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Sample records for analysis post allogeneic

  1. How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic HSCT.

    PubMed

    Fuji, S; Rovó, A; Ohashi, K; Griffith, M; Einsele, H; Kapp, M; Mohty, M; Majhail, N S; Engelhardt, B G; Tichelli, A; Savani, B N

    2016-08-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently develop glucose intolerance and post-transplant diabetes mellitus (PTDM). The clinical importance of PTDM and its detrimental impact on HSCT outcomes are under-recognized. After allo-HSCT, various mechanisms can contribute to the development of PTDM. Here we review information about hyperglycemia and PTDM after allo-HSCT as well as PTDM after solid organ transplantation and describe ways to manage hyperglycemia/PTDM after allogeneic HSCT. Taking into consideration a lack of well-established evidence in the field of allo-HSCT, more studies should be conducted in the future, which will require closer multidisciplinary collaboration between hematologists, endocrinologists and nutritionists. PMID:27042848

  2. Chemoselection of Allogeneic HSC After Murine Neonatal Transplantation Without Myeloablation or Post-transplant Immunosuppression

    PubMed Central

    Falahati, Rustom; Zhang, Jianqing; Flebbe-Rehwaldt, Linda; Shi, Yimin; Gerson, Stanton L; Gaensler, Karin ML

    2012-01-01

    The feasibility of allogeneic transplantation, without myeloablation or post-transplant immunosuppression, was tested using in vivo chemoselection of allogeneic hematopoietic stem cells (HSCs) after transduction with a novel tricistronic lentiviral vector (MGMTP140K-2A-GFP-IRES-TK (MAGIT)). This vector contains P140K-O6-methylguanine-methyltransferase (MGMTP140K), HSV-thymidine kinase (TKHSV), and enhanced green fluorescent protein (eGFP) enabling (i) in vivo chemoselection of HSC by conferring resistance to benzylguanine (BG), an inhibitor of endogenous MGMT, and to chloroethylating agents such as 1,3-bis(2-chloroethyl)nitrosourea (BCNU) and, (ii) depletion of proliferating cells such as malignant clones or transduced donor T cells mediating graft versus host disease (GVHD), by expression of the suicide gene TKHSV and Ganciclovir (GCV) administration. Non-myeloablative transplantation of transduced, syngeneic, lineage-depleted (Lin−) BM in neonates resulted in 0.67% GFP+ mononuclear cells in peripheral blood. BG/BCNU chemoselection, 4 and 8 weeks post-transplant, produced 50-fold donor cell enrichment. Transplantation and chemoselection of major histocompatibility complex (MHC)-mismatched MAGIT-transduced Lin− BM also produced similar expansion for >40 weeks. The efficacy of this allotransplant approach was validated in Hbbth3 heterozygous mice by correction of β-thalassemia intermedia, without toxicity or GVHD. Negative selection, by administration of GCV resulted in donor cell depletion without graft ablation, as re-expansion of donor cells was achieved with BG/BCNU treatment. These studies show promise for developing non-ablative allotransplant approaches using in vivo positive/negative selection. PMID:22871662

  3. Post-allogeneic Hematopoietic Stem Cell Transplantation (HSCT) changes in inorganic salivary components.

    PubMed

    Boer, C C; Correa, M E P; Tenuta, L M A; Souza, C A; Vigorito, A C

    2015-09-01

    Recent studies have considered the qualitative and quantitative assessment of salivary flow, as well the biochemical components of saliva, as possible biomarkers that might contribute to the pathogenesis of chronic graft-versus-host disease (cGHVD) in hematopoietic stem cell transplantation (HSCT) patients. The aim of this study was to evaluate prospectively the inorganic salivary status at different periods of allogeneic HSCT. Saliva collection and oral examination were performed prior to the HSCT, ​between days 8 and 10, days 80 and 100, and at the cGVHD onset. Concentrations of calcium (Ca), phosphate (Pi), chloride (Cl), magnesium (Mg), potassium (K), and sodium (Na) were performed using colorimetric reactions and atomic absorption. Fifty-five consecutive patients undergoing first allogeneic HSCT were included in this study. Between days 8 and 10, the salivary flow rate was significantly higher (p = 0.05), Pi concentration was decreased (p = 0.007), and Na and Cl were increased (p = 0.001 and p = 0.001, respectively), compared with the baseline. Salivary flow rate during the same period showed a negative correlation with Pi concentration (p = 0.02) and a positive correlation with Na and Cl concentrations (p = 0.003 and p = 0.001, respectively). The salivary flow rate was decreased between days 80 and 100 (p = 0.02) and Na, Cl, and K concentrations were increased (p = 0.03, p = 0.02, and p = 0.003, respectively). Salivary flow rate showed a negative correlation with Na and Cl (p = 0.01 and p = 0.013, respectively). At cGVHD onset, the salivary flow rate showed no statistical difference compared with the other studied periods. A trend was observed in the higher Na concentration compared with the baseline (p = 0.06) and Pi concentration presented a significant decrease (p = 0.004). Ca and Mg concentrations showed no changes during all evaluation periods. The present study showed changes in inorganic

  4. Treatment of severe post-traumatic bone defects with autologous stem cells loaded on allogeneic scaffolds.

    PubMed

    Vulcano, Ettore; Murena, Luigi; Cherubino, Paolo; Falvo, Daniele A; Rossi, Antonio; Baj, Andreina; Toniolo, Antonio

    2012-12-01

    Mesenchymal stem cells may differentiate into angiogenic and osteoprogenitor cells. The effectiveness of autologous pluripotent mesenchymal cells for treating bone defects has not been investigated in humans. We present a case series to evaluate the rationale of using nucleated cells from autologous bone marrow aspirates in the treatment of severe bone defects that failed to respond to traditional treatments. Ten adult patients (mean age, 49.6-years-old) with severe bone defects were included in this study. Lower limb bone defects were >or=5 cm3 in size, and upper limb defects .or=2 cm3. Before surgery, patients were tested for antibodies to common pathogens. Treatment consisted of bone allogeneic scaffold enriched with bone marrow nucleated cells harvested from the iliac crest and concentrated using an FDA-approved device. Postsurgery clinical and radiographic follow-up was performed at 1, 3, 6, and 12 months. To assess viability, morphology, and immunophenotype, bone marrow nucleated cells were cultured in vitro, tested for sterility, and assayed for the possible replication of adventitious (contaminating) viruses. In 9 of 10 patients, both clinical and radiographic healing of the bone defect along with bone graft integration were observed (mean time, 5.6 months); one patient failed to respond. No post-operative complications were observed. Bone marrow nucleated cells were enriched 4.49-fold by a single concentration step, and these enriched cells were free of microbial contamination. The immunophenotype of adherent cells was compatible with that of mesenchymal stem cells. We detected the replication of Epstein-Barr virus in 2/10 bone marrow cell cultures tested. Hepatitis B virus, cytomegalovirus, parvovirus B19, and endogenous retrovirus HERV-K replication were not detected. Overall, 470 to 1,150 million nucleated cells were grafted into each patient. This case series, with a mean follow-up of almost 2 years, demonstrates that an allogeneic bone scaffold

  5. Risk-factor analysis of poor graft function after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Xiao, Yang; Song, Jiayin; Jiang, Zujun; Li, Yonghua; Gao, Yang; Xu, Wenning; Lu, Ziyuan; Wang, Yaochun; Xiao, Haowen

    2014-01-01

    The objective of this study was to investigate the main risk factors for poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), to allow the improvement of transplantation outcomes through preventive measures. Clinical data for 124 patients who received allo-HSCT were analyzed retrospectively. There were 83 males (66.9%) and 41 females (33.1%) with a median age of 28 years (4-60 years). The median follow-up time was 7 months (1-116 months). Factors analyzed included age, gender, disease diagnosis, source of hematopoietic stem cells, donor type, human leukocyte antigen (HLA) matching, conditioning regimen, numbers of infused mononuclear cells and CD34(+) cells, donor-recipient sex and blood-type matching, prophylactic treatment of graft-versus-host disease (GVHD), grades of GVHD, Epstein-Barr virus or cytomegalovirus (CMV) infection, post-transplantation lymphoproliferative disorders and hepatic veno-occlusive disease. Data were analyzed by univariate and multivariate conditional logistic regression analyses. Among the 124 patients who underwent allo-HSCT, 15 developed PGF (12.1%). Univariate logistic regression analysis identified age, donor-recipient blood type and CMV infection (in 30 days) as potential risk factors for PGF. Multivariate analysis of factors with P<0.1 in univariate analysis showed that age, donor-recipient blood type and CMV infection (in 30 days) were significant risk factors for PGF. Patients were divided into subgroups based on age <20, 20-30, 30-40, and >40 years. The risk of PGF increased 2.747-fold (odds ratio (OR)=2.625, 95% confidence interval: 1.411-5.347) for each increment in age level. Patients with mismatched blood type (OR=4.051) or CMV infection (OR=9.146) had an increased risk of PGF. We conclude that age, donor-recipient blood-type matching and CMV infection are major risk factors for PGF after allo-HSCT.

  6. Analysis of donor NK and T cells infused in patients undergoing MHC-matched allogeneic hematopoietic transplantation.

    PubMed

    Pascal, V; Brunet, C; Pradel, V; Thirion, X; Andre, P; Faucher, C; Sampol, J; Dignat-George, F; Blaise, D; Vivier, E; Chabannon, C

    2002-11-01

    We retrospectively analyzed the percentages and absolute numbers of T cells, natural killer (NK) cells and NK cell subsets in cryopreserved samples of either bone marrow or blood non-T cell-depleted allogeneic MHC-matched hematopoietic grafts. Using flow cytometry, we found higher numbers of NK cells in aphereses than in bone marrow collections. We further investigated the distribution of NK cell subsets, defined by the cell surface expression of MHC class I-specific receptors, in these allogeneic grafts. The distribution of NK cell subsets from the two different origins were similar, with the exception of the CD158a/h(+) NK cell subset, whose size appeared to be smaller in bone marrow. The search for relations between the numbers of infused cells and post-transplantation events demonstrated that increasing numbers of infused T cells but not NK cells are related with decreased overall survival. Our study highlights the toxicity of infused T cells but not NK cells in allogeneic MHC-matched hematopoietic grafts. These data pave the way for further trials to investigate the effect of NK cell infusion in MHC-matched allogeneic transplantation, and in particular whether ex vivo NK cell expansion and activation may enhance the anti-tumoral effect of the procedure and decrease its morbidity.

  7. BK virus disease after allogeneic stem cell transplantation: a cohort analysis.

    PubMed

    Rorije, Nienke M G; Shea, Margaret M; Satyanarayana, Gowri; Hammond, Sarah P; Ho, Vincent T; Baden, Lindsey R; Antin, Joseph H; Soiffer, Robert J; Marty, Francisco M

    2014-04-01

    The clinical epidemiology of BK virus (BKV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. We evaluated 491 patients transplanted from January 2010 to December 2011 at a single transplant center to assess incidence, severity, and risk factors for BKV disease after HSCT. BKV disease was defined as BKV detection in urine by PCR testing in association with genitourinary symptoms without other concurrent genitourinary conditions. BKV disease occurred in 78 patients (15.9%), for an incidence rate of .47/1000 patient-days (95% confidence interval [CI], .37 to .59); BKV disease was considered severe in 27 patients (5.5%). In multivariate Cox modeling, time-dependent acute graft-versus-host disease (aGVHD) grades II to IV (adjusted hazard ratio [aHR] 4.25; 95% CI, 2.51 to 7.21), cord blood HSCT (aHR 2.28; 95% CI, 1.01 to 5.15), post-transplant mycophenolate use (aHR 3.31; 95% CI, 1.83 to 5.99), and high-dose cyclophosphamide conditioning (aHR 2.34, 95% CI 1.45 to 3.77) were significant predictors of BKV disease. Time-dependent aGVHD grades III to IV (aHR 10.5; 95% CI, 4.44 to 25.0) and cord blood HSCT (aHR 5.40; 95% CI, 1.94 to 15.0) were independent risk factors for severe BKV disease. BKV disease is common and is associated with significant and prolonged morbidity after HSCT. Prospective studies are needed to better define the morbidity of post-HSCT BKV disease and inform the design of prophylaxis and treatment trials.

  8. Plasma Elevations of Tumor Necrosis Factor-Receptor-1 at Day 7 Post Allogeneic Transplant Correlate with Graft Versus Host Disease Severity and Overall Survival in Pediatric Patients

    PubMed Central

    Kitko, Carrie L.; Paczesny, Sophie; Yanik, Gregory; Braun, Thomas; Jones, Dawn; Whitfield, Joel; Choi, Sung W.; Hutchinson, Raymond J.; Ferrara, James L. M.; Levine, John E.

    2008-01-01

    Tumor necrosis factor-α (TNF-α) is known to play a role in the pathogenesis of graft-vs-host disease (GVHD), a cause of significant morbidity and treatment-related mortality (TRM) after allogeneic hematopoietic stem cell transplantation (HCT). We measured the concentration of TNF-Receptor-1 (TNFR1) in the plasma of HCT recipients as a surrogate marker for TNF-α both prior to transplant and at day 7 in 82 children who underwent a myeloablative allogeneic HCT at the University of Michigan between 2000 and 2005. GVHD grade II-IV developed in 49% of patients at a median of 20 days after HCT. Increases in TNFR1 level at day 7 post HCT, expressed as ratios compared to pre-transplant baseline, correlated with severity of GVHD (p=0.02). In addition, day 7 TNFR1 ratios > 2.5 baseline were associated with inferior 1 year overall survival (51% vs 74%, p=0.04). As an individual biomarker, TNFR1 lacks sufficient precision to be used as a predictor for the development of GVHD. However, increases in the concentration of TNFR1, which are detectable up to two weeks in advance of clinical manifestations of GVHD, correlate with survival in pediatric HCT patients. PMID:18541194

  9. IVGEN Post Flight Analysis

    NASA Technical Reports Server (NTRS)

    Mcquillen, John; Brown, Dan; Hussey, Sam; Zoldak, John

    2014-01-01

    The Intravenous Fluid Generation (IVGEN) Experiment was a technology demonstration experiment that purified ISS potable water, mixed it with salt, and transferred it through a sterilizing filter. On-orbit performance was verified as appropriate and two 1.5 l bags of normal saline solution were returned to earth for post-flight testing by a FDA certified laboratory for compliance with United States Pharmacopiea (USP) standards. Salt concentration deviated from required values and an analysis identified probable causes. Current efforts are focused on Total Organic Content (TOC) testing, and shelf life.The Intravenous Fluid Generation (IVGEN) Experiment demonstrated the purification of ISS potable water, the mixing of the purified water with sodium chloride, and sterilization of the solution via membrane filtration. On-orbit performance was monitored where feasible and two 1.5-liter bags of normal saline solution were returned to earth for post-flight testing by a FDA-registered laboratory for compliance with United States Pharmacopeia (USP)standards [1]. Current efforts have been focused on challenge testing with identified [2] impurities (total organic-carbon), and shelf life testing. The challenge testing flowed known concentrations of contaminants through the IVGEN deionizing cartridge and membrane filters to test their effectiveness. One finding was that the filters and DI-resin themselves contribute to the contaminant load during initial startup, suggesting that the first 100 ml of fluid be discarded. Shelf life testing is ongoing and involves periodic testing of stored DI cartridges and membrane filters that are capped and sealed in hermetic packages. The testing is conducted at six month intervals measuring conductivity and endotoxins in the effluent. Currently, the packaging technique has been successfully demonstrated for one year of storage testing. The USP standards specifies that the TOC be conducted at point of generation as opposed to point of

  10. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation.

    PubMed

    Kong, Y; Zhang, J; Claxton, D F; Ehmann, W C; Rybka, W B; Zhu, L; Zeng, H; Schell, T D; Zheng, H

    2015-07-31

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1(hi)TIM-3(+) cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1(hi)TIM-3(+) T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing TN and TEMRA subsets. Importantly, increase of PD-1(hi)TIM-3(+) cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation.

  11. Influence of Previous Inflammatory Bowel Disease on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation: A Matched-Pair Analysis.

    PubMed

    Rabian, Florence; Porcher, Raphael; Sicre de Fontbrune, Flore; Lioure, Bruno; Laplace, Anne; Nguyen, Stephanie; Tabrizi, Reza; Vigouroux, Stephane; Tomowiak, Cécile; Maillard, Nathalie; Suarez, Felipe; Delage, Jeremy; Peffault de Latour, Régis; Socié, Gérard

    2016-09-01

    The idiopathic inflammatory bowel diseases (IBDs) Crohn's disease and ulcerative colitis are associated with increased risk of hematologic malignancies. Allogeneic hematopoietic stem cell transplantation (HSCT) could be a curative strategy in this setting, but has been thought to be associated with increased nonrelapse mortality (NRM). We conducted a national French retrospective analysis of patients with IBD who underwent allogeneic HSCT for hematologic malignancies and were matched with 3 controls according to recipient, donor, and transplant characteristics. Between 2004 and 2015, 18 patients with IBD underwent allogeneic HSCT. With a median follow-up of 33 months for the patients with IBD and 57 months for controls, the cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 39% for the patients with IBD and 40% for controls (hazard ratio [HR], 1.10; P = .82). The cumulative incidence of chronic GVHD at 48 months was 52% for the patients with IBD and 43% for controls (HR, 0.92; P = .89). Nonrelapse mortality at 48 months was 19% for the patients with IBD and 11% for controls (HR, 4.93; P = .067). Overall survival at 48 months was 59% for the patients with IBD and 60% for matched controls (HR, 1.35; P = .56). In conclusion, IBD should not be considered a contraindication for transplantation, and its impact on comorbidity indexes should be reduced. PMID:27246370

  12. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease.

    PubMed

    Holler, Ernst; Butzhammer, Peter; Schmid, Karin; Hundsrucker, Christian; Koestler, Josef; Peter, Katrin; Zhu, Wentao; Sporrer, Daniela; Hehlgans, Thomas; Kreutz, Marina; Holler, Barbara; Wolff, Daniel; Edinger, Matthias; Andreesen, Reinhard; Levine, John E; Ferrara, James L; Gessner, Andre; Spang, Rainer; Oefner, Peter J

    2014-05-01

    Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 μmol/L to 11.8 ± 2.8 μmol/L in all post-transplant samples and to 3.5 ± 3 μmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT.

  13. Allogeneic Hematopoietic Stem Cell Transplantation in Mantle Cell Lymphoma: A Retrospective Analysis of 7 Patients.

    PubMed

    Lamm, Wolfgang; Wohlfarth, Philipp; Bojic, Marija; Schörgenhofer, Christian; Kalhs, Peter; Raderer, Markus; Rabitsch, Werner

    2015-01-01

    Mantle cell lymphoma (MCL) is a B cell non-Hodgkin's lymphoma characterized by a poor prognosis. Many different therapeutic approaches including intensive chemotherapy as well as new targeted therapies are established. However, overall survival remains unsatisfying. As the sole curative option, allogeneic hematopoietic stem cell transplantation (HSCT) has been described, but only a limited number of patients qualify for this procedure. We have retrospectively analyzed 7 patients with stage IV MCL undergoing allogeneic HSCT at our institution. A myeloablative regimen was used in 1 patient, while the other 6 patients received reduced-intensity conditioning. Four patients had an HLA-identical sibling, and the remaining 3 patients had an HLA-identical unrelated donor. One patient developed acute graft-versus-host disease (skin, grade III; intestine, grade II). Two patients died from transplant-related causes, 3 patients died due to progressive disease and the remaining 2 patients are still in complete remission 147 and 8 months after transplantation. Allogeneic HSCT offers a therapeutic treatment option for selected patients in a relapsed/refractory setting. The incorporation of novel agents has improved the outcome of patients with MCL. Thus, the role and optimal time point of allogeneic HSCT should be reevaluated in randomized trials.

  14. Post Flight Dynamic Analysis Simulation

    NASA Technical Reports Server (NTRS)

    Gregory, B. R.

    1970-01-01

    Digital six-degrees-of-freedom, open loop Saturn 5 first stage flight evaluation simulation program obtains post flight simulation of the launch vehicle using actual flight data as input. Results are compared with measured data. For preflight analysis, the program uses predicted flight data as input.

  15. Allogeneic transplantation for primary myelofibrosis with BM, peripheral blood or umbilical cord blood: an analysis of the JSHCT

    PubMed Central

    Murata, M; Nishida, T; Taniguchi, S; Ohashi, K; Ogawa, H; Fukuda, T; Mori, T; Kobayashi, H; Nakaseko, C; Yamagata, N; Morishima, Y; Nagamura-Inoue, T; Sakamaki, H; Atsuta, Y; Suzuki, R; Naoe, T

    2014-01-01

    To determine whether a difference in donor source affects the outcome of transplantation for patients with primary myelofibrosis (PMF), a retrospective study was conducted using the national registry data on patients who received first allogeneic hematopoietic cell transplantation (HCT) with related BM (n=19), related PBSCs (n=25), unrelated BM (n=28) or unrelated umbilical cord blood (UCB; n=11). The 5-year OS rates after related BM, related PBSC and unrelated BM transplantation were 63%, 43% and 41%, respectively, and the 2-year OS rate after UCB transplantation was 36%. On multivariate analysis, the donor source was not a significant factor for predicting the OS rate. Instead, performance status (PS) ⩾2 (vs PS 0–1) predicted a lower OS (P=0.044), and RBC transfusion ⩾20 times before transplantation (vs transfusion ⩽9 times) showed a trend toward a lower OS (P=0.053). No advantage of nonmyeloablative preconditioning regimens in terms of decreasing nonrelapse mortality or increasing OS was found. Allogeneic HCT, and even unrelated BM and UCB transplantation, provides a curative treatment for PMF patients. PMID:24270391

  16. Administration of G-CSF from day +6 post-allogeneic hematopoietic stem cell transplantation in children and adolescents accelerates neutrophil engraftment but does not appear to have an impact on cost savings.

    PubMed

    O'Rafferty, Ciara; O'Brien, Mairead; Smyth, Elaine; Keane, Sinead; Robinson, Hillary; Lynam, Paul; O'Marcaigh, Aengus; Smith, Owen P

    2016-05-01

    G-CSF post-allogeneic HSCT accelerates neutrophil engraftment, but evidence that it impacts on cost-related outcomes is lacking. We performed a retrospective child and adolescent single-center cohort study examining G-CSF administration from Day +6 of allogeneic HSCT vs. ad hoc G-CSF use where clinically indicated. Forty consecutive children and adolescents undergoing allogeneic HSCT were included. End-points were as follows: time to engraftment; incidence of acute and chronic GvHD; number of patients alive at Day +100; 180-day TRM; post-transplant days in hospital; and cost of antimicrobials, TPN, and G-CSF usage. Neutrophil engraftment occurred earlier in the group that received G-CSF from Day +6. There was no difference between groups in any of the other end-points with the following exception: the cost of GCSF was significantly higher in the D + 6 G-CSF group. However, median G-CSF cost in this group amounted to only €280. There was a trend towards reduced cost of antimicrobials in the D + 6 G-CSF group, although this did not reach significance (p = 0.13). The median cost per patient of antimicrobial agents between groups differed by €1116. This study demonstrated the administration of G-CSF on Day +6 in pediatric HSCT to be safe. A further study using a larger cohort of patients is warranted to ascertain its true clinico-economic value.

  17. Effect of post remission therapy prior to reduced intensity conditioning allogeneic transplantation for acute myeloid leukemia in first complete remission

    PubMed Central

    Warlick, Erica D.; Paulson, Kristjan; Brazauskas, Ruta; Zhong, Xiaobo; Miller, Alan M.; Camitta, Bruce M.; George, Biju; Savani, Bipin N.; Ustun, Celalettin; Marks, David I.; Waller, Edmund K.; Baron, Frédéric; Freytes, César O.; Socie, Gérard; Akpek, Gorgun; Schouten, Harry C.; Lazarus, Hillard M.; Horwitz, Edwin M.; Koreth, John; Cahn, Jean-Yves; Bornhauser, Martin; Seftel, Matthew; Cairo, Mitchell S.; Laughlin, Mary J.; Sabloff, Mitchell; Ringdén, Olle; Gale, Robert Peter; Kamble, Rammurti T.; Vij, Ravi; Gergis, Usama; Mathews, Vikram; Saber, Wael; Chen, Yi-Bin; Liesveld, Jane L.; Cutler, Corey S.; Ghobadi, Armin; Uy, Geoffrey L.; Eapen, Mary; Weisdorf, Daniel J.; Litzow, Mark R.

    2013-01-01

    The impact of pre transplant (HCT) cytarabine consolidation therapy on post HCT outcomes has yet to be evaluated after reduced intensity or non-myeloablative conditioning. We analyzed 604 adults with acute myeloid leukemia (AML) in first complete remission (CR1) reported to the CIBMTR who received a RIC or NMA HCT from an HLA-identical sibling, HLA-matched unrelated donor (URD), or umbilical cord blood (UCB) donor in 2000–2010. We compared transplant outcomes based on exposure to cytarabine post remission consolidation. Three year survival rates were 36% (29–43%, 95% CI) in the no consolidation arm and 42% (37–47%, 95% CI) in the cytarabine consolidation arm (p=0.16). Disease free survival was 34% (27–41%, 95% CI) and 41% (35–46%, 95% CI) (p=0.15), respectively. Three year cumulative incidences of relapse were 37% (30–44%, 95% CI) and 38% (33–43%, 95% CI), respectively (p=0.80). Multivariate regression confirmed no effect of consolidation on relapse, DFS and survival. Prior to RIC/NMA HCT, these data suggest pre-HCT consolidation cytarabine does not significantly alter outcomes and support prompt transition to transplant as soon as morphologic CR1 is attained. If HCT is delayed while identifying a donor, our data suggest that consolidation does not increase transplant TRM and is reasonable if required. PMID:24184335

  18. Evaluation of immunomodulatory treatment based on conventional and lineage-specific chimerism analysis in patients with myeloid malignancies after myeloablative allogeneic hematopoietic cell transplantation.

    PubMed

    Zeiser, R; Spyridonidis, A; Wäsch, R; Ihorst, G; Grüllich, C; Bertz, H; Finke, J

    2005-05-01

    Both conventional chimerism analysis (CCA) and lineage-specific chimerism analysis (LCA) have potential pitfalls as diagnostic means for the detection of minimal residual disease after allogeneic hematopoietic cell transplantation (aHCT). Therefore, the present study examines the results of both methods in order to determine how predictive consecutive evaluations were, with respect to the risk that the patient would relapse during post-transplant follow-up and with respect to responsiveness to immunomodulatory treatment. A total of 168 individuals with acute myeloid leukemia (AML) (n = 137) and myelo dysplastic syndrome (n = 31) were investigated with CCA and LCA at mean intervals of 24 days (range: 11-116). The median follow-up after myeloablative aHCT was 22 months (range: 4-49). Of 168 patients, 65 experienced a clinical relapse after aHCT. CCA and LCA were comparatively sensitive and specific for relapse at the intervals of chimerism testing employed in this study. Of 32 patients, 10 who were offered donor lymphocyte infusions (DLI) treatment for increasing (n = 29) or stable (n = 3) mixed chimerism (MC) achieved at least transitory CC. The observation that all patients with increasing MC relapsed despite DLI treatment (54%) or withdrawal of immune suppression (24%) indicates that novel strategies to deal with rapidly evolving relapse in AML patients, such as shortening of chimerism monitoring intervals, need to be evaluated.

  19. Short Course of Post-Transplantation Cyclophosphamide and Bortezomib for Graft-versus-Host Disease Prevention after Allogeneic Peripheral Blood Stem Cell Transplantation Is Feasible and Yields Favorable Results: A Phase I Study.

    PubMed

    Al-Homsi, Ahmad-Samer; Cole, Kelli; Bogema, Marlee; Duffner, Ulrich; Williams, Stephanie; Mageed, Aly

    2015-07-01

    An effective graft-versus-host disease (GVHD) preventative approach that preserves the graft-versus-tumor effect after allogeneic hematopoietic stem cell transplantation (HSCT) remains elusive. Standard GVHD prophylactic regimens suppress T cells indiscriminately and are suboptimal. Conversely, post-transplantation high-dose cyclophosphamide selectively destroys proliferating alloreactive T cells, allows the expansion of regulatory T cells, and induces long-lasting clonal deletion of intrathymic antihost T cells. It has been successfully used to prevent GVHD after allogeneic HSCT. Bortezomib has antitumor activity on a variety of hematological malignancies and exhibits a number of favorable immunomodulatory effects that include inhibition of dendritic cells. Therefore, an approach that combines post-transplantation cyclophosphamide and bortezomib seems attractive. Herein, we report the results of a phase I study examining the feasibility and safety of high-dose post-transplantation cyclophosphamide in combination with bortezomib in patients undergoing allogeneic peripheral blood HSCT from matched siblings or unrelated donors after reduced-intensity conditioning. Cyclophosphamide was given at a fixed dose (50 mg/kg on days +3 and +4). Bortezomib dose was started at .7 mg/m2, escalated up to 1.3 mg/m2, and was administered on days 0 and +3. Patients receiving grafts from unrelated donors also received rabbit antithymocyte globulin. The combination was well tolerated and allowed prompt engraftment in all patients. The incidences of acute GVHD grades II to IV and grades III and IV were 20% and 6.7%, respectively. With a median follow-up of 9.1 months (range, 4.3 to 26.7), treatment-related mortality was 13.5% with predicted 2-year disease-free survival and overall survival of 55.7% and 68%, respectively. The study suggests that the combination of post-transplantation cyclophosphamide and bortezomib is feasible and may offer an effective and practical GVHD prophylactic

  20. Longitudinal analysis of antibody response to immunization in paediatric survivors after allogeneic haematopoietic stem cell transplantation

    PubMed Central

    Inaba, Hiroto; Hartford, Christine M.; Pei, Deqing; Posner, Meredith J.; Yang, Jie; Hayden, Randall T.; Srinivasan, Ashok; Triplett, Brandon M.; McCulllers, Jon A.; Pui, Ching-Hon; Leung, Wing

    2011-01-01

    Summary The long-term antibody responses to re-immunization in recipients of allogeneic haematopoietic stem cell transplantation (allo-HSCT) have not been well studied. We prospectively and longitudinally evaluated the antibody responses to 8 vaccine antigens (diphtheria, tetanus, pertussis, measles, mumps, rubella, hepatitis B, and poliovirus) and assessed the factors associated with negative titres in 210 allo-HSCT recipients at St. Jude Children’s Research Hospital. Antibody responses lasting for more than 5 years after immunization were observed in most patients for tetanus (95.7%), rubella (92.3%), poliovirus (97.9%), and, in diphtheria-tetanus-acellular pertussis (DTaP) recipients, diphtheria (100%). However, responses to pertussis (25.0%), measles (66.7%), mumps (61.5%), hepatitis B (72.9%), and diphtheria in tetanus-diphtheria (Td) recipients (48.6%) were less favourable, with either only transient antibody responses or persistently negative titres. Factors associated with vaccine failure were older age at immunization; lower CD3, CD4 or CD19 counts; higher IgM concentrations; positive recipient cytomegalovirus serology; negative titres before immunization; acute or chronic graft-versus-host disease; and radiation during preconditioning. These response patterns and clinical factors can be used to formulate re-immunization and monitoring strategies. Patients at risk for vaccine failure should have long-term follow-up; those with loss of antibody response or no seroconversion should receive booster immunizations. PMID:22017512

  1. A retrospective analysis evaluating allogeneic cancellous bone sponge for foot and ankle arthrodesis.

    PubMed

    Brigido, Stephen A; Bleazey, Scott T; Protzman, Nicole M; D'Angelantonio, Albert; Schoenhaus, Harold D

    2013-01-01

    The present retrospective case crossover study was conducted to determine the effectiveness and safety data associated with the use of an allogeneic, cancellous bone sponge in an orthopedic foot and ankle population. We reviewed the medical records of 47 subjects (80 joints) who had undergone foot and/or ankle fusion with the cancellous bone sponge. The records were reviewed up to 12 months postoperatively. The joints included in the present study were 12 ankles, 3 ankle syndesmotic fusions (with concurrent total ankle arthroplasty), 17 subtalar joints, 17 talonavicular joints, 9 calcaneocubiod joints, 1 naviculocuneiform joint, 13 first tarsometatarsal joints, 6 lesser tarsometatarsal joints, and 2 first metatarsophalangeal joints. The endpoints of the present study were solid, sustained foot and ankle fusion, as demonstrated radiographically, and the occurrence of unexpected adverse effects related to the graft. The fusion rates were compared with those reported in other studies. The patient-reported outcome variables for the present study included the visual analog pain scale and the American Orthopaedic Foot and Ankle Score. The use of a cancellous sponge showed statistically significant improvements in pain and function and comparable or better fusion rates compared with outcomes reported in other published reports.

  2. An analysis of the influence of intra-operative blood salvage and autologous transfusion on reducing the need for allogeneic transfusion in elective infrarenal abdominal aortic aneurysm repair

    PubMed Central

    Pasternak, Janko; Nikolic, Dragan; Milosevic, Djordje; Popovic, Vladan; Markovic, Vladimir

    2014-01-01

    Background An intra-operative cell salvage machine, commonly known as a “cell saver”, aspirates, washes, and filters patient’s blood during an operation so that the blood can be returned to the patient’s circulation instead of being discarded. This procedure could significantly reduce the risks related to the use of allogeneic blood and blood products in surgery. The aim of this study was to analyse the influence of intra-operative cell salvage on reducing the need for allogeneic blood in patients with asymptomatic infrarenal abdominal aortic aneurysm undergoing elective repair of the aneurysm. Material and methods We retrospectively collected data from the clinical records of patients who underwent elective infrarenal abdominal aortic aneurysm repair. Two groups were formed: the “cell saver” group, in which intra-operative cell salvage was used, and the control group, in which a cell saver was not used. Results Thirty patients underwent abdominal aortic aneurysm repair with the use of a cell saver, while 32 underwent the same operation without cell salvage. We found a significant association between use of the cell saver and a reduced need for allogeneic blood in these patients. Operations performed with the use of a cell saver lasted, on average, less time than those performed without it. The difference between pre-operative and post-operative haemoglobin levels was significantly greater in the group of patients who underwent repair with the use of a cell saver than in the control group. Conclusion The use of a cell saver in elective abdominal aortic aneurysm repair significantly reduces the need for intra-operative use of allogeneic blood. PMID:23114525

  3. The EuroChimerism concept for a standardized approach to chimerism analysis after allogeneic stem cell transplantation.

    PubMed

    Lion, T; Watzinger, F; Preuner, S; Kreyenberg, H; Tilanus, M; de Weger, R; van Loon, J; de Vries, L; Cavé, H; Acquaviva, C; Lawler, M; Crampe, M; Serra, A; Saglio, B; Colnaghi, F; Biondi, A; van Dongen, J J M; van der Burg, M; Gonzalez, M; Alcoceba, M; Barbany, G; Hermanson, M; Roosnek, E; Steward, C; Harvey, J; Frommlet, F; Bader, P

    2012-08-01

    Hematopoietic stem cell transplantation is becoming an increasingly important approach to treatment of different malignant and non-malignant disorders. There is thus growing demand for diagnostic assays permitting the surveillance of donor/recipient chimerism posttransplant. Current techniques are heterogeneous, rendering uniform evaluation and comparison of diagnostic results between centers difficult. Leading laboratories from 10 European countries have therefore performed a collaborative study supported by a European grant, the EuroChimerism Concerted Action, with the aim to develop a standardized diagnostic methodology for the detection and monitoring of chimerism in patients undergoing allogeneic stem cell transplantation. Following extensive analysis of a large set of microsatellite/short tandem repeat (STR) loci, the EuroChimerism (EUC) panel comprising 13 STR markers was established with the aim to optimally meet the specific requirements of quantitative chimerism analysis. Based on highly stringent selection criteria, the EUC panel provides multiple informative markers in any transplant setting. The standardized STR-PCR tests permit detection of donor- or recipient-derived cells at a sensitivity ranging between 0.8 and 1.6%. Moreover, the EUC assay facilitates accurate and reproducible quantification of donor and recipient hematopoietic cells. Wide use of the European-harmonized protocol for chimerism analysis presented will provide a basis for optimal diagnostic support and timely treatment decisions.

  4. Clinicopathological analysis of allogeneic hematopoietic stem cell transplantation-related membranous glomerulonephritis.

    PubMed

    Hiramatsu, Rikako; Ubara, Yoshifumi; Sawa, Naoki; Hasegawa, Eiko; Kawada, Masahiro; Imafuku, Aya; Sumida, Keiichi; Mise, Koki; Yamanouchi, Masayuki; Ueno, Toshiharu; Sekine, Akinari; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Wake, Atsushi; Taniguchi, Shuichi

    2016-04-01

    Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus-host disease after cessation of immunosuppression. Light microscopy did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. Immunofluorescence demonstrated granular deposits of immunoglobulin G (IgG; IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), whereas case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. Electron microscopy revealed electron-dense deposits in the subepithelial space of the GBM in cases 1-4. In case 5, electron-dense deposits were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic-range proteinuria relapsed in 2 patients during follow-up. Serum anti-PLA2R autoantibody was negative in 3 patients. HSCT-related MGN only occurred after UCBT. We believe that there were 2 morphologic patterns: early MGN and membranoproliferative pattern glomerulonephritis.

  5. Clinical utility of chimerism status assessed by lineage-specific short tandem repeat analysis: experience from four cases of allogeneic stem cell transplantation.

    PubMed

    Goh, Ri-Young; Cho, Sung-Suk; Song, Yoo-Jeong; Heo, Kyeong; Oh, Sung-Yong; Kim, Sung-Hyun; Kwon, Hyeok-Chan; Kim, Hyo-Jin; Han, Jin-Yeong

    2009-08-01

    Chimerism testing permits early prediction and documentation of successful engraftment, and also facilitates detection of impending graft rejection. In this study, we serially monitored chimerism status by short tandem repeat-based PCR in nucleated cells (NC), T cells and natural killer (NK) cells after myeloablative allogeneic stem cell transplantation (SCT). Four patients with myeloid malignancies showed discrepant chimerism results among those three fractions. Three patients had mixed chimerism (MC) of donor/host T cells at a time point around the onset of chronic graft-versus-host disease (GVHD). In two patients with disease relapse, MC of NK cells preceded a morphological relapse or NK cells showed a higher percentage of patient cells compared to NC. Therefore, our study shows that chimerism analysis in lineage-specific cells might be useful in predicting clinical outcome after allogeneic SCT in certain patients.

  6. Are allogenic or xenogenic screws and plates a reasonable alternative to alloplastic material for osteosynthesis--a histomorphological analysis in a dynamic system.

    PubMed

    Jacobsen, C; Obwegeser, J A

    2010-12-01

    Despite invention of titanium and resorbable screws and plates, still, one of the main challenges in bone fixation is the search for an ideal osteosynthetic material. Biomechanical properties, biocompatibility, and also cost effectiveness and clinical practicability are factors for the selection of a particular material. A promising alternative seems to be screws and plates made of bone. Recently, xenogenic bone pins and screws have been invented for use in joint surgery. In this study, screws made of allogenic sheep and xenogenic human bone were analyzed in a vital and dynamic sheep-model and compared to conventional titanium screws over a standard period of bone healing of 56 days with a constant applied extrusion force. Biomechanical analysis and histomorphological evaluation were performed. After 56 days of insertion xenogenic screws made of human bone showed significantly larger distance of extrusion of on average 173.8 μm compared to allogenic screws made of sheep bone of on average 27.8 and 29.95 μm of the titanium control group. Severe resorption processes with connective tissue interposition were found in the histomorphological analysis of the xenogenic screws in contrast to new bone formation and centripetal vascularization of the allogenic bone screw, as well as in processes of incorporation of the titanium control group. The study showed allogenic cortical bone screws as a substantial alternative to titanium screws with good biomechanical properties. In contrast to other reports a different result was shown for the xenogenic bone screws. They showed insufficient holding strength with confirmative histomorphological signs of degradation and insufficient osseointegration. Before common clinical use of xenogenic osteosynthetic material, further evaluation should be performed. PMID:20813368

  7. Gut microbiota and allogeneic transplantation.

    PubMed

    Wang, Weilin; Xu, Shaoyan; Ren, Zhigang; Jiang, Jianwen; Zheng, Shusen

    2015-08-23

    The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gut microbiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gut microbiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the

  8. Risk Factors and Impact of non-Aspergillus mold infections (NAMI) following Allogeneic HCT: A CIBMTR Infection & Immune Reconstitution analysis

    PubMed Central

    Riches, Marcie L.; Trifilio, Steven; Chen, Min; Ahn, Kwang Woo; Langston, Amelia; Lazarus, Hillard M.; Marks, David I.; Martino, Rodrigo; Maziarz, Richard T.; Papinicolou, Genofeva A.; Wingard, John R.; Young, Jo-Anne H.; Bennett, Charles L.

    2015-01-01

    Risk factors for non-Aspergillus mold infection (NAMI) and the impact on transplant outcome are poorly assessed in the current era of antifungal agents. Outcomes of 124 patients receiving allogeneic HCT diagnosed with either mucormycosis [n=72] or fusariosis [n=52] between days 0-365 after HCT are described and compared to a control cohort (n=11856). Patients with NAMI had more advanced disease [mucormycois 25%, fusariosis 23%, controls 18%; p = 0.004] and were more likely to have a KPS<90% at HCT [mucormycosis 42%, fusariosis 38%, controls 28%; p=0.048]. The 1-year survival after HCT was 22% (15–29%) for cases and was significantly inferior compared to controls [65%(64–65%); p < 0.001]. Survival from infection was similarly dismal regardless of mucormycosis [15% (8-25%)] and fusariosis [21% (11-33%)]. In multivariable analysis, NAMI was associated with a 6-fold higher risk of death (p<0.0001) regardless of the site or timing of infection. Risk factors for mucormycosis include preceding acute GVHD, prior aspergillus infection, and older age. For fusariosis, increased risks including receipt of cord blood, prior CMV infection, and transplant prior to May 2002. In conclusion, NAMI occurs infrequently, is associated with high mortality, and appears with similar frequency in the current antifungal era. PMID:26524262

  9. [Post-mortem microbiology analysis].

    PubMed

    Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

    2013-12-01

    Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population.

  10. [Post-mortem microbiology analysis].

    PubMed

    Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

    2013-12-01

    Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population. PMID:23195835

  11. The Effect of GVHD on Long-term Outcomes after Peripheral Blood Allogeneic Stem Cell Transplantation from an HLA-identical Sibling in Adult Acute Lymphocytic Leukemia: A Landmark Analysis Approach in Competing Risks.

    PubMed

    Jalali, Arash; Alimoghaddam, Kamran; Mahmoudi, Mahmood; Mohammad, Kazem; Mousavi, Seied Asadollah; Bahar, Babak; Vaezi, Mohammad; Zeraati, Hojjat; Jahani, Mohammad; Ghavamzadeh, Ardeshir

    2014-01-01

    Allogeneic Hematopoietic stem cell transplantation (HSCT) is the most effective therapy to prevent relapse in acute lymphocytic leukemia (ALL). This benefit is affected by non-relapse mortality (NRM) due to complications such as graft versus host disease (GVHD). A new approach in analyzing time-dependent covariates in competing risks is landmark analysis. So, the aim of this study is to evaluate the effect of acute and chronic GVHD on long-term outcomes, relapse and NRM, after allogeneic HSCT in adult ALL using landmark analysis. This study was conducted on 252 ALL patients who were allogeneic transplanted from an HLA-identical sibling with peripheral blood (PB) as the source of stem cell from 2004 to 2012 and were followed-up until 2013. In the first 100 days after transplant, a landmark analysis on days +10, +11, +12, +17, +24, and +31 was applied to assess the effect of acute GVHD on early relapse and NRM. Similarly, for patients alive and event-free at day +100 after transplant, a landmark analysis at time points day +101, months +4, +5, +6, +9, and +12 was applied to evaluate the effect of chronic GVHD on late relapse and NRM. Five-year LFS and OS were 35.0% (95% CI: 29.1, 42.2%) and 37.5% (95% CI: 31.3, 45.0%), respectively. Five-year cumulative incidence of relapse was 44.5% (95% CI: 37.9, 51.0%) while this was 20.4% (95% CI: 15.4, 26.0%) for NRM. The landmark analysis in the first 100 days after transplant showed that the grade III/IV of aGVHD has a lower risk of relapse but higher risk of NRM after adjustment for the EBMT risk score. For patients alive at day +100, cGVHD had no significant effect on relapse. Limited cGVHD had lower risk of NRM and after 6 month post-transplant the risk of NRM decreased and there were not important difference between the groups of cGVHD. Using advanced models enables us to estimate the effects more precisely and ultimately make inference more accurately.

  12. Allogenous tooth fragment reattachment

    PubMed Central

    Maitin, Nitin; Maitin, Shipra; Rastogi, Khushboo; Bhushan, Rajarshi

    2013-01-01

    Coronal fractures of the anterior teeth are a common form of dental trauma and its sequelae may impair the establishment and accomplishment of an adequate treatment plan. Among the various treatment options, reattachment of a crown fragment obtained from a previously extracted tooth is a conservative treatment that should be considered for crown fractures of anterior teeth. This article reports reattachment of an allogenous tooth fragment in a fractured maxillary lateral incisor in a 38-year-old patient. It is suggested that allogenous reattachment in a fractured anterior tooth serves to be a better alternative and should be further researched. Aesthetic and functional rehabilitation of a fractured complicated anterior crown using allogenous tooth fragment is a better alternative to other more conventional treatment options. PMID:23845684

  13. Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: analysis of 533 adult patients who underwent transplantation at King's College Hospital.

    PubMed

    Wang, Meng; Wang, Wenjia; Abeywardane, Ayesha; Adikarama, Malinthi; McLornan, Donal; Raj, Kavita; de Lavallade, Hugues; Devereux, Stephen; Mufti, Ghulam J; Pagliuca, Antonio; Potter, Victoria T; Mijovic, Aleksandar

    2015-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of hematopoietic stem cell transplantation (HSCT); it is often refractory to treatment and carries a high mortality. To improve understanding of the incidence, risk factors, and clinical outcome of post-transplantation AIHA, we analyzed 533 patients who received allogeneic HSCT, and we identified 19 cases of AIHA after HSCT (overall incidence, 3.6%). The median time to onset, from HSCT to AIHA, was 202 days. AIHA was associated with HSCT from unrelated donors (hazard ratio [HR], 5.28; 95% confidence interval [CI], 1.22 to 22.9; P = .026). In the majority (14 of 19; 74%) of AIHA patients, multiple agents for treatment were required, with only 9 of 19 (47%) patients achieving complete resolution of AIHA. Patients with post-transplantation AIHA had a higher overall mortality (HR, 2.48; 95% CI, 1.33 to 4.63; P = .004), with 36% (4 of 11 cases) of deaths attributable to AIHA. PMID:25262883

  14. Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: analysis of 533 adult patients who underwent transplantation at King's College Hospital.

    PubMed

    Wang, Meng; Wang, Wenjia; Abeywardane, Ayesha; Adikarama, Malinthi; McLornan, Donal; Raj, Kavita; de Lavallade, Hugues; Devereux, Stephen; Mufti, Ghulam J; Pagliuca, Antonio; Potter, Victoria T; Mijovic, Aleksandar

    2015-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of hematopoietic stem cell transplantation (HSCT); it is often refractory to treatment and carries a high mortality. To improve understanding of the incidence, risk factors, and clinical outcome of post-transplantation AIHA, we analyzed 533 patients who received allogeneic HSCT, and we identified 19 cases of AIHA after HSCT (overall incidence, 3.6%). The median time to onset, from HSCT to AIHA, was 202 days. AIHA was associated with HSCT from unrelated donors (hazard ratio [HR], 5.28; 95% confidence interval [CI], 1.22 to 22.9; P = .026). In the majority (14 of 19; 74%) of AIHA patients, multiple agents for treatment were required, with only 9 of 19 (47%) patients achieving complete resolution of AIHA. Patients with post-transplantation AIHA had a higher overall mortality (HR, 2.48; 95% CI, 1.33 to 4.63; P = .004), with 36% (4 of 11 cases) of deaths attributable to AIHA.

  15. Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse.

    PubMed

    Sobiak, Joanna; Kazimierczak, Urszula; Kowalczyk, Dariusz W; Chrzanowska, Maria; Styczyński, Jan; Wysocki, Mariusz; Szpecht, Dawid; Wachowiak, Jacek

    2015-10-01

    The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC-UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1-1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1-0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1-0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material.

  16. Investigation of allogeneic mesenchymal stem cell-based alveolar bone formation: preliminary findings.

    PubMed

    De Kok, Ingeborg J; Peter, Susan J; Archambault, Michael; van den Bos, Christian; Kadiyala, Sudha; Aukhil, Ikramuddin; Cooper, Lyndon F

    2003-08-01

    This study was designed to evaluate mesenchymal stem cell (MSC)-based alveolar bone regeneration in a canine alveolar saddle defect model. MSCs were loaded onto hydroxyapatite/tricalcium phosphate (HA/TCP) matrices. Scanning electron microscopic (SEM) evaluation demonstrated greater than 75% MSC coverage of the HA/TCP porous surface prior to placement regardless of MSC donor. Matrices, 6 mm x 6 mm x 20 mm, with and without cells, were implanted for 4 and 9 weeks, then removed for histological evaluation of bone formation. Cell-free control matrices were compared with MSC-loaded matrices post implantation. Histomorphometrical analysis showed that equivalent amounts of new bone were formed within the pores of the matrices loaded with autologous MSCs or MSCs from an unrelated donor. Bone formation in the cell-free HA/TCP matrices was less extensive. There was no histologic evidence of an immunological response to autologous MSCs. Surprisingly, allogeneic MSC implantation also failed to provoke an immune response. Analysis of circulating antibody levels against MSCs supported the hypothesis that neither autologous nor allogeneic MSCs induced a systemic response by the host. Analysis of dye-labelled MSCs in histological sections confirmed that the MSCs persisted in the implants throughout the course of the experiment. At 9 weeks, labelled cells were present within the lacunae of newly formed bone. We conclude that autologous and allogeneic MSCs have the capacity to regenerate bone within craniofacial defects.

  17. Allogeneic stem cell transplantation in chronic lymphocytic leukemia patients with 17p deletion: consult-transplant v consult-no-transplant analysis

    PubMed Central

    Poon, Michelle L.; Fox, Patricia S.; Samuels, Barry I.; O’Brien, Susan; Jabbour, Elias; Hsu, Yvonne; Gulbis, Alison; Korbling, Martin; Champlin, Richard; Abruzzo, Lynne V.; Bassett, Roland L.; Khouri, Issa F.

    2015-01-01

    Allogeneic stem cell transplantation (alloSCT) can overcome the adverse prognosis of chronic lymphocytic leukemia with 17p deletion (17p- CLL). However, its applicability remains unclear. Since 2007, our leukemia service has referred 17p- CLL patients for alloSCT at presentation. In this study, the outcomes of these patients were reviewed retrospectively to determine whether they underwent alloSCT and why patients did not undergo alloSCT. Fifty-two patients with 17p- CLL, who were referred to the transplant service from 2007 to 2010, were identified. Of these patients, 32 (62%) patients did not undergo alloSCT, mainly because of treatment- or disease-related complications (n=15). The 2-year post-referral overall survival rates of the alloSCT and non-SCT groups were 64% and 25%, respectively (p = 0.001). These findings suggest that while alloSCT is an effective therapy in 17p- CLL patients, pre-SCT complications may preclude a significant proportion of patients from undergoing the procedure. PMID:24913509

  18. Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis.

    PubMed

    Fiz, Francesco; Marini, Cecilia; Campi, Cristina; Massone, Anna Maria; Podestà, Marina; Bottoni, Gianluca; Piva, Roberta; Bongioanni, Francesca; Bacigalupo, Andrea; Piana, Michele; Sambuceti, Gianmario; Frassoni, Francesco

    2015-06-25

    Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P < .001). In long bones, ABM increased three- and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P < .01). These data document an unexpected distribution of transplanted BM into previously abandoned BM sites.

  19. Post-analysis of learned rules

    SciTech Connect

    Liu, Bing; Hsu, W.

    1996-12-31

    Rule induction research implicitly assumes that after producing the rules from a dataset, these rules will be used directly by an expert system or a human user. In real-life applications, the situation may not be as simple as that, particularly, when the user of the rules is a human being. The human user almost always has some previous concepts or knowledge about the domain represented by the dataset. Naturally, he/she wishes to know how the new rules compare with his/her existing knowledge. In dynamic domains where the rules may change over time, it is important to know what the changes are. These aspects of research have largely been ignored in the past. With the increasing use of machine learning techniques in practical applications such as data mining, this issue of post analysis of rules warrants greater emphasis and attention. In this paper, we propose a technique to deal with this problem. A system has been implemented to perform the post analysis of classification rules generated by systems such as C4.5. The proposed technique is general and highly interactive. It will be particularly useful in data mining and data analysis.

  20. Lineage-specific chimerism analysis in nucleated cells, T cells and natural killer cells after myeloablative allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Goh, Ri-Young; Kim, Sung-Hyun

    2011-01-01

    Background Chimerism analysis is an important tool for assessing the origin of hematopoietic cells after allogeneic stem cell transplantation (allo-SCT) and can be used to detect impending graft rejection and the recurrence of underlying malignant or nonmalignant diseases. Methods This study included 24 patients who underwent myeloablative allo-SCT. DNA was extracted from nucleated cells (NCs), T cells, and natural killer (NK) cells, and the chimerism status of these cell fractions was determined by STR-PCR performed using an automated fluorescent DNA analyzer. Results Twenty-three out of the 24 patients achieved engraftment. Mixed chimerism (MC) in NCs, but not in T cells and NK cells, was significantly correlated with disease relapse. MC in all cell fractions was correlated with mortality. Ten patients (41.6%) developed extensive chronic GVHD. Six patients had MC in T cells, and 3 of them had chronic GVHD. Four patients with MC and relapse received donor lymphocyte infusion (DLI), and among them, 3 had secondary relapse. Further, the chimerism status differed among different cell lineages in 6 patients with myeloid malignancies. Conclusion The implications of MC in lymphocyte subsets are an important area for future research. Chimerism analysis in lineage-specific cells permits detection of relapse and facilitates the monitoring of therapeutic interventions. These results can provide the basic data for chimerism analysis after myeloablative SCT. PMID:21461299

  1. POST-PROCESSING ANALYSIS FOR THC SEEPAGE

    SciTech Connect

    Y. SUN

    2004-09-29

    This report describes the selection of water compositions for the total system performance assessment (TSPA) model of results from the thermal-hydrological-chemical (THC) seepage model documented in ''Drift-Scale THC Seepage Model'' (BSC 2004 [DIRS 169856]). The selection has been conducted in accordance with ''Technical Work Plan for: Near-Field Environment and Transport: Coupled Processes (Mountain-Scale TH/THC/THM, Drift-Scale THC Seepage, and Post-Processing Analysis for THC Seepage) Report Integration'' (BSC 2004 [DIRS 171334]). This technical work plan (TWP) was prepared in accordance with AP-2.27Q, ''Planning for Science Activities''. Section 1.2.3 of the TWP describes planning information pertaining to the technical scope, content, and management of this report. The post-processing analysis for THC seepage (THC-PPA) documented in this report provides a methodology for evaluating the near-field compositions of water and gas around a typical waste emplacement drift as these relate to the chemistry of seepage, if any, into the drift. The THC-PPA inherits the conceptual basis of the THC seepage model, but is an independently developed process. The relationship between the post-processing analysis and other closely related models, together with their main functions in providing seepage chemistry information for the Total System Performance Assessment for the License Application (TSPA-LA), are illustrated in Figure 1-1. The THC-PPA provides a data selection concept and direct input to the physical and chemical environment (P&CE) report that supports the TSPA model. The purpose of the THC-PPA is further discussed in Section 1.2. The data selection methodology of the post-processing analysis (Section 6.2.1) was initially applied to results of the THC seepage model as presented in ''Drift-Scale THC Seepage Model'' (BSC 2004 [DIRS 169856]). Other outputs from the THC seepage model (DTN: LB0302DSCPTHCS.002 [DIRS 161976]) used in the P&CE (BSC 2004 [DIRS 169860

  2. Haploidentical T Cell-Replete Transplantation with Post-Transplantation Cyclophosphamide for Patients in or above the Sixth Decade of Age Compared with Allogeneic Hematopoietic Stem Cell Transplantation from an Human Leukocyte Antigen-Matched Related or Unrelated Donor.

