263 research outputs found

    Why Do We Go to the Cemetery? Religion, Civicness, and the Cult of the Dead in Twenty-First Century Italy

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    Background While attitudes towards death and dying have attracted much schol- arly attention, surprisingly little is known about the practice of visiting cemeteries. According to the secularization thesis, the fate of cemetery visits conforms with declining church attendance. A de-secularization theory suggests that, in the modern world, cemeteries increasingly became spaces for a society of families rather than for a religious community, suggesting that visiting the tombs of the dead might grow alongside secularization. Finally, a ‘civic community’ theory, inspired by Putnam’s work, sees cemetery visits as an expression of a social obligation among and across generations rather than a religious activity. Purpose Analyzing one of the least secular countries in Europe, Italy, we attempt to respond to an apparent paradox: Why is the share of people paying tribute to their deceased loved ones at cemeteries in areas of greater secularization higher than in more religious areas? Methods We take advantage of a rich time use dataset from a representative sam- ple of Italian families surveyed in 2013. To test our hypotheses, we run a series of nested logistic regressions for the probability of visiting the cemetery, jointly con- sidering both individual and contextual features. Results Our results confirm that individual religiosity is a pivotal predictor of cem- etery visits. Yet, even after controlling for religiosity, the probability of visiting a cemetery remains higher among people living in the more secularized part of the country. Our models show that one important reason for this divide is the differ- ent level of civicness, here measured at province level. Hence, net of individual religiosity, the frequency of cemetery visits increases with level of civicness in a community. Conclusions and Implications If religious people visit cemeteries in order to pray for the dead, our results also provide support for the hypothesis that the non-religious people living in civic societies visit cemeteries as way to connect with past genera- tions and with their own communities. Our results are thus consistent with the civic- ness hypothesis, with the caveat that religion and civicness do not seem to cancel each other out

    Integrating Abstraction Techniques for Formal Verification of Analog Designs

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    The verification of analog designs is a challenging and exhaustive task that requires deep understanding of physical behaviours. In this paper, we propose a qualitative based predicate abstraction method for the verification of a class of non-linear analog circuits. In the proposed method, system equations are automatically extracted from a circuit diagram by means of a bond graph. Verification is applied based on combining techniques from constraint solving and computer algebra along with symbolic model checking. Our methodology has the advantage of avoiding exhaustive simulation normally encountered in the verification of analog designs. To this end, we have used Dymola, Hsolver, SMV and Mathematica to implement the verification flow. We illustrate the methodology on several analog examples including Colpitts and tunnel diode oscillators

    Assessing proliferation, cell-cycle arrest and apoptotic end points in human buccal punch biopsies for use as pharmacodynamic biomarkers in drug development

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    Easily accessible normal tissues expressing the same molecular site(s) of drug action as malignant tissue offer an enhanced potential for early proof of anticancer drug mechanism and estimation of the biologically effective dose. Studies were undertaken in healthy male volunteers to assess the tolerability of single and multiple (four in 24 h) 3 mm punch biopsies of the buccal mucosa, and to determine the feasibility of detecting and quantifying a range of proliferation, cell-cycle arrest and apoptosis markers by immunohistochemistry (IHC) for use as potential pharmacodynamic (PD) end points. The biopsy procedure was well tolerated with 100% of volunteers stating that they would undergo single (n=10) and multiple (n=12) biopsies again. Total retinoblastoma protein (pRb), phosphorylated pRb (phospho-pRb), total p27, phosphorylated p27 (phospho-p27), phosphorylated-histone H3 (phospho-HH3), p21, p53, Cyclin A, Cyclin E, Ki67 all produced good signal detection, but M30, cleaved caspase 3 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling did not. Total pRb, phospho-pRb, total p27 and phospho-p27 were quantified further in a multiple biopsy study to allow components of variability to be addressed to inform future sizing decisions on intervention studies. Neither site of biopsy within the oral cavity, nor the nominal time of biopsy had any significant impact on any of the four markers expression levels. Inter- and intrasubject coefficients of variation (CVs) that could be used to size future intervention studies for pRb, phospho-pRb, total p27 and phospho-p27 were 14, 19, 18 and 16%; and 18, 29, 25 and 19%, respectively. In conclusion, quantitation of such markers in 3 mm buccal punch biopsies would be suitable to explore as PD end points within intervention studies of drugs acting on these pathways

    Multilab Direct Replication of Flavell, Beach, and Chinsky (1966): Spontaneous Verbal Rehearsal in a Memory Task as a Function of Age

