High, usual and impaired functioning in community-dwelling older men and women: Findings from the MacArthur Foundation Research Network on successful aging

The objective of this study is to determine the range of complex physical and cognitive abilities of older men and women functioning at high, medium and impaired ranges and to determine the psychosocial and physiological conditions that discriminate those in the high functioning group from those functioning at middle or impaired ranges. The subjects for this study were drawn from men and women aged 70-79 from 3 Established Populations for the Epidemiologic Study of the Elderly (EPESE) programs in East Boston MA, New Haven CT, and Durham County NC screened on the basis of criteria of physical and cognitive function. In 1988, 4030 men and women were screened as part of their annual EPESE interview. 1192 men and women met criteria for "high functioning". Age and sex-matched subjects were selected to represent the medium (n = 80) and low (n = 82) functioning groups. Physical and cognitive functioning was assessed from performance-based examinations and self-reported abilities. Physical function measures focused on balance, gait, and upper body strength. Cognitive exams assessed memory, language, abstraction, and praxis. Significant differences for every performance-based examination of physical and cognitive function were observed across functioning groups. Low functioning subjects were almost 3 times as likely to have an income of [les]$5000 compared to the high functioning group. They were less likely to have completed high school. High functioning subjects smoked cigarettes less and exercised more than others. They had higher levels of DHEA-S and peak expiratory flow rate. High functioning elders were more likely to engage in volunteer activities and score higher on scales of self-efficacy, mastery and report fewer psychiatric symptoms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31100/1/0000778.pd

Notch signaling during human T cell development

Notch signaling is critical during multiple stages of T cell development in both mouse and human. Evidence has emerged in recent years that this pathway might regulate T-lineage differentiation differently between both species. Here, we review our current understanding of how Notch signaling is activated and used during human T cell development. First, we set the stage by describing the developmental steps that make up human T cell development before describing the expression profiles of Notch receptors, ligands, and target genes during this process. To delineate stage-specific roles for Notch signaling during human T cell development, we subsequently try to interpret the functional Notch studies that have been performed in light of these expression profiles and compare this to its suggested role in the mouse

The Beta-decay Paul Trap Mk IV: Design and commissioning

The Beta-decay Paul Trap is an open-geometry, linear trap used to measure the decays of $^8$Li and $^8$B to search for a tensor contribution to the weak interaction. In the latest $^8$Li measurement of Burkey et al. (2022), $\beta$ scattering was the dominant experimental systematic uncertainty. The Beta-decay Paul Trap Mk IV reduces the prevalence of $\beta$ scattering by a factor of 4 through a redesigned electrode geometry and the use of glassy carbon and graphite as electrode materials. The trap has been constructed and successfully commissioned with $^8$Li in a new data campaign that collected 2.6 million triple coincidence events, an increase in statistics by 30% with 4 times less $\beta$ scattering compared to the previous $^8$Li data set.Comment: 17 pages, 7 figure

Intra-Individual Variability in Alzheimer's Disease and Cognitive Aging: Definitions, Context, and Effect Sizes

To explore different definitions of intra-individual variability (IIV) to summarize performance on commonly utilized cognitive tests (Mini Mental State Exam; Clock Drawing Test); compare them and their potential to differentiate clinically-defined populations; and to examine their utility in predicting clinical change in individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI).) were computed for each of these definitions in 500 simulated replicates using scores on the Mini Mental State Exam and Clock Drawing Test. IIV was computed based on test items separately (‘within test’ IIV) and the two tests together (‘across test’ IIV). The best performing definition was then used to compute IIV for a third test, the Alzheimer's Disease Assessment Scale-Cognitive, and the simulations and effect sizes were again computed. All effect size estimates based on simulated data were compared to those computed based on the total scores in the observed data. Association between total score and IIV summaries of the tests and the Clinician's Dementia Rating were estimated to test the utility of IIV in predicting clinically meaningful changes in the cohorts over 12- and 24-month intervals.ES estimates differed substantially depending on the definition of IIV and the test(s) on which IIV was based. IIV (coefficient of variation) summaries of MMSE and Clock-Drawing performed similarly to their total scores, the ADAS total performed better than its IIV summary.IIV can be computed within (items) or across (totals) items on commonly-utilized cognitive tests, and may provide a useful additional summary measure of neuropsychological test performance

