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Yes / We defined disease-modification interventions as those aiming to change the underlying pathology. We systematically searched electronic databases and previous systematic reviews for published and ongoing trials of disease-modifying treatments in mild-to-moderate dementia. We included 149/22,918 of the references found; with 81 outcome measures from 125 trials. Trials involved participants with Alzheimer's disease (AD) alone (n = 111), or AD and mild cognitive impairment (n = 8) and three vascular dementia. We divided outcomes by the domain measured (cognition, activities of daily living, biological markers, neuropsychiatric symptoms, quality of life, global). We calculated the number of trials and of participants using each outcome. We detailed psychometric properties of each outcome. We sought the views of people living with dementia and family carers in three cities through Alzheimer's society focus groups. Attendees at a consensus conference (experts in dementia research, disease-modification and harmonisation measures) decided on the core set of outcomes using these results. Recommended core outcomes were cognition as the fundamental deficit in dementia and to indicate disease modification, serial structural MRIs. Cognition should be measured by Mini Mental State Examination or Alzheimer's Disease Assessment Scale-Cognitive Subscale. MRIs would be optional for patients. We also made recommendations for measuring important, but non-core domains which may not change despite disease modification. / The National Institute for Health Research Health Technology Assessment programme

The grammar of modification is highly complex and raises numerous questions about the relation between meaning and form. This dissertation provides a study of how modified noun phrases are interpreted and examines the consequences of these results for the syntax of the nominal domain. The discussion centers on two types of modification: superlatives and stacked modification. The data comes primarily from English, but other languages are also discussed. There is initial evidence that the main claims hold across a wide range of languages. The common view on superlatives is that they have two types of interpretations which are the result of a scope ambiguity and that the contrast between them needs to be captured by means of syntactic devices. Contra this standard approach I propose a saliency theory of superlatives which claims that there is no categorical difference between these two interpretations and where the variation in the meaning of superlatives is purely pragmatic in nature. Under this view the meaning of superlatives is a function of the properties of the surrounding discourse and the context-sensitivity of superlatives is subsumed to the more general phenomenon of context-dependency in the interpretation of natural language quantifiers. The saliency theory differs from other analyses that have adopted a discourse approach in that the so-called comparative reading does not depend on the presence or interpretation of focus. Previous approaches to multiple adjectives analyzed their order in terms of the semantics of individual adjectives. I present a new set of data which shows that this is insufficient and propose an explanation that takes into account the meaning of the whole nominal phrase. This result has consequences for how the architecture of grammar should be conceived. In particular, it shows that principles of syntactic well-formedness can sometimes be sensitive to compositional semantic interpretation, as well as pragmatic information. This is in contradiction to many contemporary approaches to grammar where the semantic component has no influence on the syntactic one. / text

This thesis presents the study of films derived from the reduction of aryldiazonium salts at gold surfaces. The properties of bare polycrystalline surfaces were investigated via the observation of the electrochemical oxidation and reduction of the gold. Films derived from diazonium salts were electrochemically grafted to the gold surface. The structure and stability of these interfaces was examined through the use of redox probes, gold oxide electrochemistry and water contact angle measurements. The spontaneous reduction of aryldiazonium salts at gold surfaces was investigated and the possible applications it presented towards printing and patterning of the gold surface with films were explained. Polycrystalline gold surfaces were prepared and subjected to various treatments, to observe the behaviour of gold oxide formation and reduction at the surface. Various effects on the surface structure were observed after treatment in solvents and electrolyte solutions. The surface structure of the gold atoms frequently changed due to the high mobilities of the gold atoms, and it is difficult to achieve a reproducibly stable surface. The electrochemical modification of gold surfaces via the reduction of aryldiazonium salts was investigated. Surfaces were modified with methylphenyl and carboxyphenyl films and exposed to various treatments. Monitoring the gold oxide reduction changes enabled the surface coverage of modifier directly attached to the surface to be calculated. The films appear to be stable, loosely packed and porous. The films are flexible in nature; redox probe responses showed reversible changes after repeated sonication in solvents of differing polarities and hydrophilicities. Contact angle measurements further support the notion of films that can reorganise in response to their environment. The spontaneous reduction of aryldiazonium salts at gold surfaces was observed. Film coverage was significantly lower at the spontaneously grafted surface than for films grafted electrochemically. Gold surfaces were successfully modified via microcontact printing, and surface coverages similar to the spontaneously grafted film were achieved. Microcontact printing was also used to pattern surfaces with films derived from diazonium salts. Feature sizes down to 100 µm were successfully achieved.