Household Composition, Living Standards, and “Needs”. ESRI Working Paper No. 106, 1999

This study uses the 1987 ESRI Survey of Income Distribution, Poverty and Use of State Services and the 1994 Living in Ireland Survey to examine two issues of immediate relevance to Irish tax and social welfare policy. The first is how the living standards of different household types have been evolving in recent years. The second is the relationship between the “needs” of one household type versus another - for example a single adult versus a couple, or a couple with no children versus a couple with four children. Both issues are critical for the Inter-Departmental Working Group set up in 1998 to examine the treatment of married, cohabiting and one-parent households under the tax and social welfare codes. This study was undertaken in the first instance as a contribution to the work of that group, and is being published in order to inform the wider debate of these issues. In this introductory chapter we outline the issues to be addressed, and then look at how household composition has been changing over the period to provide the background for the remainder of the study

The Antitumor Activity of Combinations of Cytotoxic Chemotherapy and Immune Checkpoint Inhibitors Is Model-Dependent

In spite of impressive response rates in multiple cancer types, immune checkpoint inhibitors (ICIs) are active in only a minority of patients. Alternative strategies currently aim to combine immunotherapies with conventional agents such as cytotoxic chemotherapies. Here, we performed a study of PD-1 or PDL-1 blockade in combination with reference chemotherapies in four fully immunocompetent mouse models of cancer. We analyzed both the in vivo antitumor response, and the tumor immune infiltrate 4 days after the first treatment. in vivo tumor growth experiments revealed variable responsiveness to ICIs between models. We observed enhanced antitumor effects of the combination of immunotherapy with chemotherapy in the MC38 colon and MB49 bladder models, a lack of response in the 4T1 breast model, and an inhibition of ICIs activity in the MBT-2 bladder model. Flow cytometry analysis of tumor samples showed significant differences in all models between untreated and treated mice. At baseline, all the tumor models studied were predominantly infiltrated with cells harboring an immunosuppressive phenotype. Early alterations of the tumor immune infiltrate after treatment were found to be highly variable. We found that the balance between effector cells and immunosuppressive cells in the tumor microenvironment could be altered with some treatment combinations, but this effect was not always correlated with an impact on in vivo tumor growth. These results show that the combination of cytotoxic chemotherapy with ICIs may result in enhanced, similar or reduced antitumor activity, in a model- and regimen-dependent fashion. The present investigations should help to select appropriate combination regimens for ICIs

The translation, validity and reliability of the German version of the Fremantle Back Awareness Questionnaire

Background: The Fremantle Back Awareness Questionnaire (FreBAQ) claims to assess disrupted self-perception of the back. The aim of this study was to develop a German version of the Fre-BAQ (FreBAQ-G) and assess its test-retest reliability, its known-groups validity and its convergent validity with another purported measure of back perception. Methods: The FreBaQ-G was translated following international guidelines for the transcultural adaptation of questionnaires. Thirty-five patients with non-specific CLBP and 48 healthy participants were recruited. Assessor one administered the FreBAQ-G to each patient with CLBP on two separate days to quantify intra-observer reliability. Assessor two administered the FreBaQ-G to each patient on day 1. The scores were compared to those obtained by assessor one on day 1 to assess inter-observer reliability. Known-groups validity was quantified by comparing the FreBAQ-G score between patients and healthy controls. To assess convergent validity, patient\u27s FreBAQ-G scores were correlated to their two-point discrimination (TPD) scores. Results: Intra- and Inter-observer reliability were both moderate with ICC3.1 = 0.88 (95%CI: 0.77 to 0.94) and 0.89 (95%CI: 0.79 to 0.94), respectively. Intra- and inter-observer limits of agreement (LoA) were 6.2 (95%CI: 5.0±8.1) and 6.0 (4.8±7.8), respectively. The adjusted mean difference between patients and controls was 5.4 (95%CI: 3.0 to 7.8, p\u3c0.01). Patient\u27s FreBAQ-G scores were not associated with TPD thresholds (Pearson\u27s r = -0.05, p = 0.79). Conclusions: The FreBAQ-G demonstrated a degree of reliability and known-groups validity. Interpretation of patient level data should be performed with caution because the LoA were substantial. It did not demonstrate convergent validity against TPD. Floor effects of some items of the FreBAQ-G may have influenced the validity and reliability results. The clinimetric properties of the FreBAQ-G require further investigation as a simple measure of disrupted self-perception of the back before firm recommendations on its use can be made

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Characterisation of a CZT detector for dosimetry of molecular radiotherapy

A pixelated cadmium zinc telluride (CZT) detector has been characterised for the purpose of developing a quantitative single photon emission computed tomography (SPECT) system for dosimetry of molecular radiotherapy (MRT). This is the aim of the Dosimetric Imaging with CZT (DEPICT) project, which is a collaboration between the University of Liverpool, The Royal Marsden Hospital, The Royal Liverpool and Broadgreen University Hospital, and the commercial partner Kromek. CZT is a direct band gap semiconductor with superior energy resolution and stopping power compared to scintillator detectors used in current SPECT systems. The inherent detector properties have been investigated and operational parameters such as bias voltage and peaking time have been selected to optimise the performance of the system. Good energy resolution is required to discriminate γ-rays that are scattered as they are emitted from the body and within the collimator, and high photon throughput is essential due to the high activities of isotopes administered in MRT. The system has an average measured electronic noise of 3.31 keV full width at half maximum (FWHM), determined through the use of an internal pulser. The energy response of the system was measured across the energy region of interest 59.5 keV to 364.5 keV and found to be linear. The reverse bias voltage and peaking time producing the optimum FWHM and maximum photon throughput were 600 V and 0.5 μs respectively. The average dead time of the system was measured as 4.84 μs and charge sharing was quantified to be 0.71 % at 59.5 keV . A pixel sensitivity calibration map was created and planar images of the medical imaging isotopes 99mTc and 123I were acquired by coupling the device to a prototype collimator, thereby demonstrating the suitability of the detector for the DEPICT project

Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states

Constitutivism

A brief explanation and overview of constitutivism

Cross-Lineage Influenza B and Heterologous Influenza A Antibody Responses in Vaccinated Mice: Immunologic Interactions and B/Yamagata Dominance

The annually reformulated trivalent inactivated influenza vaccine (TIV) includes both influenza A/subtypes (H3N2 and H1N1) but only one of two influenza B/lineages (Yamagata or Victoria). In a recent series of clinical trials to evaluate prime-boost response across influenza B/lineages, influenza-naïve infants and toddlers originally primed with two doses of 2008–09 B/Yamagata-containing TIV were assessed after two doses of B/Victoria-containing TIV administered in the subsequent 2009–10 and 2010–11 seasons. In these children, the Victoria-containing vaccines strongly recalled antibody to the initiating B/Yamagata antigen but induced only low B/Victoria antibody responses. To further evaluate this unexpected pattern of cross-lineage vaccine responses, we conducted additional immunogenicity assessment in mice. In the current study, mice were primed with two doses of 2008–09 Yamagata-containing TIV and subsequently boosted with two doses of 2010–11 Victoria-containing TIV (Group-Yam/Vic). With the same vaccines, we also assessed the reverse order of two-dose Victoria followed by two-dose Yamagata immunization (Group-Vic/Yam). The Group-Yam/Vic mice showed strong homologous responses to Yamagata antigen. However, as previously reported in children, subsequent doses of Victoria antigen substantially boosted Yamagata but induced only low antibody response to the immunizing Victoria component. The reverse order of Group-Vic/Yam mice also showed low homologous responses to Victoria but subsequent heterologous immunization with even a single dose of Yamagata antigen induced substantial boost response to both lineages. For influenza A/H3N2, homologous responses were comparably robust for the differing TIV variants and even a single follow-up dose of the heterologous strain, regardless of vaccine sequence, substantially boosted antibody to both strains. For H1N1, two doses of 2008–09 seasonal antigen significantly blunted response to two doses of the 2010–11 pandemic H1N1 antigen. Immunologic interactions between influenza viruses considered antigenically distant and in particular the cross-lineage influenza B and dominant Yamagata boost responses we have observed in both human and animal studies warrant further evaluation

Variability and Action Mechanism of a Family of Anticomplement Proteins in Ixodes ricinus

Background: Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families. Methodology/Principal Findings: We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical o, functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. Conclusion/Significance: Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway, Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods. © 2008 Couveur et al.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe