Limbal stem cell deficiency and ocular phenotype in ectrodactyly-ectodermal dysplasia-clefting syndrome caused by p63 mutations

Objective: To describe the ocular phenotype in patients with ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome (MIM#604292) and to determine the pathogenic basis of visual morbidity. Design: Retrospective case series. Participants: Nineteen families (23 patients) affected by EEC syndrome from the United Kingdom, Ireland, and Italy. Methods: General medical examination to fulfill the diagnostic criteria for EEC syndrome and determine the phenotypic severity. Mutational analysis of p63 was performed by polymerase chain reaction-based bidirectional Sanger sequencing. All patients with EEC syndrome underwent a complete ophthalmic examination and ocular surface assessment. Limbal stem cell deficiency (LSCD) was diagnosed clinically on the basis of corneal conjunctivalization and anatomy of the limbal palisades of Vogt. Impression cytology using immunofluorescent antibodies was performed in 1 individual. Histologic and immunohistochemical analyses were performed on a corneal button and corneal pannus from 2 EEC patients. Main Outcome Measures: The EEC syndrome phenotypic severity (EEC score), best-corrected Snellen visual acuity (decimal fraction), slit-lamp biomicroscopy, tear function index, tear breakup time, LSCD, p63 DNA sequence variants, impression cytology, and corneal histopathology. Results: Eleven heterozygous missense mutations in the DNA binding domain of p63 were identified in all patients with EEC syndrome. All patients had ocular involvement and the commonest was an anomaly of the meibomian glands and lacrimal drainage system defects. The major cause of visual morbidity was progressive LSCD, which was detected in 61% (14/23). Limbal stem cell deficiency was related to advancing age and caused a progressive keratopathy, resulting in a dense vascularized corneal pannus, and eventually leading to visual impairment. Histologic analysis and impression cytology confirmed LSCD. Conclusions: Heterozygous p63 mutations cause the EEC syndrome and result in visual impairment owing to progressive LSCD. There was no relationship of limbal stem cell failure with the severity of EEC syndrome, as classified by the EEC score, or the underlying molecular defect in p63. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. © 2012 American Academy of Ophthalmology.

A Framework for Stakeholder Management and Corporate Culture

Purpose: This paper investigates the link between two knowledge areas that have not been previously linked conceptually; stakeholder management and corporate culture. Focussing on the UK Construction Industry, the research study demonstrates mutual dependency of each of these areas on the other and establishes a theoretical framework with real potential to impact positively upon industry.

Design/methodology/approach: The study utilises both qualitative and quantitative data collection and then analysis to produce results contributing to the final framework. Semi-structured interviews were used and analysed through a cognitive mapping procedure. The result of this stage, set in the context of previous research, facilitated a questionnaire to be developed which helped gather quantitative values from a larger sample to enhance the final framework.

Findings: The data suggests that stakeholder management and corporate culture are key areas of an organisation’s success, and that this importance will only grow in future. A clearly identifiable relationship was established between the two theoretical areas and a framework developed and quantified.

Originality/value: It is evident that change is needed within the UK Construction Industry. Companies must employ ethical and social stakeholder management and manage their corporate culture like any other aspect of their business. Successfully doing this will lead to more successful projects, better reputation and survival. The findings of this project begin to show how change may occur and how companies might intentionally deploy advantageous configurations of corporate culture and stakeholder management.

Punitiveness and Political Culture: Notes from Some Small Countries

Green’s (2007, 2008, 2009) recent comparative work on child-on-child homicides in England and Norway has drawn attention to political-cultural explanations to account for differences in levels of state punitiveness. His work finds support for the distinction made by Arend Lijphart (1999) between consensus and majoritarian democracy, through his argument that English majoritarian political culture created powerful incentives to exploit the homicide of James Bulger in ways that were not present in Norway. Drawing on comparative research in Ireland, Scotland and New Zealand, this article joins with Green in enlisting political culture as an important explanatory variable yet challenges the usefulness of Lijphart’s typology in explaining penal difference.

Susceptibility of streptozotocin-induced diabetic rat retinal function and ocular blood flow to acute intraocular pressure challenge.

PURPOSE: To consider whether STZ-induced hyperglycemia renders rat retinal function and ocular blood flow more susceptible to acute intraocular pressure (IOP) challenge.

METHODS: Retinal function (electroretinogram, ERG) was measured during acute IOP challenge (10-100 mmHg, 5 mmHg increments, 3 min/step, vitreal cannulation) in adult Long-Evans rats (6-week old, citrate: n=6, STZ: n=10) 4 weeks after citrate buffer or streptozotocin (STZ, 65 mg/kg, blood glucose > 15 mmol/l) injection. At each IOP, dim and bright flash (-4.56, -1.72 log cd.s.m^-2) ERG responses were recorded to measure inner retinal and ON-bipolar cell function, respectively. Ocular blood flow (laser Doppler flowmetry, citrate; n=6, STZ; n=10) was also measured during acute IOP challenge. Retinae were isolated for qPCR analysis of nitric oxide synthase mRNA expression endothelial, eNos; inducible, iNos; neuronal, nNos).

RESULTS: STZ-induced diabetes increased the susceptibility of inner retinal (IOP at 50% response, 60.1, CI: 57.0-62.0 mmHg vs. citrate: 67.5, CI: 62.1-72.4 mmHg) and ON-bipolar cell function (STZ: 60.3, CI: 58.0-62.8 mmHg vs. citrate: 65.1, CI: 58.0-62.78 mmHg) and ocular blood flow (43.9, CI: 40.8-46.8 vs. citrate: 53.4, CI: 50.7-56.1 mmHg) to IOP challenge. Citrate eyes showed elevated eNos mRNA (+49.7%) after IOP stress, an effect not found in STZ-diabetic eyes (-5.7%, P<0.03). No difference was observed for iNos or nNos (P>0.05) following IOP elevation.

CONCLUSIONS: STZ-induced diabetes increased functional susceptibility during acute IOP challenge. This functional vulnerability is associated with a reduced capacity for diabetic eyes to upregulate eNOS expression and to autoregulate blood flow in response to stress.

Catholics, Science and Civic Culture in Victorian Belfast

The connections between science and civic culture in the Victorian period have been extensively, and intensively, investigated over the past several decades. Limited attention, however, has been paid to Irish urban contexts. Roman Catholic attitudes towards science in the nineteenth century have also been neglected beyond a rather restricted set of thinkers and topics. This paper is offered as a contribution to addressing these lacunae, and examines in detail the complexities involved in Catholic engagement with science in Victorian Belfast. The political and civic geographies of Catholic involvement in scientific discussions in a divided town are uncovered through an examination of five episodes in the unfolding history of Belfast's intellectual culture. The paper stresses the importance of attending to the particularities of local politics and scientific debate for understanding the complex realities of Catholic appropriations of science in a period and urban context profoundly shaped by competing political and religious factions. It also reflects more generally on how the Belfast story supplements and challenges scholarship on the historical relations between Catholicism and science.