Domino Alkene-Isomerization–Claisen Rearrangement Strategy to Substituted Allylsilanes

A one-pot isomerization–Claisen protocol has been developed for the synthesis of highly substituted allylsilanes. Monosilylated divinyl ethers can be isomerized using a cationic iridium(I) catalyst followed by a thermal Claisen rearrangement to provide the allylsilanes in excellent yields and diastereoselectivities.

Determining the minimum clinically important differences for outcomes in the DOMINO trial

Although less likely to be reported in clinical trials than expressions of the statistical significance of differences in outcomes, whether or not a treatment has delivered a specified minimum clinically important difference (MCID) is also relevant to patients and their caregivers and doctors. Many dementia treatment randomised controlled trials (RCTs) have not reported MCIDs and, where they have been done, observed differences have not reached these.

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.

Excluding Coexistence of GMOs? The Impact of the EU Commission's 2010 Recommendation on Coexistence

In the midst of the European Union (EU) genetically modified organisms (GMOs) regime, coexistence of GM and non-GM crops alongside each other remains technically within the competence of the Member States. Post EU authorization of a GM crop, Member States may legally take appropriate measures to limit or prevent the presence of GMOs within non-GM crops. In July 2010, as part of a Cultivation Package, the Commission created a new Coexistence Recommendation that supports a flexible approach to more stringent coexistence measures by the States, while attempting to maintain control over the legitimate objectives justifying the measures. This article analyzes the impact of the 2010 Recommendation upon coexistence in the context of the existing practices and the previous 2003 Recommendation, taking into account its status as a soft law document and the ‘domino effect’. It is argued that the 2010 Recommendation may have greater practical and legal ramifications for coexistence than might first be thought. In attempting to create guidelines that allow a more flexible and inclusive approach towards national measures, the 2010 Recommendation may act as a catalyst to eventually exclude GM cultivation within Member States.

Comportamento flessionale di nodi esterni in calcestruzzo fibrorinforzato

SOMMARIO – Si presenta un macro modello di tipo reticolare in grado di riprodurre il comportamento in presenza di taglio e momento di nodi esterni trave-colonna di telai in calcestruzzo fibrorinforzato con fibre di acciaio
uncinato ed ordinario. Il caricamento del sistema è di tipo monotono come nel caso dell’analisi di pushover. Il modello considera la presenza di armature orizzontali e verticali della regione nodale e tiene in conto delle modalità
di rottura legate allo snervamento delle barre e allo schiacciamento delle regioni compresse in regime di sforzi pluriassiali. Il modello include le deformazioni flessionali della trave e della colonna in presenza di sforzo normale costante e restituisce la risposta del sistema colonna-nodo-trave (sub-assembralggio) tramite le curve carico-freccia all’estremità della semitrave. Per i singoli costituenti (trave, colonna e nodo) si è considerata la prima fessurazione, lo snervamento e lo schiacciamento delle regioni compresse e si sono fornite precise indicazioni sulla sequenza degli eventi che come è noto sono di fondamentale importanza per lo sviluppo di un progetto plastico che rispetti la gerarchia delle resistenze. Con l’uso del modello il controllo della gerarchia delle resistenze avviene a livello sezionale (lo snervamento delle barre deve avvenire prima dello schiacciamento delle regioni compresse) o di macro elemento (nella regione nodale lo snervamento delle staffe precede la crisi dei puntoni) e dell’intero elemento
sub-assemblaggio trave debole, colonna forte e nodo sovraresistente.
La risposta ottenuta con i modello proposto è in buon accordo con le risposte sperimentali disponibili in letteratura (almeno in termini di resistenza del sub-assemblaggio). Il modello è stato ulteriormente validato con analisi
numeriche agli elementi finiti condotte con il codice ATENA-2D. Le analisi numeriche sono state condotte utilizzando per il calcestruzzo fibroso adeguate leggi costitutive proposte dagli autori ed in grado di cogliere gli effetti
di softening e di resistenza residua a trazione legati alla presenza di fibre. Ulteriori sviluppi del modello saranno indirizzati a includere gli effetti di sfilamento delle barre d’armatura della trave e del conseguente degrado delle
tensioni d’aderenza per effetto di carichi monotonici e ciclici.

SUMMARY – A softened strut-and-tie macro model able to reproduce the flexural behavior of external beam-tocolumn joints with the presence of horizontal and vertical steel bars, including softening of compressed struts and yielding of main and secondary steel bars, is presented, to be used for the pushover analysis. The model proposed is able to calculate also the flexural response of fibrous reinforced concrete (FRC) beam-to-column sub-assemblages in term of a multilinear load-deflection curves. The model is able to take into account of the tensile behavior of main bars embedded in the surrounding concrete and of the softening of the compressed strut, the arrangement and percentage of the steel bars, the percentage and the geometry of steel fibers. First cracking, yielding of main steel and crushing of concrete were identified to determine the corresponding loads and displacement and to plot the simplified monotonic load-deflection curves of the sub-assemblages subjected in the column to constant vertical
load and at the tip of the beam to monotonically increasing lateral force. Through these load-delfection curves the component (beam, joint and column) that first collapse can be recognized and the capacity design can be verified.
The experimental results available in the literature are compared with the results obtained through the proposed model. Further, a validation of the proposed model is numerically made by using a non linear finite element program (ATENA-2D) able to analyze the flexural behavior of sub-assemblages.

Coexistence of GMOs in the EU – A Veritable Choice?

This chapter examines the issue of coexistence of genetically modified organisms (GMOs) alongside conventional and organic crops. The central focus is on whether there is a veritable opportunity for coexistence of all three types of crops, which allows for freedom of choice by both farmers and consumers. It commences by considering the nature of the general GM regime, the relationship between the frameworks for cultivation and the use and sale of GM food and feed, and the main elements of the cultivation regime. In light of this, the concept of coexistence is considered, with an evaluation of both the legal and practical elements. Although the general GM regime is controlled at an EU level, coexistence is apparently left to the Member States who may take appropriate coexistence measures. Nonetheless, the Commission has created Recommendations that are to guide the Member States in their choice of measures. To a great extent, what is considered ‘appropriate’ is to be determined by the economic impact upon the farmers and the relationship with the labelling thresholds. The chapter evaluates the future of coexistence, bearing in mind the continued use of the safeguard clauses, the declaration of ‘GM-free’ regions, the potential for national ‘opt-outs’ and the general practical challenges of maintaining coexistence including the ‘domino effect’. Overall, it is arguable that coexistence is a misnomer and that if the term’s meaning is strictly maintained then veritable coexistence that allows for freedom of choice by both farmers and consumers seems unattainable. Although not directly controlled by CAP, there are strong areas of overlap and they share a number of similar objectives; the chapter will conclude by considering whether the approaches in relation to CAP and the cultivation of GMOs are converging or diverging.