Prognostic limitations of donor t cell chimerism after myeloablative allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes

Donor T cell chimerism is associated with relapse outcomes after allogeneic stem cell transplantation (alloSCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, measures of statistical association do not adequately assess the performance of a prognostic biomarker, which is best characterized by its sensitivity and specificity for the chosen outcome. We analyzed donor T cell chimerism results at day 100 (D100chim) after myeloablative alloSCT for AML or MDS in 103 patients and determined its sensitivity and specificity for relapse-free survival at 6 months (RFS6) and 12 months (RFS12) post-alloSCT. The area under the receiver operating characteristic curve for RFS6 was .68, demonstrating only modest utility as a predictive biomarker, although this was greater than RFS12 at .62. Using a D100chim threshold of 65%, the specificity for RFS6 was 96.6%; however, sensitivity was poor at 26.7%. This equated to a negative predictive value of 88.5% and positive predictive value of 57.1%. Changing the threshold for D100chim to 75% or 85% modestly improved the sensitivity of D100chim for RFS6; however, this was at the expense of specificity. D100chim is specific but lacks sensitivity as a prognostic biomarker of early RFS after myeloablative alloSCT for AML or MDS. Caution is required when using D100chim to guide treatment decisions including immunologic manipulation, which may expose patients to unwarranted graft-versus-host disease

Koinonia

Themed HousingTheme Houses: Getting to the Foundations of Community, Jim McCormick A Year in the Little Yellow House, Lisa Burch Conference SpotlightBuilding Cross Cultural Community, Stuart C. Lord ArticlesStandards of Excellence in Short-Term Mission, Jenny Collins Follow Me : Intimacy with God Through Spiritual Direction, Tracy Balzer Faith, Wisdom and Grace: Walt Campbell Interviews, Steve Austin FeaturesThe President\u27s Corner Editor\u27s Disk Thinking Theologically: Learning Communities, Todd Reamhttps://pillars.taylor.edu/acsd_koinonia/1010/thumbnail.jp

MEK Inhibition Enhances Paclitaxel-induced Tumor Apoptosis

The anti-cancer drug paclitaxel (Taxol) alters microtubule assembly and activates pro-apoptotic signaling pathways. Previously, we and others found that paclitaxel activates endogenous JNK in tumor cells, and the activation of JNK contributes to tumor cell apoptosis. Here we find that paclitaxel activates the prosurvival MEK/ERK pathway, which conversely may compromise the efficacy of paclitaxel. Hence, a combination treatment of paclitaxel and MEK inhibitors was pursued to determine whether this treatment could lead to enhanced apoptosis. The inhibition of MEK/ERK with a pharmacologic inhibitor, U0126, together with paclitaxel resulted in a dramatic enhancement of apoptosis that is four times more than the additive value of the two drugs alone. Enhanced apoptosis was verified by the terminal transferase-mediated dUTP nick end labeling assay, by an enzyme-linked immunosorbent assay for histone-associated DNA fragments, and by flow cytometric analysis for DNA content. Specificity of the pharmacologic inhibitor was confirmed by the use of (a) a second MEK/ERK inhibitor and (b) a transdominant-negative MEK. Enhanced apoptosis was verified in breast, ovarian, and lung tumor cell lines, suggesting this effect is not cell type-specific. This is the first report of enhanced apoptosis detected in the presence of paclitaxel and MEK inhibition and suggests a new anticancer strategy

Integration of biological effects, fish histopathology and contaminant measurements for the assessment of fish health: A pilot application in Irish marine waters

This study investigates the use of a weight of evidence (WOE) approach to evaluate fish health status and biological effects (BEs) of contaminants for assessment of ecosystem health and discusses its potential application in support of the Marine Strategy Framework Directive (MSFD). External fish disease, liver histopathology and several BEs of contaminant exposure including 7-ethoxy resorufin O-de-ethylase (EROD), acetylcholinesterase (AChE), bile metabolites, vitellogenin (VTG) and alkali labile phosphates (ALP) were measured in two flatfish species from four locations in Ireland. Contaminant levels in fish were generally low with PCBs in fish liver below OSPAR environmental assessment criteria (EAC). There were consistencies with low PCB levels, EROD and PAH bile metabolite levels detected in fish. Dab from Cork, Dublin and Shannon had the highest relative prevalence of liver lesions associated with the carcinogenic pathway. An integrated biomarker response (IBR) showed promise to be useful for evaluation of environmental risk, although more contaminant parameters in liver are required for a full assessment with the present study

Dignity and respect during pregnancy and childbirth: a survey of the experience of disabled women

