100,467 research outputs found
FRAX-vs. T-score-based intervention thresholds for osteoporosis
No full textSummary:Many current guidelines for the assessment of osteoporosis, including those in Kuwait, initiate fracture risk assessment in men and women using BMD T-score thresholds. We compared the Kuwaiti guidelines with FRAX-based age-dependent intervention thresholds equivalent to that in women with a prior fragility fracture. FRAX-based intervention thresholds identified women at higher fracture probability than fixed T-score thresholds, particularly in the elderly.Purpose:A FRAX® model been recently calibrated for Kuwait, but guidance is needed on how to utilise fracture probabilities in the assessment and treatment of patients.Methods:We compared age-specific fracture probabilities, equivalent to women with no clinical risk factors and a prior fragility fracture (without BMD), with the age-specific fracture probabilities associated with femoral neck T-scores of −2.5 and −1.5 SD, in line with current guidelines in Kuwait. Upper and lower assessment thresholds for BMD testing were additionally explored using FRAX.Results:When a BMD T-score of −2.5 SD was used as an intervention threshold, FRAX probabilities of a major osteoporotic fracture in women aged 50 years were approximately twofold higher than those in women of the same age but with an average BMD. The increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 83 years or more, a T-score of −2.5 SD was associated with a lower probability of fracture than that of the age-matched general population with no clinical risk factors. The same phenomenon was observed from the age of 66 years at a T-score of −1.5 SD. A FRAX-based intervention threshold, defined as the 10-year probability of a major osteoporotic fracture in a woman of average BMI with a previous fracture, rose with age from 4.3% at the age of 50 years to 23%, at the age of 90 years, and identified women at increased risk at all ages. Qualitatively comparable findings were observed in the case of hip fracture probability and in men.Conclusion:Intervention thresholds based on BMD alone do not optimally target women at higher fracture risk than those on age-matched individuals without clinical risk factors, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a ‘fracture threshold’ consistently target women at higher fracture risk, irrespective of age
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
An "All Hands" Call to the Social Science Community: Establishing a Community Framework for Complexity Modeling Using Agent Based Models and Cyberinfrastructure
No full textTo date, many communities of practice (COP) in the social sciences have been struggling with how to deal with rapidly growing bodies of information. Many CoPs across broad disciplines have turned to community frameworks for complexity modeling (CFCMs) but this strategy has been slow to be discussed let alone adopted by the social sciences communities of practice (SS-CoPs). In this paper we urge the SS-CoPs that it is timely to develop and establish a CBCF for the social sciences for two major reasons: the rapid acquisition of data and the emergence of critical cybertools which can facilitate agent-based, spatially-explicit models. The goal of this paper is not to prescribe how a CFCM might be set up but to suggest of what components it might consist and what its advantages would be. Agent based models serve the establishment of a CFCM because they allow robust and diverse inputs and are amenable to output-driven modifications. In other words, as phenomena are resolved by a SS-CoP it is possible to adjust and refine ABMs (and their predictive ability) as a recursive and collective process. Existing and emerging cybertools such as computer networks, digital data collections and advances in programming languages mean the SS-CoP must now carefully consider committing the human organization to enabling a cyberinfrastructure tool. The combination of technologies with human interfaces can allow scenarios to be incorporated through 'if' 'then' rules and provide a powerful basis for addressing the dynamics of coupled and complex social ecological systems (cSESs). The need for social scientists to be more engaged participants in the growing challenges of characterizing chaotic, self-organizing social systems and predicting emergent patterns makes the application of ABMs timely. The enabling of a SS-CoP CFCM human-cyberinfrastructure represents an unprecedented opportunity to synthesize, compare and evaluate diverse sociological phenomena as a cohesive and recursive community-driven process.Community-Based Complex Models, Mathematics, Social Sciences
Pelevin’s Trinity in the novel “t”: author – protagonist – reader
No full textThe article attempts to interpret Pelevin's artistic strategy in the novel "T" by exploring its subject organization and addressing the key problems of the author, the protagonist, and the reader as they are seen by the researcher. The article analyzes the peculiarities of constructing the narrative reality in the novel "T", and goes on to discuss Pelevin's philosophic models of the development of the humankind, and the emergence of his new anthropology
