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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Electronic health records (EHRs) provide great promise for identifying cohorts and enhancing research recruitment. Such approaches are sorely needed, but there are few descriptions in the literature of prevailing practices to guide their use. A multidisciplinary workgroup was formed to examine current practices in the use of EHRs in recruitment and to propose future directions. The group surveyed consortium members regarding current practices. Over 98% of the Clinical and Translational Science Award Consortium responded to the survey. Brokered and self-service data warehouse access are in early or full operation at 94% and 92% of institutions, respectively, whereas, EHR alerts to providers and to research teams are at 45% and 48%, respectively, and use of patient portals for research is at 20%. However, these percentages increase significantly to 88% and above if planning and exploratory work were considered cumulatively. For most approaches, implementation reflected perceived demand. Regulatory and workflow processes were similarly varied, and many respondents described substantive restrictions arising from logistical constraints and limitations on collaboration and data sharing. Survey results reflect wide variation in implementation and approach, and point to strong need for comparative research and development of best practices to protect patients and facilitate interinstitutional collaboration and multisite research.
Although workhouses had been constructed before the eighteenth century some 2,000 were built in England following the enabling legislation of what is often called the Workhouse Test Act of 1723. The workhouse movement in London was particularly vigorous and highly distinctive; most London parishes of any size were operating these establishments by the middle of the eighteenth century. As the geographer David Green emphasizes, the 1834 New Poor Law in London was not followed by a wave of new building, since almost all metropolitan parishes had already integrated indoor relief as part and parcel of their mixed welfare provision. Such workhouses were designed to deter applications for relief, which could be refused if paupers would not enter them. In this sense the Workhouse Test Act anticipated the New Poor Law by over 100 years. The poor were to be subjected to the discipline of work and religious instruction. Lay religious societies, which aimed to reform the manners of the English people, were a further spur to the founding of workhouses in this period.
Tim Hitchcock's doctoral thesis is still the starting point for those interested in the early history of London's workhouses. Green's recent magisterial Pauper Capital (2010) contains the first modern analysis of their role in London's welfare system from the end of the eighteenth century.
The acclaimed Prussian naturalist Alexander von Humboldt (1769–1859) was referred to by Charles Darwin as 'the greatest scientific traveller who ever lived'. Several of his works were in the library aboard the Beagle, including the multi-volume Personal Narrative of Travels, two books on geology and Tableaux de la nature (all reissued in the Cambridge Library Collection). Darwin's copy of this two-volume 1811 New York edition of Humboldt's Political Essay (originally published in French earlier that year) is inscribed 'Buenos Ayres', suggesting he acquired it there in 1832–3, without its accompanying atlas (forthcoming). Humboldt had spent a year in Mexico in 1803–4, and was struck by its 'civilization' as compared to regions of South America that he had visited earlier on his expedition. Volume 2 of his account contains information about the population, language and key features of each district of Mexico, and about the country's agriculture.