    PubMed

    Blaise, Didier; Fürst, Sabine; Crocchiolo, Roberto; El-Cheikh, Jean; Granata, Angela; Harbi, Samia; Bouabdallah, Reda; Devillier, Raynier; Bramanti, Stephania; Lemarie, Claude; Picard, Christophe; Chabannon, Christian; Weiller, Pierre-Jean; Faucher, Catherine; Mohty, Bilal; Vey, Norbert; Castagna, Luca

    2016-01-01

    It has recently been shown that a T cell-replete allogeneic (allo) hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (haplo-ID) could be a valid treatment for hematological malignancies. However, little data exist concerning older populations. We provided transplantation to 31 patients over the age of 55 years from a haplo-ID and compared their outcomes with patients of the same ages who underwent transplantation from a matched related (MRD) or an unrelated donor (UD). All 3 groups were comparable, except for their conditioning. Patients in haplo-ID group received 2 days of post-transplantation high-dose cyclophosphamide followed by cyclosporine A and mycophenolate mofetil, whereas patients in other groups received pretransplantation antithymocyte globulin, cyclosporine A, and additional mycophenolate mofetil in case of 1-antigen mismatch. All patients but 1 in the haplo-ID group engrafted. The incidence of grades 2 to 4 acute graft-versus-host disease (GVHD) was not statistically different between recipients from haplo-ID (cumulative incidence, 23%) and MRD (cumulative incidence, 21%) transplantations but it was lower than after UD HSCT (cumulative incidence, 44%). No patient in the haplo-ID group developed severe chronic GVHD, compared with cumulative incidences of 16% and 14% after MRD (P = .02) and UD (P = .03) grafts, respectively. The cumulative incidences of relapse were similar in the 3 groups, whereas nonrelapse mortality after UD HSCT was 3-fold higher than after haplo-ID or MRD HSCT. Overall, 2-year overall survival (70%), progression-free survival (67%), and progression and severe chronic GVHD-free survival (67%) probabilities after haplo-ID did not statistically differ from MRD transplantation (78%, 64%, and 51%, respectively), although they were higher than after UD transplantation (51% [P = .08], 38% [P = .02], and 31% [P = .007]). We conclude that T cell-replete haplo-ID HSCT followed by post-transplantation high

  3. The cost of post-operative shed blood salvage after total knee arthroplasty: an analysis of 1,093 consecutive procedures

    PubMed Central

    Muñoz, Manuel; Ariza, Daniel; Campos, Arturo; Martín-Montañez, Elisa; Pavía, José

    2013-01-01

    Background Requirements for allogeneic red cell transfusion after total knee arthroplasty are still high (20–50%), and salvage and reinfusion of unwashed, filtered post-operative shed blood is an established method for reducing transfusion requirements following this operation. We performed a cost analysis to ascertain whether this alternative is likely to be cost-effective. Materials and methods Data from 1,093 consecutive primary total knee arthroplasties, managed with (reinfusion group, n=763) or without reinfusion of unwashed salvaged blood (control group, n=330), were retrospectively reviewed. The costs of low-vacuum drains, shed blood collection canisters (Bellovac ABT®, Wellspect HealthCare and ConstaVac CBC II®, Stryker), shed blood reinfusion, acquisition and transfusion of allogeneic red cell concentrate, haemoglobin measurements, and prolonged length of hospital stay were used for the blood management cost analysis. Results Patients in the reinfusion group received 152±64 mL of red blood cells from postoperatively salvaged blood, without clinically relevant incidents, and showed a lower allogeneic transfusion rate (24.5% vs 8.5%, for the control and reinfusion groups, respectively; p =0.001). There were no differences in post-operative infection rates. Patients receiving allogeneic transfusions stayed in hospital longer (+1.9 days [95% CI: 1.2 to 2.6]). As reinfusion of unwashed salvaged blood reduced the allogeneic transfusion rate, both reinfusion systems may provide net savings in different cost scenarios (€ 4.6 to € 106/patient for Bellovac ABT, and € −51.9 to € 49.9/patient for ConstaVac CBCII). Discussion Return of unwashed salvaged blood after total knee arthroplasty seems to save costs in patients with pre-operative haemoglobin between 12 and 15 g/dL. It is not cost-saving in patients with a pre-operative haemoglobin >15 g/dL, whereas in those with a pre-operative haemoglobin <12 g/dL, although cost-saving, its efficacy could be

  4. Plasma metabolomics profiling for the prediction of cytomegalovirus DNAemia and analysis of virus–host interaction in allogeneic stem cell transplant recipients.

    PubMed

    Monleón, Daniel; Giménez, Estela; Muñoz-Cobo, Beatriz; Morales, José Manuel; Solano, Carlos; Amat, Paula; Navarro, David

    2015-11-01

    Metabolomics analysis of biofluids is increasingly being recognized as a useful tool for the diagnosis and management of a number of infectious diseases. Here we showed that plasma metabolomics profiling by untargeted 1H nuclear magnetic resonance may allow the anticipation of the occurrence of cytomegalovirus (CMV) DNAemia in allogeneic stem cell transplant. For this purpose, key discriminatory metabolites were total glutathione, taurine, methylamine, trimethylamine N-oxide and lactate, all of which were upregulated in patients eventually developing CMV DNAemia. The overall classification accuracy (predictability) of the projection to latent structure discriminant analysis (PLS-DA) model in cross-validation technical replicates was 73 %. Increased levels of alanine, lactate and total fatty acids, and a shift in the fatty acid profile towards unsaturated species, were observed in patients with detectable CMV DNA in plasma. The classification accuracy of this PLS-DA model in cross-validation technical replicates was 81 %. Plasma metabolomics profiling may prove useful for identifying patients at highest risk for CMV DNAemia thus allowing early inception of antiviral therapy.

  5. Post-transplant monitoring of chimerism by lineage-specific analysis.

    PubMed

    Preuner, Sandra; Lion, Thomas

    2014-01-01

    Molecular surveillance of hematopoietic chimerism is an important part of the routine diagnostic program in patients after allogeneic stem cell transplantation. Chimerism testing permits early prediction and documentation of successful engraftment and facilitates early risk assessment of impending graft rejection. In patients transplanted for treatment of malignant hematologic disorders, monitoring of chimerism can provide an early indication of incipient disease relapse. The investigation of chimerism has therefore become an indispensable tool for the management of patients during the post-transplant period. Increasing use of reduced-intensity conditioning, which is associated with prolonged duration of mixed hematopoietic chimerism, has further increased the clinical importance of chimerism analysis. At present, the most commonly used technical approach to the investigation of chimerism is microsatellite analysis by polymerase chain reaction. The investigation of chimerism within specific leukocyte subsets isolated from peripheral blood or bone marrow samples by flow sorting- or magnetic bead-based techniques provides more specific information on processes underlying the dynamics of donor/recipient chimerism. Moreover, cell subset-specific analysis permits the assessment of impending complications at a significantly higher sensitivity, thus providing a basis for earlier treatment decisions.

  6. Chimerism testing and detection of minimal residual disease after allogeneic hematopoietic transplantation using the bioView (Duet) combined morphological and cytogenetical analysis.

    PubMed

    Shimoni, A; Nagler, A; Kaplinsky, C; Reichart, M; Avigdor, A; Hardan, I; Yeshurun, M; Daniely, M; Zilberstein, Y; Amariglio, N; Brok-Simoni, F; Rechavi, G; Trakhtenbrot, L

    2002-08-01

    Recurrent disease remains a major obstacle to cure after allogeneic transplantation. Various methods have been developed to detect minimal residual disease (MRD) after transplantation to identify patients at risk for relapse. Chimerism tests differentiate recipient and donor cells and are used to identify MRD when there are no other disease-specific markers. The detection of MRD does not always correlate with relapse risk. Chimerism testing may also identify normal hematopoietic cells or other cells not contributing to relapse. In this study we report our initial experience with a novel system that provides combined morphological and cytogenetical analysis on the same cells. This system allows rapid automatic scanning of a large number of cells, thus increasing the sensitivity of detection of small recipient population. The clinical significance of MRD detection is improved by identifying the morphology of recipient cells. Identification of recipient characteristics within blasts predicts overt relapse in leukemia patients and precedes it by a few weeks to months. Identification within mature hematopoietic cells may not be closely associated with relapse. The system also allows chimerism testing after sex-mismatched transplants, within cellular subsets, with no need for sorting of cells. The system merits further study in larger scale trials.

  7. Bidirectional Brush Seals: Post-Test Analysis

    NASA Technical Reports Server (NTRS)

    Hendricks, Robert C.; Wilson, Jack; Wu, Tom Y.; Flower, Ralph; Mullen, Robert L.

    1997-01-01

    A post-test analysis of a set of inside-diameter/outside-diameter (ID/OD) bidirectional brush seals used in three-port wave rotor tests was undertaken to determine brush bristle and configuration wear, pullout, and rotor coating wear. The results suggest that sharp changes in the pressure profiles were not well reflected in bristle tip configuration patterns or wear. Also, positive-to-negative changes in axial pressure gradients appeared to have little effect on the backing plates. Although the brushes had similar porosities, they had very different unpacked arrays. This difference could explain the departure of experimental data from computational fluid dynamics flow predictions for well-packed arrays at higher pressure drops. The rotor wear led to "car-track" scars (upper and lower wear bands) with a whipped surface between the bands. Those bands may have resulted from bristle stiffening at the fence and gap plates during alternate portions of the rotor cycle. Within the bristle response range the wear surface reflected the pressure distribution effect on bristle motion. No sacrificial metallurgical data were taken. The bristles did wear, with correspondingly more wear on the ID brush configurations than on the OD configurations; the complexity in constructing the ID brush was a factor.

  8. Role of Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem-Cell Transplantation in Older Patients With De Novo Myelodysplastic Syndromes: An International Collaborative Decision Analysis

    PubMed Central

    Koreth, John; Pidala, Joseph; Perez, Waleska S.; Deeg, H. Joachim; Garcia-Manero, Guillermo; Malcovati, Luca; Cazzola, Mario; Park, Sophie; Itzykson, Raphael; Ades, Lionel; Fenaux, Pierre; Jadersten, Martin; Hellstrom-Lindberg, Eva; Gale, Robert Peter; Beach, C.L.; Lee, Stephanie J.; Horowitz, Mary M.; Greenberg, Peter L.; Tallman, Martin S.; DiPersio, John F.; Bunjes, Donald; Weisdorf, Daniel J.; Cutler, Corey

    2013-01-01

    Purpose Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that are more common in patients aged ≥ 60 years and are incurable with conventional therapies. Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem-cell transplantation is potentially curative but has additional mortality risk. We evaluated RIC transplantation versus nontransplantation therapies in older patients with MDS stratified by International Prognostic Scoring System (IPSS) risk. Patients and Methods A Markov decision model with quality-of-life utility estimates for different MDS and transplantation states was assessed. Outcomes were life expectancy (LE) and quality-adjusted life expectancy (QALE). A total of 514 patients with de novo MDS aged 60 to 70 years were evaluated. Chronic myelomonocytic leukemia, isolated 5q– syndrome, unclassifiable, and therapy-related MDS were excluded. Transplantation using T-cell depletion or HLA-mismatched or umbilical cord donors was also excluded. RIC transplantation (n = 132) stratified by IPSS risk was compared with best supportive care for patients with nonanemic low/intermediate-1 IPSS (n = 123), hematopoietic growth factors for patients with anemic low/intermediate-1 IPSS (n = 94), and hypomethylating agents for patients with intermediate-2/high IPSS (n = 165). Results For patients with low/intermediate-1 IPSS MDS, RIC transplantation LE was 38 months versus 77 months with nontransplantation approaches. QALE and sensitivity analysis did not favor RIC transplantation across plausible utility estimates. For intermediate-2/high IPSS MDS, RIC transplantation LE was 36 months versus 28 months for nontransplantation therapies. QALE and sensitivity analysis favored RIC transplantation across plausible utility estimates. Conclusion For patients with de novo MDS aged 60 to 70 years, favored treatments vary with IPSS risk. For low/intermediate-1 IPSS, nontransplantation approaches are preferred. For intermediate-2/high IPSS, RIC

  9. Allogeneic Hematopoietic Stem Cell Transplantation after Conditioning Regimens with Fludarabine/melphalan or Fludarabine/busulfan for Patients with Hematological Malignancies: A Single-center Analysis.

    PubMed

    Yamamoto, Wataru; Andou, Taiki; Itabashi, Megumi; Koyama, Satoshi; Ishii, Yoshimi; Numata, Ayumi; Motohashi, Kenji; Hagihara, Maki; Matsumoto, Kenji; Fujisawa, Shin

    2016-01-01

    Objective Fludarabine plus melphalan (FM) and fludarabine plus busulfan (FB) are two major conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods We retrospectively analyzed patients who underwent allo-HSCT after a conditioning regimen consisting of FM or FB with/without total body irradiation for hematological malignancies between 2005 and 2014. Results There were 41 patients who met the criteria. The median follow-up time for the survivors was 3 years. Thirty-two patients received allo-HSCT after the FM regimen and nine patients received allo-HSCT after the FB regimen. Patients who received FB were older than those who received FM (p=0.041). There was no significant difference in the 3-year overall survival between patients who had received FB and those who had received FM (29.6% vs. 56.5%, p=0.267). The 3-year cumulative incidence of relapse was significantly higher in patients who had received FB than that in patients who had received FM (66.7% vs. 17.8%, p=0.004), and FB was an independent prognostic factor for relapse by a multivariate analysis (hazard ratio, 9.8; 95% confidential interval, 2.5-39.3; p=0.001). When we restricted the evaluation to patients with acute myeloid leukemia and myelodysplastic syndrome, the 3-year cumulative incidence of relapse was also significantly higher in patients who had received FB than that in patients who had received FM (75.0% vs. 16.1%, p=0.004). Conclusion The results suggest that FM may provide better disease control than FB.

  10. Functional hyposplenism following allogeneic bone marrow transplantation.

    PubMed Central

    Cuthbert, R J; Iqbal, A; Gates, A; Toghill, P J; Russell, N H

    1995-01-01

    AIMS--To investigate the incidence of functional hyposplenism in a group of patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS--Splenic function was assessed by counting the number of gluteraldehyde fixed red blood cells containing pits or indentations as examined by interference phase microscopy. Normal values are < 2% whereas splenectomy patients have values of 25 to 40%. RESULTS--Twenty eight BMT recipients (17 men, 11 women) were studied at varying periods post-transplant and the results compared with 20 healthy volunteers and 10 patients who had undergone splenectomy or had splenic atrophy because of haematological conditions. Of the 28 BMT recipients, one had undergone a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four patients, one had active extensive chronic graft versus host disease (GvHD) which has been previously reported to be associated with functional hyposplenism following transplantation. Only one of the four patients had peripheral blood red cell changes typical of hyposplenism. CONCLUSION--These results confirm that extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of functional hyposplenism may also occur following BMT in the absence of chronic GvHD and in the absence of haematological features of hyposplenism on routine blood films. This may be of significance in mediating the susceptibility to infection with encapsulating bacteria seen following allogeneic BMT. PMID:7730489

  11. The role of matched sibling donor allogeneic stem cell transplantation in pediatric high-risk acute myeloid leukemia: results from the AML-BFM 98 study

    PubMed Central

    Klusmann, Jan-Henning; Reinhardt, Dirk; Zimmermann, Martin; Kremens, Bernhard; Vormoor, Josef; Dworzak, Michael; Creutzig, Ursula; Klingebiel, Thomas

    2012-01-01

    Background The role of allogeneic stem cell transplantation in post-remission management of children with high-risk acute myeloid leukemia remains controversial. In the multi-center AML-BFM 98 study we prospectively evaluated the impact of allogeneic stem cell transplantation in children with high-risk acute myeloid leukemia in first complete remission. Design and Methods HLA-typed patients with high-risk acute myeloid leukemia, who achieved first complete remission (n=247), were included in this analysis. All patients received double induction and consolidation. Based on the availability of a matched-sibling donor, patients were allocated by genetic chance to allogeneic stem cell transplantation (n=61) or chemotherapy-only (i.e. intensification and maintenance therapy; n=186). The main analysis was done on an intention-to-treat basis according to this allocation. Results Intention-to-treat analysis did not show a significantly different 5-year disease-free survival (49±6% versus 45±4%, Plog rank=0.44) or overall survival (68±6% versus 57±4%, Plog rank=0.17) between the matched-sibling donor and no-matched-sibling donor groups, whereas late adverse effects occurred more frequently after allogeneic stem cell transplantation (72.5% versus 31.8%, PFischer<0.01). These results were confirmed by as-treated analysis corrected for the time until transplantation (5-year overall survival: 72±8% versus 60±4%, PMantel-Byar 0.21). Subgroup analysis demonstrated improved survival rates for patients with 11q23 aberrations allocated to allogeneic stem cell transplantation (5-year overall survival: 94±6% versus 52±7%, Plog-rank=0.01; n=18 versus 49) in contrast to patients without 11q23 aberrations (5-year overall survival: 58±8% versus 55±5%, Plog-rank=0.66). Conclusions Our analyses defined a genetic subgroup of children with high-risk acute myeloid leukemia who benefited from allogeneic stem cell transplantation in the prospective multi-center AML-BFM 98 study. For

  12. Platelet chimerism by polymerase chain reaction (PCR) utilizing variable number of tandem repeats (VNTR) in allogeneic stem cell transplant in children: a new novel approach to full chimerism analysis.

    PubMed

    Chou, P M; Olszewski, M; Huang, W; Silva, M; Kletzel, M

    2003-10-01

    Evaluation of chimerism following allogeneic transplantation has been performed traditionally focusing on two cellular compartments, namely lymphoid and myeloid. However, none has been described so far to evaluate platelet chimerism. In order to achieve full chimerism in all three cellular compartments, we prospectively obtained 138 samples of peripheral blood in 55 patients at different post transplant periods following allogeneic hematopoietic transplantation. Evaluation of chimerism was performed utilizing tests of variable number of tandem repeat (VNTR) and sex determination by quantitative polymerase chain reaction (PCR). Tests for platelet chimerism using platelet-rich plasma were simultaneously analyzed with samples for T-cell lymphoid and myeloid compartments. Complete donor chimerism was noted in 49 of 55 patients (89%), while the remaining six have split chimerism ranging from 34 to 98%. There is significant difference (P=0.0004) between the percentages of donor DNA in all three cellular compartments comparing the means+/-s.e.m. (myeloid 95.60+/-0.9, T-cell lymphocytes 87.6+/-1.9, and the platelets 90.8+/-1.5); however, comparison between the medians is not statistically significant. This study represents an additional step towards achieving full chimerism and the observation may help reduce the number of unnecessary platelet transfusions once chimerism is noted in that cellular compartment.

  13. Nonmyeloablative allogeneic hematopoietic cell transplantation

    PubMed Central

    Storb, Rainer; Sandmaier, Brenda M.

    2016-01-01

    Most hematological malignancies occur in older patients. Until recently these patients and those with comorbidities were not candidates for treatment with allogeneic hematopoietic transplantation because they were unable to tolerate the heretofore used high-dose conditioning regimens. The finding that many of the cures achieved with allogeneic hematopoietic transplantation were due to graft-versus-tumor effects led to the development of less toxic and well-tolerated reduced intensity and nonmyeloablative regimens. These regimens enabled allogeneic engraftment, thereby setting the stage for graft-versus-tumor effects. This review summarizes the encouraging early results seen with the new regimens and discusses the two hurdles that need to be overcome for achieving even greater success, disease relapse and graft-versus-host disease. PMID:27132278

  14. Normalization of red cell enolase level following allogeneic bone marrow transplantation in a child with Diamond-Blackfan anemia.

    PubMed

    Park, Jeong A; Lim, Yeon Jung; Park, Hyeon Jin; Kong, Sun Young; Park, Byung Kiu; Ghim, Thad T

    2010-04-01

    We describe a girl with Diamond-Blackfan anemia with accompanying red cell enolase deficiency. At the age of 9 yr old, the patient received allogeneic bone marrow transplantation from her HLA-identical sister who had normal red cell enolase activity. While the post transplant DNA analysis with short tandem repeat has continuously demonstrated a stable mixed chimerism on follow-up, the patient remains transfusion independent and continues to show a steady increase in red cell enolase activity for over two and a half years following bone marrow transplantation.

  15. Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

    PubMed Central

    Bensinger, William I.

    2007-01-01

    Despite significant improvements in survival for multiple myeloma patients through autologous stem-cell transplantation (SCT) and the introduction of novel drugs, the disease remains incurable for all but a small fraction of patients. Only allogeneic SCT is potentially curative, due in part to a graft-versus-myeloma effect. High transplant-related mortality with allogeneic SCT is currently the major limitation to wider use of this potentially curative modality. Mortality can be reduced through the use of lower-intensity conditioning regimens which allow engraftment of allogeneic stem cells, but this comes at a cost of higher rates of disease progression and relapse. Promising studies to improve outcomes of allogeneic transplants include the use of more intensive non-myeloablative conditioning regimens, tandem transplants, peripheral blood cells, graft engineering to improve the graft-versus-myeloma activity while reducing graft-versus-host disease (GVHD), post-transplant maintenance, and targeted conditioning therapies such as bone-seeking radioisotopes. PMID:18070719

  16. Risk factors for relapse after allogeneic transplantation in acute myeloid leukemia

    PubMed Central

    Ossenkoppele, Gert J.; Janssen, Jeroen J.W.M.; van de Loosdrecht, Arjan A.

    2016-01-01

    Acute myeloid leukemia is a clonal neoplasm derived from myeloid progenitor cells with a varying outcome. The initial goal of treatment is the achievement of complete remission, defined for over 40 years by morphology. However, without additional post-remission treatment the majority of patients relapse. In many cases of acute myeloid leukemia, allogeneic stem cell transplantation offers the best prospects of cure. In 2013, 5608 stem cell transplantations in acute myeloid leukemia were performed in Europe (5228 allogeneic and 380 autologous stem cell transplantations). Most stem cell transplantations are performed in first complete remission. However, despite a considerable reduction in the chance of relapse, in most studies, overall survival benefit of allogeneic stem cell transplantation is modest due to substantial non-relapse mortality. Here we discuss the many factors related to the risk of relapse after allogeneic stem cell transplantation. PMID:26721801

  17. Pre/Post Data Analysis - Simple or Is It?

    NASA Technical Reports Server (NTRS)

    Feiveson, Al; Fiedler, James; Ploutz-Snyder, Robert

    2011-01-01

    This slide presentation reviews some of the problems of data analysis in analyzing pre and post data. Using as an example, ankle extensor strength (AES) experiments, to measure bone density loss during bed rest, the presentation discusses several questions: (1) How should we describe change? (2) Common analysis methods for comparing post to pre results. (3) What do we mean by "% change"? and (4) What are we testing when we compare % changes?

  18. Racial differences in allogeneic hematopoietic cell transplantation outcomes among African Americans and whites.

    PubMed

    Hamilton, B K; Rybicki, L; Sekeres, M; Kalaycio, M; Hanna, R; Sobecks, R; Dean, R; Duong, H; Hill, B T; Bolwell, B; Copelan, E

    2015-06-01

    The impact of race on outcome has been identified in a number of cancers, with African Americans having poorer survival compared with whites. We conducted a study to investigate the association of race with allogeneic hematopoietic cell transplant (HCT) outcomes. We identified 789 patients (58 African Americans and 731 whites) who underwent allogeneic HCT for hematologic disorders. There were no significant differences between African Americans and white patients in gender, performance status or comorbidity score. However, African Americans were younger than whites (median 40 years versus 47 years, P=0.003) and were more likely to be in remission at HCT (74% versus 57%, P=0.011), to have an HLA-mismatched donor (36% versus 14%, P<0.001), to have positive donor or recipient CMV serostatus (90% versus 69%, P<0.001) and to have received a cord blood transplant (21% versus 6%, P<0.001). In univariate analysis, African Americans had worse overall survival (OS) (HR 1.41, P=0.026) compared with whites, with no significant differences in acute or chronic GvHD, non-CMV infection or relapse. However, after adjusting for several transplant and disease-related factors in multivariate analysis, the OS difference between African Americans and whites became nonsignificant (HR 1.27, P=0.18). These results suggest that race in and of itself does not lead to worse survival post HCT.

  19. Production of donor-derived offspring by allogeneic transplantation of spermatogonia in the yellowtail (Seriola quinqueradiata).

    PubMed

    Morita, Tetsuro; Kumakura, Naoki; Morishima, Kagayaki; Mitsuboshi, Toru; Ishida, Masashi; Hara, Takashi; Kudo, Satomi; Miwa, Misako; Ihara, Shoko; Higuchi, Kentaro; Takeuchi, Yutaka; Yoshizaki, Goro

    2012-06-01

    Although the yellowtail (Seriola quinqueradiata) is the fish most commonly farmed in Japan, breeding of this species has not yet started. This is primarily due to the lack of sufficiently sophisticated methods for manipulating gametogenesis, which makes it difficult to collect gametes from specific dams and sires. If it were possible to produce large numbers of surrogate fish by transplanting germ cells isolated from donor individuals harboring desirable genetic traits, then the probability of acquiring gametes carrying the donor-derived haplotype would increase, and breeding programs involving this species might increase as a result. As a first step, we established a method for the allogeneic transplantation of yellowtail spermatogonia and the production of donor-derived offspring. Donor cells were collected from immature (10-month-old) yellowtail males with testes containing abundant type A spermatogonia, labeled with PKH26 fluorescent dye, and transferred into the peritoneal cavities of 8-day-old larvae. Fluorescence observation at 28 days post-transplantation revealed that PKH26-labeled cells were incorporated into recipients' gonads. To assess whether donor-derived spermatogonia could differentiate into functional gametes in the allogeneic recipient gonads, gametes collected from nine male and four female adult recipients were fertilized with wild-type eggs and milt. Analysis of microsatellite DNA markers confirmed that some of the first filial (F(1)) offspring were derived from donor fish, with the average contribution of donor-derived F(1) offspring being 66% and the maximum reaching 99%. These findings confirmed that our method was effective for transplanting yellowtail spermatogonia into allogeneic larvae to produce donor-derived offspring. PMID:22460666

  20. New frontiers in pediatric allogeneic stem cell transplantation

    PubMed Central

    Talano, Julie-An M.; Pulsipher, Michael A.; Symons, Heather J.; Militano, Olga; Shereck, Evan B.; Giller, Roger H.; Hancock, Laura; Morris, Erin; Cairo, Mitchell S.

    2015-01-01

    The inaugural meeting of “New Frontiers in Pediatric Allogeneic Stem Cell Transplantation” organized by the Pediatric Blood and Transplant Consortium (PBMTC) was held at the American Society of Pediatric Hematology and Oncology Annual Meeting. This meeting provided an international platform for physicians and investigators active in the research and utilization of pediatric allogeneic stem cell transplantation (AlloSCT) in children and adolescents with malignant and non-malignant disease, to share information and develop future collaborative strategies. The primary objectives of the conference included: 1) to present advances in AlloSCT in pediatric ALL and novel pre- and post-immunotherapy; 2) to highlight new strategies in alternative allogeneic stem cell donor sources for children and adolescents with non-malignant hematological disorders; 3) to discuss timing of immune reconstitution after AlloSCT and methods of facilitating more rapid recovery of immunity; 4) to identify strategies of utilizing AlloSCT in pediatric myeloproliferative disorders (MPD); 5) to develop diagnostic and therapeutic approaches to hematological complications post pediatric AlloSCT; 6) to enhance the understanding of new novel cellular therapeutic approaches to pediatric malignant and non-malignant hematological disorders; and 7) to discuss optimizing drug therapy in pediatric recipients of AlloSCT. This paper will provide a brief overview of the conference. PMID:24820213

  1. High-throughput allogeneic antibody detection using protein microarrays.

    PubMed

    Paul, Jed; Sahaf, Bita; Perloff, Spenser; Schoenrock, Kelsi; Wu, Fang; Nakasone, Hideki; Coller, John; Miklos, David

    2016-05-01

    Enzyme-linked immunosorbent assays (ELISAs) have traditionally been used to detect alloantibodies in patient plasma samples post hematopoietic cell transplantation (HCT); however, protein microarrays have the potential to be multiplexed, more sensitive, and higher throughput than ELISAs. Here, we describe the development of a novel and sensitive microarray method for detection of allogeneic antibodies against minor histocompatibility antigens encoded on the Y chromosome, called HY antigens. Six microarray surfaces were tested for their ability to bind recombinant protein and peptide HY antigens. Significant allogeneic immune responses were determined in male patients with female donors by considering normal male donor responses as baseline. HY microarray results were also compared with our previous ELISA results. Our overall goal was to maximize antibody detection for both recombinant protein and peptide epitopes. For detection of HY antigens, the Epoxy (Schott) protein microarray surface was both most sensitive and reliable and has become the standard surface in our microarray platform. PMID:26902899

  2. Production of good manufacturing practice-grade cytotoxic T lymphocytes specific for Epstein-Barr virus, cytomegalovirus and adenovirus to prevent or treat viral infections post-allogeneic hematopoietic stem cell transplant.

    PubMed

    Sili, Uluhan; Leen, Ann M; Vera, Juan F; Gee, Adrian P; Huls, Helen; Heslop, Helen E; Bollard, Catherine M; Rooney, Cliona M

    2012-01-01

    Infections with a range of common community viruses remain a major cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation. T cells specific for cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenoviruses can safely prevent and infections with these three most common culprits, but the manufacture of individual T cell lines for each virus would be prohibitive in terms of time and cost. We have demonstrated that T cells specific for all three viruses can be manufactured in a single culture using monocytes and EBV-transformed B lymphoblastoid cell lines (LCLs), both transduced with an adenovirus vector expressing pp65 of CMV, as antigen-presenting cells. Trivirus-specific T cell lines produced from healthy stem cell donors could prevent and treat infections with all three viruses, not only in the designated recipient, but in unrelated, partially-HLA-matched third party recipients. We now provide the details and logistics of T cell manufacture.

  3. Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR.

    PubMed

    Mizutani, M; Hara, M; Fujita, H; Aoki, J; Kanamori, H; Ohashi, K; Usuki, K; Fukuda, T; Chou, T; Tanaka, J; Atsuta, Y; Takami, A

    2016-05-01

    Although allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor (MSD) is a potentially curative post-remission treatment for adults with acute myeloid leukemia (AML) in their first CR, transplant-related morbidity and mortality remains a major drawback. We retrospectively compared the outcomes of patients who underwent autologous peripheral blood stem cell transplantation (auto-PBSCT; n=375) with those who underwent allogeneic bone marrow transplantation (allo-BMT; n=521) and allo-PBSCT (n=380) from MSDs for adults with AML/CR1, in which propensity score models were used to adjust selection biases among patients, primary physicians and institutions to overcome ambiguity in the patients' background information. Both the multivariate analysis and propensity score models indicated that the leukemia-free survival rate of auto-PBSCT was not significantly different from that of allo-BMT (hazard ratio (HR), 1.23; 95% confidence interval (CI), 0.92 to 1.66; P=0.16) and allo-PBSCT (HR, 1.13; 95% CI, 0.85-1.51; P=0.40). The current results suggest that auto-PBSCT remains a promising alternative treatment for patients with AML/CR1 in the absence of an available MSD. PMID:26808566

  4. T-Shaped Frame Critical and Post-Critical Analysis

    NASA Astrophysics Data System (ADS)

    Doicheva, Albena

    2016-03-01

    The paper shows solution of a T-shaped frame, strength- ened with two linear springs, regarding critical and post-critical analysis. The solution is exact using the Euler elastic approach and the frame of reference, originated in the point of column axis inflexion. The derived Numerical results show the effect of the springs strengthening for the crit- ical and the post-critical system behaviour. The influence of the geometry change is analyzed, as well.

  5. Post-Operative Auto-Transfusion in Total Hip or Knee Arthroplasty: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Haien, Zhao; Yong, Jiang; Baoan, Ma; Mingjun, Guo; Qingyu, Fan

    2013-01-01

    Background Total hip or knee arthroplasty is an elective procedure that is usually accompanied by substantial blood loss, which may lead to acute anemia. As a result, almost half of total joint arthroplasty patients receive allogeneic blood transfusions (ABT). Many studies have shown that post-operative auto-transfusion (PAT) significantly reduces the need for ABT, but other studies have questioned the efficacy of this method. Methods The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Checklist S1. To evaluate the efficacy of PAT, we conducted a Cochrane systematic review that combined all available data from randomized controlled trials. Data from the six included trials were pooled for analysis. We then calculated relative risks with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes. Findings and Conclusion To our knowledge, this is the first meta-analysis to compare the clinical results between PAT and a control in joint replacement patients. This meta-analysis has proven that the use of a PAT reinfusion system reduced significantly the demand for ABT, the number of patients who require ABT and the cost of hospitalization after total knee and hip arthroplasty. This study, together with other previously published data, suggests that PAT drains are beneficial. Larger, sufficiently powered studies are necessary to evaluate the presumed reduction in the incidence of infection as well as DVT after joint arthroplasty with the use of PAT. PMID:23372816

  6. Cell salvage for minimising perioperative allogeneic blood transfusion

    PubMed Central

    Carless, Paul A; Henry, David A; Moxey, Annette J; O’Connell, Dianne; Brown, Tamara; Fergusson, Dean A

    2014-01-01

    Background Concerns regarding the safety of transfused blood have prompted reconsideration of the use of allogeneic (from an unrelated donor) red blood cell (RBC) transfusion, and a range of techniques to minimise transfusion requirements. Objectives To examine the evidence for the efficacy of cell salvage in reducing allogeneic blood transfusion and the evidence for any effect on clinical outcomes. Search methods We identified studies by searching CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE (1950 to June 2009), EMBASE (1980 to June 2009), the internet (to August 2009) and bibliographies of published articles. Selection criteria Randomised controlled trials with a concurrent control group in which adult patients, scheduled for non-urgent surgery, were randomised to cell salvage (autotransfusion) or to a control group who did not receive the intervention. Data collection and analysis Data were independently extracted and the risk of bias assessed. Relative risks (RR) and weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Data were pooled using a random-effects model. The primary outcomes were the number of patients exposed to allogeneic red cell transfusion and the amount of blood transfused. Other clinical outcomes are detailed in the review. Main results A total of 75 trials were included. Overall, the use of cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 38% (RR 0.62; 95% CI 0.55 to 0.70). The absolute reduction in risk (ARR) of receiving an allogeneic RBC transfusion was 21% (95% CI 15% to 26%). In orthopaedic procedures the RR of exposure to RBC transfusion was 0.46 (95% CI 0.37 to 0.57) compared to 0.77 (95% CI 0.69 to 0.86) for cardiac procedures. The use of cell salvage resulted in an average saving of 0.68 units of allogeneic RBC per patient (WMD −0.68; 95% CI −0.88 to −0.49). Cell salvage did not appear to impact adversely on clinical outcomes. Authors’ conclusions

  7. Surgical technique for allogeneic uterus transplantation in macaques

    PubMed Central

    Obara, Hideaki; Kisu, Iori; Kato, Yojiro; Yamada, Yohei; Matsubara, Kentaro; Emoto, Katsura; Adachi, Masataka; Matoba, Yusuke; Umene, Kiyoko; Nogami, Yuya; Banno, Kouji; Tsuchiya, Hideaki; Itagaki, Iori; Kawamoto, Ikuo; Nakagawa, Takahiro; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Saiki, Yoko; Sato, Shin-ichi; Nakagawa, Kenshi; Shiina, Takashi; Aoki, Daisuke; Kitagawa, Yuko

    2016-01-01

    No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac artery. Before perfusion, 150 mL of whole blood was obtained from the donor for subsequent blood transfusion to the recipient. Four uterine grafts were orthotopically transplanted to recipients. End-to-side anastomosis was performed to the iliac vessels on one side in case 1 and iliac vessels on both sides in case 2; aorto-aorto/cavo-caval anastomosis was performed in cases 3 and 4. Arterial blood flow of the uterine grafts was determined by intraoperative indocyanine green (ICG) angiography. ICG angiography results showed sufficient blood flow to all uterine grafts, and anaemia did not progress. Under appropriate immune suppression, all recipients survived for more than 90 days post-transplantation, without any surgical complications. We describe a surgical technique for allogeneic UTx in cynomolgus macaques. PMID:27786258

  8. Acute phase serum proteins in syngeneic and allogeneic mouse pregnancy.

    PubMed Central

    Waites, G T; Bell, A M; Bell, S C

    1983-01-01

    The levels of two murine acute phase proteins, serum amyloid P component (SAP) and haptoglobin, have been measured in the serum of C57BL/10 female mice during syngeneic and allogeneic pregnancy. Both syngeneic and allogeneic pregnancy resulted in alterations in the levels of these proteins as compared to those observed in virgin females. Syngeneic mating resulted in an increase in concentration of both proteins during the final 3 days of pregnancy. During allogeneic pregnancy, SAP levels, after a transient increase on day 4, rose from days 6-8 and, after remaining relatively stable, increased from day 12 to reach maximum levels on day 18 of pregnancy. Levels fell dramatically during the immediate post-partum period. In contrast, although levels of haptoglobin also increased from days 6-8, for the remainder of pregnancy these increased levels remained stable. The implications of these findings are discussed in relation to the mechanisms of regulation of acute phase reactants and the immunological relationship between the mother and fetus. PMID:6409477

  9. Probabilistic structural analysis of space propulsion system LOX post

    NASA Technical Reports Server (NTRS)

    Newell, J. F.; Rajagopal, K. R.; Ho, H. W.; Cunniff, J. M.

    1990-01-01

    The probabilistic structural analysis program NESSUS (Numerical Evaluation of Stochastic Structures Under Stress; Cruse et al., 1988) is applied to characterize the dynamic loading and response of the Space Shuttle main engine (SSME) LOX post. The design and operation of the SSME are reviewed; the LOX post structure is described; and particular attention is given to the generation of composite load spectra, the finite-element model of the LOX post, and the steps in the NESSUS structural analysis. The results are presented in extensive tables and graphs, and it is shown that NESSUS correctly predicts the structural effects of changes in the temperature loading. The probabilistic approach also facilitates (1) damage assessments for a given failure model (based on gas temperature, heat-shield gap, and material properties) and (2) correlation of the gas temperature with operational parameters such as engine thrust.

  10. Analysis of the Relevance of Posts in Asynchronous Discussions

    ERIC Educational Resources Information Center

    Azevedo, Breno T.; Reategui, Eliseo; Behar, Patrícia A.

    2014-01-01

    This paper presents ForumMiner, a tool for the automatic analysis of students' posts in asynchronous discussions. ForumMiner uses a text mining system to extract graphs from texts that are given to students as a basis for their discussion. These graphs contain the most relevant terms found in the texts, as well as the relationships between them.…

  11. CHRONIC ALLOGENEIC DISEASE

    PubMed Central

    Armstrong, Martine Y. K.; Gleichmann, Ernst; Gleichmann, Helga; Beldotti, Lorraine; Andre-Schwartz, Janine; Schwartz, Robert S.

    1970-01-01

    The incidence of lymphomas in 371 CAF1 mice injected with BALB/c spleen cells was compared with that in 324 control CAF1 mice. A high incidence of lymphomas was found in the treated mice, but not in the control animals. The development of the neoplasms was a function of the number of parental cells administered. Analyses of the injected mice for the presence of donor cells indicated that the majority of the injected parental cells lost antihost activity, probably within 24 hr of their administration. The tumors were of host origin, as judged by transplantation tests and antigenic analysis of tumor cells. PMID:5523966

  12. A fatal case of acute HHV-6 myocarditis following allogeneic haemopoietic stem cell transplantation.

    PubMed

    Brennan, Yvonne; Gottlieb, David J; Baewer, David; Blyth, Emily

    2015-11-01

    Human herpesvirus 6 (HHV-6) is an ubiquitous virus that can reactivate in immunocompromised hosts, resulting in diverse clinical sequelae. We describe a case of fatal acute HHV-6 myocarditis in a patient who underwent allogeneic haemopoietic stem cell transplantation (HSCT). To our knowledge, this is the first reported case of biopsy proven HHV-6 myocarditis post-HSCT.

  13. Advanced Post-Irradiation Examination Capabilities Alternatives Analysis Report

    SciTech Connect

    Jeff Bryan; Bill Landman; Porter Hill

    2012-12-01

    An alternatives analysis was performed for the Advanced Post-Irradiation Capabilities (APIEC) project in accordance with the U.S. Department of Energy (DOE) Order DOE O 413.3B, “Program and Project Management for the Acquisition of Capital Assets”. The Alternatives Analysis considered six major alternatives: ? No Action ? Modify Existing DOE Facilities – capabilities distributed among multiple locations ? Modify Existing DOE Facilities – capabilities consolidated at a few locations ? Construct New Facility ? Commercial Partnership ? International Partnerships Based on the alternatives analysis documented herein, it is recommended to DOE that the advanced post-irradiation examination capabilities be provided by a new facility constructed at the Materials and Fuels Complex at the Idaho National Laboratory.

  14. Who is fit for allogeneic transplantation?

    PubMed Central

    Sandmaier, Brenda M.

    2010-01-01

    The use of allogeneic hematopoietic cell transplantation (HCT) has expanded progressively, facilitated by the increasing availability of unrelated donors and cord blood, and the inclusion of older patients as transplantation candidates. Indications remain diagnosis-dependent. As novel nontransplantation modalities have been developed concurrently, many patients come to HCT only when no longer responding to such therapy. However, patients with refractory or advanced disease frequently relapse after HCT, even with high-dose conditioning, and more so with reduced-intensity regimens as used for patients of older age or with comorbid conditions. Thus, patients with high-risk malignancies who have substantial comorbidities or are of advanced age are at high risk of both relapse and nonrelapse mortality and should probably not be transplanted. Being in remission or at least having shown responsiveness to pre-HCT therapy is generally associated with increased transplantation success. In addition, to handle the stress associated with HCT, patients need a good social support system and a secure financial net. They must be well informed, not only about the transplantation process, but also about expected or potential post-HCT events, including graft-versus-host disease and delayed effects that may become manifest only years after HCT. PMID:20702782

  15. VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires.

    PubMed

    Shugay, Mikhail; Bagaev, Dmitriy V; Turchaninova, Maria A; Bolotin, Dmitriy A; Britanova, Olga V; Putintseva, Ekaterina V; Pogorelyy, Mikhail V; Nazarov, Vadim I; Zvyagin, Ivan V; Kirgizova, Vitalina I; Kirgizov, Kirill I; Skorobogatova, Elena V; Chudakov, Dmitriy M

    2015-11-01

    Despite the growing number of immune repertoire sequencing studies, the field still lacks software for analysis and comprehension of this high-dimensional data. Here we report VDJtools, a complementary software suite that solves a wide range of T cell receptor (TCR) repertoires post-analysis tasks, provides a detailed tabular output and publication-ready graphics, and is built on top of a flexible API. Using TCR datasets for a large cohort of unrelated healthy donors, twins, and multiple sclerosis patients we demonstrate that VDJtools greatly facilitates the analysis and leads to sound biological conclusions. VDJtools software and documentation are available at https://github.com/mikessh/vdjtools. PMID:26606115

  16. VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires

    PubMed Central

    Bolotin, Dmitriy A.; Britanova, Olga V.; Putintseva, Ekaterina V.; Pogorelyy, Mikhail V.; Nazarov, Vadim I.; Zvyagin, Ivan V.; Kirgizova, Vitalina I.; Kirgizov, Kirill I.; Skorobogatova, Elena V.; Chudakov, Dmitriy M.

    2015-01-01

    Despite the growing number of immune repertoire sequencing studies, the field still lacks software for analysis and comprehension of this high-dimensional data. Here we report VDJtools, a complementary software suite that solves a wide range of T cell receptor (TCR) repertoires post-analysis tasks, provides a detailed tabular output and publication-ready graphics, and is built on top of a flexible API. Using TCR datasets for a large cohort of unrelated healthy donors, twins, and multiple sclerosis patients we demonstrate that VDJtools greatly facilitates the analysis and leads to sound biological conclusions. VDJtools software and documentation are available at https://github.com/mikessh/vdjtools. PMID:26606115

  17. Electron spin resonance analysis of heme-nitrosyl and reduced iron-sulfur centered complexes in allogeneic, heterotopic cardiac transplants: effects of treatment with pyrrolidine dithiocarbamate.

    PubMed

    Nakanishi, A L; Roza, A M; Adams, M B; Seibel, R; Moore-Hilton, G; Kalyanaraman, B; Pieper, G M

    1998-07-15

    Inhibition of inducible nitric oxide synthase (iNOS) prolongs allograft survival suggesting a role for nitric oxide (.NO) in allograft rejection. Induction of iNOS is regulated by the oxidant-sensitive, nuclear factor kappa B (NF-kappaB) in many cell types. In the present study using electron spin resonance (ESR) spectroscopy, we evaluated whether pyrrolidine dithiocarbamate (PDTC), a metal chelator and antioxidant, might limit .NO production during the development of rejection in cardiac allografts. We performed either isogeneic (Lewis to Lewis) or allogeneic (Wistar-Furth to Lewis) heterotopic abdominal cardiac transplantation. Allograft recipients received daily injections of PDTC or aminoguanidine (a known inhibitor of iNOS). At postoperative days 4 or 6, grafted and native hearts of transplant recipients were flushed with cardioplegic solution to remove blood contamination. ESR data of allografts revealed a triplet nitrogen signal (aN=17.5 G) and centered at g=2.012 and an additional broad signal at g=2.08. This signal was not seen in either isografts or native hearts of either isograft or allograft recipients. Based upon these parameters, these signals are attributed to nitrosomyoglobin. This signal was inhibited by treatment with aminoguanidine or PDTC. Under these conditions, PDTC also prolonged graft survival from 6.6+/-0.2 to 11.7+/-0.3 days. Thus, it is conceivable that nitrosylmyoglobin formation precedes rejection in cardiac allografts and inhibition of nitrosomyoglobin with agents such as PDTC contribute to improved graft survival. PMID:9667497

  18. T Cell Receptor Excision Circle (TREC) Monitoring after Allogeneic Stem Cell Transplantation; a Predictive Marker for Complications and Clinical Outcome

    PubMed Central

    Gaballa, Ahmed; Sundin, Mikael; Stikvoort, Arwen; Abumaree, Muhamed; Uzunel, Mehmet; Sairafi, Darius; Uhlin, Michael

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established treatment modality for a variety of malignant diseases as well as for inborn errors of the metabolism or immune system. Regardless of disease origin, good clinical effects are dependent on proper immune reconstitution. T cells are responsible for both the beneficial graft-versus-leukemia (GVL) effect against malignant cells and protection against infections. The immune recovery of T cells relies initially on peripheral expansion of mature cells from the graft and later on the differentiation and maturation from donor-derived hematopoietic stem cells. The formation of new T cells occurs in the thymus and as a byproduct, T cell receptor excision circles (TRECs) are released upon rearrangement of the T cell receptor. Detection of TRECs by PCR is a reliable method for estimating the amount of newly formed T cells in the circulation and, indirectly, for estimating thymic function. Here, we discuss the role of TREC analysis in the prediction of clinical outcome after allogeneic HSCT. Due to the pivotal role of T cell reconstitution we propose that TREC analysis should be included as a key indicator in the post-HSCT follow-up. PMID:27727179

  19. Post-Optimality Analysis In Aerospace Vehicle Design

    NASA Technical Reports Server (NTRS)

    Braun, Robert D.; Kroo, Ilan M.; Gage, Peter J.

    1993-01-01

    This analysis pertains to the applicability of optimal sensitivity information to aerospace vehicle design. An optimal sensitivity (or post-optimality) analysis refers to computations performed once the initial optimization problem is solved. These computations may be used to characterize the design space about the present solution and infer changes in this solution as a result of constraint or parameter variations, without reoptimizing the entire system. The present analysis demonstrates that post-optimality information generated through first-order computations can be used to accurately predict the effect of constraint and parameter perturbations on the optimal solution. This assessment is based on the solution of an aircraft design problem in which the post-optimality estimates are shown to be within a few percent of the true solution over the practical range of constraint and parameter variations. Through solution of a reusable, single-stage-to-orbit, launch vehicle design problem, this optimal sensitivity information is also shown to improve the efficiency of the design process, For a hierarchically decomposed problem, this computational efficiency is realized by estimating the main-problem objective gradient through optimal sep&ivity calculations, By reducing the need for finite differentiation of a re-optimized subproblem, a significant decrease in the number of objective function evaluations required to reach the optimal solution is obtained.

  20. FARO base case post-test analysis by COMETA code

    SciTech Connect

    Annunziato, A.; Addabbo, C.

    1995-09-01

    The paper analyzes the COMETA (Core Melt Thermal-Hydraulic Analysis) post test calculations of FARO Test L-11, the so-called Base Case Test. The FARO Facility, located at JRC Ispra, is used to simulate the consequences of Severe Accidents in Nuclear Power Plants under a variety of conditions. The COMETA Code has a 6 equations two phase flow field and a 3 phases corium field: the jet, the droplets and the fused-debris bed. The analysis shown that the code is able to pick-up all the major phenomena occurring during the fuel-coolant interaction pre-mixing phase.

  1. Cost of post-operative intravenous iron therapy in total lower limb arthroplasty: a retrospective, matched cohort study

    PubMed Central

    Muñoz, Manuel; Gómez-Ramírez, Susana; Martín-Montañez, Elisa; Naveira, Enrique; Seara, Javier; Pavía, José

    2014-01-01

    Background Requirements for allogeneic red cell transfusion after total lower limb arthroplasty are still high (20–50%), and post-operative intravenous iron has been shown to reduce transfusion requirements for this surgery. We performed a cost analysis to ascertain whether this alternative is also likely to be cost-effective. Materials and methods Data from 182 matched-pairs of total lower limb arthroplasty patients, managed with a restrictive transfusion protocol and without (control group) or with post-operative intravenous iron (iron group), were retrospectively reviewed. Acquisition and administration costs of iron (iron sucrose or ferric carboxymaltose) and allogeneic red cell concentrates, haemoglobin measurements, and prolonged stay in hospital were used for blood management cost analysis. Results Patients in the iron group received 600 mg intravenous iron, without clinically relevant incidents, and had a lower allogeneic transfusion rate (11.5% vs 26.4% for the iron and control groups, respectively; p=0.001). The reduction in transfusion rate was more pronounced in anaemic patients (17% vs 40%; p=0.015) than in non-anaemic ones (9.6% vs 21.2%; p=0.011). There were no differences with respect to post-operative infection rate. Patients receiving allogeneic transfusion stayed in hospital longer (+1.9 days [95% CI: 1.2–2.6]). As intravenous iron reduces the allogeneic transfusion rate, both iron formulations were cost-neutral in the different cost scenarios (−25.5 to 62.1 €/patient for iron sucrose, and −51.1 to 64.4 €/patient for ferric carboxymaltose). Discussion In patients presenting with or without pre-operative anaemia, post-operative intravenous iron after total lower limb arthroplasty seems to be safe and is associated with reduced transfusion rates, without incremental costs. For anaemic patients, its efficacy could be increased by associating some other blood-saving method. PMID:24120595

  2. Analysis of cytokine production and V beta T-cell receptor subsets in irradiated recipients receiving portal or peripheral venous reconstitution with allogeneic bone marrow cells, with or without additional anti-cytokine monoclonal antibodies.

    PubMed Central

    Gorczynski, R M; Chen, Z; Zeng, H; Gorczynski, L; Terzioglu, E

    1998-01-01

    Irradiated (800 rads) AKR mice received intravenous (i.v.) reconstitution with a mixture of B10.BR T-depleted bone marrow cells and spleen cells. Only in groups of mice treated additionally with i.v. cyclophosphamide (Cy; 150 mg/kg), 24 hr before transplantation, was long-term (> 60% at 50 days) survival seen. In mice receiving only irradiation all animals died by 30 days post-transplantation. Histological changes consistent with graft-versus-host disease (GVHD) were seen in the liver of reconstituted mice at 30 days, along with an organ-specific increase in V beta 3 T-cell receptor-positive (TCR+) cells. No such increase in V beta 3 TCR+ cells was seen in the spleen from the same mice. These data are consistent with a tissue antigen-driven expansion of V beta 3 TCR+ cells associated with GVHD in the liver in this model. When we analysed cytokine production in vitro from CD3+ cells restimulated with 'host' (AKR) antigen-presenting cells (APC), we found a transition in cytokine production from preferential synthesis of type-1 cytokines [interleukin-2 (IL-2) and interferon-gamma (IFN-gamma)] at early times (day 15) post-reconstitution to increased production of type-2 cytokines [IL-4, transforming growth factor-beta (TGF-beta) and IL-10] at later times (day 30) post-reconstitution in Cy-treated recipients. Animals not receiving Cy did not show this 'switch' in cytokine production at later time points. We have observed a similar polarization in cytokine production, along with increased graft survival, in recipients of vascularized and non-vascularized allografts after portal venous (p.v.), but not i.v., pretransplant donor-specific immunization. We next studied AKR mice receiving 800 rads and subsequently reconstituted with B10.BR stem cells via the p.v. route. Again these mice showed prolonged survival (> 50% at 50 days), with polarization to IL-4, IL-10 and TGF-beta on restimulation of CD3+ cells in vitro at 30 days post-transplant and increased V beta 3 TCR+ cells

  3. Long-term oral complications of allogeneic haematopoietic SCT.

    PubMed

    Hull, K M; Kerridge, I; Schifter, M

    2012-02-01

    This study assessed the incidence of long-term oral complications in 88 survivors of allogeneic haematopoietic cell transplantation (HCT). Patients examined were between 6 months and 6 years post-HCT and aged from 19 to 65 years. Subjects were investigated for both the subjective and objective features of long-term adverse oral effects of HCT. The most common oral symptoms reported were xerostomia (44%, n=39) and reduction in taste (20%, n=18). Only a minority of patients (15%) reported that oral disease had a significant adverse impact upon their quality of life. The majority of patients (53%) had clinical markers of oral chronic GVHD (cGVHD). The most frequently identified feature was salivary hypofunction, with 34% of subjects demonstrating a reduction in stimulated saliva. Oral mucosal changes consistent with cGVHD affected 21% of subjects. Oral cGVHD commonly occurs after allogeneic HCT, often coexists with cutaneous, hepatic or ocular cGVHD and may lead to debilitating symptoms. Transplant type and pre-existing acute GVHD are the major risk factors for oral cGVHD. The identification of risk factors specific for oral cGVHD may allow clinicians some foresight into identifying patients at high risk of developing oral cGVHD and encourage attention to education, regular oral surveillance and rigorous preventative oral health strategies both pre- and post-transplant. PMID:21441960

  4. Financial burden in recipients of allogeneic hematopoietic cell transplantation.

    PubMed

    Khera, Nandita; Chang, Yu-hui; Hashmi, Shahrukh; Slack, James; Beebe, Timothy; Roy, Vivek; Noel, Pierre; Fauble, Veena; Sproat, Lisa; Tilburt, Jon; Leis, Jose F; Mikhael, Joseph

    2014-09-01

    Although allogeneic hematopoietic cell transplantation (HCT) is an expensive treatment for hematological disorders, little is known about the financial consequences for the patients who undergo this procedure. We analyzed factors associated with its financial burden and its impact on health behaviors of allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482 patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo Clinic, to collect information regarding current financial concerns, household income, employment, insurance, out-of-pocket expenses, and health and functional status. A multivariable logistic regression analysis identified factors associated with financial burden and treatment nonadherence. Of the 268 respondents (56% response rate), 73% reported that their sickness had hurt them financially. All patients for whom the insurance information was available (missing, n = 13) were insured. Forty-seven percent of respondents experienced financial burden, such as household income decreased by >50%, selling/mortgaging home, or withdrawing money from retirement accounts. Three percent declared bankruptcy. Younger age and poor current mental and physical functioning increased the likelihood of financial burden. Thirty-five percent of patients reported deleterious health behaviors because of financial constraints. These patients were likely to be younger, have lower education, and with a longer time since HCT. Being employed decreased the likelihood of experiencing financial burden and treatment nonadherence due to concern about costs. A significant proportion of allogeneic HCT survivors experience financial hardship despite insurance coverage. Future research should investigate potential interventions to help at-risk patients and prevent adverse financial outcomes after this life-saving procedure.

