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OBJECTIVES/SPECIFIC AIMS: Our objective is to understand the influence of the features comprising metabolic syndrome (central obesity, raised fasting plasma glucose, triglycerides, blood pressure, and decreased HDL cholesterol) on brain structure in men and women. With the understanding that MetS is a strong predictor of gray matter volume loss in specific brain regions, in this study we sought to quantify the influence of each of the metabolic syndrome biometric variables on the structures involved in the neural signature of metabolic syndrome. METHODS/STUDY POPULATION: We conducted multiple linear regression analyses on a cross-sectional sample of 800 individuals from the Genetics of Brian Structure (GOBS) image archive (352 men and 448 women). GOBS is an offshoot of the San Antonio Heart Study involving an extended pedigree of Mexican Americans from the greater San Antonio area. Its goal is to localize, identify, and characterize genes/quantitative trait loci associated with variations in brain structure and function (Winkler, 2010). The archive has continuously added participants from approximately 40 families since 2006. Neuroanatomic (T1-weighted MRI scans obtained on a Siemens 3T scanner and processed using FSL), neurocognitive, and biometric phenotypes have been obtained for each subject (including blood lipids). Linear regressions were run using SPSS and incorporated biometric and gray matter volume values obtained from 800 GOBS participants. RESULTS/ANTICIPATED RESULTS: Linear regressions incorporating metabolic syndrome variables as dependent variables and gray matter volume from regions involved in the neural signature of metabolic syndrome as predictors show significant predictive patterns that are largely similar between men and women, with some differences. Another linear regression conducted with gray matter volume from the neural signature of metabolic syndrome as the dependent variable and metabolic syndrome variables as predictors show that waist circumference and triglycerides are the greatest predictors of gray matter volume loss in men, and fasting plasma glucose and waist circumference are the greatest predictors of gray matter volume loss in women. DISCUSSION/SIGNIFICANCE OF IMPACT: Significant sex differences in the relationships between metabolic syndrome variables and gray matter volume changes between brain regions comprising the neural signature of metabolic syndrome were identified. waist circumference, fasting plasma glucose, and triglycerides are the most reliable predictors of gray matter volume loss. The variance in gray matter volume of the neural signature of metabolic syndrome in men is more significantly explained by waist circumference and triglycerides (when accounting for age) and in women is more significantly explained by waist circumference and fasting plasma glucose (when accounting for age). A model of metabolic syndrome that emphasizes a risk of neurodegeneration should focus on waist circumference for both men and women and weigh the remaining variables accordingly by sex (triglycerides in men and fasting plasma glucose in women).
OBJECTIVES/SPECIFIC AIMS: The development of new anti-cancer agents for children requires an inherently longer timeline than in adults. The 3+3 study design for Phase 1 dose escalation trials is commonly used to estimate the maximum tolerated dose and assess safety. The Rolling 6 study design was developed to shorten the study conduct timeline. METHODS/STUDY POPULATION: This study compares twenty Phase 1 COG Pilot and Phase 1 Consortium trials that employed the Rolling 6 design with hypothetical results under the assumption that a 3+3 design had been executed. The number of evaluable patients required to complete the study, number of DLTs, number of inevaluable patients, overall study duration, time suspended to enrollment (i.e., waiting for DLT evaluation), and DLT risk are compared between study designs using Wilcoxon’s signed rank test. RESULTS/ANTICIPATED RESULTS: The Rolling 6 study design required less time to complete the studies compared with 3+3 design (median 273 vs. 297 days, P = 0.01). In general, the Rolling 6 study design required more patients, had more inevaluable patients, and there were more dose limiting toxicity (DLT) events. However, there was no significant difference in DLT risk (median 0.15 vs. 0.17, P = 0.72). DISCUSSION/SIGNIFICANCE OF IMPACT: The Rolling 6 study design effectively shortens the study conduct timeline compared with the traditional 3+3 design for Phase 1 COG Pilot and Phase 1 Consortium trials without increasing the risk of toxicity.
Strongyloidiasis is a neglected tropical disease caused by the roundworm Strongyloides stercoralis affecting 30–100 million people worldwide. Many Southeast-Asian countries report a high prevalence of S. stercoralis infection, but there are little data from Vietnam. Here, we evaluated the seroprevalence of S. stercoralis related to geography, sex and age in Vietnam through serological testing of anonymized sera. Sera (n = 1710, 1340 adults and 270 children) from an anonymized age-stratified serum bank from four regions in Vietnam between 2012 and 2013 were tested using a commercial Strongyloides ratti immunoglobulin G ELISA. Seroreactivity was found in 29·1% (390/1340) of adults and 5·5% (15/270) of children. Male adults were more frequently seroreactive than females (33·3% vs. 24·9%, P = 0·001). The rural central highlands had the highest seroprevalence (42·4% of adults). Seroreactivity in the other regions was 29·9% (Hue) and 26·0% and 18·2% in the large urban centres of Hanoi and Ho Chi Minh City, respectively. We conclude that seroprevalence of S. stercoralis was high in the Vietnamese adult population, especially in rural areas.