Background: Despite the increasing number of women with disability globally becoming pregnant, there is currently limited research about their experiences. A national survey of women’s experience of dignity and respect during pregnancy and childbirth raised concerns about the possibility of women with disability having unequal care with overall less choice and control. To address this further we conducted a study to explore the experiences of dignity and respect in childbirth of women with disability. Methods: The study involved a self-selecting, convenience sample of 37 women who had given birth in the United Kingdom and Ireland and had completed an internet-based survey. Women were identified through online networks and groups of and for disabled parents and for people with specific medical conditions. Data were collected using an online survey tool. Survey data were analysed using descriptive statistics. Thematic analysis was used for open questions. Results: Despite generally positive responses, just over half of the group of women expressed dissatisfaction with care provision. Only 19% thought that reasonable adjustments or accommodations had been made for them (7/37). When reasonable adjustments were not in place, participants’ independence and dignity were undermined. More than a quarter of women felt they were treated less favourably because of their disability (10/37, 27%). At all points in the pregnancy continuum more than a quarter of women felt their rights were either poorly or very poorly respected; however this was greatest in the postnatal period (11/35, 31%). In addition, more than half of the women (20/36, 56%) felt that maternity care providers did not have appropriate awareness of or attitudes to disability. Conclusions: Women’s experiences of dignity and respect in childbirth revealed that a significant proportion of women felt their rights were poorly respected and that they were treated less favourably because of their disability. This suggests that there is a need to look more closely at individualised care. It was also evident that more consideration is required to improve attitudes of maternity care providers to disability and services need to adapt to provide reasonable adjustments to accommodate disability, including improving continuity of carer

Realising the Ambition - Being Me : National Practice Guidance for Early Years in Scotland

Since 2013 there has been a determined focus by the Scottish Government to work towards realising the ambition for Scotland to be the best place for children to grow up in and learn. Changes to the Children and Young People (Scotland) Act 2014, have resulted in our youngest children, particularly those from birth to starting school, being at the heart of significant new developments. In 2014 Scottish Government started to increase the number of hours of funded provision to 600 hours for 3 and 4 year olds and some two year olds. The national practice guidance, “Building the Ambition” was commissioned at this time to complement the new policy developments and to support practitioners. The further expansion of funded Early Learning and Childcare (ELC) to 1140 hours per year for all 3 and 4 year olds, and for around a quarter of 2 year olds will be available from August 2020. This expansion to 1140 hours seeks not only to extend funded places, but to also improve the quality of our ELC provision across Scotland. We know that the earliest years of life are crucial for every child. Evidence tells us that, if our early learning and childcare offer is to help children fulfil their potential and contribute to closing the poverty related gap in children’s outcomes, it has to be high quality. To support the expansion it was decided to refresh the original Building the Ambition, incorporating and updating relevant aspects of the Pre-Birth to Three guidance and extending across the child’s learning journey into the early years of primary school. This new guidance, Realising the Ambition: Being Me, reflects the original principles and philosophy of Building the Ambition and complements the current policy direction of ELC and early primary education. It aspires to support practitioners in delivering what babies and young children need most and how we can most effectively deliver this in Scotland to give children the best start in life. The practice guidance aims to support anyone who works with and for babies and young children across all areas of Scotland. It has been designed to: build confidence and capability of those who work with children and families from pre-birth to starting school and beyond; make links between practice, theory and policy guidance to reinforce aspects of high quality provision and the critical role practitioners play; clarify some aspects of current practice and provide a reference which practitioners can easily use; support improvement and quality by encouraging discussion, self reflection and questioning about relevant practice in each setting, and; provide advice on achieving the highest quality of ELC and early primary provision that will enable young children to experience and to play their own part in Scotland being the best place in the world to grow up

Absolut “copper catalyzation perfected”; robust living polymerization of NIPAM : Guinness is good for SET-LRP

The controlled polymerization of N-isopropyl acrylamide (NIPAM) is reported in a range of international beers, wine, ciders and spirits utilizing Cu(0)-mediated living radical polymerization (SET-LRP). Highly active Cu(0) is first formed in situ by the rapid disproportionation of [Cu(I)(Me6-Tren)Br] in the commercial water–alcohol mixtures. Rapid, yet highly controlled, radical polymerization follows (Đ values as low as 1.05) despite the numerous chemicals of diverse functionality present in these solvents e.g. alpha acids, sugars, phenols, terpenoids, flavonoids, tannins, metallo-complexes, anethole etc. The results herein demonstrate the robust nature of the aqueous SET-LRP protocol, underlining its ability to operate efficiently in a wide range of complex chemical environments