  5. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines.

    PubMed

    Styczynski, Jan; van der Velden, Walter; Fox, Christopher P; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per

    2016-07-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged. PMID:27365460

  6. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines.

    PubMed

    Styczynski, Jan; van der Velden, Walter; Fox, Christopher P; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per

    2016-07-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.

  7. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines

    PubMed Central

    Styczynski, Jan; van der Velden, Walter; Fox, Christopher P.; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per

    2016-01-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged. PMID:27365460

  8. Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Adults with Relapsed and Refractory Mantle Cell Lymphoma: A Single Center Analysis in the Rituximab Era

    PubMed Central

    Mussetti, Alberto; Devlin, Sean M.; Castro-Malaspina, Hugo R; Barker, Juliet N.; Giralt, Sergio A.; Zelenetz, Andrew D.

    2015-01-01

    Relapsed and refractory (rel/ref) mantle cell lymphoma (MCL) portends a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only potentially curative therapy in this setting. We analyzed survival outcomes of 29 recipients of non-myeloablative allo-HSCT for rel/ref MCL, and studied possible prognostic factors in this setting. The cumulative incidence of disease progression and non-relapse mortality at 3 years were 28% (95% confidence interval [CI]: 13-46%) and 29% (95%CI: 13-47%), respectively. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) at days +100 and +180 were 34% (95%CI: 18-52%) and 45% (95%CI: 26-62%), respectively. With a median follow-up in survivors of 53 (range 24-83) months, the 3-year overall survival (OS) and progression-free survival (PFS) were 54% (95%CI: 38-76%) and 41% (95%CI: 26-64%), respectively. In vivo T-cell depletion with alemtuzumab (n=6) was associated with inferior 3-year PFS (0% vs. 51%, p=0.007) and OS (17% vs. 64%, p=0.014). Conversely, a second line international prognostic index (sIPI) at transplantation equal to 0 (no risk factors) was associated with an improved 3-year PFS (52% vs. 22%, p=0.020) and OS (71% vs. 22%, p=0.006) compared to sIPI ≥1. Performing an allo-HSCT before 2007 was associated with a decreased 3-year OS (25% vs. 76%, p=0.015) but not with a significantly inferior PFS (17% vs. 59%, p=0.058). In this single center series, we report encouraging results with allo-HSCT for patients with rel/ref MCL. High alemtuzumab doses should probably be avoided in this context. PMID:26146802

  9. Early establishment of hematopoietic chimerism following allogeneic peripheral blood stem cell transplantation in comparison with allogeneic bone marrow transplantation.

    PubMed

    Nakao, S; Zeng, W; Yamazaki, H; Wang, H; Takami, A; Sugimori, N; Miura, Y; Shiobara, S; Matsuda, T; Shinagawa, Y; Harada, M

    1999-04-01

    To characterize the process of the establishment of complete chimerism after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), we determined the origin of leukocytes in peripheral blood (PB) obtained from 23 patients in the very early period after allo-PBSCT using amplification of mini- or microsatellite regions of genomic DNA. Donor-specific alleles were amplified from the PB obtained at day 8 post-transplant for 19 allo-PBSCT patients. Among the 19 patients, 12 showed only donor-specific alleles (complete chimerism) while 7 did both donor and host-specific alleles (mixed chimerism). Although donor specific alleles were amplified in 10 of 12 patients who received allogeneic bone marrow transplantation (allo-BMT) similarly to allo-PBSCT, all of these ten showed mixed chimerism. When the chimeric state was examined in PB samples obtained serially at 2-3-day intervals post-transplant, host-specific alleles in allo-PBSCT patients were not detectable in the PB much earlier than those in allo-BMT patients. These findings indicate that the appearance of donor-derived cells associated with the disappearance of host-derived cells in the circulation occurs earlier after allo-PBSCT as compared with allo-BMT, leading to the rapid establishment of complete chimerism.

  10. Risk factors for vancomycin-resistant enterococcus bacteremia and its influence on survival after allogeneic hematopoietic cell transplantation.

    PubMed

    Tavadze, M; Rybicki, L; Mossad, S; Avery, R; Yurch, M; Pohlman, B; Duong, H; Dean, R; Hill, B; Andresen, S; Hanna, R; Majhail, N; Copelan, E; Bolwell, B; Kalaycio, M; Sobecks, R

    2014-10-01

    Vancomycin-resistant enterococcus (VRE) is a well-known infectious complication among immunocompromised patients. We performed a retrospective analysis to identify risk factors for the development of VRE bacteremia (VRE-B) within 15 months after allogeneic hematopoietic cell transplantation (alloHCT) and to determine its prognostic importance for other post-transplant outcomes. Eight hundred consecutive adult patients who underwent alloHCT for hematologic diseases from 1997 to 2011 were included. Seventy-six (10%) developed VRE-B at a median of 46 days post transplant. Year of transplant, higher HCT comorbidity score, a diagnosis of ALL, unrelated donor and umbilical cord blood donor were all significant risk factors on multivariable analysis for the development of VRE-B. Sixty-seven (88%) died within a median of 1.1 months after VRE-B, but only four (6%) of these deaths were attributable to VRE. VRE-B was significantly associated with worse OS (hazard ratio 4.28, 95% confidence interval 3.23-5.66, P<0.001) in multivariable analysis. We conclude that the incidence of VRE-B after alloHCT has increased over time and is highly associated with mortality, although not usually attributable to VRE infection. Rather than being the cause, this may be a marker for a complicated post-transplant course. Strategies to further enhance immune reconstitution post transplant and strict adherence to infection prevention measures are warranted. PMID:25111516

  11. Pre-transplant achievement of negativity in minimal residual disease and French-American-British L1 morphology predict superior outcome after allogeneic transplant for Philadelphia chromosome positive acute lymphoblastic leukemia: an analysis of Southeast Asian patients.

    PubMed

    Ma, Liyuan; Hao, Siguo; Diong, Colin; Goh, Yeow-Tee; Gopalakrishnan, Sathish; Ho, Aloysius; Hwang, William; Koh, Liang-Piu; Koh, Mickey; Lim, Zi-Yi; Loh, Yvonne; Poon, Michelle; Tan, Lip-Kun; Tan, Patrick; Linn, Yeh-Ching

    2015-05-01

    To better understand predictive factors and improve the clinical outcome of allogeneic transplant for patients with Philadelphia positive acute lymphoblastic leukemia, we analyzed 67 Southeast Asian patients transplanted in our institutions. Multivariate analysis showed that disease status before transplant, year of transplant and, interestingly, French-American-British (FAB) subtype had a significant impact on overall survival (OS) and non-relapse mortality. Patients who were minimal residual disease (MRD) negative at transplant had a 3-year OS of 73% compared to those who were MRD positive (45%) and refractory (0%). The 3-year cumulative incidence of relapse was 18% and 36% for the MRD negative and positive groups, respectively. FAB L1 subtype had a significantly superior 3-year OS of 63% vs. 29% for L2 subtype. Pre-transplant use of a tyrosine kinase inhibitor significantly improved outcomes in univariate but not multivariate analysis, as it served to induce more patients into MRD negativity, which was the factor that directly improved transplant outcome.

  12. Regression analysis exploring teacher impact on student FCI post scores

    NASA Astrophysics Data System (ADS)

    Mahadeo, Jonathan V.; Manthey, Seth R.; Brewe, Eric

    2013-01-01

    High School Modeling Workshops are designed to improve high school physics teachers' understanding of physics and how to teach using the Modeling method. The basic assumption is that the teacher plays a critical role in their students' physics education. This study investigated teacher impacts on students' Force Concept Inventory scores, (FCI), with the hopes of identifying quantitative differences between teachers. This study examined student FCI scores from 18 teachers with at least a year of teaching high school physics. This data was then evaluated using a General Linear Model (GLM), which allowed for a regression equation to be fitted to the data. This regression equation was used to predict student post FCI scores, based on: teacher ID, student pre FCI score, gender, and representation. The results show 12 out of 18 teachers significantly impact their student post FCI scores. The GLM further revealed that of the 12 teachers only five have a positive impact on student post FCI scores. Given these differences among teachers it is our intention to extend our analysis to investigate pedagogical differences between them.

  13. A POST ANALYSIS OF A PREVENTIVE AND CHRONIC HEALTHCARE TOOL.

    PubMed

    Borrayo, Brooke D; O'Lawrence, Henry

    2016-01-01

    This study uses the data set from Kaiser Permanente to examine the post implementation of a preventive and chronic care that utilizes clinical information system, delivery system design, and clinical decision support to maximize the office visit. The analysis suggests a significant positive relationship between frequency of utilization rates to address preventive and chronic care gaps. There is no implication of a significant positive relationship with the successfully captured rate, which satisfies closing the care gap within 45 days. The use of the preventive care tool will assist members in satisfying the preventive care gap, cervical cancer screening, within 45 days of the encounter. PMID:27483973

  14. Patient education in allogeneic hematopoietic cell transplant: what patients wish they had known about quality of life.

    PubMed

    Jim, H S L; Quinn, G P; Gwede, C K; Cases, M G; Barata, A; Cessna, J; Christie, J; Gonzalez, L; Koskan, A; Pidala, J

    2014-02-01

    Quality of life (QOL) is increasingly recognized as an important clinical outcome of hematopoietic cell transplantation (HCT), but patient education is often overlooked. The aim of the current qualitative study was to examine education regarding post-HCT QOL from the patient's perspective. Allogeneic HCT recipients participated in one of four focus groups. Participants were asked to recall what they had been told about post-HCT QOL as they were preparing for transplant, how their QOL differed from what they expected and how to educate future patients about post-HCT QOL. Verbatim transcripts were coded for both a priori and emergent themes using content analysis. A total of 24 patients participated (54% female, mean age 51, range 23-73 years). Participants frequently expressed the desire for additional education regarding post-HCT QOL, particularly late complications. They noted that late complications were often unexpected, had a profound impact on their QOL and threatened their ongoing sense of recovery. They emphasized that the timing, content and format of education regarding QOL should be flexible to meet their diverse needs. Findings from the current study draw attention to the importance of patient education regarding post-HCT QOL as well as additional QOL research designed with patient education in mind.

  15. Patient education in allogeneic hematopoietic cell transplant: What patients wish they had known about quality of life

    PubMed Central

    Jim, Heather S.L.; Quinn, Gwendolyn P.; Gwede, Clement K.; Cases, Mallory G.; Barata, Anna; Cessna, Julie; Christie, Juliette; Gonzalez, Luis; Koskan, Alexis; Pidala, Joseph

    2013-01-01

    Quality of life (QOL) is increasingly recognized as an important clinical outcome of hematopoietic cell transplantation (HCT), but patient education is often overlooked. The goal of the current qualitative study was to examine education regarding post-HCT QOL from the patient’s perspective. Allogeneic HCT recipients participated in one of four focus groups. Participants were asked to recall what they had been told about post-HCT QOL as they were preparing for transplant, how their QOL differed from what they expected, and how to educate future patients about post-HCT QOL. Verbatim transcripts were coded for both a priori and emergent themes using content analysis. A total of 24 patients participated (54% female, mean age 51, range 23-73). Participants frequently expressed the desire for additional education regarding post-HCT QOL, particularly late complications. They noted that late complications were often unexpected, had a profound impact on their QOL, and threatened their ongoing sense of recovery. They emphasized that the timing, content, and format of education regarding QOL should be flexible to meet their diverse needs. Findings from the current study draw attention to the importance of patient education regarding post-HCT QOL as well as additional QOL research designed with patient education in mind. PMID:24121210

  16. Effectiveness of preoperative autologous blood donation for protection against allogeneic blood exposure in adult spinal deformity surgeries: a propensity-matched cohort analysis

    PubMed Central

    Kelly, Michael P.; Zebala, Lukas P.; Kim, Han Jo; Sciubba, Daniel M.; Smith, Justin S.; Shaffrey, Christopher I.; Bess, Shay; Klineberg, Eric; Mundis, Gregory; Burton, Douglas; Hart, Robert; Soroceanu, Alex; Schwab, Frank; Lafage, Virginie

    2015-01-01

    OBJECT The goal of this study was to examine the effectiveness of preoperative autologous blood donation (PABD) in adult spinal deformity (ASD) surgery. METHODS Patients undergoing single-stay ASD reconstructions were identified in a multicenter database. Patients were divided into groups according to PABD (either PABD or NoPABD). Propensity weighting was used to create matched cohorts of PABD and NoPABD patients. Allogeneic (ALLO) exposure, autologous (AUTO) wastage (unused AUTO), and complication rates were compared between groups. RESULTS Four hundred twenty-eight patients were identified as meeting eligibility criteria. Sixty patients were treated with PABD, of whom 50 were matched to 50 patients who were not treated with PABD (NoPABD). Nearly one-third of patients in the PABD group (18/60, 30%) did not receive any autologous transfusion and donated blood was wasted. In 6 of these cases (6/60, 10%), patients received ALLO blood transfusions without AUTO. In 9 cases (9/60, 15%), patients received ALLO and AUTO blood transfusions. Overall rates of transfusion of any type were similar between groups (PABD 70% [42/60], NoPABD 75% [275/368], p = 0.438). Major and minor in-hospital complications were similar between groups (Major PABD 10% [6/60], NoPABD 12% [43/368], p = 0.537; Minor PABD 30% [18/60], NoPABD 24% [87/368], p = 0.499). When controlling for potential confounders, PABD patients were more likely to receive some transfusion (OR 15.1, 95% CI 2.1–106.7). No relationship between PABD and ALLO blood exposure was observed, however, refuting the concept that PABD is protective against ALLO blood exposure. In the matched cohorts, PABD patients were more likely to sustain a major perioperative cardiac complication (PABD 8/50 [16%], NoPABD 1/50 [2%], p = 0.046). No differences in rates of infection or wound-healing complications were observed between cohorts. CONCLUSIONS Preoperative autologous blood donation was associated with a higher probability of

  17. Post mitigation impact risk analysis for asteroid deflection demonstration missions

    NASA Astrophysics Data System (ADS)

    Eggl, Siegfried; Hestroffer, Daniel; Thuillot, William; Bancelin, David; Cano, Juan L.; Cichocki, Filippo

    2015-08-01

    Even though mankind believes to have the capabilities to avert potentially disastrous asteroid impacts, only the realization of mitigation demonstration missions can validate this claim. Such a deflection demonstration attempt has to be cost effective, easy to validate, and safe in the sense that harmless asteroids must not be turned into potentially hazardous objects. Uncertainties in an asteroid's orbital and physical parameters as well as those additionally introduced during a mitigation attempt necessitate an in depth analysis of deflection mission designs in order to dispel planetary safety concerns. We present a post mitigation impact risk analysis of a list of potential kinetic impactor based deflection demonstration missions proposed in the framework of the NEOShield project. Our results confirm that mitigation induced uncertainties have a significant influence on the deflection outcome. Those cannot be neglected in post deflection impact risk studies. We show, furthermore, that deflection missions have to be assessed on an individual basis in order to ensure that asteroids are not inadvertently transported closer to the Earth at a later date. Finally, we present viable targets and mission designs for a kinetic impactor test to be launched between the years 2025 and 2032.

  18. Post-optimality analysis in aerospace vehicle design

    NASA Technical Reports Server (NTRS)

    Braun, Robert D.; Kroo, Ilan M.; Gage, Peter J.

    1993-01-01

    This analysis pertains to the applicability of optimal sensitivity information to aerospace vehicle design. The present analysis demonstrates that post-optimality information generated through first-order computations can be used to accurately predict file effect of constraint and parameter perturbations on the optimal solution. This assessment is based on the solution of an aircraft design problem in which the post-optimality estimates are shown to be within a few percent of the true solution over the practical range of constraint and parameter variations. Through solution of a reusable, single-stage-to-orbit, launch vehicle design problem, this optimal sensitivity information is also shown to improve the efficiency of the design process. For a hierarchically decomposed problem, this computational efficiency is realizable by estimating the main-problem objective gradient through optimal sensitivity calculations. By reducing the need for finite differentiation of a re-optimized subproblem, a significant decrease in the number of objective function evaluations required to reach the optimal solution is obtained.

  19. Multi-Institutional Study of Post-Transplantation Cyclophosphamide As Single-Agent Graft-Versus-Host Disease Prophylaxis After Allogeneic Bone Marrow Transplantation Using Myeloablative Busulfan and Fludarabine Conditioning

    PubMed Central

    Kanakry, Christopher G.; O'Donnell, Paul V.; Furlong, Terry; de Lima, Marcos J.; Wei, Wei; Medeot, Marta; Mielcarek, Marco; Champlin, Richard E.; Jones, Richard J.; Thall, Peter F.; Andersson, Borje S.; Luznik, Leo

    2014-01-01

    Purpose The clinical safety and efficacy of intravenous busulfan and fludarabine (IV Bu/Flu) myeloablative conditioning as well as graft-versus-host disease (GVHD) prophylaxis with high-dose, post-transplantation cyclophosphamide (PTCy) have been demonstrated independently in several single-institutional studies. We hypothesized that combining these two promising approaches in a multi-institutional study of human leukocyte antigen (HLA) -matched bone marrow transplantation would provide low rates of severe acute and chronic GVHD, low toxicity, and effective disease control. Patients and Methods Ninety-two adult patients (median age, 49 years; range, 21 to 65 years) with high-risk hematologic malignancies were enrolled at three centers (clinical trial No. NCT00809276). Forty-five patients received related allografts, and 47 received unrelated allografts. GVHD prophylaxis was solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4. Results The cumulative incidences of grades 2 to 4 acute, grades 3 to 4 acute, and chronic GVHD were 51%, 15%, and 14%, respectively. Nonrelapse mortality (NRM) at 100 days and 1 year were 9% and 16%, respectively. With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P = .0005; OS, P = .019). Conclusion This multi-institutional study demonstrates that PTCy can be safely and effectively combined with IV Bu/Flu myeloablative conditioning and confirms PTCy's efficacy as single-agent, short-course GVHD prophylaxis for both acute and chronic GVHD after bone marrow transplantation from HLA-matched donors. PMID:25267759

  20. Increasing chimerism after allogeneic stem cell transplantation is associated with longer survival time.

    PubMed

    Tang, Xiaowen; Alatrash, Gheath; Ning, Jing; Jakher, Haroon; Stafford, Patricia; Zope, Madhushree; Shpall, Elizabeth J; Jones, Roy B; Champlin, Richard E; Thall, Peter F; Andersson, Borje S

    2014-08-01

    Donor chimerism after allogeneic stem cell transplantation (allo-SCT) is commonly used to predict overall survival (OS) and disease-free survival (DFS). Because chimerism is observed at 1 or more times after allo-SCT and not at baseline, if chimerism is in fact associated with OS or DFS, then the occurrence of either disease progression or death informatively censors (terminates) the observed chimerism process. This violates the assumptions underlying standard statistical regression methods for survival analysis, which may lead to biased conclusions. To assess the association between the longitudinal post-allo-SCT donor chimerism process and OS or DFS, we analyzed data from 195 patients with acute myelogenous leukemia (n = 157) or myelodysplastic syndrome (n = 38) who achieved complete remission after allo-SCT following a reduced-toxicity conditioning regimen of fludarabine/intravenous busulfan. Median follow-up was 31 months (range, 1.1 to 105 months). Fitted joint longitudinal-survival time models showed that a binary indicator of complete (100%) donor chimerism and increasing percent of donor T cells were significantly associated with longer OS, whereas decreasing percent of donor T cells was highly significantly associated with shorter OS. Our analyses illustrate the usefulness of modeling repeated post-allo-SCT chimerism measurements as individual longitudinal processes jointly with OS and DFS to estimate their relationships.

  1. Minimal residual disease monitoring and preemptive immunotherapy in myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Mo, Xiao-Dong; Qin, Ya-Zhen; Zhang, Xiao-Hui; Xu, Lan-Ping; Wang, Yu; Yan, Chen-Hua; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-08-01

    This study investigated the efficacy of minimal residual disease (MRD) monitoring and MRD-directed preemptive immunotherapy in high-risk myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT). MRD assessment consisted of Wilms' tumor gene 1 (WT1) detection with PCR and leukemia-associated immunophenotypic pattern examination with multiparameter flow cytometry (FCM). Post-HSCT, 31 patients were positive for WT1, and 8, for FCM; positivity for WT1 (18.6 vs. 6.1 %, P = 0.040) or FCM (62.5 vs. 3.6 %, P < 0.001) indicated a higher 2-year relapse rate. Twenty-one patients met our combined criteria for MRD, and the presence of MRD was associated with a higher 2-year relapse rate (27.3 vs. 4.5 %, P = 0.003). Preferentially expressed antigen of melanoma (PRAME) expression alone was not an appropriate MRD marker; however, it suggested that the MRD-positive patients may fail to respond to preemptive immunotherapy. In patients positive for both PRAME and MRD, the relapse rate was 60 % despite preemptive immunotherapy. Multivariate analysis confirmed the association between the increased relapse rate and positivity for both PRAME and MRD (hazard ratio = 42.8, P = 0.001). MRD monitoring predicted relapse in high-risk MDS post-HSCT patients, and PRAME- and MRD-positive patients did not benefit from preemptive immunotherapy.

  2. Allogeneic T cell responses are regulated by a specific miRNA-mRNA network

    PubMed Central

    Sun, Yaping; Tawara, Isao; Zhao, Meng; Qin, Zhaohui S.; Toubai, Tomomi; Mathewson, Nathan; Tamaki, Hiroya; Nieves, Evelyn; Chinnaiyan, Arul M.; Reddy, Pavan

    2013-01-01

    Donor T cells that respond to host alloantigens following allogeneic bone marrow transplantation (BMT) induce graft-versus-host (GVH) responses, but their molecular landscape is not well understood. MicroRNAs (miRNAs) regulate gene (mRNA) expression and fine-tune the molecular responses of T cells. We stimulated naive T cells with either allogeneic or nonspecific stimuli and used argonaute cross-linked immunoprecipitation (CLIP) with subsequent ChIP microarray analyses to profile miR responses and their direct mRNA targets. We identified a unique expression pattern of miRs and mRNAs following the allostimulation of T cells and a high correlation between the expression of the identified miRs and a reduction of their mRNA targets. miRs and mRNAs that were predicted to be differentially regulated in allogeneic T cells compared with nonspecifically stimulated T cells were validated in vitro. These analyses identified wings apart-like homolog (Wapal) and synaptojanin 1 (Synj1) as potential regulators of allogeneic T cell responses. The expression of these molecular targets in vivo was confirmed in MHC-mismatched experimental BMT. Targeted silencing of either Wapal or Synj1 prevented the development of GVH response, confirming a role for these regulators in allogeneic T cell responses. Thus, this genome-wide analysis of miRNA-mRNA interactions identifies previously unrecognized molecular regulators of T cell responses. PMID:24216511

  3. Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: which way to go?

    PubMed

    Mamidi, Murali Krishna; Dutta, Susmita; Bhonde, Ramesh; Das, Anjan Kumar; Pal, Rajarshi

    2014-12-01

    Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue.

  4. Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits.

    PubMed

    Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

    2016-01-01

    Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

  5. Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits

    PubMed Central

    Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

    2016-01-01

    Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo. PMID:26915044

  6. [Single nucleotide polymorphism and its application in allogeneic hematopoietic stem cell transplantation--review].

    PubMed

    Li, Su-Xia

    2004-12-01

    Single nucleotide polymorphism (SNP) is the third genetic marker after restriction fragment length polymorphism (RFLP) and short tandem repeat. It represents the most density genetic variability in the human genome and has been widely used in gene location, cloning, and research of heredity variation, as well as parenthood identification in forensic medicine. As steady heredity polymorphism, single nucleotide polymorphism is becoming the focus of attention in monitoring chimerism and minimal residual disease in the patients after allogeneic hematopoietic stem cell transplantation. The article reviews SNP heredity characterization, analysis techniques and its applications in allogeneic stem cell transplantation and other fields.

  7. The Inflammatory Cytokine IL-21 is Expressed by Splenic Neutrophils in Response to Transplantation of Allogeneic Cells

    PubMed Central

    Thompson, John S.; Hardin, Debra L.; Glass, Judy F.; Dziba, Joshua; Campion, Jeffrey; Brown, Stephen A.

    2016-01-01

    We have previously reported that GR-1 neutrophil/monocytes rose dramatically in the spleen, peaked by day 7 and declined through day 14. This period corresponded to the peak of acute Graft-Versus-Host Disease (aGVHD) in BALB/c mice transplanted with allogeneic donor cells. We now asked: what cytokines did these splenic neutrophil/monocytes express on day 7 and 14 post transplant? BALB/c mice were transplanted with allogeneic B6 or syngeneic BALB/c donor cells. Long term survival was recorded through day 31. Other groups were sacrificed on days 3, 5, 7, 14, 21 and 31 days post transplant to record the total number of cells in the spleens and their phenotypes. Neutrophils were isolated from the spleens of mice transplanted with B6 and BALB/c cells on days 7 and 14. Daily body weight demonstrated a transient drop in the syngeneic transplants on day 2 but a much greater drop with its nadir at day 7 and never fully recovering through 31 days. CD8/CD4 T lymphocytes peaked in the spleen on day 5 and were followed on day 7 by GR-I cells in all of the allogeneic transplants. In syngeneic transplants this early rise in lymphocytes did not occur and GR-1 cells peaked on day 14. Highly purified neutrophils were isolated in two separate experiments from the spleens on days 7 and 14 post transplant. In both experiments day 7 allogeneic neutrophils expressed significantly elevated levels of Interleukin-21 (IL-21) mRNA whereas the day 7 and 14 syngeneic cells expressed lower but significant levels of TNFα. Intracellular IL-21 was demonstrated in the allogeneic neutrophils on day 7 before and after in vitro stimulation. In conclusion Purified neutrophils isolated from the spleen on day 7, the early peak of allogeneic transplantation a GVHD, express high levels of IL-21 message and intracellular IL-21. PMID:27774526

  8. Cost analysis of post-polio certification immunization policies.

    PubMed Central

    Sangrujee, Nalinee; Cáceres, Victor M.; Cochi, Stephen L.

    2004-01-01

    OBJECTIVE: An analysis was conducted to estimate the costs of different potential post-polio certification immunization policies currently under consideration, with the objective of providing this information to policy-makers. METHODS: We analyzed three global policy options: continued use of oral poliovirus vaccine (OPV); OPV cessation with optional inactivated poliovirus vaccine (IPV); and OPV cessation with universal IPV. Assumptions were made on future immunization policy decisions taken by low-, middle-, and high-income countries. We estimated the financial costs of each immunization policy, the number of vaccine-associated paralytic poliomyelitis (VAPP) cases, and the global costs of maintaining an outbreak response capacity. The financial costs of each immunization policy were based on estimates of the cost of polio vaccine, its administration, and coverage projections. The costs of maintaining outbreak response capacity include those associated with developing and maintaining a vaccine stockpile in addition to laboratory and epidemiological surveillance. We used the period 2005-20 as the time frame for the analysis. FINDINGS: OPV cessation with optional IPV, at an estimated cost of US$ 20,412 million, was the least costly option. The global cost of outbreak response capacity was estimated to be US$ 1320 million during 2005-20. The policy option continued use of OPV resulted in the highest number of VAPP cases. OPV cessation with universal IPV had the highest financial costs, but it also had the least number of VAPP cases. Sensitivity analyses showed that global costs were sensitive to assumptions on the cost of the vaccine. Analysis also showed that if the price per dose of IPV was reduced to US$ 0.50 for low-income countries, the cost of OPV cessation with universal IPV would be the same as the costs of continued use of OPV. CONCLUSION: Projections on the vaccine price per dose and future coverage rates were major drivers of the global costs of post

  9. Emoting infertility online: A qualitative analysis of men's forum posts.

    PubMed

    Hanna, Esmée; Gough, Brendan

    2016-07-01

    Relatively little research on infertility focuses exclusively or significantly on men's experiences, particularly in relation to emotional aspects. Evidence that does exist around male infertility suggests that it is a distressing experience for men, due to stigma, threats to masculinity and the perceived need to suppress emotions, and that men and women experience infertility differently. Using thematic analysis, this article examines the online emoting of men in relation to infertility via forum posts from a men-only infertility discussion board. It was noted that men 'talked' to each other about the emotional burdens of infertility, personal coping strategies and relationships with others. Three major themes were identified following in-depth analysis: 'the emotional rollercoaster', 'the tyranny of infertility' and 'infertility paranoia'. This article then offers insights into how men experience infertility emotionally, negotiate the emotional challenges involved (especially pertaining to diagnosis, treatment outcomes and their intimate relationships) and how they share (and find value in doing so) with other men the lived experience of infertility. PMID:27246813

  10. SHEFEX II Flight Instrumentation And Preparation Of Post Flight Analysis

    NASA Astrophysics Data System (ADS)

    Thiele, Thomas; Siebe, Frank; Gulhan, Ali

    2011-05-01

    A main disadvantage of modern TPS systems for re- entry vehicles is the expensive manufacturing and maintenance process due to the complex geometry of these blunt nose configurations. To reduce the costs and to improve the aerodynamic performance the German Aerospace Center (DLR) is following a different approach using TPS structures consisting of flat ceramic tiles. To test these new sharp edged TPS structures the SHEFEX I flight experiment was designed and successfully performed by DLR in 2005. To further improve the reliability of the sharp edged TPS design at even higher Mach numbers, a second flight experiment SHEFEX II will be performed in September 2011. In comparison to SHEFEX I the second flight experiment has a fully symmetrical shape and will reach a maximum Mach number of about 11. Furthermore the vehicle has an active steering system using four canards to control the flight attitude during re-entry, e.g. roll angle, angle of attack and sideslip. After a successful flight the evaluation of the flight data will be performed using a combination of numerical and experimental tools. The data will be used for the improvement of the present numerical analysis tools and to get a better understanding of the aerothermal behaviour of sharp TPS structures. This paper presents the flight instrumentation of the SHEFEX II TPS. In addition the concept of the post flight analysis is presented.

  11. Effect of immune modulation in relapsed peripheral T-cell lymphomas after post-allogeneic stem cell transplantation: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

    PubMed

    Mamez, A C; Lévy, V; Chevallier, P; Blaise, D; Vigouroux, S; Xhaard, A; Fegueux, N; Contentin, N; Beguin, Y; Ifrah, N; Bulabois, C E; Suarez, F; Yakoub-Agha, I; Turlure, P; Deconink, E; Lamy, T; Cahn, J Y; Huynh, A; Maury, S; Fornecker, L M; Ouzegdouh, M; Bay, J O; Guillerm, G; Maillard, N; Michallet, M; Malfuson, J V; Bourhis, J H; Rialland, F; Oumedaly, R; Jubert, C; Leblond, V; Boubaya, M; Mohty, M; Nguyen, S

    2016-03-01

    Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell lymphoma who relapsed after allogeneic transplant in 27 SFGM-TC centers. Relapse occurred after a median of 2.8 months. Patients were then treated with non-immunologic strategies (chemotherapy, radiotherapy) and/or immune modulation (donor lymphocyte infusions (DLI) and/or discontinuation of immunosuppressive therapy). Median overall survival (OS) after relapse was 6.1 months (DLI group: 23.6 months, non-DLI group: 3.6 months). Among the 14 patients who received DLI, 9 responded and 2 had stable disease. Among the remaining 49 patients, a complete response accompanied by extensive chronic GvHD was achieved in two patients after tapering of immunosuppressive drugs. Thirty patients received radio-chemotherapy, with an overall response rate of 50%. In multivariate analysis, chronic GvHD (odds ratio: 11.25 (2.68-48.21), P=0.0009) and skin relapse (odds ratio: 4.15 (1.04-16.50), P=0.043) were associated with a better response to treatment at relapse. In a time-dependent analysis, the only factor predictive of OS was the time from transplantation to relapse (hazards ratio: 0.33 (0.17-0.640), P=0.0009). This large series provides encouraging evidence of a true GvL effect in this disease. PMID:26595076

  12. The potential benefit of allogeneic over autologous transplantation in patients with very early relapsed and refractory follicular lymphoma with prior remission duration of ≤12 months.

    PubMed

    Lunning, Matthew A; Migliacci, Jocelyn C; Hilden, Patrick; Devlin, Sean M; Castro-Malaspina, Hugo; Giralt, Sergio; Perales, Miguel-Angel; Zelenetz, Andrew D; Moskowitz, Craig H; Sauter, Craig S

    2016-04-01

    Early relapsed or refractory follicular lymphoma (FL) warrants consolidation with transplantation, though graft source modality remains controversial. We analysed the outcomes of 44 patients transplanted with either autologous or allogeneic graft sources in the post-rituximab era. No difference in event-free (EFS) or overall survival (OS) was observed between allogeneic (81% and 81%) and autologous transplantation (64% and 70%) at 3 years. There was a significant difference in EFS between allogeneic and autologous transplantation patients with previous remission duration of ≤12 months (80% and 42% at 3 years, P < 0·015). Very early relapsed FL may warrant consideration of allogeneic over autologous transplantation in the appropriate setting.

  13. Analysis of heat generation using ultrasonic vibration for post removal.

    PubMed

    Dominici, John T; Clark, Stephen; Scheetz, James; Eleazer, Paul D

    2005-04-01

    This study measured the temperature of the root surface and post during the application of ultrasonic vibration to cemented posts to simulate post removal procedure. Root canal therapy was performed on ten extracted maxillary incisors. A stainless steel Parapost was cemented into each prepared post space. Ultrasonic vibration was applied to the post and temperatures were recorded at the coronal post and the cervical root surface. Data were analyzed with ANOVA using the independent variables of (a) time of ultrasonic application (15, 30, 45 and 60 s) and 2) location (post and root surface). Greater temperature increase was observed at the post (52.6 degrees C, SD 11.1; 82.6 degrees C, SD 20.1; 111.0 degrees C, SD 29.1; 125.3 degrees C, SD 33.2) compared to the root surface (9.5 degrees C, SD 4.6; 17.5 degrees C, SD 4.8; 25.4 degrees C, SD 7.3; 32.2 degrees C, SD 8.1) for each time period, P < 0.001. Ultrasonic application to the post for longer than 15 s generates high temperature on the root surface.

  14. Autologous is Superior to Allogeneic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukemia in Second Complete Remission

    PubMed Central

    Chakrabarty, Jennifer L. Holter; Rubinger, Morel; Le-Rademacher, Jennifer; Wang, Hai-Lin; Grigg, Andrew; Selby, George B.; Szer, Jeffrey; Rowe, Jacob M.; Weisdorf, Daniel J.; Tallman, Martin S.

    2014-01-01

    PURPOSE To identify favored choice of transplantation in patients with acute promyelocytic leukemia in second complete remission. PATIENTS We studied 294 acute promyelocytic leukemia (APL) patients receiving allogeneic (n=232) or autologous (62) hematopoietic cell transplantation (HCT) in second complete remission (CR2) reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR) from 1995 to 2006 including pre-HCT PML/RAR∝ status in 155 (49% of allogeneic and 66% of autologous). METHODS Patient characteristics and transplant characteristics including treatment related mortality, overall survival, and disease free survival were collected and analyzed for both univariate and multivariate outcomes. RESULTS With median follow-up of 115 (allogeneic) and 72 months (autologous), 5-year disease-free survival (DFS) favored autologous 63% (49-75%) compared to allogeneic 50% (44-57%) (p=0.10) and overall survival (OS) 75% (63-85%) vs. 54% (48-61%) (p=.002) Multivariate analysis showed significantly worse DFS after allogeneic HCT (HR=1.88, 95% CI=1.16-3.06, p=0.011) and age >40 years (HR=2.30, 95% CI 1.44-3.67, p=0.0005). OS was significantly worse after allogeneic HCT (HR=2.66, 95%CI 1.52-4.65, p=0.0006; age >40 (HR=3.29, 95% CI 1.95-5.54, p<0.001) and CR1<12 months (HR=1.56 95% CI 1.07-2.26, p=0.021). Positive pre-HCT PML-RAR∝ status in 17/114 allogeneic and 6/41 autologous transplants did not influence relapse, treatment failure or survival in either group. The survival advantage for autografting was attributable to increased 3 years TRM: allogeneic 30%; autologous 2%, and GVHD. CONCLUSION We conclude that autologous HCT yields superior overall survival for APL in CR2. Long term DFS in autologous recipients, even with MRD+ grafts remains an important subject for further study. PMID:24691221

  15. Finite element analysis and fracture resistance testing of a new intraradicular post

    PubMed Central

    YAMAMOTO, Eron Toshio Colauto; PAGANI, Clovis; da SILVA, Eduardo Galera; NORITOMI, Pedro Yoshito; UEHARA, André Yugou; KEMMOKU, Daniel Takanori

    2012-01-01

    Objectives The objective of the present study was to evaluate a prefabricated intraradicular threaded pure titanium post, designed and developed at the São José dos Campos School of Dentistry - UNESP, Brazil. This new post was designed to minimize stresses observed with prefabricated post systems and to improve cost-benefits. Material and methods Fracture resistance testing of the post/core/root complex, fracture analysis by microscopy and stress analysis by the finite element method were used for post evaluation. The following four prefabricated metal post systems were analyzed: group 1, experimental post; group 2, modification of the experimental post; group 3, Flexi Post, and group 4, Para Post. For the analysis of fracture resistance, 40 bovine teeth were randomly assigned to the four groups (n=10) and used for the fabrication of test specimens simulating the situation in the mouth. The test specimens were subjected to compressive strength testing until fracture in an EMIC universal testing machine. After fracture of the test specimens, their roots were sectioned and analyzed by microscopy. For the finite element method, specimens of the fracture resistance test were simulated by computer modeling to determine the stress distribution pattern in the post systems studied. Results The fracture test presented the following averages and standard deviation: G1 (45.63±8.77), G2 (49.98±7.08), G3 (43.84±5.52), G4 (47.61±7.23). Stress was homogenously distributed along the body of the intraradicular post in group 1, whereas high stress concentrations in certain regions were observed in the other groups. These stress concentrations in the body of the post induced the same stress concentration in root dentin. Conclusions The experimental post (original and modified versions) presented similar fracture resistance and better results in the stress analysis when compared with the commercial post systems tested (08/2008-PA/CEP). PMID:23032204

  16. WPSS is a strong prognostic indicator for clinical outcome of allogeneic transplant for myelodysplastic syndrome in Southeast Asian patients.

    PubMed

    Ma, Liyuan; Hao, Siguo; Diong, Colin; Goh, Yeow-Tee; Gopalakrishnan, Sathish; Ho, Aloysius; Hwang, William; Koh, Liang-Piu; Koh, Mickey; Lim, Zi-Yi; Loh, Yvonne; Poon, Michelle; Tan, Lip-Kun; Tan, Patrick; Linn, Yeh-Ching

    2015-05-01

    To better understand the predictive factors and improve clinical outcome of allogeneic transplant for patients with myelodysplastic syndrome (MDS), we retrospectively analyzed the post-transplant outcome of 60 Southeast Asian patients with MDS. Multivariate analysis showed that WHO classification-based Prognostic Scoring System (WPSS) significantly affect overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), and cumulative incidence of non-relapse mortality (CINRM). Stratified by WPSS into very low/low, intermediate, high, and very high-risk categories, 3-year OS was 100, 61, 37, and 18% (p = 0.02); PFS was 100, 55, 32, and 18% (p = 0.014); CIR was 12, 24, 38, and 59% (p = 0.024); CINRM was 0, 6, 12, and 26% (p = 0.037), respectively. WHO classification, Revised International Prognostic Scoring System (IPSS-R), IPSS-R-defined cytogenetic risk groups, donor gender, and acute and chronic graft vs host disease (GVHD) also influenced different aspects of transplant outcome. We found that WPSS is a powerful predictor of post-transplant outcome. WPSS provides an important model not only for prognostication but also for exploration of further post-transplant measures such as immunological maneuvers or novel therapy to improve the poor outcome of high-risk patients.

  17. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    PubMed Central

    Muscogiuri, Giovanna; Palomba, Stefano; Serio, Bianca; Sessa, Mariarosaria; Giudice, Valentina; Ferrara, Idalucia; Tauchmanovà, Libuse; Colao, Annamaria; Selleri, Carmine

    2014-01-01

    Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT. PMID:24883377

  18. Endocrinopathies after allogeneic and autologous transplantation of hematopoietic stem cells.

    PubMed

    Orio, Francesco; Muscogiuri, Giovanna; Palomba, Stefano; Serio, Bianca; Sessa, Mariarosaria; Giudice, Valentina; Ferrara, Idalucia; Tauchmanovà, Libuse; Colao, Annamaria; Selleri, Carmine

    2014-01-01

    Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90-99% of women and 60-90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40-50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT. PMID:24883377

  19. Optimal timing of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome

    PubMed Central

    Alessandrino, Emilio Paolo; Porta, Matteo G Della; Malcovati, Luca; Jackson, Christopher H; Pascutto, Cristiana; Bacigalupo, Andrea; Teresa van Lint, Maria; Falda, Michele; Bernardi, Massimo; Onida, Francesco; Guidi, Stefano; Iori, Anna Paola; Cerretti, Raffaella; Marenco, Paola; Pioltelli, Pietro; Angelucci, Emanuele; Oneto, Rosi; Ripamonti, Francesco; Rambaldi, Alessandro; Bosi, Alberto; Cazzola, Mario

    2013-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Registry studies have shown that advanced disease stage at transplantation is associated with inferior overall survival. To define the optimal timing of allogeneic HSCT, we carried out a decision analysis by studying 660 patients who received best supportive care and 449 subjects who underwent transplantation. Risk assessment was based on both the International Prognostic Scoring System (IPSS) and the World Health Organization classification-based Prognostic Scoring System (WPSS). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of allogeneic HSCT on survival. This model estimated life expectancy from diagnosis according to treatment policy at different risk stages. Relative to supportive care, estimated life expectancy increased when transplantation was delayed from the initial stages until progression to intermediate-1 IPSS-risk or to intermediate WPSS-risk stage, and then decreased for higher risks. Modeling decision analysis on WPSS versus IPSS allowed better estimation of the optimal timing of transplantation. These observations indicate that allogeneic HSCT offers optimal survival benefits when the procedure is performed before MDS patients progress to advanced disease stages. Am. J. Hematol. 88:581–588, 2013. © 2013 Wiley Periodicals, Inc. PMID:23606215

  20. Timed Sequential Busulfan and Post Transplant Cyclophosphamide for Allogeneic Transplantation

    ClinicalTrials.gov

    2016-09-08

    Other Diseases of Blood and Blood-forming Organs; Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Myelodysplastic Syndrome; Myeloproliferative Syndrome; Non-Hodgkins Lymphoma; Hodgkins Lymphoma; Multiple Myeloma

  1. Diffuse gastrointestinal bleeding and BK polyomavirus replication in a pediatric allogeneic haematopoietic stem cell transplant patient.

    PubMed

    Koskenvuo, M; Lautenschlager, I; Kardas, P; Auvinen, E; Mannonen, L; Huttunen, P; Taskinen, M; Vettenranta, K; Hirsch, H H

    2015-01-01

    Patients undergoing haematopoietic stem cell transplantation (HSCT) are at high risk of severe gastrointestinal bleeding caused by infections, graft versus host disease, and disturbances in haemostasis. BK polyomavirus (BKPyV) is known to cause hemorrhagic cystitis, but there is also evidence of BKV shedding in stool and its association with gastrointestinal disease. We report putative association of BKPyV replication with high plasma viral loads in a pediatric HSCT patient developing hemorrhagic cystitis and severe gastrointestinal bleeding necessitating intensive care. The observation was based on chart review and analysis of BKPyV DNA loads in plasma and urine as well as retrospective BKPyV-specific IgM and IgG measurements in weekly samples until three months post-transplant. The gastrointestinal bleeding was observed after a >100-fold increase in the plasma BKPyV loads and the start of hemorrhagic cystitis. The BKPyV-specific antibody response indicated past infection prior to transplantation, but increasing IgG titers were seen following BKPyV replication. The gastrointestinal biopsies were taken at a late stage of the episode and were no longer informative of BK polyomavirus involvement. In conclusion, gastrointestinal complications with bleeding are a significant problem after allogeneic HSCT to which viral infections including BKPyV may contribute. PMID:25542476

  2. Primary Graft Failure after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

    PubMed Central

    Olsson, Richard F.; Logan, Brent R.; Chaudhury, Sonali; Zhu, Xiaochun; Akpek, Görgün; Bolwell, Brian J.; Bredeson, Christopher N.; Dvorak, Christopher C.; Gupta, Vikas; Ho, Vincent T.; Lazarus, Hillard M.; Marks, David I.; Ringdén, Olle T.H.; Pasquini, Marcelo C.; Schriber, Jeffrey R.; Cooke, Kenneth R.

    2015-01-01

    Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs. 7.3%; P<0.001). A 4-fold increase of PGF was observed in myeloproliferative disorders compared to acute leukemia (P<0.001). Other risk factors for PGF included recipient age below 30, HLA-mismatch, male recipients of female donor grafts, ABO-incompatibility, busulfan/cyclophosphamide conditioning, and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 108/kg were associated with PGF (OR 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post-transplant may provide the rationale for an early request for additional hematopoietic stem cells. PMID:25772027

  3. An Analysis of Access Barriers to Post-Secondary Education

    ERIC Educational Resources Information Center

    Vaccaro, Angelo

    2012-01-01

    Post-Secondary Education (PSE) in Ontario and in Canada has expanded on both the demand and supply sides in the last couple of decades. As of 2007, 50% of the population aged 18 to 24 was enrolled in post-secondary institutions. Enrolment in Ontario universities grew from 10,000 in 1960 to approximately 400,000 in 2007 (Clark, Moran, Skolnik, &…

  4. Three-dimensional finite element analysis of the effects of posts on stress distribution in dentin.

    PubMed

    Ho, M H; Lee, S Y; Chen, H H; Lee, M C

    1994-10-01

    A finite element analysis was conducted to study the influence of posts on dentinal stress in pulpless teeth. Three-dimensional models of an intact Chinese maxillary central incisor with and without post restoration were analyzed. When the tooth was subjected to masticatory and traumatic loads, stress distributions in dentin were similar whether or not the post was present. Maximal dentinal stresses were reduced by only 7% to 10% and 10% to 14.5%, respectively, with gold alloy and stainless steel posts. Thus the reinforcement effects from posts appeared limited in pulpless incisors.

  5. Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury.

    PubMed

    Man, Zhentao; Hu, Xiaoqing; Liu, Zhenlong; Huang, Hongjie; Meng, Qingyang; Zhang, Xin; Dai, Linghui; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Zhou, Chunyan; Ao, Yingfang

    2016-11-01

    Cartilage tissue engineering is the hotspot of cartilage repair. The allogenic chondrocytes appear to be a promising source of seed cells in cartilage tissue engineering. In this study, we aimed to transplant allogenic chondrocytes with chitosan hydrogel (CS)-demineralized bone matrix (DBM) hybrid scaffold (CS/DBM) to repair rabbit cartilage injury with one-step operation. After the CS/DBM scaffold was successfully fabricated, it showed that the porous CS filled the large pores of DBM, which improved the distribution of seed cells in the CS/DBM scaffold. The allogenic chondrocytes at second passage were transplanted with different scaffolds to repair rabbit cartilage injury. Twenty-four weeks after surgery, the cartilage defect in the CS/DBM group was successfully filled as shown by MRI. Moreover, the histological score of CS/DBM group was significantly higher than that of the other groups. On the aspect of biomechanical property, the regenerated cartilage in the CS/DBM group were superior to those in the other groups as determined by nanoindentation. Meanwhile, no obvious inflammatory response was observed after the transplantation of allogenic chondrocytes at 24 weeks post-surgery. Furtherly, gene expression profile for cells within the repair tissue was compared with the allogenic chondrocytes before transplantation using Agilent microarray and RT-qPCR. The results showed that some genes beneficial to cartilage regeneration, such as BMP-7, HGF, and IGF-1, were upregulated one month after transplantation. Consequently, our study demonstrated that the transplantation of allogenic chondrocytes with CS/DBM scaffold successfully repaired rabbit cartilage injury with only one-step operation, thereby providing new insights into cartilage tissue engineering. PMID:27636153

  6. Event-free survival and cost-effectiveness in adult acute lymphoblastic leukaemia in first remission treated with allogeneic transplantation.

    PubMed

    Orsi, C; Bartolozzi, B; Messori, A; Bosi, A

    2007-10-01

    Allogeneic transplantation in patients with acute lymphoblastic leukaemia in first remission (ALL-CR1) has been studied in several clinical trials. However, no pooled survival analysis has yet been done. We conducted a survival meta-analysis to compare allogeneic transplantation vs chemotherapy or autologous transplantation using an intention-to-treat approach. Our study included the controlled clinical trials, wherein allocation to allogeneic transplant was based on donor availability. The event-free individual survival data were reconstructed on the basis of published information and Kaplan-Meier graphs. We then generated the meta-analytic event-free survival curves for the two treatments. The mean survival gain per patient was estimated and a simplified cost-effectiveness assessment was carried out. In the allogeneic transplantation group, 293 patients were examined and 479 as controls (four trials). The event-free survival difference was statistically significant (P=0.011). The relative risk for event occurrence was 0.79 for the experimental group vs the controls (95% CI: 0.66-0.96; P=0.017). The mean survival gain was 1 year per patient. The cost per life-year gained was less than the conventional threshold of 50,000 euros. Allogeneic transplantation in ALL-CR1 improves event-free survival as compared to chemotherapy or autologous transplantation. Its cost-effectiveness profile is acceptable. PMID:17660839

  7. Psychosocial adjustment of pediatric patients after allogeneic stem cell transplantation.

    PubMed

    Felder-Puig, R; Peters, C; Matthes-Martin, S; Lamche, M; Felsberger, C; Gadner, H; Topf, R

    1999-07-01

    The purpose of this study was to assess the psychosocial adjustment of patients who had been treated with allogeneic stem cell transplantation (SCT) in our clinic. Selection criteria for patients were to be aged 14-30 years at the time of the follow-up, to be at least 2 years post-SCT and to have a very good knowledge of German. Among 31 eligible patients, 26 participated (84% response rate). The patients were between 15 and 27 years old and were on average 7 years (range 2-13) post-SCT. Research instruments consisted of a demographic questionnaire and various subscales of established psychological measures for which data from a sample of bone cancer survivors and population norms were available. About 35% of patients showed high levels of anxiety, 62% appeared to be extremely sensitive and vulnerable, and 35% showed strong, unfulfilled needs in their love lives. In the other domains tested (self-esteem, family and peer relationships, school/vocational performance, etc), no noticeable differences were found between the subjects and comparable populations. There was no significant association between psychosocial outcome and demographic features or clinical data. Our results suggest that patients who underwent SCT in their childhood or adolescence are at risk of developing long-term emotional or social problems. Due to the retrospective design of our study and the small sample size, no predictive factors for psychosocial distress could be identified.

  8. Repository post-sealing risk analysis using MACRO. [MACRO

    SciTech Connect

    Kaufman, A.M.; Edwards, L.L.; O'Connell, W.J.

    1980-02-14

    MACRO, a code to propagate probability distributions through a set of linked models, is currently under development at Lawrence Livermore Laboratory. An early version of this code, MACRO1, has been used to assess post-sealing dose to man for simple repository and site models based on actual site data.

  9. Understanding Students' Online Interaction: Analysis of Discussion Board Postings

    ERIC Educational Resources Information Center

    Song, Liyan; McNary, Scot W.

    2011-01-01

    The purpose of this paper was to report on the findings of a study examining students' online interaction patterns. The context of the study was a graduate online class delivered via Blackboard[R]. The primary data for the study came from students' discussion board postings, online learning journals, and course grades. Various data analysis…

  10. Engineering Post-Graduate Programmes: A Quality and Productivity Analysis

    ERIC Educational Resources Information Center

    Soares de Mello, Joao Carlos C. B.; Gomes, Eliane Goncalves; Meza, Lidia Angulo; Soares de Mello, Maria Helena C.; Soares de Mello, Adelino Jose R.

    2006-01-01

    Post-graduate courses are periodically evaluated in accordance with not always very clear criteria by CAPES (Co-ordinating Committee for Teaching Staff Improvement). These criteria try to measure, among other things, academic productivity (including quantity and quality of scientific production), number of classes given by teachers, time to…

  11. Design and analysis of post-marketing research.

    PubMed

    Zhou, Xiao-Hua Andrew; Yang, Wei

    2013-07-01

    A post-marketing study is an integral part of research that helps to ensure a favorable risk-benefit profile for approved drugs used in the market. Because most of post-marketing studies use observational designs, which are liable to confounding, estimation of the causal effect of a drug versus a comparative one is very challenging. This article focuses on methodological issues of importance in designing and analyzing studies to evaluate the safety of marketed drugs, especially marketed traditional Chinese medicine (TCM) products. Advantages and limitations of the current designs and analytic methods for postmarketing studies are discussed, and recommendations are given for improving the validity of postmarketing studies in TCM products.

  12. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    PubMed

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL). PMID:27000734

  13. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    PubMed

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  14. A randomized control trial of a psychosocial intervention for caregivers of allogeneic hematopoietic stem cell transplant patients: Effects on distress

    PubMed Central

    Laudenslager, Mark L.; Simoneau, Teri L.; Kilbourn, Kristin; Natvig, Crystal; Philips, Sam; Spradley, Janet; Benitez, Patrick; McSweeney, Peter; Mikulich-Gilbertson, Susan K.

