The Minority Aging Research Study (MARS) is a longitudinal, epidemiologic cohort study of decline in cognitive function and risk of Alzheimer's disease (AD) in older African Americans, with brain ...donation after death added as an optional component for those willing to consider organ donation. In this manuscript, we first summarize the study design and methods of MARS. We then provide details of ongoing efforts to achieve neuropathologic data on over 100 African Americans participating in MARS and in three other clinical-pathologic cohort studies at Rush University Medical Center. The results examine strategies for recruiting and consenting African Americans without dementia; (2) efforts to maintain high rates of follow-up participation; (3) strategies for achieving high rates of agreement to brain donation; and (4) the methodology of obtaining rapid brain autopsy at death. The implications of these efforts are discussed.
The Multilayer Connectome of Caenorhabditis elegans Bentley, Barry; Branicky, Robyn; Barnes, Christopher L ...
PLOS computational biology/PLoS computational biology,
12/2016, Letnik:
12, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Connectomics has focused primarily on the mapping of synaptic links in the brain; yet it is well established that extrasynaptic volume transmission, especially via monoamines and neuropeptides, is ...also critical to brain function and occurs primarily outside the synaptic connectome. We have mapped the putative monoamine connections, as well as a subset of neuropeptide connections, in C. elegans based on new and published gene expression data. The monoamine and neuropeptide networks exhibit distinct topological properties, with the monoamine network displaying a highly disassortative star-like structure with a rich-club of interconnected broadcasting hubs, and the neuropeptide network showing a more recurrent, highly clustered topology. Despite the low degree of overlap between the extrasynaptic (or wireless) and synaptic (or wired) connectomes, we find highly significant multilink motifs of interaction, pinpointing locations in the network where aminergic and neuropeptide signalling modulate synaptic activity. Thus, the C. elegans connectome can be mapped as a multiplex network with synaptic, gap junction, and neuromodulator layers representing alternative modes of interaction between neurons. This provides a new topological plan for understanding how aminergic and peptidergic modulation of behaviour is achieved by specific motifs and loci of integration between hard-wired synaptic or junctional circuits and extrasynaptic signals wirelessly broadcast from a small number of modulatory neurons.
Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, ...sex and gender have not yet been adequately integrated into many of these approaches.
The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD.
The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research.
The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.
The COMET Handbook: version 1.0 Williamson, Paula R; Altman, Douglas G; Bagley, Heather ...
Trials,
06/2017, Letnik:
18, Številka:
Suppl 3
Journal Article
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The selection of appropriate outcomes is crucial when designing clinical trials in order to compare the effects of different interventions directly. For the findings to influence policy and practice, ...the outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. It is now widely acknowledged that insufficient attention has been paid to the choice of outcomes measured in clinical trials. Researchers are increasingly addressing this issue through the development and use of a core outcome set, an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area.Accumulating work in this area has identified the need for guidance on the development, implementation, evaluation and updating of core outcome sets. This Handbook, developed by the COMET Initiative, brings together current thinking and methodological research regarding those issues. We recommend a four-step process to develop a core outcome set. The aim is to update the contents of the Handbook as further research is identified.
The pattern of synaptic connections among neurons defines the circuit structure, which constrains the computations that a circuit can perform. The strength of synaptic connections is costly to ...measure yet important for accurate circuit modeling. Synaptic surface area has been shown to correlate with synaptic strength, yet in the emerging field of connectomics, most studies rely instead on the counts of synaptic contacts between two neurons. Here we quantified the relationship between synaptic count and synaptic area as measured from volume electron microscopy of the larval Drosophila central nervous system. We found that the total synaptic surface area, summed across all synaptic contacts from one presynaptic neuron to a postsynaptic one, can be accurately predicted solely from the number of synaptic contacts, for a variety of neurotransmitters. Our findings support the use of synaptic counts for approximating synaptic strength when modeling neural circuits.
Nonlinear optical devices and their implementation into modern nanophotonic architectures are constrained by their usually moderate nonlinear response. Recently, epsilon-near-zero (ENZ) materials ...have been found to have a strong optical nonlinearity, which can be enhanced through the use of cavities or nano-structuring. Here, we study the pump dependent properties of the plasmon resonance in the ENZ region in a thin layer of indium tin oxide (ITO). Exciting this mode using the Kretschmann-Raether configuration, we study reflection switching properties of a 60 nm layer close to the resonant plasmon frequency. We demonstrate a thermal switching mechanism, which results in a shift in the plasmon resonance frequency of 20 THz for a TM pump intensity of 70 GW cm
. For degenerate pump and probe frequencies, we highlight an additional two-beam coupling contribution, not previously isolated in ENZ nonlinear optics studies, which leads to an overall pump induced change in reflection from 1% to 45%.
