Assessing the determinants of public confidence in the police: A case study of a post-conflict community in Northern Ireland

Drawing upon original survey research this article seeks to identify the generative processes that influence perceptions of the police in the context of an inner-city neighbourhood in Northern Ireland that has been affected by increases in crime and disorder in the aftermath of the peace process. Conceptually we draw upon recent research from England and Wales that outlines confidence in the police in terms of instrumental and expressive dimensions. We apply this framework and consider whether it provides a useful template for understanding the post-conflict dynamics of police-community relations in our study area. Contrary to much received wisdom our analysis suggests that instrumental concerns about crime and illegal activity are a more influential predictor of attitudes to the police than expressive concerns with disorder and anti-social behaviour. Consequently our discussion points to the variance in local and national survey data and questions the degree to which the latter can usefully inform our understanding of trends and developments in discrete micro-spaces. Our conclusion outlines the potential policy implications for state policing practice in deprived urban spaces.

Identification of Galanin and Its Receptor GalR1 as Novel Determinants of Resistance to Chemotherapy and Potential Biomarkers in Colorectal Cancer

Purpose: A major factor limiting the effective clinical management of colorectal cancer (CRC) is resistance to chemotherapy. Therefore, the identification of novel, therapeutically targetable mediators of resistance is vital.Experimental design: We used a CRC disease-focused microarray platform to transcriptionally profile chemotherapy-responsive and nonresponsive pretreatment metastatic CRC liver biopsies and in vitro samples, both sensitive and resistant to clinically relevant chemotherapeutic drugs (5-FU and oxaliplatin). Pathway and gene set enrichment analyses identified candidate genes within key pathways mediating drug resistance. Functional RNAi screening identified regulators of drug resistance.

Results: Mitogen-activated protein kinase signaling, focal adhesion, cell cycle, insulin signaling, and apoptosis were identified as key pathways involved in mediating drug resistance. The G-protein-coupled receptor galanin receptor 1 (GalR1) was identified as a novel regulator of drug resistance. Notably, silencing either GalR1 or its ligand galanin induced apoptosis in drug-sensitive and resistant cell lines and synergistically enhanced the effects of chemotherapy. Mechanistically, GalR1/galanin silencing resulted in downregulation of the endogenous caspase-8 inhibitor FLIP(L), resulting in induction of caspase-8-dependent apoptosis. Galanin mRNA was found to be overexpressed in colorectal tumors, and importantly, high galanin expression correlated with poor disease-free survival of patients with early-stage CRC.

Conclusion: This study shows the power of systems biology approaches to identify key pathways and genes that are functionally involved in mediating chemotherapy resistance. Moreover, we have identified a novel role for the GalR1/galanin receptor-ligand axis in chemoresistance, providing evidence to support its further evaluation as a potential therapeutic target and biomarker in CRC. Clin Cancer Res; 18(19); 5412–26. © 2012 AACR.

Genome-wide association study to identify genetic determinants of severe asthma

BACKGROUND: The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. OBJECTIVE: To identify common genetic variants affecting susceptibility to severe asthma. METHODS: A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480?889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. RESULTS: An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. CONCLUSIONS: The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.

A conceptualization of the determinants of small business website adoption

As evidence mounts on the importance of small businesses and the opportunities presented by website adoption globally, it becomes important to understand the key issues that determine website adoption. However, the extant literature relating to small business website adoption is fragmented and fails to provide an understanding of what determines adoption.Therefore the key contribution of this article to current knowledge is the development of a conceptualization, supported by the literature, that will provide an interpretation of what determines small business website adoption. Critically, this is the first article to incorporate the important role that the small business marketing context plays within Internet technology adoption. The article develops nine hypotheses, which relate to the critical interactions and integration, within and between four determinant groupings underpinning the conceptualization.The nine hypotheses will guide and direct future research towards generating an empirically based understanding of what determines small business website adoption.

