Prognostic Impact of Monocyte Count at Presentation in Mantle Cell Lymphoma

Increased number of circulating monocytes at presentation has been recently associated with shorter survival in Hodgkin lymphoma, follicular lymphoma and diffuse large B cell lymphoma. This study aimed to assess the prognostic impact of the absolute monocyte count (AMC) at diagnosis in mantle cell lymphoma (MCL). From the series of MCL cases recorded on the databases of the Oncology Institute of Southern Switzerland in Bellinzona (Switzerland) and the Division of Haematology of the Amedeo Avogadro University of Eastern Piedmont in Novara (Italy), the AMC at diagnosis was available in 97 cases. Cox regression was used for both univariate and multivariate analysis. With a median follow up of 7 years, the 5-year overall survival (OS) was 29% for patients with AMC >500/ul and 62% for patients with AMC

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 value of the stem-like group in colorectal cancer using a panel of immunohistochemistry markers

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the Western world. It is becoming increasingly clear that CRC is a diverse disease, as exemplified by the identification of subgroups of CRC tumours that are driven by distinct biology. Recently, a number of studies have begun to define panels of diagnostically relevant markers to align patients into individual subgroups in an attempt to give information on prognosis and treatment response. We examined the immunohistochemical expression profile of 18 markers, each representing a putative role in cancer development, in 493 primary colorectal carcinomas using tissue microarrays. Through unsupervised clustering in stage II cancers, we identified two cluster groups that are broadly defined by inflammatory or immune-related factors (CD3, CD8, COX-2 and FOXP3) and stem-like factors (CD44, LGR5, SOX2, OCT4). The expression of the stem-like group markers was associated with a significantly worse prognosis compared to cases with lower expression. In addition, patients classified in the stem-like subgroup displayed a trend towards a benefit from adjuvant treatment. The biologically relevant and poor prognostic stem-like group could also be identified in early stage I cancers, suggesting a potential opportunity for the identification of aggressive tumors at a very early stage of the disease.

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.

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.

Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer

A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5'-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5'-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer.