Trends in nontariff barriers of developed countries : 1966-1986

While major concerns have been expressed about the spread of non-tariff barriers (NTBs) in developing countries, the lack of empirical information on the dimensions of the increase has affected the related policy debates. Using inventories of NTBs in developed countries compiled for 1966 and 1986, this study develops quantitative information on the major expansions of NTBs that occurred over this 20 year period. The paper finds that in 1966 NTBs affected 25 percent of developed countries imports, while in 1986 this share has increased to 48 percent. A second major point documented in the study is that the spread of NTBs has been uneven across countries and industrial sectors. Third, this study shows that the increased resort to discriminatory NTBs like"voluntary"export restraints (particularly in the U.S.) caused a significantly higher share of trade to be"affected"by NTBs than suggested by commonly used trade coverage ratios. The findings concerning the extent that NTBs have proliferated in some sectors (and countries) also increases the importance of establishing effective procedures for liberalization of these measures in multilateral trade negotiations like the Uruguay Round.Environmental Economics&Policies,TF054105-DONOR FUNDED OPERATION ADMINISTRATION FEE INCOME AND EXPENSE ACCOUNT,Economic Theory&Research,Trade Policy,Transport and Trade Logistics

5-hydroxymethylcytosine profiling as an indicator of cellular state

A Laird is supported by the Medical Research Council Scottish Clinical Pharmacology and Pathology Programme, The Royal College of Surgeons of Edinburgh Robertson’s Trust and The Melville Trust for the Care and Cure of Cancer. J Thomson is supported by the MARCAR project. Work in RR Meehan’s laboratory is supported by the Medical Research Council, the BBSRC and by the Innovative Medicine Initiative Joint Undertaking (IMI JU) under grant agreement number 115001 (MARCAR project).DNA methylation is widely studied in the context of cancer. However, the rediscovery of 5-hydroxymethylation of DNA adds a new layer of complexity to understanding the epigenetic basis of development and disease, including carcinogenesis. There have been significant advances in techniques for the detection of 5-hydroxymethylcytosine and, with this, greater insight into the distribution, regulation and function of this mark, which are reviewed here. Better understanding of the associated pathways involved in regulation of, and by, 5-hydroxymethylcytosine may give promise to new therapeutic targets. We discuss evidence to support the view of 5-hydroxymethylcytosine as a unique and dynamic mark of cellular state. These 5-hydroxymethylcytosine profiles may offer optimism for the development of diagnostic, prognostic and predictive biomarkers.Peer reviewe

SYSTEMS-2: a randomised phase II study of radiotherapy dose escalation for pain control in malignant pleural mesothelioma

SYSTEMS-2 is a randomised study of radiotherapy dose escalation for pain control in 112 patients with malignant pleural mesothelioma (MPM). Standard palliative (20Gy/5#) or dose escalated treatment (36Gy/6#) will be delivered using advanced radiotherapy techniques and pain responses will be compared at week 5. Data will guide optimal palliative radiotherapy in MPM

On the X-ray properties of submm-selected galaxies

We present an analysis of the X-ray properties of 35 submm galaxies(SMGs) in the CDF-N. Using a sample of robust 850micron-selected galaxies, with accurate positions from Spitzer and/or radio counterparts, we find 16 objects (45+/-8%) with significant X-ray detections in the 2Ms Chandra data. 6 of these SMGs (~17+/-6%) have measured X-ray luminosities or upper limits consistent with those expected based on the far-infrared (FIR) or radio-derived star formation rate (SFR), and hence with the X-rays coming solely from star formation. In another 7 sources (20+/-7%) a dominant AGN contribution to the X-ray emission is required, while in 3 more it is unclear whether stellar process or accretion are responsible. Stacking of the X-ray undetected SMGs reveals a highly significant detection. If due to star formation, this corresponds to an average X-ray derived SFR of ~150 Msun/yr. We deduce that the AGN fraction in SMGs based on X-ray observations is 20-29 (+/-7) %, which is towards the lower limit of previous estimates. Spectral analysis shows that in general the SMGs are not heavily obscured in the X-ray but most of the SMGs classfied as AGN show absorption with N_H in excess of 10^22 cm^-2. Of the secure AGN, the bolometric luminosity appears to be dominated by the AGN in only 3 cases. In ~85% of the SMGs, the X-ray spectrum effectively rules out an AGN contribution that dominates the bolometric emission, even if the AGN is Compton thick. The evidence therefore suggests that intense star formation accounts for both the FIR and X-ray emission in most SMGs. We argue that, rather than having an especially high AGN fraction or duty cycle, SMGs have a high X-ray detection rate at very faint fluxes partly because of their high star formation rates and, in rarer cases, because the submm emission is from an AGN.(abridged)Comment: 12 pages, 5 figures, accepted for publication in MNRA

