Inhibition of platelet-derived growth factor promotes pericyte loss and angiogenesis in ischemic retinopathy

We investigated whether inhibition of platelet-derived growth factor (PDGF) receptor tyrosine kinase activity would affect pericyte viability, vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR-2) expression and angiogenesis in a model of retinopathy of prematurity (ROP). ROP was induced in Sprague Dawley rats by exposure to 80% oxygen from postnatal (P) days 0 to 11 (with 3 hours/day in room air), and then room air from P12-18 (angiogenesis period). Shams were neonatal rats in room air from P0-18. STI571, a potent inhibitor of PDGF receptor tyrosine kinase, was administered from P12-18 at 50 or 100 mg/kg/day intraperitoneal (i.p.). Electron microscopy revealed that pericytes in the inner retina of both sham and ROP rats appeared normal; however STI571 induced a selective pericyte and vascular smooth muscle degeneration. Immunolabeling for caspase-3 and a-smooth muscle cell actin in consecutive paraffin sections of retinas confirmed that these degenerating cells were apoptotic pericytes. In all groups, VEGF and VEGFR-2 gene expression was located in ganglion cells, the inner nuclear layer, and retinal pigment epithelium. ROP was associated with an increase in both VEGF and VEGFR-2 gene expression and blood vessel profiles in the inner retina compared to sham rats. STI571 at both doses increased VEGF and VEGFR-2 mRNA and exacerbated angiogenesis in ROP rats, and in sham rats at 100 mg/kg/day. In conclusion, PDGF is required for pericyte viability and the subsequent prevention of VEGF/VEGFR-2 overexpression and angiogenesis in ROP.

Multiplex RT-PCR for the detection of leukemia-associated translocations - Validation and application to routine molecular diagnostic practice

The aim of this study was to validate the application of a commercially available multiplex reverse transcription polymerase chain reaction (RT-PCR) assay [He-mavision-7 System] for the seven most common leukemia translocations for routine molecular diagnostic hematopathology practice. A total of 98 samples, comprising four groups, were evaluated: Group 1, 16 diagnostic samples molecularly positive by our existing laboratory-developed assays for PML-RARalpha/t (15; 17) or BCR-ABL/t (9;22); Group 2, 51 diagnostic samples negative by our laboratory-developed assays for PML-RARalpha/t (15;17) or BCR-ABL/t (9;22); Group 3, 21 prospectively analyzed diagnostic cases, without prior molecular studies; and Group 4, 10 minimal residual disease (MRD) samples. Analysis of the two previously studied cohorts (Groups 1 and 2) confirmed the diagnostic sensitivity and specificity of the multiplex assay with regard to these two translocations. Additionally, however, in the

Cultural threat and anti-immigrant prejudice: The case of Protestants in Northern Ireland

Using data from the 2002 and 2009 Northern Ireland Life and Times (NILT) surveys, we examine attitudes towards immigrant and ethnic minority groups in Northern Ireland. We suggest that Protestant and unionist communities experience a higher level of cultural threat than Catholic and nationalist communities on account of the ‘parity of esteem’ principle that has informed changes in the province since the Belfast Agreement of 1998. Our analyses confirm that, while there is evidence for some level of anti-immigrant sentiment across all groups, Protestants and unionists do indeed report relatively more negative attitudes towards a range of immigrant and ethnic target groups compared to Catholic, nationalist, or respondents who do not identify with either religious or political category. The analyses further suggest that their higher level of perceived cultural threat partially accounts for this difference. We suggest that cultural threat can be interpreted as a response to changes in Northern Ireland that have challenged the dominant status enjoyed by Protestants and unionists in the past.