    2015-01-01

    Caregivers of patients receiving allogeneic hematopoietic stem cell transplants (Allo-HSCT) serve a pivotal role in patient care but experience high stress, anxiety, and depression as a result. We theorized that a stress management adapted for Allo-HSCT caregivers would reduce distress compared to treatment as usual (TAU). From 267 consecutive caregivers of Allo-HSCT patients approached, 148 (mean=53.5 years, 75.7% female) were randomized to either psychosocial intervention (n=74) or TAU (n=74). Eight 1-on-1 stress management sessions delivered across the 100 day post-transplant period focused on understanding stress, changing role(s) as caregiver, cognitive behavioral stress management, pacing respiration, and identifying social support. Primary outcomes included perceived stress (psychological) and salivary cortisol awakening response (CAR) (physiological). Randomized groups were not statistically different at baseline. Mixed models analysis of covariance (intent-to-treat) showed that intervention was associated with significantly lower caregiver stress 3 months post-transplant (Mean=20.0, CI95=17.9-22.0) compared to TAU (Mean=23.0, CI95=21.0-25.0) with an effect size (ES) of 0.39 (p=0.039). Secondary psychological outcomes, including depression and anxiety, were significantly reduced with ESs of 0.46 and 0.66 respectively. Caregiver CAR did not differ from non-caregiving controls at baseline and was unchanged by intervention. Despite significant caregiving burden, this psychosocial intervention significantly mitigated distress in Allo-HSCT caregivers. PMID:25961767

  15. Stress distribution of endodontically treated teeth with titanium alloy post and carbon fiber post with different alveolar bone height: A three-dimensional finite element analysis

    PubMed Central

    Singh, S. Vijay; Bhat, Manohar; Gupta, Saurabh; Sharma, Deepak; Satija, Harsha; Sharma, Sumeet

    2015-01-01

    Objective: A three-dimensional (3D) finite element analysis (FEA) on the stress distribution of endodontically treated teeth with titanium alloy post and carbon fiber post with different alveolar bone height. Materials and Methods: The 3D model was fabricated using software to represent an endodontically treated mandibular second premolar with post and restored with a full ceramic crown restoration, which was then analyzed using FEA using FEA ANSYS Workbench V13.0 (ANSYS Inc., Canonsburg, Pennsylvania, U.S.A) software. Results: The FEA showed the maximum stresses of 137.43 Mpa in dentin with alveolar bone height of 4 mm when the titanium post was used, 138.48 Mpa when carbon fiber post was used as compared to 105.91 Mpa in the model with alveolar bone height of 2 mm from the cement enamel junction (CEJ) when the titanium post was used and 107.37 Mpa when the carbon fiber post was used. Conclusions: Stress was observed more in alveolar bone height level of 4 mm from CEJ than 2 mm from CEJ. Stresses in the dentin were almost similar when the carbon fiber post was compared to titanium post. However, stresses in the post and the cement were much higher when titanium post was used as compared to carbon fiber post. PMID:26430375

  16. Post Buckling Progressive Failure Analysis of Composite Laminated Stiffened Panels

    NASA Astrophysics Data System (ADS)

    Anyfantis, Konstantinos N.; Tsouvalis, Nicholas G.

    2012-06-01

    The present work deals with the numerical prediction of the post buckling progressive and final failure response of stiffened composite panels based on structural nonlinear finite element methods. For this purpose, a progressive failure model (PFM) is developed and applied to predict the behaviour of an experimentally tested blade-stiffened panel found in the literature. Failure initiation and propagation is calculated, owing to the accumulation of the intralaminar failure modes induced in fibre reinforced composite materials. Hashin failure criteria have been employed in order to address the fiber and matrix failure modes in compression and tension. On the other hand, the Tsai-Wu failure criterion has been utilized for addressing shear failure. Failure detection is followed with the introduction of corresponding material degradation rules depending on the individual failure mechanisms. Failure initiation and failure propagation as well as the post buckling ultimate attained load have been numerically evaluated. Final failure behaviour of the simulated stiffened panel is due to sudden global failure, as concluded from comparisons between numerical and experimental results being in good agreement.

  17. Chimerism of allogeneic mesenchymal cells in bone marrow, liver, and spleen after mesenchymal stem cells infusion.

    PubMed

    Meleshko, Alexander; Prakharenia, Irina; Kletski, Semen; Isaikina, Yanina

    2013-12-01

    Although an infusion of culture-expanded MSCs is applied in clinic to improve results of HSCs transplantation and for a treatment of musculoskeletal disorders, homing, and engraftment potential of culture-expanded MSC in humans is still obscure. We report two female patients who received allogeneic BM transplantation as a treatment of hematological diseases and a transplantation of MSCs from third-party male donors. Both patients died within one yr of infectious complications. Specimens of paraffin-embedded blocks of tissues from transplanted patients were taken. The aim of the study was to estimate possible homing and engraftment of allogeneic BM-derived MSCs in some tissues/organs of recipient. Sensitive real-time quantitative PCR analysis was applied with SRY gene as a target. MSC chimerism was found in BM, liver, and spleen of both patients. We conclude that sensitive RQ-PCR analysis is acceptable for low-level chimerism evaluation even in paraffin-embedded tissue specimens.

  18. Toll like receptor polymorphisms in allogeneic hematopoietic cell transplantation

    PubMed Central

    Kornblit, Brian; Enevold, Christian; Wang, Tao; Spellman, Stephen; Haagenson, Mike; Lee, Stephanie J; Müller, Klaus

    2014-01-01

    To assess the impact of the genetic variation in toll-like receptors (TLR) on outcome after allogeneic myeloablative conditioning hematopoietic cell transplantation (HCT) we have investigated 29 single nucleotide polymorphisms (SNP) across 10 TLRs in 816 patients and donors. Only donor genotype of TLR8 rs3764879, which is located on the X chromosome, was significantly associated with outcome at the Bonferroni corrected level P≤0.001. Male hemizygosity and female homozygosity for the minor allele were significantly associated with disease free survival (DFS) (hazard ratio (HR) 1.47 (95% confidence interval (CI) 1.16–1.85); P=0.001). Further analysis stratified by donor sex due to confounding by sex, was suggestive for associations with overall survival (male donor: HR 1.41 (95% CI 1.09–1.83), P=0.010); female donor: (HR 2.78 (95% CI 1.43–5.41), P=0.003), DFS (male donor: HR 1.45 (95% CI 1.12–1.87), P=0.005; female donor: HR 2.34 (95% CI 1.18–4.65), P=0.015) and treatment related mortality (male donor: HR 1.49 (95% CI 1.09–2.04), P=0.012; female donor: HR 3.12 (95% CI 1.44–6.74), P=0.004). In conclusion our findings suggest that the minor allele of TLR8 rs3764879 of the donor is associated with outcome after myeloablative conditioned allogeneic HCT. PMID:25464115

  19. Toll-like receptor polymorphisms in allogeneic hematopoietic cell transplantation.

    PubMed

    Kornblit, Brian; Enevold, Christian; Wang, Tao; Spellman, Stephen; Haagenson, Mike; Lee, Stephanie J; Müller, Klaus

    2015-02-01

    To assess the impact of the genetic variation in toll-like receptors (TLRs) on outcome after allogeneic myeloablative conditioning hematopoietic cell transplantation (HCT), we investigated 29 single nucleotide polymorphisms across 10 TLRs in 816 patients and donors. Only donor genotype of TLR8 rs3764879, which is located on the X chromosome, was significantly associated with outcome at the Bonferroni-corrected level P ≤ .001. Male hemizygosity and female homozygosity for the minor allele were significantly associated with disease-free survival (hazard ratio [HR], 1.47 [95% confidence interval {CI}, 1.16 to 1.85]; P = .001). Further analysis stratified by donor sex due to confounding by sex was suggestive for associations with overall survival (male donor: HR, 1.41 [95% CI, 1.09 to 1.83], P = .010; female donor: HR, 2.78 [95% CI, 1.43 to 5.41], P = .003), disease-free survival (male donor: HR, 1.45 [95% CI, 1.12 to 1.87], P = .005; female donor: HR, 2.34 [95% CI, 1.18 to 4.65], P = .015), and treatment-related mortality (male donor: HR, 1.49 [95% CI, 1.09 to 2.04], P = .012; female donor: HR, 3.12 [95% CI, 1.44 to 6.74], P = .004). In conclusion, our findings suggest that the minor allele of TLR8 rs3764879 of the donor is associated with outcome after myeloablative conditioned allogeneic HCT. PMID:25464115

  20. G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts

    PubMed Central

    Peixoto, Eduardo; Messinger, Shari; Mantero, Alejandro; Padilla-Téllez, Nathalia D.; Baidal, David A.; Alejandro, Rodolfo; Ricordi, Camillo; Inverardi, Luca

    2016-01-01

    Background Allogeneic human islet transplantation is an effective therapy for the treatment of patients with Type 1 Diabetes (T1D). The low number of islet transplants performed worldwide and the different transplantation protocols used limit the identification of the most effective therapeutic options to improve the efficacy of this approach. Methods We present a retrospective analysis on the data collected from 44 patients with T1D who underwent islet transplantation at our institute between 2000 and 2007. Several variables were included: recipient demographics and immunological characteristics, donor and transplant characteristics, induction protocols, and additional medical treatment received. Immunosuppression was induced with anti-CD25 (Daclizumab), alone or in association with anti-tumor necrosis factor alpha (TNF-α) treatments (Etanercept or Infliximab), or with anti-CD52 (Alemtuzumab) in association with anti-TNF-α treatments (Etanercept or Infliximab). Subsets of patients were treated with Filgrastim for moderate/severe neutropenia and/or Exenatide for post prandial hyperglycemia. Results The analysis performed indicates a negative association between graft survival (c-peptide level ≥ 0.3 ng/ml) and islet infusion volume, with the caveat that, the progressive reduction of infusion volumes over the years has been paralleled by improved immunosuppressive protocols. A positive association is instead suggested between graft survival and administration of Exenatide and Filgrastim, alone or in combination. Conclusion This retrospective analysis may be of assistance to further improve long-term outcomes of protocols for transplant of islets and other organs. PMID:27285580

  1. A Post-Monte-Carlo Sensitivity Analysis Code

    2000-04-04

    SATOOL (Sensitivity Analysis TOOL) is a code for sensitivity analysis, following an uncertainity analysis with Monte Carlo simulations. Sensitivity analysis identifies those input variables, whose variance contributes dominatly to the variance in the output. This analysis can be used to reduce the variance in the output variables by redefining the "sensitive" variables with greater precision, i.e. with lower variance. The code identifies a group of sensitive variables, ranks them in the order of importance andmore » also quantifies the relative importance among the sensitive variables.« less

  2. Comparison of outcomes after two standards-of-care reduced-intensity conditioning regimens and two different graft sources for allogeneic stem cell transplantation in adults with hematologic diseases: a single-center analysis.

    PubMed

    Le Bourgeois, Amandine; Mohr, Catherine; Guillaume, Thierry; Delaunay, Jacques; Malard, Florent; Loirat, Marion; Peterlin, Pierre; Blin, Nicolas; Dubruille, Viviane; Mahe, Beatrice; Gastinne, Thomas; Le Gouill, Steven; Moreau, Philippe; Mohty, Mohamad; Planche, Lucie; Lode, Laurence; Bene, Marie-Christine; Chevallier, Patrice

    2013-06-01

    Recent advances in allogeneic stem cell transplantation (allo-HSCT) have included the advent of reduced-intensity conditioning (RIC) regimens to decrease the toxicity of myeloablative allo-SCT and the use of double umbilical cord blood (dUCB) units as a graft source in adults lacking a suitable donor. The FB2A2 regimen (fludarabine 30 mg/kg/day for 5-6 days + i.v. busulfan 3.6 mg/kg/day for 2 days + rabbit antithymocyte globulin 2.5 mg/kg/day for 2 days) supported by peripheral blood stem cells (PBSCs) and the TCF regimen (fludarabine 200 mg/m² for 5 days + cyclophosphamide 50 mg/kg for 1 day + low-dose [2 Gy] total body irradiation) supported by dUCB units are currently the most widely used RIC regimens in many centers and could be considered standard of care in adults eligible for an RIC allo-SCT. Here we compared, retrospectively, the outcomes of adults patients who received the FB2A2-PBSC RIC regimen (n = 52; median age, 59 years; median follow-up, 19 months) and those who received the dUCB-TCF RIC regimen (n = 39; median age, 56 years; median follow-up, 20 months) for allo-SCT between January 2007 and November 2010. There were no significant between-group differences in patient and disease characteristics. Cumulative incidences of engraftment, acute grade II-IV and chronic graft-versus-host disease were similar in the 2 groups. The median time to platelet recovery, incidence of early death (before day +100), and 2-year nonrelapse mortality were significantly higher in the dUCB-TCF group (38 days versus 0 days [P <.0001]; 20.5% versus 4% [P = .05], and 26.5% versus 6% [P = .02], respectively). The groups did not differ in terms of 2-year overall survival (62% for FB2A2-PBSC versus 61% for dUCB-TCF), disease-free survival (59% versus 50.5%), or relapse incidence (35.5% versus 23%). In multivariate analysis, the presence of a lymphoid disorder was associated with a significantly higher 2-year overall survival (hazard ratio, 0.42; 95% confidence interval, 0

  3. Iodine-131-metaiodobenzylguanidine therapy with reduced-intensity allogeneic stem cell transplantation in recurrent neuroblastoma.

    PubMed

    Takahashi, Hiroka; Manabe, Atsushi; Aoyama, Chiaki; Kamiya, Takahiro; Kato, Itaru; Takusagawa, Ayako; Ogawa, Chitose; Ozawa, Miwa; Hosoya, Ryota; Yokoyama, Kunihiko

    2008-03-01

    Neuroblastoma is the most common extracranial solid tumor of childhood, and iodine-131-metaiodobenzylguanidine (MIBG) therapy is a new approach for grade IV neuroblastoma. We describe the case history of a 3-year-old girl with recurrent neuroblastoma who received MIBG therapy with reduced-intensity allogeneic stem cell transplantation (RIST) because of an extensive bone marrow involvement. The post-transplant course was uneventful and complete chimerism was obtained. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. The patient remained in remission for 3 months after RIST until the second relapse. MIBG therapy combined with RIST warrants further trials.

  4. Relapse of lymphoma after allogeneic hematopoietic cell transplantation: management strategies and outcome.

    PubMed

    Wudhikarn, Kitsada; Brunstein, Claudio G; Bachanova, Veronika; Burns, Linda J; Cao, Qing; Weisdorf, Daniel J

    2011-10-01

    The outcome and management of relapsed lymphoma after allogeneic hematopoietic cell transplantation (HCT) is difficult. Therapeutic options may include donor lymphocyte infusion (DLI), reduction of immunosuppression (RIS), chemotherapy, radiation, immunotherapy, second HCT, and experimental treatments, but reported data contrasting the response and efficacy of these salvage treatments are limited. We describe the treatments, response, prognosis, and long-term survival of 72 patients with relapse of lymphoma after allogeneic HCT. Between 1991 and 2007, 227 lymphoma patients underwent allogeneic HCT. Of these, 72 (32%) developed relapse/progression after their HCT at a median of 99 days (0-1898 days); 37 had early (<100 days) post-HCT relapse. Forty-four had non-Hodgkin lymphoma (7 mantle cell, 5 indolent, 15 diffuse large B cell, 4 Burkitt's, and 13 T/Natural Killer cell), and 28 patients had Hodgkin lymphoma. At the time of HCT, 62 patients were in remission (22 in complete [CR] and 40 in partial [PR]), 1 had stable whereas 9 had progressive disease. Seventeen cases received myeloablative and 55 received a reduced-intensity conditioning regimen. At relapse, most patients had generalized lymphadenopathy, extranodal organ involvement, and advanced disease. Five patients received no intervention for the post-HCT relapse. Immunosuppressive treatment was reduced or withdrawn as the first-line therapy in 58 patients (80.5%); 47 were treated using combinations of conventional chemotherapy (n = 22), rituximab (n = 27), interferon (IFN) (n = 1), DLI (n = 7), second HCT (n = 2), local radiation (n = 23), and other therapy (n = 6). Thirty-eight patients had an objective response (CR in 30, PR in 8), and 2 had stable disease (SD). At the post-HCT relapse, favorable prognostic factors for survival after HCT included good ECOG performance status (0-2), normal lactate dehydrogenase (LDH), early stage disease (stage I-III), isolated extranodal organ involvement, and later relapse

  5. Systematic Nutritional Support in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

    PubMed

    Fuji, Shigeo; Einsele, Hermann; Savani, Bipin N; Kapp, Markus

    2015-10-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) has become an established treatment modality for various hematological diseases. However, in allogeneic HSCT, patients often suffer from severe gastrointestinal complications caused by the conditioning regimen and acute/chronic graft-versus-host disease, which requires support by multidisciplinary nutritional support teams (NST). In addition, pretransplantation nutritional status can affect the clinical outcome after allogeneic HSCT. Therefore, it is important to refer the patient to a NST when becoming aware of nutritional problems before allogeneic HSCT. It is also important to follow nutritional status over the long term, as patients often suffer from various nutritional problems, such as malnutrition and metabolic syndrome, even late after allogeneic HSCT. In summary, NST can contribute to the improvement of nutritional status and possibly prognosis at every stage before and after allogeneic HSCT. Here, we aim to give a comprehensive overview of current understanding about nutritional support in allogeneic HSCT and try to provoke a constructive discussion to stimulate further investigation.

  6. The evolution of treatment strategies for patients with chronic myeloid leukemia relapsing after allogeneic bone marrow transplantation: Can tyrosine kinase inhibitors replace donor lymphocyte infusions?

    PubMed Central

    Zeidner, Joshua F.; Zahurak, Marianna; Rosner, Gary L.; Gocke, Christopher D.; Jones, Richard J.; Smith, Douglas

    2014-01-01

    The optimal treatment for chronic myeloid leukemia (CML) relapsing following allogeneic bone marrow transplantation (alloBMT) is unknown. We performed a single-center retrospective analysis of 71 consecutive patients undergoing alloBMT for CML from 1995–2008. A multi-state model was used to quantify the cumulative incidences of complete molecular response (CMR) and death following alloBMT. The primary analysis was the comparison of three treatment interventions (tyrosine kinase inhibitor: TKI, donor lymphocyte infusion: DLI, and TKI+DLI) for relapsed disease post-alloBMT. Forty-five (63%) patients relapsed post-alloBMT (molecular relapse: n=16, cytogenetic relapse: n=20, hematologic relapse: n=2, advanced phase relapse: n=7) and 40 patients underwent one of three treatments: TKI-only (n=13), DLI-only (n=11), or TKI+DLI (n=16). Although not statistically significant, the TKI-only group had the highest cumulative incidence of CMR and the lowest cumulative incidence of death compared to DLI and TKI+DLI. These data support the finding that TKI therapy is active in the post-alloBMT setting. PMID:24712979

  7. A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10 -1082 promoter genotype as predictor of disease progression

    PubMed Central

    von Euw, Erika M; Barrio, María M; Furman, David; Levy, Estrella M; Bianchini, Michele; Peguillet, Isabelle; Lantz, Olivier; Vellice, Alejandra; Kohan, Abraham; Chacón, Matías; Yee, Cassian; Wainstok, Rosa; Mordoh, José

    2008-01-01

    Background Sixteen melanoma patients (1 stage IIC, 8 stage III, and 7 stage IV) were treated in a Phase I study with a vaccine (DC/Apo-Nec) composed of autologous dendritic cells (DCs) loaded with a mixture of apoptotic/necrotic allogeneic melanoma cell lines (Apo-Nec), to evaluate toxicity and immune responses. Also, IL-10 1082 genotype was analyzed in an effort to predict disease progression. Methods PBMC were obtained after leukapheresis and DCs were generated from monocytes cultured in the presence of GM-CSF and IL-4 in serum-free medium. Immature DCs were loaded with gamma-irradiated Apo-Nec cells and injected id without adjuvant. Cohorts of four patients were given four vaccines each with 5, 10, 15, or 20 × 106 DC/Apo-Nec cell per vaccine, two weeks apart. Immune responses were measured by ELISpot and tetramer analysis. Il-10 genotype was measured by PCR and corroborated by IL-10 production by stimulated PBMC. Results Immature DCs efficiently phagocytosed melanoma Apo-Nec cells and matured after phagocytosis as evidenced by increased expression of CD83, CD80, CD86, HLA class I and II, and 75.2 ± 16% reduction in Dextran-FITC endocytosis. CCR7 was also up-regulated upon Apo-Nec uptake in DCs from all patients, and accordingly DC/Apo-Nec cells were able to migrate in vitro toward MIP-3 beta. The vaccine was well tolerated in all patients. The DTH score increased significantly in all patients after the first vaccination (Mann-Whitney Test, p < 0.05). The presence of CD8+T lymphocytes specific to gp100 and Melan A/MART-1 Ags was determined by ELISpot and tetramer analysis in five HLA-A*0201 patients before and after vaccination; one patient had stable elevated levels before and after vaccination; two increased their CD8 + levels, one had stable moderate and one had negligible levels. The analysis of IL-10 promoter -1082 polymorphism in the sixteen patients showed a positive correlation between AA genotype, accompanied by lower in vitro IL-10 production by

  8. Analysis of post-harvest fungicides by micellar electrokinetic chromatography.

    PubMed

    Rodríguez, R; Picó, Y; Font, G; Mañes, J

    2001-07-27

    A method based on solid-phase extraction (SPE) and micellar electrokinetic chromatography (MEKC) was developed for the simultaneous determination of carbendazim, imazalil, methylthiophanate, O-phenylphenol, prochloraz, procimidone, thiabendazole and triadimefon residues in grape, lettuce, orange and tomato. Selectivity and resolution were studied changing the pH and the concentration of the buffer, the type and concentration of surfactant and the methanol content in the mobile phase. A buffer consisting of 4 mM borate with 75 mM sodium cholate (pH 9.2) gave the best results. The recoveries of the fungicides in spiked fruit and vegetable samples ranged from 30 to 105%, and the limits of detection were between 0.1 and 1 mg kg(-1). The reproducibility and repeatability of the combination of SPE pretreatment and MEKC were good for all the compounds, except for imazalil and O-phenylphenol in oranges, due to some matrix compounds interfering with the separation. The method was applied to post harvest treated samples, and the fungicides were sometimes detected at concentration levels lower than maximum residue limits (MRLs). PMID:11521888

  9. Shear Force at the Cell-Matrix Interface: Enhanced Analysis for Microfabricated Post Array Detectors

    PubMed Central

    Lemmon, Christopher A.; Sniadecki, Nathan J.; Ruiz, Sami Alom; Tan, John L.; Romer, Lewis H.; Chen, Christopher S.

    2006-01-01

    The interplay of mechanical forces between the extracellular environment and the cytoskeleton drives development, repair, and senescence in many tissues. Quantitative definition of these forces is a vital step in understanding cellular mechanosensing. Microfabricated post array detectors (mPADs) provide direct measurements of cell-generated forces during cell adhesion to extracellular matrix. A new approach to mPAD post labeling, volumetric imaging, and an analysis of post bending mechanics determined that cells apply shear forces and not point moments at the matrix interface. In addition, these forces could be accurately resolved from post deflections by using images of post tops and bases. Image analysis tools were then developed to increase the precision and throughput of post centroid location. These studies resulted in an improved method of force measurement with broad applicability and concise execution using a fully automated force analysis system. The new method measures cell-generated forces with less than 5%error and less than 90 seconds of computational time. Using this approach, we demonstrated direct and distinct relationships between cellular traction force and spread cell surface area for fibroblasts, endothelial cells, epithelial cells and smooth muscle cells. PMID:16708468

  10. Finite element analysis of weakened roots restored with composite resin and posts.

    PubMed

    Coelho, Carla Santina de Miranda; Biffi, João Carlos Gabrielli; Silva, Gisele Rodrigues da; Abrahão, Anthony; Campos, Roberto Elias; Soares, Carlos José

    2009-11-01

    Finite element analysis (FEA) was used to investigate the influence of different post systems on the stress distribution of weakened teeth under oblique-load application. A maxillary central incisor root obtained from a sound tooth was weakened by partial removal of dentin inside the root canal. Seven two-dimensional numerical models, one from the sound tooth and six from the weakened root restored with composite resin and post systems were created as follows - ST: sound tooth; CPC: cast CuAl post and core; SSP: stainless steel post + composite core; GP: fiberglass + composite core; CP: carbon fiber + composite core; ZP: zirconium dioxide post + composite core; TP: titanium post + composite core. The numerical models were considered to be restored with a leucite-reinforced all-ceramic crown and received a 45 masculine occlusal load (10 N) on the lingual surface.All the materials and structures were considered linear elastic, homogeneous, and isotropic, with the exception of fiberglass and carbon fiber posts which assumed orthotropic behavior. The numerical models were plotted and meshed with isoparametric elements, and the results were analyzed using von Mises and Sy stress criteria. When compared with the sound tooth, FEA revealed differences in stress distribution when post systems were used. Among the restored teeth, the use of CPC, SSP, ZP, and TP resulted in higher stress concentration in the post itself when compared to GP and CP. Therefore, results from the FEA images suggested that the use of non-metallic post systems could result in improved mechanical behavior for the weakened restored teeth. PMID:20019417

  11. Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Wunderli, Werner; Meerbach, Astrid; Güngör, Tayfun; Guengoer, Tayfun; Berger, Christoph; Greiner, Oliver; Caduff, Rosmarie; Trkola, Alexandra; Bossart, Walter; Gerlach, Daniel; Schibler, Manuel; Cordey, Samuel; McKee, Thomas Alexander; Van Belle, Sandra; Kaiser, Laurent; Tapparel, Caroline

    2011-01-01

    Infants with severe primary combined immunodeficiency (SCID) and children post-allogeneic hematopoietic stem cell transplantation (HSCT) are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA) techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients. PMID:22096580

  12. Allogeneic and autologous bone marrow transplantation for acute nonlymphocytic leukemia.

    PubMed

    Hurd, D D

    1987-12-01

    Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients. PMID:3321445

  13. Survival of AML patients relapsing after allogeneic hematopoietic cell transplantation: a CIBMTR study

    PubMed Central

    Bejanyan, Nelli; Weisdorf, Daniel J.; Logan, Brent R.; Wang, Hai-Lin; Devine, Steven M.; de Lima, Marcos; Bunjes, Donald W.; Zhang, Mei-Jie

    2015-01-01

    Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990–2010) during first or second complete remission (CR) to identify factors associated with longer post-relapse survival. Median time of post HCT relapse was 7 months (mo; range, 1–177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy (CT) alone (n=660), donor lymphocyte infusion (DLI)±CT (n=202; %), or 2nd alloHCT±CT ±DLI (n=369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 mo (range, <1–193). Survival for all patients was 23% at 1 year post-relapse; however, 3-yr overall survival correlated with time from HCT to relapse (4% for relapse during 1–6 mo period, 12% during 6 mo-2 yr, 26% during 2–3 yr, and 38% for ≥3 yr). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (RR 0.55 for 6 mo-2 yr, RR 0.39 for 2–3 yr, and RR 0.28 for ≥3 yr; p<0.0001) and a 1st HCT using reduced-intensity conditioning (RR=0.77; 95% CI 0.66–0.88, p=0.0002). In contrast, inferior survival was associated with age >40 yr (RR=1.42, 95% CI 1.24–1.64; p<0.0001), active GVHD at relapse (RR=1.25, 95% CI 1.13–1.39; p<0.0001), adverse cytogenetics (RR=1.37, 95% CI 1.09–1.71; p=0.0062), mismatched URD (RR=1.61, 95% CI 1.22–2.13; p=0.0008), and use of cord blood for 1st HCT (RR=1.23, 95% CI 1.06–1.42; p=0.0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 mo after their initial alloHCT had better survival and may benefit from intensive therapy such as 2nd alloHCT±DLI. PMID:25460355

  14. CT60 single-nucleotide polymorphism as a surrogate marker for donor lymphocyte infusion outcome after allogeneic cell transplantation for acute leukemia.

    PubMed

    Metaxas, Y; Bertz, H; Spyridonidis, A; Spyroupoulou-Vlachou, M; Porzelius, C; Finke, J

    2012-03-01

    The benefit of survival at the expense of new GVHD after DLI for acute leukemia following human allogeneic hematopoietic cell transplantation (allo-HCT) remains a matter of controversy. The detection of biological markers predicting this outcome would be an enormous breakthrough. The purpose of this study was the analysis of CT60 single-nucleotide polymorphism (SNP) of the CTLA-4 T-regulatory gene as a surrogate marker for DLI outcome in this difficult setting. Using Pyrosequencing, we genotyped the alleles of the CT60 SNP of 79 DLI donors and correlated them with the post-DLI outcome of their matching recipients. The presence of a donor 'AA' or 'AG' CT60 genotype vs a 'GG' genotype was an independent factor for remaining in complete chimerism/remission post-DLI (odds ratio (OR) 2.61 vs 0.42, respectively, P=0.05). Further, in cases with evident post-DLI allo-reactivity the importance of an 'AA' or 'AG' vs a 'GG' genotype gained significance for ongoing complete chimerism (OR 4.35 vs 0.32, P=0.03). Neither alterations in cumulative DLI dose nor any other clinical parameter significantly weakened the importance of CT60 SNP. Our results provide evidence for the necessity of genotyping CT60 SNP prior to DLI administration in patients with acute leukemia. PMID:21552305

  15. Practical post-calibration uncertainty analysis: Yucca Mountain, Nevada, USA

    NASA Astrophysics Data System (ADS)

    James, S. C.; Doherty, J.; Eddebbarh, A.

    2009-12-01

    The values of parameters in a groundwater flow model govern the precision of predictions of future system behavior. Predictive precision, thus, typically depends on an ability to infer values of system properties from historical measurements through calibration. When such data are scarce, or when their information content with respect to parameters that are most relevant to predictions of interest is weak, predictive uncertainty may be high, even if the model is “calibrated.” Recent advances help recognize this condition, quantitatively evaluate predictive uncertainty, and suggest a path toward improved predictive accuracy by identifying sources of predictive uncertainty and by determining what observations will most effectively reduce this uncertainty. We demonstrate linear and nonlinear predictive error/uncertainty analyses as applied to a groundwater flow model of Yucca Mountain, Nevada, the US’s proposed site for disposal of high-level radioactive waste. Both of these types uncertainty analysis are readily implemented as an adjunct to model calibration with medium to high parameterization density. Linear analysis yields contributions made by each parameter to a prediction’s uncertainty and the worth of different observations, both existing and yet-to-be-gathered, toward reducing this uncertainty. Nonlinear analysis provides more accurate characterization of the uncertainty of model predictions while yielding their (approximate) probability distribution functions. This paper applies the above methods to a prediction of specific discharge and confirms the uncertainty bounds on specific discharge supplied in the Yucca Mountain Project License Application. Furthermore, Monte Carlo simulations confirm that hydrogeologic units thought to be flow barriers have probability distributions skewed toward lower permeabilities.

  16. Present and Future of Allogeneic Natural Killer Cell Therapy

    PubMed Central

    Lim, Okjae; Jung, Mi Young; Hwang, Yu Kyeong; Shin, Eui-Cheol

    2015-01-01

    Natural killer (NK) cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation revealed the antitumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions. PMID:26089823

  17. Adult allogeneic bone marrow transplantation: initial experience in the University Hospital, Kuala Lumpur.

    PubMed

    Teh, A; Bosco, J J; Leong, K W; Saw, M H; Menaka, N; Devashanti, P

    1997-03-01

    Prior to 1993, bone marrow transplantation for adult patients was not available in Malaysia. Adult allogeneic bone marrow transplantation commenced in Malaysia when the first transplant was conducted at the University Hospital, Kuala Lumpur on 2 November 1993. Up till July 1995, 10 adult bone marrow transplants had been conducted at the University Hospital. Five patients had acute myeloid leukaemia in first remission, 4 had chronic myeloid leukaemia and 1 had acute lymphoblastic leukaemia in first partial remission. The age range of patients at the time of transplant is 16-40 years (mean 25.5 years). All patients engrafted successfully and the survival for the first 100 days post-transplant is 90%. One patient demonstrated haematological relapse post-transplant but achieved remission with donor buffy-coat infusion. The mean drug cost incurred was RM28,269 for the first 100 days. Locally available adult allogeneic bone marrow transplantation is safe, affordable and has comparable results with reputable overseas transplant centres.

  18. Chimerism of bone marrow mesenchymal stem/stromal cells in allogeneic hematopoietic cell transplantation: is it clinically relevant?

    PubMed

    Miura, Yasuo; Yoshioka, Satoshi; Yao, Hisayuki; Takaori-Kondo, Akifumi; Maekawa, Taira; Ichinohe, Tatsuo

    2013-01-01

    Multipotent mesenchymal stem/stromal cells (MSCs) have been extensively used as a transplantable cell source for regenerative medicine and immunomodulatory therapy. Specifically in allogeneic hematopoietic stem cell transplantation (HSCT), co-transplantation or post-transplant infusion of MSCs derived from bone marrow (BM) of non-self donors has been implicated in accelerating hematopoietic recovery, ameliorating graft-vs.-host disease, and promoting tissue regeneration. However, irrespective of the use of MSC co-administration, post-transplant chimerism of BM-derived MSCs after allogeneic HSCT has been reported to remain of host origin, suggesting that the infused donor MSCs are immunologically rejected or not capable of long-term engraftment in the host microenvironment. Also, hematopoietic cell allografts currently used for HSCT do not seem to contain sufficient amount of MSCs or their precursors to reconstitute host BM microenvironment. Since the toxic conditioning employed in allo-HSCT may impair the function of host MSCs to maintain hematopoietic/regenerative stem cell niches and to provide a local immunomodulatory milieu, we propose that new directions for enhancing immunohematopoietic reconstitution and tissue repair after allogeneic HSCT include the development of strategies to support functional replenishment of residual host MSCs or to support more efficient engraftment of infused donor MSCs. Future areas of research should include in vivo tracking of infused MSCs and detection of their microchimeric presence in extra-marrow sites as well as in BM.

  19. Cost of allogeneic and autologous blood transfusion in Canada. Canadian Cost of Transfusion Study Group.

    PubMed Central

    Tretiak, R; Laupacis, A; Rivière, M; McKerracher, K; Souêtre, E

    1996-01-01

    OBJECTIVE: To determine the cost, from a societal perspective, of blood transfusion in Canada. STUDY DESIGN: Cost-structure analysis. SETTING: Data were collected from eight hospitals and from six blood centres operated by the Canadian Red Cross Society in four provinces. OUTCOME MEASURES: Costs associated with four stages of transfusion-- collection, production, distribution and delivery--in 1933 were assessed. Costs were divided into the following categories; personnel, purchases, external services, overhead, donors' time, patients' time (for autologous transfusion), wastage and infection. RESULTS: The mean overall cost of a transfusion performed on an inpatient basis was $210 per unit of red blood cells for an allogeneic transfusion and $338 per unit of blood for an autologous transfusion. The mean cost of an allogeneic transfusion performed on an outpatient basis was $280 per unit of red blood cells. CONCLUSION: The costs determined in this study can be used in future studies comparing the cost-effectiveness of allogeneic transfusion with that of alternative methods. PMID:8625000

  20. Prediction of hospital failure: a post-PPS analysis.

    PubMed

    Gardiner, L R; Oswald, S L; Jahera, J S

    1996-01-01

    This study investigates the ability of discriminant analysis to provide accurate predictions of hospital failure. Using data from the period following the introduction of the Prospective Payment System, we developed discriminant functions for each of two hospital ownership categories: not-for-profit and proprietary. The resulting discriminant models contain six and seven variables, respectively. For each ownership category, the variables represent four major aspects of financial health (liquidity, leverage, profitability, and efficiency) plus county marketshare and length of stay. The proportion of closed hospitals misclassified as open one year before closure does not exceed 0.05 for either ownership type. Our results show that discriminant functions based on a small set of financial and nonfinancial variables provide the capability to predict hospital failure reliably for both not-for-profit and proprietary hospitals.

  1. Whole-body UVB irradiation during allogeneic hematopoietic cell transplantation is safe and decreases acute graft-versus-host disease.

    PubMed

    Kreutz, Marina; Karrer, Sigrid; Hoffmann, Petra; Gottfried, Eva; Szeimies, Rolf-Markus; Hahn, Joachim; Edinger, Matthias; Landthaler, Michael; Andreesen, Reinhard; Merad, Miriam; Holler, Ernst

    2012-01-01

    Depletion of host Langerhans cells (LCs) prevents cutaneous graft-versus-host disease (GvHD) in mice. We analyzed whether UVB irradiation is tolerated during the course of human allogeneic hematopoietic cell transplantation and whether depletion of LCs by broadband UVB could improve GvHD outcome. A total of 17 patients received six whole-body UVB irradiations with 75% of the individually determined minimal erythemal dose after conditioning with a reduced intensity protocol. LCs, dermal dendritic cells (DCs), and macrophages were analyzed before and after UVB irradiation by immunohistochemical analysis. Circulating blood cells and serum factors were analyzed in parallel. In striking contrast to previous data, our irradiation protocol was well tolerated in all patients. UVB treatment decreased the number of LCs and also affected dermal DCs. UVB-treated patients also had significantly higher 25-hydroxyvitamin D3 serum levels and higher numbers of circulating CD4+ FoxP3+ regulatory T cells. Strikingly, nine out of nine patients with complete LC depletion (<1 LC per field) developed only grade I GvHD or no GvHD up to day 100. Our results strongly suggest that prophylactic UVB irradiation post transplant is safe and should be further explored as a clinical strategy to prevent acute (skin) GvHD.

  2. Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome.

    PubMed

    Radujkovic, Aleksandar; Becker, Natalia; Benner, Axel; Penack, Olaf; Platzbecker, Uwe; Stölzel, Friedrich; Bornhäuser, Martin; Hegenbart, Ute; Ho, Anthony D; Dreger, Peter; Luft, Thomas

    2015-10-27

    Allogeneic stem cell transplantation (alloSCT) represents a curative therapeutic option for patients with myelodysplastic syndrome (MDS), but relapse and non-relapse mortality (NRM) limit treatment efficacy. Based on our previous observation in acute myeloid leukemia we investigated the impact of pre-transplant weight loss on post-transplant outcome in MDS patients. A total of 111 patients diagnosed with MDS according to WHO criteria transplanted between 2000 and 2012 in three different transplant centers were included into the analysis. Data on weight loss were collected from medical records prior to conditioning therapy and 3-6 months earlier. Patient, disease and transplant characteristics did not differ between patients with weight loss (2-5%, n = 17; > 5%, n = 17) and those without (n = 77). In a mixed effect model, weight loss was associated with higher risk MDS (p = 0.046). In multivariable analyses, pre-transplant weight loss exceeding 5% was associated with a higher incidence of relapse (p < 0.001) and NRM (p = 0.007). Pre-transplant weight loss of 2-5% and > 5% were independent predictors of worse disease-free (p = 0.023 and p < 0.001, respectively) and overall survival (p = 0.043 and p < 0.001, respectively). Our retrospective study suggests that MDS patients losing weight prior to alloSCT have an inferior outcome after transplantation. Prospective studies addressing pre-transplant nutritional interventions are highly warranted.

  3. Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome

    PubMed Central

    Radujkovic, Aleksandar; Becker, Natalia; Benner, Axel; Penack, Olaf; Platzbecker, Uwe; Stölzel, Friedrich; Bornhäuser, Martin; Hegenbart, Ute; Ho, Anthony D.; Dreger, Peter; Luft, Thomas

    2015-01-01

    Allogeneic stem cell transplantation (alloSCT) represents a curative therapeutic option for patients with myelodysplastic syndrome (MDS), but relapse and non-relapse mortality (NRM) limit treatment efficacy. Based on our previous observation in acute myeloid leukemia we investigated the impact of pre-transplant weight loss on post-transplant outcome in MDS patients. A total of 111 patients diagnosed with MDS according to WHO criteria transplanted between 2000 and 2012 in three different transplant centers were included into the analysis. Data on weight loss were collected from medical records prior to conditioning therapy and 3–6 months earlier. Patient, disease and transplant characteristics did not differ between patients with weight loss (2–5%, n = 17; > 5%, n = 17) and those without (n = 77). In a mixed effect model, weight loss was associated with higher risk MDS (p = 0.046). In multivariable analyses, pre-transplant weight loss exceeding 5% was associated with a higher incidence of relapse (p < 0.001) and NRM (p = 0.007). Pre-transplant weight loss of 2–5% and > 5% were independent predictors of worse disease-free (p = 0.023 and p < 0.001, respectively) and overall survival (p = 0.043 and p < 0.001, respectively). Our retrospective study suggests that MDS patients losing weight prior to alloSCT have an inferior outcome after transplantation. Prospective studies addressing pre-transplant nutritional interventions are highly warranted. PMID:26360778

  4. Systemic Administration of Allogeneic Mesenchymal Stem Cells Does Not Halt Osteoporotic Bone Loss in Ovariectomized Rats

    PubMed Central

    Sun, Yuxin; Lin, Sien; Gu, Weidong; Liu, Yamei; Zhang, Jinfang; Chen, Lin; Li, Gang

    2016-01-01

    Mesenchymal stem cells (MSCs) have innate ability to self-renew and immunosuppressive functions, and differentiate into various cell types. They have become a promising cell source for treating many diseases, particular for bone regeneration. Osteoporosis is a common metabolic bone disorder with elevated systemic inflammation which in turn triggers enhanced bone loss. We hypothesize that systemic infusion of MSCs may suppress the elevated inflammation in the osteoporotic subjects and slow down bone loss. The current project was to address the following two questions: (1) Will a single dose systemic administration of allogenic MSCs have any effect on osteoporotic bone loss? (2) Will multiple administration of allogenic MSCs from single or multiple donors have similar effect on osteoporotic bone loss? 18 ovariectomized (OVX) rats were assigned into 3 groups: the PBS control group, MSCs group 1 (receiving 2x106 GFP-MSCs at Day 10, 46, 91 from the same donor following OVX) and MSCs group 2 (receiving 2x106 GFP-MSCs from three different donors at Day 10, 46, 91). Examinations included Micro-CT, serum analysis, mechanical testing, immunofluorescence staining and bone histomorphometry analysis. Results showed that BV/TV at Day 90, 135, BMD of TV and trabecular number at Day 135 in the PBS group were significantly higher than those in the MSCs group 2, whereas trabecular spacing at Day 90, 135 was significantly smaller than that in MSCs group 2. Mechanical testing data didn’t show significant difference among the three groups. In addition, the ELISA assay showed that level of Rantes in serum in MSCs group 2 was significantly higher than that of the PBS group, whereas IL-6 and IL-10 were significantly lower than those of the PBS group. Bone histomorphometry analysis showed that Oc.S/BS and Oc.N/BS in the PBS group were significant lower than those in MSCs group 2; Ob.S/BS and Ob.N/BS did not show significant difference among the three groups. The current study

  5. Patients' perception of health-related quality of life during the first year after autologous and allogeneic stem cell transplantation.

    PubMed

    Andersson, I; Ahlberg, K; Stockelberg, D; Persson, L-O

    2011-05-01

    Little attention has been paid to examine health-related quality of life (HRQoL) the first year post-transplant, despite that this period is crucial for returning to normal life and functioning and to prevent delayed psychosocial adjustment. The purpose of the present study was to describe HRQoL after autologous versus allogeneic stem cell transplantations during the first year post-transplant. The allogeneic group was further divided into two groups: allogeneic stem cell transplantation after reduced intensive conditioning and allogeneic stem cell transplantation after myeloablative conditioning. All together 202 patients were enrolled in the study. HRQoL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the treatment-specific module High-Dose Chemotherapy (HDC-19). The questionnaires were filled out at six occasions (from inclusion to 12 months after transplantation). The reduced intensive conditioning group seemed to recover in the same way as the autologous group and these two groups were closer in their scoring compared with the myeloablative conditioning group. One month after the transplantation there were no significant differences in change scores between the autologous and reduced intensive conditioning group, and 1 year after the transplantation levels of symptoms and functioning were back to baseline or better. The myeloablative conditioning group, who perceived more symptoms and lower levels of functioning during the whole period, was still impaired in 10 out of 29 scales 1 year after the transplantation and no significant improvements compared with baseline were observed for this group.

  6. Plasma Fractionation Enriches Post-Myocardial Infarction Samples Prior to Proteomics Analysis

    PubMed Central

    de Castro Brás, Lisandra E.; DeLeon, Kristine Y.; Ma, Yonggang; Dai, Qiuxia; Hakala, Kevin; Weintraub, Susan T.; Lindsey, Merry L.

    2012-01-01

    Following myocardial infarction (MI), matrix metalloproteinase-9 (MMP-9) levels increase, and MMP-9 deletion improves post-MI remodeling of the left ventricle (LV). We provide here a technical report on plasma-analysis from wild type (WT) and MMP-9 null mice using fractionation and mass-spectrometry-based proteomics. MI was induced by coronary artery ligation in male WT and MMP-9 null mice (4–8 months old; n = 3/genotype). Plasma was collected on days 0 (pre-) and 1 post-MI. Plasma proteins were fractionated and proteins in the lowest (fraction 1) and highest (fraction 12) molecular weight fractions were separated by 1-D SDS-PAGE, digested in-gel with trypsin and analyzed by HPLC-ESI-MS/MS on an Orbitrap Velos. We tried five different fractionation protocols, before reaching an optimized protocol that allowed us to identify over 100 proteins. Serum amyloid A substantially increased post-MI in both genotypes, while alpha-2 macroglobulin increased only in the null samples. In fraction 12, extracellular matrix proteins were observed only post-MI. Interestingly, fibronectin-1, a substrate of MMP-9, was identified at both day 0 and day 1 post-MI in the MMP-9 null mice but was only identified post-MI in the WT mice. In conclusion, plasma fractionation offers an improved depletion-free method to evaluate plasma changes following MI. PMID:22778955

  7. Comparison of chimerism and minimal residual disease monitoring for relapse prediction after allogeneic stem cell transplantation for adult acute lymphoblastic leukemia.

    PubMed

    Terwey, Theis Helge; Hemmati, Philipp Georg; Nagy, Marion; Pfeifer, Heike; Gökbuget, Nicola; Brüggemann, Monika; Le Duc, Tanja Melinh; le Coutre, Philipp; Dörken, Bernd; Arnold, Renate

    2014-10-01

    Little data are available on the relative merits of chimerism and minimal residual disease (MRD) monitoring for relapse prediction after allogeneic hematopoietic stem cell transplantation (HCT). We performed a retrospective analysis of serial chimerism assessments in 101 adult HCT recipients with acute lymphoblastic leukemia (ALL) and of serial MRD assessments in a subgroup of 22 patients. All patients had received myeloablative conditioning. The cumulative incidence of relapse was significantly higher in the patients with increasing mixed chimerism (in-MC) compared with those with complete chimerism, low-level MC, and decreasing MC, but the sensitivity of in-MC detection with regard to relapse prediction was only modest. In contrast, MRD assessment was highly sensitive and specific. Patients with MRD positivity after HCT had the highest incidence of relapse among all prognostic groups analyzed. The median time from MRD positivity to relapse was longer than the median time from detection of in-MC, but in some cases in-MC preceded MRD positivity. We conclude that MRD assessment is a powerful prognostic tool that should be included in the routine post-transplantation monitoring of patients with ALL, but chimerism analysis may provide additional information in some cases. Integration of these tools and clinical judgment should allow optimal decision making with regard to post-transplantation therapeutic interventions.

  8. The in vitro generation of multi-tumor antigen-specific cytotoxic T cell clones: Candidates for leukemia adoptive immunotherapy following allogeneic stem cell transplantation.

    PubMed

    Mohamed, Yehia S; Bashawri, Layla A; Vatte, Chittibabu; Abu-Rish, Eman Y; Cyrus, Cyril; Khalaf, Wafaa S; Browning, Michael J

    2016-09-01

    Adoptive T-cell immunotherapy is a promising approach to manage and maintain relapse-free survival of leukemia patients, especially following allogeneic stem cell transplantation. Post-transplant adoptive immunotherapy using cytotoxic T lymphocytes (CTLs) of the donor origin provide graft-versus-tumor effects, with or without graft-versus-host disease. Myeloid leukemias express immunogenic leukemia associated antigens (LAAs); such as WT-1, PRAME, MAGE, h-TERT and others, most of them are able to induce specific T cell responses whenever associated with the proper co-stimulation. We investigated the ability of a LAA-expressing hybridoma cell line to induce CTL clones in PBMCs of HLA-matched healthy donors in vitro. The CTL clones were induced by repetitive co-culture with LAAs-expressing, HLA-A*0201(+) hybrid cell line, generated by fusion of leukemia blasts to human immortalized APC (EBV-sensitized B-lymphoblastoid cell line; HMy2). The induced cytotoxic T cell clones were phenotypically and functionally characterized by pentamer analysis, IFN-γ release ELISPOT and cellular cytotoxicity assays. All T cell lines showed robust peptide recognition and functional activity when sensitized with HLA-A*0201-restricted WT-1235-243, hTERT615-624 or PRAME100-108 peptides-pulsed T2 cells, in addition to partially HLA-matched leukemia blasts. This study demonstrates the feasibility of developing multi-tumor antigen-specific T cell lines in allogeneic PBMCs in vitro, using LAA-expressing tumor/HMy2 hybrid cell line model, for potential use in leukemia adoptive immunotherapy in partially matched donor-recipient setting. PMID:27490939

  9. Assessing the technical efficiency of health posts in rural Guatemala: a data envelopment analysis

    PubMed Central

    Hernández, Alison R.; Sebastián, Miguel San

    2014-01-01

    Introduction Strengthening health service delivery to the rural poor is an important means of redressing inequities. Meso-level managers can help enhance efficiency in the utilization of existing resources through the application of practical tools to analyze routinely collected data reflecting inputs and outputs. This study aimed to assess the efficiency and change in productivity of health posts over two years in a rural department of Guatemala. Methods Data envelopment analysis was used to measure health posts’ technical efficiency and productivity change for 2008 and 2009. Input/output data were collected from the regional health office of Alta Verapaz for 34 health posts from the 19 districts comprising the health region. Results Technical efficiency varied widely across health posts, with mean scores of 0.78 (SD=0.24) and 0.75 (SD=0.21) in 2008 and 2009, respectively. Overall, productivity increased by 4%, though 47% of health posts experienced a decline in productivity. Results were combined on a bivariate plot to identify health posts at the high and low extremes of efficiency, which should be followed up to determine how and why their production processes are operating differently. Conclusions Assessing efficiency using the data that are available at the meso-level can serve as a first step in strengthening performance. Further work is required to support managers in the routine application of efficiency analysis and putting the results to use in guiding efforts to improve service delivery and increase utilization. PMID:24461356

  10. The Impact of Guided Notes on Post-Secondary Student Achievement: A Meta-Analysis

    ERIC Educational Resources Information Center

    Larwin, Karen H.; Larwin, David A.

    2013-01-01

    The common practice of using of guided notes in the post-secondary classroom is not fully appreciated or understood. In an effort to add to the existing research about this phenomenon, the current investigation expands on previously published research and one previously published meta-analysis that examined the impact of guided notes on…

  11. The School-to-Work Transition of Canadian Post-Secondary Graduates: A Dynamic Analysis

    ERIC Educational Resources Information Center

    Finnie, Ross

    2004-01-01

    This paper reports the results of an empirical analysis of the school-to-work transition of Canadian post-secondary graduates based on three waves of the National Graduates Surveys, representing those who successfully completed their programmes at Canadian colleges and universities in 1982, 1986, and 1990. Information was gathered during…

  12. An Analysis of Foster Care Placement History and Post-Secondary Graduation Rates

    ERIC Educational Resources Information Center

    Day, Angelique; Dworsky, Amy; Feng, Wenning

    2013-01-01

    Prior research has document significant disparities in post-secondary educational attainment between young adults who had been in foster care and their peers in the general population. This study uses survival analysis to compare the four-year college graduation rate of students who had been in foster care to the graduation rate of first…

  13. Campus Sustainability Governance in Canada: A Content Analysis of Post-Secondary Institutions' Sustainability Policies

    ERIC Educational Resources Information Center

    Vaughter, Philip; McKenzie, Marcia; Lidstone, Lauri; Wright, Tarah

    2016-01-01

    Purpose: This paper aims to provide an overview of a content analysis of sustainability policies from Canadian post-secondary education institutions. The paper reports findings on the orientations to sustainability evident in the policies; references to other policies within the documents; and other key themes on how sustainability is engaged in…

  14. Intrasplenic transplantation of allogeneic hepatocytes prolongs survival in anhepatic rats.

    PubMed

    Arkadopoulos, N; Lilja, H; Suh, K S; Demetriou, A A; Rozga, J

    1998-11-01

    To examine whether hepatocytes transplanted in the spleen can function as an ectopic liver, we performed hepatocyte transplantation in rats that were rendered anhepatic. Total hepatectomy was performed by using a novel single-stage technique. Following hepatectomy, Group 1 rats (n = 16) were monitored until death to determine survival time without prior intervention. Group 2 anhepatic rats (n = 20) were sacrificed at various times to measure blood hepatocyte growth factor (HGF) and transforming growth factor beta1 (TGF-beta1) levels. Group 3 (n = 16) rats received intrasplenic injection of isolated hepatocytes (2.5 x 10(7) cells/rat) followed by total hepatectomy after 3 days. Group 4 (n = 12) sham-transplanted rats received intrasplenic saline infusion, and after 3 days they were rendered anhepatic. Group 2, 3, and 4 rats were maintained on daily Cyclosporine A (10 mg/kg; intramuscularly). Group 1 anhepatic rats survived for 22.4 +/- 5.2 hours (standard deviation). The anhepatic state was associated with a progressive and statistically significant rise in blood HGF and TGF-beta1 levels. Rats that received hepatocyte transplantation before total hepatectomy had a significantly longer survival time than sham-transplanted anhepatic controls (34.1 +/- 8.5 vs. 15.5 +/- 4.8 hrs, P < .01). Additionally, at 12 hours post-hepatectomy, transplanted rats had significantly lower blood ammonia, prothrombin time, international normalized ratio, and TGF-beta1 levels when compared with sham-transplanted controls. In conclusion, intrasplenic transplantation of allogeneic hepatocytes prolonged survival, improved blood chemistry, and lowered blood TGF-beta1 levels in rats rendered anhepatic. PMID:9794923

  15. Relapse after allogeneic stem cell transplantation

    PubMed Central

    Barrett, A John; Battiwalla, Minoo

    2012-01-01

    Since allogeneic stem cell transplantation (SCT) represents an intensive curative treatment for high-risk malignancies, its failure to prevent relapse leaves few options for successful salvage treatment. While many patients have a high early mortality from relapse, some respond and have sustained remissions, and a minority has a second chance of cure with appropriate therapy. The prognosis for relapsed hematological malignancies after SCT depends on four factors: the time elapsed from SCT to relapse (with relapses occurring within 6 months having the worst prognosis), the disease type (with chronic leukemias and some lymphomas having a second possibility of cure with further treatment), the disease burden and site of relapse (with better treatment success if disease is treated early), and the conditions of the first transplant (with superior outcome for patients where there is an opportunity to increase either the alloimmune effect, the specificity of the antileukemia effect with targeted agents or the intensity of the conditioning in a second transplant). These features direct treatments toward either modified second transplants, chemotherapy, targeted antileukemia therapy, immunotherapy or palliative care. PMID:21083034

  16. Kinetics of iron removal by phlebotomy in patients with iron overload after allogeneic hematopoietic cell transplantation

    PubMed Central

    Eisfeld, Ann-Kathrin; Krahl, Rainer; Jaekel, Nadja; Niederwieser, Dietger; Al-Ali, Haifa Kathrin

    2012-01-01

    Excess body iron could persist for years after allogeneic hematopoietic cell transplantation (HCT) with possible deleterious sequels. An iron depletive therapy with phlebotomy seems rational. Kinetics of iron removal by phlebotomy without erythropoietin support in non-thalassemic adult patients with iron overload after HCT and the impact of pre- and post-HCT hemochromatosis (HFE) genotype on iron mobilization were investigated. Patients and methods: Phlebotomy was initiated in 61 recipients of allografts due to hematologic malignancies (median age 48 years) after a median of 18 months. The prephlebotomy median serum ferritin (SF) was 1697ng/ml and the median number of blood transfusions 28 units. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST), alkaline phosphates (AP), and bilirubin were elevated in 55.7%, 64% and 11.5% patients respectively. HFE-genotype was elucidated by polymerase chain reaction using hybridization probes and melting curve analysis. Results: Phlebotomy was well-tolerated irrespective of age or conditioning. A negative iron balance in 80% of patients (median SF 1086 ng/ml) and a rise in hemoglobin were observed (p<0.0001). Higher transfusional burden and SF were associated with a greater iron mobilization per session (p=0.02). In 58% of patients, a plateau after an initial steady decline in SF was followed by a second decline under further phlebotomy. The improvement in ALT (p=0.002), AST (p=0.03), AP (p=0.01), and bilirubin (p<0.0001) did not correlate with the decline in SF. Mutant HFE-gene variants were detected in 14/55 (25%) pre-HCT and 22/55 (40%) patients post-HCT. Overall, dissimilar pre- and posttransplantational HFE-genotypes were detected in 20/55 (40%) patients. Posttransplantational mutant HFE variants correlated with a slower decline in SF (p=0.007). Conclusions: Phlebotomy is a convenient therapy of iron overload in survivors of HCT. A negative iron balance and a rise in hemoglobin were observed in the majority of

  17. TOPP: A post-processor for TOPAZ, the one dimensional pipe flow analysis code

    SciTech Connect

    Martin, R.W.

    1987-07-01

    TOPP is a Lawrence Livermore National Laboratory (LLNL) post-processor for producing graphical results from the one dimensional pipe flow analysis code, TOPAZ. TOPAZ was written by W. S. Winters of Sandia National Laboratory, Livermore (SNLL) and is available on the CRAY computers at LLNL. The SNLL version of TOPAZ produces a very limited set of variables that can be used as input to a post-processor. The version at LLNL has been modified to output every time-dependent variable to an absolute binary file at the user specified minor edit frequency. TOPP reads this absolute binary file and produces a variety of graphical results. 2 refs.

  18. TRINITY II: A post-processing program for two-dimensional finite element analysis data

    SciTech Connect

    Glick, J.H.; Gartling, D.K.

    1988-05-01

    TRINITY II is a program for post-processing data from two-dimensional finite element analyses. The program provides graphical display of mesh and solution data as well as data manipulation, file editing and selective printing of data. TRINITY II accepts data from any analysis code that employs the EXODUS file format; post-processing can be done interactively or in batch mode using any graphics device supported by the Sandia Virtual Device Interface. The capabilities and use of the program are described. 4 refs.

  19. Analysis of dentinal stress distribution of maxillary central incisors subjected to various post-and-core applications.

    PubMed

    Toksavul, Suna; Zor, Mehmet; Toman, Muhitten; Güngör, Mehmet Ali; Nergiz, Ibrahim; Artunç, Celal

    2006-01-01

    This study evaluated the stress distribution on an endodontically treated maxillary central incisor restored with different post-and-core systems by using a three-dimensional finite element analysis model. Seven three-dimensional finite element models were created. Each model contained cortical bone, cancelous bone, periodontal ligament, 3 mm apical root canal filling, post-and-core and all-ceramic crowns. Two different pre-fabricated zirconia ceramic post systems, a glass fiber-reinforced post system and a titanium post system were modeled. As a control, an all-ceramic crown on an endodontically treated maxillary central incisor without a post-and-core was modeled. Each model received a 45 degrees oblique occlusal load at a constant intensity of 100 N. In each model, the ratio of Von Mises stress distribution was compared. The greatest stresses were observed in the coronal third of the roots on facial surfaces. The ratio of Von Mises stress distribution in dentin for the zirconia ceramic post (CosmoPost) and ceramic core (Cosmo Ingot), zirconia ceramic post (CosmoPost) and composite core (Tetric Ceram), glass fiber-reinforced post (FRC Postec) and composite core (Tetric Ceram), titanium post (Er post) and composite core (Tetric Ceram), zirconia ceramic post (Cerapost) and ceramic core (Cosmo Ingot), zirconia ceramic post (Cerapost) and composite core (Tetric Ceram) and the control group were 0.886, 0.889, 0.988, 0.924, 0.889, 0.893 and 1, respectively. The stress concentrations in dentin created by two different zirconia ceramic post systems were nearly the same. The zirconia ceramic post systems created slightly less stress concentration in dentin than the glass fiber-reinforced and titanium posts.

  20. Long duration exposure facility post-flight thermal analysis, part 1

    NASA Technical Reports Server (NTRS)

    Berrios, William M.; Sampair, Thomas R.

    1992-01-01

    Results of the post-flight thermal analysis of the Long Duration Exposure Facility (LDEF) mission are presented. The LDEF mission thermal analysis was verified by comparing the thermal model results to flight data from the LDEF Thermal Measurements System (THERM). Post-flight calculated temperature uncertainties have been reduced to under +/- 18 F from the pre-flight uncertainties of +/- 40 F. The THERM consisted of eight temperature sensors, a shared tape recorder, a standard LDEF flight battery, and an electronics control box. The temperatures were measured at selected locations on the LDEF structure interior during the first 390 days of flight and recorded for post-flight analysis. After the LDEF retrieval from Space on 12 Jan. 1990, the tape recorder was recovered from the spacecraft and the data reduced for comparison to the LDEF predicted temperatures. The LDEF mission temperatures were calculated prior to the LDEF deployment on 7 Apr. 1980, and updated after the LDEF retrieval with the following actual flight parameter data: including thermal fluxes, spacecraft attitudes, thermal coatings degradation, and contamination effects. All updated data used for the calculation of post-flight temperatures is also presented in this document.

  1. Long duration exposure facility post-flight thermal analysis, part 2

    NASA Technical Reports Server (NTRS)

    Berrios, William M.; Sampair, Thomas R.

    1992-01-01

    Results of the post-flight thermal analysis for the Long Duration Exposure Facility (LDEF) mission are presented. The LDEF mission thermal analysis was verified by comparing the thermal model results to flight data from the LDEF Thermal Measurements System (THERM). Post-flight calculated temperature uncertainties have been reduced to under +/- 18 F from the pre-flight uncertainties of +/- 40 F. The THERM consisted of eight temperature sensors, a shared tape recorder, a standard LDEF flight battery, and an electronics control box. The temperatures were measured at selected locations on the LDEF structure interior during the first 390 days of flight and recorded for post-flight analysis. After the LDEF retrieval from Space on 12 Jan. 1990, the tape recorder was recovered from the spacecraft and the data reduced for comparison to the LDEF predicted temperatures. The LDEF mission temperatures were calculated prior to the LDEF deployment on 7 Apr. 1980, and updated after the LDEF retrieval with the following actual flight parameter data: thermal fluxes, spacecraft attitudes, thermal coatings degradation, and contamination effects. All updated data used for calculation of post-flight temperatures is also presented in this document.

  2. Analysis of Post-Deployment Cognitive Performance and Symptom Recovery in U.S. Marines

    PubMed Central

    Haran, F. J.; Alphonso, Aimee L.; Creason, Alia; Campbell, Justin S.; Johnson, Dagny; Young, Emily; Tsao, Jack W.

    2013-01-01

    Background Computerized neurocognitive testing (NCAT) has been proposed to be useful as a screening tool for post-deployment cognitive deficits in the setting of mild traumatic brain injury (mTBI). We assessed the clinical utility of post-injury/post-deployment Automated Neurocognitive Assessment Metric (ANAM) testing, using a longitudinal design to compare baseline ANAM tests with two post-deployment ANAM tests in a group of Marines who experienced combat during deployment. Methods and Findings Post-deployment cognitive performance and symptom recovery were compared in a subsample of 1324 U.S. Marines with high rates of combat exposure during deployment. Of the sample, 169 Marines had available baseline and twice repeated post-deployment ANAM results. A retrospective analysis of the ANAM data, which consisted of a self-report questionnaire about deployment-related blast exposure, recent history of mTBI, current clinical symptoms, and cognitive performance. Self-reported concussion sustained anytime during deployment was associated with a decrease in cognitive performance measured between 2–8 weeks post-deployment. At the second post-deployment test conducted on average eight months later, performance on the second simple reaction time test, in particular, remained impaired and was the most consistent and sensitive indicator of the cognitive decrements. Additionally, post-concussive symptoms were shown to persist in injured Marines with a self-reported history of concussion for an additional five months after most cognitive deficits resolved. Results of this study showed a measurable deployment effect on cognitive performance, although this effect appears to resolve without lasting clinical sequelae in those without history of deployment-related concussion. Conclusions These results highlight the need for a detailed clinical examination for service members with history of concussion and persistent clinical symptoms. Reliance solely upon computerized

  3. Motivational Interviewing Post-Stroke: An Analysis of Stroke Survivors' Concerns and Adjustment.

    PubMed

    Auton, Malcolm F; Patel, Kulsum; Carter, Bernie; Hackett, Maree; Thornton, Tim; Lightbody, Catherine E; Leathley, Michael J; Watkins, Caroline L

    2016-01-01

    Our earlier research demonstrated that participation in four sessions of motivational interviewing (MI) early post-stroke has a positive impact on stroke survivors' mood. However, the theoretical underpinnings of MI in supporting adjustment (rather than its traditional use in supporting behavior change) require clarification. This article describes a content analysis of MI transcripts for 10 participants in our previous study, to identify the focus of discussions (patient "concerns") and potential effective components of our MI approach. Patients' post-stroke concerns were shown in 16 categories, including frustration, family impact, and getting well. There was a pattern of change discourse across sessions: "Sustain talk" (reasons for not changing) reduced from Session 1 onward, "change talk" (intent to change) increased then reduced, and "change expressed" (changes achieved) increased from Sessions 1 to 4. MI facilitates healthy adjustment post-stroke in some patients, in turn affecting mood, but clarification of how this effect is achieved requires further exploration. PMID:25904673

  4. Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma

    PubMed Central

    Klyuchnikov, Evgeny; Bacher, Ulrike; Ahn, Kwang Woo; Carreras, Jeanette; Kröger, Nicolaus M.; Hari, Parameswaran N.; Ku, Grace H.; Ayala, Ernesto; Chen, Andy I.; Chen, Yi-Bin; Cohen, Jonathon B.; Freytes, César O.; Gale, Robert Peter; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed A.; Lazarus, Hillard M.; Martino, Rodrigo; Mussetti, Alberto; Savani, Bipin N.; Schouten, Harry C.; Usmani, Saad Z.; Wiernik, Peter H.; Wirk, Baldeep; Smith, Sonali M.; Sureda, Anna; Hamadani, Mehdi

    2015-01-01

    Grade-3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade-3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. A total of 197 patients undergoing first RIC allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naïve patients were excluded. Allo-HCT recipients were younger; more heavily pretreated, and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS) and overall survival (OS) for auto-HCT vs. allo-HCT groups were 4% vs. 27% (p<0.001); 61% vs. 20% (p<0.001); 36% vs. 51% (p=0.07) and 59% vs. 54% (p=0.7), respectively. On multivariate analysis auto-HCT was associated with reduced risk of NRM (RR=0.20; p=0.001). Within the first 11months post-HCT auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; p=0.003) and inferior PFS (RR=3.2; p=0.005). In the first 24 months post-HCT, auto-HCT was associated with improved OS (RR=0.42; p=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; p=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors. PMID:26437062

  5. Failure mode analysis of a post-tension anchored dam using linear finite element analysis

    NASA Astrophysics Data System (ADS)

    Corn, Aimee

    There are currently over 84,000 dams in the United States, and the average age of those dams is 52 years. Concrete gravity dams are the second most common dam type, with more than 3,000 in the United States. Current engineering technology and technical understanding of hydrologic and seismic events has resulted in significant increases to the required design loads for most dams; therefore, many older dams do not have adequate safety for extreme loading events. Concrete gravity dams designed and constructed in the early 20th century did not consider uplift pressures beneath the dam, which reduces the effective weight of the structure. One method that has been used to enhance the stability of older concrete gravity dams includes the post-tension anchor (PTA) system. Post-tensioning infers modifying cured concrete and using self-equilibrating elements to increase the weight of the section, which provides added stability. There is a lack of historical evidence regarding the potential failure mechanisms for PTA concrete gravity dams. Of particular interest, is how these systems behave during large seismic events. The objective of this thesis is to develop a method by which the potential failure modes during a seismic event for a PTA dam can be evaluated using the linear elastic finite element method of analysis. The most likely potential failure modes (PFM) for PTA designs are due to tensile failure and shear failure. A numerical model of a hypothetical project was developed to simulate PTAs in the dam. The model was subjected to acceleration time-history motions that simulated the seismic loads. The results were used to evaluate the likelihood of tendon failure due to both tension and shear. The results from the analysis indicated that the PTA load increased during the seismic event; however, the peak load in the tendons was less than the gross ultimate tensile strength (GUTS) and would not be expected to result in tensile failure at the assumed project. The analysis

  6. Prophylactic clipping and post-polypectomy bleeding: a meta-analysis and systematic review

    PubMed Central

    Boumitri, Christine; Mir, Fazia A.; Ashraf, Imran; Matteson-Kome, Michelle L.; Nguyen, Douglas L.; Puli, Srinivas R.; Bechtold, Matthew L.

    2016-01-01

    Background Bleeding after polypectomy is a common issue associated with colonoscopy. To help prevent post-polypectomy bleeding, many endoscopists place clips at the site. However, this practice remains controversial. Therefore, we performed a meta-analysis of the efficacy of clip placement in the prevention of post-polypectomy bleeding. Methods Multiple databases, including Embase, Scopus, MEDLINE/PubMed, CINAHL, Cochrane databases, and recent abstracts from major American meetings were searched in April 2016. Using the DerSimonian and Laird (random effects) model with odds ratio (OR), a meta-analysis was performed of post-polypectomy bleeding with prophylactic clip versus no prophylactic clip. Results Five hundred and thirty potential articles and abstracts were discovered. Thirty-five articles were reviewed, with 12 studies satisfying the inclusion criteria. No statistically significant difference in prophylactic clipping versus no prophylactic clipping for post-polypectomy bleeding in all polyps was found when all studies (OR 1.49; 95% CI: 0.56–4.00; P=0.42), only peer-reviewed studies where abstracts were excluded (OR 0.84; 95% CI: 0.42–1.69; P=0.63), and only randomized controlled trials (OR 1.24; 95% CI: 0.69–2.24; P=0.47) were analyzed. Conclusions The use of prophylactic clipping for all polypectomies does not seem to prevent post-polypectomy bleeding and should not be a routine practice. However, for large polyps (>2 cm), prophylactic clipping may or may not be beneficial in preventing post-polypectomy bleeding. Further studies are required to fully evaluate this subgroup.

  7. Retrospective analysis of post-mortem findings in 1,444 aged donkeys.

    PubMed

    Morrow, L D; Smith, K C; Piercy, R J; du Toit, N; Burden, F A; Olmos, G; Gregory, N G; Verheyen, K L P

    2011-01-01

    The aim of this study was to describe and report the prevalence of conditions found at necropsy examination of UK donkeys. Records from 1,444 donkeys over a 7-year period were included in the analysis. Sixty-one categories of post-mortem finding were identified from 9,744 observations. The four most prevalent conditions noted were dental disorder (78.7%), vascular disease other than aneurysm (60.9%), arthritis (55.4%) and foot disorder (44.8%). Gastric ulceration was found in 42% of the donkeys and gastrointestinal impaction in 18.6%. The most frequent combination of two post-mortem findings in the same animal was arthritis and dental disorder. The most common disorders were associated with age, body weight and/or body condition post mortem and, for some disorders, gender. For many of the post-mortem findings, crude associations were found between the presence of one finding and the odds of also having certain other post-mortem findings. This study is the first to summarize all conditions noted at necropsy examination for a large group of donkeys. The findings increase knowledge of diseases and conditions of this species and may be useful when investigating the relevance of various pathological conditions in the live animal.

  8. Diffuse alveolar hemorrhage: retrospective review of clinical outcome in allogeneic transplant recipients treated with aminocaproic acid.

    PubMed

    Wanko, Sam O; Broadwater, Gloria; Folz, Rodney J; Chao, Nelson J

    2006-09-01

    Diffuse alveolar hemorrhage (DAH) after allogeneic hematopoietic stem cell transplantation (HSCT) is often fatal. Standard therapy with high-dose corticosteroid is not always effective. There is paucity of data in the literature about other potentially useful agents, such as aminocaproic acid (Amicar) in the post-transplantation setting. We retrospectively reviewed our data on 115 consecutive patients who underwent HSCT and had pulmonary complications, with the aim of determining the overall clinical outcome in recipients of allogeneic transplants and in the subgroup of these patients who were treated with concomitant Solu-Medrol and aminocaproic acid. Aminocaproic acid was added at the discretion of the attending physician. We identified 14 allogeneic transplant recipients (median age, 41 years) with 15 episodes of DAH who were treated with Solu-Medrol (250 mg to 1 g intravenously per day). Of these, 8 patients also received concomitant aminocaproic acid at 1000 mg intravenously every 6 hours. Failure to improve was the most common reason for adding aminocaproic acid. The incidence of DAH was 12.2% (10.3% in myeloablative versus 1.9% in nonmyeloablative recipients). The overall 100-day DAH mortality and median transplantation survival were 60% and 99 days, respectively. Among the subset of patients treated with the combination of Solu-Medrol and aminocaproic acid, we observed a 100-day DAH mortality and median transplantation survival of 44% and 167 days, respectively, compared with 83% and 96.5 days in those treated with Solu-Medrol alone. The median time to DAH was 40.5 days, and the median time to death was 53 days in the combined treatment group compared with 29.5 days in those treated with steroid alone. There were no significant differences in coagulation parameters between subsets. Infections (yeast, respiratory syncytial virus, herpes simplex virus, and parainfluenza) were isolated and treated from 6 diagnostic bronchial alveolar lavage samples and were

  9. A Juggling Act: A Feminist Post-Structuralist Analysis of Girls' and Boys' Talk in the Secondary Classroom.

    ERIC Educational Resources Information Center

    Baxter, Judith

    2002-01-01

    Argues that post-structuralist discourse analysis has a strong contribution to make to feminist and educational research, examining how the use of feminist post-structuralist discourse analysis (FPDA) can be tricky. Highlights an ethnographic study of secondary school girls' and boys' speech in class. Suggests that FPDA can produce powerful…

  10. The Treatment of Dyslipidemia in Allogeneic Hematopoietic Stem Cell Transplant Patients

    PubMed Central

    Marini, Bernard L.; Choi, Sung Won; Byersdorfer, Craig Alan; Cronin, Simon; Frame, David G.

    2015-01-01

    As survival rates in allogeneic hematopoietic stem cell transplantation (HSCT) continue to improve, attention to long-term complications, including cardiovascular disease, become a major concern. Cardiovascular disease and dyslipidemia are a common, yet often overlooked occurrence post-HSCT that results in significant morbidity and mortality. There is also increasing evidence that several anti-hyperlipidemia medications, the HMG-CoA reductase inhibitors in particular, may have a role in modulating graft-versus-host disease (GVHD). However, factors such as drug-drug interactions, adverse effect profiles, and the relative efficacy in lowering cholesterol and triglyceride levels must be taken into account when choosing safe and effective lipid lowering therapy in this setting. This review seeks to provide guidance to the clinician in the management of dyslipidemia in the allogeneic HSCT population, taking into account the recently published ACC/AHA guidelines on hyperlipidemia management, special considerations in this challenging population, and the evidence for each agent’s potential role in modulating GVHD. PMID:25459644

  11. The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia

    PubMed Central

    Oehler, Vivian G.; Gooley, Ted; Snyder, David S.; Johnston, Laura; Lin, Allen; Cummings, Carrie C.; Chu, Su; Bhatia, Ravi; Forman, Stephen J.; Negrin, Robert S.; Appelbaum, Frederick R.; Radich, Jerald P.

    2007-01-01

    The impact of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) on subsequent allogeneic transplantation is uncertain. To better understand this relationship, we retrospectively compared 145 patients with CML receiving IM for a minimum of 3 months before allogeneic hematopoietic cell transplantation (HCT) to 231 patients with CML who did not. IM treatment was associated with no increase in early hepatotoxicity or engraftment delay after HCT compared with the historical cohort. In addition, there was no statistically significant difference in the IM-treated cohort compared with the historical cohort with regard to overall survival, disease-free survival, relapse, and nonrelapse mortality. For chronic-phase (CP) patients, IM response prior to HCT was associated with post-HCT outcome. Patients who underwent transplantation in CP with a suboptimal response or a loss of response on IM had a statistically significant higher hazard of mortality when compared with CP patients who achieved a complete cytogenetic response (CCR) or major cytogenetic response (MCR) on IM (HR = 5.31, 95% confidence interval [CI] 1.13-25.05, P = .03). These data indicate that pre-HCT IM is not associated with increased transplant-related morbidity (TRM) or poorer outcomes. However, patients with a suboptimal or loss of IM response before HCT do worse, suggesting a more aggressive disease course for these patients. PMID:17062727

  12. The regulation of allogeneic human cells and tissue products as biomaterials.

    PubMed

    Yano, Kazuo; Tsuyuki, Kenichiro; Watanabe, Natsumi; Kasanuki, Hiroshi; Yamato, Masayuki

    2013-04-01

    The current definition of biomaterials differs vastly from it of just a decade ago. According to advancing technologies, it encompasses unpredictable materials such as engineered human cells and tissue. These biomaterials also have to be approved to use in health care business by regulatory authority, which are defined as drug, medical device, or biologics in the regulation. This Leading Opinion Paper addresses the regulatory issues of engineered human cells and tissue products using allogeneic cells that should have a great possibility to develop therapeutics for life-threating diseases or orphan diseases. Six allogeneic human cells and tissue products derived from neonatal or infant fibroblasts and/or keratinocytes were approved as medical devices or biologics in the United States as well as a hematopoietic cell product. For five of the seven products, well-controlled comparative clinical trials were conducted as pre-approval evaluation followed by post-approval evaluation. Although these products avoid a sterilization process usually used for medical devices, no serious malfunction that would lead to class 1 recall was reported. This article would provide insight for development of the engineered human cells and tissue.

  13. Venous Thromboembolism after Allogeneic Pediatric Hematopoietic Stem Cell Transplantation: A Single-Center Study

    PubMed Central

    Azık, Fatih; Gürlek Gökçebay, Dilek; Tavil, Betül; Işık, Pamir; Tunç, Bahattin; Uçkan, Duygu

    2015-01-01

    Objective: Venous thromboembolism (VTE) in children who undergo hematopoietic stem cell transplantation (HSCT) has high morbidity. The aim of this study is to assess the incidence of VTE in allogeneic pediatric HSCT recipients and the contribution of pretransplant prothrombotic risk factors to thrombosis. Materials and Methods: We retrospectively evaluated 92 patients between April 2010 and November 2012 undergoing allogeneic HSCT who had completed 100 days post-HSCT. Before HSCT, coagulation profiles; acquired and inherited prothrombotic risk factors including FV G1691A (factor V Leiden), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations; and serum homocysteine and lipoprotein (a), plasma antithrombin III, protein C, and protein S levels were obtained from all patients. Results: In the screening of thrombophilia, 8 patients (9%) were heterozygous for factor V Leiden, 5 (6%) were homozygous for MTHFR 677TT, 12 (14%) were homozygous for MTHFR 1298CC, and 2 (2%) were heterozygous for prothrombin G20210A mutation. We observed VTE in 5 patients (5.4%); a prothrombotic risk factor was found in 3 out of these 5 patients, while 4 out of 5 patients had central venous catheters. It was determined there was no significant relationship between VTE and inherited prothrombotic risk factors. Conclusion: VTE after HSCT seems to be a low-frequency event that may be due to low-dose, low-molecular-weight heparin prophylaxis, and the role of inherited prothrombotic risk factors cannot be entirely excluded without a prospective study. PMID:25912774

  14. Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.

    PubMed

    Yoo, Sang Woo; Chung, Eun Jin; Kim, Sun Young; Ko, Jeong Hee; Baek, Hey Sung; Lee, Hyun Ju; Oh, Sung Hee; Jeon, Seok Cheol; Lee, Woong Soo; Park, Chan Kum; Lee, Chul Hoon

    2012-06-01

    EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT. PMID:21923886

  15. Cellular therapy following allogeneic stem-cell transplantation

    PubMed Central

    Rager, Alison

    2011-01-01

    Allogeneic hematopoietic stem-cell transplantation (HSCT) is the most effective approach for many patients with hematologic malignancies. Unfortunately, relapse remains the most common cause of death after allogeneic HSCT, and the prognosis of relapsed disease is poor for most patients. Induction of a graft-versus-leukemia (GVL), or graft-versus-tumor, effect through the use of donor leukocyte infusion (DLI), or donor lymphocyte infusion, has been remarkably successful for relapsed chronic myelogenous leukemia. Unfortunately, response to DLI in other hematologic malignancies is much less common and depends on many factors including histology, pace and extent of relapse, and time from HSCT to relapse. Furthermore, graft-versus-host disease (GVHD) is common after DLI and often limits successful immunotherapy. Ultimately, manipulations to minimize GVHD while preserving or enhancing GVL are necessary to improve outcomes for relapse after allogeneic HSCT. PMID:23556106

  16. Severe weight loss in 3 months after allogeneic hematopoietic SCT was associated with an increased risk of subsequent non-relapse mortality.

    PubMed

    Fuji, S; Mori, T; Khattry, N; Cheng, J; Do, Y R; Yakushijin, K; Kohashi, S; Fukuda, T; Kim, S-W

    2015-01-01

    Patients after allogeneic hematopoietic SCT (HSCT) are at risk of malnutrition. To assess the impact of malnutrition after allogeneic HSCT on transplant outcomes, we conducted a retrospective study. Adult patients who received allogeneic HSCT from 2000 to 2009 for standard-risk leukemia and achieved disease-free survival up to 3 months after allogeneic HSCT were included. From participating centers, 145 patients were enrolled. Median age was 46 years (19-68). Patients were classified based on weight loss during 3 months after allogeneic HSCT as follows: normal group (weight loss <5%, n=53), mild malnutrition group (5%⩽weight loss<10%, n=47), severe malnutrition group (10% ⩽weight loss, n=45). The cumulative incidences of 2-year nonrelapse mortality (NRM) were 3.8% in the normal group, 8.5% in the mild malnutrition group and 27.3% in the severe malnutrition group. The probabilities of a 2-year OS were 73.2% in the normal group, 74.5% in the mild malnutrition group and 55.3% in the severe malnutrition group. In multivariate analysis, severe malnutrition was associated with an increased risk of NRM and a worse OS. In conclusion, weight loss ⩾10% was associated with a worse clinical outcome. Prospective studies that identify patients at risk of malnutrition and intervention by a nutritional support team are warranted. PMID:25285803

  17. Polychlorinated biphenyls (PCBs) depress allogeneic natural cytotoxicity by earthworm coelomocytes

    SciTech Connect

    Suzuki, M.M.; Cooper, E.L.; Eyambe, G.S.; Goven, A.J.; Fitzpatrick, L.C.; Venables, B.J. |

    1995-10-01

    Coelomocytes of the earthworm Lumbricus terrestris caused significant spontaneous allogeneic cytotoxicity in a 24-h trypan blue assay, but not in an assay using lactate dehydrogenase (LDH) release. Allogeneic cytotoxicity assays using cells from worms exposed to polychlorinated biphenyls (PCBs) suggest that PCBs can suppress a natural killing (NK-like) reaction. The implications of this work are twofold: understanding the evolution of natural killing (NK-like) activity and providing preliminary information on how spontaneous killing, a component of cellular immunity, may be compromised by pollutants.

  18. Teeth restored using fiber-reinforced posts: in vitro fracture tests and finite element analysis.

    PubMed

    Schmitter, M; Rammelsberg, P; Lenz, J; Scheuber, S; Schweizerhof, K; Rues, S

    2010-09-01

    In dentistry the restoration of decayed teeth is challenging and makes great demands on both the dentist and the materials. Hence, fiber-reinforced posts have been introduced. The effects of different variables on the ultimate load on teeth restored using fiber-reinforced posts is controversial, maybe because the results are mostly based on non-standardized in vitro tests and, therefore, give inhomogeneous results. This study combines the advantages of in vitro tests and finite element analysis (FEA) to clarify the effects of ferrule height, post length and cementation technique used for restoration. Sixty-four single rooted premolars were decoronated (ferrule height 1 or 2 mm), endodontically treated and restored using fiber posts (length 2 or 7 mm), composite fillings and metal crowns (resin bonded or cemented). After thermocycling and chewing simulation the samples were loaded until fracture, recording first damage events. Using UNIANOVA to analyze recorded fracture loads, ferrule height and cementation technique were found to be significant, i.e. increased ferrule height and resin bonding of the crown resulted in higher fracture loads. Post length had no significant effect. All conventionally cemented crowns with a 1-mm ferrule height failed during artificial ageing, in contrast to resin-bonded crowns (75% survival rate). FEA confirmed these results and provided information about stress and force distribution within the restoration. Based on the findings of in vitro tests and computations we concluded that crowns, especially those with a small ferrule height, should be resin bonded. Finally, centrally positioned fiber-reinforced posts did not contribute to load transfer as long as the bond between the tooth and composite core was intact. PMID:20227533

  19. TC-2 post Helios experiment data review. [postflight systems analysis of spacecraft performance

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Data are presented from a systems postflight analysis of the Centaur Launch Vehicle and Helios. Also given is a comparison of data from preflight analyses. Topics examined are: (1) propellant behavior; (2) helium usage; (3) propellant tank pressurization; (4) propellant tank thermodynamics; (5) component heating; thermal control; and thermal protection system; (6) main engine system; (7) H2O2 consumption; (8) boost pump post-meco performance; and (9) an overview of other systems.

  20. Ethical issues in the documentary data analysis of Internet posts and archives.

    PubMed

    Sixsmith, J; Murray, C D

    2001-05-01

    The documentary analysis of e-mail posts and archives for qualitative research has been outlined elsewhere. Although there is an increase in the number of studies being conducted on listserv and newsgroup material in health research, this has not always been accompanied by a careful, in-depth consideration of the concomitant ethical issues. Therefore, this article outlines the ethical considerations surrounding this form of research, including issues of accessing voices, consent, privacy, anonymity, interpretation, and ownership and authorship of research material.

  1. Molecular analysis of post-harvest withering in grape by AFLP transcriptional profiling

    PubMed Central

    Zamboni, Anita; Minoia, Leone; Ferrarini, Alberto; Tornielli, Giovanni Battista; Zago, Elisa; Delledonne, Massimo; Pezzotti, Mario

    2008-01-01

    Post-harvest withering of grape berries is used in the production of dessert and fortified wines to alter must quality characteristics and increase the concentration of simple sugars. The molecular processes that occur during withering are poorly understood, so a detailed transcriptomic analysis of post-harvest grape berries was carried out by AFLP-transcriptional profiling analysis. This will help to elucidate the molecular mechanisms of berry withering and will provide an opportunity to select markers that can be used to follow the drying process and evaluate different drying techniques. AFLP-TP identified 699 withering-specific genes, 167 and 86 of which were unique to off-plant and on-plant withering, respectively. Although similar molecular events were revealed in both withering processes, it was apparent that off-plant withering induced a stronger dehydration stress response resulting in the high level expression of genes involved in stress protection mechanisms, such as dehydrin and osmolite accumulation. Genes involved in hexose metabolism and transport, cell wall composition, and secondary metabolism (particularly the phenolic and terpene compound pathways) were similarly regulated in both processes. This work provides the first comprehensive analysis of the molecular events underpinning post-harvest withering and could help to define markers for different withering processes. PMID:19010774

  2. Micromechanics Analysis Code Post-Processing (MACPOST) User Guide. 1.0

    NASA Technical Reports Server (NTRS)

    Goldberg, Robert K.; Comiskey, Michele D.; Bednarcyk, Brett A.

    1999-01-01

    As advanced composite materials have gained wider usage. the need for analytical models and computer codes to predict the thermomechanical deformation response of these materials has increased significantly. Recently, a micromechanics technique called the generalized method of cells (GMC) has been developed, which has the capability to fulfill this -oal. Tc provide a framework for GMC, the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) has been developed. As MAC/GMC has been updated, significant improvements have been made to the post-processing capabilities of the code. Through the MACPOST program, which operates directly within the MSC/PATRAN graphical pre- and post-processing package, a direct link between the analysis capabilities of MAC/GMC and the post-processing capabilities of MSC/PATRAN has been established. MACPOST has simplified the production, printing. and exportation of results for unit cells analyzed by MAC/GMC. MACPOST allows different micro-level quantities to be plotted quickly and easily in contour plots. In addition, meaningful data for X-Y plots can be examined. MACPOST thus serves as an important analysis and visualization tool for the macro- and micro-level data generated by MAC/GMC. This report serves as the user's manual for the MACPOST program.

  3. Allogeneic hematopoietic cell transplantation without fluconazole and fluoroquinolone prophylaxis.

    PubMed

    Heidenreich, D; Kreil, S; Nolte, F; Reinwald, M; Hofmann, W-K; Klein, S A

    2016-01-01

    Fluoroquinolone (FQ) and fluconazole prophylaxis is recommended for patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). However, due to an uncertain scientific basis and the increasing emergence of resistant germs, this policy should be questioned. Therefore, FQ and fluconazole prophylaxis was omitted in alloHCT at our center. In this retrospective analysis, all consecutive patients (n = 63) who underwent first alloHCT at our institution from September 2010 to September 2013 were included. Patients neither received FQ nor fluconazole prophylaxis. Day 100 mortality, incidence of febrile neutropenia, bacterial infections, and invasive fungal diseases (IFD) were assessed. Sixteen patients who started conditioning under antimicrobial treatment/prophylaxis due to pre-existing neutropenia (3/16), IFD (12/16), or aortic valve replacement (1/16) were excluded from the analysis. Finally, 47 patients were transplanted without prophylaxis as intended. Day 100 mortality was 9 %. Febrile neutropenia occurred in 62 % (29/47); 17/47 patients (36 %) experienced a blood stream infection (BSI) with detection of Gram-positive bacteria in 14 patients, Gram-negative bacteria in five patients, and candida in one patient, respectively. Coagulase-negative staphylococci were the most frequently isolated Gram-positive bacteria; 12/21 isolated Gram-positive and 3/6 Gram-negative bacteria were FQ resistant. In 21 % (10/47) of the patients, IFD (1x proven, 1x probable, and 8x possible) were diagnosed. To conclude, all three criteria, day 100 mortality, the incidence of IFD, and BSI, are in the range of published data for patients transplanted with FQ and fluconazole prophylaxis. These data demonstrate that alloHCT is feasible without FQ and fluconazole prophylaxis.

  4. Measurement uncertainty analysis of low-dose-rate prostate seed brachytherapy: post-implant dosimetry.

    PubMed

    Gregory, Kent J; Pattison, John E; Bibbo, Giovanni

    2015-03-01

    The minimal dose covering 90 % of the prostate volume--D 90--is arguably the most important dosimetric parameter in low-dose-rate prostate seed brachytherapy. In this study an analysis of the measurement uncertainties in D 90 from low-dose-rate prostate seed brachytherapy was conducted for two common treatment procedures with two different post-implant dosimetry methods. The analysis was undertaken in order to determine the magnitude of D 90 uncertainty, how the magnitude of the uncertainty varied when D 90 was calculated using different dosimetry methods, and which factors were the major contributors to the uncertainty. The analysis considered the prostate as being homogeneous and tissue equivalent and made use of published data, as well as original data collected specifically for this analysis, and was performed according to the Guide to the expression of uncertainty in measurement (GUM). It was found that when prostate imaging and seed implantation were conducted in two separate sessions using only CT images for post-implant analysis, the expanded uncertainty in D 90 values were about 25 % at the 95 % confidence interval. When prostate imaging and seed implantation were conducted during a single session using CT and ultrasound images for post-implant analysis, the expanded uncertainty in D 90 values were about 33 %. Methods for reducing these uncertainty levels are discussed. It was found that variations in contouring the target tissue made the largest contribution to D 90 uncertainty, while the uncertainty in seed source strength made only a small contribution. It is important that clinicians appreciate the overall magnitude of D 90 uncertainty and understand the factors that affect it so that clinical decisions are soundly based, and resources are appropriately allocated.

  5. The Role of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin Lymphoma

    PubMed Central

    Holmberg, Leona; Maloney, David G.

    2011-01-01

    Patients with Hodgkin lymphoma are usually cured by primary therapy using chemotherapy alone or combined modality therapy with external beam radiation. Patients who do not experience a complete remission or those who experience relapse may by salvaged by high-dose therapy and autologous hematopoietic stem cell transplantation (ASCT). Success of this approach is largely dependent on the tumor being sensitive to salvage chemotherapy before transplant. More studies are showing the predictive value of functional imaging in this setting. Allogeneic hematopoietic stem cell transplantation has greater risk of nonrelapse mortality and is generally reserved for patients who experience relapse post-ASCT, but may provide long-term survival for some patients through graft-versus-tumor immune effects. PMID:21917627

  6. Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation

    PubMed Central

    2013-01-01

    Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases. PMID:24341630

  7. A problem-solving education intervention in caregivers and patients during allogeneic hematopoietic stem cell transplantation.

    PubMed

    Bevans, Margaret; Wehrlen, Leslie; Castro, Kathleen; Prince, Patricia; Shelburne, Nonniekaye; Soeken, Karen; Zabora, James; Wallen, Gwenyth R

    2014-05-01

    The aim of this study was to determine the effect of problem-solving education on self-efficacy and distress in informal caregivers of allogeneic hematopoietic stem cell transplantation patients. Patient/caregiver teams attended three 1-hour problem-solving education sessions to help cope with problems during hematopoietic stem cell transplantation. Primary measures included the Cancer Self-Efficacy Scale-transplant and Brief Symptom Inventory-18. Active caregivers reported improvements in self-efficacy (p < 0.05) and distress (p < 0.01) post-problem-solving education; caregiver responders also reported better health outcomes such as fatigue. The effect of problem-solving education on self-efficacy and distress in hematopoietic stem cell transplantation caregivers supports its inclusion in future interventions to meet the multifaceted needs of this population.

  8. Financial Impact of Allogeneic Hematopoietic Cell Transplantation on Patients and Families over 2-years: Results from a Multicenter Pilot Study

    PubMed Central

    Denzen, Ellen M.; Thao, Viengneesee; Hahn, Theresa; Lee, Stephanie J.; McCarthy, Philip L.; Rizzo, J. Douglas; Ammi, Monique; Drexler, Rebecca; Flesch, Susan; James, Heather; Omondi, Nancy; Murphy, Elizabeth; Pederson, Kate; Majhail, Navneet S.

    2016-01-01

    Hematopoietic cell transplantation (HCT) is a procedure that can significantly influence the socioeconomic wellbeing of patients, caregivers and their families. Among 30 allogeneic HCT recipients and their caregivers enrolled on a pilot study evaluating the feasibility of studying financial impact of HCT, 16 agreed to participate in the long-term phase, completed a baseline questionnaire and received phone interviews at 6, 12, 18 and 24 months post-HCT. Analyses showed that by 2-years post-HCT, 54% of patients who previously contributed to household earnings had not returned to work and 80% of patients/caregivers reported transplant as having moderate to great impact on household income. However, patients’ level of confidence in their ability to meet household financial obligations increased from baseline to 2-years. A relatively large proportion of patients reported inability to pay for medical care through this time period. Case studies demonstrated patient individual perception of financial impact of HCT varies considerably, regardless of actual income. We demonstrate the feasibility of conducting a study to evaluate financial impact of allogeneic HCT through 2-years post-transplantation. Some patients/caregivers continue to experience significant long-term financial burden after this procedure. Our study lays the foundation for a larger evaluation of patient/caregiver financial burden associated with HCT. PMID:27088381

  9. [T lymphocyte receptors after allogenic bone marrow transplantation].

    PubMed

    Vilmer, E; Schumpp, M; Sigaux, F; Boiron, M; Bensussan, A

    1988-01-01

    Following allogeneic bone marrow transplantation, prominent expansion of peripheral T cells (40%) bearing gamma T cell receptor was observed in some patients. Biochemical, functional and molecular analyses were performed to characterize this T cell receptor and to understand its role in the immunodeficient state after transplantation.

  10. Allogeneic Marrow Transplantation in Patients With Severe Systemic Sclerosis

    PubMed Central

    Nash, Richard A.; McSweeney, Peter A.; Nelson, J. Lee; Wener, Mark; Georges, George E.; Langston, Amelia A.; Shulman, Howard; Sullivan, Keith M.; Lee, Julie; Henstorf, Gretchen; Storb, Rainer; Furst, Daniel E.

    2010-01-01

    Objective To evaluate the safety and efficacy of allogeneic hematopoietic cell transplantation (HCT) after myeloablative conditioning in patients with severe systemic sclerosis (SSc). Methods Eligibility criteria for the study included SSc patients with features indicative of a poor prognosis. The myeloablative conditioning regimen included busulfan, cyclophosphamide, and antithymocyte globulin. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and methotrexate. Bone marrow was transplanted from HLA-identical siblings. Results Two patients with diffuse cutaneous SSc and lung involvement who were refractory to conventional immunosuppressive treatment were enrolled in the study. In patient 1, there were no complications related to the conditioning regimen, and GVHD did not develop after transplantation. At 5 years after HCT, there was nearly complete resolution of the scleroderma and marked improvement in physical functioning. Internal organ function improved (lung) or remained stable. On examination of serial skin biopsy samples, there was resolution of the dermal fibrosis. Patient 2 experienced skin toxicity from the conditioning regimen and hypertensive crisis that was likely related to high-dose corticosteroids given for treatment of GVHD. Although this patient experienced an improvement in scleroderma and overall functioning, a fatal opportunistic infection developed 17 months after HCT. Conclusion Allogeneic HCT may result in sustained remission of SSc. GVHD and opportunistic infections are the major risks associated with allogeneic HCT for SSc, as for allogeneic HCT in general. PMID:16732546

  11. Actinomycosis after allogeneic hematopoietic stem cell transplantation despite penicillin prophylaxis.

    PubMed

    Barraco, F; Labussière-Wallet, H; Valour, F; Ducastelle-Leprêtre, S; Nicolini, F-E; Thomas, X; Ferry, T; Dumitrescu, O; Michallet, M; Ader, F

    2016-08-01

    Actinomycosis is a rare chronic and multifaceted disease caused by Actinomyces species frequently mimicking malignancy or other chronic granulomatous lung diseases. We report 4 original presentations of actinomycosis arising under supposed penicillin prophylaxis in allogeneic stem cell transplantation recipients. PMID:27203624

  12. Post-Mortem Tissue Biopsies Obtained at Minimally Invasive Autopsy: An RNA-Quality Analysis

    PubMed Central

    Kap, Marcel; Weustink, Annick C.; Riegman, Peter H. J.; Oosterhuis, J. Wolter

    2014-01-01

    Introduction Bereaved relatives often refuse to give consent for post-mortem investigation of deceased cancer patients, mainly because of the mutilation due to conventional autopsy (CA). Minimally invasive autopsy (MIA) may be a more acceptable alternative and, if implemented in clinical practice, creates an opportunity to more often obtain post-mortem tissue samples of (recurred) primary tumors and metastases for molecular research. As a measure for tissue quality for molecular studies, we hereby present a feasibility study, comparing the RNA quality of MIA and CA samples, and fresh frozen samples as reference. Materials and methods Tissue samples of heart, liver and kidney were prospectively collected from 24 MIAs followed by CA, and compared to corresponding archival fresh frozen tissue. After RNA isolation and RT-qPCR, RNA integrity numbers (RIN) and GAPDH expression (six amplicon sizes ranging from 71 to 530 base pairs) were measured. RIN values and GAPDH Cq values were analyzed and compared between all sample groups and post-mortem intervals (PMI). Results RIN values in MIA samples were significantly higher than those in CA samples. GAPDH was expressed significantly higher in MIA samples than in CA samples and 530 bp PCR products could be measured in all cases. GAPDH expression was significantly lower in samples with PMI >15 hours. As expected, the samples of the fresh frozen reference standard performed best in all analyses. Conclusion MIA samples showed better RNA quality than CA samples, probably due to shorter PMI. Both had lower RNA quality and expression levels than fresh frozen tissue, however, remaining GAPDH RNA was still sufficiently intact. Therefore, other highly expressed genes are most likely also detectable. Gene array analysis should be performed to gain insight into the quality of entire post-mortem genomes. Reducing PMI will further improve the feasibility of demanding molecular research on post-mortem tissues, this is most likely more

  13. Post-traumatic growth following acquired brain injury: a systematic review and meta-analysis

    PubMed Central

    Grace, Jenny J.; Kinsella, Elaine L.; Muldoon, Orla T.; Fortune, Dónal G.

    2015-01-01

    The idea that acquired brain injury (ABI) caused by stroke, hemorrhage, infection or traumatic insult to the brain can result in post-traumatic growth (PTG) for individuals is increasingly attracting psychological attention. However, PTG also attracts controversy as a result of ambiguous empirical findings. The extent that demographic variables, injury factors, subjective beliefs, and psychological health are associated with PTG following ABI is not clear. Consequently, this systematic review and meta-analysis explores the correlates of variables within these four broad areas and PTG. From a total of 744 published studies addressing PTG in people with ABI, eight studies met inclusion criteria for detailed examination. Meta-analysis of these studies indicated that growth was related to employment, longer education, subjective beliefs about change post-injury, relationship status, older age, longer time since injury, and lower levels of depression. Results from homogeneity analyses indicated significant inter-study heterogeneity across variables. There is general support for the idea that people with ABI can experience growth, and that various demographics, injury-related variables, subjective beliefs and psychological health are related to growth. The contribution of social integration and the forming of new identities post-ABI to the experience of PTG is explored. These meta-analytic findings are however constrained by methodological limitations prevalent in the literature. Clinical and research implications are discussed with specific reference to community and collective factors that enable PTG. PMID:26321983

  14. Pediatric donor cell leukemia after allogeneic hematopoietic stem cell transplantation in AML patient from related donor.

    PubMed

    Bobadilla-Morales, Lucina; Pimentel-Gutiérrez, Helia J; Gallegos-Castorena, Sergio; Paniagua-Padilla, Jenny A; Ortega-de-la-Torre, Citlalli; Sánchez-Zubieta, Fernando; Silva-Cruz, Rocio; Corona-Rivera, Jorge R; Zepeda-Moreno, Abraham; González-Ramella, Oscar; Corona-Rivera, Alfredo

    2015-01-01

    Here we present a male patient with acute myeloid leukemia (AML) initially diagnosed as M5 and with karyotype 46,XY. After induction therapy, he underwent a HLA-matched allogeneic hematopoietic stem cell transplantation, and six years later he relapsed as AML M1 with an abnormal karyotype //47,XX,+10[2]/47,XX,+11[3]/48,XX,+10,+11[2]/46,XX[13]. Based on this, we tested the possibility of donor cell origin by FISH and molecular STR analysis. We found no evidence of Y chromosome presence by FISH and STR analysis consistent with the success of the allogeneic hematopoietic stem cell transplantation from the female donor. FISH studies confirmed trisomies and no evidence of MLL translocation either p53 or ATM deletion. Additionally 28 fusion common leukemia transcripts were evaluated by multiplex reverse transcriptase-polymerase chain reaction assay and were not rearranged. STR analysis showed a complete donor chimerism. Thus, donor cell leukemia (DCL) was concluded, being essential the use of cytological and molecular approaches. Pediatric DCL is uncommon, our patient seems to be the sixth case and additionally it presented a late donor cell leukemia appearance. Different extrinsic and intrinsic mechanisms have been considered to explain this uncommon finding as well as the implications to the patient. PMID:25674158

  15. Pediatric donor cell leukemia after allogeneic hematopoietic stem cell transplantation in AML patient from related donor.

    PubMed

    Bobadilla-Morales, Lucina; Pimentel-Gutiérrez, Helia J; Gallegos-Castorena, Sergio; Paniagua-Padilla, Jenny A; Ortega-de-la-Torre, Citlalli; Sánchez-Zubieta, Fernando; Silva-Cruz, Rocio; Corona-Rivera, Jorge R; Zepeda-Moreno, Abraham; González-Ramella, Oscar; Corona-Rivera, Alfredo

    2015-01-01

    Here we present a male patient with acute myeloid leukemia (AML) initially diagnosed as M5 and with karyotype 46,XY. After induction therapy, he underwent a HLA-matched allogeneic hematopoietic stem cell transplantation, and six years later he relapsed as AML M1 with an abnormal karyotype //47,XX,+10[2]/47,XX,+11[3]/48,XX,+10,+11[2]/46,XX[13]. Based on this, we tested the possibility of donor cell origin by FISH and molecular STR analysis. We found no evidence of Y chromosome presence by FISH and STR analysis consistent with the success of the allogeneic hematopoietic stem cell transplantation from the female donor. FISH studies confirmed trisomies and no evidence of MLL translocation either p53 or ATM deletion. Additionally 28 fusion common leukemia transcripts were evaluated by multiplex reverse transcriptase-polymerase chain reaction assay and were not rearranged. STR analysis showed a complete donor chimerism. Thus, donor cell leukemia (DCL) was concluded, being essential the use of cytological and molecular approaches. Pediatric DCL is uncommon, our patient seems to be the sixth case and additionally it presented a late donor cell leukemia appearance. Different extrinsic and intrinsic mechanisms have been considered to explain this uncommon finding as well as the implications to the patient.

  16. Post-Buckling and Ultimate Strength Analysis of Stiffened Composite Panel Base on Progressive Damage

    NASA Astrophysics Data System (ADS)

    Zhang, Guofan; Sun, Xiasheng; Sun, Zhonglei

    Stiffened composite panel is the typical thin wall structure applied in aerospace industry, and its main failure mode is buckling subjected to compressive loading. In this paper, the development of an analysis approach using Finite Element Method on post-buckling behavior of stiffened composite structures under compression was presented. Then, the numerical results of stiffened panel are obtained by FE simulations. A thorough comparison were accomplished by comparing the load carrying capacity and key position strains of the specimen with test. The comparison indicates that the FEM results which adopted developed methodology could meet the demand of engineering application in predicting the post-buckling behavior of intact stiffened structures in aircraft design stage.

  17. Computational and statistical methods for high-throughput analysis of post-translational modifications of proteins.

    PubMed

    Schwämmle, Veit; Verano-Braga, Thiago; Roepstorff, Peter

    2015-11-01

    The investigation of post-translational modifications (PTMs) represents one of the main research focuses for the study of protein function and cell signaling. Mass spectrometry instrumentation with increasing sensitivity improved protocols for PTM enrichment and recently established pipelines for high-throughput experiments allow large-scale identification and quantification of several PTM types. This review addresses the concurrently emerging challenges for the computational analysis of the resulting data and presents PTM-centered approaches for spectra identification, statistical analysis, multivariate analysis and data interpretation. We furthermore discuss the potential of future developments that will help to gain deep insight into the PTM-ome and its biological role in cells. This article is part of a Special Issue entitled: Computational Proteomics.

  18. Signature Based Detection of User Events for Post-mortem Forensic Analysis

    NASA Astrophysics Data System (ADS)

    James, Joshua Isaac; Gladyshev, Pavel; Zhu, Yuandong

    This paper introduces a novel approach to user event reconstruction by showing the practicality of generating and implementing signature-based analysis methods to reconstruct high-level user actions from a collection of low-level traces found during a post-mortem forensic analysis of a system. Traditional forensic analysis and the inferences an investigator normally makes when given digital evidence, are examined. It is then demonstrated that this natural process of inferring high-level events from low-level traces may be encoded using signature-matching techniques. Simple signatures using the defined method are created and applied for three popular Windows-based programs as a proof of concept.

  19. Continuous Versus Group Sequential Analysis for Post-Market Drug and Vaccine Safety Surveillance

    PubMed Central

    Silva, I. R.; Kulldorff, M.

    2016-01-01

    Summary The use of sequential statistical analysis for post-market drug safety surveillance is quickly emerging. Both continuous and group sequential analysis have been used, but consensus is lacking as to when to use which approach. We compare the statistical performance of continuous and group sequential analysis in terms of type I error probability; statistical power; expected time to signal when the null hypothesis is rejected; and the sample size required to end surveillance without rejecting the null. We present a mathematical proposition to show that for any group sequential design there always exists a continuous sequential design that is uniformly better. As a consequence, it is shown that more frequent testing is always better. Additionally, for a Poisson based probability model and a flat rejection boundary in terms of the log likelihood ratio, we compare the performance of various continuous and group sequential designs. Using exact calculations, we found that, for the parameter settings used, there is always a continuous design with shorter expected time to signal than the best group design. The two key conclusions from this article are (i) that any post-market safety surveillance system should attempt to obtain data as frequently as possible, and (ii) that sequential testing should always be performed when new data arrives without deliberately waiting for additional data. PMID:26011024

  20. Continuous versus group sequential analysis for post-market drug and vaccine safety surveillance.

    PubMed

    Silva, I R; Kulldorff, M

    2015-09-01

    The use of sequential statistical analysis for post-market drug safety surveillance is quickly emerging. Both continuous and group sequential analysis have been used, but consensus is lacking as to when to use which approach. We compare the statistical performance of continuous and group sequential analysis in terms of type I error probability; statistical power; expected time to signal when the null hypothesis is rejected; and the sample size required to end surveillance without rejecting the null. We present a mathematical proposition to show that for any group sequential design there always exists a continuous sequential design that is uniformly better. As a consequence, it is shown that more frequent testing is always better. Additionally, for a Poisson based probability model and a flat rejection boundary in terms of the log likelihood ratio, we compare the performance of various continuous and group sequential designs. Using exact calculations, we found that, for the parameter settings used, there is always a continuous design with shorter expected time to signal than the best group design. The two key conclusions from this article are (i) that any post-market safety surveillance system should attempt to obtain data as frequently as possible, and (ii) that sequential testing should always be performed when new data arrives without deliberately waiting for additional data.

  1. Analysis of nonstandard and home-made explosives and post-blast residues in forensic practice

    NASA Astrophysics Data System (ADS)

    Kotrlý, Marek; Turková, Ivana

    2014-05-01

    Nonstandard and home-made explosives may constitute a considerable threat and as well as a potential material for terrorist activities. Mobile analytical devices, particularly Raman, or also FTIR spectrometers are used for the initial detection. Various sorts of phlegmatizers (moderants) to decrease sensitivity of explosives were tested, some kinds of low viscosity lubricants yielded very good results. If the character of the substance allows it, phlegmatized samples are taken in the amount of approx.0.3g for a laboratory analysis. Various separation methods and methods of concentrations of samples from post-blast scenes were tested. A wide range of methods is used for the laboratory analysis. XRD techniques capable of a direct phase identification of the crystalline substance, namely in mixtures, have highly proved themselves in practice for inorganic and organic phases. SEM-EDS/WDS methods are standardly employed for the inorganic phase. In analysing post-blast residues, there are very important techniques allowing analysis at the level of separate particles, not the overall composition in a mixed sample.

