Conceptual and Measurement Challenges in Research on Cognitive Reserve

Cognitive reserve, broadly conceived, encompasses aspects of brain structure and function that optimize individual performance in the presence of injury or pathology. Reserve is defined as a feature of brain structure and/or function that modifies the relationship between injury or pathology and performance on neuropsychological tasks or clinical outcomes. Reserve is challenging to study for two reasons. The first is: reserve is a hypothetical construct, and direct measures of reserve are not available. Proxy variables and latent variable models are used to attempt to operationalize reserve. The second is: in vivo measures of neuronal pathology are not widely available. It is challenging to develop and test models involving a risk factor (injury or pathology), a moderator (reserve) and an outcome (performance or clinical status) when neither the risk factor nor the moderator are measured directly. We discuss approaches for quantifying reserve with latent variable models, with emphasis on their application in the analysis of data from observational studies. Increasingly latent variable models are used to generate composites of cognitive reserve based on multiple proxies. We review the theoretical and ontological status of latent variable modeling approaches to cognitive reserve, and suggest research strategies for advancing the field

Nowe media w bibliotece : materiały z polsko-niemieckiej konferencji bibliotekarzy, Zielona Góra 14-16 kwietnia 2004 = Neue Medien in der Bibliothek : Materialien aus der deutsch-polnischen Konferenz der Bibliothekaren und Bibliothekarinnen, Zielona Góra den 14-16. April 2004

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Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

<div><p>Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in <i>Cftr^F508del</i> homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the <i>F508del-CFTR</i> mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from <i>F508del</i> homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both <i>in vivo</i>, in mice, and <i>in vitro</i>, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 <i>F508del-CFTR</i> homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells <i>in vivo</i>, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of <i>TNF/TNF-alpha (tumor necrosis factor)</i> and <i>CXCL8</i> (<i>chemokine [C-X-C motif] ligand 8</i>) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the <i>F508del-CFTR</i> mutation.</p></div

Enviromental genotoxicity evaluation: Bayesian approach for a mixture statistical model

The data analyzed in this paper are part of the results described in Bueno et al. (2000). Three cytogenetics endpoints were analyzed in three populations of a species of wild rodent – Akodon montensis – living in an industrial, an agricultural, and a preservation area at the Itajaí Valley, State of Santa Catarina, Brazil. The polychromatic/normochromatic ratio, the mitotic index, and the frequency of micronucleated polychromatic erythrocites were used in an attempt to establish a genotoxic profile of each area. It was assumed that the three populations were in the same conditions with respect to the influence of confounding factors such as animal age, health, nutrition status, presence of pathogens, and intra- and inter-populational genetic variability. Therefore, any differences found in the endpoints analyzed could be attributed to the external agents present in each area. The statistical models used in this paper are mixtures of negative-binomials and Poisson variables. The Poisson variables are used as approximations of binomials for rare events. The mixing distributions are beta densities. The statistical analyzes are under the bayesian perspective, as opposed to the frequentist ones often considered in the literature, as for instance in Bueno et al. (2000)

Landscape-scale drivers of glacial ecosystem change in the montane forests of the eastern Andean flank, Ecuador

Understanding the impact of landscape-scale disturbance events during the last glacial period is vital in accu- rately reconstructing the ecosystem dynamics of montane environments. Here, a sedimentary succession from the tropical montane cloud forest of the eastern Andean flank of Ecuador provides evidence of the role of non- climate drivers of vegetation change (volcanic events, fire regime and herbivory) during the late-Pleistocene. Multiproxy analysis (pollen, non-pollen palynomorphs, charcoal, geochemistry and carbon content) of the se- diments, radiocarbon dated to ca. 45–42 ka, provide a snap shot of the depositional environment, vegetation community and non-climate drivers of ecosystem dynamics. The geomorphology of the Vinillos study area, along with the organic‐carbon content, and aquatic remains suggest deposition took place near a valley floor in a swamp or shallow water environment. The pollen assemblage initially composed primarily of herbaceous types (Poaceae-Asteraceae-Solanaceae) is replaced by assemblages characterised by Andean forest taxa, (first Melastomataceae-Weinmannia-Ilex, and later, Alnus-Hedyosmum-Myrica). The pollen assemblages have no modern analogues in the tropical montane cloud forest of Ecuador. High micro-charcoal and rare macro-charcoal abundances co-occur with volcanic tephra deposits suggesting transportation from extra-local regions and that volcanic eruptions were an important source of ignition in the wider glacial landscape. The presence of the coprophilous fungi Sporormiella reveals the occurrence of herbivores in the glacial montane forest landscape. Pollen analysis indicates a stable regional vegetation community, with changes in vegetation population co- varying with large volcanic tephra deposits suggesting that the structure of glacial vegetation at Vinillos was driven by volcanic activity