Validity of a novel computerized cognitive battery for mild cognitive impairment

BACKGROUND: The NeuroTrax Mindstreams computerized cognitive assessment system was designed for widespread clinical and research use in detecting mild cognitive impairment (MCI). However, the capability of Mindstreams tests to discriminate elderly with MCI from those who are cognitively healthy has yet to be evaluated. Moreover, the comparability between these tests and traditional neuropsychological tests in detecting MCI has not been examined. METHODS: A 2-center study was designed to assess discriminant validity of tests in the Mindstreams Mild Impairment Battery. Participants were 30 individuals diagnosed with MCI, 29 with mild Alzheimer's disease (AD), and 39 healthy elderly. Testing was with the Mindstreams battery and traditional neuropsychological tests. Receiver operating characteristic (ROC) analysis was used to examine the ability of Mindstreams and traditional measures to discriminate those with MCI from cognitively healthy elderly. Between-group comparisons were made (Mann-Whitney U test) between MCI and healthy elderly and between MCI and mild AD groups. RESULTS: Mindstreams outcome parameters across multiple cognitive domains significantly discriminated among MCI and healthy elderly with considerable effect sizes (p < 0.05). Measures of memory, executive function, visual spatial skills, and verbal fluency discriminated best, and discriminability was at least comparable to that of traditional neuropsychological tests in these domains. CONCLUSIONS: Mindstreams tests are effective in detecting MCI, providing a comprehensive profile of cognitive function. Further, the enhanced precision and ease of use of these computerized tests make the NeuroTrax system a valuable clinical tool in the identification of elderly at high risk for dementia

Indentation Hardness Measurements at Macro-, Micro-, and Nanoscale: A Critical Overview

The Brinell, Vickers, Meyer, Rockwell, Shore, IHRD, Knoop, Buchholz, and nanoindentation methods used to measure the indentation hardness of materials at different scales are compared, and main issues and misconceptions in the understanding of these methods are comprehensively reviewed and discussed. Basic equations and parameters employed to calculate hardness are clearly explained, and the different international standards for each method are summarized. The limits for each scale are explored, and the different forms to calculate hardness in each method are compared and established. The influence of elasticity and plasticity of the material in each measurement method is reviewed, and the impact of the surface deformation around the indenter on hardness values is examined. The difficulties for practical conversions of hardness values measured by different methods are explained. Finally, main issues in the hardness interpretation at different scales are carefully discussed, like the influence of grain size in polycrystalline materials, indentation size effects at micro-and nanoscale, and the effect of the substrate when calculating thin films hardness. The paper improves the understanding of what hardness means and what hardness measurements imply at different scales.Funding Agencies|Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University ((Faculty Grant SFO Mat LiU) [2009 00971]</p

Dementia and Physical Activity (DAPA) - an exercise intervention to improve cognition in people with mild to moderate dementia: Study protocol for a randomized controlled trial