  2. Lesson Learned from AGILE and LARES ASI Projects About MATED Data Collection and Post Analysis

    NASA Astrophysics Data System (ADS)

    Carpentiero, Rita; Mrchetti, Ernesto; Natalucci, Silvia; Portelli, Claudio

    2012-07-01

    ASI has managed and collected data on project development of two scientific all-Italian missions: AGILE and LARES. Collection of the Model And Test Effectiveness Database (MATED) data, concerning Project, AIV (Assembly Integration and Verification) and NCR (Non Conformance Report) aspects has been performed by the Italian Space Agency (ASI), using available technical documentation of both AGILE e LARES projects. In this paper some consideration on the needs of 'real time' data collection is made, together with proposal of front end improvement of this tool. In addition a preliminary analysis of MATED effectiveness related to the above ASI projects will be presented in a bottom-up and post verification approach.

  3. Application of the Post-Boiling-Transition Standard to Licensing Analysis

    SciTech Connect

    Mizokami, Shinya; Kitamura, Hideya; Kudo, Yoshiro; Komura, Seiichi; Nagata, Yoshifumi; Morooka, Shinichi

    2005-10-15

    To ensure fuel integrity, light water reactor cores are designed to avoid the onset of boiling transition (BT) inside the fuel assembly that leads to a deterioration of the heat transfer characteristics and subsequent excessive rise of the fuel-cladding temperature in the anticipated operational occurrences (AOOs). However, some boiling water reactors' AOO events result in immediate scram or suppression of the reactor power due to an increase in the reactor coolant void fraction. Recent studies show that a short duration of dryout inside the fuel assembly only leads to a small rise in the fuel-cladding temperature and thus does not pose a threat to fuel integrity. Many tests on BT and an improved comprehension of its mechanism have led to the development of a methodology to appropriately assess the fuel-cladding temperature after BT has been reached. The Standards Committee of the Atomic Energy Society of Japan has therefore proposed a cladding temperature criterion after BT. Applying the post-BT standard enables the value of the operating limit minimum critical power ratio (OLMCPR) to be decreased by allowing for a short duration of dryout. We calculated the fuel-cladding temperature and dryout duration in the load rejection condition without a bypass event. The calculated results show that both the fuel-cladding temperature and dryout duration meet the post-BT standard in the case of a small OLMCPR, which is determined by the loss of feedwater heating. This enables a more efficient reactor core to be designed by applying the post-BT standard to licensing analysis. The possibility of applying a post-BT standard is demonstrated from the results of this work.

  4. Three-dimensional finite element analysis of stress distribution in composite resin cores with fiber posts of varying diameters.

    PubMed

    Okamoto, Kazuhiko; Ino, Teruno; Iwase, Naoki; Shimizu, Eitaroh; Suzuki, Megumi; Satoh, Goh; Ohkawa, Shuji; Fujisawa, Masanori

    2008-01-01

    Using three-dimensional finite element analysis (3D-FEA), stress distributions in the remaining radicular tooth structure were investigated under the condition of varying diameters of fiber post for fiber post-reinforced composite resin cores (fiber post and core) in maxillary central incisors. Four 3D-FEA models were constructed: (1) fiber post (ø1.2, ø1.4, and ø1.6 mm) and composite resin core; and (2) gold-cast post and core. Maximum stresses in the tooth structure for fiber post and core were higher than that for gold-cast post and core. In the former models, stresses in the tooth structure as well as in the composite resin were slightly reduced with increase in fiber post diameter. These results thus suggested that to reduce stress in the remaining radicular tooth with a large coronal defect, it is recommended to accompany a composite resin core with a fiber post of a large diameter. PMID:18309611

  5. Ex post power economic analysis of record of decision operational restrictions at Glen Canyon Dam.

    SciTech Connect

    Veselka, T. D.; Poch, L. A.; Palmer, C. S.; Loftin, S.; Osiek, B; Decision and Information Sciences; Western Area Power Administration

    2010-07-31

    On October 9, 1996, Bruce Babbitt, then-Secretary of the U.S. Department of the Interior signed the Record of Decision (ROD) on operating criteria for the Glen Canyon Dam (GCD). Criteria selected were based on the Modified Low Fluctuating Flow (MLFF) Alternative as described in the Operation of Glen Canyon Dam, Colorado River Storage Project, Arizona, Final Environmental Impact Statement (EIS) (Reclamation 1995). These restrictions reduced the operating flexibility of the hydroelectric power plant and therefore its economic value. The EIS provided impact information to support the ROD, including an analysis of operating criteria alternatives on power system economics. This ex post study reevaluates ROD power economic impacts and compares these results to the economic analysis performed prior (ex ante) to the ROD for the MLFF Alternative. On the basis of the methodology used in the ex ante analysis, anticipated annual economic impacts of the ROD were estimated to range from approximately $15.1 million to $44.2 million in terms of 1991 dollars ($1991). This ex post analysis incorporates historical events that took place between 1997 and 2005, including the evolution of power markets in the Western Electricity Coordinating Council as reflected in market prices for capacity and energy. Prompted by ROD operational restrictions, this analysis also incorporates a decision made by the Western Area Power Administration to modify commitments that it made to its customers. Simulated operations of GCD were based on the premise that hourly production patterns would maximize the economic value of the hydropower resource. On the basis of this assumption, it was estimated that economic impacts were on average $26.3 million in $1991, or $39 million in $2009.

  6. Chronic active Epstein-Barr virus infection with marked pericardial effusion successfully treated with allogeneic peripheral blood stem cell transplantation.

    PubMed

    Matsui, Shinichiro; Takeda, Yusuke; Isshiki, Yusuke; Yamazaki, Atsuko; Nakao, Sanshiro; Takaishi, Koji; Nagao, Yuhei; Hasegawa, Nagisa; Togasaki, Emi; Shimizu, Ryoh; Kawajiri, Chika; Sakai, Shio; Mimura, Naoya; Takeuchi, Masahiro; Ohwada, Chikako; Sakaida, Emiko; Iseki, Tohru; Imadome, Ken-Ichi; Nakaseko, Chiaki

    2016-05-01

    A 23-year-old woman presented with a persistent fever and shortness of breath. Computed tomography showed marked pericardial effusion, hepatosplenomegaly, and cervical and mediastinal lymph node swelling. Epstein-Barr virus (EBV) antibody titers were abnormally elevated, and the copy number of EBV-DNA was increased in peripheral blood. Based on these observations, she was diagnosed with chronic active EBV infection (CAEBV). The EBV-infected cells in her peripheral blood were CD4(+)T lymphocytes. Fever and pericardial effusion improved following treatment with a combination of prednisolone, etoposide, and cyclosporine; however, peripheral blood EBV-DNA levels remained high. The patient underwent allogeneic peripheral blood stem cell transplantation from an EBV-seronegative, HLA-matched sibling donor, with fludarabine and melphalan conditioning. The post-transplantation course was uneventful, except for mild skin acute graft-versus-host disease (grade 2). EBV-DNA became undetectable in peripheral blood 98 days post transplantation. She has since been in good health without disease recurrence. CAEBV is a potentially fatal disease caused by persistent EBV infection of T lymphocytes or natural killer cells, thus requiring prompt treatment and allogeneic transplantation. Pericardial effusion is rarely observed in CAEBV and can impede its diagnosis. Therefore, we should be aware that patients may present with marked pericardial effusion as an initial manifestation of CAEBV. PMID:27263789

  7. High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia — an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

    PubMed Central

    Czerw, Tomasz; Labopin, Myriam; Schmid, Christoph; Cornelissen, Jan J.; Chevallier, Patrice; Blaise, Didier; Kuball, Jürgen; Vigouroux, Stephane; Garban, Frédéric; Lioure, Bruno; Fegueux, Nathalie; Clement, Laurence; Sandstedt, Anna; Maertens, Johan; Guillerm, Gaëlle; Bordessoule, Dominique

    2016-01-01

    Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 × 10^6/kg and >8.25 × 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes. PMID:27036034

  8. Cytotoxic activity of allogeneic natural killer cells on U251 glioma cells in vitro.

    PubMed

    Guo, Meng; Wu, Tingting; Wan, Lixin

    2016-07-01

    The present study aimed to observe the cytotoxic activity of allogeneic natural killer (NK) cells on U251 glioma cells and to investigate their mechanism of action to establish an effective treatment strategy for neuroglioma. Cell survival curves, colony formation assays and karyotype analysis were performed to investigate the characteristics of U251 glioma cells. The present study demonstrated that natural killer group 2, member D (NKG2D)‑major histocompatibility complex class I‑related chain A/B (MICA/B) interactions contributed to the cytotoxic effect of NK cells on K562 and U251 cells. In antibody‑blocking assays to inhibit NKG2D ligands, the cytotoxic activity was not completely attenuated, which suggested that other signaling pathways contribute to the cytotoxic activity of NK cells on tumor cells in addition to the NKG2D‑mediated activity. The present study identified that the expression levels of NKG2D ligands on the surface of target cells influenced the strength of the NK cell immune response. Furthermore, allogeneic NK cells were observed to kill glioma cells in vitro, and this anticancer activity is associated with the rate of NKG2D expression on the surface of glioma cells.

  9. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.

    PubMed

    Dhédin, Nathalie; Huynh, Anne; Maury, Sébastien; Tabrizi, Reza; Beldjord, Kheira; Asnafi, Vahid; Thomas, Xavier; Chevallier, Patrice; Nguyen, Stéphanie; Coiteux, Valérie; Bourhis, Jean-Henri; Hichri, Yosr; Escoffre-Barbe, Martine; Reman, Oumedaly; Graux, Carlos; Chalandon, Yves; Blaise, Didier; Schanz, Urs; Lhéritier, Véronique; Cahn, Jean-Yves; Dombret, Hervé; Ifrah, Norbert

    2015-04-16

    Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678. PMID:25587040

  10. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.

    PubMed

    Dhédin, Nathalie; Huynh, Anne; Maury, Sébastien; Tabrizi, Reza; Beldjord, Kheira; Asnafi, Vahid; Thomas, Xavier; Chevallier, Patrice; Nguyen, Stéphanie; Coiteux, Valérie; Bourhis, Jean-Henri; Hichri, Yosr; Escoffre-Barbe, Martine; Reman, Oumedaly; Graux, Carlos; Chalandon, Yves; Blaise, Didier; Schanz, Urs; Lhéritier, Véronique; Cahn, Jean-Yves; Dombret, Hervé; Ifrah, Norbert

    2015-04-16

    Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678.

  11. Impact of pretransplant body mass index on the clinical outcome after allogeneic hematopoietic SCT.

    PubMed

    Fuji, S; Takano, K; Mori, T; Eto, T; Taniguchi, S; Ohashi, K; Sakamaki, H; Morishima, Y; Kato, K; Miyamura, K; Suzuki, R; Fukuda, T

    2014-12-01

    To elucidate the impact of pretransplant body mass index (BMI) on the clinical outcome, we performed a retrospective study with registry data including a total of 12 050 patients (age ⩾18 years) who received allogeneic hematopoietic SCT (HSCT) between 2000 and 2010. Patients were stratified as follows: BMI<18.5 kg/m(2), Underweight, n=1791; 18.5⩽BMI<25, Normal, n=8444; 25⩽BMI<30, Overweight, n=1591; BMI⩾30, Obese, n=224. The median age was 45 years (range, 18-77). A multivariate analysis showed that the risk of relapse was significantly higher in the underweight group and lower in the overweight and obese groups compared with the normal group (hazard ratio (HR), 1.16, 0.86, and 0.74, respectively). The risk of GVHD was significantly higher in the overweight group compared with the normal group. The risk of non-relapse mortality (NRM) was significantly higher in the overweight and obese group compared with the normal group (HR 1.19 and HR 1.43, respectively). The probability of OS was lower in the underweight group compared with the normal group (HR 1.10, P=0.018). In conclusion, pretransplant BMI affected the risk of relapse and NRM after allogeneic HSCT. Underweight was a risk factor for poor OS because of an increased risk of relapse. Obesity was a risk factor for NRM.

  12. Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission - a review from the Acute Leukemia Working Party of the EBMT

    PubMed Central

    Sengsayadeth, Salyka; Savani, Bipin N.; Blaise, Didier; Malard, Florent; Nagler, Arnon; Mohty, Mohamad

    2015-01-01

    Acute myeloid leukemia is the most common indication for an allogeneic hematopoietic cell transplant. The introduction of reduced intensity conditioning has expanded the recipient pool for transplantation, which has importantly made transplant an option for the more commonly affected older age groups. Reduced intensity conditioning allogeneic transplantation is currently the standard of care for patients with intermediate or high-risk acute myeloid leukemia and is now most often employed in older patients and those with medical comorbidities. Despite being curative for a significant proportion of patients, post-transplant relapse remains a challenge in the reduced intensity conditioning setting. Herein we discuss the studies that demonstrate the feasibility of reduced intensity conditioning allogeneic transplants, compare the outcomes of reduced intensity conditioning versus chemotherapy and conventional myeloablative conditioning regimens, describe the optimal donor and stem cell source, and consider the impact of post-remission consolidation, comorbidities, center experience, and more intensive (reduced toxicity conditioning) regimens on outcomes. Additionally, we discuss the need for further prospective studies to optimize transplant outcomes. PMID:26130513

  13. Ex Vivo Expanded Allogeneic Mesenchymal Stem Cells With Bone Marrow Transplantation Improved Osteogenesis in Infants With Severe Hypophosphatasia.

    PubMed

    Taketani, Takeshi; Oyama, Chigusa; Mihara, Aya; Tanabe, Yuka; Abe, Mariko; Hirade, Tomohiro; Yamamoto, Satoshi; Bo, Ryosuke; Kanai, Rie; Tadenuma, Taku; Michibata, Yuko; Yamamoto, Soichiro; Hattori, Miho; Katsube, Yoshihiro; Ohnishi, Hiroe; Sasao, Mari; Oda, Yasuaki; Hattori, Koji; Yuba, Shunsuke; Ohgushi, Hajime; Yamaguchi, Seiji

    2015-01-01

    Patients with severe hypophosphatasia (HPP) develop osteogenic impairment with extremely low alkaline phosphatase (ALP) activity, resulting in a fatal course during infancy. Mesenchymal stem cells (MSCs) differentiate into various mesenchymal lineages, including bone and cartilage. The efficacy of allogeneic hematopoietic stem cell transplantation for congenital skeletal and storage disorders is limited, and therefore we focused on MSCs for the treatment of HPP. To determine the effect of MSCs on osteogenesis, we performed multiple infusions of ex vivo expanded allogeneic MSCs for two patients with severe HPP who had undergone bone marrow transplantation (BMT) from asymptomatic relatives harboring the heterozygous mutation. There were improvements in not only bone mineralization but also muscle mass, respiratory function, and mental development, resulting in the patients being alive at the age of 3. After the infusion of MSCs, chimerism analysis of the mesenchymal cell fraction isolated from bone marrow in the patients demonstrated that donor-derived DNA sequences existed. Adverse events of BMT were tolerated, whereas those of MSC infusion did not occur. However, restoration of ALP activity was limited, and normal bony architecture could not be achieved. Our data suggest that multiple MSC infusions, following BMT, were effective and brought about clinical benefits for patients with lethal HPP. Allogeneic MSC-based therapy would be useful for patients with other congenital bone diseases and tissue disorders if the curative strategy to restore clinically normal features, including bony architecture, can be established.

  14. Tissue-Related Hypoxia Attenuates Proinflammatory Effects of Allogeneic PBMCs on Adipose-Derived Stromal Cells In Vitro

    PubMed Central

    Bobyleva, Polina I.; Andreeva, Elena R.; Gornostaeva, Aleksandra N.; Buravkova, Ludmila B.

    2016-01-01

    Human adipose tissue-stromal derived cells (ASCs) are considered a perspective tool for regenerative medicine. Depending on the application mode ASC/allogeneic immune cell interaction can occur in the systemic circulation under plenty high concentrations of O2 and in target tissues at lower O2 levels. Here we examined the effects of allogeneic PHA-stimulated peripheral blood mononuclear cells (PBMCs) on ASCs under ambient (20%) oxygen and “physiological” hypoxia (5% O2). As revealed with microarray analysis ASCs under 20% O2 were more affected by activated PBMCs, which was manifested in differential expression of more than 300 genes, whereas under 5% O2 only 140 genes were changed. Altered gene pattern was only partly overlapped at different O2 conditions. Under O2 ASCs retained their proliferative and differentiative capacities, mesenchymal phenotype, and intracellular organelle' state. ASCs were proinflammatory activated on transcription level that was confirmed by their ability to suppress activation and proliferation of mitogen-stimulated PBMCs. ASC/PBMCs interaction resulted in anti-inflammatory shift of paracrine mediators in conditioning medium with significant increase of immunosuppressive LIF level. Our data indicated that under both ambient and tissue-related O2 ASCs possessed immunosuppressive potential and maintained functional activity. Under “physiological” hypoxia ASCs were less susceptible to “priming” by allogeneic mitogen-activated PBMCs. PMID:26880965

  15. Clinical and immunological correction of DOCK8 deficiency by allogeneic hematopoietic stem cell transplantation following a reduced toxicity conditioning regimen.

    PubMed

    Boztug, Heidrun; Karitnig-Weiß, Cäcilia; Ausserer, Bernd; Renner, Ellen D; Albert, Michael H; Sawalle-Belohradsky, Julie; Belohradsky, Bernd H; Mann, Georg; Horcher, Ernst; Rümmele-Waibel, Alexandra; Geyeregger, Rene; Lakatos, Karoly; Peters, Christina; Lawitschka, Anita; Matthes-Martin, Susanne

    2012-10-01

    Dedicator of cytokinesis 8 protein (DOCK8) deficiency is a combined immunodeficiency disorder characterized by an expanding clinical picture with typical features of recurrent respiratory or gastrointestinal tract infections, atopic eczema, food allergies, chronic viral infections of the skin, and blood eosinophilia often accompanied by elevated serum IgE levels. The only definitive treatment option is allogeneic hematopoietic stem cell transplantation (HSCT). We report a patient with early severe manifestation of DOCK8 deficiency, who underwent unrelated allogeneic HSCT at the age of 3 years following a reduced toxicity conditioning regimen. The transplant course was complicated by pulmonary aspergilloma pretransplantation, adenovirus (ADV) reactivation, and cytomegalovirus (CMV) pneumonitis 4 weeks after transplantation. With antifungal and antiviral treatment the patient recovered. Seven months after transplantation the patient is in excellent clinical condition. Eczematous rash, chronic viral skin infections, and food allergies have subsided, associated with normalization of IgE levels and absolute numbers of eosinophils. Chimerism analysis shows stable full donor chimerism. DOCK8 deficiency can be successfully cured by allogeneic HSCT. This treatment option should be considered early after diagnosis, as opportunistic infections and malignancies that occur more frequently during the natural course of the disease are associated with higher morbidity and mortality. PMID:22897717

  16. Donor CD4 T Cell Diversity Determines Virus Reactivation in Patients After HLA-Matched Allogeneic Stem Cell Transplantation

    PubMed Central

    Ritter, J; Seitz, V; Balzer, H; Gary, R; Lenze, D; Moi, S; Pasemann, S; Seegebarth, A; Wurdack, M; Hennig, S; Gerbitz, A; Hummel, M

    2015-01-01

    Delayed reconstitution of the T cell compartment in recipients of allogeneic stem cell grafts is associated with an increase of reactivation of latent viruses. Thereby, the transplanted T cell repertoire appears to be one of the factors that affect T cell reconstitution. Therefore, we studied the T cell receptor beta (TCRβ) gene rearrangements of flow cytometry–sorted CD4+ and CD8+ T cells from the peripheral blood of 23 allogeneic donors before G-CSF administration and on the day of apheresis. For this purpose, TCRβ rearrangements were amplified by multiplex PCR followed by high-throughput amplicon sequencing. Overall, CD4+ T cells displayed a significantly higher TCRβ diversity compared to CD8+ T cells irrespective of G-CSF administration. In line, no significant impact of G-CSF treatment on the TCR Vβ repertoire usage was found. However, correlation of the donor T cell repertoire with clinical outcomes of the recipient revealed that a higher CD4+ TCRβ diversity after G-CSF treatment is associated with lower reactivation of cytomegalovirus and Epstein–Barr virus. By contrast, no protecting correlation was observed for CD8+ T cells. In essence, our deep TCRβ analysis identifies the importance of the CD4+ T cell compartment for the control of latent viruses after allogeneic stem cell transplantation. PMID:25873100

  17. Analysis of post-blood meal flight distances in mosquitoes utilizing zoo animal blood meals

    PubMed Central

    Greenberg, Jacob A.; DiMenna, Mark A.; Hanelt, Ben

    2012-01-01

    We assessed the post-blood meal flight distance of four mosquito species in a unique environment using blood meal analysis. Mosquitoes were trapped at the Rio Grande Zoo in Albuquerque, NM, and the blood source of blood-engorged mosquitoes was identified. The distance from the enclosure of the animal serving as a blood source to the trap site was then determined. We found that mosquitoes captured at the zoo flew no more than 170 m with an average distance of 106.7 m after taking a blood meal. This is the first study in which the flight distance of wild mosquitoes has been assessed using blood meal analysis and the first in which zoo animals have served as the exclusive source of blood meals. PMID:22548540

  18. Post-game analysis: An initial experiment for heuristic-based resource management in concurrent systems

    NASA Technical Reports Server (NTRS)

    Yan, Jerry C.

    1987-01-01

    In concurrent systems, a major responsibility of the resource management system is to decide how the application program is to be mapped onto the multi-processor. Instead of using abstract program and machine models, a generate-and-test framework known as 'post-game analysis' that is based on data gathered during program execution is proposed. Each iteration consists of (1) (a simulation of) an execution of the program; (2) analysis of the data gathered; and (3) the proposal of a new mapping that would have a smaller execution time. These heuristics are applied to predict execution time changes in response to small perturbations applied to the current mapping. An initial experiment was carried out using simple strategies on 'pipeline-like' applications. The results obtained from four simple strategies demonstrated that for this kind of application, even simple strategies can produce acceptable speed-up with a small number of iterations.

  19. Dynamic analysis of a pre-and-post ice impacted blade

    NASA Technical Reports Server (NTRS)

    Abumeri, G. H.; Reddy, E. S.; Murthy, P. L. N.; Chamis, C. C.

    1992-01-01

    The dynamic characteristics of an engine blade are evaluated under pre-and-post ice impact conditions using the NASA in-house computer code BLASIM. The ice impacts the leading edge of the blade causing severe local damage. The local structural response of the blade due to the ice impact is predicted via a transient response analysis by modeling only a local patch around the impact region. After ice impact, the global geometry of the blade is updated using deformations of the local patch and a free vibration analysis is performed. The effects of ice impact location, size and ice velocity on the blade mode shapes and natural frequencies are investigated. The results indicate that basic nature of the mode shapes remains unchanged after impact and that the maximum variation in natural frequencies occurs for the twisting mode of the blade.

  20. Dynamic analysis of a pre-and-post ice impacted blade

    NASA Technical Reports Server (NTRS)

    Abumeri, G. H.; Reddy, E. S.; Murthy, P. L. N.; Chamis, C. C.

    1992-01-01

    The dynamic characteristics of an engine blade are evaluated under pre-and-post ice impact conditions using the NASA in-house computer code BLASIM. The ice impacts the leading edge of the blade causing severe local damage. The local structural response of the blade due to the ice impact is predicted via a transient response analysis by modeling only a local patch around the impact region. After ice impact, the global geometry of the blade is updated using deformations of the local patch and a free vibration analysis is performed. The effects of ice impact location, ice size and ice velocity on the blade mode shapes and natural frequencies are investigated. The results indicate that basic nature of the mode shapes remains unchanged after impact and that the maximum variation in natural frequencies occurs for the twisting mode of the blade.

  1. Post-buckling and Large Amplitude Free Vibration Analysis of Composite Beams: Simple Intuitive Formulation

    NASA Astrophysics Data System (ADS)

    Gunda, Jagadish Babu; Venkateswara Rao, Gundabathula

    2016-04-01

    Post-buckling and large amplitude free vibration analysis of composite beams with axially immovable ends is investigated in the present study using a simple intuitive formulation. Geometric nonlinearity of Von-Karman type is considered in the analysis which accounts for mid-plane stretching action of the beam. Intuitive formulation uses only two parameters: the critical bifurcation point and the axial stretching force developed due to membrane stretching action of the beam. Hinged-hinged, clamped-clamped and clamped-hinged boundary conditions are considered. Numerical accuracy of the proposed analytical closed-form solutions obtained from the intuitive formulation are compared to available finite element solutions for symmetric and asymmetric layup schemes of laminated composite beam which indicates the confidence gained on the present formulation.

  2. Establishment of Definitions and Review Process for Consistent Adjudication of Cause-Specific Mortality After Allogeneic Unrelated Donor Hematopoietic Cell Transplantation

    PubMed Central

    Preus, Leah; Zhu, Xiaochun; Hansen, John A.; Martin, Paul J.; Yan, Li; Liu, Song; Spellman, Stephen; Tritchler, David; Clay, Alyssa

    2015-01-01

    Clinical trials commonly use adjudication committees to refine endpoints, but observational research or genome-wide association studies rarely do. Our goals were to establish definitions of cause-specific death after unrelated donor allogeneic hematopoietic cell transplantation (URD-HCT), estimate discordance between reported and adjudicated cause-specific death, and identify factors contributing to inconsistency in cause-specific deathdetermination. A consensus panel adjudicated cause-specific deathin 1,484 patients who died within 1 year after HCT, derived from 3,532 acute leukemia or myelodysplasia patients after URD-HCT 2000-2011 reported by 151 U.S. transplant centers to CIBMTR. Deaths were classified as disease-related (DRM) or transplant-related (TRM). The panel agreed with >99% of deaths reported by centers as DRM and 80% reported as TRM. Year of transplant (cohort effect) and disease status significantly influenced agreement between panel and centers. Sensitivity analysis of deaths <100 days post-transplant yielded lowest agreement between the panel and centers for myelodysplastic syndrome patients. Standard pre-defined criteria for adjudicating cause-specific deathled to consistent application to similar clinical scenarios and clearer delineation of cause-specific deathcategories. Other studies of competing events like cancer-specific vs treatment-related mortality would benefit from our results. Our detailed algorithm should result in more consistent reporting of cause-specific deathby centers. PMID:26028504

  3. Early recipient chimerism testing in the T- and NK-cell lineages for risk assessment of graft rejection in pediatric patients undergoing allogeneic stem cell transplantation.

    PubMed

    Breuer, S; Preuner, S; Fritsch, G; Daxberger, H; Koenig, M; Poetschger, U; Lawitschka, A; Peters, C; Mann, G; Lion, T; Matthes-Martin, S

    2012-03-01

    Timely diagnosis of impending graft rejection is crucial for effective therapeutic intervention after allogeneic hematopoietic stem cell transplantation (SCT). We have investigated the predictive potential of early leukocyte subset-specific chimerism for graft loss in children undergoing SCT. In total, 192 pediatric patients transplanted for the treatment of malignant and non-malignant diseases after reduced-intensity or myeloablative conditioning were investigated. Surveillance of lineage-specific chimerism was initiated upon first appearance of leukocyte counts amenable to cell sorting. Graft rejection occurred in 23 patients between 24 and 492 days post-transplant (median 63 days). The first chimerism analysis of T and NK cells performed at a median of 20 days after SCT identified three different risk groups that were independent from the conditioning regimen: recipient chimerism (RC) levels in T cells below 50% indicated a very low risk of rejection (1.4%), whereas high levels of RC (>90%) both in T and NK cells heralded graft loss in the majority of patients (90%) despite therapeutic interventions. RC >50% in T cells and ≤90% in NK cells defined an intermediate-risk group in which timely immunotherapy frequently prevented rejection. Early assessment of T- and NK-cell chimerism can therefore be instrumental in the risk assessment and therapeutic management of imminent graft rejection.

  4. Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the infectious diseases working party (AGIHO) of the german society of haematology and oncology.

    PubMed

    Krüger, W H; Bohlius, J; Cornely, O A; Einsele, H; Hebart, H; Massenkeil, G; Schüttrumpf, S; Silling, G; Ullmann, A J; Waldschmidt, D T; Wolf, H-H

    2005-08-01

    Patients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Bacteria and fungi predominate the first phase until engraftment. During the second phase, from engraftment to about day 100, major infectious problems are caused by fungi and cytomegalovirus. Both pathogens remain important under continued immunosuppression, however, in the late post-transplantation period infections with encapsulated bacteria may become a problem. In this review the Infectious Diseases Working Party of the DGHO gives recommendations for prophylaxis of infections under allogeneic stem cell transplantation with drugs and other measures. The aim of the group was to do this on an evidence-based-medicine rating, if possible.

  5. Pancytopenia after allogeneic bone marrow transplant due to copper deficiency.

    PubMed

    Hudspeth, Michelle; Turner, Amy; Miller, Nicole; Lazarchick, John

    2014-05-01

    Pancytopenia occurring 1 year or later after allogeneic bone marrow transplantation typically prompts a primary consideration for relapse. We present the case of a 15-year old-girl who underwent transplantation for therapy-related myelodysplasia secondary to Ewing sarcoma treatment who developed pancytopenia with myelodysplasia 1 year after transplant due to copper deficiency. Copper deficiency is an important consideration in the evaluation of pancytopenia and myelodysplasia in pediatric patients.

  6. Aspergillus Thyroiditis after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Ataca, Pinar; Atilla, Erden; Saracoglu, Pelin; Yilmaz, Gulden; Civriz Bozdag, Sinem; Toprak, Selami Kocak; Yuksel, Meltem Kurt; Ceyhan, Koray; Topcuoglu, Pervin

    2015-01-01

    Aspergillus thyroiditis is a rare disorder detected in immunocompromised patients during disseminated infections. Early management is essential to prevent high mortality. A 61-year-old allogeneic stem cell male recipient presented with painful thyroid nodular enlargement. He had low TSH and low free T4 levels. The thyroid ultrasound showed a hypoechoic nodule; biopsy indicated suppurative Aspergillus thyroiditis. He was successfully treated by amphotericin B. PMID:26640727

  7. Toxoplasmosis after allogeneic stem cell transplantation--a single centre experience.

    PubMed

    Busemann, Christoph; Ribback, Silvia; Zimmermann, Kathrin; Sailer, Verena; Kiefer, Thomas; Schmidt, Christian A; Schulz, Katrin; Steinmetz, Ivo; Dombrowski, Frank; Dölken, Gottfried; Krüger, William H

    2012-07-01

    Toxoplasmosis is a rare but possibly underestimated complication following allogeneic stem cell transplantation with a high mortality rate. One reason might be the limitation of the diagnostic instruments relying mainly on imaging and molecular-based techniques. In this report, we present three cases of toxoplasmosis identified among 155 allograft recipients treated at Greifswald University Hospital. Widely disseminated toxoplasmosis was detected post-mortem in two patients allografted for high-risk multiple myeloma. Clinical signs suspicious for toxoplasmosis occurred after days +32 and +75, respectively. In one case, serology and conventional Toxoplasma gondii PCR, targeting the B1 gene, revealed negative results, while in the other patient, toxoplasmosis was not investigated. Both patients received pentamidine for Pneumocystis jirovecii pneumonia (PcP) prophylaxis. The third patient, a 68-year-old woman allografted for AML, developed cerebral toxoplasmosis from day +395 after allogeneic SCT with typical signs in magnetic resonance tomography. Toxoplasma DNA was amplified from one of two samples of cerebrospinal fluid. The patient died of disseminated toxoplasmosis despite immediate initiation of therapy. Retrospective comparative testing of clinical specimens by the conventional T. gondii PCR and by a real-time PCR targeting a 529-bp genomic fragment suggests a higher sensitivity of the latter method in our patients. In conclusion, we suggest a rigorous real-time PCR monitoring for high-risk patients or patients with signs of infections suspicious for toxoplasmosis, even though low-copy results are presently difficult to interpret. Our reported cases might also encourage the use of trimethoprim-sufmethoxazole instead of pentamidine for PcP prophylaxis in those patients.

  8. Immune Reconstitution and Graft-Versus-Host Reactions in Rat Models of Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

    Zinöcker, Severin; Dressel, Ralf; Wang, Xiao-Nong; Dickinson, Anne M.; Rolstad, Bent

    2012-01-01

    Allogeneic hematopoietic cell transplantation (alloHCT) extends the lives of thousands of patients who would otherwise succumb to hematopoietic malignancies such as leukemias and lymphomas, aplastic anemia, and disorders of the immune system. In alloHCT, different immune cell types mediate beneficial graft-versus-tumor (GvT) effects, regulate detrimental graft-versus-host disease (GvHD), and are required for protection against infections. Today, the “good” (GvT effector cells and memory cells conferring protection) cannot be easily separated from the “bad” (GvHD-causing cells), and alloHCT remains a hazardous medical modality. The transplantation of hematopoietic stem cells into an immunosuppressed patient creates a delicate environment for the reconstitution of donor blood and immune cells in co-existence with host cells. Immunological reconstitution determines to a large extent the immune status of the allo-transplanted host against infections and the recurrence of cancer, and is critical for long-term protection and survival after clinical alloHCT. Animal models continue to be extremely valuable experimental tools that widen our understanding of, for example, the dynamics of post-transplant hematopoiesis and the complexity of immune reconstitution with multiple ways of interaction between host and donor cells. In this review, we discuss the rat as an experimental model of HCT between allogeneic individuals. We summarize our findings on lymphocyte reconstitution in transplanted rats and illustrate the disease pathology of this particular model. We also introduce the rat skin explant assay, a feasible alternative to in vivo transplantation studies. The skin explant assay can be used to elucidate the biology of graft-versus-host reactions, which are known to have a major impact on immune reconstitution, and to perform genome-wide gene expression studies using controlled combinations of minor and major histocompatibility between the donor and the recipient

  9. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses.

    PubMed

    Owens, Sean D; Kol, Amir; Walker, Naomi J; Borjesson, Dori L

    2016-01-01

    Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM) or adipose tissue derived MSCs (ad-MSCs) were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89%) were positive for anti-bovine serum albumin (BSA) antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection. PMID:27648075

  10. Allogeneic Antigen Composition for Preparing Universal Cancer Vaccines

    PubMed Central

    Balashova, Elena E.

    2016-01-01

    Recently it was demonstrated that tumors induce specific changes to the surface of human endothelial cells thereby providing the basis for designing endothelial cell-based vaccines that directly target antigens expressed by the tumor endothelium. The present report extends these studies in vitro by investigating the efficacy of allogeneic antigens with regard to their ability to target immune responses against the tumor vasculature since alloantigens simplify vaccine development and implementation in clinical practice. We demonstrated that allogeneic SANTAVAC (Set of All Natural Target Antigens for Vaccination Against Cancer), which presents a specifically prepared composition of cell surface antigens from tumor-stimulated endothelial cells, allows targeting of the tumor vasculature with efficacy of 17, where efficacy represents the killing rate of target cells before normal cells are adversely affected, and efficacy of 60, where efficacy represents the fold decrease in the number of target cells and directly relates to tumor growth arrest. These data suggest that allogeneic SANTAVAC may be considered an antigenic composition that following administration in the presence of respective adjuvants may be clinically tested as a therapeutic or prophylactic universal cancer vaccine without adverse side effects to the normal vasculature. PMID:27781211

  11. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

    PubMed Central

    2016-01-01

    Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM) or adipose tissue derived MSCs (ad-MSCs) were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89%) were positive for anti-bovine serum albumin (BSA) antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection. PMID:27648075

  12. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

    PubMed Central

    2016-01-01

    Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM) or adipose tissue derived MSCs (ad-MSCs) were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89%) were positive for anti-bovine serum albumin (BSA) antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.

  13. SHIPi Enhances Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Fernandes, Sandra; Brooks, Robert; Gumbleton, Matthew; Park, Mi-Young; Russo, Christopher M.; Howard, Kyle T.; Chisholm, John D.; Kerr, William G.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) is a highly effective procedure enabling long-term survival for patients with hematologic malignancy or heritable defects. Although there has been a dramatic increase in the success rate of HSCT over the last two decades, HSCT can result in serious, sometimes untreatable disease due to toxic conditioning regimens and Graft-versus-Host-Disease. Studies utilizing germline knockout mice have discovered several candidate genes that could be targeted pharmacologically to create a more favorable environment for transplant success. SHIP1 deficiency permits improved engraftment of hematopoietic stem-progenitor cells (HS-PCs) and produces an immunosuppressive microenvironment ideal for incoming allogeneic grafts. The recent development of small molecule SHIP1 inhibitors has opened a different therapeutic approach by creating transient SHIP1-deficiency. Here we show that SHIP1 inhibition (SHIPi) mobilizes functional HS-PC, accelerates hematologic recovery, and enhances donor HS-PC engraftment in both allogeneic and autologous transplant settings. We also observed the expansion of key cell populations known to suppress host-reactive cells formed during engraftment. Therefore, SHIPi represents a non-toxic, new therapeutic that has significant potential to improve the success and safety of therapies that utilize autologous and allogeneic HSCT. PMID:26052545

  14. Thiotepa-based versus total body irradiation-based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

    PubMed

    Eder, Sandra; Labopin, Myriam; Arcese, William; Or, Reuven; Majolino, Ignazio; Bacigalupo, Andrea; de Rosa, Gennaro; Volin, Liisa; Beelen, Dietrich; Veelken, Hendrik; Schaap, Nicolaas P M; Kuball, Jurgen; Cornelissen, Jan; Nagler, Arnon; Mohty, Mohamad

    2016-01-01

    Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting.

  15. Comparing Social Network Analysis of Posts with Counting of Posts as a Measurement of Learners' Participation in Facebook Discussions

    ERIC Educational Resources Information Center

    Lee, Hye Yeon; Lee, Hyeon Woo

    2016-01-01

    With the currently growing interest in social network services, many college courses use social network services as platforms for discussions, and a number of studies have been conducted on the use of social network analysis to measure students' participation in online discussions. This study aims to demonstrate the difference between counting…

  16. Sharing feelings online: studying emotional well-being via automated text analysis of Facebook posts.

    PubMed

    Settanni, Michele; Marengo, Davide

    2015-01-01

    Digital traces of activity on social network sites represent a vast source of ecological data with potential connections with individual behavioral and psychological characteristics. The present study investigates the relationship between user-generated textual content shared on Facebook and emotional well-being. Self-report measures of depression, anxiety, and stress were collected from 201 adult Facebook users from North Italy. Emotion-related textual indicators, including emoticon use, were extracted form users' Facebook posts via automated text analysis. Correlation analyses revealed that individuals with higher levels of depression, anxiety expressed negative emotions on Facebook more frequently. In addition, use of emoticons expressing positive emotions correlated negatively with stress level. When comparing age groups, younger users reported higher frequency of both emotion-related words and emoticon use in their posts. Also, the relationship between online emotional expression and self-report emotional well-being was generally stronger in the younger group. Overall, findings support the feasibility and validity of studying individual emotional well-being by means of examination of Facebook profiles. Implications for online screening purposes and future research directions are discussed.

  17. The Orion Exploration Flight Test Post Flight Solid Particle Flight Environment Inspection and Analysis

    NASA Technical Reports Server (NTRS)

    Miller, Joshua E.

    2016-01-01

    Orbital debris in the millimeter size range can pose a hazard to current and planned spacecraft due to the high relative impact speeds in Earth orbit. Fortunately, orbital debris has a relatively short life at lower altitudes due to atmospheric effects; however, at higher altitudes orbital debris can survive much longer and has resulted in a band of high flux around 700 to 1,500 km above the surface of the Earth. While large orbital debris objects are tracked via ground based observation, little information can be gathered about small particles except by returned surfaces, which until the Orion Exploration Flight Test number one (EFT-1), has only been possible for lower altitudes (400 to 500 km). The EFT-1 crew module backshell, which used a porous, ceramic tile system with surface coatings, has been inspected post-flight for potential micrometeoroid and orbital debris (MMOD) damage. This paper describes the pre- and post-flight activities of inspection, identification and analysis of six candidate MMOD impact craters from the EFT-1 mission.

  18. Forest Fires and Post - Fire Regeneration in Algeria Analysis with Satellite Data

    NASA Astrophysics Data System (ADS)

    Zegrar, Ahmed

    2016-07-01

    The Algerian forests are characterized by a particularly flammable material and fuel. The wind, the relief and the slope facilitates the propagation of fire. The use of remote sensing data multi-­dates, combined with other types of data of various kinds on the environment and forest burned, opens up interesting perspectives for the management of post-­fire regeneration. In this study the use of multi-­temporal remote sensing image Alsat-­1 and Landsat combined with other types of data concerning both background and burned down forest appears to be promising in evaluating and spatial and temporal effects of post fire regeneration. A spatial analysis taking into consideration the characteristics of the burned down site in the North West of Algeria, allowed to better account new factors to explain the regeneration and its temporal and spatial variation. We intended to show the potential use of remote sensing data from satellite ALSAT-­1, of spatial resolution of 32 m. . This approach allows showing the contribution of the data of Algerian satellite ALSAT in the detection and the well attended some forest fires in Algeria.

  19. Post failure localization instabilities in chemically active creeping faults: Steady-state bifurcation and transient analysis

    NASA Astrophysics Data System (ADS)

    Alevizos, S.; Poulet, T.; Veveakis, M.

    2014-12-01

    In this study we emphasize in the post failure evolution of a creeping fault, and provide temporal and spatial modes of evolution. In particular we study the behavior of a fluid-saturated fault under shear, based on the assumption that the fabric presents rate- and temperature dependent response to shear loading. A creeping fault of this type can, under certain conditions, produce excess heat due to shear heating, reaching temperatures which are high enough for triggering endothermic chemical reactions. We focus on the decomposition reactions and incorporate excess pore pressure generation and variations of the porosity due to the chemical effects (a process called chemical pressurization). After deriving the corresponding system of equations in the region of the ultra-cataclastic core, we study the influence of the model parameters, namely the frictional, hydraulic and chemical properties of the material, along with the boundary conditions of the problem, on the behavior of the fault and through a non-linear bifurcation analysis we provide regimes of stable-frictional sliding and pressurization. Furthermore, the system is integrated in time to extract its temporal behavior, providing regimes of stable creep, non-periodic and periodic seismic slip events due to chemical pressurization, depending on their frictional properties. It is shown that this chemically induced seismic slip is an ultra-localized event in the post failure regime. It takes place in an extremely narrow band, 2 orders of magnitude narrower than the initial one, verifying the field observations.

  20. Gravitational waves from compact binaries inspiralling along post-Newtonian accurate eccentric orbits: Data analysis implications

    SciTech Connect

    Tessmer, Manuel; Gopakumar, Achamveedu

    2008-10-15

    Compact binaries inspiralling along eccentric orbits are plausible gravitational-wave (GW) sources for the ground-based laser interferometers. We explore the losses in the event rates incurred when searching for GWs from compact binaries inspiralling along post-Newtonian accurate eccentric orbits with certain obvious nonoptimal search templates. For the present analysis, GW signals having 2.5 post-Newtonian (PN) accurate orbital evolution are modeled following the phasing formalism, presented by T. Damour, A. Gopakumar, and B. R. Iyer [Phys. Rev. D 70, 064028 (2004)]. We demonstrate that the search templates that model in a gauge-invariant manner GWs from compact binaries inspiralling under quadrupolar radiation reaction along 2PN accurate circular orbits are very efficient in capturing our somewhat realistic GW signals. However, three types of search templates based on the adiabatic, complete adiabatic, and gauge-dependent complete nonadiabatic approximants, detailed in P. Ajith, B. R. Iyer, C. A. K. Robinson, and B. S. Sathyaprakash, Phys. Rev. D 71, 044029 (2005), relevant for the circular inspiral under the quadrupolar radiation reaction were found to be inefficient in capturing the above-mentioned eccentric signal. We conclude that further investigations will be required to probe the ability of various types of PN accurate circular templates, employed to analyze the LIGO/VIRGO data, to capture GWs from compact binaries having tiny orbital eccentricities.

  1. Gravitational waves from compact binaries inspiralling along post-Newtonian accurate eccentric orbits: Data analysis implications

    NASA Astrophysics Data System (ADS)

    Tessmer, Manuel; Gopakumar, Achamveedu

    2008-10-01

    Compact binaries inspiralling along eccentric orbits are plausible gravitational-wave (GW) sources for the ground-based laser interferometers. We explore the losses in the event rates incurred when searching for GWs from compact binaries inspiralling along post-Newtonian accurate eccentric orbits with certain obvious nonoptimal search templates. For the present analysis, GW signals having 2.5 post-Newtonian (PN) accurate orbital evolution are modeled following the phasing formalism, presented by T. Damour, A. Gopakumar, and B. R. Iyer [Phys. Rev. D 70, 064028 (2004)PRVDAQ0556-282110.1103/PhysRevD.70.064028]. We demonstrate that the search templates that model in a gauge-invariant manner GWs from compact binaries inspiralling under quadrupolar radiation reaction along 2PN accurate circular orbits are very efficient in capturing our somewhat realistic GW signals. However, three types of search templates based on the adiabatic, complete adiabatic, and gauge-dependent complete nonadiabatic approximants, detailed in P. Ajith, B. R. Iyer, C. A. K. Robinson, and B. S. Sathyaprakash, Phys. Rev. D 71, 044029 (2005)PRVDAQ0556-282110.1103/PhysRevD.71.044029, relevant for the circular inspiral under the quadrupolar radiation reaction were found to be inefficient in capturing the above-mentioned eccentric signal. We conclude that further investigations will be required to probe the ability of various types of PN accurate circular templates, employed to analyze the LIGO/VIRGO data, to capture GWs from compact binaries having tiny orbital eccentricities.

  2. Sharing feelings online: studying emotional well-being via automated text analysis of Facebook posts

    PubMed Central

    Settanni, Michele; Marengo, Davide

    2015-01-01

    Digital traces of activity on social network sites represent a vast source of ecological data with potential connections with individual behavioral and psychological characteristics. The present study investigates the relationship between user-generated textual content shared on Facebook and emotional well-being. Self-report measures of depression, anxiety, and stress were collected from 201 adult Facebook users from North Italy. Emotion-related textual indicators, including emoticon use, were extracted form users’ Facebook posts via automated text analysis. Correlation analyses revealed that individuals with higher levels of depression, anxiety expressed negative emotions on Facebook more frequently. In addition, use of emoticons expressing positive emotions correlated negatively with stress level. When comparing age groups, younger users reported higher frequency of both emotion-related words and emoticon use in their posts. Also, the relationship between online emotional expression and self-report emotional well-being was generally stronger in the younger group. Overall, findings support the feasibility and validity of studying individual emotional well-being by means of examination of Facebook profiles. Implications for online screening purposes and future research directions are discussed. PMID:26257692

  3. Sharing feelings online: studying emotional well-being via automated text analysis of Facebook posts.

    PubMed

    Settanni, Michele; Marengo, Davide

    2015-01-01

    Digital traces of activity on social network sites represent a vast source of ecological data with potential connections with individual behavioral and psychological characteristics. The present study investigates the relationship between user-generated textual content shared on Facebook and emotional well-being. Self-report measures of depression, anxiety, and stress were collected from 201 adult Facebook users from North Italy. Emotion-related textual indicators, including emoticon use, were extracted form users' Facebook posts via automated text analysis. Correlation analyses revealed that individuals with higher levels of depression, anxiety expressed negative emotions on Facebook more frequently. In addition, use of emoticons expressing positive emotions correlated negatively with stress level. When comparing age groups, younger users reported higher frequency of both emotion-related words and emoticon use in their posts. Also, the relationship between online emotional expression and self-report emotional well-being was generally stronger in the younger group. Overall, findings support the feasibility and validity of studying individual emotional well-being by means of examination of Facebook profiles. Implications for online screening purposes and future research directions are discussed. PMID:26257692

  4. Physical rehabilitation in post-conflict settings: analysis of public policy and stakeholder networks.

    PubMed

    Blanchet, Karl; Girois, Susan; Urseau, Isabelle; Smerdon, Christine; Drouet, Yann; Jama, Ali

    2014-01-01

    Physical rehabilitation plays a determinant role in post-conflict contexts to restore disabled citizens' mobility and independence. While the main objectives of any physical rehabilitation programme are to ensure that the services provided are accessible and of good quality to meet existing needs, it is intended that the services need to be supported over the long term by public health and social welfare authorities. This article presents the results of a study conducted in three post-conflict countries on the relationships between the level of commitment of national governments to rehabilitation services and the influence of social networks on national policy related to physical rehabilitation. From a policy and resource standpoint, the environment in Nepal is the most favourable for creating leverage at the national level to influence the commitment of ministries in the rehabilitation sector, compared with Cambodia and Somaliland. Stakeholder network analysis in Nepal, furthermore, reveals a dominant civil society and private sector supporting rehabilitation services, including intense involvement of local organisations and user groups. Implications for Rehabilitation Physical rehabilitation is not on the top of the agenda of governments in fragile states. The commitment and involvement of national authorities in the rehabilitation sector is positively influenced by civil society and international organisations. The denser the social network of the rehabilitation sector is, the more influence the actors can exert influence over national authorities. PMID:23672208

  5. Longitudinal Changes in Body Mass and Composition in Survivors of Childhood Hematologic Malignancies After Allogeneic Hematopoietic Stem-Cell Transplantation

    PubMed Central

    Inaba, Hiroto; Yang, Jie; Kaste, Sue C.; Hartford, Christine M.; Motosue, Megan S.; Chemaitilly, Wassim; Triplett, Brandon M.; Shook, David R.; Pui, Ching-Hon; Leung, Wing

    2012-01-01

    Purpose To measure longitudinal changes in body mass and composition in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem-cell transplantation (HSCT). Patients and Methods Body mass index (BMI) was analyzed in 179 survivors by category (underweight, healthy-weight, overweight, and obese) and by z score. Fat and lean body mass measured by dual-energy x-ray absorptiometry was analyzed as z scores. Results Over a median 6.6 years of follow-up, BMI z scores diminished significantly (0.32 pre-HSCT v −0.60 at 10 years post-HSCT; P < .001). Mean z scores for fat mass stayed within population norms, but those for lean mass remained below normal levels and diminished significantly over time (P = .018). Pre-HSCT BMI category and/or z score were strongly predictive of post-HSCT BMI (P < .001) and of fat and lean mass z scores (both P < .001). Survivors with extensive chronic graft-versus-host disease were more likely than others to have low BMI (P = .004) and low lean mass (P < .001) post-HSCT. Older age at HSCT (P = .015) and T-cell–depleted graft (P = .018) were predictive of lower post-HSCT BMI. Female patients had higher body fat (P = .002) and lower lean mass (P = .013) z scores than male patients, and black patients had higher fat mass z scores than white patients (P = .026). Conclusion BMI declines significantly after allogeneic HSCT for childhood hematologic malignancies, reflecting primarily a substantial decrease in lean mass but not fat mass. Monitoring and preservation of BMI and lean mass are vital, especially in those with the identified risk factors. PMID:23032628

  6. Post-16 Physics and Chemistry Uptake: Combining Large-Scale Secondary Analysis with In-Depth Qualitative Methods

    ERIC Educational Resources Information Center

    Hampden-Thompson, Gillian; Lubben, Fred; Bennett, Judith

    2011-01-01

    Quantitative secondary analysis of large-scale data can be combined with in-depth qualitative methods. In this paper, we discuss the role of this combined methods approach in examining the uptake of physics and chemistry in post compulsory schooling for students in England. The secondary data analysis of the National Pupil Database (NPD) served…

  7. Error analysis in post linac to driver linac transport beam line of RAON

    NASA Astrophysics Data System (ADS)

    Kim, Chanmi; Kim, Eun-San

    2016-07-01

    We investigated the effects of magnet errors in the beam transport line connecting the post linac to the driver linac (P2DT) in the Rare Isotope Accelerator in Korea (RAON). The P2DT beam line is bent by 180-degree to send the radioactive Isotope Separation On-line (ISOL) beams accelerated in Linac-3 to Linac-2. This beam line transports beams with multi-charge state 132Sn45,46,47. The P2DT beam line includes 42 quadrupole, 4 dipole and 10 sextupole magnets. We evaluate the effects of errors on the trajectory of the beam by using the TRACK code, which includes the translational and the rotational errors of the quadrupole, dipole and sextupole magnets in the beam line. The purpose of this error analysis is to reduce the rate of beam loss in the P2DT beam line. The distorted beam trajectories can be corrected by using six correctors and seven monitors.

  8. A pilot DTI analysis in patients with recent onset post-traumatic stress disorder

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Li, Liang; Li, Baojuan; Zhang, Xi; Lu, Hongbing

    2016-03-01

    To explore the alteration in white matter between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, who survived from the same coal mine flood disaster, the diffusion tensor imaging (DTI) sequences were analyzed using DTI studio and statistical parametric mapping (SPM) packages in this paper. From DTI sequence, the fractional anisotropy (FA) value describes the degree of anisotropy of a diffusion process, while the apparent diffusion coefficient (ADC) value reflects the magnitude of water diffusion. The DTI analyses between PTSD and non-PTSD indicate lower FA values in the right caudate nucleus, right middle temporal gyrus, right fusiform gyrus, and right superior temporal gyrus, and higher ADC values in the right superior temporal gyrus and right corpus callosum of the subjects with PTSD. These results are partly in line with our previous volume and cortical thickness analyses, indicating the importance of multi-modality analysis for PTSD.

  9. A guide to genome-wide association analysis and post-analytic interrogation.

    PubMed

    Reed, Eric; Nunez, Sara; Kulp, David; Qian, Jing; Reilly, Muredach P; Foulkes, Andrea S

    2015-12-10

    This tutorial is a learning resource that outlines the basic process and provides specific software tools for implementing a complete genome-wide association analysis. Approaches to post-analytic visualization and interrogation of potentially novel findings are also presented. Applications are illustrated using the free and open-source R statistical computing and graphics software environment, Bioconductor software for bioinformatics and the UCSC Genome Browser. Complete genome-wide association data on 1401 individuals across 861,473 typed single nucleotide polymorphisms from the PennCATH study of coronary artery disease are used for illustration. All data and code, as well as additional instructional resources, are publicly available through the Open Resources in Statistical Genomics project: http://www.stat-gen.org.

