Incidence and management of rhinosinusitis after complex orbitofacial reconstruction.

OBJECTIVE: To examine the sinus-related sequelae of free flap reconstruction for complex orbitofacial defects. STUDY DESIGN: Retrospective chart review METHODS: Demographic, clinical, and radiographic data on a series of 55 patients who had undergone free tissue transfer for orbitofacial reconstruction was retrospectively reviewed. Follow-up of ≥ 3 months was available for 49 patients. Outcome measures studied included clinical or radiographic evidence of sinusitis and the need for sinus surgery. RESULTS: The most commonly involved sinuses were the ethmoid (n=40) and maxillary (n=38) sinuses, and the anterolateral thigh was the most common flap used (n=41). Clinical and/or radiographic sinusitis was evident in 21 patients (43%), and 10 patients (20%) required sinus surgery at some point during follow-up. Involvement of multiple sinuses in the initial orbitofacial surgery was associated with a significantly increased need for subsequent sinus surgery (p=0.009). Adjuvant radiotherapy and adjuvant chemo-radiotherapy were associated with a significantly increased risk for the development of rhinosinusitis (p=0.045 and 0.016 respectively). CONCLUSION: Rhinosinusitis and the need for operative management of sinus obstruction are common in patients having undergone complex orbitofacial reconstruction. Careful management of the paranasal sinuses is an important component of the multidisciplinary treatment of such patients

Advancing Interpretative Phenomenological Analysis as a Novel Methodological Tool in Deepening Insights and Amplifying the Voices of Women Mentees in Leadership Development Programmes in Irish Higher Education Institutions

Positioned within the field of Educational Leadership, this paper asserts the value of adopting Interpretative Phenomenological Analysis (IPA), as a qualitative methodological approach to explore and unravel the lived experience of women mentees (academics, professional, management and support services staff) in leadership mentoring relationships in an Irish Higher Education context. The research context focuses on the intersection of leadership mentoring and gender in Irish academia, prompted by the under-representation of women in senior positions, coupled with IPA as an under-utilised methodology in educational leadership research. Women’s’ voices are an important part of the process of consciousness-raising in discourses within Educational Leadership, of making what is invisible, visible; more especially in terms of enablers and barriers to women’s career advancement. Giving time and space to hear these voices, through the utility of IPA, allows their stories to unfold, by attending to their experiences, understanding, perceptions and views, of being in a leadership mentoring relationship. This paper showcases five distinctive features of IPA: (a) epistemological grounding, (b) amplifying individual voice, (c) inductive deepening of insights, (d) versatility and flexibility, and (e) co-creation between researcher and women mentees, to reveal what it is like for these women. In the process of this unveiling, IPA can make an iridescent contribution to the discourse on gender equality, leadership development, policy practice and action within an Irish higher education context

Commemoration or corruption? The feast-days of Abbán, Lommán, and Ailbe

A saint’s feast-day represents the date of his/her death. It is recorded under a calendar date in martyrologies and saints’ calendars. The meaning of a feastday is contradicted when a saint is given two feast-days in a martyrology. Why might a second feast-day be recorded for a saint? This article attempts to cast some light on the matter by examining Irish martyrological entries for three different saints: St. Abbán of Moyarney and Killabban, St. Lommán of Trim, and St. Ailbe of Emly, all believed to have lived at some point between the fifth to seventh centuries. The names of these three saints are commonly recorded under two separate calendar dates in most of the Irish martyrologies. This article will compare the different Irish martyrological sources in which their feast-days are recorded. It will also offer some consideration of other genealogical and hagiographical detail on the saints. This approach will demonstrate that the attestation of a second feast-day for each saint dates to a period no later than the eighth century. Lastly, this article argues that reasons for the attestation of a second feast-day can vary, depending on the individual cultural identities of each of the three saints

E1B attenuated adenoviral therapy for recurrent squamous cell cancer of the head and neck

Recurrent head and neck cancer is a disease which causes significant morbidity and mortality. Despite advances in surgical reconstruction and in chemotherapy and radiotherapy, current treatments for this disease give poor responses which are of short duration. Because of this, there is a need for new biological therapies to be developed. An example of this is the E1B deleted adenovirus, Onyx-015, which has been shown to selectively replicate in and lyse cells with non-functional p53 (Bischoff et al,1996). This virus may be therapeutically useful in the treatment of a wide range of tumours since p53 abnormalities are very common in human cancer. The aims of this thesis were to determine if this virus would selectively replicate in and lyse head and neck squamous cell carcinoma cell lines with non-functional p53, to determine if the virus could cause tumour regression of subcutaneous tumours derived from human head and neck tumour cell lines in a nude mouse xenograft model, and lastly to determine if this virus could be given safely by intratumoural injection to patients with recurrent head and neck cancer and whether it could produce an anti-tumour response. Using a panel of human head and neck squamous cell carcinoma cell lines of known p53 sequence and function, replication of the E1B attenuated adenovirus, Onyx-015, was tested by cytopathic effect assays, hexon protein staining and quantified by flow cytometry. These assays showed that replication was more efficient in cell lines with non-functional p53 confirming the previously published work in other cell types by Bischoff et al,1996. The cell line BICR16, derived from a patient with recurrent head and neck cancer, was used for in-vivo testing by intratumoural injection of subcutaneous xenografts in nude mice. We showed tumour regression in all virus injected tumours. In contrast, diluent injected tumours continued to grow exponentially. To determine the incidence of p53 inactivation in recurrent head and neck cancer, the p53 status of 22 recurrent head and neck tumours was evaluated by gene sequencing, mdm2 expression and HPV expression. Overall we have shown that there is a greater incidence of p53 mutations in recurrent disease compared to primary disease. However the incidence of HPV infection and mdm2 overexpression was similar to reported studies in primary disease. Nevertheless, we show that the overall incidence of p53 alterations is very high at 95%. This may be one factor which accounts for the poor response of this disease to radiotherapy and chemotherapy and implies new therapies which either restore p53 function or which act in a p53 independent manner may prove to be beneficial in this disease. (Abstract shortened by ProQuest.)

