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OBJECTIVES/SPECIFIC AIMS: The serotonin receptor 6 (5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. METHODS/STUDY POPULATION: In total, 28 healthy male subjects (age range: 23–52 years) were scanned with 11C-GSK215083 on the HR+PET scanner. Time-activity curves in regions-of-interest were fitted with multilinear analysis-1 method. Binding potentials (BPND) were calculated using cerebellum as the reference region and corrected for partial volume effects. RESULTS/ANTICIPATED RESULTS: In 5-HT6 rich areas, regional 11C-GSK215083 displayed a negative correlation between BPND and age in the caudate (r=−0.41, p=0.03) (14% change per decade), and putamen (r=−0.30, p=0.04) (11% change per decade), but not in the ventral striatum and pallidum. Negative correlation with age was also seen in cortical regions (r=−0.41, p=0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first in vivo study in humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.
Relative to purebreeding, crossbreeding in the hill flock has been shown to increase lamb growth rates from birth to weaning by up to 12% and weight of lamb weaned by up to 24%, depending on ewe and ram breeds concerned (Carson et al 2001). Traditionally crossbred females produced in the hill are sold to the lowland as replacement females, so that potential hybrid vigour effects associated with crossbreeds are not fully exploited in the hill environment. A research programme has been established in Northern Ireland to investigate the potential for retaining crossbred females in the hill environment, as replacement breeding females, to improve the genetic potential of the hill flock. This paper presents the results from the first phase of the study which involved the production of the crossbred lambs from Scottish Blackface ewes (over 3-years) and the first year of the second phase, an evaluation of the performance of crossbred ewes as breeding females in the hill sector.
Lameness is a significant problem leading to reduced dairy cow productivity and welfare. Housing and management factors are known to influence lameness levels in dairy cows (Haskell et al., 2006). Furthermore, lameness management strategies are also key factors affecting the incidence of lameness (e.g. early detection of lameness (Whay, 2002) and claw trimming (Manske et al., 2002)). It is likely that knowledge factors influence lameness management strategies (Mill and Ward, 1994). The current study aimed to gain a better understanding of the relationship between lameness knowledge levels and the incidence of lameness on-farm. This is part of a wider survey aimed at understanding how knowledge, attitude, perception, and management factors affect lameness levels on dairy farms.
Lowland sheep farmers in Northern Ireland depend heavily on the hill sector for replacement breeding ewes. Thus changes in the genetics of the ewes and rams used in the hills are likely to have major implications on the performance of lowland breeding ewes. Crossbred females were produced in the study by Carson et al. (2000) as a result of crossing Scottish Blackface and Wicklow Cheviot ewes with a range of sire breeds. The objective of this study was to provide information on the productivity of these crossbred females for lowland producers.
Ventilator-associated pneumonia (VAP) is a frequent complication of severe burn injury. Comparing the current ventilator-associated event-possible VAP definition to the pre-2013 VAP definition, we identified considerably fewer VAP cases in our burn ICU. The new definition does not capture many VAP cases that would have been reported using the pre-2013 definition.
Aging is associated with performance reductions in executive function and episodic memory, although there is substantial individual variability in cognition among older adults. One factor that may be positively associated with cognition in aging is physical activity. To date, few studies have objectively assessed physical activity in young and older adults, and examined whether physical activity is differentially associated with cognition in aging. Young (n=29, age 18–31 years) and older adults (n=31, ages 55–82 years) completed standardized neuropsychological testing to assess executive function and episodic memory capacities. An experimental face-name relational memory task was administered to augment assessment of episodic memory. Physical activity (total step count and step rate) was objectively assessed using an accelerometer, and hierarchical regressions were used to evaluate relationships between cognition and physical activity. Older adults performed more poorly on tasks of executive function and episodic memory. Physical activity was positively associated with a composite measure of visual episodic memory and face-name memory accuracy in older adults. Physical activity associations with cognition were independent of sedentary behavior, which was negatively correlated with memory performance. Physical activity was not associated with cognitive performance in younger adults. Physical activity is positively associated with episodic memory performance in aging. The relationship appears to be strongest for face-name relational memory and visual episodic memory, likely attributable to the fact that these tasks make strong demands on the hippocampus. The results suggest that physical activity relates to cognition in older, but not younger adults. (JINS, 2015, 21, 780–790)
The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841–850)
The traditional metric for the efficiency of a numerical algorithm has been the number of arithmetic operations it performs. Technological trends have long been reducing the time to perform an arithmetic operation, so it is no longer the bottleneck in many algorithms; rather, communication, or moving data, is the bottleneck. This motivates us to seek algorithms that move as little data as possible, either between levels of a memory hierarchy or between parallel processors over a network. In this paper we summarize recent progress in three aspects of this problem. First we describe lower bounds on communication. Some of these generalize known lower bounds for dense classical (O(n3)) matrix multiplication to all direct methods of linear algebra, to sequential and parallel algorithms, and to dense and sparse matrices. We also present lower bounds for Strassen-like algorithms, and for iterative methods, in particular Krylov subspace methods applied to sparse matrices. Second, we compare these lower bounds to widely used versions of these algorithms, and note that these widely used algorithms usually communicate asymptotically more than is necessary. Third, we identify or invent new algorithms for most linear algebra problems that do attain these lower bounds, and demonstrate large speed-ups in theory and practice.