  10. Digital PCR to assess hematopoietic chimerism after allogeneic stem cell transplantation.

    PubMed

    Stahl, Tanja; Böhme, Manja U; Kröger, Nicolaus; Fehse, Boris

    2015-06-01

    Analysis of hematopoietic chimerism after allogeneic stem cell transplantation represents a crucial method to evaluate donor-cell engraftment. Whereas sensitivity of classical approaches for chimerism monitoring is limited to ≥1%, quantitative polymerase chain reaction (qPCR)-based techniques readily detect one patient cell in >1,000 donor cells, thus facilitating application of chimerism assessment as a surrogate for minimal residual disease. However, due to methodologic specificities, qPCR combines its high sensitivity with limited resolution power in the state of mixed chimerism (e.g., >10% patient cells). Our aim was to overcome this limitation by employing a further development of qPCR, namely digital PCR (dPCR), for chimerism analysis. For proof-of-principle, we established more than 10 dPCR assays detecting Indel polymorphisms or Y-chromosome sequences and tested them on artificial cell mixtures and patient samples. Employing artificial cell mixtures, we found that dPCR allows exact quantification of chimerism over several orders of magnitude. Digital PCR results proved to be highly reproducible (deviation <5%), particularly in the "difficult" range of mixed chimerism. Excellent performance of the new assays was confirmed by analysis of multiple retrospective blood samples from patients after allogeneic stem cell transplantation, in comparison with established qPCR (14 patients) and short-tandem repeat PCR (4 patients) techniques. Finally, dPCR is easy to perform, needs only small amounts of DNA for chimerism assessment (65 ng corresponds to a sensitivity of approximately 0.03%), and does not require the use of standard curves and replicate analysis. In conclusion, dPCR represents a very promising method for routine chimerism monitoring.

  11. Allogeneic Mature Human Dendritic Cells Generate Superior Alloreactive Regulatory T Cells in the Presence of IL-15.

    PubMed

    Litjens, Nicolle H R; Boer, Karin; Zuijderwijk, Joke M; Klepper, Mariska; Peeters, Annemiek M A; Prens, Errol P; Verschoor, Wenda; Kraaijeveld, Rens; Ozgur, Zeliha; van den Hout-van Vroonhoven, Mirjam C; van IJcken, Wilfred F J; Baan, Carla C; Betjes, Michiel G H

    2015-06-01

    Expansion of Ag-specific naturally occurring regulatory T cells (nTregs) is required to obtain sufficient numbers of cells for cellular immunotherapy. In this study, different allogeneic stimuli were studied for their capacity to generate functional alloantigen-specific nTregs. A highly enriched nTreg fraction (CD4(+)CD25(bright)CD127(-) T cells) was alloantigen-specific expanded using HLA-mismatched immature, mature monocyte-derived dendritic cells (moDCs), or PBMCs. The allogeneic mature moDC-expanded nTregs were fully characterized by analysis of the demethylation status within the Treg-specific demethylation region of the FOXP3 gene and the expression of both protein and mRNA of FOXP3, HELIOS, CTLA4, and cytokines. In addition, the Ag-specific suppressive capacity of these expanded nTregs was tested. Allogeneic mature moDCs and skin-derived DCs were superior in inducing nTreg expansion compared with immature moDCs or PBMCs in an HLA-DR- and CD80/CD86-dependent way. Remarkably, the presence of exogenous IL-15 without IL-2 could facilitate optimal mature moDC-induced nTreg expansion. Allogeneic mature moDC-expanded nTregs were at low ratios (<1:320), potent suppressors of alloantigen-induced proliferation without significant suppression of completely HLA-mismatched, Ag-induced proliferation. Mature moDC-expanded nTregs were highly demethylated at the Treg-specific demethylation region within the FOXP3 gene and highly expressed of FOXP3, HELIOS, and CTLA4. A minority of the expanded nTregs produced IL-10, IL-2, IFN-γ, and TNF-α, but few IL-17-producing nTregs were found. Next-generation sequencing of mRNA of moDC-expanded nTregs revealed a strong induction of Treg-associated mRNAs. Human allogeneic mature moDCs are highly efficient stimulator cells, in the presence of exogenous IL-15, for expansion of stable alloantigen-specific nTregs with superior suppressive function. PMID:25917092

  12. Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Mendorf, Alexander; Klyuchnikov, Evgeny; Langebrake, Claudia; Rohde, Holger; Ayuk, Francis; Regier, Marc; Christopeit, Maximilian; Zabelina, Tatjana; Bacher, Adelbert; Stübig, Thomas; Wolschke, Christine; Bacher, Ulrike; Kröger, Nicolaus

    2015-01-01

    Toxoplasmosis and infections by other opportunistic agents such as Pneumocystis jirovecii constitute life-threatening risks for patients after allogeneic hematopoietic stem cell transplantation. Trimethoprim/sulfamethoxazole (TMP-SMX) has been well established for post-transplant toxoplasmosis and pneumocystis prophylaxis, but treatment may be limited due to toxicity. We explored atovaquone as an alternative and compared it with TMP-SMX regarding toxicity and efficacy during the first 100 days after transplantation in 155 consecutive adult stem cell recipients. Eight patients with a prior history of TMP-SMX intolerance received atovaquone as first-line prophylaxis. TMP-SMX was used for 141 patients as first-line strategy, but 13 patients (9.2%) were later switched to atovaquone due to TMP-SMX toxicity or gastrointestinal symptoms. No active toxoplasmosis or active P. jirovecii infection developed under continued prophylaxis with either TMP-SMX or atovaquone. However, for reasons of TMP-SMX and/or atovaquone toxicity, 7 patients were unable to tolerate any efficacious toxoplasmosis prophylaxis and therefore obtained inhalative pentamidine as P. jirovecii prophylaxis but no toxoplasmosis prophylaxis. Importantly, 2 of these patients developed severe toxoplasmosis. In summary, atovaquone appears as a valid alternative for at least some post-transplant patients who cannot tolerate TMP-SMX. This should be further confirmed by multicenter trials. PMID:25968483

  13. Role of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia

    PubMed Central

    Lussana, Federico; Rambaldi, Alessandro

    2014-01-01

    Adult acute lymphoblastic leukemia (ALL) is a heterogeneous disease, due to the expression of different biological and clinical risk factors, for which allogeneic stem cell transplantation (alloHSCT) is an effective consolidation therapy. The non-relapse mortality of alloHSCT remains significantly higher compared with that of conventional chemotherapy. Therefore, one of the main challenges in the care of ALL is to establish a more precise prognostic definition to select patients who could take advantage from an alloHSCT. Currently, the use of minimal residual disease following induction and early consolidation therapy has improved the prognostic accuracy in defining ALL risk class. In Philadelphia-positive ALL, the introduction of tyrosine kinase inhibitors pre and post alloHSCT appears to improve outcomes significantly and, in the absence of specially designed clinical trials, alloHSCT remains the most effective post-remission therapy. Nowadays, alloHSCT can be performed according to various modalities encompassing the use of different conditioning regimens, as well as distinct donors and stem cell source, with a significant accessibility to transplant. PMID:25408851

  14. Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Mendorf, Alexander; Klyuchnikov, Evgeny; Langebrake, Claudia; Rohde, Holger; Ayuk, Francis; Regier, Marc; Christopeit, Maximilian; Zabelina, Tatjana; Bacher, Adelbert; Stübig, Thomas; Wolschke, Christine; Bacher, Ulrike; Kröger, Nicolaus

    2015-01-01

    Toxoplasmosis and infections by other opportunistic agents such as Pneumocystis jirovecii constitute life-threatening risks for patients after allogeneic hematopoietic stem cell transplantation. Trimethoprim/sulfamethoxazole (TMP-SMX) has been well established for post-transplant toxoplasmosis and pneumocystis prophylaxis, but treatment may be limited due to toxicity. We explored atovaquone as an alternative and compared it with TMP-SMX regarding toxicity and efficacy during the first 100 days after transplantation in 155 consecutive adult stem cell recipients. Eight patients with a prior history of TMP-SMX intolerance received atovaquone as first-line prophylaxis. TMP-SMX was used for 141 patients as first-line strategy, but 13 patients (9.2%) were later switched to atovaquone due to TMP-SMX toxicity or gastrointestinal symptoms. No active toxoplasmosis or active P. jirovecii infection developed under continued prophylaxis with either TMP-SMX or atovaquone. However, for reasons of TMP-SMX and/or atovaquone toxicity, 7 patients were unable to tolerate any efficacious toxoplasmosis prophylaxis and therefore obtained inhalative pentamidine as P. jirovecii prophylaxis but no toxoplasmosis prophylaxis. Importantly, 2 of these patients developed severe toxoplasmosis. In summary, atovaquone appears as a valid alternative for at least some post-transplant patients who cannot tolerate TMP-SMX. This should be further confirmed by multicenter trials.

  15. ProteomeScout: a repository and analysis resource for post-translational modifications and proteins

    PubMed Central

    Matlock, Matthew K.; Holehouse, Alex S.; Naegle, Kristen M.

    2015-01-01

    ProteomeScout (https://proteomescout.wustl.edu) is a resource for the study of proteins and their post-translational modifications (PTMs) consisting of a database of PTMs, a repository for experimental data, an analysis suite for PTM experiments, and a tool for visualizing the relationships between complex protein annotations. The PTM database is a compendium of public PTM data, coupled with user-uploaded experimental data. ProteomeScout provides analysis tools for experimental datasets, including summary views and subset selection, which can identify relationships within subsets of data by testing for statistically significant enrichment of protein annotations. Protein annotations are incorporated in the ProteomeScout database from external resources and include terms such as Gene Ontology annotations, domains, secondary structure and non-synonymous polymorphisms. These annotations are available in the database download, in the analysis tools and in the protein viewer. The protein viewer allows for the simultaneous visualization of annotations in an interactive web graphic, which can be exported in Scalable Vector Graphics (SVG) format. Finally, quantitative data measurements associated with public experiments are also easily viewable within protein records, allowing researchers to see how PTMs change across different contexts. ProteomeScout should prove useful for protein researchers and should benefit the proteomics community by providing a stable repository for PTM experiments. PMID:25414335

  16. Cochlear neuropathy in human presbycusis: confocal analysis of hidden hearing loss in post-mortem tissue

    PubMed Central

    Viana, Lucas M.; O’Malley, Jennifer T.; Burgess, Barbara J.; Jones, Dianne D.; Oliveira, Carlos A.C.P.; Santos, Felipe; Merchant, Saumil N.; Liberman, Leslie D.; Liberman, M. Charles

    2015-01-01

    Recent animal work has suggested that cochlear synapses are more vulnerable than hair cells in both noise-induced and age-related hearing loss. This synaptopathy is invisible in conventional histopathological analysis, because cochlear nerve cell bodies in the spiral ganglion survive for years, and synaptic analysis requires special immunostaining or serial-section electron microscopy. Here, we show that the same quadruple-immunostaining protocols that allow synaptic counts, hair cell counts, neuronal counts and differentiation of afferent and efferent fibers in mouse can be applied to human temporal bones, when harvested within 9 hrs post-mortem and prepared as dissected whole mounts of the sensory epithelium and osseous spiral lamina. Quantitative analysis of five “normal” ears, aged 54 to 89 yrs, without any history of otologic disease, suggests that cochlear synaptopathy and the degeneration of cochlear nerve peripheral axons, despite a near-normal hair cell population, may be an important component of human presbycusis. Although primary cochlear nerve degeneration is not expected to affect audiometric thresholds, it may be key to problems with hearing in noise that are characteristic of declining hearing abilities in the aging ear. PMID:26002688

  17. Nitrogen Species in the Post-Pinatubo Stratosphere: Model Analysis Utilizing UARS Measurements. Appendix F

    NASA Technical Reports Server (NTRS)

    Danilin, Michael Y.; Rodriguez, Jose M.; Hu, Wenjie; Ko, Malcolm K. W.; Weisenstein, Debra K.; Kumer, John B.; Mergenthaler, John L.; Russell, James M., III; Koike, Makoto; Yue, Glenn K.

    1999-01-01

    We present an analysis of the impact of heterogeneous chemistry on the partitioning of nitrogen species measured by the Upper Atmosphere Research Satellite (UARS) instruments. The UARS measurements utilized include N2O, HNO3, and ClONO2 from the cryogenic limb array etalon spectrometer (CLAES), version 7 (v.7), and temperature, methane, ozone, H2O, HCl, NO and NO2 from the halogen occultation experiment (HALOE), version 18. The analysis is carried out for the UARS data obtained between January 1992 and September 1994 in the 100- to 1-mbar (approx. 17-47 km) altitude range and over 10 deg latitude bins from 70 deg S to 70 deg N. The spatiotemporal evolution of aerosol surface area density (SAD) is adopted from analysis of the Stratospheric Aerosol and Gas Experiment (SAGE) II data. A diurnal steady state photochemical box model, constrained by the temperature, ozone, H2O, CH4, aerosol SAD, and columns of O2 and O3 above the point of interest, has been used as the main tool to analyze these data. Total inorganic nitrogen (NOY) is obtained by three different methods: (1) as a sum of the UARS-measured NO, NO2, HNO3, and ClONO2; (2) from the N2O-NOY correlation; and (3) from the CH4-NOY correlation. To validate our current understanding of stratospheric heterogeneous chemistry for post-Pinatubo conditions, the model-calculated monthly averaged NO(x)/NO(y) ratios and the NO, NO2, and HNO3 profiles are compared with the UARS-derived data. In general, the UARS-constrained box model captures the main features of nitrogen species partitioning in the post-Pinatubo years, such as recovery of NO(x) after the eruption, their seasonal variability and vertical profiles. However, the model underestimates the NO2 content, particularly in the 30- to 7-mbar (approx. 23-32 km) range. Comparisons of the calculated temporal behavior of the partial columns of NO2 and HNO3 and ground-based measurements at 45 deg S and 45 deg N are also presented. Our analysis indicates that ground

  18. Nitrogen Species in the Post-Pinatubo Stratosphere: Model Analysis Utilizing UARS Measurements

    NASA Technical Reports Server (NTRS)

    Danilin, Michael Y.; Rodriguez, Jose M.; Hu, Wen-Jie; Ko, Malcolm K. W.; Weisenstein, Debra K.; Kumer, John B.; Mergenthaler, John L.; Russel, James M., III; Koike, Makoto; Yue, Glenn K.

    1999-01-01

    We present an analysis of the impact of heterogeneous chemistry on the partitioning of nitrogen species measured by the Upper Atmosphere Research Satellite (UARS) instruments. The UARS measurements utilized include N2O, HNO3, and ClONO2 from the cryogenic limb array etalon spectrometer (CLAES), version 7 (v.7), and temperature, methane, ozone, H2O, HCl, NO and NO2 from the halogen occultation experiment (HALOE), version 18. The analysis is carried out for the UARS data obtained between January 1992 and September 1994 in the 100-to 1-mbar (approx. 17-47 km) altitude range and over 10 degrees latitude bins from 70 S to 70 N. The spatiotemporal evolution of aerosol surface area density (SAD) is adopted from analysis of the Stratospheric Aerosol and Gas Experiment (SAGE) II data. A diurnal steady state photochemical box model, constrained by the temperature, ozone, H2O, CH4, aerosol SAD, and columns of O2 and O3 above the point of interest, has been used as the main tool to analyze these data. Total inorganic nitrogen (NOy) is obtained by three different methods: (1) as a sum of the UARS-measured NO, NO2, HNO3, and ClONO2; (2) from the N2O-NOy correlation, and (3) from the CH4-NOy correlation. To validate our current understanding of stratospheric heterogeneous chemistry for post-Pinatubo conditions, the model-calculated monthly averaged NOx/NOy ratios and the NO, NO2, and HNO3 profiles are compared with the UARS-derived data. In general, the UARS-constrained box model captures the main features of nitrogen species partitioning in the post-Pinatubo years, such as recovery of NOx after the eruption, their seasonal variability and vertical profiles. However, the model underestimates the NO2 content, particularly in the 30- to 7-mbar (approx.23-32 km) range. Comparisons of the calculated temporal behavior of the partial columns of NO2 and HNO3 and ground-based measurements at 45 S and 45 N are also presented. Our analysis indicates that ground-based and HALOE v.18

  19. Post-mastectomy Radiation Therapy for T3N0: A SEER Analysis

    PubMed Central

    Johnson, Matthew E.; Handorf, Elizabeth A.; Martin, Jeffrey M.; Hayes, Shelly B.

    2015-01-01

    Background There is conflicting evidence regarding the benefit of post-mastectomy radiation therapy (PMRT) for pathologic stage T3N0M0 breast cancers. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database to investigate the benefit of PMRT in these patients. Methods We queried the SEER database for T3N0M0 breast cancer patients diagnosed from 2000–2010 who underwent modified radical mastectomy. We excluded males, patients with unknown radiation timing/type, other primary tumors, or survival <6 months. 2525 patients were included in this analysis. We performed univariate and multivariate statistical analysis using Chi-squared tests, log rank test, and Cox proportional hazards regression. Primary endpoints were overall survival (OS) and breast cancer-specific survival (CSS). Results Of the 2525 patients identified, 1063 received PMRT. The median follow-up was 56 months (range: 6–131). On univariate analysis, PMRT improved OS (76.5% vs. 61.8%, p<0.01) and CSS (85.0% vs. 82.4%, p<0.01) at 8 years. The use of PMRT remained significant on multivariate analysis: PMRT improved OS (HR 0.63, p<0.001) and CSS (HR 0.77, p=0.045). Low tumor grade (p<0.01) and marital status "married" (p=0.01) also predicted for improved CSS on multivariate analysis. Conclusion(s) PMRT was associated with significant improvements in both CSS and OS in patients with T3N0M0 breast cancers treated with modified radical mastectomy from 2000 to 2010. PMRT should be strongly considered in T3N0M0 patients. PMID:24985911

  20. Regional analysis of distribution of pre and post 2015 Nepal Earthquake landslides

    NASA Astrophysics Data System (ADS)

    Valagussa, Andrea; Frattini, Paolo; Crosta, Giovanni; Valbuzzi, Elena

    2016-04-01

    A magnitude 7.8 earthquake struck Nepal on April 25, 2015. Three landslide inventories have been prepared in four districts: Dhading (1885 km2), Sindhupalchok (2488 km2), Rasuwa (1522 km2) and Nuwakot (1194 km2), that are located north of Kathmandu. These inventories extend 14 to 138 km SE from the epicenter of the main shock (April 25, 2015), 4.5 to 143 km NW from the epicenter of the main aftershock (May 12, 2015), and 34 to 136 km from the Main Frontal Thrust. The first inventory is a coseismic and post-seismic landslide inventory based on multi-temporal images (Google Earth, Google Crisis maps, Bing maps), and helicopter-based video. The second one is a pre-event shallow landslide inventory. In these two inventories the most abundant landslide types are: debris flows, shallow translational slides, and rockfalls. The third is a deep seated landslide inventory, in which the most represented landslide types are rock avalanches, slumps, rockslides and deep-seated gravitational slope deformations (DSGSD). All the landslides have been mapped as individual polygons. For the analysis we focus our attention on four districts: First we studied how the landslide frequency density changes as a function of topographic parameters (i.e. slope gradient, slope aspect, and elevation). The analyses have been based on the ASTER Global Digital Elevation Model (ASTER GDEM). For coseismic and post-seismic landslides we observed that the mean slope gradient at which the landslide occurs is higher with respect to the two other inventories (50° and 30/40° respectively). The slope aspect of coseismic and post-seismic landslides is also different, with a larger frequency of landslides towards SW, whereas in pre-event landslides the most common slope aspect is SE. This could be related to the direction of the seismic wave. At least the coseismic and post-seismic landslides occur, in mean, at an elevation lower than the pre-event landslides. We also analyzed the relationship between the

  1. Post-analysis report on Chesapeake Bay data processing. [spectral analysis and recognition computer signature extension

    NASA Technical Reports Server (NTRS)

    Thomson, F.

    1972-01-01

    The additional processing performed on data collected over the Rhode River Test Site and Forestry Site in November 1970 is reported. The techniques and procedures used to obtain the processed results are described. Thermal data collected over three approximately parallel lines of the site were contoured, and the results color coded, for the purpose of delineating important scene constituents and to identify trees attacked by pine bark beetles. Contouring work and histogram preparation are reviewed and the important conclusions from the spectral analysis and recognition computer (SPARC) signature extension work are summarized. The SPARC setup and processing records are presented and recommendations are made for future data collection over the site.

  2. Osteogenic activity of bone marrow-derived mesenchymal stem cells (BMSCs) seeded on irradiated allogenic bone.

    PubMed

    Tohma, Yasuaki; Dohi, Yoshiko; Ohgushi, Hajime; Tadokoro, Mika; Akahane, Manabu; Tanaka, Yasuhito

    2012-02-01

    Allogenic bone grafting, a technique used in orthopaedic surgery, has several problems, including low osteogenic activity. To overcome the problem, this study aimed to determine whether in vivo osteogenesis could be enhanced using allogenic irradiated bone grafts after seeding with autologous bone marrow-derived mesenchymal stem cells (BMSCs). The allogenic bone cylinders were extracted from ACI rats and sterilized by irradiation. Donor BMSCs were obtained from fresh Fischer 344 (F344) rat bone marrow by cell culture. The allogenic bone with or without BMSCs were transplanted subcutaneously into syngeneic F344 rats. At 4 weeks after transplantation, high alkaline phosphatase (ALP) activity, bone-specific osteocalcin mRNA expression and newly formed bone were detected in the allogenic bone with BMSCs. The origin of the newly formed bone was derived from cultured donor BMSCs. However, none of these identifiers of osteogenesis were detected in either the fresh or the irradiated allogenic bone without BMSCs. These results indicate the availability of autologous BMSCs to heighten the osteogenic response of allogenic bone. Our present tissue-engineering method might contribute to a wide variety of allogenic bone grafting techniques in clinical settings.

  3. [Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank].

    PubMed

    Barriga, Francisco; Wietstruck, Angélica; Rojas, Nicolás; Bertin, Pablo; Pizarro, Isabel; Carmona, Amanda; Guilof, Alejandro; Rojas, Iván; Oyarzún, Enrique

    2013-08-01

    Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

  4. The need for complementary hydraulic analysis in post-restoration monitoring of river restoration projects

    NASA Astrophysics Data System (ADS)

    Endreny, T. A.; Soulman, M. M.

    2011-03-01

    River restoration design methods are incrementally improved by studying and learning from monitoring data in previous projects. In this paper, we report post-restoration monitoring data for a Natural Channel Design (NCD) restoration project along 1600 m (10 channel wavelengths) of the Batavia Kill in the Catskill Mountains, NY, implemented in 2001 and 2002. The NCD project used a reference-reach to determine channel form, empirical relations between the project site and reference site bankfull dimensions to size channel geometry, and hydraulic and sediment computations to test channel capacity and sediment stability. In addition 12 cross-vanes and 48 j-hook vanes used in NCD for river training were installed to protect against bank erosion and maintain scour pools for fish habitat. Changes in pool depths were monitored with surveys from 2002-2004, and then after the channel-altering April 2005 flood. Aggradation in pools was attributed to cross-vane arms not concentrating flow in the center of the channel, which subsequently caused flow splitting and 4 partial point bar avulsions during the 2005 flood. Hydrodynamic simulation at the 18 m3s-1 bankfull flow suggested avulsions occurred where vanes allowed erosive bank scour to initiate the avulsion cut, and once the flow was split, the diminished in-channel flow caused more aggradation in the pools. In this project post-restoration monitoring had detected aggradation and considered it a problem. The lesson for the larger river restoration community is monitoring protocol should include complementary hydraulic and sediment analysis to comprehend potential consequences and develop preventative maintenance. River restoration and monitoring teams should be trained in robust hydraulic and sediment analytical methods that help them extend project restoration goals.

  5. BOT3P: Bologna Transport Analysis Pre-Post-Processors Version 1.0

    SciTech Connect

    Orsi, Roberto

    2002-11-15

    BOT3P is a set of standard FORTRAN 77 language programs that were developed at the ENEA-Bologna Nuclear Data Centre. BOT3P aims to give the users of the DORT and TORT deterministic transport codes some useful diagnostic tools to prepare and to check their input data files. It also includes some plotting programs that can be employed both as preprocessors and as postprocessors of a transport analysis. The BOT3P plotting programs use the RSCORS Graphics System subroutines, included in the DOORS-3.3 and earlier software package together with the Oak Ridge National Laboratory DORT and TORT transport codes.BOT3P was developed on a DIGITAL UNIX ALPHA 500/333 workstation and successfully used in some complex applications such as the VENUS-1 and VENUS-3 neutron shielding benchmarks. BOT3P was tested on an IBM RS/6000 workstation also and is designed to run on most UNIX platforms.The following programs are included in the package: GGDM, DDM, GGTM, DTM2, DTM3, and RVARSCL. GGDM and GGTM generate the geometrical and material entries for DORT and TORT, respectively. DDM is a DORT graphics pre/post processor. DTM2 and DTM3 are graphics pre/post processors showing cuts and three-dimensional views of the TORT model, respectively. RVARSCL reads DORT/TORT 'VARSCL' sequential format files and selects and writes the data required by the user in new files to be visualized by DDM, DTM2, and DTM3 as postprocessor applications.The package is publicly available from the Organization for Economic Cooperation and Development/Nuclear Energy Agency Data Bank (NEA-1627)

  6. Evaluation of a post-processing approach for multiscale analysis of biphasic mechanics of chondrocytes.

    PubMed

    Sibole, Scott C; Maas, Steve; Halloran, Jason P; Weiss, Jeffrey A; Erdemir, Ahmet

    2013-10-01

    Understanding the mechanical behaviour of chondrocytes as a result of cartilage tissue mechanics has significant implications for both evaluation of mechanobiological function and to elaborate on damage mechanisms. A common procedure for prediction of chondrocyte mechanics (and of cell mechanics in general) relies on a computational post-processing approach where tissue-level deformations drive cell-level models. Potential loss of information in this numerical coupling approach may cause erroneous cellular-scale results, particularly during multiphysics analysis of cartilage. The goal of this study was to evaluate the capacity of first- and second-order data passing to predict chondrocyte mechanics by analysing cartilage deformations obtained for varying complexity of loading scenarios. A tissue-scale model with a sub-region incorporating representation of chondron size and distribution served as control. The post-processing approach first required solution of a homogeneous tissue-level model, results of which were used to drive a separate cell-level model (same characteristics as the sub-region of control model). The first-order data passing appeared to be adequate for simplified loading of the cartilage and for a subset of cell deformation metrics, for example, change in aspect ratio. The second-order data passing scheme was more accurate, particularly when asymmetric permeability of the tissue boundaries was considered. Yet, the method exhibited limitations for predictions of instantaneous metrics related to the fluid phase, for example, mass exchange rate. Nonetheless, employing higher order data exchange schemes may be necessary to understand the biphasic mechanics of cells under lifelike tissue loading states for the whole time history of the simulation.

  7. [Photoelastic stress analysis of root dentin with different composite resin post and core systems and crowns].

    PubMed

    Takei, Hidenori

    2010-03-01

    Much research has been reported about post and core systems with composite resin, but the influence of the different types of prefabricated posts on the distribution of stress in the root has not yet been elucidated. It is necessary to clarify the influence of the relationship between core and crown materials to obtain combined restorations. The aim of this study is to analyze the influence of the combination of various post and core systems and different kinds of crown material on the stress distribution in the root. Six 2-dimensional photoelastic premolar models were designed. Three types of post and core systems (composite resin post and core, composite resin core with the fiber post, and composite resin core with a prefabricated stainless steel post) and two kinds of crown materials (metal and hybrid-type hard composite resin) were fabricated and cemented to each model. In these models, we applied a load of 200 N at an angle of 45 degrees to the tooth axis and analyzed the fringe order using a transmission polariscope. As a result, it has been clarified that the combination of the post and core and the crown plays an important role in preventing stress concentration within root Stress concentration can be prevented using a crown fabricated with a high-elastic modulus for the post and core with a high-elastic modulus, and a crown fabricated with a low-elastic modulus for the post and core with a low-elastic modulus.

  8. Specific allogeneic unresponsiveness in the adult host: present-day experimental models

    SciTech Connect

    Rapaport, F.T.; Bachvaroff, R.J.; Cronkite, E.; Chanana, A.; Sato, T.; Asari, H.; Waltzer, W.C.

    1982-01-01

    As part of a long-term intensive effort to apply the induction of adult allogensic unresponsiveness to the transplantation problem, two techniques to control the variability in the persistence of immunologically competent postthymic cells iin the treated host and/or the inoculum of autologous marrow returned to the host after irradiation are described. The first consisted of exposing the peripheral blood of prospective recipients to a 5-week course of extra-corporeal irradiation (ECIB), the other of exposing the stored autologous marrow scheduled to repopulate a given recipient to methyl-prednisolone (MPd) and DNase prior to renifusion into the recipient. Serial analysis of bone marrow cell samples at various intervals before and after treatment was undertaken. The significance of the disappearance of a particular population of nonnuclear cells from the samples, and the association of such disappearance with increased success in the induction of allogeneic unresponsiveness is discussed. (ACR)

  9. Nitrogen Species in the Post-Pinatubo Stratosphere: Model Analysis Utilizing UARS Measurements

    NASA Technical Reports Server (NTRS)

    Danilin, M. Y.; Rodriquez, J. M.; Hu, W.; Ko, M. K. W.; Weisenstein, D. K.; Mergenthaler, J. L.; Russell, J. M., III; Koike, M.; Yue, G. K.

    1998-01-01

    We present an analysis of the impact of heterogeneous chemistry on the partitioning of nitrogen species measured by the Upper Atmosphere Research Satellite (UARS) instruments. The UARS measurements utilized include: N2O, HNO3 and ClONO2 (Cryogen Limb Array Etalon Spectrometer (CLAES), version 7), temperature, methane, ozone, H2O, HCl, NO and NO2 (HALogen Occultation Experiment (HALOE), version 18). The analysis is carried out for the data from January 1992 to September 1994 in the 100-1 mbar (approx.17-47 km) altitude range and over 10 degree latitude bins from 70degS to 70degN. Temporal-spatial evolution of aerosol surface area density (SAD) is adopted according to the Stratospheric Aerosol and Gas Experiment (SAGE) 11 data. A diurnal steady-state photochemical box model, constrained by the temperature, ozone, H2O, CH4, aerosol SAD and columns of O2 and O3 above the point of interest, has been used as the main tool to analyze these data. Total inorganic nitrogen (NO(y)) is obtained by three different methods: (1) as a sum of the UARS measured NO, NO2, HNO3, and ClONO2; (2) from the N2O-NO(y) correlation, and (3) from the CH4-NO(y) correlation. To validate our current understanding of stratospheric heterogeneous chemistry for post-Pinatubo conditions, the model-calculated NO(x)/NO(y) ratios and the NO, NO2, and HNO3 profiles are compared to the UARS-derived data. In general, the UARS-constrained box model captures the main features of nitrogen species partitioning in the post-Pinatubo years. However, the model underestimates the NO2 content, particularly, in the 30-7 mbar (approx. 23-32 km) range. Comparisons of the calculated temporal behavior of the partial columns of NO2 and HNO3 and ground based measurements at 45degS and 45degN are also presented. Our analysis indicates that ground-based and HALOE v. 18 measurements of the NO2 vertical columns are consistent within the range of their uncertainties and are systematically higher (up to 50%) than the model

  10. Nitrogen Species in the Post-Pinatubo Stratosphere: Model Analysis Utilizing UARS Measurements

    NASA Technical Reports Server (NTRS)

    Danilin, M. Y.; Rodriguez, J. M.; Hu, W.; Ko, M. K. W.; Weisenstein, D. K.; Kumer, J. B.; Mergenthaler, J. L.; Russell, J. M., III; Koike, M.; Yue, G. K.

    1998-01-01

    We present an analysis of the impact of heterogeneous chemistry on the partitioning of nitrogen species measured by the Upper Atmosphere Research Satellite (UARS) instruments. The UARS measurements utilized include: N2O, HNO3 and ClONO2 (Cryogen Limb Array Etalon Spectrometer (CLAES), version 7), temperature, methane, ozone, H2O, HCI, NO and NO2 (HALogen Occultation Experiment (HALOE), version 18). The analysis is carried out for the data from January 1992 to September 1994 in the 100-1 mbar (approximately 17-47 km) altitude range and over 10 degree latitude bins from 70 deg S to 70 deg N. Temporal-spatial evolution of aerosol surface area density (SAD) is adopted according to the Stratospheric Aerosol and Gas Experiment (SAGE) II data. A diurnal steady-state photochemical box model, constrained by the temperature, ozone, H2O, CH4, aerosol SAD and columns of O2 and O3 above the point of interest, has been used as the main tool to analyze these data. Total inorganic nitrogen (NOy) is obtained by three different methods: (1) as a sum of the UARS measured NO, NO2, HNO3, and CIONO2; (2) from the N2O-NOy correlation, (3) from the CH4-NOy correlation. To validate our current understanding of stratospheric heterogeneous chemistry for post-Pinatubo conditions, the model-calculated NOx/NOy ratios and the NO, NO2, and HNO3 profiles are compared to the UARS-derived data. In general, the UARS-constrained box model captures the main features of nitrogen species partitioning in the post-Pinatubo years. However, the model underestimates the NO2 content, particularly, in the 30-7 mbar (approximately 23-32 km) range. Comparisons of the calculated temporal behavior of the partial columns of NO2 and HNO3 and ground based measurements at 45 deg S and 45 deg N are also presented. Our analysis indicates that ground-based and HALOE v.18 measurements of the NO2 vertical columns are consistent within the range of their uncertainties and are systematically higher (up to 50%) than the model

  11. Gait analysis in a pre- and post-ischemic stroke biomedical pig model.

    PubMed

    Duberstein, Kylee Jo; Platt, Simon R; Holmes, Shannon P; Dove, C Robert; Howerth, Elizabeth W; Kent, Marc; Stice, Steven L; Hill, William D; Hess, David C; West, Franklin D

    2014-02-10

    Severity of neural injury including stroke in human patients, as well as recovery from injury, can be assessed through changes in gait patterns of affected individuals. Similar quantification of motor function deficits has been measured in rodent animal models of such injuries. However, due to differences in fundamental structure of human and rodent brains, there is a need to develop a large animal model to facilitate treatment development for neurological conditions. Porcine brain structure is similar to that of humans, and therefore the pig may make a more clinically relevant animal model. The current study was undertaken to determine key gait characteristics in normal biomedical miniature pigs and dynamic changes that occur post-neural injury in a porcine middle cerebral artery (MCA) occlusion ischemic stroke model. Yucatan miniature pigs were trained to walk through a semi-circular track and were recorded with high speed cameras to detect changes in key gait parameters. Analysis of normal pigs showed overall symmetry in hindlimb swing and stance times, forelimb stance time, along with step length, step velocity, and maximum hoof height on both fore and hindlimbs. A subset of pigs were again recorded at 7, 5 and 3 days prior to MCA occlusion and then at 1, 3, 5, 7, 14 and 30 days following surgery. MRI analysis showed that MCA occlusion resulted in significant infarction. Gait analysis indicated that stroke resulted in notable asymmetries in both temporal and spatial variables. Pigs exhibited lower maximum front hoof height on the paretic side, as well as shorter swing time and longer stance time on the paretic hindlimb. These results support that gait analysis of stroke injury is a highly sensitive detection method for changes in gait parameters in pig.

  12. Software Analysis of Uncorrelated MS1 Peaks for Discovery of Post-Translational Modifications.

    PubMed

    Pascal, Bruce D; West, Graham M; Scharager-Tapia, Catherina; Flefil, Ricardo; Moroni, Tina; Martinez-Acedo, Pablo; Griffin, Patrick R; Carvalloza, Anthony C

    2015-12-01

    The goal in proteomics to identify all peptides in a complex mixture has been largely addressed using various LC MS/MS approaches, such as data dependent acquisition, SRM/MRM, and data independent acquisition instrumentation. Despite these developments, many peptides remain unsequenced, often due to low abundance, poor fragmentation patterns, or data analysis difficulties. Many of the unidentified peptides exhibit strong evidence in high resolution MS(1) data and are frequently post-translationally modified, playing a significant role in biological processes. Proteomics Workbench (PWB) software was developed to automate the detection and visualization of all possible peptides in MS(1) data, reveal candidate peptides not initially identified, and build inclusion lists for subsequent MS(2) analysis to uncover new identifications. We used this software on existing data on the autophagy regulating kinase Ulk1 as a proof of concept for this method, as we had already manually identified a number of phosphorylation sites Dorsey, F. C. et al (J. Proteome. Res. 8(11), 5253-5263 (2009)). PWB found all previously identified sites of phosphorylation. The software has been made freely available at http://www.proteomicsworkbench.com . Graphical Abstract ᅟ.

  13. Software Analysis of Uncorrelated MS1 Peaks for Discovery of Post-Translational Modifications

    NASA Astrophysics Data System (ADS)

    Pascal, Bruce D.; West, Graham M.; Scharager-Tapia, Catherina; Flefil, Ricardo; Moroni, Tina; Martinez-Acedo, Pablo; Griffin, Patrick R.; Carvalloza, Anthony C.

    2015-12-01

    The goal in proteomics to identify all peptides in a complex mixture has been largely addressed using various LC MS/MS approaches, such as data dependent acquisition, SRM/MRM, and data independent acquisition instrumentation. Despite these developments, many peptides remain unsequenced, often due to low abundance, poor fragmentation patterns, or data analysis difficulties. Many of the unidentified peptides exhibit strong evidence in high resolution MS1 data and are frequently post-translationally modified, playing a significant role in biological processes. Proteomics Workbench (PWB) software was developed to automate the detection and visualization of all possible peptides in MS1 data, reveal candidate peptides not initially identified, and build inclusion lists for subsequent MS2 analysis to uncover new identifications. We used this software on existing data on the autophagy regulating kinase Ulk1 as a proof of concept for this method, as we had already manually identified a number of phosphorylation sites Dorsey, F. C. et al (J. Proteome. Res. 8(11), 5253-5263 (2009)). PWB found all previously identified sites of phosphorylation. The software has been made freely available at http://www.proteomicsworkbench.com .

  14. Nonlinear Analysis and Post-Test Correlation for a Curved PRSEUS Panel

    NASA Technical Reports Server (NTRS)

    Gould, Kevin; Lovejoy, Andrew E.; Jegley, Dawn; Neal, Albert L.; Linton, Kim, A.; Bergan, Andrew C.; Bakuckas, John G., Jr.

    2013-01-01

    The Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) concept, developed by The Boeing Company, has been extensively studied as part of the National Aeronautics and Space Administration's (NASA s) Environmentally Responsible Aviation (ERA) Program. The PRSEUS concept provides a light-weight alternative to aluminum or traditional composite design concepts and is applicable to traditional-shaped fuselage barrels and wings, as well as advanced configurations such as a hybrid wing body or truss braced wings. Therefore, NASA, the Federal Aviation Administration (FAA) and The Boeing Company partnered in an effort to assess the performance and damage arrestments capabilities of a PRSEUS concept panel using a full-scale curved panel in the FAA Full-Scale Aircraft Structural Test Evaluation and Research (FASTER) facility. Testing was conducted in the FASTER facility by subjecting the panel to axial tension loads applied to the ends of the panel, internal pressure, and combined axial tension and internal pressure loadings. Additionally, reactive hoop loads were applied to the skin and frames of the panel along its edges. The panel successfully supported the required design loads in the pristine condition and with a severed stiffener. The panel also demonstrated that the PRSEUS concept could arrest the progression of damage including crack arrestment and crack turning. This paper presents the nonlinear post-test analysis and correlation with test results for the curved PRSEUS panel. It is shown that nonlinear analysis can accurately calculate the behavior of a PRSEUS panel under tension, pressure and combined loading conditions.

  15. Glycoproteomic analysis of seven major allergenic proteins reveals novel post-translational modifications.

    PubMed

    Halim, Adnan; Carlsson, Michael C; Madsen, Caroline Benedicte; Brand, Stephanie; Møller, Svenning Rune; Olsen, Carl Erik; Vakhrushev, Sergey Y; Brimnes, Jens; Wurtzen, Peter Adler; Ipsen, Henrik; Petersen, Bent L; Wandall, Hans H

    2015-01-01

    Allergenic proteins such as grass pollen and house dust mite (HDM) proteins are known to trigger hypersensitivity reactions of the immune system, leading to what is commonly known as allergy. Key allergenic proteins including sequence variants have been identified but characterization of their post-translational modifications (PTMs) is still limited. Here, we present a detailed PTM(1) characterization of a series of the main and clinically relevant allergens used in allergy tests and vaccines. We employ Orbitrap-based mass spectrometry with complementary fragmentation techniques (HCD/ETD) for site-specific PTM characterization by bottom-up analysis. In addition, top-down mass spectrometry is utilized for targeted analysis of individual proteins, revealing hitherto unknown PTMs of HDM allergens. We demonstrate the presence of lysine-linked polyhexose glycans and asparagine-linked N-acetylhexosamine glycans on HDM allergens. Moreover, we identified more complex glycan structures than previously reported on the major grass pollen group 1 and 5 allergens, implicating important roles for carbohydrates in allergen recognition and response by the immune system. The new findings are important for understanding basic disease-causing mechanisms at the cellular level, which ultimately may pave the way for instigating novel approaches for targeted desensitization strategies and improved allergy vaccines.

  16. Glycoproteomic Analysis of Seven Major Allergenic Proteins Reveals Novel Post-translational Modifications*

    PubMed Central

    Halim, Adnan; Carlsson, Michael C.; Madsen, Caroline Benedicte; Brand, Stephanie; Møller, Svenning Rune; Olsen, Carl Erik; Vakhrushev, Sergey Y.; Brimnes, Jens; Wurtzen, Peter Adler; Ipsen, Henrik; Petersen, Bent L.; Wandall, Hans H.

    2015-01-01

    Allergenic proteins such as grass pollen and house dust mite (HDM) proteins are known to trigger hypersensitivity reactions of the immune system, leading to what is commonly known as allergy. Key allergenic proteins including sequence variants have been identified but characterization of their post-translational modifications (PTMs) is still limited. Here, we present a detailed PTM1 characterization of a series of the main and clinically relevant allergens used in allergy tests and vaccines. We employ Orbitrap-based mass spectrometry with complementary fragmentation techniques (HCD/ETD) for site-specific PTM characterization by bottom-up analysis. In addition, top-down mass spectrometry is utilized for targeted analysis of individual proteins, revealing hitherto unknown PTMs of HDM allergens. We demonstrate the presence of lysine-linked polyhexose glycans and asparagine-linked N-acetylhexosamine glycans on HDM allergens. Moreover, we identified more complex glycan structures than previously reported on the major grass pollen group 1 and 5 allergens, implicating important roles for carbohydrates in allergen recognition and response by the immune system. The new findings are important for understanding basic disease-causing mechanisms at the cellular level, which ultimately may pave the way for instigating novel approaches for targeted desensitization strategies and improved allergy vaccines. PMID:25389185

  17. Effects of 3D PIV post-processing on impulse and force analysis in vortical flows

    NASA Astrophysics Data System (ADS)

    Mendelson, Leah; Techet, Alexandra

    2014-11-01

    Vortical flows measured using 3D PIV techniques are fundamentally filtered versions of physical phenomena, with velocity information lost below the length and time scales of the measurement system. In the context of propulsive vortices, such as those generated during biological locomotion, these factors, combined with experimental noise and error, can lead to inaccuracies in analysis of the vortex momentum and net thrust. As a result, while 3D velocity measurements remove many of the assumptions required to analyze planar PIV data, they should not be considered absolute physical quantities. Our work focuses on post-processing for 3D PIV data sets to enable the extraction of accurate, quantitative 3D force measurements for unsteady vortical propulsion. In this study, we compare utilizing measurement signal processing techniques, orthogonal decomposition, and identification of coherent structures to measure the impulse of a canonical vortex ring generated by a mechanical piston. In particular, we consider the ability of these methods to confront the influences of limited spatial resolution and arbitrary geometries, and make recommendations for a general procedure for propulsion analysis from 3D PIV data, regardless of which PIV technique is used to obtain the velocity fields.

  18. Struggles for recognition: a content analysis of messages posted on the Internet

    PubMed Central

    Andersen, Anders Johan W; Svensson, Tommy

    2012-01-01

    Background The Internet has enlarged the possibilities of human communication and opened new ways of exploring perceptions of mental health. This study is part of a research project aiming to explore, describe, and analyze different discourses of mental health in Norway and Sweden, using material from Internet-based services. Aim To examine messages posed by users of publicly available question-and-answer services and to describe their content. Methods A Web search was used to identify Norwegian and Swedish Websites offering mental health services by email or posted messages. A total of 601 messages from 20 services, 10 Norwegian and 10 Swedish, were analyzed by means of qualitative content analysis and further interpreted in light of the social theory of recognition by Honneth. Results Eight categories emerged from the analysis: family life, couples, others, violence, the ungovernable, self-image, negotiating normality, and life struggles. These categories were then grouped into three themes: (1) relationship to significant others, (2) relationship to self, and (3) relationship to the social community. The themes promoted an understanding of mental health as closely connected to political and social factors. Conclusions The results showed a variety of concerns from various parts of life and empowered the view that mental health should be understood broadly, at a conceptual level. Mental health emerged as a deeply relational concept that emphasized the equal distribution of chances in life. It strengthened the moral grammar of social inclusion and the acceptance of plurality in social life. PMID:22888257

  19. Nutritional status of patients submitted to transplantation of allogeneic hematopoietic stem cells: a retrospective study

    PubMed Central

    Ferreira, Érika Elias; Guerra, Daiane Cristina; Baluz, Kátia; de Resende Furtado, Wander; da Silva Bouzas, Luis Fernando

    2014-01-01

    Objective This study aimed to describe and compare the nutritional status of adult patients submitted to allogeneic hematopoietic stem cell transplantation at two different time points (admission and discharge). Methods A retrospective, descriptive and quantitative study was performed based on clinical, laboratory and nutritional data obtained from medical records of adult patients of both genders submitted to allogeneic hematopoietic stem cell transplantation in a bone marrow transplantation reference center in Rio de Janeiro in the period from 2010 to 2013. Statistical analysis was performed using the SPSS software (version 22.0). Results Sixty-four patients were evaluated. The mean age was 42.1 ± 3.2 years and the most prevalent disease was acute myeloid leukemia (39%). There was a high prevalence of gastrointestinal symptoms including nausea (100%), vomiting (97%) and mucositis (93%). Between admission and discharge there was a significant decrease in the median weight (−2.5 kg; 71.5 vs. 68.75 kg; p-value < 0.001), body mass index (−0.9 kg/m2; 24.8 vs. 24.4 kg/m2; p-value < 0.001), and serum albumin levels (−0.2 g/dL; 3.7 vs. 3.6 g/dL; p-value = 0.024). The survival time after hematopoietic stem cell transplantation correlated negatively with C-reactive protein at discharge (CC = −0.72; p-value < 0.001) and positively with serum albumin levels (CC = 0.56; p-value = 0.004) and with high total protein level at discharge (CC = 0.53; p-value = 0.006). Conclusion Our results suggest that patients submitted to allogeneic hematopoietic stem cell transplantation have compromised nutritional status during the hospital stay for transplantation. PMID:25453651

  20. Analysis of the real EADGENE data set: Multivariate approaches and post analysis (Open Access publication)

    PubMed Central

    Sørensen, Peter; Bonnet, Agnès; Buitenhuis, Bart; Closset, Rodrigue; Déjean, Sébastien; Delmas, Céline; Duval, Mylène; Glass, Liz; Hedegaard, Jakob; Hornshøj, Henrik; Hulsegge, Ina; Jaffrézic, Florence; Jensen, Kirsty; Jiang, Li; de Koning, Dirk-Jan; Cao, Kim-Anh Lê; Nie, Haisheng; Petzl, Wolfram; Pool, Marco H; Robert-Granié, Christèle; San Cristobal, Magali; Lund, Mogens Sandø; van Schothorst, Evert M; Schuberth, Hans-Joachim; Seyfert, Hans-Martin; Tosser-Klopp, Gwenola; Waddington, David; Watson, Michael; Yang, Wei; Zerbe, Holm

    2007-01-01

    The aim of this paper was to describe, and when possible compare, the multivariate methods used by the participants in the EADGENE WP1.4 workshop. The first approach was for class discovery and class prediction using evidence from the data at hand. Several teams used hierarchical clustering (HC) or principal component analysis (PCA) to identify groups of differentially expressed genes with a similar expression pattern over time points and infective agent (E. coli or S. aureus). The main result from these analyses was that HC and PCA were able to separate tissue samples taken at 24 h following E. coli infection from the other samples. The second approach identified groups of differentially co-expressed genes, by identifying clusters of genes highly correlated when animals were infected with E. coli but not correlated more than expected by chance when the infective pathogen was S. aureus. The third approach looked at differential expression of predefined gene sets. Gene sets were defined based on information retrieved from biological databases such as Gene Ontology. Based on these annotation sources the teams used either the GlobalTest or the Fisher exact test to identify differentially expressed gene sets. The main result from these analyses was that gene sets involved in immune defence responses were differentially expressed. PMID:18053574

  1. Detection of looseness degree of dental posts using natural frequency analysis.

    PubMed

    Hsieh, Sung-Chih; Lin, Shu-Li; Huang, Yung-Kai; Chang, Wei-Jen; Yuan, Chia-Chun; Lo, Yi-June; Lee, Sheng-Yang; Huang, Haw-Ming

    2013-08-01

    This study examines the relationship between the retention force and natural frequency of dental posts cemented with zinc phosphate cement. Forty-two decoronated maxillary incisors were collected and embedded in resin blocks. The 7-mm post spaces were prepared for all test samples prior to cementing the 13-mm Para-Posts with zinc phosphate cement. The natural frequency values and retention forces of the zinc phosphate cement-cemented Para-Posts in various liquid/powder mixing ratios were measured. Thereafter, the natural frequency values of the zinc phosphate cement-cemented posts were continuously detected during ultrasonic vibration. Moreover, both the natural frequency values and the dislodgement forces in response to ultrasonic vibrations were measured for the pretreated post samples. Results showed that the natural frequency values of the posts significantly decreased from 8.8 ± 0.8 to 5.0 ± 0.5 kHz (P < 0.05) before and after ultrasound treatment, respectively. The natural frequency values and the dislodgement forces of tested posts had a highly linear relationship (R² = 0.99, P < 0.05). These findings suggest that natural frequency is a variable for monitoring the stability status of zinc phosphate cement-cemented dental posts.

  2. 3D-FE analysis of functionally graded structured dental posts.

    PubMed

    Abu Kasim, Noor H; Madfa, Ahmed A; Hamdi, Mohd; Rahbari, Ghahnavyeh R

    2011-01-01

    This study aimed to compare the biomechanical behaviour of functionally graded structured posts (FGSPs) and homogenous-type posts in simulated models of a maxillary central incisor. Two models of FGSPs consisting of a multilayer xTi-yHA composite design, where zirconia and alumina was added as the first layer for models A and B respectively were compared to homogenous zirconia post (model C) and a titanium post (model D). The amount of Ti and HA in the FGSP models was varied in gradations. 3D-FEA was performed on all models and stress distributions were investigated along the dental post. In addition, interface stresses between the posts and their surrounding structures were investigated under vertical, oblique, and horizontal loadings. Strain distribution along the post-dentine interface was also investigated. The results showed that FGSPs models, A and B demonstrated better stress distribution than models C and D, indicating that dental posts with multilayered structure dissipate localized and interfacial stress and strain more efficiently than homogenous-type posts. PMID:22123011

  3. Understanding Impact and Implications of Data Standards on Post Disaster Risk Analysis

    NASA Astrophysics Data System (ADS)

    Stevenson, Robert

    2010-05-01

    Although the physical and humanitarian effects of a natural catastrophe are often bound to the locality of the event the financial impacts can have global effects. This is particularly prominent in the re/insurance community, where through a number of market mechanisms and re/insurance structures financial loss is mitigated amongst many companies across the globe. The level of risk a company wishes to retain, given an event, represents the level of risk decision makers deem acceptable. Catastrophe risk modelling tools aid the estimation of risk retention and transfer mechanisms, and increasingly the level of capital required to withstand a catastrophic event. These tools rely on appropriate representations hazard, exposure, vulnerability and insurance conditions that reflect the reality of risk. In addition, accurate estimation of loss potential in the aftermath of a catastrophic event equally relies on the data available to assess the scale of damages experienced and to provide views on the likely scale of loss. A coherent and focussed data and modelling strategy is required to ensure that the risk assessment made is as accurate as possible. A fundamental factor in determining the accuracy of catastrophe output, is the quality of data entered. It is of vital importance, therefore, to have an understanding of both the data used as well as the standard of this data, which will so powerfully impact upon the decision making process. This is perhaps best illustrated through the study of historical events, such as Hurricane Katrina and Ike. The extent of data variance in post disaster analysis clearly demonstrates issues of data discrepancies, vintage, resolution and uncertainty propagation, and reflects on the standard of the original data utilized for modelling purposes and decision making. Using experience gained from recent events, this paper will explore current data variabilities, and the impacts on effective loss estimation, both in relation to reinsurance

  4. Radar rainfall estimation in the context of post-event analysis of flash-flood events

    NASA Astrophysics Data System (ADS)

    Bouilloud, Ludovic; Delrieu, Guy; Boudevillain, Brice; Kirstetter, Pierre-Emmanuel

    2010-11-01

    SummaryA method to estimate rainfall from radar data for post-event analysis of flash-flood events has been developed within the EC-funded HYDRATE project. It follows a pragmatic approach including careful analysis of the observation conditions for the radar system(s) available for the considered case. Clutter and beam blockage are characterised by dry-weather observations and simulations based on a digital terrain model of the region of interest. The vertical profile of reflectivity (VPR) is either inferred from radar data if volume scanning data are available or simply defined using basic meteorological parameters (idealised VPR). Such information is then used to produce correction factor maps for each elevation angle to correct for range-dependent errors. In a second step, an effective Z-R relationship is optimised to remove the bias over the hit region. Due to limited data availability, the optimisation is carried out with reference to raingauge rain amounts measured at the event time scale. Sensitivity tests performed with two well-documented rain events show that a number of Z = aRb relationships, organised along hyperbolic curves in the (a and b) parameter space, lead to optimum assessment results in terms of the Nash coefficient between the radar and raingauge estimates. A refined analysis of these equifinality patterns shows that the “total additive conditional bias” can be used to discriminate between the Nash coefficient equifinal solutions. We observe that the optimisation results are sensitive to the VPR description and also that the Z-R optimisation procedure can largely compensate for range-dependent errors, although this shifts the optimal coefficients in the parameter space. The time-scale dependency of the equifinality patterns is significant, however near-optimal Z-R relationships can be obtained at all time scales from the event time step optimisation.

  5. An analysis of Social Work Oncology Network Listserv Postings on the Commission of Cancer's distress screening guidelines.

    PubMed

    Burg, Mary Ann; Adorno, Gail; Hidalgo, Jorge

    2012-01-01

    This is a qualitative study of listserv postings by members of the Social Work Oncology Network (SWON) in response to the Commission on Cancer's 2011 guidelines for distress screening of cancer patients. Archived listserv postings for the period of December 2010 to November 2011 were deidentified and a sample was derived by a list of keywords for the analysis. Aims of the study included describing the general categories and themes of the postings devoted to the new distress screening standard and examining the process of facilitation of mutual support and information exchange by oncology social workers in response to the new screening standards. During the 12-month timeframe there were 242 unique listserv postings sampled for the analysis. Oncology social worker (OSW) discussion of the distress screening guidelines remained a constant topic over the 12 months, and major themes that emerged from the data included processes of implementation of distress screening in cancer centers, screening policies and protocols, screening tool choice, and oncology social worker professional identity. The SWON listserv members used the listserv as a mechanism to post their requests for information on screening, to share their experiences in the beginning stages of implementing the guidelines, and to build support for legitimizing oncology social workers as the lead profession in the implementation of the guidelines in member cancer centers.