Most mid-life and older adults are not achieving recommended physical activity (PA) targets and effective interventions are needed to increase and maintain PA long-term for health benefits. The Pedometer And Consultation Evaluation (PACE-UP) trial, a three-armed primary care pedometer-based walking intervention in those aged 45–75 years, demonstrated increased PA levels at 12 months. A three-year follow-up was conducted to evaluate long-term PA maintenance, including a qualitative component.
To examine facilitators and barriers to PA maintenance in mid-life and older adults previously involved in a PA trial.
Semi-structured telephone interviews were conducted with 60 PACE-UP participants across all study arms. Interviews were audio-recorded, transcribed verbatim and coded independently by researchers, prior to thematic analysis.
Two-thirds of participants felt since the PACE-UP trial they had an awareness of PA, with the pedometer reported as ‘kick-starting’ regular activity, and then helped them to maintain regular activity. PA facilitators included: maintaining good health, self-motivation, social support and good weather. Lack of time was the most frequently cited barrier. Other barriers were often the inverse of the facilitators; for example, poor health and bad weather. Participants described the type of ‘top-up’ intervention they would find beneficial to aid PA maintenance (eg, text messages, online resources and walking groups).
A challenge for future PA interventions is to transform barriers into facilitators; for example, educating trial participants about the value of PA for many chronic health conditions to change this from inhibiting to promoting PA. Participants provided ideas for encouraging PA maintenance which could be incorporated into future interventions.
The 2020 EU biodiversity strategy aims to halt the loss of biodiversity and ecosystem services, but this requires effective monitoring to determine whether these aims are achieved. Common bird monitoring continuously assesses changes in the avian community, providing a powerful tool for monitoring temporal changes in the abundance and distribution of these upper trophic level consumers. Two-thirds of Denmark’s land area is intensively farmed, so agricultural habitats make a major contribution to Danish biodiversity. We looked for changes in abundance amongst farmland birds in Denmark during 1987–2014 to test for reductions in declines and to predict whether the 2020-target can be expected to be achieved. Sixteen specialist farmland species were those showing the most rapid declines amongst 102 common breeding species in Denmark. Of these, those species nesting on the ground showed significant long-term declines, which was not the case for those that nest elsewhere, i.e. in hedgerows, trees and buildings. There was no evidence to suggest that these trends were attributable to widespread declines in long-distance migrant species (as reported elsewhere), which may be affected by conditions at other times in the annual cycle. We therefore conclude that continued declines in specialist farmland breeding bird species are due to contemporary agricultural changes within Denmark and urge habitat- and species-specific analysis to identify the core causes of these changes and halt the declines.
In the outer layers of the Sun (≈ 30% by radius), energy is transported by convection. The nature of the highly stratified and compressible convective flow is determined from the components of the energy flux (internal, kinetic, viscous, magnetic and radiative). Local suppressions or enhancements of any of these components may give rise to measurable changes in the emergent radiation.
On the solar surface there is direct evidence for modulation of the emerging heat flux covering a large range in spatial and temporal scales, particularly associated with concentrated magnetic fields (e.g. sunspots, plages). Associated with these surface features is the observation that the characteristics of convective motions are also modified. In the deeper layers, the interaction of convection and magnetic fields will play an important role in readjusting the local emerging heat flux and thus should contribute to the modulation of the total solar irradiance.
The task of calculating the response of the convection zone structure to developing active regions, and the solar activity cycle in general is difficult and complex due to the highly non-linear nature of the interaction of convection and magnetic fields. Theoretical work has ranged from empirical and global structure models, all the way to fine scale compressible convection simulations. This paper will highlight some recent theoretical advances that may have a direct bearing on the understanding of solar luminosity and irradiance variations and outline the important problems that must be addressed and what observational constraints may be used.
This paper will discuss issues relating to the detailed numerical simulation of solar magnetic fields, those on the small scale which are directly observable on the surface, and those on larger scales whose properties must be deduced indirectly from phenomena such as the sunspot cycle. Results of simulations using the ADISM technique will be presented to demonstrate the importance of the treatment of Alfvén waves, the boundary conditions, and the statistical evolution of small scale convection with magnetic fields. To study the large scale fields and their time dependence, the magnetic resistivity plays an important role; its use will be discussed in the paper.
