Ethnoreligious change in Northern Ireland and Zimbabwe:A comparative study of how religious havens can have ethnic significance

This study compares the internal dynamics of religious change in the 'post-evangelical' Ikon community in Belfast, Northern Ireland, and a charismatic, multiethnic congregation in Harare, Zimbabwe. Although the theological ideas behind Ikon and the congregation vary widely, the processes whereby both groups manage change are broadly similar and have wider theoretical significance. Accordingly, this article analyses how people use the religious resources of their traditions to construct 'havens' in which change is facilitated. Havens are conceived of as safe spaces where people use religious resources to challenge ethnic boundaries and power structures. They can be seen to function as mechanisms for disrupting long-entrenched feedback patterns of opposition and conflict. © 2010 The Editor of Ethnopolitics.

Northern Ireland, America and the Emerging Church Movement: Exploring the Significance of Peter Rollins andthe Ikon Collective

The Emerging Church Movement (ECM) is a primarily Western religious phenomenon, identifiable by its critical ‘deconstruction’ of ‘modern’ religion. While most prominent in North America, especially the United States, some of the most significant contributors to the ECM ‘conversation’ have been the Belfast-based Ikon Collective and one of its founders, philosopher Peter Rollins. Their rootedness in the unique religious, political and social landscape of Northern Ireland in part explains their position on the ‘margins’ of the ECM, and provides many of the resources for their contributions. Ikon’s development of ‘transformance art’ and its ‘leaderless’ structure raise questions about the institutional viability of the wider ECM. Rollins’ ‘Pyrotheology’ project, grounded in his reading of post-modern philosophy, introduces more radical ideas to the ECM conversation. Northern Ireland’s ‘Troubles’ and ‘marginal’ location provides the ground from which Rollins and Ikon have been able to expose the boundaries of the ECM and raise questions about just how far the ECM may go in its efforts to transform Western Christianity.

Significance of tagI and mfd genes in the virulence of non-typeable Haemophilus influenzae

Non-typeable Haemophilus influenzae (NTHi) is an opportunist pathogen well adapted to the human upper respiratory tract and responsible for many respiratory diseases. In the human airway, NTHi is exposed to pollutants, such as alkylating agents, that damage its DNA. In this study, we examined the significance of genes involved in the repair of DNA alkylation damage in NTHi virulence. Two knockout mutants, tagI and mfd, encoding N(3)methyladenine-DNA glycosylase I and the key protein involved in transcription-coupled repair, respectively, were constructed and their virulence in a BALB/c mice model was examined. This work shows that N-3-methyladenine-DNA glycosylase I is constitutively expressed in NTHi and that it is relevant for its virulence.

The prognostic significance of PD-L1 in bladder cancer

Immunotherapy is a promising strategy for the treatment of various types of cancer. An antibody that targets programmed death ligand-1 (PD-L1) pathway has been shown to be active towards various types of cancer, including melanoma and lung cancer. MPDL3280A, an anti‑PD-L1 antibody, has shown clear clinical activity in PD-L1-overexpressing bladder cancer with an objective response rate of 40-50%, resulting in a breakthrough therapy designation granted by FDA. These events pronounce the importance of targeting the PD-L1 pathway in the treatment of bladder cancer. In the present study, we investigated the prognostic significance of the expression of three genes in the PD-L1 pathway, including PD-L1, B7.1 and PD-1, in three independent bladder cancer datasets in the Gene Expression Omnibus database. PD-L1, B7.1 and PD-1 were significantly associated with clinicopathological parameters indicative of a more aggressive phenotype of bladder cancer, such as a more advanced stage and a higher tumor grade. In addition, a high level expression of PD-L1 was associated with reduced patient survival. Of note, the combination of PD-L1 and B7.1 expression, but not other combinations of the three genes, were also able to predict patient survival. Our findings support the development of anti-PD-L1, which blocks PD-L1-PD-1 and B7.1-PD-L1 interactions, in treatment of bladder cancer. The observations were consistent in the three independent bladder cancer datasets consisting of a total of 695 human bladder specimens. The datasets were then assessed and it was found that the expression levels of the chemokine CC-motif ligand (CCL), CCL3, CCL8 and CCL18, were correlated with the PD-L1 expression level, while ADAMTS13 was differentially expressed in patients with a different survival status (alive or deceased). Additional investigations are required to elucidate the role of these genes in the PD-L1-mediated immune system suppression and bladder cancer progression. In conclusion, findings of this study suggested that PD-L1 is an important prognostic marker and a therapeutic target for bladder cancer.

