14 research outputs found

    The New Testament and empire: on the importance of theory

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    Peer reviewed.Discussions on the relationship between empires and biblical texts can benefit greatly from the theorisation of empire. It entails perceiving empire as a constantly constructed entity, by both the powerful and the subjugated, as well as the concomitant responses situated in attraction to and subversion of empire, i.e. its negotiation. The discussion is primarily related to the 1st century CE context, but finds important sociorhetorical antecedents in ancient Israelite history and textual traditions.Research Institute for Theology and Religio

    Geindividualiseerde karaktertekening in die toesprake van Thoekudides : Nikias

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    Proefskrif (M.A.) -- Universiteit van Stellenbosch, 1988.Full text to be digitised and attached to bibliographic record

    Current opinion on optimal systemic treatment for metastatic colorectal cancer: outcome of the ACTG/AGITG expert meeting ECCO 2013

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    The treatment of metastatic colorectal cancer has evolved greatly in the last 15 years, involving combined chemotherapy protocols and, in more recent times, new biologic agents. Clinical benefit from the use of targeted therapy with bevacizumab, aflibercept, cetuximab, panitumumab and regorafenib in the treatment of metastatic colorectal cancer is now well established with median overall survival accepted as over 24 months, and with super selection for extended RAS patients higher again. The optimal timing of treatment options requires careful consideration of predictive biomarkers, and importantly the potential for interactions, to derive the maximal benefit. A group of colorectal subspecialty medical oncologists from Australia, the USA, the Netherlands and Germany met during ECCO 2013 to discuss current practice. Subsequent new data from the American Society of Clinical Oncology were also reviewed. This article reviews the evidence discussed in support of modern treatments for colorectal cancer and the decision-making behind the treatment choices, with their benefits and risk

    Update on optimal treatment for metastatic colorectal cancer from the ACTG/AGITG expert meeting: ECCO 2015

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    The treatment of metastatic CRC (mCRC) has evolved over the last 20 years, from fluoropyrimidines alone to combination chemotherapy and new biologic agents. Median overall survival is now over 24 months for RAS mutated (MT) patients and over 30 months for RAS wild-type (WT) patients. However, there are subgroups of patients with BRAF V600E MT CRC who have a significantly poorer outlook. Newer treatment options are also being explored in select subgroups of patients (anti-HER 2 in HER2 positive mCRC and immunotherapy in patients with defective mismatch repair (dMMR)). The best use of these systemic treatment options, as well as surgery in well-selected patients requires careful consideration of predictive biomarkers and importantly, the optimal sequence in which therapies should be given to derive maximal benefit. A group of colorectal subspecialty medical oncologists from Australia, USA, The Netherlands and Germany met during ECCO 2015 in Vienna to review current practic

    Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma

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    PURPOSE: Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial. PATIENTS AND METHODS: In all, 1,256 patients with resected stage III melanoma were randomly assigned to observation (n = 629) or PEG-IFN-α-2b (n = 627) for an intended duration of 5 years. Stratification factors were microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumor thickness, sex, and center. Recurrence-free survival (RFS; primary end point), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed for the intent-to-treat population. RESULTS: At 7.6 years median follow-up, 384 recurrences or deaths had occurred with PEG-IFN-α-2b versus 406 in the observation group (hazard ratio [HR], 0.87; 95% CI, 0.76 to 1.00; P = .055); 7-year RFS rate was 39.1% versus 34.6%. There was no difference in OS (P = .57). In stage III-N1 ulcerated melanoma, RFS (HR, 0.72; 99% CI, 0.46 to 1.13; P = .06), DMFS (HR, 0.65; 99% CI, 0.41 to 1.04; P = .02), and OS (HR, 0.59; 99% CI, 0.35 to 0.97; P = .006) were prolonged with PEG-IFN-α-2b. PEG-IFN-α-2b was discontinued for toxicity in 37% of patients. CONCLUSION: Adjuvant PEG-IFN-α-2b for stage III melanoma had a positive impact on RFS, which was marginally significant and slightly diminished versus the benefit seen at prior follow-up (median, 3.8 years). No significant increase in DMFS or OS was noted in the overall population. Patients with ulcerated melanoma and lower disease burden had the greatest benefit

