Validation of a coupled, multiple response assessment for upper-division thermal physics

Currently there are no assessment instruments available for upper-division thermal physics, though several introductory assessments are currently available. Notably missing from these introductory assessment are items targeting statistical mechanics. This leaves a gap in the content that can be assessed by upper-division thermal physics faculty. In this paper, we present a new, upper-division thermal physics assessment that explicitly addresses both classical thermodynamics and statistical mechanics: The Upper-level Statistical and Thermodynamics Evaluation for Physics (U-STEP). We piloted the U-STEP in multiple classes across various institutions during three semesters, and collected over 600 student responses in total. Here, we present multiple measures of validity and reliability for the U-STEP. We utilized classical test theory to determine item difficulties and discriminations, and differential item functioning to identify potential bias in assessment items that can manifest as performance gaps between different genders and races. The completed U-STEP will be the first upper-division thermal physics assessment available, and one of the first standardized physics assessments to explicitly address identification of possible item bias during the development process. &nbsp;</p

Sleep discrepancy and cognitive function in community-dwelling older adults

This was the first study to use cluster analysis to characterise sleep discrepancy (the discordance between self-reported and objective sleep) across multiple sleep parameters, in community-dwelling older adults. For sleep efficiency, negative discrepancy (the tendency to self-report worse sleep than objectively-measured) was associated with poorer memory, independent of insomnia severity, depressive symptoms and objective sleep. This suggests a unique role for sleep discrepancy as a possible risk factor for future cognitive decline, and warrants the need for further research

DDK dependent regulation of TOP2A at centromeres revealed by a chemical genetics approach

In eukaryotic cells the CDC7/DBF4 kinase, also known as DBF4-dependent kinase (DDK), is required for the firing of DNA replication origins. CDC7 is also involved in replication stress responses and its depletion sensitises cells to drugs that affect fork progression, including Topoisomerase 2 poisons. Although CDC7 is an important regulator of cell division, relatively few substrates and bona-fide CDC7 phosphorylation sites have been identified to date in human cells. In this study, we have generated an active recombinant CDC7/DBF4 kinase that can utilize bulky ATP analogues. By performing in vitro kinase assays using benzyl-thio-ATP, we have identified TOP2A as a primary CDC7 substrate in nuclear extracts, and serine 1213 and serine 1525 as in vitro phosphorylation sites. We show that CDC7/DBF4 and TOP2A interact in cells, that this interaction mainly occurs early in S-phase, and that it is compromised after treatment with CDC7 inhibitors. We further provide evidence that human DBF4 localises at centromeres, to which TOP2A is progressively recruited during S-phase. Importantly, we found that CDC7/DBF4 down-regulation, as well S1213A/S1525A TOP2A mutations can advance the timing of centromeric TOP2A recruitment in S-phase. Our results indicate that TOP2A is a novel DDK target and have important implications for centromere biology

The Large-scale J=3-2 and J=2-1 CO Emission from M17 and its Implications for Extragalactic CO Observations

We observed a 10x20 pc region of the molecular cloud M17 in the 12CO and 13CO J=3-2 and J=2-1 transitions to determine their global behavior and to assess the reliability of using ratios of CO line intensities integrated over an entire cloud to determine the physical conditions within the cloud. Both the 12CO/13CO J=2-1 and J=3-2 line ratios correlate with the 13CO integrated intensity, with smaller line ratios observed at locations with large integrated intensities. This correlation is likely due to variations in the column density from one position to another within M17. The 12CO and 13CO (J=3-2/J=2-1) line ratios show no significant variation from place to place within M17, even on the peak of the photon-dominated region. A Large Velocity Gradient analysis of globally averaged line ratios gives results in reasonable agreement with the results obtained for individual lines-of-sight through the cloud, which suggests that the typical physical conditions in a molecular cloud can be determined using CO line ratios integrated over the entire cloud. There appears to be a clear trend of increasing 12CO/13CO J=2-1 and J=3-2 line ratios as one moves from Galactic molecular cloud cores to entire Galactic molecular clouds to normal galaxies. The most likely explanation of the high line ratios for normal galaxies is a significant contribution to the CO emission by low column density material, such as diffuse molecular clouds or the outer envelopes of giant molecular clouds.Comment: 26 pages, 6 figures, 2 tables. Accepted for publication in Ap

Social contact networks and mixing among students in K-12 schools in Pittsburgh, PA

Students attending schools play an important role in the transmission of influenza. In this study, we present a social network analysis of contacts among 1,828 students in eight different schools in urban and suburban areas in and near Pittsburgh, Pennsylvania, United States of America, including elementary, elementary-middle, middle, and high schools. We collected social contact information of students who wore wireless sensor devices that regularly recorded other devices if they are within a distance of 3 meters. We analyzed these networks to identify patterns of proximal student interactions in different classes and grades, to describe community structure within the schools, and to assess the impact of the physical environment of schools on proximal contacts. In the elementary and middle schools, we observed a high number of intra-grade and intra-classroom contacts and a relatively low number of inter-grade contacts. However, in high schools, contact networks were well connected and mixed across grades. High modularity of lower grades suggests that assumptions of homogeneous mixing in epidemic models may be inappropriate; whereas lower modularity in high schools suggests that homogenous mixing assumptions may be more acceptable in these settings. The results suggest that interventions targeting subsets of classrooms may work better in elementary schools than high schools. Our work presents quantitative measures of age-specific, school-based contacts that can be used as the basis for constructing models of the transmission of infections in schools

Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

Validation of a priori candidate Alzheimer’s disease SNPs with brain amyloid-beta deposition

The accumulation of brain amyloid β (Aβ) is one of the main pathological hallmarks of Alzheimer’s disease (AD). However, the role of brain amyloid deposition in the development of AD and the genetic variants associated with this process remain unclear. In this study, we sought to identify associations between Aβ deposition and an a priori evidence based set of 1610 genetic markers, genotyped from 505 unrelated individuals (258 Aβ+ and 247 Aβ−) enrolled in the Australian Imaging, Biomarker & Lifestyle (AIBL) study. We found statistically significant associations for 6 markers located within intronic regions of 6 genes, including AC103796.1-BDNF, PPP3R1, NGFR, KL, ABCA7 & CALHM1. Although functional studies are required to elucidate the role of these genes in the accumulation of Aβ and their potential implication in AD pathophysiology, our findings are consistent with results obtained in previous GWAS efforts

Physical activity and brain amyloid beta: A longitudinal analysis of cognitively unimpaired older adults

Introduction: The current study evaluated the relationship between habitual physical activity (PA) levels and brain amyloid beta (A ) over 15 years in a cohort of cognitively unimpaired older adults. Methods: PA and A measures were collected over multiple timepoints from 731 cognitively unimpaired older adults participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Aging. Regression modeling examined cross-sectional and longitudinal relationships between PA and brain A . Moderation analyses examined apolipoprotein E (APOE) 4 carriage impact on the PA-A relationship. Results: PA was not associated with brain A at baseline ( = –0.001, p = 0.72) or over time ( = –0.26, p = 0.24). APOE 4 status did not moderate the PA-A relationship over time ( = 0.12, p = 0.73). Brain A levels did not predict PA trajectory ( = –54.26, p = 0.59). Discussion: Our study did not identify a relationship between habitual PA and brain A levels. Highlights: Physical activity levels did not predict brain amyloid beta (A ) levels over time in cognitively unimpaired older adults ( ≥ 60 years of age). Apolipoprotein E (APOE) 4 carrier status did not moderate the physical activity–brain A relationship over time. Physical activity trajectories were not impacted by brain A levels

Rates of age- and amyloid β-associated cortical atrophy in older adults with superior memory performance

Introduction: Superior cognitive performance in older adults may reflect underlying resistance to age-associated neurodegeneration. While elevated amyloid b (Ab) deposition (Ab1) has been associated with increased cortical atrophy, it remains unknown whether “SuperAgers” may be protected from Ab-associated neurodegeneration. Methods: Neuropsychologically defined SuperAgers (n 5 172) and cognitively normal for age (n 5 172) older adults from the Australian Imaging, Biomarkers and Lifestyle study were case matched. Rates of cortical atrophy over 8 years were examined by SuperAger classification and Ab status. Results: Of the case-matched SuperAgers and cognitively normal for age older adults, 40.7% and 40.1%, respectively, were Ab1. Rates of age- and Ab-associated atrophy did not differ between the groups on any measure. Ab2 individuals displayed the slowest rates of atrophy. Discussion: Maintenance of superior memory in late life does not reflect resistance to age- or Abassociated atrophy. However, those individuals who reached old age without cognitive impairment nor elevated Ab deposition (i.e. Ab2) displayed reduced rates of cortical atrophy

Suboptimal self-reported sleep efficiency and duration are associated with faster accumulation of brain amyloid beta in cognitively unimpaired older adults

INTRODUCTION: This study investigated whether self-reported sleep quality is associated with brain amyloid beta (AB) accumulation. METHODS: Linear mixed effect model analyses were conducted for 189 cognitively unimpaired (CU) older adults (mean ± standard deviation 74.0 ± 6.2; 53.2% female), with baseline self-reported sleep data, and positron emission tomography-determined brain AB measured over a minimum of three time points (range 33.3–72.7 months). Analyses included random slopes and intercepts, interaction for apolipoprotein E (APOE) 4 allele status, and time, adjusting for sex and baseline age. RESULTS: Sleep duration \u3c 6 hours, in APOE 4 carriers, and sleep efficiency \u3c 65%, in the whole sample and APOE 4 non-carriers, is associated with faster accumulation of brain AB. DISCUSSION: These findings suggest a role for self-reported suboptimal sleep efficiency and duration in the accumulation of Alzheimer\u27s disease (AD) neuropathology in CU individuals. Additionally, poor sleep efficiency represents a potential route via which individuals at lower genetic risk may progress to preclinical AD. Highlights: In cognitively unimpaired older adults self-report sleep is associated with brain amyloid beta (AB) accumulation. Across sleep characteristics, this relationship differs by apolipoprotein E (APOE) genotype. Sleep duration \u3c 6 hours is associated with faster brain AB accumulation in APOE 4 carriers. Sleep efficiency \u3c 65% is associated with faster brain AB accumulation in APOE 4 non-carriers. Personalized sleep interventions should be studied for potential to slow AB accumulation