Measuring industry-science links through inventor-author relations: A profiling method
No full textIn this pilot study we examine the performance of text-based profiling in recovering a set of validated inventor-author links. In a first step we match patents and publications solely based on their similarity in content. Next, we compare inventor and author names on the highest ranked matches for the occurrence of name matches. Finally, we compare these candidate matches with the names listed in a validated set of inventor-author names. Our text-based profile methodology performs significantly better than a random matching of patents and publications, suggesting that text-based profiling is a valuable complementary tool to the name searches used in previous studies.innovation; industry-science links; text-based profiling;
Aging- and obesity-associated metabolic reprogramming suppresses CD8+ T cell responses
No full textAging and obesity are growing global health issues and are associated with increased susceptibility towards infectious diseases, increased cancer risk and decreased vaccination efficacy. CD8+ T cells are the main effectors of cell-mediated adaptive immunity and form antigen-specific memory after pathogen clearance. However, upon antigen persistence during cancer or chronic infections, T cells become dysfunctional, a state termed T cell exhaustion. In CD8+ T cells, the transcription factor T cell factor 1 (TCF1, encoded by Tcf7) is a stemness marker and high expression is associated with CD8+ T cell longevity and superior functionality. The aim of this study was to identify synergistic effects of aging and obesity on the CD8+ T cell phenotype and function as well as on the plasma metabolite profile to ultimately find a causal relation.
A diet-induced obesity mouse model of young and aged mice was used to study the effect of aging and obesity on the CD8+ T cell phenotype as well as on the plasma metabolite profile. Flow cytometric analysis of naïve CD8+ T cells revealed a terminally differentiated, exhausted CD8+ T cell phenotype with reduced TCF1 expression in aged obese compared to young lean mice. Mass spectrometric analysis of plasma samples identified the tryptophan metabolite 3-Indolepropionic acid (3-IPA) to be synergistically decreased by aging and obesity. Treatment of primary murine and human CD8+ T cells with 3-IPA in therapeutic concentrations, increased TCF1 expression as well as other stemness markers and reversed T cell exhaustion in vitro. Using the lymphocytic choriomeningitis virus (LCMV) infection model, 3-IPA pre-treatment of antigen-specific CD8+ T cells rescued aging- and obesity-impaired anti-viral CD8+ T cell effector and memory functions.
To elucidate the molecular mechanism how 3-IPA increases CD8+ T cell stemness, a pull-down experiment was performed and γ-catenin was identified as a 3-IPA-binding protein. Further investigations revealed decelerated degradation of γ-catenin and its close homologue β-catenin upon 3-IPA treatment in activated CD8+ T cells. Moreover, 3-IPA treatment increased Tcf7 promoter activity in a luciferase assay, while the role of β- and γ-catenin in this context remains elusive.
In summary, aging and obesity synergistically decreased stemness, recall capacity and anti-viral effector functions of CD8+ T cells, thus making them a detrimental combination. Treatment of CD8+ T cells with 3-IPA restored those defects, suggesting a therapeutic potential of 3-IPA to overcome aging- and obesity-mediated CD8+ T cell dysfunctionality
Wave turbulence of a rotating array of quantized vortices in the T → 0 temperature limit
No full textThe dynamics of quantized vortices in the zero temperature limit is currently of great interest, particularly in the case of the Fermi superfluid He-B. Here we study wave turbulence, generated by the librating motion of a rotating cylindrical container filled with He-B, in the limit of vanishing viscous forces at temperatures . The polarization of the quantized vortices with respect to the axis of rotation is measured using non-invasive NMR techniques. We observe a decrease of the polarization when the librating motion is started, and a two-stage relaxation process when the modulation of the rotation velocity is stopped. The first relaxation process is associated with the dissipation of large-scale flow stored in inertial waves and the solid body rotation of the vortex array. From the decay of these energy reservoirs we determine the rate of energy dissipation of large-scale flow. The later second process is related to the relaxation of Kelvin waves on individual vortices. This process is monitored by the recovery of the polarization. The existence of a Kelvin wave cascade at the lowest temperatures is currently a central open question. We supply some evidence for the cascade
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