Recent advances in remote sensing of solar‐induced chlorophyll fluorescence (SIF) have garnered wide interest from the biogeoscience and Earth system science communities, due to the observed ...linearity between SIF and gross primary productivity (GPP) at increasing spatiotemporal scales. Three recent studies, Maguire et al., (2020, https://doi.org/10.1029/2020GL087858), He et al. (2020, https://doi.org/10.1029/2020GL087474), and Marrs et al. (2020, https://doi.org/10.1029/2020GL087956) highlight a nonlinear relationship between fluorescence and photochemical yields and show empirical evidence for the decoupling of SIF, stomata, and the carbon reactions of photosynthesis. Such mechanistic studies help advance our understanding of what SIF is and what it is not. We argue that these findings are not necessarily contradictory to the linear SIF‐GPP relationship observed at the satellite scale and provide context for where, when, and why fluorescence and photosynthesis diverge at smaller spatiotemporal scales. Understanding scale dependencies of remote sensing data is crucial for interpreting SIF as a proxy for GPP.
Plain Language Summary
When exposed to light, plants re‐emit a small amount of light from chlorophyll molecules called fluorescence. Remote sensing instruments are now capable of measuring chlorophyll fluorescence (which is emitted between 650–850 nm) from canopies to the globe (solar‐induced chlorophyll fluorescence; SIF). A growing number of papers have highlighted an empirical linear relationship between SIF and whole‐ecosystem photosynthesis (gross primary productivity; GPP). These advances have excited the broader Earth science research community, but recent studies have pointed out that the linear SIF‐GPP relationship at coarse scales does not hold true at smaller spatiotemporal scales. In this commentary, we synthesize three recent studies that provide insight into the relationship between fluorescence and photosynthesis at leaf and canopy scales, under natural and controlled conditions. At fine spatiotemporal scales, fluorescence can be decoupled with photosynthetic carbon uptake, but we argue that satellite measurements are often too coarse in time and space to observe the SIF‐photosynthesis decoupling and that the integration of canopy processes explains the observed linearity. As such, SIF plays an important role as an estimate of GPP at spatial and temporal scales relevant for monitoring global terrestrial productivity, benchmarking terrestrial biosphere and earth system models, and managing ecosystems.
Key Points
Solar‐induced fluorescence (SIF) is widely used as a remote estimate of ecosystem gross primary productivity (GPP), but why does it work?
Three recent studies point to inherent nonlinearities in the fluorescence‐photosynthesis relationship at fine spatiotemporal scales
We synthesize mechanisms to suggest that these results are not contradictory to the increasingly linear SIF:GPP relationship across scales
A substantial body of evidence points to the heritability of dietary preferences. While vegetarianism has been practiced for millennia in various societies, its practitioners remain a small minority ...of people worldwide, and the role of genetics in choosing a vegetarian diet is not well understood. Dietary choices involve an interplay between the physiologic effects of dietary items, their metabolism, and taste perception, all of which are strongly influenced by genetics. In this study, we used a genome-wide association study (GWAS) to identify loci associated with strict vegetarianism in UK Biobank participants. Comparing 5,324 strict vegetarians to 329,455 controls, we identified one SNP on chromosome 18 that is associated with vegetarianism at the genome-wide significant level (rs72884519, beta = -0.11, P = 4.997 x 10.sup.-8 ), and an additional 201 suggestively significant variants. Four genes are associated with rs72884519: TMEM241, RIOK3, NPC1, and RMC1. Using the Functional Mapping and Annotation (FUMA) platform and the Multi-marker Analysis of GenoMic Annotation (MAGMA) tool, we identified 34 genes with a possible role in vegetarianism, 3 of which are GWAS-significant based on gene-level analysis: RIOK3, RMC1, and NPC1. Several of the genes associated with vegetarianism, including TMEM241, NPC1, and RMC1, have important functions in lipid metabolism and brain function, raising the possibility that differences in lipid metabolism and their effects on the brain may underlie the ability to subsist on a vegetarian diet. These results support a role for genetics in choosing a vegetarian diet and open the door to future studies aimed at further elucidating the physiologic pathways involved in vegetarianism.
The purpose of this article is to review the place of Humanism in religious education in England and Wales and to initiate a debate on the importance currently accorded to it. Our discussion begins ...with a short account of historical efforts to include the study of Humanism in religious education, followed by an equally short account of more recent educational policy documents and reports supporting the inclusion of Humanism. Our enquiry considers the issue of how many (self-identifying) humanists there are, for it is in terms of adherents and supporters that humanists often frame their case for inclusion. The relationship between those who identify as humanist and those who identify as non-religious is then considered. This is followed by a review of the place of Humanism in a small sample of agreed syllabuses. The conclusion is reached that there is a case for a reassessment of the degree of focus on Humanism in religious education. This conclusion raises challenges for religious educators going forward, two of which are considered and positive policies are proposed.
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