Genes of the Interleukin-18 Pathway Are Associated With Susceptibility to Barrett's Esophagus and Esophageal Adenocarcinoma

To investigate the association of genetic polymorphisms of the interleukin-18 (IL-18) pathway to Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Most cases of EAC arise in a background of reflux-induced BE. Genetic influences in this pathway are poorly understood. IL-18 is a multifunctional cytokine implicated in anti-tumor immunity. A number of polymorphisms of the IL-18 and IL-18 receptor-accessory protein (IL-18RAP) genes have been reported to alter gene expression and have recently been linked to inflammatory processes and various tumors, but have not heretofore been studied in BE and EAC.

“Boundary-setting as a core activity in complex public systems”

Title: Boundary-setting as a core activity in complex public systems
Authors: Joanne Murphy & Mary Lee Rhodes

The definition of the boundary of a system is at the core of any systems approach (Midgley 2000; 2003). By defining boundaries we enable – and delimit – the range of outcomes sought and the actions and resources that can be brought to bear. In complex adaptive systems (CAS) analysis, the conceptualisaion and definition of boundaries is particularly challenging as they are constantly undergoing redefinition through agent action, interaction and entry/exit. (Rhodes et al 2011). The concept of ‘boundaries’ appears regularly in a wide range of literature around public management, administration, geopolitics, regeneration and organisational development. Discussions around boundaries focus on many things from concrete physical manifestations and barriers, to virtual interfaces between one organisational unit and another, or even entirely theoretical demarcations between different schools of thought (Kaboolian, 1998, Levi-Faur, 2004, Agranoff & McGuire, 2004).

However, managing ‘beyond’ such boundaries is a routinely recurring aspiration that transcends sectors and local concerns. Unsurprisingly then, there is an increasing understanding of the need to acknowledge and manage such boundaries (whether they be physical, social or organisational) within public management as a discipline (Currie et al 2007, Fitzsimmons and White, 1997, Murtagh, 2002). This paper explores the impact of boundaries on public management strategic decision-making in the sectors of urban regeneration and healthcare. In particular, it focuses on demarcations to physical space, communal identity and within professional relationships in these sectors.

The first section describes the research that gave rise to the paper and the cases examined. Next we briefly define what we mean by boundaries. We explore issues that have emerged from our analysis of urban regeneration and health care singularly, before looking at how the concept of boundaries is a recurrent concern across the sectors. The main contribution of the paper is an exploration of how a CAS lens can bring a new insight into the concept of boundaries and decision-making in the two sets of case studies. This discussion will concentrate on initial conditions, bifurcation and adaptation as key CAS factors in relation to boundaries. We conclude with a brief discussion on the benefits of a CAS lens to an analysis of boundaries in public management decision-making.
References:

Agranoff, R. and McGuire, M. (2003) Collaborative Public Management: Strategies for Local Government. Washington, DC: Georgetown Univ. Press.

Currie, G., Lockett, A. (2007) “A critique of transformational leadership: moral, professional & contingent dimensions of leadership within public services organizations”. Human Relations 60: 341-370.

Fitzsimmons and White, (1997) "Crossing boundaries: communication between professional groups", Journal of Management in Medicine, Vol. 11 Iss: 2, pp.96 – 101

Kaboolian, L. (1998) “The New Public Management: Challenging the Boundaries of the Management vs. Administration Debate” Public Administration Review Vol. 58, No. 3 pp.189-193

Levi-Faur D. and Vigoda-Gadot Eran (eds) (2004) International Public Policy and Management: Policy Learning Beyond Regional, Cultural and Political Boundaries, Marcel Dekker,
Midgley, G. (ed) (2003) Systems Thinking. London: Sage Publications

Midgley, G. (2000) Systemic Intervention: Philosophy, Methodology and Practice. New York, NY: Kluwer.

Murtagh, B. (2002). The Politics of Territory: Policy and Segregation in Northern Ireland. Basingstoke, Palgrave.

Rhodes, ML, Joanne Murphy, Jenny Muir, John Murray (2011) Public Management & Complexity Theory: Richer Decision Making in Irish Public Services, UK: Routledge

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Common variant at 16p11.2 conferring risk of psychosis

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association (GWA) study, meta-analysis and follow-up (totaling as many as 18,206 cases and 42,536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7,469 bipolar disorder cases, 1,535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46,160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T], OR = 1.08, P = 6.6 × 10−11). The new variant is located within a 593 kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P = 0.0039 in the public GIANT consortium dataset; P = 0.00047 in 22,651 additional Icelanders).

John Rich as Opera Patron

This article traces the sustained support that theatre manager John Rich offered to operatic endeavours in 18th-century London. Rich effectively entered the contemporary discourse regarding the valid definition of opera through the kinds of works he supported, and also through the prefatory comments to two works staged at his theatre.