E1B Attenuated Adenoviruses in Genetic Therapy for Cancer

The E1B deleted adenovirus, Onyx-015, has been shown to selectively replicate in and lyse cells with nonfunctional p53 (Bischoff et a1,1996). This virus may be therapeutically useful in the treatment of a wide range of tumours since p53 abnormalities are very common in human cancer. The aims of this thesis were to develop an immunocompetent mouse model to study the role of the immune system in this form of therapy, to further examine the mechanism of selectivity of Onyx-015 for cells with non-functional p53, and lastly to determine whether or not Onyx-015 could increase the cytotoxicity to DNA damaging agents in functional and non-functional p53 cells. We have shown that human adenoviruses will infect rodent cell lines but with variable infectivity. In tissues with high infectivity, productive virus infection only occurs in mouse epidermal cells but is 25 to 50 fold less efficient compared to the human ovarian adenocarcinoma cell line A2780Cp70. The efficiency of replication in mouse epidermal cells is dependent on the expression of the early gene E1A and this correlated with the expression of the nuclear factor ϕAP3 , a transcriptional repressor of the E1A promotor. Replication is shown to be 20 fold greater in squamous (well differentiated ) epidermal cell lines in which there is a high expression of E1A and low ϕAP3 expression compared to clonally related spindle (poorly differentiated) epidermal cell lines. Using mouse epidermal cell lines of known p53 status and function, the selective replication of Onyx-015 for cells with non-functional p53 is in general agreement with that reported in human cell lines. However, some cell lines with wild type p53 function do allow replication of Onyx-015 and we postulate that this is determined by 2 factors, the expression of E1A and the ability for Onyx-015 to repress p21 levels. Using the squamous epidermal cell line PDVc57, in-vivo studies in both nude mouse and syngeneic mouse tumour xenograft models showed decreased tumour growth with intratumoural virus injection compared to diluent injected tumours. However, viral replication is markedly reduced in the syngeneic host suggesting limitation of viral replication by the immune system. Using the paired cell lines A2780 (functional p53) and the cisplatin resistant variant A2780Cp70 (non-functional p53) we have shown that replication is dependent on S-phase entry of the host infected cell and this correlated with E2F induction. In the cell line A2780, S phase entry and viral replication is limited due to virus induced p53 mediated apoptosis. We suggest that this is mediated by E1A induction of p19ARF. In contrast, A2780Cp70 allows a productive virus infection since apoptosis does not occur due to the absence of functional p53 and high expression of the anti-apoptotic factor E1B19kDa. We have shown that in the cell line with nonfunctional p53 (A2780Cp70), cytotoxicity to both cisplatin and radiation is increased by preinfecting cells with Onyx-015. In the cell line with functional p53 (A2780), preinfection with Onyx-015 for 72 hours also resulted in increased cytotoxicity to both cisplain and radiation. In contrast, preinfection of A2780 for 24 hours followed by cisplatin resulted in an antagonistic interaction leading to reduced drug sensitivity. It is suggested that this was due to p21 induction causing a reduction in the S-phase cell population. Further in vivo and clinical studies investigating the role of the immune system in this form of therapy and in the use of combination therapies are therefore warranted

Cultural Differences in ARCHES: A European Participatory Research Project—Working with Mixed Access Preferences in Different Cultural Heritage Sites

This article discusses the differences and difficulties that the ARCHES project has encountered when setting up and working with participatory research groups as part of a large-scale European project. The article seeks to clarify how participation is experienced across different international partners and research groups. This is explored in relation to recruitment of exploration groups, understanding participatory research, and challenging the definitions of disability. It also shares our methods of working with the participants and the impact upon those ways of working within different cultural environments. The article aims to guide future projects alike

Kleine Schritte zum institutionellen Wandel

Die Arbeit der indischen Organisation Gram Vikas zeigt, dass Social Entrepreneurs Institutionen nicht nur verändern, sondern auch neu schaffen. Diese Institutional Entrepreneurs können zentrale Akteure für einen institutionellen Wandel sein

Kleine Schritte zum institutionellen Wandel

Die Arbeit der indischen Organisation Gram Vikas zeigt, dass Social Entrepreneurs Institutionen nicht nur verändern, sondern auch neu schaffen. Diese Institutional Entrepreneurs können zentrale Akteure für einen institutionellen Wandel sein