A Population-Based Study of IGF Axis Polymorphisms and the Esophageal Inflammation, Metaplasia, Adenocarcinoma Sequence

BACKGROUND & AIMS: Insulin-like growth factor (IGF) axis plays a key role in cell development, proliferation, and survival and is implicated in the etiology of several cancers. Few studies have examined the relationship between genetic variation of this axis and esophageal adenocarcinoma (EAC) or its precursors. METHODS: In a population-based case-control study, we investigated the association of common polymorphisms of IGF-1, IGF-2, IGF-1 receptor, IGF binding protein -3, growth hormones (GH) 1 and GH2, and GH receptor with reflux esophagitis (RE), Barrett esophagus (BE), and EAC. Two hundred and thirty RE, 224 BE, 227 EAC cases, and 260 controls were studied. Gene polymorphisms were identified using publicly available online resources; 102 IGF axis tag and putatively functional single-nucleotide polymorphisms (SNPs) were analyzed using MassARRAY iPLEX and Taqman assays. Results were analyzed using Haploview.
RESULTS: Three polymorphisms were disease-associated. IGF1 SNP rs6214 was associated with BE (adjusted P = .039). Using GG genotype as reference, odds ratio for BE in AA (wild-type) was 0.43 (95% confidence interval [CI], 0.24-0.75). GH receptor SNP rs6898743 was associated with EAC (adjusted P = .0112). With GG as reference, odds ratio for EAC in CC (wildtype) genotype was 0.42 (95% CI, 0.23-0.76). IGF1 (CA)(17) 185-bp allele was associated with RE (adjusted P = .0116). Using IGF1(non17) as reference, odds ratio for RE in IGF1(17) carriers was 7.29 (95% CI, 1.57-46.7).
CONCLUSIONS: In this study, 3 polymorphisms of IGF genes were associated with EAC or its precursors. These polymorphisms may be markers of disease risk; independent validation of our findings is required. These results suggest the IGF pathway is involved in EAC development.

Professional perspectives on decision making about the long-term care of older people

With the increasing pressure on social and health care resources, professionals have to be more explicit in their decision making regarding the long-term care of older people. This grounded theory study used 19 focus groups and nine semi-structured interviews (99 staff in total) to explore professional perspectives on this decision making. Focus group participants and interviewees comprised care managers, social workers, consultant geriatricians, general medical practitioners, community nurses, home care managers, occupational therapists and hospital discharge support staff. The emerging themes spanned context, clients, families and services. Decisions were often prompted by a crisis, hindering professionals seeking to make a measured assessment. Fear of burglary and assault, and the willingness and availability of family to help were major factors in decisions about living at home. Service availability in terms of public funding for community care, the availability of home care workers and workload pressures on primary care services influenced decision 'thresholds' regarding admission to institutional care. Assessment tools designed to assist decision making about the long-term care of older people need to take into account the critical aspects of individual fears and motivation, family support and the availability of publicly funded services as well as functional and medical needs.

Building Autonomous Sensitive Artificial Listeners

This paper describes a substantial effort to build a real-time interactive multimodal dialogue system with a focus on emotional and non-verbal interaction capabilities. The work is motivated by the aim to provide technology with competences in perceiving and producing the emotional and non-verbal behaviours required to sustain a conversational dialogue. We present the Sensitive Artificial Listener (SAL) scenario as a setting which seems particularly suited for the study of emotional and non- verbal behaviour, since it requires only very limited verbal understanding on the part of the machine. This scenario allows us to concentrate on non-verbal capabilities without having to address at the same time the challenges of spoken language understanding, task modeling etc. We first report on three prototype versions of the SAL scenario, in which the behaviour of the Sensitive Artificial Listener characters was determined by a human operator. These prototypes served the purpose of verifying the effectiveness of the SAL scenario and allowed us to collect data required for building system components for analysing and synthesising the respective behaviours. We then describe the fully autonomous integrated real-time system we created, which combines incremental analysis of user behaviour, dialogue management, and synthesis of speaker and listener behaviour of a SAL character displayed as a virtual agent. We discuss principles that should underlie the evaluation of SAL-type systems. Since the system is designed for modularity and reuse, and since it is publicly available, the SAL system has potential as a joint research tool in the affective computing research community.

'A new sword on an old anvil': W.B.Yeats, Robert Graves and the Anglo-Irish Tradition

Throughout his writing life, Robert Graves was consistently and often publicly hostile to the work of W.B. Yeats, whilst still also owing a considerable debt to the older poet (who he never met). This essay explores Graves' complex responses to Yeats, arguing that his antagonism may be understood in the light of his own Anglo-Irish background, and is implicated in his relations with his father, Alfred Perceval Graves, as well as his experience of the First World War. Probing the suggestiveness of Graves's claim in 1959 that his poems 'remain true to the Anglo-Irish poetic tradition into which I was born', it traces the relation between Yeats and Graves through correspondence, critical writings, and through a comparative reading of Yeats's A Vision and Graves's The White Goddess, and reveals underlying similarities in their critical and mythological thinking in spite of Graves's public disavowal of the Yeatsian aesthetic.