How the ship of fools was ship-wrecked - The Irish crisis and response

For a decade and half the Irish economy was the poster-boy of Europe. With substantial growth rates, an open economy, flexible labour markets and low levels of taxation, Ireland was seen as evidence of the success of neoliberal policies. Yet in the matter of a few short years Ireland has turned into a one of the peripheral black-holes (along with Greece and Portugal) that are threatening to bring down the whole Eurozone project. Given this context the paper will address two key questions. Firstly how did the much eulogised Celtic Tiger fall so far and so fast? And, secondly, what has been the government’s response to the fall and crash of the Irish economy? These two questions will be addressed through both a general historical analysis of the developments of Irish society up to the crash in 2008 and then the responses to it. Secondly by an analysis of two specific elements of that development; namely the much discussed low corporation tax rate and the failure of social housing to deliver decent affordable homes for those at the bottom of society. The third element is a review of the banking and sovereign debt crisis that led to the IMF/EU deal in November 2010 and a brief outlining of its implications for public finances, especially the question of default. The paper concludes by placing the Irish crisis in a global context.

Second-order NMR spectra at high field of common organic functional groups

The proton NMR spectra of aryl n-propyl sulfides gave rise to what may appear to be first-order proton NMR spectra. Upon oxidation to the corresponding sulfone, the spectra changed appearance dramatically and were clearly second-order. A detailed analysis of these second-order spectra, in the sulfone series, provided vicinal coupling constants which indicated that these compounds had a moderate preference for the anti-conformer, reflecting the much greater size of the sulfone over the sulfide. It also emerged, from this study, that the criterion for observing large second-order effects in the proton NMR spectra of 1,2-disubstituted ethanes was that the difference in vicinal coupling constants must be large and the difference in geminal coupling constants must be small. n-Propyl triphenylphosphonium bromide and 2-trimethylsilylethanesulfonyl chloride, and derivatives thereof, also exhibited second-order spectra, again due to the bulky substituents. Since these spectra are second-order due to magnetic nonequivalence of the nuclei in question, not chemical shifts, the proton spectra are perpetually second-order and can never be rendered first-order by using higher field NMR spectrometers.

Multiculturalism, freedom of religion, equality, and the British constitution: The JFS case considered

In the JFS case, the Supreme Court of the United Kingdom held that the admissions policy of a Jewish faith school constituted unlawful racial discrimination because it used the Orthodox Jewish interpretation of who is Jewish as a criterion for determining admission to the school. A detailed discussion of the case is located in the context of two broader debates in Britain, which are characterized as constitutional in character or, at least, as possessing constitutional properties. The first is the debate concerning the treatment of minority groups, multiculturalism, and the changing perceptions in public policy of the role of race and religion in national life. It is suggested that this debate has become imbued with strong elements of what has been termed “post-multiculturalism”. The second debate is broader still, and pertains to shifting approaches to “constitutionalism” in Britain. It is suggested that, with the arrival of the European Convention on Human Rights and EU law, the U.K. has seen a shift from a pragmatic approach to constitutional thinking, in which legislative compromise played a key part, to the recognition of certain quasi-constitutional principles, allowing the judiciary greatly to expand its role in protecting individual rights while requiring the judges, at the same time, to articulate a principled basis for doing so. In both these debates, the principle of equality plays an important role. The JFS case is an important illustration of some of the implications of these developments.

Regulatory regime change in Turkish banks:Reactive or proactive?

This paper examines the positive contributions made toward restructuring the regulatory framework of Turkey's banking and financial sectors prior to and post the 2000–2001 financial crisis. Drawing on a framework initially developed by Onis and Senses, 2007 and Onis and Senses, 2009 and further referred to by Onis, 2009 and Onis, 2010 it argues that financial reforms undertaken by the Turkish government would not have been successful without the strong support of domestic coalitions. While the external pressures put on the Turkish government from the International Monetary Fund, The World Bank and the European Union for financial reforms were necessary to kick start the reforms as a reactive process, these pressures on their own may have served only the interests of financial business elites at the expense of the broader stakeholders. Empirical data for the study was collected from documentary analysis of key financial institutions and interviews with twenty major Turkish regulatory agents and other stakeholders. The paper then discusses how the perceptions of these stakeholders are embodied into, and have influenced, regulatory regime change in Turkey from a reactive state to a more proactive one.

Conservation status and reproduction of the critically endangered freshwater pearl mussel (Margaritifera margaritifera).