The significance of combining VEGFA, FLT1, and KDR expressions in colon cancer patient prognosis and predicting response to bevacizumab

Targeting angiogenesis through inhibition of the vascular endothelial growth factor (VEGF) pathway has been successful in the treatment of late stage colorectal cancer. However, not all patients benefit from inhibition of VEGF. Ras status is a powerful biomarker for response to anti-epidermal growth factor receptor therapy; however, an appropriate biomarker for response to anti-VEGF therapy is yet to be identified. VEGF and its receptors, FLT1 and KDR, play a crucial role in colon cancer progression; individually, these factors have been shown to be prognostic in colon cancer; however, expression of none of these factors alone was predictive of tumor response to anti-VEGF therapy. In the present study, we analyzed the expression levels of VEGFA, FLT1, and KDR in two independent colon cancer datasets and found that high expression levels of all three factors afforded a very poor prognosis. The observation was further confirmed in another independent colon cancer dataset, wherein high levels of expression of this three-gene signature was predictive of poor prognosis in patients with proficient mismatch repair a wild-type KRas status, or mutant p53 status. Most importantly, this signature also predicted tumor response to bevacizumab, an antibody targeting VEGFA, in a cohort of bevacizumab-treated patients. Since bevacizumab has been proven to be an important drug in the treatment of advanced stage colon cancer, our results suggest that the three-gene signature approach is valuable in terms of its prognostic value, and that it should be further evaluated in a prospective clinical trial to investigate its predictive value to anti-VEGF treatment.

Incidence and significance of the JAK2 V617F mutation in patients with chronic myeloproliferative disorders

BACKGROUND: The chronic myeloproliferative disorders (MPD) are clonal haemopoietic stem cell disorders.

AIMS: The incidence of JAK2 V617F mutation was sought in a population of patients with MPD.

METHODS: The JAK2 V617 mutation status was determined in 79 patients with known MPD and 59 patients with features suggestive of MPD.

RESULTS: The mutation was found in patients with polycythaemia vera, essential thrombocythaemia, idiopathic myelofibrosis and in patients with other chronic myeloproliferative disorders. Eight JAK2 V617F positive cases were identified amongst those patients with features suggestive of MPD.

CONCLUSIONS: The incidence of the JAK2 V617F mutation in MPD patients is similar to that reported by other groups. The assay confirmed and refined the diagnosis of several patients with features indicative of MPD. We suggest screening for this mutation in all patients with known and suspected MPD as identification is valuable in classification and is a potential target for signal transduction therapy.

Mixed chimaerism; detection and significance following BMT

Residual recipient haematopoietic cells may coexist with donor haemopoietic tissue following BMT. This is known as mixed chimaerism. The incidence of mixed chimaerism varies with the sensitivity of the detection system used; DNA based methodologies are the most sensitive. The influence of mixed chimaerism on leukaemia relapse and graft rejection is unclear. The lineages in which mixed chimaerism occurs may affect outcome.

The significance of interconnector counter-trading in a security constrained electricity market

Throughout the European Union there is an increasing amount of wind generation being dispatched-down due to the binding of power system operating constraints from high levels of wind generation. This paper examines the impact a system non-synchronous penetration limit has on the dispatch-down of wind and quantifies the significance of interconnector counter-trading to the priority dispatching of wind power. A fully coupled economic dispatch and security constrained unit commitment model of the Single Electricity Market of the Republic of Ireland and Northern Ireland and the British Electricity Trading and Transmission Arrangement was used in this study. The key finding was interconnector counter-trading reduces the impact the system non-synchronous penetration limit has on the dispatch-down of wind. The capability to counter-trade on the interconnectors and an increase in system non-synchronous penetration limit from 50% to 55% reduces the dispatch-down of wind by 311 GW h and decreases total electricity payments to the consumer by €1.72/MW h. In terms of the European Union electricity market integration, the results show the importance of developing individual electricity markets that allow system operators to counter-trade on interconnectors to ensure the priority dispatch of the increasing levels of wind generation.