On 24 January 1914, the Board elected Josiah Gilbart Smyly as the next Librarian. (See Figure 21.) He was the Professor of Latin and one of the few Fellows at the time to have published anything of significance. Within months, Europe had descended into war. The College and its Library could not fail to be affected by this and by the rising of 1916, but the long-term impact of those events paled in comparison to the political and financial implications of Irish independence in 1922. Throughout that turbulent period Smyly, who relinquished the Chair of Latin in 1915 for the Regius Chair of Greek, which he held alongside the Librarianship until 1927, spent most of his time deciphering papyri and left the Library in the care of the senior Assistant Librarian.
The post of senior Assistant Librarian was held by Alfred de Burgh from 1896 until his death in 1929. Readers were largely unaware of his presence behind the scenes, attempting to impose some order on the flood of material arriving from the Copyright Agency, handling staff matters and dealing on an almost daily basis with Sir Thomas Manly Deane during the planning of the 1937 Reading Room. A contemporary College newspaper described his daily routine: ‘every morning at ten o'clock he appeared, a thin, black-clad figure, rapidly crossing the Fellows’ Garden, vanished into the upper regions of the Library, and was seen no more, until, on the stroke of four, he recrossed the Garden, always with the same intent and preoccupied air, and disappeared through the Nassau Street gate’. (See Figure 17.)
The Board did not immediately fill the vacancy left by Todd's death, but appointed the Assistant Librarian, Benjamin Dickson, to be the acting Librarian. With the summer intervening, it took several months before the process of appointing a new Librarian began in earnest. When it did, Dickson put his name forward, as did Richard Gibbings, now Professor of Ecclesiastical History, and William Reeves, now rector of Tynan, County Armagh, and librarian of the Diocese of Armagh. Interest in the filling of the post was not confined to the College community. The Irish Times published a lengthy editorial in which it compared the relative merits of Dickson and Reeves, whom it regarded as the principal candidates. It claimed that the Library was better supplied ‘with ancient than with modern books’, and in a clear reference to Dickson said that what was needed was a Librarian ‘conversant with the latter department’. In the end the Board selected none of those candidates and again chose to appoint one of its own members, John Adam Malet, a Senior Fellow, elected Librarian on 27 November 1869.
Malet's career to date had been singularly undistinguished, his only publication having been the catalogue of the Library's Roman coins compiled 30 years earlier, though he is credited with having discovered and identified the oldest record of the College, known as the Particular Book, in what was described as a ‘waste-paper-basket store’ in the Library. As Librarian, his relationship with the Board and with other Fellows was an uneasy one, and his tenure of office was characterised by apparently impetuous decisions, several of which subsequently had to be reversed. His dealings with Dickson were problematical from the start. Having been passed over for the Librarianship, Dickson had been invited to continue as the Assistant Librarian, initially for 5 years, at a salary of £100, and had agreed. The Library minute book records his appointment as the Assistant Librarian, but includes a note by Thomas French that Malet had ‘obliged’ him to write this, even though Dickson had actually been appointed by the Board to be the ‘Second Librarian’. The University Calendar for 1870 follows French in listing Dickson as the Second Librarian and Hunt as the Assistant Librarian.
In 1850–1, three Royal Commissions were set up to enquire into the state of the universities of Oxford, Cambridge and Dublin (the Scottish universities having been the subject of a similar commission two decades earlier). Unlike Oxford and Cambridge, where recommendations for far-reaching reforms were proposed, Trinity and its Library emerged relatively unscathed, and the Commission's recommendations regarding the Library generally coincided with the views expressed by the less conservative members of the College community. All three reports covered the university libraries in some detail. Those for Dublin and Cambridge provided statistical information, but that for Oxford contained few figures about the Bodleian.
The total number of volumes in Trinity was about 105,000, which made it larger than Edinburgh and Glasgow (both of which had around 70,000) but considerably smaller than Cambridge (170,000) and the Bodleian (220,000). The libraries were reported as growing at significantly different rates, the Bodleian at between 6,000 and 7,000 volumes a year, Cambridge at about 5,000 and Trinity at only 1,500 to 2,000. The figure quoted for Trinity is initially puzzling, as the number of items received from Stationers’ Hall was considerably larger than that, comprising about 3,500 ‘articles’, as Todd described them; in addition, approximately 750 volumes a year were acquired by purchase or donation. Although many of the ‘volumes’ received by legal deposit were pamphlets, which were eventually to be bound together, often more than twenty to a volume, and would subsequently be counted as a single item, there is still a considerable discrepancy between the two figures. Todd explained this as being due partly to the cataloguing backlog that he had inherited and partly to those legal-deposit books ‘deemed too insignificant to be placed in the Library’.