Optimization of an ether series of mGluR5 positive allosteric modulators: Molecular determinants of MPEP site interaction crossover

We report the optimization of a series of non-MPEP site metabotropic glutamate receptor 5 (mGlu5) pos. allosteric modulators (PAMs) based on a simple acyclic ether series. Modifications led to a gain of MPEP site interaction through incorporation of a chiral amide in conjunction with a nicotinamide core. A highly potent PAM, 8v (VU0404251), was shown to be efficacious in a rodent model of psychosis. These studies suggest that potent PAMs within topol. similar chemotypes can be developed to preferentially interact or not interact with the MPEP allosteric binding site.

Phylogeny versus body size as determinants of food web structure

Food webs are the complex networks of trophic interactions that stoke the metabolic fires of life. To understand what structures these interactions in natural communities, ecologists have developed simple models to capture their main architectural features. However, apparently realistic food webs can be generated by models invoking either predator-prey body-size hierarchies or evolutionary constraints as structuring mechanisms. As a result, this approach has not conclusively revealed which factors are the most important. Here we cut to the heart of this debate by directly comparing the influence of phylogeny and body size on food web architecture. Using data from 13 food webs compiled by direct observation, we confirm the importance of both factors. Nevertheless, phylogeny dominates in most networks. Moreover, path analysis reveals that the size-independent direct effect of phylogeny on trophic structure typically outweighs the indirect effect that could be captured by considering body size alone. Furthermore, the phylogenetic signal is asymmetric: closely related species overlap in their set of consumers far more than in their set of resources. This is at odds with several food web models, which take only the view-point of consumers when assigning interactions. The echo of evolutionary history clearly resonates through current food webs, with implications for our theoretical models and conservation priorities.

International Projects and Cross-Cultural Adjustment of British Expatriates in Middle East: A Qualitative Investigation of Influencing Factors

Increased globalisation within the British AEC (Architectural, Engineering and Construction) sector has increased the need for companies to transfer staff to manage their overseas operations. To be able to perform abroad, expatriates must harmonise themselves to the conditions prevailing in the host country. These include getting accustomed to living, working and interacting with the host country nationals. The process is commonly referred to as 'cross-cultural adjustment'. Various factors influence the process of adjustment. In order to identify these issues, a qualitative study was undertaken, which mainly comprised of comprehensive literature review, individual interviews and focus group discussion with British expatriates working on international AEC assignments in Middle Eastern countries. Through interpretative approach, the current study aims to understand the concept of cross-cultural adjustment of British Expatriates based in Middle East and their influencing factors.

The findings suggest that success of expatriation does not entirely rest on an expatriate's ability but also on organisational support and assistance that expatriates receive prior to and during the assignment. Organisational factors such as selection mechanisms, job design, training, logistical and social support, mentoring, etc., influence various facets of expatriate adjustment. Striking cultural contrasts between British and Arab culture both in work and non work situations also dictate the level of support required by the expatriate, suggesting that relocation to less developed, remote or politically unstable regions, demands additional support and consideration by the parent company. This study is relevant to the AEC companies employing British expatriates, who need to be cognisant of the issues highlighted above to make rational and informed decisions when handling international assignments in the Middle East.

Strategies for Effective Management of Health and Safety in Confined Site Construction

The overall aim of this research is to identify and catalogue the numerous managerial strategies for effective management of health and safety on a confined, urban, construction site. A mixed methods methodology was adopted using interviews and focus group discussions on three selected case studies of confined construction sites. In addition to these, a questionnaire survey was used based on the findings from the interviews and the focus group discussions. The top five key strategies include (1) Employ safe system of work plans to mitigate personnel health and safety issues; (2) Inform personnel, before starting on-site, of the potential issues using site inductions; (3) Effective communication among site personnel; (4) Draft and implement an effective design site layout prior to starting on-site; and (5) Use of banksman (traffic co-ordinator) to segregate personnel from vehicular traffic. The construction sector is one of the leading industries in accident causation and with the continued development and regeneration of our urban centres, confined site construction is quickly becoming the norm - an environment which only fuels accident creation within the construction sector. This research aids on-site management that requires direction and assistance in the identification and implementation of key strategies for the management of health and safety, particularly in confined construction site environments.