Energy efficiency: what has research delivered in the last 40 years?

This article presents a critical assessment of 40 years of research that may be brought under the umbrella of energy efficiency, spanning different aggregations and domains-from individual producing and consuming agents to economy-wide effects to the role of innovation to the influence of policy. After 40 years of research, energy efficiency initiatives are generally perceived as highly effective. Innovation has contributed to lowering energy technology costs and increasing energy productivity. Energy efficiency programs in many cases have reduced energy use per unit of economic output and have been associated with net improvements in welfare, emission reductions, or both. Rebound effects at the macro level still warrant careful policy attention, as they may be nontrivial. Complexity of energy efficiency dynamics calls for further methodological and empirical advances, multidisciplinary approaches, and granular data at the service level for research in this field to be of greatest societal benefit

NuSTAR and INTEGRAL Observations of a Low/Hard State of 1E1740.7-2942

The microquasar 1E1740.7-2942, also known as the "Great Annihilator," was observed by NuSTAR in the summer of 2012. We have analyzed in detail two observations taken ~2 weeks apart, for which we measure hard and smooth spectra typical of the low/hard state. A few weeks later the source flux declined significantly. Nearly simultaneous coverage by INTEGRAL is available from its Galactic Center monitoring campaign lasting ~2.5 months. These data probe the hard state spectrum from 1E1740.7-2942 before the flux decline. We find good agreement between the spectra taken with IBIS/ISGRI and NuSTAR, with the measurements being compatible with a change in flux with no spectral variability. We present a detailed analysis of the NuSTAR spectral and timing data and upper limits for reflection of the high energy emission. We show that the high energy spectrum of this X-ray binary is well described by thermal Comptonization

Wasting Breath in Hamlet

This is the final version. Available on open access from Palgrave via the DOI in this recordThis chapter draws on instances of disordered breathing in Hamlet in order to examine the cultural signifcance of sighs in the early modern period, as well as in the context of current work in the feld of medical humanities. Tracing the medical history of sighing in ancient and early modern treatises of the passions, the chapter argues that sighs, in the text and the performance of the tragedy, exceed their conventional interpretation as symptoms of pain and disrupt meaning on the page and on stage. In the light of New Materialist theory, the air circulating in Hamlet is shown to dismantle narratives of representation, posing new questions for the future of medical humanities

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Delayed Imitation of Lipsmacking Gestures by Infant Rhesus Macaques (Macaca mulatta)

Human infants are capable of accurately matching facial gestures of an experimenter within a few hours after birth, a phenomenon called neonatal imitation. Recent studies have suggested that rather than being a simple reflexive-like behavior, infants exert active control over imitative responses and ‘provoke’ previously imitated gestures even after a delay of up to 24 h. Delayed imitation is regarded as the hallmark of a sophisticated capacity to control and flexibly engage in affective communication and has been described as an indicator of innate protoconversational readiness. However, we are not the only primates to exhibit neonatal imitation, and delayed imitation abilities may not be uniquely human. Here we report that 1-week-old infant rhesus macaques (Macaca mulatta) who show immediate imitation of a lipsmacking gesture also show delayed imitation of lipsmacking, facilitated by a tendency to refrain from lipsmacking toward a still face during baseline measurements. Individual differences in delayed imitation suggest that differentially matured cortical mechanisms may be involved, allowing some newborns macaques to actively participate in communicative exchanges from birth. Macaque infants are endowed with basic social competencies of intersubjective communication that indicate cognitive and emotional commonality between humans and macaques, which may have evolved to nurture an affective mother-infant relationship in primates