Background: Dementia is more common in older than in younger people, and as a result of the ageing of the population in developed countries, it is becoming more prevalent. Drug treatments for dementia are limited, and the main support offered to people with dementia and their families is generally services to mitigate against loss of function. Physical exercise is a candidate non-pharmacological treatment for dementia. Methods/Design: DAPA is a randomised controlled trial funded by the National Institute for Health Research Health Technology Assessment programme to estimate the effect of a 4-month, moderate- to hard-intensity exercise training programme and subsequent advice to remain active, on cognition (primary outcome) at 12 months in people with mild to moderate dementia. Community-dwelling participants (with their carers where possible), who are able to walk 3 metres without human assistance, able to undertake an exercise programme and do not have any unstable or terminal illness are recruited. Participants are then randomised by an independent statistician using a computerised random number generator to usual care or exercise at a 2:1 ratio in favour of exercise. The exercise intervention comprises 29, 1-hour-long exercise classes, run twice weekly at suitable venues such as leisure centres, which include aerobic exercise (on static bikes) and resistance exercise (using weights). Goals for independent exercise are set while the classes are still running, and supported thereafter with phone calls. The primary outcome is measured using ADAS-cog. Secondary outcome measures include behavioural symptoms, functional ability, quality of life and carer burden. Primary and secondary outcomes will be measured at baseline and at 6 and 12 months after randomisation, by researchers masked to participant randomisation in the participants' own homes. An economic evaluation will be carried out in parallel to the RCT, as will a qualitative study capturing the experiences of participants, carers and staff delivering the intervention. Discussion: The DAPA study will be the first large, randomised trial of the cognitive effects of exercise on people with dementia. The intervention is designed to be capable of being delivered within the constraints of NHS service provision, and the economic evaluation will allow assessment of its cost-effectiveness. Trial registration: DAPA was registered with the ISRCTN database on 29 July 2011, registration number ISRCTN32612072. © 2016 Atherton et al

Comparative Study of Hematopoietic Differentiation between Human Embryonic Stem Cell Lines

Directed differentiation of human embryonic stem cells (hESCs) into any desired cell type has been hailed as a therapeutic promise to cure many human diseases. However, substantial roadblocks still exist for in vitro differentiation of hESCs into distinct cell types, including T lymphocytes. Here we examined the hematopoietic differentiation potential of six different hESC lines. We compare their ability to develop into CD34+ or CD34+CD45+ hematopoietic precursor populations under several differentiation conditions. Comparison of lymphoid potential of hESC derived- and fetal tissue derived-hematopoietic precursors was also made. We found diverse hematopoietic potential between hESC lines depending on the culture or passage conditions. In contrast to fetal-derived hematopoietic precursors, none of the CD34+ precursors differentiated from hESCs were able to develop further into T cells. These data underscore the difficulties in the current strategy of hESC forward differentiation and highlight distinct differences between CD34+ hematopoietic precursors generated in vitro versus in vivo

Collagen-Like Proteins in Pathogenic E. coli Strains

The genome sequences of enterohaemorrhagic E. coli O157:H7 strains show multiple open-reading frames with collagen-like sequences that are absent from the common laboratory strain K-12. These putative collagens are included in prophages embedded in O157:H7 genomes. These prophages carry numerous genes related to strain virulence and have been shown to be inducible and capable of disseminating virulence factors by horizontal gene transfer. We have cloned two collagen-like proteins from E. coli O157:H7 into a laboratory strain and analysed the structure and conformation of the recombinant proteins and several of their constituting domains by a variety of spectroscopic, biophysical, and electron microscopy techniques. We show that these molecules exhibit many of the characteristics of vertebrate collagens, including trimer formation and the presence of a collagen triple helical domain. They also contain a C-terminal trimerization domain, and a trimeric α-helical coiled-coil domain with an unusual amino acid sequence almost completely lacking leucine, valine or isoleucine residues. Intriguingly, these molecules show high thermal stability, with the collagen domain being more stable than those of vertebrate fibrillar collagens, which are much longer and post-translationally modified. Under the electron microscope, collagen-like proteins from E. coli O157:H7 show a dumbbell shape, with two globular domains joined by a hinged stalk. This morphology is consistent with their likely role as trimeric phage side-tail proteins that participate in the attachment of phage particles to E. coli target cells, either directly or through assembly with other phage tail proteins. Thus, collagen-like proteins in enterohaemorrhagic E. coli genomes may have a direct role in the dissemination of virulence-related genes through infection of harmless strains by induced bacteriophages