The significance of bruising in the pre-mobile infant

The majority of children in our society are loved andcherished. The occasional cases of intentional injury to a childresulting in death or significant harm evoke powerful anduncomfortable feelings (Devaney et al, 2013), and the publicoutcry may result in health and social workers facing criticism.Identifying whether an infant is at risk of abuse is a challengefor practitioners, and can be a source of stress and anxiety(Brandon et al, 2011). Bruising is a strong indicator of childabuse involving intentional injury (Kemp et al, 2014). Theincidence of bruising correlates to developmental stage, withnon-mobile infants least likely to incur bruising. Therefore, itspresence in pre-mobile infants requires immediate assessment.A search of the literature around bruising in pre-mobile infantsrevealed themes of missed opportunities for early intervention,the role of the father in the family and the significance of childdevelopment. Sharing of knowledge and expertise within themultidisciplinary team is key to safeguarding infants.

The Prognostic Significance of Combining VEGFA, FLT1 and KDR mRNA Expressions in Brain Tumors

Tumor cells require angiogenesis to deliver nutrients and oxygen to support their fast growth and metabolism. The vascular endothelial growth factor (VEGF) pathway plays an important role in promoting angiogenesis, including tumor-induced angiogenesis. Recent clinical trials have demonstrated the benefit of targeting VEGF in the treatment of glioblastoma. However, the prognostic significance of the expression of VEGFA and its receptors VEGFR1 (FLT1) and VEGFR2 (KDR) are still largely elusive. In the present study, we aimed to investigate the prognostic significance of these three factors, alone or in combination, in glioma patients. Gene mRNA expression was extracted from three independent brain tumor cohorts totaling 242 patients and the association between gene expression and survival was tested. We found that when VEGFA, FLT1 and KDR expressions were considered alone, only VEGFA demonstrated a significant association with patient survival. Patients with high expression of both VEGFA and either receptor had significantly worse survival than patients expressing both factors at a low level. Importantly, we found that those patients whose tumors overexpressed all three genes had a significantly shorter survival compared to those patients with a low level expression of these genes. Our results suggest that a high level expression of VEGFA and its receptors, both FLT1 and KDR, may be required for brain tumor progression, and that these three factors should be considered together as a prognostic indicator for brain tumor patients.

The prognostic significance of protein tyrosine phosphatase 4A2 in breast cancer

Although PTP4A3 has been shown to be a very important factor in promoting cancer progression, the role of its close family member PTP4A2 is still largely unknown. Recent reports have shown contradicting results on the role of PTP4A2 in breast cancer progression. Considering this, we aimed to investigate the prognostic value of PTP4A2 in five independent breast cancer data sets (minimum 198 patients per cohort, totaling 1,124 patients) in the Gene Expression Omnibus Database. We found that high expression of PTP4A2 was a favorable prognostic marker in all five independent breast cancer data sets, as well as in the combined cohort, with a hazard ratio of 0.68 (95% confidence interval =0.56-0.83; P<0.001). Low PTP4A2 expression was associated with estrogen receptor-negative tumors and tumors with higher histological grading; furthermore, low expression was inversely correlated with the expression of genes involved in proliferation, including MKI67 and the MCM gene family encoding the minichromosome maintenance proteins. These findings suggest that PTP4A2 may play a role in breast cancer progression by dysregulating cell proliferation. PTP4A2 expression was positively correlated with ESR1, the gene encoding estrogen receptor-alpha, and inversely correlated with EGFR expression, suggesting that PTP4A2 may be involved in these two important oncogenic pathways. Together, our results suggest that expression of PTP4A2 is a favorable prognostic marker in breast cancer.