Statistical Analyses of Second Indoor Bio-Release Field Evaluation Study at Idaho National Laboratory

In September 2008 a large-scale testing operation (referred to as the INL-2 test) was performed within a two-story building (PBF-632) at the Idaho National Laboratory (INL). The report “Operational Observations on the INL-2 Experiment” defines the seven objectives for this test and discusses the results and conclusions. This is further discussed in the introduction of this report. The INL-2 test consisted of five tests (events) in which a floor (level) of the building was contaminated with the harmless biological warfare agent simulant Bg and samples were taken in most, if not all, of the rooms on the contaminated floor. After the sampling, the building was decontaminated, and the next test performed. Judgmental samples and probabilistic samples were determined and taken during each test. Vacuum, wipe, and swab samples were taken within each room. The purpose of this report is to study an additional four topics that were not within the scope of the original report. These topics are: 1) assess the quantitative assumptions about the data being normally or log-normally distributed; 2) evaluate differences and quantify the sample to sample variability within a room and across the rooms; 3) perform geostatistical types of analyses to study spatial correlations; and 4) quantify the differences observed between surface types and sampling methods for each scenario and study the consistency across the scenarios. The following four paragraphs summarize the results of each of the four additional analyses. All samples after decontamination came back negative. Because of this, it was not appropriate to determine if these clearance samples were normally distributed. As Table 1 shows, the characterization data consists of values between and inclusive of 0 and 100 CFU/cm2 (100 was the value assigned when the number is too numerous to count). The 100 values are generally much bigger than the rest of the data, causing the data to be right skewed. There are also a significant number of zeros. Using QQ plots these data characteristics show a lack of normality from the data after contamination. Normality is improved when looking at log(CFU/cm2). Variance component analysis (VCA) and analysis of variance (ANOVA) were used to estimate the amount of variance due to each source and to determine which sources of variability were statistically significant. In general, the sampling methods interacted with the across event variability and with the across room variability. For this reason, it was decided to do analyses for each sampling method, individually. The between event variability and between room variability were significant for each method, except for the between event variability for the swabs. For both the wipes and vacuums, the within room standard deviation was much larger (26.9 for wipes and 7.086 for vacuums) than the between event standard deviation (6.552 for wipes and 1.348 for vacuums) and the between room standard deviation (6.783 for wipes and 1.040 for vacuums). Swabs between room standard deviation was 0.151, while both the within room and between event standard deviations are less than 0.10 (all measurements in CFU/cm2)

Using airborne LiDAR Survey to explore historic-era archaeological landscapes of Montserrat in the eastern Caribbean

This article describes what appears to be the first archaeological application of airborne LiDAR survey to historic-era landscapes in the Caribbean archipelago, on the island of Montserrat. LiDAR is proving invaluable in extending the reach of traditional pedestrian survey into less favorable areas, such as those covered by dense neotropical forest and by ashfall from the past two decades of active eruptions by the Soufrière Hills volcano, and to sites in localities that are inaccessible on account of volcanic dangers. Emphasis is placed on two aspects of the research: first, the importance of ongoing, real-time interaction between the LiDAR analyst and the archaeological team in the field; and second, the advantages of exploiting the full potential of the three-dimensional LiDAR point cloud data for purposes of the visualization of archaeological sites and features

Nonmyeloablative Unrelated Donor Hematopoietic Cell Transplantation to Treat Patients with Poor-Risk, Relapsed, or Refractory Multiple Myeloma

AbstractThe purpose of this study was to determine long-term outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in patients with poor-risk multiple myeloma. A total of 24 patients were enrolled; 17 patients (71%) had chemotherapy-refractory disease, and 14 (58%) experienced disease relapse or progression after previous autologous transplantation. Thirteen patients underwent planned autologous transplantation followed 43–135 days later with unrelated transplantation, whereas 11 proceeded directly to unrelated transplantation. All 24 patients were treated with fludarabine (90 mg/m2) and 2 Gy of total body irradiation before HLA-matched unrelated peripheral blood stem cell transplantation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. The median follow-up was 3 years after allografting. One patient experienced nonfatal graft rejection. The incidences of acute grades II and III and chronic graft-versus-host disease were 54%, 13%, and 75%, respectively. The 3-year nonrelapse mortality (NRM) was 21%. Complete responses were observed in 10 patients (42%); partial responses, in 4 (17%). At 3 years, overall survival (OS) and progression-free survival (PFS) rates were 61% and 33%, respectively. Patients receiving tandem autologous-unrelated transplantation had superior OS and PFS (77% and 51%) compared with patients proceeding directly to unrelated donor transplantation (44% and 11%) (PFS P value = .03). In summary, for patients with poor-risk, relapsed, or refractory multiple myeloma, cytoreductive autologous HCT followed by nonmyeloablative conditioning and unrelated HCT is an effective treatment approach, with low NRM, high complete remission rates, and prolonged disease-free survival