1. Freshwater unionoids are one of the most threatened animal groups worldwide and the freshwater pearl mussel Margaritifera margaritifera is currently listed as critically endangered in Europe. The ‘EC Habitats & Species Directive’ requires that EU member states monitor the distribution and abundance of this species and report regularly on its conservation status.
2. The pearl mussel meta-population in Northern Ireland was surveyed to assess temporal population trends in Special Areas of Conservation (SACs) and mussel reproduction throughout its range.
3. Mussels occurred in six rivers and numbers within three SAC designated sites remained stable between 2004-07 and 2011. The discovery of >8,000 previously unknown individuals in the Owenreagh River contributed to an overall increase (+56.8%) in the total known population. All populations actively reproduced during 2010 with approximately half of all individuals gravid. Moreover, suitable salmonid hosts occurred at all sites with 10.7% of salmon and 22.8% of trout carrying encysted glochidia. Populations were composed entirely of aged individuals with little evidence of recent recruitment.
4. We infer that the break in the life cycle must occur during the juvenile stage when glochidia metamorphose and settle into the interstitial spaces within the substrate. Water quality parameters, most notably levels of suspended solids, exceeded the recommended maximum thresholds in all rivers.
5. We posit that the deposition of silt may be the main cause of juvenile mortality contributing to a lack of recruitment. Consequently, all populations were judged to be in ‘unfavourable’ conservation status. Catchment-level management plans are urgently needed to reduce siltation with the aim of improving recruitment. Our results have implications for the success of ex-situ conservation programmes; specifically, the size at which captive bred juveniles are released into the wild. Further research is required to assess the vulnerabilities of early life stages of M. margaritifera to siltation.

A Randomized, Double-Blind, Dose-Finding, Multicenter, Phase 2 Study of Radium Chloride (Ra 223) in Patients with Bone Metastases and Castration-Resistant Prostate Cancer

BACKGROUND: Patients with castration-resistant prostate cancer (CRPC) and bone metastases have an unmet clinical need for effective treatments that improve quality of life and survival with a favorable safety profile. OBJECTIVE: To prospectively evaluate the efficacy and safety of three different doses of radium chloride (Ra 223) in patients with CRPC and bone metastases. DESIGN, SETTING, AND PARTICIPANTS: In this phase 2 double-blind multicenter study, 122 patients were randomized to receive three injections of Ra 223 at 6-wk intervals, at doses of 25 kBq/kg (n=41), 50 kBq/kg (n=39), or 80 kBq/kg (n=42). The study compared the proportion of patients in each dose group who had a confirmed decrease of =50% in baseline prostate-specific antigen (PSA) levels. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Efficacy was evaluated using blood samples to measure PSA and other tumor markers, recorded skeletal-related events, and pain assessments. Safety was evaluated using adverse events (AEs), physical examination, and clinical laboratory tests. The Jonckheere-Terpstra test assessed trends between groups. RESULTS AND LIMITATIONS: The study met its primary end point with a statistically significant dose-response relationship in confirmed =50% PSA declines for no patients (0%) in the 25-kBq/kg dose group, two patients (6%) in the 50-kBq/kg dose group, and five patients (13%) in the 80-kBq/kg dose group (p=0.0297). A =50% decrease in bone alkaline phosphatase levels was identified in six patients (16%), 24 patients (67%), and 25 patients (66%) in the 25-, 50-, and 80-kBq/kg dose groups, respectively (p

Energy efficiency investments in the home: Swiss homeowners and expectations about future energy prices

Using conjoint choice experiments, we surveyed 473 Swiss homeowners about their preferences for energy efficiency home renovations.We find that homeowners are responsive to the upfront costs of the renovation projects, governmentoffered rebates, savings in energy expenses, time horizon over which such savings would be realized, and thermal comfort improvement. The implicit discount rate is low, ranging from 1.5 to 3%, depending on model specification. This is consistent with Hassett and Metcalf (1993) and Metcalf and Rosenthal (1995), and with the fact that our scenarios contain no uncertainty. Respondents who feel completely uncertain about future energy prices are more likely to select the status quo (no renovations) in any given choice task and weight the costs of the investments more heavily than the financial gains (subsidies and savings on the energy bills). Renovations are more likely when respondents believe that climate change considerations are important determinants of home renovations. Copyright © 2013 by the IAEE. All rights reserved.