AEGIS-X: The Chandra Deep Survey of the Extended Groth Strip

We present the AEGIS-X survey, a series of deep Chandra ACIS-I observations of the Extended Groth Strip. The survey comprises pointings at 8 separate positions, each with nominal exposure 200ks, covering a total area of approximately 0.67 deg2 in a strip of length 2 degrees. We describe in detail an updated version of our data reduction and point source detection algorithms used to analyze these data. A total of 1325 band-merged sources have been found to a Poisson probability limit of 4e-6, with limiting fluxes of 5.3e-17 erg/cm2/s in the soft (0.5-2 keV) band and 3.8e-16 erg/cm2/s in the hard (2-10 keV) band. We present simulations verifying the validity of our source detection procedure and showing a very small, <1.5%, contamination rate from spurious sources. Optical/NIR counterparts have been identified from the DEEP2, CFHTLS, and Spitzer/IRAC surveys of the same region. Using a likelihood ratio method, we find optical counterparts for 76% of our sources, complete to R(AB)=24.1, and, of the 66% of the sources that have IRAC coverage, 94% have a counterpart to a limit of 0.9 microJy at 3.6 microns (m(AB)=23.8). After accounting for (small) positional offsets in the 8 Chandra fields, the astrometric accuracy of the Chandra positions is found to be 0.8 arcsec RMS, however this number depends both on the off-axis angle and the number of detected counts for a given source. All the data products described in this paper are made available via a public website.Comment: 17 pages, 9 figures. Accepted for publication in ApJS. Data products are available at http://astro.imperial.ac.uk/research/aegis

Excess AGN Activity in the z=2.30 Protocluster in HS 1700+64

We present the results of spectroscopic, narrow-band and X-ray observations of a z=2.30 protocluster in the field of the QSO HS 1700+643. Using a sample of BX/MD galaxies, which are selected to be at z~2.2-2.7 by their rest-frame ultraviolet colours, we find that there are 5 protocluster AGN which have been identified by characteristic emission-lines in their optical/near-IR spectra; this represents an enhancement over the field significant at ~98.5 per cent confidence. Using a ~200 ks Chandra/ACIS-I observation of this field we detect a total of 161 X-ray point sources to a Poissonian false-probability limit of 4x10^{-6} and identify 8 of these with BX/MD galaxies. Two of these are spectroscopically confirmed protocluster members and are also classified as emission-line AGN. When compared to a similarly selected field sample the analysis indicates this is also evidence for an enhancement of X-ray selected BX/MD AGN over the field, significant at ~99 per cent confidence. Deep Lya narrow-band imaging reveals that a total of 4/123 Lya emitters (LAEs) are found to be associated with X-ray sources, with two of these confirmed protocluster members and one highly likely member. We do not find a significant enhancement of AGN activity in this LAE sample over that of the field (result significant at only 87 per cent confidence). The X-ray emitting AGN fractions for the BX/MD and LAE samples are found to be 6.9_{-4.4}^{+9.2} and 2.9_{-1.6}^{+2.9} per cent, respectively, for protocluster AGN with L_{2-10 keV}>4.6x10^{43} erg s^{-1} at z=2.30. These findings are similar to results from the z=3.09 protocluster in the SSA 22 field found by Lehmer et al. (2009), in that both suggest AGN activity is favoured in dense environments at z>2.Comment: 8 pages, 2 figures. Accepted for publication in MNRAS

X-ray observations of sub-mm LABOCA galaxies in the eCDFS

We explore the X-ray properties of the 126 sub-mm galaxies (SMGs) of the LABOCA survey in the CDFS and the eCDFS regions. SMGs are believed to experience massive episodes of star-formation. Our goal is to examine whether star-formation coexists with AGN activity, determine the fraction of highly obscured AGN and finally to obtain an idea of the dominant power-mechanism in these sources. Using Spitzer and radio arc-second positions for the SMGs, we find 14 sources with significant X-ray detections. For most of these there are only photometric redshifts available, with their median redshift being ~2.3. Taking into account only the CDFS area which has the deepest X-ray observations, we estimate an X-ray AGN fraction of <26+/-9 % among SMGs. The X-ray spectral properties of the majority of the X-ray AGN which are associated with SMGs are consistent with high obscuration, 10^23 cm-2, but there is no unambiguous evidence for the presence of Compton-thick sources. Detailed Spectral Energy Distribution fittings show that the bulk of total IR luminosity originates in star-forming processes, although a torus component is usually present. Finally, stacking analysis of the X-ray undetected SMGs reveals a signal in the soft (0.5-2 keV) and marginally in the hard (2-5 keV) X-ray band. The hardness ratio of the stacked signal is relatively soft (-0.40+/-0.10) corresponding to a photon index of ~1.6. This argues against a high fraction of Compton-thick sources among the X-ray undetected SMGs.Comment: 13 pages, to appear in A&