Measuring workforce segregation: religious composition of private-sector employees at individual sites in Northern Ireland

In this paper I examine the scope of publicly available information on the religious composition of employees in private-sector companies in Northern Ireland. I highlight the unavailability of certain types of monitoring data and the impact of data aggregation at company as opposed to site level. Both oversights lead to underestimates of the extent of workplace segregation in Northern Ireland. The ability to provide more-coherent data on workplace segregation, by religion, in Northern Ireland is crucial in terms of advancing equality and other social-justice agendas. I argue that a more-accurate monitoring of religious composition of workplaces is part of an overall need to develop a spatial approach in which the importance of ethnically territorialised spaces in the reproduction of ethnosectarian disputation is understood.

Towards an Acceptable Level of Violence: Institutional Lessons from Northern Ireland

Institutional and economic development has recently returned to the forefront of economic analysis. The use of case studies (both historical and contemporary) has been important in this revival. Likewise, it has been argued recently by economic methodologists that historical context provides a kind of ‘‘laboratory’’ for the researcher interested in real world economic phenomena. Counterterrorism economics, in contrast with much of the rest of the literature on terrorism, has all too rarely drawn upon detailed contextual case studies. This article seeks to help remedy this problem. Archival evidence, including previously unpublished material on the DeLorean case, is an important feature of this article. The article examines how an inter-related strategy, which traded-off economic, security, and political considerations, operated during the Troubles. Economic repercussions of this strategy are discussed. An economic analysis of technical and organizational change within paramilitarism is also presented. A number of institutional lessons are discussed including: the optimal balance between carrot versus stick, centralization relative to decentralization, the economics of intelligence operations, and tit-for-tat violence. While existing economic models are arguably correct in identifying benefits from politico-economic decentralization, they downplay the element highlighted by institutional analysis.

Property rights and competing for the affections of Demos: The Impact of the 1867 Reform Act on stock prices

The 1867 Reform Act in Britain extended the electoral franchise to the skilled but propertyless urban working classes. Using stock market data and exploiting the fact that foreign and domestic equities traded simultaneously on the London market, this paper finds that investors in British firms reacted negatively to the passage of this Act. We suggest that this finding is consistent with investors foreseeing future alterations of property rights arising from the pressure that the large newly enfranchised group would bring to bear on government policy. We also suggest that our findings appear to be more consistent with the Tory political competition explanation for the Act rather than the Whig threat-of-revolution explanation.

WASP-23b: a transiting hot Jupiter around a K dwarf and its Rossiter-McLaughlin effect

We report the discovery of a new transiting planet in the southern hemisphere. It was found by the WASP-south transit survey and confirmed photometrically and spectroscopically by the 1.2 m Swiss Euler telescope, LCOGT 2m Faulkes South Telescope, the 60 cm TRAPPIST telescope, and the ESO 3.6 m telescope. The orbital period of the planet is 2.94 days. We find that it is a gas giant with a mass of 0.88 ± 0.10 MJ and an estimated radius of 0.96 ± 0.05 RJ. We obtained spectra during transit with the HARPS spectrograph and detect the Rossiter-McLaughlin effect despite its small amplitude. Because of the low signal-to-noise ratio of the effect and a small impact parameter, we cannot place a strong constraint on the projected spin-orbit angle. We find two conflicting values for the stellar rotation. We find, via spectral line broadening, that v sin I = 2.2 ± 0.3 km s-1, while applying another method, based on the activity level using the index log R'_HK, gives an equatorial rotation velocity of only v = 1.35 ± 0.20 km s-1. Using these as priors in our analysis, the planet might be either misaligned or aligned. This result raises doubts about the use of such priors. There is evidence of neither eccentricity nor any radial velocity drift with time. Using WASP-South photometric observations confirmed with LCOGT Faulkes South Telescope, the 60 cm TRAPPIST telescope, the CORALIE spectrograph and the camera from the Swiss 1.2 m Euler Telescope placed at La Silla, Chile, as well as with the HARPS spectrograph, mounted on the ESO 3.6 m, also at La Silla, under proposal 084.C-0185. The data is publicly available at the CDS Strasbourg and on demand to the main author.RV data is only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/531/A24Appendix is available in electronic form at http://www.aanda.org

Fast Retinal Vessel Detection and Measurement Using Wavelets and Edge Location Refinement

