The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells.

Lentiviral vectors designed for the treatment of the hemoglobinopathies require the inclusion of regulatory and strong enhancer elements to achieve sufficient expression of the β-globin transgene. Despite the inclusion of these elements, the efficacy of these vectors may be limited by transgene silencing due to the genomic environment surrounding the integration site. Barrier insulators can be used to give more consistent expression and resist silencing even with lower vector copies. Here, the barrier activity of an insulator element from the human ankyrin-1 gene was analyzed in a lentiviral vector carrying an antisickling human β-globin gene. Inclusion of a single copy of the Ankyrin insulator did not affect viral titer, and improved the consistency of expression from the vector in murine erythroleukemia cells. The presence of the Ankyrin insulator element did not change transgene expression in human hematopoietic cells in short-term erythroid culture or in vivo in primary murine transplants. However, analysis in secondary recipients showed that the lentiviral vector with the Ankyrin element preserved transgene expression, whereas expression from the vector lacking the Ankyrin insulator decreased in secondary recipients. These studies demonstrate that the Ankyrin insulator may improve long-term β-globin expression in hematopoietic stem cells for gene therapy of hemoglobinopathies

The role of Galectin-1 and Galectin-3 in the mucosal immune response to <i>Citrobacter rodentium</i> infection

Despite their abundance at gastrointestinal sites, little is known about the role of galectins in gut immune responses. We have therefore investigated the Citrobacter rodentium model of colonic infection and inflammation in Galectin-1 or Galectin- 3 null mice. Gal-3 null mice showed a slight delay in colonisation after inoculation with C. rodentium and a slight delay in resolution of infection, associated with delayed T cell, macrophage and dendritic cell infiltration into the gut mucosa. However, Gal-1 null mice also demonstrated reduced T cell and macrophage responses to infection. Despite the reduced T cell and macrophage response in Gal-1 null mice, there was no effect on C. rodentium infection kinetics and pathology. Overall, Gal-1 and Gal-3 play only a minor role in immunity to a gut bacterial pathogen.Centro de Investigación y Desarrollo en Criotecnología de Alimento

Learning clinical skills in the simulation suite: the lived experiences of student nurses involved in peer teaching and peer assessment

Summary Background The benefits of peer teaching and assessment are well documented within nurse education literature. However, research to date has predominantly focused on the advantages and disadvantages for the inexperienced learner, with a dearth of knowledge relating to the perceptions of senior nursing students involved in teaching their peers. Aim This study sought to investigate the student experience of taking part in a peer teaching and assessment initiative to include the perceptions of both first year nursing students and second/third year participants. Method Data were collected via open-ended questionnaires and analysed with qualitative Framework analysis. Findings This initiative received a generally positive response both from students being taught and also from those acting as facilitators. Perceived benefits included the social learning experience, development of teaching skills, self-awareness and the opportunity to communicate both good and bad news. Suggestions for improvement included additional time working in small groups, specific supplementary learning materials and the introduction of peer teaching and assessment into other areas of the Adult Nursing Programme. Conclusions Peer teaching and assessment principles represent valuable strategies which can be utilised in nurse education to develop clinical skills and prepare nurses for real-life scenarios. Further research needs to investigate how to enhance the student learning experience and to fully exploit the potential for simulated experience to prepare students for their future role as registered nurses in clinical practice

Using linked routinely collected health data to describe prostate cancer treatment in New South Wales, Australia: a validation study

<p>Abstract</p> <p>Background</p> <p>Population-based patterns of care studies are important for monitoring cancer care but conducting them is expensive and resource-intensive. Linkage of routinely collected administrative health data may provide an efficient alternative. Our aim was to determine the accuracy of linked routinely collected administrative data for monitoring prostate cancer care in New South Wales (NSW), Australia.</p> <p>Methods</p> <p>The NSW Prostate Cancer Care and Outcomes Study (PCOS), a population-based survey of patterns of care for men aged less than 70 years diagnosed with prostate cancer in NSW, was linked to the NSW Cancer Registry, electronic hospital discharge records and Medicare and Pharmaceutical claims data from Medicare Australia. The main outcome measures were treatment with radical prostatectomy, any radiotherapy, external beam radiotherapy, brachytherapy or androgen deprivation therapy, and cancer staging. PCOS data were considered to represent the true treatment status. The sensitivity and specificity of the administrative data were estimated and relevant patient characteristics were compared using chi-squared tests.</p> <p>Results</p> <p>The validation data set comprised 1857 PCOS patients with treatment information linked to Cancer Registry records. Hospital and Medicare claims data combined described treatment more accurately than either one alone. The combined data accurately recorded radical prostatectomy (96% sensitivity) and brachytherapy (93% sensitivity), but not androgen deprivation therapy (76% sensitivity). External beam radiotherapy was rarely captured (5% sensitivity), but this was improved by including Medicare claims for radiation field setting or dosimetry (86% sensitivity). False positive rates were near 0%. Disease stage comparisons were limited by one-third of cases having unknown stage in the Cancer Registry. Administrative data recorded treatment more accurately for cases in urban areas.</p> <p>Conclusions</p> <p>Cancer Registry and hospital inpatient data accurately captured radical prostatectomy and brachytherapy treatment, but not external beam radiotherapy or disease stage. Medicare claims data substantially improved the accuracy with which all major treatments were recorded. These administrative data combined are valid for population-based studies of some aspects of prostate cancer care.</p