Alterations of immune response of non-small lung cancer with azacytidine

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

Cardio-respiratory studies in acute myocardial infarction

Shock or severe cardiac failure developing in the course of acute myocardial infarction is an ominous event with a grave prognosis. Despite its frequent occurrence, the precise haemodynamic alterations which occur in cardiogenic shock have not been clearly defined. To date there is no uniform agreement about the therapeutic management of these severely ill patients and the widely different therapeutic measures being advocated only emphasise the uncertainty about the precise pathogenesis of shock complicating acute myocardial infarction.This thesis reviews developments in the concept of myocardial infarction and describes haemodynamic and respiratory studies in patients with acute myocardial infarction.The investigations show that nearly all patients with recent myocardial infarction have abnormal cardio-respiratory function. Even in patients with so called 'uncomplicated' myocardial infarction cardiac output is in the low normal range and the mixed venous oxygen saturation is reduced. A number of these patients have a raised pulmonary arterial pressure. Mismatching of ventilation and perfusion results in arterial hypoxia. The clinical diagnosis of left ventricular failure is not always easy and the abnormal cardio- respiratory function suggests that sub -clinical left ventricular failure is a relatively common finding in acute myocardial infarction.In patients with cardiogenic shock or clinical left ventricular failure, the disorders of cardiac and pulmonary function are more marked but the similarity of the abnormalities suggests that left ventricular failure is present in both groups. The finding of raised pulmonary arterial pressures in the patients with cardiogenic shock is in accord with this view. In general the more severely ill the patient the greater is the degree of cardiac failure and respiratory abnormality.The thesis also documents attempts to treat the impaired left ventricular function in cardiogenic shock by digitalis and acid-base correction and comments on the failure of this approach.The failure to alter the course of cardiogenic shock by pharmacological agents is similar to the reports of many other investigators. Pain and anxiety are present in many of these patient and this can be relieved by opiates, but recent reports have suggested that morphine can produce marked hypotension in patients with acute myocardial infarction and that morphine should be used with great caution, if at all. A detailed examination of the circulatory effects of morphine and heroin in myocardial infarction is presented. The results suggest that morphine is a suitable analgesic for the relief of pain in acute myocardial infarction

The evolution of the Compton thick fraction and the nature of obscuration for AGN in the Chandra Deep Field South

(Abridged) We present the results from the X-ray spectral analysis of high-z AGN in the CDFS, making use of the new 4Ms data set and new X-ray spectral models from Brightman & Nandra, which account for Compton scattering and the geometry of the circumnuclear material. Our goals are to ascertain to what extent the torus paradigm of local AGN is applicable at earlier epochs and to evaluate the evolution of the Compton thick fraction (f_CT) with z, important for XRB synthesis models and understanding the accretion history of the universe. In addition to the torus models, we measure the fraction of scattered nuclear light, f_scatt known to be dependant on covering factor of the circumnuclear materal, and use this to aid in our understanding of its geometry. We find that the covering factor of the circumnuclear material is correlated with NH, and as such the most heavily obscured AGN are in fact also the most geometrically buried. We come to these conclusions from the result that f_scatt decreases as NH increases and from the prevalence of the torus model with the smallest opening angle as best fit model in the fits to the most obscured AGN. We find that a significant fraction of sources (~ 20%) in the CDFS are likely to be buried in material with close to 4 pi coverage having been best fit by the torus model with a 0\degree opening angle. Furthermore, we find 41 CTAGN in the CDFS using the new torus models, 29 of which we report here for the first time. We bin our sample by z in order to investigate the evolution of f_CT. Once we have accounted for biases and incompleteness we find a significant increase in the intrinsic f_CT, normalised to LX= 10^43.5 erg/s, from \approx 20% in the local universe to \approx 40% at z=1-4.Comment: Accepted for publication in MNRA