Can grass biomethane be an economically viable biofuel for the farmer and the consumer?

Farm incomes in Ireland are in decline and many farmers would operate at a loss in the absence of subsidies. Agriculture is responsible for 27% of Ireland's greenhouse gas emissions and is the largest contributing sector. Penetration of renewable energy in the heat and transport sectors is falling short of targets, and there is no clear plan for achieving them. The anaerobic digestion of grass to produce biogas or biomethane is put forward as a multifaceted solution, which could help meet energy and emissions targets, reduce dependence on imported energy, and provide additional farm income. This paper addresses the economic viability of such a system. Grass biogas/biomethane fares poorly under the current combined heat and power tariff structure, which is geared toward feedstock that attracts a gate fee. Tariff structures similar to those used in other countries are necessary for the industry to develop. Equally, regulation should be implemented to allow injection of biomethane into the gas grid in Ireland. Blends of natural gas and biomethane can be sold, offering a cost-competitive green fuel. Sale as a renewable transport fuel could allow profitability for the farmer and savings for the consumer, but suffers due to the lack of a market. Under current conditions, the most economically viable outlet for grass biomethane is sale as a renewable heating fuel. The key to competitiveness is the existing natural gas infrastructure that enables distribution of grass biomethane, and the renewable energy targets that allow renewable fuels to compete against each other. © 2010 Society of Chemical Industry and John Wiley & Sons, Ltd.

Is everyone Irish on St Patrick's Day? Divergent expectations and experiences of collective self-objectification at a multicultural parade

We examine experiences of collective self-objectification (CSO) (or its failure) among participants in a ‘multicultural’ St Patrick's Day parade. A two-stage interview study was carried out in which 10 parade participants (five each from ethnic majority and minority groups) were interviewed before and after the event. In pre-event interviews, all participants understood the parade as an opportunity to enact social identities, but differed in the category definitions and relations they saw as relevant. Members of the white Irish majority saw the event as being primarily about representing Ireland in a positive, progressive, light, whereas members of minority groups saw it as an opportunity to have their groups' identities and belonging in Ireland recognized by others. Post-event interviews revealed that, for the former group, the event succeeded in giving expression to their relevant category definitions. The latter group, on the other hand, cited features of the event such as inauthentic costume design and a segregated structure as reasons for why the event did not provide the group recognition they sought. The accounts revealed a variety of empowering and disempowering experiences corresponding to the extent of enactment. We consider the implications in terms of CSO, the performative nature of dual identities, as well as the notion of multicultural recognition.

Incubation or Induction? Gendered Identity Work in the Context of Technology Business Incubation

While there is a substantial body of literature exploring the influence of business incubation upon early stage firms, this debate remains almost entirely gender blind. This article challenges this assumption by adopting a feminist perspective to reveal business incubation as a gendered process shaping the identity work undertaken by women seeking legitimacy as technology venturers. In so doing, we critically evaluate prevailing normative analyses of the business incubation process and entrepreneurial legitimation. To illustrate this argument, we draw upon empirical evidence which reveals technology incubation as a legitimating induction process encouraging women to reproduce masculinized representations of the normative technology entrepreneur.

An exploration of business model development in the commercialization of technology innovations

Research on business model development has focused on the relationships between elements of value conceptualization and organization having a linear sequence in which business models are first designed and then implemented. Another stream of research points to business model development with these elements interacting in a cyclical manner. There is a need to improve our understanding of the connective mechanisms and dynamics involved in business model development, particularly from the challenging perspective of commercializing innovations. The aim of this paper was to explore business model development during the commercialization of innovations through a case-based qualitative study. This study found from four case studies that specific elements of business model development, representative of the conceptualization of value and organizing for value creation, integrate in a dynamic and cyclical process in the commercialization of technology innovations. The study provides empirical evidence that adds new insights to literature on sequential and more interactive processes of business model development. It also contributes to literature on business model development and particularly how it relates to the commercialization of innovations.