SECTION SUMMARY Clause Samples
A "Section summary" clause provides a brief overview of the main points or provisions contained within a particular section of a contract or document. It typically outlines the key obligations, rights, or procedures addressed in that section, helping readers quickly grasp the essential content without reading the full text. This clause is especially useful for lengthy or complex agreements, as it enhances clarity and aids in navigation by summarizing critical information at a glance.
SECTION SUMMARY. Although the presence of the low activity T allele could lead to higher levels of histamine resulting in raised blood pressure due to greater activation of H3 autoreceptors, an arguably more likely hypothesis is that the more common C allele would carry the risk. In this case, higher enzyme activity would lead to reduced levels of histamine relative to T carriers, which would in turn lead to less competition with antipsychotics for H1 receptors causing more sedation. Less endogenous histamine alongside chronic blockade of H1 receptors may also affect the ability to respond to dehydration by inhibiting vasopressin release. It will be important to identify possible harmful mechanisms such as this in the prescription of antipsychotics to help inform future prescribing practice.
SECTION SUMMARY. The 5HTTLPR polymorphism results in a 44 bp deletion in the promoter of the serotonin transporter gene, SLC6A4. The allele with the deletion (S) is associated with an approximately 3- fold lower rate of transcription than the long (L) allele, leading to less messenger RNA (mRNA) and functional consequences which are supported by animal studies and in vivo imaging in humans. Given the good body of evidence from post-mortem studies in humans linking serotonergic dysfunction with psychotic symptoms in DLB/PDD and AD, 5HTTLPR is a good candidate polymorphism and has the potential to contribute to a mechanistic explanation of these symptoms. 5HTTLPR is one of the most well studied polymorphisms in AD psychosis research. Of the nine independent studies carried out to date, four have reported a significant association, two with the LL genotype, one with the SS genotype and one interaction with the COMT val158met polymorphism. The inconsistent findings may be the result of a number of methodological differences, which are discussed in more detail in section 1.4.7, however they do provide an indication that this polymorphism may be of potential importance to the pathogenesis of psychotic symptoms in AD. There is also an urgent need to extend this research in DLB/PDD, with the goal of identifying common mechanisms which underpin the same symptoms in different types of dementia.
SECTION SUMMARY. The following sections outline the required tasks, as well as their inter-relationships, for the deployment of the Pre-1xRTT Products and the Specification compliant Products replacing said Pre-1xRTT Products in accordance with this Amendment.
SECTION SUMMARY. In post mortem studies, a greater burden of NFT pathology has been associated with psychotic symptoms in AD with a good degree of consistency, suggesting AD with psychotic symptoms may represent a form of the disease with a more severe pathology. Further exploration of this hypothesis is possible through a genetic association approach because of the advantage of being able to serially evaluate participants and correlate ‘real time’ clinical data with genetic variation which has known functional significance. One such source of variation is the extended MAPT haplotype which has been shown to affect total tau transcription and 4R isoform expression in a brain region specific manner with possible implications for NFT pathology and thus psychosis.
SECTION SUMMARY. The analysis developed in the preceding sections is complex and employs a diverse set of theoretical devices. This is partly due to the complexity of the empirical pattern and moreover motivated by the desire to relate the Kutchi facts to more familiar patterns and theoretical proposals. The analysis consists of the following core pieces: – split ergativity is due to a structural asymmetry between the perfective and the non- perfective aspect. The latter is more complex as it contains a locality boundary absent in the former. This boundary affects case assignment (albeit not visibly in Kutchi) and constitutes a barrier for @-probes. – There are two @-probes in the verbal spine: T contains a person and number probe and v a number and gender probe. If a locality boundary is present, both probes agree ²’ We use the notation [1+] to refer to a combination of a [speaker] feature with some other person feature (either [person] or [hearer]). Nothing hinges on this notational shorthand. ²8 This analysis predicts that 1Pl pronouns in object position should likewise be only optionally specified for number. While intriguing, this prediction cannot be directly tested. Whenever the subject is anything other than 1st person, it controls agreement. If it is 1st person, an anaphor has to be used to refer to a 1st person object. It is hence impossible to have agreement with a 1st person object. ²ª As noted in section 2.2. above, the choice between subject and object agreement correlates with emphasis. Subject agreement puts emphasis on the subject, while object agreement emphasizes the object. Under the account offered here, subject agreement arises only if the subject bears a number specification, which is semantically redundant. It seems reasonable to assume that using a pronoun with more features than are strictly necessary will induce an emphasis implicature for general pragmatic reasons. with the subject. If a boundary is present and the verb is transitive, T agrees with the subject and v with the object. – If both probes agree with the same element, @-complete verb agreement results. If they agree with distinct elements, the highest probe is spelled out, yielding defective agreement. In most cases it is T that is realized. – A post-syntactic impoverishment rule deletes person in the singular if no gender specification is present. This derives the fact that defective subject agreement in the singular does not only lack gender but also person. – 1st person singular sub...
