122 research outputs found

    Renormalization of composite operators

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    The blocked composite operators are defined in the one-component Euclidean scalar field theory, and shown to generate a linear transformation of the operators, the operator mixing. This transformation allows us to introduce the parallel transport of the operators along the RG trajectory. The connection on this one-dimensional manifold governs the scale evolution of the operator mixing. It is shown that the solution of the eigenvalue problem of the connection gives the various scaling regimes and the relevant operators there. The relation to perturbative renormalization is also discussed in the framework of the ϕ3\phi^3 theory in dimension d=6d=6.Comment: 24 pages, revtex (accepted by Phys. Rev. D), changes in introduction and summar

    Immune checkpoint inhibitors: new strategies to checkmate cancer

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    Immune checkpoint inhibitors (ICIs) targeting Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4) or Programmed cell Death protein 1 (PD-1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proven challenging. This review summarises the mechanisms of action of ICIs and outlines important pre-clinical work that contributed to their development. We explore clinical data that has led to disease-specific drug licensing, and highlight key clinical trials that have revealed ICI efficacy across a range of malignancies. We describe how ICIs have been used as part of combination therapies, and explore their future prospects in this area. We conclude by discussing the incorporation of these new immunotherapeutics into precision approaches to cancer therapy

    Wegner-Houghton equation and derivative expansion

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    We study the derivative expansion for the effective action in the framework of the Exact Renormalization Group for a single component scalar theory. By truncating the expansion to the first two terms, the potential UkU_k and the kinetic coefficient ZkZ_k, our analysis suggests that a set of coupled differential equations for these two functions can be established under certain smoothness conditions for the background field and that sharp and smooth cut-off give the same result. In addition we find that, differently from the case of the potential, a further expansion is needed to obtain the differential equation for ZkZ_k, according to the relative weight between the kinetic and the potential terms. As a result, two different approximations to the ZkZ_k equation are obtained. Finally a numerical analysis of the coupled equations for UkU_k and ZkZ_k is performed at the non-gaussian fixed point in D<4D<4 dimensions to determine the anomalous dimension of the field.Comment: 15 pages, 3 figure

    Anthropogenic Space Weather

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    Anthropogenic effects on the space environment started in the late 19th century and reached their peak in the 1960s when high-altitude nuclear explosions were carried out by the USA and the Soviet Union. These explosions created artificial radiation belts near Earth that resulted in major damages to several satellites. Another, unexpected impact of the high-altitude nuclear tests was the electromagnetic pulse (EMP) that can have devastating effects over a large geographic area (as large as the continental United States). Other anthropogenic impacts on the space environment include chemical release ex- periments, high-frequency wave heating of the ionosphere and the interaction of VLF waves with the radiation belts. This paper reviews the fundamental physical process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure

    Moderate drinking before the unit: medicine and life assurance in Britain and the US c.1860–1930

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    This article describes the way in which “Anstie’s Limit” – a particular definition of moderate drinking first defined in Britain in the 1860s by the physician Francis Edmund Anstie (1833–1874) – became established as a useful measure of moderate alcohol consumption. Becoming fairly well-established in mainstream Anglophone medicine by 1900, it was also communicated to the public in Britain, North America and New Zealand through newspaper reports. However, the limit also travelled to less familiar places, including life assurance offices, where a number of different strategies for separating moderate from excessive drinkers emerged from the dialogue between medicine and life assurance. Whilst these ideas of moderation seem to have disappeared into the background for much of the twentieth century, re-emerging as the “J-shaped” curve, these early developments anticipate many of the questions surrounding uses of the “unit” to quantify moderate alcohol consumption in Britain today. The article will therefore conclude by exploring some of the lessons of this story for contemporary discussions of moderation, suggesting that we should pay more attention to whether these metrics work, where they work and why

    El Niño Southern Oscillation signal in a new East Antarctic ice core, Mount Brown South

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    Abstract. Paleoclimate archives, such as high-resolution ice core records, provide a means to investigate long-term (multi-centennial) climate variability. Until recently, the Law Dome (Dome Summit South) ice core record remained one of few long-term high-resolution records in East Antarctica. A new ice core drilled in 2017/2018 at Mount Brown South, approximately 1000 km west of Law Dome, provides an additional high-resolution record that will likely span the last millennium in the Indian Ocean sector of East Antarctica. Here, we compare snowfall accumulation rates and sea salt concentrations in the upper portion (~21 m) of the Mount Brown South record, and an updated Law Dome record over the period 1975–2016. Annual sea salt concentrations from the Mount Brown South record preserves a stronger signal for the El Niño-Southern Oscillation (ENSO; in austral winter and spring, r = 0.521, p r = −0.387, p = 0.018, Niño 3.4). The Mount Brown South and Law Dome ice cores record inverse signals for the ENSO, suggesting the occurrence of distinct moisture and aerosol intrusions. We suggest that ENSO-related sea surface temperature anomalies in the equatorial Pacific drive atmospheric teleconnections in the southern mid-latitudes. These anomalies are associated with a weakening (strengthening) of regional westerly winds to the north of Mount Brown South that corresponds to years of low (high) sea salt deposition at Mount Brown South during La Niña (El Niño) events. The Mount Brown South annual sea salt record when complete will offer a new proxy record for reconstructions of the ENSO over the recent millennium, along with improved understanding of regional atmospheric variability in the southern Indian Ocean in addition to that derived from Law Dome

    A shooting algorithm for problems with singular arcs

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    In this article we propose a shooting algorithm for a class of optimal control problems for which all control variables appear linearly. The shooting system has, in the general case, more equations than unknowns and the Gauss-Newton method is used to compute a zero of the shooting function. This shooting algorithm is locally quadratically convergent if the derivative of the shooting function is one-to-one at the solution. The main result of this paper is to show that the latter holds whenever a sufficient condition for weak optimality is satisfied. We note that this condition is very close to a second order necessary condition. For the case when the shooting system can be reduced to one having the same number of unknowns and equations (square system) we prove that the mentioned sufficient condition guarantees the stability of the optimal solution under small perturbations and the invertibility of the Jacobian matrix of the shooting function associated to the perturbed problem. We present numerical tests that validate our method.Comment: No. RR-7763 (2011); Journal of Optimization, Theory and Applications, published as 'Online first', January 201

    An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

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    New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact

    Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

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    notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

    Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns Findings From the Pregnancy and Childhood Epigenetics Consortium

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    Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development
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