Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders

Background: Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT). Methods: Data from 38 centers worldwide, including indication, donor, conditioning regimen, graft-versus-host disease, and outcome, were analyzed. Conditioning was classified as myeloablative conditioning (MAC) if it contained radiotherapy or alkylators and reduced-intensity conditioning (RIC) if no alkylators and/or 150 mg/m(2) fludarabine or less and 40 mg/kg cyclophosphamide or less were used. Results: Fifty-five new, 14 updated, and 18 previously published patients were analyzed. Median age at HCT was 48 months (range, 1.5-552 months). Twenty-nine patients underwent transplantation for infection, 21 had malignancy, 13 had bone marrow failure, 13 received pre-emptive transplantation, 5 had multiple indications, and 6 had no information. Twenty-two received MAC, 59 received RIC, and 4 were infused; information was unavailable for 2 patients. Seventy-three of 77 patients with DNA ligase IV deficiency, Cernunnos-XLF deficiency, or Nijmegen breakage syndrome received conditioning. Survival was 53 (69%) of 77 and was worse for those receiving MAC than for those receiving RIC (P=.006). Most deaths occurred early after transplantation, suggesting poor tolerance of conditioning. Survival in patients with AT was 25%. Forty-one (49%) of 83 patients experienced acute GvHD, which was less frequent in those receiving RIC compared with those receiving MAC (26/56 [46%] vs 12/21 [57%], P=.45). Median follow-up was 35 months (range, 2-168 months). No secondary malignancies were reported during 15 years of follow-up. Growth and developmental delay remained after HCT; immune-mediated complications resolved. Conclusion: RIC HCT resolves DNA repair disorder associated immunodeficiency. Long-term follow-up is required for secondary malignancy surveillance. Routine HCT for AT is not recommended.Peer reviewe

A universal dictionary of acquisition and contracting terms

This thesis is the initial effort to establish a universal dictionary of acquisition and contracting terminology. As a continuation of research initiated by LCDR Daniel Ryan, SC, USN to establish a basis for defining words and terms used in the field of contracting, the fifty terms selected for this thesis were taken from the dictionary of acquisition and contracting terms which is maintained through thesis research conducted within the National Contract Management Association. This work differs from previous research in that it takes the terms from those efforts and attempts to attain, through questionnaire results from four national acquisition and contracting professional associations, a general consensus for commonly held terminology. This research is the initial effort conducted by students at the Naval Postgraduate School, Monterey, California.http://archive.org/details/auniversaldictio1094539848Lieutenant, United States NavyApproved for public release; distribution is unlimited

Connecting Chemistry to Community with Deliberative Democracy

Science education communities have called for rethinking curricula to improve student understanding of the nature of science and the role of science in addressing controversial modern issues such as climate change, energy policy, and pollution levels. One approach to meeting this call is integrating these topics into class activities that require students to use discussion and scientific approaches to solve problems and deliberate potential policy solutions. Deliberative democracy (DD) is one such active learning approach in which students work in peer groups to reach a consensus on a scientific topic relevant to both real-world issues and course content. During DD modules, students are asked to explore both the scientific data and public perception surrounding a topic by reading related peer-reviewed and media articles. Students evaluate the information provided by these sources, have the opportunity to research their own sources, deliberate in groups, and arrive at an evidence-supported position on a science policy. There are some examples in the literature of using DD in nonmajors science courses, and recently Portland State University (PSU) began incorporating DD modules into both on-sequence and off-sequence general chemistry courses for science majors enrolling between 60 and 200 students. This chapter provides background on DD, explains how DD has been adapted for majors-level general chemistry at PSU, highlights perceptions of DD by students and instructors, and describes how feedback from PSU students and instructors is informing future DD implementation at PSU