1,003 research outputs found

    JUSTICE WILLIAM BRENNAN JR: "CONSTITUTIONAL VISIONS TAKE FIVE VOTES"

    Get PDF
    JUSTICE WILLIAM BRENNAN JR: "CONSTITUTIONAL VISIONS TAKE FIVE VOTES

    Dead man talking: The hanging of Davey Haggart

    Get PDF
    David Haggart was hanged for murder in 1821. Before he died he wrote an account of his life that sold well and generated a lot of comment, mostly of outrage. His posthumously published Life was not the only medium for this 'dead man talking.' So too was his cranium, measured by leading Edinburgh phrenologist George Combe and argued over in scientific and literary journals for almost a decade after his death. This is not a biography of David Haggart but a thesis about how he and the many people who attempted to explain his delinquency interpreted what he called 'the sporting life' and others called crime. It examines six 'versions' of him; that of the court that tried him, his own Life, his readers' responses, the theories of the phrenologists, the story told on the streets, and the cinema's attempt to portray him a century and a half later. What the world made of him was of particular importance because his criminal career coincided with major changes in society. Scotland was fast becoming urbanised. The population was both rising and moving, placing strains on poor relief, policing and housing. Although the period of most intense industrialisation lay ahead, working lives were changing in both countryside and town, and economic recession in the years following the Napoleonic Wars fuelled discontents and exacerbated poverty. It will be argued that both popular and scientific literature about wrongdoers changed significantly in the 1820s. In answering the question, 'What made Davey Haggart steal and murder?', the literature opened out to address the larger question of moral agency and even the possibility that nature and the environment might have shaped him, shaped all of us

    Evaluation of the Interaction Between TGF β and Nitric Oxide in the Mechanisms of Progression of Colon Carcinoma

    Get PDF
    It is recognised that stromal cells determine cancer progression. We have previously shown that active TGFβ produced by rat colon carcinoma cells modulated NO production in rat endothelial cells. To elucidate the role of TGFβ and NO in the mechanisms of interaction of colon carcinoma cells with stromal cells and in cancer progression, we transfected REGb cells, a regressive colon carcinoma clone secreting latent TGFβ, with a cDNA encoding for a constitutively-secreted active TGFβ. Out of 20 injected rats only one tumour progressed, which was resected and sub-cultured (ReBeta cells). ReBeta cells secreted high levels of active TGFβ. The adhesive properties of REGb and Rebeta cells to endothelial cells were similar, showing that the secretion of active TGFβ is not involved in tumour cell adhesion to endothelial cells. ReBeta, but not REGb, cell culture supernatants inhibited cytokine-dependent NO secretion by endothelial cells, but inhibition of NO production was similar in co-cultures of REGb or ReBeta cells with endothelial cells. Therefore, secretion of active TGFβ regulated endothelial NO synthase activity when tumour cells were distant from, but not in direct contact with, endothelial cells. However, only ReBeta cells inhibited cytokine-dependent secretion of NO in coculture with macrophages, indicating that the active-TGFβ-NO axis confers an advantage for tumour cells in their interaction with macrophages rather than endothelial cells in cancer progressio

    Geographic contrasts between pre- and postzygotic barriers are consistent with reinforcement in Heliconius butterflies.

    Get PDF
    Identifying the traits causing reproductive isolation and the order in which they evolve isfundamental to understanding speciation. Here, we quantify prezygotic and intrinsicpostzygotic isolation between allopatric, parapatric and sympatric populations of thebutterflies Heliconius elevatus and Heliconius pardalinus. Sympatric populations from theAmazon (H. elevatus and H. p. butleri) exhibit strong prezygotic isolation and rarely mate incaptivity; however, hybrids are fertile. Allopatric populations from the Amazon(H. p. butleri) and Andes (H. p. sergestus) mate freely when brought together in captivity, butthe female F1 hybrids are sterile. Parapatric populations (H. elevatus and H. p. sergestus)exhibit both assortative mating and sterility of female F1s. Assortative mating in sympatricpopulations is consistent with reinforcement in the face of gene flow, where the driving force,selection against hybrids, is due to disruption of mimicry and other ecological traits ratherthan hybrid sterility. In contrast, the lack of assortative mating and hybrid sterility observedin allopatric populations suggests that geographic isolation enables the evolution of intrinsicpostzygotic reproductive isolation. Our results show how the types of reproductive barriersthat evolve between species may depend on geography

    Visual Optics and Biophotonics Lab, Institute of Optics (CSIC): recent achievements, lines of research and future directions

    Get PDF
    The Visual Optics and Biophotonics Lab (Institute of Optics, CSIC) develops non-invasive optical techniques for the evaluation of the normal and pathological eye. We present experimental developments and recent results of applications in the fields of myopia and presbyopia and their correction techniques, as well as work in progress and future directions.El Laboratorio de Óptica Visual y Biofotónica del Instituto de Óptica del CSIC desarrolla técnicas ópticas no invasivas para la evaluación del ojo normal y patológico. Presentamos desarrollos experimentales y resultados recientes de aplicaciones en los campos de la miopía, presbicia y sus técnicas de corrección, así como trabajo en curso y direcciones futuras.La financiación reciente del grupo viene dada por dos proyectos del Ministerio de Educación y Ciencia (BFM2002-02638, FIS2005-04382), tres proyectos de la Comunidad Autónoma de Madrid (CAM08.7/0010.1/2000, CAM08.7/004.1/2003, GR/SAL/0387/2004), un Proyecto de Cooperación España-EEUU, una Acción Integrada, siete contratos de investigación con la industria, y un European Young Investigator Award. Además se han concedido a los distintos miembros del grupo becas y contratos postdoctorales I3P-CSIC, becas FPI, FPU, CSIC-Unidades Asociadas y de la Comunidad de Madrid.Peer reviewe