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    Work by Flavell, Beach, and Chinsky indicated a change in the spontaneous production of overt verbalization behaviors when comparing young children (age 5) with older children (age 10). Despite the critical role that this evidence of a change in verbalization behaviors plays in modern theories of cognitive development and working memory, there has been only one other published near replication of this work. In this Registered Replication Report, we relied on researchers from 17 labs who contributed their results to a larger and more comprehensive sample of children. We assessed memory performance and the presence or absence of verbalization behaviors of young children at different ages and determined that the original pattern of findings was largely upheld: Older children were more likely to verbalize, and their memory spans improved. We confirmed that 5- and 6-year-old children who verbalized recalled more than children who did not verbalize. However, unlike Flavell et al., substantial proportions of our 5- and 6-year-old samples overtly verbalized at least sometimes during the picture memory task. In addition, continuous increase in overt verbalization from 7 to 10 years old was not consistently evident in our samples. These robust findings should be weighed when considering theories of cognitive development, particularly theories concerning when verbal rehearsal emerges and relations between speech and memory

    How “Humane” Is Your Endpoint?—Refining the Science-Driven Approach for Termination of Animal Studies of Chronic Infection

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    Public concern on issues such as animal welfare or the scientific validity and clinical value of animal research is growing, resulting in increasing regulatory demands for animal research. Abiding to the most stringent animal welfare standards, while having scientific objectives as the main priority, is often challenging. To do so, endpoints of studies involving severe, progressive diseases need to be established considering how early in the disease process the scientific objectives can be achieved. We present here experimental studies of tuberculosis (TB) in mice as a case study for an analysis of present practice and a discussion of how more refined science-based endpoints can be developed. A considerable proportion of studies in this field involve lethal stages, and the establishment of earlier, reliable indicators of disease severity will have a significant impact on animal welfare. While there is an increasing interest from scientists and industry in moving research in this direction, this is still far from being reflected in actual practice. We argue that a major limiting factor is the absence of data on biomarkers that can be used as indicators of disease severity. We discuss the possibility of complementing the widely used weight loss with other relevant biomarkers and the need for validation of these parameters as endpoints. Promotion of ethical guidelines needs to be coupled with systematic research in order to develop humane endpoints beyond the present euthanasia of moribund animals. Such research, as we propose here for chronic infection, can show the way for the development and promotion of welfare policies in other fields of research. Research on chronic infection relies heavily on the use of animals, as only the integral animal body can model the full aspect of an infection. That animals are generally made to develop a disease in infection studies exacerbates the tension between human benefit and animal well-being, which characterizes all biomedical research with animals. Scientists typically justify animal research with reference to potential human benefits, but if accepting the assumption that human benefits can offset animal suffering, it still needs to be argued that the same benefits could not be achieved with less negative effects on animal welfare. Reducing the animal welfare problems associated with research (“refinement” [1]) is therefore crucial in order to render animal-based research less of an ethical problem and to assure public trust in research. Studies that are designed to measure time of death or survival percentages present a particularly challenging situation in which at least some of the animals are made to die from the disease. These studies are frequent in experimental research on severe infections. The scientific community, industry, and regulatory authorities have responded to the ethical concerns over studies in which animals die from severe disease by developing new policies and guidelines for the implementation of humane endpoints as a key refinement measure (e.g., [2]–[4]). The most widely used definition considers a humane endpoint to be the earliest indicator in an animal experiment of severe pain, severe distress, suffering, or impending death [5], underlining that ideally such indicators should be identified before the onset of the most severe effects. Euthanizing animals, rather than awaiting their “spontaneous” death, is important to avoid unnecessary suffering in studies in which data on survival is thought to be required for scientific or legal reasons. However, several questions remain open regarding how humane endpoints are to be applied to address real animal welfare problems. We used TB experiments in mice as a case study to highlight the potential to establish biomarkers of disease progress that can replace survival time as a measure of disease severity.Fundação para a Ciência e Tecnologia (SFRH/BD/38337/2007)

    Activation of Latent HIV Using Drug-Loaded Nanoparticles

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    Antiretroviral therapy is currently only capable of controlling HIV replication rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T cells, which persists even in the presence of HAART. It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target and activate primary human CD4+ T-cells and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was synergistically enhanced by the HDAC inhibitor sodium butyrate. Furthermore, LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a particle capable of both activating latent virus and inhibiting viral spread. Taken together these data demonstrate the ability of nanotechnological approaches to provide improved methods for activating latent HIV and provide key proof-of-principle experiments showing how novel delivery systems may enhance future HIV therapy
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