    Dual-isoform hUBE3A gene transfer improves behavioral and seizure outcomes in Angelman syndrome model mice

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    Loss of the maternal UBE3A allele causes Angelman syndrome (AS), a debilitating neurodevelopmental disorder. Here, we devised an AS treatment strategy based on reinstating dual-isoform expression of human UBE3A (hUBE3A) in the developing brain. Kozak sequence engineering of our codon-optimized vector (hUBE3Aopt) enabled translation of both short and long hUBE3A protein isoforms at a near-endogenous 3:1 (short/long) ratio, a feature that could help to support optimal therapeutic outcomes. To model widespread brain delivery and early postnatal onset of hUBE3A expression, we packaged the hUBE3Aopt vector into PHP.B capsids and performed intracerebroventricular injections in neonates. This treatment significantly improved motor learning and innate behaviors in AS mice, and it rendered them resilient to epileptogenesis and associated hippocampal neuropathologies induced by seizure kindling. hUBE3A overexpression occurred frequently in the hippocampus but was uncommon in the neocortex and other major brain structures; furthermore, it did not correlate with behavioral performance. Our results demonstrate the feasibility, tolerability, and therapeutic potential for dual-isoform hUBE3A gene transfer in the treatment of AS

    Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity:A systematic review and meta-analysis of individual patient data

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    Background: The best-known cause of intolerance to fluoropyrimidines is dihydropyrimidine dehydrogenase (DPD) deficiency, which can result from deleterious polymorphisms in the gene encoding DPD (DPYD), including DPYD*2A and c.2846A>T. Three other variants—DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A—have been associated with DPD deficiency, but no definitive evidence for the clinical validity of these variants is available. The primary objective of this systematic review and meta-analysis was to assess the clinical validity of c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity.  Methods: We did a systematic review of the literature published before Dec 17, 2014, to identify cohort studies investigating associations between DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A and severe (grade ≥3) fluoropyrimidine-associated toxicity in patients treated with fluoropyrimidines (fluorouracil, capecitabine, or tegafur-uracil as single agents, in combination with other anticancer drugs, or with radiotherapy). Individual patient data were retrieved and analysed in a multivariable analysis to obtain an adjusted relative risk (RR). Effect estimates were pooled by use of a random-effects meta-analysis. The threshold for significance was set at a p value of less than 0·0167 (Bonferroni correction).  Findings: 7365 patients from eight studies were included in the meta-analysis. DPYD c.1679T>G was significantly associated with fluoropyrimidine-associated toxicity (adjusted RR 4·40, 95% CI 2·08–9·30, pA/HapB3 (1·59, 1·29–1·97, pA and fluoropyrimidine-associated toxicity was not significant (adjusted RR 1·52, 95% CI 0·86–2·70, p=0·15). Analysis of individual types of toxicity showed consistent associations of c.1679T>G and c.1236G>A/HapB3 with gastrointestinal toxicity (adjusted RR 5·72, 95% CI 1·40–23·33, p=0·015; and 2·04, 1·49–2·78, pT were also significantly associated with severe fluoropyrimidine-associated toxicity (adjusted RR 2·85, 95% CI 1·75–4·62, pG and c.1236G>A/HapB3 are clinically relevant predictors of fluoropyrimidine-associated toxicity. Upfront screening for these variants, in addition to the established variants DPYD*2A and c.2846A>T, is recommended to improve the safety of patients with cancer treated with fluoropyrimidines

    Bible Translation and Reconstruction Hermeneutics

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    The role that Africa has played in the history of Bible translation since the event of the LXX is impressive. Yet, there is still a lot that Africa can contribute to Bible translation theory and practice. Following a previous study on this topic (Loba-Mkole 2008), this paper attempts to articulate how African theology of reconstruction can contribute to enhance new ways of understanding and doing Bible translation in Africa. Jesse N. K. Mugambi remains one of the most known proponents of reconstruction theology in Africa. The first section of the present study seeks to appreciate Mugambi’s contribution in the light of other similar writings, especially those from Kinshasa school of theology and Charles Villa-Vicencio from South Africa. Generally speaking, reconstruction paradigm is meant to rebuild all sectors of life in Africa, including Church ministries of which Bible translation constitutes an integral part. The second part will point out areas in which reconstruction paradigm is able to contribute specifically in the field of Bible translation
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