The aberrant asynchronous replication — characterizing lymphocytes of cancer patients — is erased following stem cell transplantation

<p>Abstract</p> <p>Background</p> <p>Aberrations of allelic replication timing are epigenetic markers observed in peripheral blood cells of cancer patients. The aberrant markers are non-cancer-type-specific and are accompanied by increased levels of sporadic aneuploidy. The study aimed at following the epigenetic markers and aneuploidy levels in cells of patients with haematological malignancies from diagnosis to full remission, as achieved by allogeneic stem cell transplantation (alloSCT).</p> <p>Methods</p> <p><it>TP53 </it>(a tumor suppressor gene assigned to chromosome 17), <it>AML1 </it>(a gene assigned to chromosome 21 and involved in the leukaemia-abundant 8;21 translocation) and the pericentomeric satellite sequence of chromosome 17 (<it>CEN17</it>) were used for replication timing assessments. Aneuploidy was monitored by enumerating the copy numbers of chromosomes 17 and 21. Replication timing and aneuploidy were detected cytogenetically using fluorescence <it>in situ </it>hybridization (FISH) technology applied to phytohemagglutinin (PHA)-stimulated lymphocytes.</p> <p>Results</p> <p>We show that aberrant epigenetic markers are detected in patients with hematological malignancies from the time of diagnosis through to when they are scheduled to undergo alloSCT. These aberrations are unaffected by the clinical status of the disease and are displayed both during accelerated stages as well as in remission. Yet, these markers are eradicated completely following stem cell transplantation. In contrast, the increased levels of aneuploidy (irreversible genetic alterations) displayed in blood lymphocytes at various stages of disease are not eliminated following transplantation. However, they do not elevate and remain unchanged (stable state). A demethylating anti-cancer drug, 5-azacytidine, applied in vitro to lymphocytes of patients prior to transplantation mimics the effect of transplantation: the epigenetic aberrations disappear while aneuploidy stays unchanged.</p> <p>Conclusions</p> <p>The reversible nature of the replication aberrations may serve as potential epigenetic blood markers for evaluating the success of transplant or other treatments and for long-term follow up of the patients who have overcome a hematological malignancy.</p

Outcome of transplantation for acute lymphoblastic leukemia in children with down syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106900/1/pbc24918.pd

Outcome of Transplantation for Acute Myelogenous Leukemia in Children with Down Syndrome

AbstractData on outcomes of allogeneic transplantation in children with Down syndrome and acute myelogenous leukemia (DS-AML) are scarce and conflicting. Early reports stress treatment-related mortality as the main barrier; a recent case series points to posttransplantation relapse. We reviewed outcome data for 28 patients with DS-AML reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2009 and performed a first matched-pair analysis of 21 patients with DS-AML and 80 non-DS AML controls. The median age at transplantation for DS-AML was 3 years, and almost half of the cohort was in second remission. The 3-year probability of overall survival was only 19%. In multivariate analysis, adjusting for interval from diagnosis to transplantation, risks of relapse (hazard ratio [HR], 2.84; P < .001; 62% versus 37%) and transplant-related mortality (HR, 2.52; P = .04; 24% versus 15%) were significantly higher for DS-AML compared to non-DS AML. Overall mortality risk (HR, 2.86; P < .001; 21% versus 52%) was significantly higher for DS-AML. Both transplant-related mortality and relapse contribute to higher mortality. Excess mortality in DS-AML patients can only effectively be addressed through an international multicenter effort to pilot strategies aimed at lowering both transplant-related mortality and relapse risks

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management