    Optimal Timing for Oocyte Denudation and Intracytoplasmic Sperm Injection

    Get PDF
    Objectives. To analyze the impact of oocyte denudation and microinjection timings on intracytoplasmic sperm injection (ICSI) outcomes. Study Design. We included ICSI cycles with the following parameters: rank 1 or 2, female age <36 years, male factor infertility, long protocol using GnRH agonist and rFSH for ovarian stimulation, and use of freshly ejaculated sperm (=110). Several ICSI parameters were analyzed according to the time between oocyte retrieval and denudation (1) and the time between denudation and ICSI (2) using a statistical logistic regression analysis. Results. Neither 1 nor 2 had a significant influence on the Metaphase II (MII) rate but the fertilisation rate (FR) showed a significant improvement when 1 was longer (optimal results at 1=3 hours) while FR significantly decreased with the increase of 2. Optimal implantation (IR) and pregnancy (PR) rates were obtained when 1 was around 2 hours. Conclusion. Incubation of oocytes around 2 hours between retrieval and denudation may not increase MII rate but appears to lead to the optimal combination of FR and IR

    Actin dynamics regulation by TTC7A/PI4KIIIα limits DNA damage and cell death under confinement

    Get PDF
    Background: The actin cytoskeleton has a crucial role in the maintenance of the immune homeostasis by controlling various cellular processes, including cell migration. Mutations in TTC7A have been described as the cause of a primary immunodeficiency associated to different degrees of gut involvement and alterations in the actin cytoskeleton dynamics. Objectives: This study investigates the impact of TTC7A deficiency in immune homeostasis. In particular, the role of the TTC7A/phosphatidylinositol 4 kinase type III α pathway in the control of leukocyte migration and actin dynamics. Methods: Microfabricated devices were leveraged to study cell migration and actin dynamics of murine and patient-derived leukocytes under confinement at the single-cell level. Results: We show that TTC7A-deficient lymphocytes exhibit an altered cell migration and reduced capacity to deform through narrow gaps. Mechanistically, TTC7A-deficient phenotype resulted from impaired phosphoinositide signaling, leading to the downregulation of the phosphoinositide 3-kinase/AKT/RHOA regulatory axis and imbalanced actin cytoskeleton dynamics. TTC7A-associated phenotype resulted in impaired cell motility, accumulation of DNA damage, and increased cell death in dense 3-dimensional gels in the presence of chemokines. Conclusions: These results highlight a novel role of TTC7A as a critical regulator of lymphocyte migration. Impairment of this cellular function is likely to contribute to the pathophysiology underlying progressive immunodeficiency in patients.</p

    Exposure-based interventions for the management of individuals with high levels of needle fear across the lifespan: A clinical practice guideline and call for further research

    Get PDF
    Needle fear typically begins in childhood and represents an important health-related issue across the lifespan. Individuals who are highly fearful of needles frequently avoid health care. Although guidance exists for managing needle pain and fear during procedures, the most highly fearful may refuse or abstain from such procedures. The purpose of a clinical practice guideline (CPG) is to provide actionable instruction on the management of a particular health concern; this guidance emerges from a systematic process. Using evidence from a rigorous systematic review interpreted by an expert panel, this CPG provides recommendations on exposure-based interventions for high levels of needle fear in children and adults. The AGREE-II, GRADE, and Cochrane methodologies were used. Exposure-based interventions were included. The included evidence was very low quality on average. Strong recommendations include the following. In vivo (live/in person) exposure-based therapy is recommended (vs. no treatment) for children seven years and older and adults with high levels of needle fear. Non-in vivo (imaginal, computer-based) exposure (vs. no treatment) is recommended for individuals (over seven years of age) who are unwilling to undergo in vivo exposure. Although there were no included trials which examined children < 7 years, exposure-based interventions are discussed as good clinical practice. Implementation considerations are discussed and clinical tools are provided. Utilization of these recommended practices may lead to improved health outcomes due to better health care compliance. Research on the understanding and treatment of high levels of needle fear is urgently needed; specific recommendations are provided

    Exposure-based Interventions for the management of individuals with high levels of needle fear across the lifespan: a clinical practice guideline and call for further research

    Get PDF
    Needle fear typically begins in childhood and represents an important health-related issue across the lifespan. Individuals who are highly fearful of needles frequently avoid health care. Although guidance exists for managing needle pain and fear during procedures, the most highly fearful may refuse or abstain from such procedures. The purpose of a clinical practice guideline (CPG) is to provide actionable instruction on the management of a particular health concern; this guidance emerges from a systematic process. Using evidence from a rigorous systematic review interpreted by an expert panel, this CPG provides recommendations on exposure-based interventions for high levels of needle fear in children and adults. The AGREE-II, GRADE, and Cochrane methodologies were used. Exposure-based interventions were included. The included evidence was very low quality on average. Strong recommendations include the following. In vivo (live/in person) exposure-based therapy is recommended (vs. no treatment) for children seven years and older and adults with high levels of needle fear. Non-in vivo (imaginal, computer-based) exposure (vs. no treatment) is recommended for individuals (over seven years of age) who are unwilling to undergo in vivo exposure. Although there were no included trials which examined children \u3c 7 years, exposure-based interventions are discussed as good clinical practice. Implementation considerations are discussed and clinical tools are provided. Utilization of these recommended practices may lead to improved health outcomes due to better health care compliance. Research on the understanding and treatment of high levels of needle fear is urgently needed; specific recommendations are provided
    corecore