii, chronica de summis Pontificibus et Imperatoribus, à Christo ad annum 1277. — 2.° Capita nonnulla ad morum doctrinam pertinentia. — 3.° Vita et miracula sancti Benedicti. — Ad hujusce codicis calcem haec leguntur : Anno Domini 1272. Philippus, Rex Franciae, die Veneris ante passionem Domini venit apud Malleziacum invitatus à reverendo patre domino Radulpho, tunc temporis Abbate dicti loci, ibidemque manducavit et pernoctavit, in crastinoque recessit.

Baluzianus

summa feudorum : authore domino Ardicone de Broilo de Verona

Colbertinus

1.° Henrici de Amondavilla practica chirurgiae : pars ferè dimidia desideratur. — 2.° Jesu, filii Haly, epistola, sive tractatus de aegritudinibus oculorum, et earum curatione. — 3.° Anonymi fragmentum de meteoris. — 4.° Avicennae liber de viribus cordis et medicinis cordialibus ; interprete Arnaldo de Villanova. — 5.° Anonymi tractatus de aedificatione, nutritione, conservatione et transportatione apum. — 6.° Liber de coquina, sive de praeparatione ciborum. — 7.° Alius tractatus de coquina : gallico idiomate. — 8.° Excerpta è libro Palladii Tauri Aemiliani, de agricultura. — 9.° Liber de vindemiis à domino Burgundo, Pisano, de graeco in latinum fideliter translatus. — 10.° Joannis Mesuae chirurgia, quam Ferrarius Judaeus, Chirurgus, ex arabico sermone in latinum transtulit : libris quinque. — 11.° Flores veterum Poëtarum Latinorum. — 12.° Anonymi libellus de simplici medicina. — 13.° Joannis Mesuae practica, abbreviata à Magistro Joanne de Palma.

Philiberti de la Mare

Pseaume CIII. Benedic anima mea Domino, etc.

[Bible. A.T. Psaumes (français). Extrait. 18.. ?]

Metallo-organic domino reactions: C-H versus C-C bond breaking

HL and MeL are prepared by condensing benzil dihydrazone with 2-formylpyridine and 2-acetylpyridine, respectively, in 1:2 molar proportions. While in a reaction with [Ru-(C6H6)Cl-2](2), HL yields the cation [Ru(C6H6){5,6-diphenyl-3-(pyridin-2-yl)- 1,2,4-triazine}Cl](+), MeL gives the cation [Ru(C6H6)(MeL)Cl](+). Both the cations are isolated as their hexafluorophosphate salts and characterised by X-ray crystallography. In the case of HL, double domino electrocyclic/elimination reactions are found to occur. The electrocyclic reaction occurs in a C=N-N=C-C=N fragment of HL and the elimination reaction involves breaking of a C-H bond of HL. Density functional calculations on model complexes indicate that the identified electrocyclic reaction is thermochemically as well as kinetically feasible for both HL and MeL in the gas phase. For a double domino reaction, similar to that operative in HL, to occur for MeL, breaking of a C-C bond would be required in the elimination step. Our model calculations show the energy barrier for this elimination step to be much higher (329.1 kJ mol(-1)) for MeL than that for HL (96.3 kJ mol(-1)). Thus, the domino reaction takes place for HL and not for MeL. This accounts for the observed stability of [Ru(C6H6)-(MeL)Cl](+) under the reaction conditions employed.

Organocatalytic domino reaction of cyanosulfones: access to complex cyclohexane systems with quaternary carbon centers

When ε-nitro-a,β-unsaturated esters are added to conjugated cyanosulfones in the presence of a bifunctional thiourea catalyst, a highly stereoselective domino reaction occurs to generate complex cyclohexanes with up to four stereogenic centers, one of which is quaternary in nature. Therefore, it is demonstrated that, like nitro compounds, sulfones can undergo an asymmetric intramolecular conjugate addition to r,β- unsaturated esters in the presence of a bifunctional organocatalyst.

The inverse domino effect: are economic reforms contagious?

This article examines whether a country's economic reforms are affected by reforms adopted by other countries. Our theoretical model predicts that reforms are more likely when factors of production are internationally mobile and reforms are pursued in other economies. Using the change in the Index of Economic Freedom as the measure of market-liberalizing reforms and panel data (144 countries, 1995–2006), we test our model. We find evidence of the spillover of reforms. Moreover, consistent with our model, international trade is not a vehicle for the diffusion of economic reforms; rather the most important mechanism is geographical or cultural proximity.