Comparing international coverage of 9/11 : towards an interdisciplinary explanation of the construction of news

This article presents an interdisciplinary model attempting to explain how news is constructed by relying on the contributions of different fields of study: News Sociology, Political Communications, International Communications, International Relations. It is a first step towards developing a holistic theoretical approach to what shapes the news, which bridges current micro to macro approaches. More precisely the model explains news variation across different media organization and countries by focusing on the different way the sense of newsworthiness of journalists is affected by three main variables: national interest, national journalistic culture, and editorial policy of each media organization. The model is developed on the basis of an investigation into what shaped the media coverage of 9/11 in eight elite newspapers across the US, France, Italy and Pakistan

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER

The incidence of liver injury in Uyghur patients treated for TB in Xinjiang Uyghur autonomous region, China, and its association with hepatic enzyme polymorphisms nat2, cyp2e1, gstm1 and gstt1.

BACKGROUND AND OBJECTIVE: Of three first-line anti-tuberculosis (anti-TB) drugs, isoniazid is most commonly associated with hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, NAT2, CYP2E1, GSTM1and GSTT1, that code for drug-metabolizing enzymes. This study evaluated whether the polymorphisms in these enzymes were associated with an increased risk of anti-TB drug-induced hepatitis in patients and could potentially be used to identify patients at risk of liver injury. METHODS AND DESIGN: In a cross-sectional study, 2244 tuberculosis patients were assessed two months after the start of treatment. Anti-TB drug-induced liver injury (ATLI) was defined as an ALT, AST or bilirubin value more than twice the upper limit of normal. NAT2, CYP2E1, GSTM1 and GSTT1 genotypes were determined using the PCR/ligase detection reaction assays. RESULTS: 2244 patients were evaluated, there were 89 cases of ATLI, a prevalence of 4% 9 patients (0.4%) had ALT levels more than 5 times the upper limit of normal. The prevalence of ATLI was greater among men than women, and there was a weak association with NAT2*5 genotypes, with ATLI more common among patients with the NAT2*5*CT genotype. The sensitivity of the CT genotype for identifying patients with ATLI was 42% and the positive predictive value 5.9%. CT ATLI was more common among slow acetylators (prevalence ratio 2.0 (95% CI 0.95,4.20) )compared to rapid acetylators. There was no evidence that ATLI was associated with CYP2E1 RsaIc1/c1genotype, CYP2E1 RsaIc1/c2 or c2/c2 genotypes, or GSTM1/GSTT1 null genotypes. CONCLUSIONS: In Xinjiang Uyghur TB patients, liver injury was associated with the genetic variant NAT2*5, however the genetic markers studied are unlikely to be useful for screening patients due to the low sensitivity and low positive predictive values for identifying persons at risk of liver injury

Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

Article approval pendingPaediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children

Narrowband Biphotons: Generation, Manipulation, and Applications

In this chapter, we review recent advances in generating narrowband biphotons with long coherence time using spontaneous parametric interaction in monolithic cavity with cluster effect as well as in cold atoms with electromagnetically induced transparency. Engineering and manipulating the temporal waveforms of these long biphotons provide efficient means for controlling light-matter quantum interaction at the single-photon level. We also review recent experiments using temporally long biphotons and single photons.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

Cavity Induced Interfacing of Atoms and Light

This chapter introduces cavity-based light-matter quantum interfaces, with a single atom or ion in strong coupling to a high-finesse optical cavity. We discuss the deterministic generation of indistinguishable single photons from these systems; the atom-photon entanglement intractably linked to this process; and the information encoding using spatio-temporal modes within these photons. Furthermore, we show how to establish a time-reversal of the aforementioned emission process to use a coupled atom-cavity system as a quantum memory. Along the line, we also discuss the performance and characterisation of cavity photons in elementary linear-optics arrangements with single beam splitters for quantum-homodyne measurements.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

Gross-Neveu Models, Nonlinear Dirac Equations, Surfaces and Strings

Recent studies of the thermodynamic phase diagrams of the Gross-Neveu model (GN2), and its chiral cousin, the NJL2 model, have shown that there are phases with inhomogeneous crystalline condensates. These (static) condensates can be found analytically because the relevant Hartree-Fock and gap equations can be reduced to the nonlinear Schr\"odinger equation, whose deformations are governed by the mKdV and AKNS integrable hierarchies, respectively. Recently, Thies et al have shown that time-dependent Hartree-Fock solutions describing baryon scattering in the massless GN2 model satisfy the Sinh-Gordon equation, and can be mapped directly to classical string solutions in AdS3. Here we propose a geometric perspective for this result, based on the generalized Weierstrass spinor representation for the embedding of 2d surfaces into 3d spaces, which explains why these well-known integrable systems underlie these various Gross-Neveu gap equations, and why there should be a connection to classical string theory solutions. This geometric viewpoint may be useful for higher dimensional models, where the relevant integrable hierarchies include the Davey-Stewartson and Novikov-Veselov systems.Comment: 27 pages, 1 figur

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd