Influence of tumors on protective anti-tumor immunity and the effects of irradiation

Innate and adaptive immunity play important roles in the development and progression of cancer and it is becoming apparent that tumours can influence the induction of potentially protective responses in a number of ways. The prevalence of immunoregulatory T cell populations in the circulation and tumours of patients with cancer is increased, and the presence of these cells appears to present a major barrier to the induction of tumour immunity. One aspect of tumour-mediated immunoregulation which has received comparatively little attention is that which is directed towards natural killer (NK) cells, although evidence that the phenotype and function of NK cell populations are modified in patients with cancer is accumulating.Although the precise mechanisms underlying these localised and systemic immunoregulatory effects remain unclear, tumour-derived factors appear, in part at least, to be involved. The effects could be manifested by an altered function and/or via an influence on the migratory properties of individual cell subsets. A better insight into endogenous immunoregulatory mechanisms and the capacity of tumours to modify the phenotype and function of innate and adaptive immune cells might assist the development of new immunotherapeutic approaches and improve the management of patients with cancer.This article reviews current knowledge relating to the influence of tumours on protective anti-tumour immunity and considers the potential influence that radiation-induced effects might have on the prevalence, phenotype and function of innate and adaptive immune cells in patients with cancer

Target fragmentation at polarized HERA: a test of universal topological charge screening in QCD

Topological charge screening has been proposed as the mechanism responsible for the anomalous suppression in the first moment of the polarized proton structure function -- the `proton spin' effect. An immediate consequence is that this suppression should be target-independent, since the screening is a fundamental property of the QCD vacuum. Here, we study the possibility of testing the target-independent suppression in semi-inclusive target fragmentation processes at polarized HERA

Does context matter? A multilevel analysis of neighborhood disadvantage and children\u27s sleep health

Objectives: To determine how demographic, socioeconomic, and neighborhood characteristics are associated with bedtimes among US kindergarteners. Design: Parents reported bedtimes of their children as well as personal, household, and residential characteristics via interviews in the Early Childhood Longitudinal Study-Kindergarten (ECLS-K) Class of 1998–1999. The ECLS-K links individual households to US Census tracts. Setting: A random selection of 1,280 schools and surrounding communities in the US. Participants: A random selection of 16,936 kindergarteners and their parents. Measurements: The 2 outcomes were regular and latest weekday bedtimes of kindergarteners. Through a series of nested multilevel regression models, these outcomes were regressed on individual- and neighborhood- level variables, including race/ethnicity, sex, family type, household income, mother’s educational attainment, neighborhood disorder, and several additional neighborhood characteristics. Results: Models showed significant (P \u3c .05) bedtime disparities by race/ethnicity, sex, family income, and mother’s educational attainment. Additionally, models tended to indicate that kindergarteners from disadvantaged neighborhoods experienced later bedtimes than children from more advantaged areas. Neighborhood characteristics accounted for a portion of racial/ethnic differences, suggesting that bedtime disparities are partly rooted in disparate environmental conditions. Conclusions: Reducing disparities in childhood sleep may require programs that target not only children and their parents, but also the communities in which they reside

Resummed spinning waveforms from five-point amplitudes

We compute the classical tree-level five-point amplitude for the two-to-two scattering of spinning celestial objects with the emission of a graviton. Using this five-point amplitude, we then turn to the computation of the leading-order time-domain gravitational waveform. The method we describe is suitable for arbitrary values of classical spin of Kerr black holes and does not require any expansion in powers of the spin. In this paper we illustrate it in the simpler case of the scattering of one Kerr and one Schwarzschild black hole. An important ingredient of our calculation is a novel form of the Compton amplitude with spinning particles including contact terms derived from matching to black-hole perturbation theory calculations. This ensures that our waveform is valid up to at least fourth order in the spin. Our method can be applied immediately to generate improved waveforms once higher-order contact terms in the Compton amplitude become available. Finally, we show the formula for the gravitational memory to all orders in the spin, which is in agreement with our results.Comment: 53 pages, 6 figures. v2:typos fixed, references adde

Amplitudes, Hopf algebras and the colour-kinematics duality

It was recently proposed that the kinematic algebra featuring in the colour-kinematics duality for scattering amplitudes in heavy-mass effective field theory (HEFT) and Yang-Mills theory is a quasi-shuffle Hopf algebra. The associated fusion product determines the structure of the Bern-Carrasco-Johansson (BCJ) numerators, which are manifestly gauge invariant and with poles corresponding to heavy-particle exchange. In this work we explore the deep connections between the quasi-shuffle algebra and general physical properties of the scattering amplitudes. First, after proving the double-copy form for gravitational HEFT amplitudes, we show that the coproducts of the kinematic algebra are in correspondence with factorisations of BCJ numerators on massive poles. We then study an extension of the standard quasi-shuffle Hopf algebra to a non-abelian version describing BCJ numerators with all possible gluon orderings. This is achieved by tensoring the original algebra with a particular Hopf algebra of orderings. In this extended version, a specific choice of the coproduct in the algebra of orderings leads to an antipode in the resulting Hopf algebra that has the interpretation of reversing the gluons' order within each BCJ numerator.Comment: 51 pages, minor corrections, version accepted to JHE

Pleural myxoid liposarcoma: features of 2 cases and associated literature review

Primary pleural myxoid liposarcoma is a rare entity and no agreed treatment options have been formulated once diagnosis has been made. We report two cases with subsequent management and make recommendations for treatment pathways in these rare cases

From Localized Mild Hyperthermia to Improved Tumor Oxygenation: Physiological Mechanisms Critically Involved in Oncologic Thermo-Radio-Immunotherapy.

(1) Background: Mild hyperthermia (mHT, 39-42 °C) is a potent cancer treatment modality when delivered in conjunction with radiotherapy. mHT triggers a series of therapeutically relevant biological mechanisms, e.g., it can act as a radiosensitizer by improving tumor oxygenation, the latter generally believed to be the commensurate result of increased blood flow, and it can positively modulate protective anticancer immune responses. However, the extent and kinetics of tumor blood flow (TBF) changes and tumor oxygenation are variable during and after the application of mHT. The interpretation of these spatiotemporal heterogeneities is currently not yet fully clarified. (2) Aim and methods: We have undertaken a systematic literature review and herein provide a comprehensive insight into the potential impact of mHT on the clinical benefits of therapeutic modalities such as radio- and immuno-therapy. (3) Results: mHT-induced increases in TBF are multifactorial and differ both spatially and with time. In the short term, changes are preferentially caused by vasodilation of co-opted vessels and of upstream normal tissue vessels as well as by improved hemorheology. Sustained TBF increases are thought to result from a drastic reduction of interstitial pressure, thus restoring adequate perfusion pressures and/or HIF-1α- and VEGF-mediated activation of angiogenesis. The enhanced oxygenation is not only the result of mHT-increased TBF and, thus, oxygen availability but also of heat-induced higher O2 diffusivities, acidosis- and heat-related enhanced O2 unloading from red blood cells. (4) Conclusions: Enhancement of tumor oxygenation achieved by mHT cannot be fully explained by TBF changes alone. Instead, a series of additional, complexly linked physiological mechanisms are crucial for enhancing tumor oxygenation, almost doubling the initial O2 tensions in tumors

From Localized Mild Hyperthermia to Improved Tumor Oxygenation: Physiological Mechanisms Critically Involved in Oncologic Thermo-Radio-Immunotherapy

(1) Background: Mild hyperthermia (mHT, 39-42 °C) is a potent cancer treatment modality when delivered in conjunction with radiotherapy. mHT triggers a series of therapeutically relevant biological mechanisms, e.g., it can act as a radiosensitizer by improving tumor oxygenation, the latter generally believed to be the commensurate result of increased blood flow, and it can positively modulate protective anticancer immune responses. However, the extent and kinetics of tumor blood flow (TBF) changes and tumor oxygenation are variable during and after the application of mHT. The interpretation of these spatiotemporal heterogeneities is currently not yet fully clarified. (2) Aim and methods: We have undertaken a systematic literature review and herein provide a comprehensive insight into the potential impact of mHT on the clinical benefits of therapeutic modalities such as radio- and immuno-therapy. (3) Results: mHT-induced increases in TBF are multifactorial and differ both spatially and with time. In the short term, changes are preferentially caused by vasodilation of co-opted vessels and of upstream normal tissue vessels as well as by improved hemorheology. Sustained TBF increases are thought to result from a drastic reduction of interstitial pressure, thus restoring adequate perfusion pressures and/or HIF-1α- and VEGF-mediated activation of angiogenesis. The enhanced oxygenation is not only the result of mHT-increased TBF and, thus, oxygen availability but also of heat-induced higher O$_{2}$ diffusivities, acidosis- and heat-related enhanced O$_{2}$ unloading from red blood cells. (4) Conclusions: Enhancement of tumor oxygenation achieved by mHT cannot be fully explained by TBF changes alone. Instead, a series of additional, complexly linked physiological mechanisms are crucial for enhancing tumor oxygenation, almost doubling the initial O$_{2}$ tensions in tumors