Increased Adiposity, Dysregulated Glucose Metabolism and Systemic Inflammation in Galectin-3 KO Mice

PMCID: PMC3579848This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Predictors of Workplace Bullying and Cyber-Bullying in New Zealand

Background: The negative effects of in-person workplace bullying (WB) are well established. Less is known about cyber-bullying (CB), in which negative behaviours are mediated by technology. Drawing on the conservation of resources theory, the current research examined how individual and organisational factors were related to WB and CB at two time points three months apart. Methods: Data were collected by means of an online self-report survey. Eight hundred and twenty-six respondents (58% female, 42% male) provided data at both time points. Results: One hundred and twenty-three (15%) of participants had been bullied and 23 (2.8%) of participants had been cyber-bullied within the last six months. Women reported more WB, but not more CB, than men. Worse physical health, higher strain, more destructive leadership, more team conflict and less effective organisational strategies were associated with more WB. Managerial employees experienced more CB than non-managerial employees. Poor physical health, less organisational support and less effective organisational strategies were associated with more CB. Conclusion: Rates of CB were lower than those of WB, and very few participants reported experiencing CB without also experiencing WB. Both forms of bullying were associated with poorer work environments, indicating that, where bullying is occurring, the focus should be on organisational systems and processes

Exile Anthology: A Special Sesquicentennial Issue

Horses by Deborah S. Appleton 1 Man and His World by Clark Baise 2-11 South Dakota, Route 34 by Bonnie Bishop 12 Heads and Tails by Tim Cockey 13-17 When The Bough Breaks by Alison Orleans Conte 17 Poem by Christine Cooper (Oosterbaan) 18 Flood on the Jemez by Doug Cox 19 San Antonia Canyon by Doug Cox 19 Canyon Poems by Doug Cox 19 Busy Being Born by Lindrith Davies 20-26 The Queen is Dead, Long Life The Queen by James Funaro 27 The Gates of Hell by James Funaro 28 What The Chorus Said by James Funaro 28 Coronado by James Gallant 29-35 The End Of Art by Dianne L. Goss 35 Visiting Relatives by Cynthia Hohn 36-38 Swinging by Kathy Kerchner 39 The Big House by Kim McMullen 40-47 Seasons by Dan Pancake 48 Basho\u27s Road by D. Patnode 49 Back Home by D. Patnode 49 Basket Charm by Angela Peckenpaugh 50 There Is something by Deborah Pope 51 Twilight Loneliness by Robert Smyth 52 Molting by Robert Smyth 52 Parkman by Mary S. Treco 53 The Guest by Dennis Trudell 54 The Wormwood Review by Dennis Trudell 55 Milkweed by Bonnie L. Verburg 56 Orion Falling by Lawrence Weber 57 Third by Lawrence Weber 58 Cover Drawing: Kim Fleishma

‘Is this a time of beautiful chaos?’: reflecting on international feminist legal methods

This article considers how Margaret Jane Radin’s theory of the feminist double bind can bring conceptual clarity to the difficulties feminisms face in engaging with political and legal institutions of global governance. I draw on her theory to reinitiate a conversation on ideal and nonideal theory, in order to answer the call of key proponents in international legal feminism to reevaluate methodologies in critiquing mainstream institutions. By providing an account of how to navigate the double bind, this article brings conceptual clarity to the tension between resistance and compliance that has been argued to lie at the heart of the feminist project in international law. I demonstrate how this theoretical framework can foster greater pluralist perspectives in feminist engagement of ideal theories to temper the deradicalising and conservative risk of navigating feasibility constrained nonideal strategies

Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis

National Institutes of Health grants GM-38765 and P50-DE016191 (C.N.S.), Welcome Trust Programme grant 086867/Z/08/Z (R.J.F. and M.P.) and Project grant 085903/Z/08 (R.J.F.) and Arthritis Research Campaign UK fellowships 18445 and 18103 (to L.V.N. and D.C., respectively). M.S. received a National Research Service Award from the NHLBI (HL087526)