SECTION SUMMARY. Compared to serotonin, there is less research surrounding dopaminergic neurotransmission and psychotic symptoms in AD. However the evidence that does exist, along with the previous positive associations of COMT val158met in AD psychosis studies suggests this polymorphism and by extension dopaminergic neurotransmission may be important in the aetiology of psychotic symptoms. Although only two out of three previous studies have reported the val allele as a risk for psychosis this is indicative of lower dopaminergic neurotransmission, probably in the frontal cortical areas, being associated with psychosis in AD. With the same finding being reported in a preliminary DLB study, there is an indication that psychotic mechanisms are perhaps shared in the two disorders. Given what is known about COMT expression in the brain, it could be speculated that frontal cortical regions are important in this mechanism. However, it is important to note that these regions are also implicated in cognition which is itself a correlate of psychotic symptoms, providing a further reason to clarify the role of this polymorphism in well characterised cohorts.
SECTION SUMMARY. AD, DLB and PDD together account for more than 70% of dementia cases. They are characterised by different patterns of progression clinically. Pathologically, the presence of NFTs and amyloid plaques distinguishes AD from DLB and PDD where Lewy bodies constitute the main hallmark pathological feature. Distinguishing between DLB and PDD, either clinically or pathologically is difficult and most experts support their grouping together for research purposes. Psychotic symptoms (delusions and hallucinations) are common in DLB/PDD and AD. They are of central importance to each type of dementia because of their negative impact on disease course and the paucity of effective treatments which currently exist. While well tolerated, cholinesterase inhibitors only appear to be of modest benefit in the treatment of visual hallucinations, and not effective at all in a large proportion of individuals with DLB and PDD. With regard to antipsychotics, the best evidence base for the treatment of psychotic symptoms in DLB/PDD appears to be clozapine, but tolerability issues and an FDA black box warning limit its use. The picture is similar in AD. There is some modest evidence from meta-analyses that memantine may, in addition to being effective in the treatment of cognitive and functional decline, confer some benefit to the treatment of psychotic symptoms. However, more recent clinical trials have been disappointing. Antipsychotics have repeatedly been associated with increased mortality and a number of other side effects including sedation, oedema and pneumonia, and as a consequence guidance on their use in AD is restricted to short-term risperidone prescription, which itself appears to be only modestly effective. There is an urgent need to identify safer and more effective therapies for psychosis in people with AD and DLB/PDD. The first step in addressing this need has to be a greater understanding of the mechanisms underlying psychosis in dementia and in the absence of animal models genetic studies have a pivotal role to play in elucidating these. Moreover, genetic studies also have the potential to identify subgroups of likely poor responders, raising the possibility of more targeted therapeutic approaches using existing drugs.
SECTION SUMMARY. In summary, there have been no post-mortem investigations into the role of dopaminergic neurotransmission and cognitive decline in AD. However, there is evidence from a wider body of genetic association studies that the COMT val158met polymorphism is associated with cognitive decline in healthy adults, those with neuropsychiatric syndromes and more broadly cognitive performance in PD. Conversely, the literature surrounding 5HTTLPR and cognitive decline is sparse; the only study conducted to date failed to find an association but there evidence from post-mortem studies in AD implicating 5HT in cognitive decline. Frontal cortical serotonin concentration and 5HT1A receptor density and 5HT2A receptor density in the temporal cortex are associated with rate of cognitive decline in AD. Given that cognitive impairment may have confounded previous research into 5HTTLPR and psychosis it would be prudent to consider the role of both polymorphisms in cognitive decline in AD. Indeed this would be essential in order to fully explore the relationship of these two polymorphisms and psychosis in AD.