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The entorhinal cortex (EC) is the first cortical region affected by tau pathology in Alzheimer’s disease (AD), but its functions remain unclear. The EC is thought to support memory binding, which can be tested using the Visual Short-Term Memory Binding Test (VSTMBT). We aimed to test whether VSTMBT performance can identify individuals with preclinical AD before noticeable episodic memory impairment and whether these performances are related to amyloid (Aβ) pathology and/or EC tau burden.
Methods:
Ninety-four participants underwent the VSTMBT (including a shape-only condition (SOC) and a shape-color binding condition (SCBC)), standard neuropsychological assessment including the Preclinical Alzheimer Cognitive Composite (PACC5), an Aβ status examination, a 3D-T1 MRI and a [18F]-MK-6240 tau-PET scan. Participants were classified as follows: 54 Aβ-negative cognitively normal (Aβ − CN), 22 Aβ-positive CN (Aβ + CN, preclinical AD), and 18 Aβ + individuals with Mild Cognitive Impairment (Aβ + MCI, prodromal AD).
Results:
Aβ + CN individuals performed worse than Aβ-CN participants in the SCBC while the SOC only distinguished Aβ − CN from MCI participants. The SCBC performance was predicted by tau burden in the EC after adjusting for Aβ, white matter hypointensities, inferior temporal cortex (ITC) tau burden, age, sex, and education. The SCBC was more sensitive than the PACC5 in identifying CN individuals with a positive tau-PET scan.
Conclusion:
Impaired visual short-term memory binding performance was evident from the preclinical stage of sporadic AD and related to tau pathology in the EC, suggesting that SCBC performance could detect early tau pathology in the EC among CN individuals.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test’s performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.
Methods:
This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported.
Key Results:
A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide.
Conclusions:
The digital site-less approach employed in the “Test Us At Home” study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.
To explore associations between maternal pre-pregnancy exposure to arsenic in diet and non-cardiac birth defects.
Design:
This is a population-based, case–control study using maternal responses to a dietary assessment and published arsenic concentration estimates in food items to calculate average daily total and inorganic arsenic exposure during the year before pregnancy. Assigning tertiles of total and inorganic arsenic exposure, logistic regression analysis was used to estimate OR for middle and high tertiles, compared to the low tertile.
Setting:
US National Birth Defects Prevention Study, 1997–2011.
Participants:
Mothers of 10 446 children without birth defects and 14 408 children diagnosed with a non-cardiac birth defect.
Results:
Maternal exposure to total dietary arsenic in the middle and high tertiles was associated with a threefold increase in cloacal exstrophy, with weak positive associations (1·2–1·5) observed either in both tertiles (intercalary limb deficiency) or the high tertile only (encephalocele, glaucoma/anterior chamber defects and bladder exstrophy). Maternal exposure to inorganic arsenic showed mostly weak, positive associations in both tertiles (colonic atresia/stenosis, oesophageal atresia, bilateral renal agenesis/hypoplasia, hypospadias, cloacal exstrophy and gastroschisis), or the high (glaucoma/anterior chamber defects, choanal atresia and intestinal atresia stenosis) or middle (encephalocele, intercalary limb deficiency and transverse limb deficiency) tertiles only. The remaining associations estimated were near the null or inverse.
Conclusions:
This exploration of arsenic in diet and non-cardiac birth defects produced several positive, but mostly weak associations. Limitations in exposure assessment may have resulted in exposure misclassification. Continued research with improved exposure assessment is recommended to identify if these associations are true signals or chance findings.
The years between 1258 and 67 comprise one of the most influential periods in the Middle Ages in England. This turbulent decade witnessed a bitter power struggle between King Henry III and his baronsover who should control the government of the realm. Before England eventually descended into civil war, a significant proportion of the baronage had attempted to transform its governance by imposingon the crown a programme of legislative and administrative reform far more radical and wide-ranging than Magna Carta in 1215. Constituting a critical stage in the development of parliament, the reformist movement would remain unsurpassed in its radicalism until the upheavals of the seventeenth century. Simon de Montfort, the baronial champion, became the first leader of a political movement to seize power and govern in the king's name. The essays collected here offer the most recent research into and ideas on this pivotal period. Several contributions focus upon the roles played in the political struggle by particular sections of thirteenth-century society, including the Midland knights and their political allegiances, aristocratic women, and the merchant elite in London. The events themselves constitute the second major theme of this volume, with subjects such as the secret revolution of 1258, Henry III's recovery of power in 1261, and the little studied maritime theatre during the civil wars of 1263-7 being considered.
Adrian Jobson is an Associate Lecturer at Canterbury Christ Church University.
Contributors: Sophie Ambler, Nick Barratt, David Carpenter, Peter Coss, Mario Fernandes, Andrew H. Hershey, Adrian Jobson, Lars Kjaer, John A. McEwan, Tony Moore, Fergus Oakes, H.W. Ridgeway, Christopher David Tilley, Benjamin L. Wild, Louise J. Wilkinson.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.
SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, Pfor trend ≤0·030). This association was replicated for rs4334089 in the validation cohort (Pfor trend=0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.
Objectives: Relatively few studies have investigated relationships between performance on clinical memory measures and indexes of underlying neuropathology related to Alzheimer’s disease (AD). This study investigated predictive relationships between Free and Cued Selective Reminding Test (FCSRT) cue efficiency (CE) and free-recall (FR) measures and brain amyloid levels, hippocampal volume (HV), and regional cortical thickness. Methods: Thirty-one older controls without memory complaints and 60 patients presenting memory complaints underwent the FCSRT, amyloid imaging using [F18]-flutemetamol positron emission tomography, and surface-based morphometry (SBM) using brain magnetic resonance imaging. Three groups were considered: patients with high (Aβ+P) and low (Aβ− P) amyloid load and controls with low amyloid load (Aβ− C). Results: Aβ+P showed lower CE than both Aβ− groups, but the Aβ− groups did not differ significantly. In contrast, FR discriminated all groups. SBM analyses revealed that CE indexes were correlated with the cortical thickness of a wider set of left-lateralized temporal and parietal regions than FR. Regression analyses demonstrated that amyloid load and left HV independently predicted FCSRT scores. Moreover, CE indexes were predicted by the cortical thickness of some regions involved in early AD, such as the entorhinal cortex. Conclusions: Compared to FR measures, CE indexes appear to be more specific for differentiating persons on the basis of amyloid load. Both CE and FR performance were predicted independently by brain amyloid load and reduced left HV. However, CE performance was also predicted by the cortical thickness of regions known to be atrophic early in AD. (JINS, 2016, 22, 991–1004)
A mixed integer linear programming model was developed to simulate the decision environment faced by an entry-level vegetable producer contemplating production for the whole-sale market. The model included activities which permitted consideration of 13 vegetable crops within a spring, summer, and fall rotational system. Rotations were permitted within given bounds established by marketing, rotational, and price risk constraints. Rotations were generally stable with respect to markets and relative to crop mixes as target income and acceptable negative deviation levels were varied. Spring and fall broccoli and turnip greens and late spring-summer yellow and zucchini squash were dominant crops in the triple crop rotations in the Atlanta and Cincinnati markets.
The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR < 0.1) and six others met our ‘suggestive’ criterion (FDR <0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.
Agricultural economics occupies an unique position in most agriculture programs because it and rural sociology are the only social sciences among a broad array of plant, animal, and technical disciplines. As economic and technological changes have added to the complexity, of U.S. agriculture, the relative importance of agricultural economics has increased. The demand for individuals possessing knowledge of the technical aspects of agriculture and the ability to evaluate the social and economic ramifications of alternatives is increasing.