The relationship between changes in retinal vessel morphology and the onset and progression of diseases such as diabetes, hypertension and retinopathy of prematurity (ROP) has been the subject of several large scale clinical studies. However, the difficulty of quantifying changes in retinal vessels in a sufficiently fast, accurate and repeatable manner has restricted the application of the insights gleaned from these studies to clinical practice. This paper presents a novel algorithm for the efficient detection and measurement of retinal vessels, which is general enough that it can be applied to both low and high resolution fundus photographs and fluorescein angiograms upon the adjustment of only a few intuitive parameters. Firstly, we describe the simple vessel segmentation strategy, formulated in the language of wavelets, that is used for fast vessel detection. When validated using a publicly available database of retinal images, this segmentation achieves a true positive rate of 70.27%, false positive rate of 2.83%, and accuracy score of 0.9371. Vessel edges are then more precisely localised using image profiles computed perpendicularly across a spline fit of each detected vessel centreline, so that both local and global changes in vessel diameter can be readily quantified. Using a second image database, we show that the diameters output by our algorithm display good agreement with the manual measurements made by three independent observers. We conclude that the improved speed and generality offered by our algorithm are achieved without sacrificing accuracy. The algorithm is implemented in MATLAB along with a graphical user interface, and we have made the source code freely available. 

Information disclosure and depositor discipline in the Chinese banking sector

We investigate the relationship between information disclosure and depositor behaviour in the Chinese banking sector. Specifically, we enquire whether enhanced information disclosure enables investors to more effectively infer a banking institution's risk profile, thereby influencing their deposit decisions. Utilising an unbalanced panel, incorporating financial data from 169 Chinese banks over the 1998–2009 period, we employ generalised-method-of-moments (GMM) estimation procedures to control for potential endogeneity, unobserved heterogeneity, and persistence in the dependent variable. We uncover evidence that: (i) the growth rate of deposits is sensitive to bank fundamentals after controlling for macroeconomic factors, diversity in ownership structure, and government intervention; (ii) a bank publicly disclosing more transparent information in its financial reports, is more likely to experience growth in its deposit base; and (iii) banks characterised by high information transparency, well-capitalised and adopted international accounting standards, are more able to attract funds by offering higher interest rates.

Down with MNE-centric theories! Market entry and expansion as the bundling of MNE and local assets

Both Anderson and Gatignon and the Uppsala internationalization model see the initial mode of foreign market entry and subsequent modes of operation as unilaterally determined by multinational enterprises (MNEs) arbitraging control and risk and increasing their commitment as they gain experience in the target market. OLI and internalization models do recognize that foreign market entry requires the bundling of MNE and complementary local assets, which they call location or country-specific advantages, but implicitly assume that those assets are freely accessible to MNEs. In contrast to both of these MNE-centric views, I explicitly consider the transactional characteristics of complementary local assets and model foreign market entry as the optimal assignment of equity between their owners and MNEs. By looking at the relative efficiency of the different markets in which MNE and complementary local assets are traded, and at how these two categories of assets match, I am able to predict whether equity will be held by MNEs or by local firms, or shared between them, and whether MNEs will enter through greenfields, brownfields, or acquisitions. The bundling model I propose has interesting implications for the evolution of the MNE footprint in host countries, and for the reasons behind the emergence of Dragon MNEs.

Bio-port Free Energy City

In an age of depleting oil reserves and increasing energy demand, humanity faces a stalemate between environmentalism and politics, where crude oil is traded at record highs yet the spotlight on being ‘green’ and sustainable is stronger than ever. A key theme on today’s political agenda is energy independence from foreign nations, and the United Kingdom is bracing itself for nuclear renaissance which is hoped will feed the rapacious centralised system that the UK is structured upon. But what if this centralised system was dissembled, and in its place stood dozens of cities which grow and monopolise from their own energy? Rather than one dominant network, would a series of autonomous city-based energy systems not offer a mutually profitable alternative? Bio-Port is a utopian vision of a ‘Free Energy City’ set in Liverpool, where the old dockyards, redundant space, and the Mersey Estuary have been transformed into bio-productive algae farms. Bio-Port Free Energy City is a utopian ideal, where energy is superfluous; in fact so abundant that meters are obsolete. The city functions as an energy generator and thrives from its own product with minimal impact upon the planet it inhabits. Algaculture is the fundamental energy source, where a matrix of algae reactors swamp the abandoned dockyards; which themselves have been further expanded and reclaimed from the River Mersey. Each year, the algae farm is capable of producing over 200 million gallons of bio-fuel, which in-turn can produce enough electricity to power almost 2 million homes. The metabolism of Free-Energy City is circular and holistic, where the waste products of one process are simply the inputs of a new one. Livestock farming – once traditionally a high-carbon countryside exercise has become urbanised. Cattle are located alongside the algae matrix, and waste gases emitted by farmyards and livestock are largely sequestered by algal blooms or anaerobically converted to natural gas. Bio-Port Free Energy City mitigates the imbalances between ecology and urbanity, and exemplifies an environment where nature and the human machine can function productively and in harmony with one another. According to James Lovelock, our population has grown in number to the point where our presence is perceptibly disabling the planet, but in order to reverse the effects of our humanist flaws, it is vital that new eco-urban utopias are realised.

Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types

Background: MicroRNAs (miRNAs) are a class of small RNA molecules that regulate expression of specific mRNA targets. They can be released from cells, often encapsulated within extracellular vesicles (EVs), and therefore have the potential to mediate intercellular communication. It has been suggested that certain miRNAs may be selectively exported, although the mechanism has yet to be identified. Manipulation of the miRNA content of EVs will be important for future therapeutic applications. We therefore wished to assess which endogenous miRNAs are enriched in EVs and how effectively an overexpressed miRNA would be exported.

Results: Small RNA libraries from HEK293T cells and vesicles before or after transfection with a vector for miR-146a overexpression were analysed by deep sequencing. A subset of miRNAs was found to be enriched in EVs; pathway analysis of their predicted target genes suggests a potential role in regulation of endocytosis. RT-qPCR in additional cell types and analysis of publicly available data revealed that many of these miRNAs tend to be widely preferentially exported. Whilst overexpressed miR-146a was highly enriched both in transfected cells and their EVs, the cellular:EV ratios of endogenous miRNAs were not grossly altered. MiR-451 was consistently the most highly exported miRNA in many different cell types. Intriguingly, Argonaute2 (Ago2) is required for miR-451 maturation and knock out of Ago2 has been shown to decrease expression of other preferentially exported miRNAs (eg miR-150 and miR-142-3p).

Conclusion: The global expression data provided by deep sequencing confirms that specific miRNAs are enriched in EVs released by HEK293T cells. Observation of similar patterns in a range of cell types suggests that a common mechanism for selective miRNA export may exist.

Demo: Have a Chat with Sensitive Artificial Listeners

Sensitive Artificial Listeners (SAL) are virtual dialogue partners based on audiovisual analysis and synthesis. Despite their very limited verbal understanding, they intend to engage the user in a conversation by paying attention to the user’s emotions and non- verbal expressions. The SAL characters have their own emotionally defined personality, and attempt to drag the user towards their dom- inant emotion through a combination of verbal and non-verbal ex- pression. The demonstrator shows the publicly available, fully au- tonomous SAL system.

The impact of nonadherence to inhaled long-acting β - adrenoceptor agonist/corticosteroid combination therapy on healthcare costs in difficult-to-control asthma

Background: Asthma is a leading, preventable cause of morbidity, mortality and cost. A disproportionate amount of the cost is generated by the 5-10%of patients with difficult-to-control asthma, who are prescribed treatment at step 4/5 of the Global Initiative for Asthma (GINA) guidelines. We have previously demonstrated a high prevalence of nonadherence to inhaled combination therapy (i.e. long-acting ß -adrenoceptor agonist [ß - agonist] and corticosteroid) in this population. The aim of this study was to examine the costs of healthcare utilization in a nonadherent group of patients with difficult-to-control asthma compared with adherent subjects. We also wished to examine potential savings if nonadherence to inhaled combination therapy could be addressed. All costs were measured from the perspective of a publicly funded health service Methods: Adherence was determined through examination of patient prescription refill behaviour and validated with a medical concordance interview. Data on healthcare use were collected from a patient survey and hospital records that included prescribed medicines, hospital admissions, intensive care unit (ICU) admissions and other unscheduled healthcare visits associated with asthma care. Activity was monetized using standard UK references and between-group comparisons based on a series of univariate and multivariate regression analyses. Results: Cost differences were identified for inhaled combination therapy, nebulizer, short acting b2-agonists and hospital costs excluding and including ICU admissions between adherent and nonadherent subjects. Compared with a group who have refractory asthma and who are adherent with medication, additional healthcare costs in nonadherent subjects are offset by the reduction in costs associated with reduced medication utilization. However, if nonadherence can be successfully targeted and hospital admissions avoided in this population, there is a potential $475 ($843-$368) saving per patient, per annum. Conclusion: Nonadherence is an important cause of difficult-to-control asthma. A uniform cost for subjects with difficult-to-control disease can be applied to economic analyses, independent of adherence, as increased healthcare utilization costs are offset by the reduced medication cost due to poor adherence. However, there are substantial potential savings in subjects with difficult-to-control asthma, who are nonadherent to inhaled combination therapy, if cost effective strategies for nonadherence are developed. © 2011 Adis Data Information BV. All rights reserved.