The death of Peter Brown and the start of the present writer's incumbency of the Librarianship might seem an appropriate point to end this narrative. The final years of the twentieth century, however, saw such dramatic changes in universities and their libraries that to conclude in 1983 seems premature. This final section must inevitably be less analytical than previous chapters, but it seeks to chronicle as objectively as possible the main development of the Library up to the formal opening of the Ussher Library in 2003.
During these two decades the Library was served by three Librarians: Peter Fox from 1984 until 1994, when he was appointed Librarian of the University of Cambridge; Bill Simpson, who had been the Librarian of the University of London and was at Trinity from 1994 until 2002, when he moved to Manchester as University Librarian and Director of the John Rylands Library; and Robin Adams, who had been the College's Deputy Librarian since 1991 and was appointed Librarian in 2002.
The first four decades of the seventeenth century were a time of relative peace and increasing prosperity for the fledgling College, but in 1641 all was to change, in the wake of the political upheavals under way across the water. Wentworth, the former Lord Deputy and later Earl of Strafford, was executed in May 1641. Four years later the same fate befell William Laud, Archbishop of Canterbury and Chancellor of the University of Dublin. In 1640, James Ussher, who was the Vice-Chancellor, as well as Archbishop of Armagh, made a routine visit to England, from which he never returned. Rebellion broke out in Ireland in October 1641, and the Provost, Richard Washington, along with several of the Fellows, followed the Vice-Chancellor to England. The College, which had already been forbidden by Parliament to elect any more Fellows, remained without a Provost until 1645. Throughout the anarchy of the 1640s it staggered on, receiving very few students and being forced to sell plate to survive, because many of its estates had fallen into the hands of the insurgents and income from rents had almost dried up. It received a little help from the government in the form of small grants, but these were hard won. One petition to the Lords Justices described the College as being in danger of having to be dissolved through poverty, and pleaded that, even if the scholars could not be kept together, ‘for the preservation of learning…at least the fabric of the house and public library may be preserved’.
The academic standing of Trinity in the second quarter of the eighteenth century has been dismissed by the standard modern history of the College. ‘It must be confessed that few of the Fellows of the time showed evidence of even a blighted promise or of intellectual creativity,’ say its authors, who claim to have been unable to trace a single word, not even a sermon or a textbook, published between 1722 and 1753 by anyone in possession of a Fellowship. However, even if the written output from those in academic positions in the College was minimal, there was a level of intellectual curiosity and excitement among many who had passed through its doors. In part, this was manifested in a growing passion for book-collecting among members of the clergy, lawyers and doctors, many of whom were Trinity graduates. This group of like-minded individuals patronised the Dublin and London booksellers, with some also buying at continental sales, and in due course theirs was a passion from which Trinity and other institutional libraries in the country were to benefit. The donations to the College from Ashe and Palliser have already been noted, and they were to be followed by Claudius Gilbert's library and the manuscripts and pamphlets acquired by John Stearne. Most of Stearne's printed books and the extensive collection built up by Narcissus Marsh were bequeathed to the library founded by Marsh in Dublin. William King, Marsh's successor as Archbishop of Dublin, owned a library of about seven thousand books which he intended should become a public resource, perhaps in his former diocese of Derry, a place that he considered was more in need of books than the capital. At his death in 1729, however, he had left no specific instructions concerning the library, and so it passed with the rest of his estate to his nephew Robert Dougatt, Keeper of Marsh's Library, and subsequently to Dougatt's nephew Robert Spence, who sold about six thousand of the books to Theophilus Bolton, Archbishop of Cashel, some time in the 1730s. Bolton added them to his own substantial collection to create a new diocesan library which, though it has enjoyed mixed fortunes over the succeeding centuries, continues to survive in Cashel as the Bolton Library.
The granting of legal-deposit status in 1801 and the arrival of the Fagel collection the following year transformed the Library both in size and status. The impact of the legal-deposit legislation would be a gradual one; the impact of acquiring the Fagel library, on the other hand, was immediate. The size of the College Library was increased by about 40 per cent at a stroke, and a collection that was essentially secular in nature and continental in origin was added to a library that had grown over the previous two centuries principally on the basis of books acquired by or for Protestant clergy.
The process of buying the Fagel collection began formally on 31 May 1798, when the governors of the Erasmus Smith Schools, meeting in the Committee Room of the Irish House of Lords, decided ‘that the surplus money now in hand belonging to the Charity may be well applied in purchasing the library of the Greffier Faghel of The Hague, for the use of Trinity College’.