The emergence of invasive fungal wound infections (IFIs) in combat casualties led to development of a combat trauma-specific IFI case definition and classification. Prospective data were collected from 1133 US military personnel injured in Afghanistan (June 2009–August 2011). The IFI rates ranged from 0·2% to 11·7% among ward and intensive care unit admissions, respectively (6·8% overall). Seventy-seven IFI cases were classified as proven/probable (n = 54) and possible/unclassifiable (n = 23) and compared in a case-case analysis. There was no difference in clinical characteristics between the proven/probable and possible/unclassifiable cases. Possible IFI cases had shorter time to diagnosis (P = 0·02) and initiation of antifungal therapy (P = 0·05) and fewer operative visits (P = 0·002) compared to proven/probable cases, but clinical outcomes were similar between the groups. Although the trauma-related IFI classification scheme did not provide prognostic information, it is an effective tool for clinical and epidemiological surveillance and research.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Over the past decade, a growing number of deep imaging surveys have started to provide meaningful constraints on the population of extrasolar giant planets at large orbital separation. Primary targets for these surveys have been carefully selected based on their age, distance and spectral type, and often on their membership to young nearby associations where all stars share common kinematics, photometric and spectroscopic properties. The next step is a wider statistical analysis of the frequency and properties of low mass companions as a function of stellar mass and orbital separation. In late 2009, we initiated a coordinated European Large Program using angular differential imaging in the H band (1.66 μm) with NaCo at the VLT. Our aim is to provide a comprehensive and statistically significant study of the occurrence of extrasolar giant planets and brown dwarfs at large (5-500 AU) orbital separation around ~150 young, nearby stars, a large fraction of which have never been observed at very deep contrast. The survey has now been completed and we present the data analysis and detection limits for the observed sample, for which we reach the planetary-mass domain at separations of ≳50 AU on average. We also present the results of the statistical analysis that has been performed over the 75 targets newly observed at high-contrast. We discuss the details of the statistical analysis and the physical constraints that our survey provides for the frequency and formation scenario of planetary mass companions at large separation.
This paper demonstrates that although modern BMIs in the US have increased, 19th century BMIs in Philadelphia were lower than elsewhere within Pennsylvania, indicating that urbanization and agricultural commercialization were associated with lower BMIs. After controlling for stature, blacks consistently had greater BMI values than mulattos and whites; therefore, there is no evidence of a 19th century mulatto BMI advantage in the industrializing North. Farmers' BMIs were consistently heavier than those of non-farmers.
Government policies relating to red meat production take account of the carbon footprint, environmental impact, and contributions to human health and nutrition, biodiversity and food security. This paper reviews the impact of grazing on these parameters and their interactions, identifying those practices that best meet governments’ strategic goals. The recent focus of research on livestock grazing and biodiversity has been on reducing grazing intensity on hill and upland areas. Although this produces rapid increases in sward height and herbage mass, changes in structural diversity and plant species are slower, with no appreciable short-term increases in biodiversity so that environmental policies that simply involve reductions in numbers of livestock may not result in increased biodiversity. Furthermore, upland areas rely heavily on nutrient inputs to pastures so that withdrawal of these inputs can threaten food security. Differences in grazing patterns among breeds increase our ability to manage biodiversity if they are matched appropriately to different conservation grazing goals. Lowland grassland systems differ from upland pastures in that additional nutrients in the form of organic and inorganic fertilisers are more frequently applied to lowland pastures. Appropriate management of these nutrient applications is required, to reduce the associated environmental impact. New slurry-spreading techniques and technologies (e.g. the trailing shoe) help reduce nutrient losses but high nitrogen losses from urine deposition remain a key issue for lowland grassland systems. Nitrification inhibitors have the greatest potential to successfully tackle this problem. Greenhouse gas (GHG) emissions are lower from indoor-based systems that use concentrates to shorten finishing periods. The challenge is to achieve the same level of performance from grass-based systems. Research has shown potential solutions through the use of forages containing condensed tannins or establishing swards with a high proportion of clover and high-sugar grasses. Relative to feeding conserved forage or concentrates, grazing fresh grass not only reduces GHG emissions but also enhances the fatty acid composition of meat in terms of consumer health. It is possible to influence biodiversity, nutrient utilisation, GHG emissions and the nutritional quality of meat in grass-based systems, but each of these parameters is intrinsically linked and should not be considered in isolation. Interactions between these parameters must be considered carefully when policies are being developed, in order to ensure that strategies designed to achieve positive gains in one category do not lead to a negative impact in another. Some win–win outcomes are identified.