  6. Identifying Multimedia Production Competencies and Skills of Instructional Design and Technology Professionals: An Analysis of Recent Job Postings

    ERIC Educational Resources Information Center

    Sugar, William; Hoard, Brent; Brown, Abbie; Daniels, Lee

    2012-01-01

    In an effort to document necessary multimedia production competencies of Instructional Design and Technology graduates, a recent analysis of over 7 months' worth of Instructional Design and Technology job advertisements (n = 615) were conducted. Specific job skills from these postings were categorized and analyzed. The data set includes three job…

  7. Analysis of Post-Fire Vegetation Recovery in the Mediterranean Basin using MODIS Derived Vegetation Indices

    NASA Astrophysics Data System (ADS)

    Hawtree, Daniel; San Miguel, Jesus; Sedano, Fernando; Kempeneers, Pieter

    2010-05-01

    The Mediterranean basin region is highly susceptible to wildfire, with approximately 60,000 individual fires and half a million ha of natural vegetation burnt per year. Of particular concern in this region is the impact of repeated wildfires on the ability of natural lands to return to a pre-fire state, and of the possibility of desertification of semi-arid areas. Given these concerns, understanding the temporal patterns of vegetation recovery is important for the management of environmental resources in the region. A valuable tool for evaluating these recovery patterns are vegetation indices derived from remote sensing data. Previous research on post-fire vegetation recovery conducted in this region has found significant variability in recovery times across different study sites. It is unclear what the primary variables are affecting the differences in the rates of recovery, and if any geographic patterns of behavior exist across the Mediterranean basin. This research has primarily been conducted using indices derived from Landsat imagery. However, no extensive analysis of vegetation regeneration for large regions has been published, and assessment of vegetation recovery on the basis of medium-spatial resolution imagery such as that of MODIS has not yet been analyzed. This study examines the temporal pattern of vegetation recovery in a number of fire sites in the Mediterranean basin, using data derived from MODIS 16 -day composite vegetation indices. The intent is to develop a more complete picture of the temporal sequence of vegetation recovery, and to evaluate what additional factors impact variations in the recovery sequence. In addition, this study evaluates the utility of using MODIS derived vegetation indices for regeneration studies, and compares the findings to earlier studies which rely on Landsat data. Wildfires occurring between the years 2000 and 2004 were considered as potential study sites for this research. Using the EFFIS dataset, all wildfires

  8. The History of Post-Secondary Finance in Alberta - An Analysis

    ERIC Educational Resources Information Center

    Hauserman, Calvin P.; Stick, Sheldon L.

    2005-01-01

    Post-secondary systems throughout Canada and the United States have struggled with funding issues during most of the last decade of the 20th Century, and the new millennium did not open with great enthusiasm for change. This article examines the impact of post-secondary education funding changes in Alberta, Canada, by tracing the historical…

  9. Asynchronous Electronic Discussion Group: Analysis of Postings and Perception of In-Service Teachers

    ERIC Educational Resources Information Center

    Kim, Tina Lim Swee; Wah, Wong Kiet; Lee, Tan Ai

    2007-01-01

    This paper examines the practice of online discussion in a course specially tailored for in-service teachers who are pursuing their basic degree qualification at a teacher training institute. Analyses of postings to the asynchronous electronic discussion group were made according to the type of postings as proposed by Poole (2000). Four focus…

  10. Stress generated by customized glass fiber posts and other types by photoelastic analysis.

    PubMed

    Bosso, Kátia; Gonini Júnior, Alcides; Guiraldo, Ricardo Danil; Berger, Sandrine Bittencourt; Lopes, Murilo Baena

    2015-01-01

    Endodontic posts are necessary to provide adequate retention and support when no sufficient remaining structure is available to retain the core. There are different materials and techniques to construct post-and-core, but there is no consensus about which one promotes better stress distribution on the remaining tooth structure. This study aimed to quantify and evaluate the distribution of stress in the root produced by customized glass fiber posts compared to different endodontic posts. Twenty-five simulated roots from photoelastic resin were made and divided into 5 groups: CPC, cast post-and-core; SP, screw post; CF, carbon fiber post; GF, glass fiber post; and CGF, customized glass fiber post. After cementing CPC and SP posts with zinc phosphate cement, and CF, GF and CGF posts with resin cement, resin cores were made for groups 2-5. Specimens were evaluated with vertical or 45° oblique loading. To analyze the fringes, the root was divided into 6 parts: palatal cervical, palatal middle, palatal apical, vestibular cervical, vestibular middle, and vestibular apical. The formed fringes were photographed and quantified. Data were recorded and subjected to two-way ANOVA and Tukey's test (5%). SP (1.95±0.60) showed higher stress (p<0.05) compared to the others (CPC-0.52±0.74; CF-0.50±0.75, GF-0.23±0.48 and CGF-0.45±0.83). All posts showed high stress in apical third (CPC-1.40±0.65; SP-2.30±0.44, CF-1.80±0.45, GF-1.20±0.45, CGF-1.70±1.03) Low stress was found in cervical third (CPC-0.20±0.45; CF-0.00±0.00, GF-0.00±0.00, CGF-0.00±0.00), except by SP (1.90±0.65), which showed statistical difference (p<0.05). Customized post showed high stress concentration at the root and conventional glass fiber posts showed more favorable biomechanical behavior.

  11. A targeted change-detection procedure by combining change vector analysis and post-classification approach

    NASA Astrophysics Data System (ADS)

    Ye, Su; Chen, Dongmei; Yu, Jie

    2016-04-01

    In remote sensing, conventional supervised change-detection methods usually require effective training data for multiple change types. This paper introduces a more flexible and efficient procedure that seeks to identify only the changes that users are interested in, here after referred to as "targeted change detection". Based on a one-class classifier "Support Vector Domain Description (SVDD)", a novel algorithm named "Three-layer SVDD Fusion (TLSF)" is developed specially for targeted change detection. The proposed algorithm combines one-class classification generated from change vector maps, as well as before- and after-change images in order to get a more reliable detecting result. In addition, this paper introduces a detailed workflow for implementing this algorithm. This workflow has been applied to two case studies with different practical monitoring objectives: urban expansion and forest fire assessment. The experiment results of these two case studies show that the overall accuracy of our proposed algorithm is superior (Kappa statistics are 86.3% and 87.8% for Case 1 and 2, respectively), compared to applying SVDD to change vector analysis and post-classification comparison.

  12. Post-Test Analysis of a 10-Year Sodium Heat Pipe Life Test

    NASA Technical Reports Server (NTRS)

    Rosenfeld, John H.; Locci, Ivan E.; Sanzi, James L.; Hull, David R.; Geng, Steven M.

    2011-01-01

    High-temperature heat pipes are being evaluated for use in energy conversion applications such as fuel cells, gas turbine re-combustors, Stirling cycle heat sources; and with the resurgence of space nuclear power both as reactor heat removal elements and as radiator elements. Long operating life and reliable performance are critical requirements for these applications. Accordingly, long-term materials compatibility is being evaluated through the use of high-temperature life test heat pipes. Thermacore, Inc., has carried out a sodium heat pipe 10-year life test to establish long-term operating reliability. Sodium heat pipes have demonstrated favorable materials compatibility and heat transport characteristics at high operating temperatures in air over long time periods. A representative one-tenth segment Stirling Space Power Converter heat pipe with an Inconel 718 envelope and a stainless steel screen wick has operated for over 87,000 hr (10 years) at nearly 700 C. These life test results have demonstrated the potential for high-temperature heat pipes to serve as reliable energy conversion system components for power applications that require long operating lifetime with high reliability. Detailed design specifications, operating history, and post-test analysis of the heat pipe and sodium working fluid are described. Lessons learned and future life test plans are also discussed.

  13. Post-test thermomechanical calculations and preliminary data analysis for the Spent Fuel Test: Climax

    SciTech Connect

    Butkovich, T.R.; Patrick, W.C.

    1985-09-01

    The Spent Fuel Test - Climax (SFT-C) was conducted to evaluate the feasibility of retrievable deep geologic storage of commercially generated, spent nuclear-reactor fuel assemblies. Thermomechanical response of the SFT-C was calculated before the test began using the finite-element structural analysis code ADINA and its companion heat transfer code ADINAT. While we found that the level of agreement between measured and calculated rock displacements was quite good, we needed to revise certain aspects of the heat transfer calculation, material properties, and in situ stresses to incorporate information obtained during and after the heated phase of the test. The post-test calculations reported here were performed using the best available input parameters, thermal and mechanical properties, and power levels that were directly measured or inferred from measurements made during the test. This report documents the results of these calculations and compares those results with selected measurements made during the 3-year heating phase and 6-month cooling phase of the SFT-C.

  14. Post-experimental analysis of a solid oxide fuel cell stack using hybrid seals

    NASA Astrophysics Data System (ADS)

    Thomann, O.; Rautanen, M.; Himanen, O.; Tallgren, J.; Kiviaho, J.

    2015-01-01

    A post-experimental analysis of a SOFC stack is presented. The stack was operated for 1800 h at 700 °C with air and hydrogen and contained hybrid glass-Thermiculite 866 seals. The goal of this work was to investigate the sealing microstructure and possible corrosion during mid-term operation. It was found that hybrid seals could effectively compensate for manufacturing tolerances of cells and other components due to the compliance of the glass layer. Additionally, different interfaces were investigated for corrosion. Corrosion was not observed at two-phase interfaces such as Crofer 22 APU/glass, glass/electrolyte and glass/Thermiculite 866. The three-phase interface between Crofer 22 APU/glass/hydrogen exhibited no corrosion. Some evidence of non-systematic corrosion was found at the Crofer 22 APU/glass/air interface. The possible reasons for the corrosion are discussed. Lastly, dual exposure to humid hydrogen and air of the 0.2 mm Crofer 22 APU interconnect had no detrimental effect on the corrosion compared to air exposure. Overall the hybrid seals used in combination with the thin interconnects were found to be a promising solution due to the low leak rate and limited material interactions.

  15. Scale analysis of pre- and post-midnight ESF bubbles at storm time and quiet time

    NASA Astrophysics Data System (ADS)

    Chen, K. Y.; Su, S. Y.; Yeh, H. C.; Liu, C. H.

    This paper investigates intermediate scale plasma structures observed by ROCSAT-1 in the equatorial F region The empirical mode decomposition EMD method of Hilbert-Huang transform HHT technique is utilized to develop a procedure of scale analysis that allows the mutually correlated components in velocity density and relative density gradient to be identified and extracted Comparing the three data sets good match in wave form is found for velocity and density in scales between kilometers and hundred meters It implies that there are electric fields proportional to density fluctuation -- delta N N in the form similar to what is expected for the Rayleigh Taylor instability In smaller scales velocity and density don t correlate to each other more the good match is then found in velocity and density gradient This is the manifestation of the Boltzmann relation By studying the cases in post-midnight and pre-midnight under storm time and quiet time we find the one-to-one match hold although it is known that ESF bubbles can be driven by different mechanisms under different conditions In other words the spatial structures of electric field in the intermediate scale will always be correlated to the density structures in a manner of delta E sim - delta N N independent of the mechanisms driving the ESF bubbles It is interesting to note that the relation delta V z quad sim delta N N for irregularities in scale of kilometers holds only for ESF occurs within -5 dip latitude while the Boltzmann relation delta

  16. In Silico Analysis of Correlations between Protein Disorder and Post-Translational Modifications in Algae

    PubMed Central

    Kurotani, Atsushi; Sakurai, Tetsuya

    2015-01-01

    Recent proteome analyses have reported that intrinsically disordered regions (IDRs) of proteins play important roles in biological processes. In higher plants whose genomes have been sequenced, the correlation between IDRs and post-translational modifications (PTMs) has been reported. The genomes of various eukaryotic algae as common ancestors of plants have also been sequenced. However, no analysis of the relationship to protein properties such as structure and PTMs in algae has been reported. Here, we describe correlations between IDR content and the number of PTM sites for phosphorylation, glycosylation, and ubiquitination, and between IDR content and regions rich in proline, glutamic acid, serine, and threonine (PEST) and transmembrane helices in the sequences of 20 algae proteomes. Phosphorylation, O-glycosylation, ubiquitination, and PEST preferentially occurred in disordered regions. In contrast, transmembrane helices were favored in ordered regions. N-glycosylation tended to occur in ordered regions in most of the studied algae; however, it correlated positively with disordered protein content in diatoms. Additionally, we observed that disordered protein content and the number of PTM sites were significantly increased in the species-specific protein clusters compared to common protein clusters among the algae. Moreover, there were specific relationships between IDRs and PTMs among the algae from different groups. PMID:26307970

  17. Comparing pre- and post-copulatory mate competition using social network analysis in wild crickets

    PubMed Central

    Fisher, David N.; Rodríguez-Muñoz, Rolando

    2016-01-01

    Sexual selection results from variation in success at multiple stages in the mating process, including competition before and after mating. The relationship between these forms of competition, such as whether they trade-off or reinforce one another, influences the role of sexual selection in evolution. However, the relationship between these 2 forms of competition is rarely quantified in the wild. We used video cameras to observe competition among male field crickets and their matings in the wild. We characterized pre- and post-copulatory competition as 2 networks of competing individuals. Social network analysis then allowed us to determine 1) the effectiveness of precopulatory competition for avoiding postcopulatory competition, 2) the potential for divergent mating strategies, and 3) whether increased postcopulatory competition reduces the apparent reproductive benefits of male promiscuity. We found 1) limited effectiveness of precopulatory competition for avoiding postcopulatory competition; 2) males do not specifically engage in only 1 type of competition; and 3) promiscuous individuals tend to mate with each other, which will tend to reduce variance in reproductive success in the population and highlights the trade-off inherent in mate guarding. Our results provide novel insights into the works of sexual competition in the wild. Furthermore, our study demonstrates the utility of using network analyses to study competitive interactions, even in species lacking obvious social structure. PMID:27174599

  18. High-frequency ultrasound analysis of post-mitotic arrest cell death

    PubMed Central

    Pasternak, Maurice M.; Wirtzfeld, Lauren A.; Kolios, Michael C.; Czarnota, Gregory J.

    2016-01-01

    Non-invasive monitoring of cancer cell death would permit rapid feedback on treatment response. One technique showing such promise is quantitative ultrasound. High-frequency ultrasound spectral radiofrequency analysis was used to study cell death in breast cancer cell samples. Quantitative ultrasound parameters, including attenuation, spectral slope, spectral 0-MHz-intercept, midband fit, and fitted parameters displayed significant changes with paclitaxel-induced cell death, corresponding to observations of morphological changes seen in histology and electron microscopy. In particular, a decrease in spectral slope from 0.24±0.07 dB/MHz to 0.04±0.09 dB/MHz occurred over 24 hours of treatment time and was identified as an ultrasound parameter capable of differentiating post-mitotic arrest cell death from classical apoptosis. The formation of condensed chromatin aggregates of 1 micron or greater in size increased the number of intracellular scatterers, consistent with a hypothesis that nuclear material is a primary source of ultrasound scattering in dying cells. It was demonstrated that the midband fit quantitatively correlated to cell death index, with a Pearson R-squared value of 0.99 at p<0.01. These results suggest that high-frequency ultrasound can not only qualitatively assess the degree of cancer cell death, but may be used to quantify the efficacy of chemotherapeutic treatments. PMID:27226984

  19. In Silico Analysis of Correlations between Protein Disorder and Post-Translational Modifications in Algae.

    PubMed

    Kurotani, Atsushi; Sakurai, Tetsuya

    2015-08-20

    Recent proteome analyses have reported that intrinsically disordered regions (IDRs) of proteins play important roles in biological processes. In higher plants whose genomes have been sequenced, the correlation between IDRs and post-translational modifications (PTMs) has been reported. The genomes of various eukaryotic algae as common ancestors of plants have also been sequenced. However, no analysis of the relationship to protein properties such as structure and PTMs in algae has been reported. Here, we describe correlations between IDR content and the number of PTM sites for phosphorylation, glycosylation, and ubiquitination, and between IDR content and regions rich in proline, glutamic acid, serine, and threonine (PEST) and transmembrane helices in the sequences of 20 algae proteomes. Phosphorylation, O-glycosylation, ubiquitination, and PEST preferentially occurred in disordered regions. In contrast, transmembrane helices were favored in ordered regions. N-glycosylation tended to occur in ordered regions in most of the studied algae; however, it correlated positively with disordered protein content in diatoms. Additionally, we observed that disordered protein content and the number of PTM sites were significantly increased in the species-specific protein clusters compared to common protein clusters among the algae. Moreover, there were specific relationships between IDRs and PTMs among the algae from different groups.

  20. Superior osteogenesis in transplanted allogeneic canine skull following chemical sterilization

    SciTech Connect

    Prolo, D.J.; Pedrotti, P.W.; Burres, K.P.; Oklund, S.

    1982-08-01

    Sterilization of allogeneic bone increases the availability of this tissue for supplanting skeletal defects and effecting fusions. The optimal sterilant destroys micro-organisms, preserves the physical and chemical integrity of bone and possibly even reduces immunogenicity. Cortical bone of skull heals slowly and is variably resorbed. Of 36 dogs, spontaneous regeneration in 72 paired 20 mm defects was constant but always incomplete, and restored only about one third of the cross-sectional area of the defect at six months. The repair in defects replaced with canine allogeneic bony disc, sterilized with ethylene oxide (n . 9), gamma irradiation (n . 7), or methanol/chloroform/iodoacetic acid (n . 7) and then lyophilizedd, was compared with repair in defects filled with aseptically procured lyophilized only (n . 23) discs from the same donor. Criteria for evaluation of implants at six months included volume of defect filled, radiodensity, extent of fusion around circumference, revascularization, and remodeling. Bony discs sterilized with methanol/chloroform/iodoacetic acid remodeled at a superior rate (p less than 0.01). Radiation sterilization resulted in diminished density and inferentially reduced protection of the brain (p less than 0.025). Ethylene oxide, lyophilized implants, and implants lyophilized only produced comparable repair. Whereas an acceptable cranioplasty was achieved in 86% of methanol/chloroform/iodoacetic acid, lyophilize implants, all other alloimplants served an osteoconductive function with a successful repair occurring in 56% to 58%.

  1. Decellularized allogeneic intervertebral disc: natural biomaterials for regenerating disc degeneration

    PubMed Central

    Hu, Zhijun; Chen, Kai; Shan, Zhi; Chen, Shuai; Wang, Jiying; Mo, Jian; Ma, Jianjun; Xu, Wenbing; Qin, An; Fan, Shunwu

    2016-01-01

    Intervertebral disc degeneration is associated with back pain and disc herniation. This study established a modified protocol for intervertebral disc (IVD) decellularization and prepared its extracellular matrix (ECM). By culturing mesenchymal stem cells (MSCs)(3, 7, 14 and 21 days) and human degenerative IVD cells (7 days) in the ECM, implanting it subcutaneously in rabbit and injecting ECM microparticles into degenerative disc, the biological safety and efficacy of decellularized IVD was evaluated both in vitro and in vivo. Here, we demonstrated that cellular components can be removed completely after decellularization and maximally retain the structure and biomechanics of native IVD. We revealed that allogeneic ECM did not evoke any apparent inflammatory reaction in vivo and no cytotoxicity was found in vitro. Moreover, IVD ECM can induce differentiation of MSCs into IVD-like cells in vitro. Furthermore, allogeneic ECM microparticles are effective on the treatment of rabbit disc degeneration in vivo. In conclusion, our study developed an optimized method for IVD decellularization and we proved decellularized IVD is safe and effective for the treatment of degenerated disc diseases. PMID:26933821

  2. Allogeneic hematopoietic cell transplantation: the state of the art

    PubMed Central

    Gyurkocza, Boglarka; Rezvani, Andrew; Storb, Rainer F

    2010-01-01

    Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative procedure for a variety of hematologic malignancies. The field has evolved substantially over the past decade, with advances in patient and donor selection, stem cell sources, supportive care, prevention of complications and reduced-toxicity preparative regimens. As a result, the indications for HCT and the pool of eligible patients have expanded significantly. In this article, we provide an overview of the major aspects of allogeneic HCT, and focus specifically on areas of active research and on novel approaches to challenges in the field. Specifically, we will discuss approaches to reduce the toxicity of the preparative regimen, with the goal of increasing the safety and applicability of HCT. The availability of suitable donors may be an obstacle to wider application of HCT. We review three major approaches to broadening the donor pool: the use of HLA-mismatched unrelated donors, umbilical cord blood and HLA-haploidentical family donors. Graft-versus-host disease remains a major cause of morbidity and mortality after HCT. We review recent advances in the understanding of this phenomenon, and novel prophylactic and therapeutic approaches that hold the promise of further improving the safety of the procedure. We conclude with a speculative outline of the next 5 years of research in the field of HCT. PMID:20871781

  3. Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary syndrome.

    PubMed

    Lechowicz, M J; Lazarus, H M; Carreras, J; Laport, G G; Cutler, C S; Wiernik, P H; Hale, G A; Maharaj, D; Gale, R P; Rowlings, P A; Freytes, C O; Miller, A M; Vose, J M; Maziarz, R T; Montoto, S; Maloney, D G; Hari, P N

    2014-11-01

    We describe outcomes after allogeneic hematopoietic cell transplantation (HCT) for mycosis fungoides and Sezary syndrome (MF/SS). Outcomes of 129 subjects with MF/SS reported to the Center for the International Blood and Marrow Transplant from 2000-2009. Median time from diagnosis to transplant was 30 (4-206) months and most subjects were with multiply relapsed/ refractory disease. The majority (64%) received non-myeloablative conditioning (NST) or reduced intensity conditioning (RIC). NST/RIC recipients were older in age compared with myeloablative recipients (median age 51 vs 44 years, P=0.005) and transplanted in recent years. Non-relapse mortality (NRM) at 1 and 5 years was 19% (95% confidence interval (CI) 12-27%) and 22% (95% CI 15-31%), respectively. Risk of disease progression was 50% (95% CI 41-60%) at 1 year and 61% (95% CI 50-71%) at 5 years. PFS at 1 and 5 years was 31% (95% CI 22-40%) and 17% (95% CI 9-26%), respectively. OS at 1 and 5 years was 54% (95% CI 45-63%) and 32% (95% CI 22-44%), respectively. Allogeneic HCT in MF/SS results in 5-year survival in approximately one-third of patients and of those, half remain disease-free. PMID:25068422

  4. The aetiology of post-traumatic stress following childbirth: a meta-analysis and theoretical framework.

    PubMed

    Ayers, S; Bond, R; Bertullies, S; Wijma, K

    2016-04-01

    There is evidence that 3.17% of women report post-traumatic stress disorder (PTSD) after childbirth. This meta-analysis synthesizes research on vulnerability and risk factors for birth-related PTSD and refines a diathesis-stress model of its aetiology. Systematic searches were carried out on PsycINFO, PubMed, Scopus and Web of Science using PTSD terms crossed with childbirth terms. Studies were included if they reported primary research that examined factors associated with birth-related PTSD measured at least 1 month after birth. In all, 50 studies (n = 21 429) from 15 countries fulfilled inclusion criteria. Pre-birth vulnerability factors most strongly associated with PTSD were depression in pregnancy (r = 0.51), fear of childbirth (r = 0.41), poor health or complications in pregnancy (r = 0.38), and a history of PTSD (r = 0.39) and counselling for pregnancy or birth (r = 0.32). Risk factors in birth most strongly associated with PTSD were negative subjective birth experiences (r = 0.59), having an operative birth (assisted vaginal or caesarean, r = 0.48), lack of support (r = -0.38) and dissociation (r = 0.32). After birth, PTSD was associated with poor coping and stress (r = 0.30), and was highly co-morbid with depression (r = 0.60). Moderator analyses showed that the effect of poor health or complications in pregnancy was more apparent in high-risk samples. The results of this meta-analysis are used to update a diathesis-stress model of the aetiology of postpartum PTSD and can be used to inform screening, prevention and intervention in maternity care.

  5. Post Tyrrhénian deformation analysis in the Sahel coast (Eastern Tunisia): seismotectonic events implication

    NASA Astrophysics Data System (ADS)

    Mejrei, H.; Ghribi, R.; Bouaziz, S.; Balescu, S.

    2012-04-01

    The eastern coast of Tunisia is characterized by Pleistocene coastal deposits considered as a reference of interglacial high sea levels. In this region, the stratigraphy of Tunisian Pleistocene deposits was first established on the basis of geomorphological, lithostratigraphic, biostratigraphic criteria and U/Th data. They have been subdivided into three superimposed formations, from the oldest to the recent "Douira, Rejiche and Chebba" including coastal marine (Strombus bubonius), lagoonal and eolian sediments. These marine formations are organized into parallel bars to the actual shoreline overlaying unconformably the Mio-Pliocene and "Villafranchian" deposits. A luminescence dating method IRSL applied to alkali feldspar grains from the two sandy marines units of the Douira formation demonstrate for the first time the presence of two successive interglacial high sea level events correlative of MIS 7 and MIS 9. These sandy marine units are separated by a major erosional surface and by a continental pedogenised loamy deposit related to a low sea level event which might be assigned to MIS 8. Variations in the height of these marine unit (+13 to +32m) in the Sahel coast reflect a significant tectonic deformations and show precious geomorphological and tectonic markers. An extensive brittle deformations analysis has been carried out in several sites. A detailed analysis of fracturing is based on studies of fault-slip data population and of joint sets. It allows reconstructions of post Tyrrhenian stress regimes which are characterized by N170-016 compression and N095-100 extension. In this paper we present, the combination of IRSL data applied to these raised marine deposits and a reconstruction of tectonic evolution in term of stress pattern evolution since the Tyrrhenian allowed us to assign an accurate the recent tectonic calendar. These reconstituted events will be replaced and will be discussed in the regional setting of sismotectonic activities of the north

  6. Hydraulic analysis of river training cross-vanes as part of post-restoration monitoring

    NASA Astrophysics Data System (ADS)

    Endreny, T. A.; Soulman, M. M.

    2011-07-01

    River restoration design methods are incrementally improved by studying and learning from monitoring data in previous projects. In this paper we report post-restoration monitoring data and simulation analysis for a Natural Channel Design (NCD) restoration project along 1600 m of the Batavia Kill (14 km2 watershed) in the Catskill Mountains, NY. The restoration project was completed in 2002 with goals to reduce bank erosion and determine the efficacy of NCD approaches for restoring headwater streams in the Catskill Mountains, NY. The NCD approach used a reference-reach to determine channel form, empirical relations between the project site and reference site bankfull dimensions to size channel geometry, and hydraulic and sediment computations based on a bankfull (1.3 yr return interval) discharge to test channel capacity and sediment stability. The NCD project included 12 cross-vanes and 48 j-hook vanes as river training structures along 19 meander bends to protect against bank erosion and maintain scour pools for fish habitat. Monitoring data collected from 2002 to 2004 were used to identify aggradation of pools in meander bends and below some structures. Aggradation in pools was attributed to the meandering riffle-pool channel trending toward step-pool morphology and cross-vane arms not concentrating flow in the center of the channel. The aggradation subsequently caused flow splitting and 4 partial point bar avulsions during a spring 2005 flood with a 25-yr return interval. Processing the pre-flood monitoring data with hydraulic analysis software provided clues the reach was unstable and preventative maintenance was needed. River restoration and monitoring teams should be trained in robust hydraulic analytical methods that help them extend project restoration goals and structure stability.

  7. The aetiology of post-traumatic stress following childbirth: a meta-analysis and theoretical framework.

    PubMed

    Ayers, S; Bond, R; Bertullies, S; Wijma, K

    2016-04-01

    There is evidence that 3.17% of women report post-traumatic stress disorder (PTSD) after childbirth. This meta-analysis synthesizes research on vulnerability and risk factors for birth-related PTSD and refines a diathesis-stress model of its aetiology. Systematic searches were carried out on PsycINFO, PubMed, Scopus and Web of Science using PTSD terms crossed with childbirth terms. Studies were included if they reported primary research that examined factors associated with birth-related PTSD measured at least 1 month after birth. In all, 50 studies (n = 21 429) from 15 countries fulfilled inclusion criteria. Pre-birth vulnerability factors most strongly associated with PTSD were depression in pregnancy (r = 0.51), fear of childbirth (r = 0.41), poor health or complications in pregnancy (r = 0.38), and a history of PTSD (r = 0.39) and counselling for pregnancy or birth (r = 0.32). Risk factors in birth most strongly associated with PTSD were negative subjective birth experiences (r = 0.59), having an operative birth (assisted vaginal or caesarean, r = 0.48), lack of support (r = -0.38) and dissociation (r = 0.32). After birth, PTSD was associated with poor coping and stress (r = 0.30), and was highly co-morbid with depression (r = 0.60). Moderator analyses showed that the effect of poor health or complications in pregnancy was more apparent in high-risk samples. The results of this meta-analysis are used to update a diathesis-stress model of the aetiology of postpartum PTSD and can be used to inform screening, prevention and intervention in maternity care. PMID:26878223

  8. Post-Messinian evolution of the Florence Ridge area (Western Cyprus Arc), Part I: Morphostructural analysis

    NASA Astrophysics Data System (ADS)

    Sellier, N. C.; Loncke, L.; Vendeville, B. C.; Mascle, J.; Zitter, T.; Woodside, J.; Loubrieu, B.

    2013-04-01

    The Florence Ridge, part of the western Cyprus arc, is a compressional relief that was eroded during the Messinian salinity crisis while deposition of salt occurred North (Antalya basin) and South (Herodotus abyssal plain). In order to better assess the impact of salt-tectonics in the Florence Ridge region deformations, we conducted a morpho-structural analysis of available multibeam and seismic data (Simed and Prismed II campaigns). It is indeed a crucial issue to distinguish crustal and gravity driven structures in the compressional to strike-slip belts of the eastern Mediterranean. Along the Antalya basin, we mainly observed multi-directional tectonic rafts typical of gravity gliding above salt. On the Florence Ridge itself, the base of salt evolves laterally to a Messinian erosional surface that erodes a series of stacked nappes. This surface is involved in recent faulting. South of the Florence Ridge, a nearly 100 km wide fold belt characterizes the Herodotus abyssal plain. Three different zones parallel to the Florence Ridge appear within this fold belt. Those are respectively from North to South zones A, B and C. Zone A is characterized mainly by small-wavelength folding and faulting. Approaching Zone B, a long extensional graben deforms the seafloor. Zone B stands ~ 100 to 200 m higher than zones A and C. There, salt welding seems common. In the easternmost zone B deep sub-circular bathymetric depressions are associated with extremely thick and fan-shaped depocenters probably emplaced in relation with active sub-salt thrusts. Many evidences suggest post-Messinian uplift in this zone. Zone C shows medium to high wavelength salt-cored folds. Wavelength of those folds increase approaching the distal Nile deep-sea fan. Within zone C, a nearly undeformed domain exists approaching the Eratosthenes seamount. 'En echelon' folds bound this flat domain suggesting lateral salt extrusion at the junction between zone C and the distal Nile deep-sea fan. To conclude

  9. Clinical Factors Associated with Dose of Loop Diuretics After Pediatric Cardiac Surgery: Post Hoc Analysis.

    PubMed

    Haiberger, Roberta; Favia, Isabella; Romagnoli, Stefano; Cogo, Paola; Ricci, Zaccaria

    2016-06-01

    A post hoc analysis of a randomized controlled trial comparing the clinical effects of furosemide and ethacrynic acid was conducted. Infants undergoing cardiac surgery with cardiopulmonary bypass were included in order to explore which clinical factors are associated with diuretic dose in infants with congenital heart disease. Overall, 67 patients with median (interquartile range) age of 48 (13-139) days were enrolled. Median diuretic dose was 0.34 (0.25-0.4) mg/kg/h at the end of postoperative day (POD) 0 and it significantly decreased (p = 0.04) over the following PODs; during this period, the ratio between urine output and diuretic dose increased significantly (p = 0.04). Age (r -0.26, p = 0.02), weight (r -0.28, p = 0.01), cross-clamp time (r 0.27, p = 0.03), administration of ethacrynic acid (OR 0.01, p = 0.03), and, at the end of POD0, creatinine levels (r 0.3, p = 0.009), renal near-infrared spectroscopy saturation (-0.44, p = 0.008), whole-blood neutrophil gelatinase-associated lipocalin levels (r 0.30, p = 0.01), pH (r -0.26, p = 0.02), urinary volume (r -0.2755, p = 0.03), and fluid balance (r 0.2577, p = 0.0266) showed a significant association with diuretic dose. At multivariable logistic regression cross-clamp time (OR 1.007, p = 0.04), use of ethacrynic acid (OR 0.2, p = 0.01) and blood pH at the end of POD0 (OR 0.0001, p = 0.03) was independently associated with diuretic dose. Early resistance to loop diuretics continuous infusion is evident in post-cardiac surgery infants: Higher doses are administered to patients with lower urinary output. Independently associated variables with diuretic dose in our population appeared to be cross-clamping time, the administration of ethacrynic acid, and blood pH. PMID:26961571

  10. Clinical Factors Associated with Dose of Loop Diuretics After Pediatric Cardiac Surgery: Post Hoc Analysis.

    PubMed

    Haiberger, Roberta; Favia, Isabella; Romagnoli, Stefano; Cogo, Paola; Ricci, Zaccaria

    2016-06-01

    A post hoc analysis of a randomized controlled trial comparing the clinical effects of furosemide and ethacrynic acid was conducted. Infants undergoing cardiac surgery with cardiopulmonary bypass were included in order to explore which clinical factors are associated with diuretic dose in infants with congenital heart disease. Overall, 67 patients with median (interquartile range) age of 48 (13-139) days were enrolled. Median diuretic dose was 0.34 (0.25-0.4) mg/kg/h at the end of postoperative day (POD) 0 and it significantly decreased (p = 0.04) over the following PODs; during this period, the ratio between urine output and diuretic dose increased significantly (p = 0.04). Age (r -0.26, p = 0.02), weight (r -0.28, p = 0.01), cross-clamp time (r 0.27, p = 0.03), administration of ethacrynic acid (OR 0.01, p = 0.03), and, at the end of POD0, creatinine levels (r 0.3, p = 0.009), renal near-infrared spectroscopy saturation (-0.44, p = 0.008), whole-blood neutrophil gelatinase-associated lipocalin levels (r 0.30, p = 0.01), pH (r -0.26, p = 0.02), urinary volume (r -0.2755, p = 0.03), and fluid balance (r 0.2577, p = 0.0266) showed a significant association with diuretic dose. At multivariable logistic regression cross-clamp time (OR 1.007, p = 0.04), use of ethacrynic acid (OR 0.2, p = 0.01) and blood pH at the end of POD0 (OR 0.0001, p = 0.03) was independently associated with diuretic dose. Early resistance to loop diuretics continuous infusion is evident in post-cardiac surgery infants: Higher doses are administered to patients with lower urinary output. Independently associated variables with diuretic dose in our population appeared to be cross-clamping time, the administration of ethacrynic acid, and blood pH.

  11. Quality of life, social challenges, and psychosocial support for long-term survivors after allogeneic hematopoietic stem-cell transplantation.

    PubMed

    Norkin, Maxim; Hsu, Jack W; Wingard, John R

    2012-01-01

    Over the last two decades quality of life (QoL) and the social challenges of allogeneic hematopoietic stem cell transplant (allo-HSCT) survivors have been emerging as subjects of extensive research and are now considered as very important aspects in the pretransplant evaluation and management of allo-HSCT recipients. Recognition of QoL challenges in allo-HSCT survivors allows timely interventions leading to improvement of post-transplant outcomes. It needs to be recognized that long-lasting life changes associated with survivorship after allo-HSCT also significantly affect QoL of partners of allo-HSCT survivors. Currently, resources should be focused on how research findings can be used by patients, their partners, and physicians to optimize QoL and psychosocial adjustment.

  12. Sex Differences in Hookah-Related Images Posted on Tumblr: A Content Analysis.

    PubMed

    Primack, Brian A; Carroll, Mary V; Shensa, Ariel; Davis, Wesley; Levine, Michele D

    2016-01-01

    Hookah tobacco smoking is prevalent, widespread, and associated with large amounts of toxicants. Hookah tobacco smoking may be viewed differently by males and females. For example, females have been drawn to types of tobacco that are flavored, milder, and marketed as more social and exotic. Individuals often use the growing segment of anonymous social networking sites, such as Tumblr, to learn about potentially dangerous or harmful behaviors. We used a systematic process involving stratification by time of day, day of week, and search term to gather a sample of 140 Tumblr posts related to hookah tobacco smoking. After a structured codebook development process, 2 coders independently assessed all posts in their entirety, and all disagreements were easily adjudicated. When data on poster sex and age were available, we found that 77% of posts were posted by females and 35% were posted by individuals younger than 18. The most prominent features displayed in all posts were references to or images of hookahs themselves, sexuality, socializing, alcohol, hookah smoke, and tricks performed with hookah smoke. Compared with females, males more frequently posted images of hookahs and alcohol-related images or references. This information may help guide future research in this area and the development of targeted interventions to curb this behavior. PMID:26890733

  13. Sex Differences in Hookah-Related Images Posted on Tumblr: A Content Analysis.

    PubMed

    Primack, Brian A; Carroll, Mary V; Shensa, Ariel; Davis, Wesley; Levine, Michele D

    2016-01-01

    Hookah tobacco smoking is prevalent, widespread, and associated with large amounts of toxicants. Hookah tobacco smoking may be viewed differently by males and females. For example, females have been drawn to types of tobacco that are flavored, milder, and marketed as more social and exotic. Individuals often use the growing segment of anonymous social networking sites, such as Tumblr, to learn about potentially dangerous or harmful behaviors. We used a systematic process involving stratification by time of day, day of week, and search term to gather a sample of 140 Tumblr posts related to hookah tobacco smoking. After a structured codebook development process, 2 coders independently assessed all posts in their entirety, and all disagreements were easily adjudicated. When data on poster sex and age were available, we found that 77% of posts were posted by females and 35% were posted by individuals younger than 18. The most prominent features displayed in all posts were references to or images of hookahs themselves, sexuality, socializing, alcohol, hookah smoke, and tricks performed with hookah smoke. Compared with females, males more frequently posted images of hookahs and alcohol-related images or references. This information may help guide future research in this area and the development of targeted interventions to curb this behavior.

  14. A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy

    PubMed Central

    Spielmann, Guillaume; Bollard, Catherine M.; Kunz, Hawley; Hanley, Patrick J.; Simpson, Richard J.

    2016-01-01

    Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy. PMID:27181409

  15. Human histology of allogeneic block grafts for alveolar ridge augmentation: case report.

    PubMed

    Morelli, Thiago; Neiva, Rodrigo; Wang, Hom-Lay

    2009-12-01

    Autogenous bone grafts obtained from the mandibular symphysis or ramus are the primary donor sites for harvesting bone in the oral cavity to correct ridge deficiencies. Although such bone grafts can be successful, several concerns remain, such as donor site morbidity, nerve paresthesia, devitalization of natural teeth, and postoperative complications (eg, swelling, discomfort, and pain). To avoid these concerns and overcome the limited amount of autogenous intraoral bone for grafting, allogeneic block grafts were introduced. The purposes of this paper were to introduce allogeneic block grafts, demonstrate the integration of these allogeneic block grafts into the recipient site by detailed histology, and describe the step-by-step surgical technique of how this graft was used in a patient. A literature search was conducted to identify papers related to allogeneic block grafting, and papers were reviewed and summarized. The advantages and disadvantages of allogeneic block grafting were presented based on the literature and the authors' experience. One patient treated with allogeneic block graft was illustrated. The histologic evidence obtained from this patient indicated good bone remodeling and significant amount of new bone formation. The literature and clinical experience have shown that allogeneic block grafts can be used successfully to augment deficient ridges. PMID:20072743

  16. Significance of Persistent Cytogenetic Abnormalities at Myeloablative Allogeneic Stem Cell Transplantation in First Complete Remission

    PubMed Central

    Oran, Betul; Popat, Uday; Rondon, Gabriella; Ravandi, Farhad; Garcia-Manero, Guillermo; Abruzzo, Lynn; Andersson, Borje S.; Bashir, Qaiser; Chen, Julianne; Kebriaei, Partow; Khouri, Issa F.; Koca, Ebru; Qazilbash, Muzaffar H.; Champlin, Richard; de Lima, Marcos

    2014-01-01

    Risk stratification is important to identify acute myeloid leukemia (AML) patients that might benefit from allogeneic hematopoietic stem cell transplantation (allo-HCT) in first complete remission (CR1). We retrospectively studied 150 AML patients with diagnostic cytogenetic abnormalities receiving myeloablative allo-HCT in CR1 to determine the prognostic impact of persistent cytogenetic abnormalities at allo-HCT. Three risk groups were identified: First group of patients with favorable/intermediate cytogenetics at diagnosis (n=49) and the second group with unfavorable cytogenetics at diagnosis but without the presence of persistent abnormal clone at allo-HCT (n=83) had similar 3-year leukemia free survival (LFS) of 58%-60% despite increased 3-year relapse incidence (RI) of 32.3% observed in the second risk group versus 16.8% in the first group. Third group of patients with unfavorable cytogenetics at diagnosis and persistence of that clone at allo-HCT (n=15) represented the worst prognostic group with 3-year RI of 57.5% and 3-year LFS of 29.2%. These data suggest that AML patients with unfavorable cytogenetics at diagnosis and persistence of abnormal clone at allo-HCT have high risk of relapse after allo-HCT. These patients should be considered for clinical trials designed to optimize conditioning regimens and/or to use preemptive strategies in the post-transplant setting to decrease the relapse incidence. PMID:22982533

  17. Lenalidomide Maintenance for High Risk Multiple Myeloma after Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

    Alsina, Melissa; Becker, Pamela S.; Zhong, Xiaobo; Adams, Alexia; Hari, Parameswaran; Rowley, Scott; Stadtmauer, Edward A.; Vesole, David H.; Logan, Brent; Weisdorf, Daniel; Qazilbash, Muzaffar; Popplewell, Leslie L.; McClune, Brian; Bensinger, William; Riches, Marcie; Giralt, Sergio A.; Pasquini, Marcelo C.

    2016-01-01

    Allogeneic hematopoietic cell transplantation (alloHCT) with reduced intensity conditioning is an appealing option for patients with high risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1–21 of 28 days cycles, with intra-patient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age 54 years) with high risk MM were enrolled at 8 centers between 2009–2012. The median time from alloHCT to LEN initiation was 96 days (66–171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%).Most common reasons for discontinuation were aGVHD (37%) and disease progression (37%). Cumulative incidence of grades III–IV acute GVHD from time of initiation of Len was 17%. Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplant related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN post alloHCT is feasible at lower doses, although associated with a 38% incidence of aGVHD. Survival outcomes observed in this high risk MM population warrant further study of this approach. PMID:24769014

  18. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia

    PubMed Central

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T.; Bhatt, Vijaya Raj

    2016-01-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials. PMID:27247754

  19. Relationship between HMGB1 and PAI-1 after allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Nomura, Shosaku; Maeda, Yoshinobu; Ishii, Kazuyoshi; Katayama, Yuta; Yagi, Hideo; Fujishima, Naoto; Ota, Shuichi; Moriyama, Masato; Ikezoe, Takayuki; Miyazaki, Yasuhiko; Hayashi, Kunio; Fujita, Shinya; Satake, Atsushi; Ito, Tomoki; Kyo, Taiichi; Tanimoto, Mitsune

    2016-01-01

    Background Conditioning regimens including total body irradiation (TBI) or cyclophosphamide can mobilize high-mobility group box 1 (HMGB1) to peripheral blood. Additionally, increased plasminogen activator inhibitor (PAI)-1 levels are associated with post-allogeneic hematopoietic stem cell transplantation (aHSCT). However, changes to circulating levels of HMGB1 after aHSCT are poorly understood. Materials and methods The study cohort included 289 patients who underwent aHSCT at one of 25 institutions in Japan. We have investigated the relationship between HMGB1 and PAI-1 following aHSCT. A significant increase in HMGB1 levels occurred after conditioning treatment. Additionally, levels of HMGB1 at day 0 were significantly increased in TBI+ patients and cyclophosphamide/TBI patients. Conclusion Our data revealed that an increased level of HMGB1 at day 0 following aHSCT correlates with increased PAI-1 after aHSCT, which is consistent with previous reports. Increased HMGB1 at day 0 after a conditioning regimen may play a role in transplantation-associated coagulopathy following aHSCT, because PAI-1 can accelerate procoagulant activity. PMID:26848281

  20. Bone marrow-derived hematopoietic stem and progenitor cells infiltrate allogeneic and syngeneic transplants.

    PubMed

    Fan, Z; Enjoji, K; Tigges, J C; Toxavidis, V; Tchipashivili, V; Gong, W; Strom, T B; Koulmanda, M

    2014-12-01

    Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineage(negative) Sca-1(+) cKit(+) ("LSK") cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic "LSK" HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, "LSK" HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intramedullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs.

  1. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia.

    PubMed

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T; Bhatt, Vijaya Raj

    2016-06-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials.

  2. A survey of fertility and sexual health following allogeneic haematopoietic stem cell transplantation in New South Wales, Australia.

    PubMed

    Dyer, Gemma; Gilroy, Nicole; Bradford, Jennifer; Brice, Lisa; Kabir, Masura; Greenwood, Matt; Larsen, Stephen R; Moore, John; Hertzberg, Mark; Kwan, John; Brown, Louisa; Hogg, Megan; Huang, Gillian; Tan, Jeff; Ward, Christopher; Kerridge, Ian

    2016-02-01

    Four hundred and twenty-one adult allogeneic haematopoietic stem cell transplant (HSCT) survivors participated in a cross-sectional study to assess sexual dysfunction and infertility post-transplant. Survey instruments included the Sydney Post-Blood and Marrow Transplant (BMT) Survey, Functional Assessment of Cancer Treatment (FACT) - BMT, the Depression, Anxiety, Stress Scales (DASS 21), the Chronic Graft-versus-Host Disease (cGVHD) Activity Assessment- Patient Self Report (Form B), the Lee cGVHD Symptom Scale and The Post-Traumatic Growth Inventory. Most HSCT survivors reported sexual difficulties (51% of males; 66% of females). Men reported erectile dysfunction (79%) and decreased libido (61·6%) and women reported loss of libido (83%), painful intercourse (73%) and less enjoyment of sex (68%). Women also commonly reported vaginal dryness (73%), vaginal narrowing (34%) and vaginal irritation (26%). Woman had much higher rates of genital cGvHD than men (22% vs. 5%). Age and cGVHD were significantly associated with sexual dysfunction. Few survivors had children following transplant (3·3%). However, for those of reproductive age at HSCT, 22% reported trying to conceive, with 10·3% reporting success. This study is the largest to date exploring sexual function in survivors of allo-HSCT. This data provides the basis for health service reform to better meet the needs of HSCT survivors, including evidence to support counselling and education both pre- and post-transplant. PMID:26847746

  3. Finite element stress analysis of short-post core and over restorations prepared with different restorative materials.

    PubMed

    Gurbuz, Taskin; Sengul, Fatih; Altun, Ceyhan

    2008-07-01

    The present study was conducted to determine the effect on the distribution of stress with the use of short-post cores and over restorations composed of different materials. The restorative materials used were namely two different composite resin materials (Valux Plus and Tetric Flow), a polyacid-modified resin material (Dyract AP), and a woven polyethylene fiber combination (Ribbond Fiber + Bonding agent + Tetric Flow). Finite element analysis (FEA) was used to develop a model for the maxillary primary anterior teeth. A masticatory force of 100 N was applied at 148 degrees to the incisal edge of the palatal surface of the crown model. Stress distributions and stress values were compared using von Mises criteria. The tooth model was assumed to be isotropic, homogeneous, elastic, and asymmetrical. It was observed that the highest stress usually occurred in the cervical area of the tooth when Tetric Flow was used as the short-post core and over restoration material. The same maximum stress value was also obtained when Ribbond fiber + Tetric Flow material was used for the short-post core. The results of FEA showed that the mechanical properties and elastic modulus of the restorative material influenced the stresses generated in enamel, dentin, and restoration when short-post core restorations were loaded incisally. Resin-based restorative materials with higher elastic moduli were found to be unsuitable as short-post core materials in endodontically treated maxillary primary anterior teeth. PMID:18833762

  4. Evaluation of Temperature and Stress Distribution on 2 Different Post Systems Using 3-Dimensional Finite Element Analysis

    PubMed Central

    Değer, Yalçın; Adigüzel, Özkan; Özer, Senem Yiğit; Kaya, Sadullah; Polat, Zelal Seyfioğlu; Bozyel, Bejna

    2015-01-01

    Background The mouth is exposed to thermal irritation from hot and cold food and drinks. Thermal changes in the oral cavity produce expansions and contractions in tooth structures and restorative materials. The aim of this study was to investigate the effect of temperature and stress distribution on 2 different post systems using the 3-dimensional (3D) finite element method. Material/Methods The 3D finite element model shows a labio-lingual cross-sectional view of the endodontically treated upper right central incisor and supporting periodontal ligament with bone structures. Stainless steel and glass fiber post systems with different physical and thermal properties were modelled in the tooth restored with composite core and ceramic crown. We placed 100 N static vertical occlusal loading onto the center of the incisal surface of the tooth. Thermal loads of 0°C and 65°C were applied on the model for 5 s. Temperature and thermal stresses were determined on the labio-lingual section of the model at 6 different points. Results The distribution of stress, including thermal stress values, was calculated using 3D finite element analysis. The stainless steel post system produced more temperature and thermal stresses on the restorative materials, tooth structures, and posts than did the glass fiber reinforced composite posts. Conclusions Thermal changes generated stresses in the restorative materials, tooth, and supporting structures. PMID:26615495

  5. Finite element stress analysis of short-post core and over restorations prepared with different restorative materials.

    PubMed

    Gurbuz, Taskin; Sengul, Fatih; Altun, Ceyhan

    2008-07-01

    The present study was conducted to determine the effect on the distribution of stress with the use of short-post cores and over restorations composed of different materials. The restorative materials used were namely two different composite resin materials (Valux Plus and Tetric Flow), a polyacid-modified resin material (Dyract AP), and a woven polyethylene fiber combination (Ribbond Fiber + Bonding agent + Tetric Flow). Finite element analysis (FEA) was used to develop a model for the maxillary primary anterior teeth. A masticatory force of 100 N was applied at 148 degrees to the incisal edge of the palatal surface of the crown model. Stress distributions and stress values were compared using von Mises criteria. The tooth model was assumed to be isotropic, homogeneous, elastic, and asymmetrical. It was observed that the highest stress usually occurred in the cervical area of the tooth when Tetric Flow was used as the short-post core and over restoration material. The same maximum stress value was also obtained when Ribbond fiber + Tetric Flow material was used for the short-post core. The results of FEA showed that the mechanical properties and elastic modulus of the restorative material influenced the stresses generated in enamel, dentin, and restoration when short-post core restorations were loaded incisally. Resin-based restorative materials with higher elastic moduli were found to be unsuitable as short-post core materials in endodontically treated maxillary primary anterior teeth.

  6. Acute myeloid leukemia of donor origin after allogeneic stem cell transplantation from a sibling who harbors germline XPD and XRCC3 homozygous polymorphisms

    PubMed Central

    2011-01-01

    A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two years after treatment, the patient developed an acute myeloid leukemia (AML) which harbored del(11q23) in 8% of the blast cells. The patient was submitted for allogeneic stem cell transplantation (aSCT) from her HLA-compatible sister. Ten months after transplantation, she relapsed with an AML with basophilic maturation characterized by CD45low CD33high, CD117+, CD13-/+, HLA Drhigh, CD123high, and CD203c+ blast cells lacking expression of CD7, CD10, CD34, CD15, CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the emergence of a new clone with t(2;14) and FISH analysis indicated the presence of MLL gene rearrangement consistent with del(11q23). Interestingly, AML blast cell DNA tested with microsatellite markers showed the same pattern as the donor's, suggesting that this AML emerged from donor cells. Additionally, polymorphisms of the XPA, XPD, XRCC1, XRCC3 and RAD51 DNA repair genes revealed three unfavorable alleles with low DNA repair capacity. In summary, we report the first case of AML involving XPD and XRCC3 polymorphisms from donor origin following allogeneic stem cell transplantation and highlight the potential need for careful analysis of DNA repair gene polymorphisms in selecting candidate donors prior to allogeneic stem cell transplantation. PMID:21951951

  7. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

    PubMed Central

    Craddock, Charles; Labopin, Myriam; Robin, Marie; Finke, Juergen; Chevallier, Patrice; Yakoub-Agha, Ibrahim; Bourhis, Jean Henri; Sengelov, Henrik; Blaise, Didier; Luft, Thomas; Hallek, Michael; Kröger, Nicolaus; Nagler, Arnon; Mohty, Mohamad

    2016-01-01

    Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients received additional donor lymphocyte infusions. Forty-six of 157 (25%) assessable patients responded to azacitidine therapy: 24 (15%) achieved a complete remission and 22 a partial remission. Response rates were higher in patients transplanted in complete remission (P=0.04) and those transplanted for myelodysplastic syndromes (P=0.023). In patients who achieved a complete remission, the 2-year overall survival was 48% versus 12% for the whole population. Overall survival was determined by time to relapse post transplant more than six months (P=0.001) and percentage of blasts in the bone marrow at time of relapse (P=0.01). The concurrent administration of donor lymphocyte infusion did not improve either response rates or overall survival in patients treated with azacitidine. An azacitidine relapse prognostic score was developed which predicted 2-year overall survival ranging from 3%–37% (P=0.00001). We conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required. PMID:27081178

  8. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia.

    PubMed

    Craddock, Charles; Labopin, Myriam; Robin, Marie; Finke, Juergen; Chevallier, Patrice; Yakoub-Agha, Ibrahim; Bourhis, Jean Henri; Sengelov, Henrik; Blaise, Didier; Luft, Thomas; Hallek, Michael; Kröger, Nicolaus; Nagler, Arnon; Mohty, Mohamad

    2016-07-01

    Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients received additional donor lymphocyte infusions. Forty-six of 157 (25%) assessable patients responded to azacitidine therapy: 24 (15%) achieved a complete remission and 22 a partial remission. Response rates were higher in patients transplanted in complete remission (P=0.04) and those transplanted for myelodysplastic syndromes (P=0.023). In patients who achieved a complete remission, the 2-year overall survival was 48% versus 12% for the whole population. Overall survival was determined by time to relapse post transplant more than six months (P=0.001) and percentage of blasts in the bone marrow at time of relapse (P=0.01). The concurrent administration of donor lymphocyte infusion did not improve either response rates or overall survival in patients treated with azacitidine. An azacitidine relapse prognostic score was developed which predicted 2-year overall survival ranging from 3%-37% (P=0.00001). We conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required. PMID:27081178

  9. Engraftment of Syngeneic and Allogeneic Endothelial Cells, Hepatocytes and Cholangiocytes into Partially Hepatectomized Rats Previously Treated with Mitomycin C1

    PubMed Central

    Brilliant, Kate E.; Mills, David R.; Callanan, Helen M.; Hixson, Douglas C.

    2009-01-01

    Background Pretreatment with retrorsine crosslinks host hepatocyte DNA and prevents proliferation after partial hepatectomy (PH), allowing selective expansion of transplanted progenitors. Shortcomings are length of protocol and carcinogenicity of retrorsine. Methods This report describes a rapid liver repopulation protocol using mitomycin C (MMC) to block proliferation of rat hepatocytes in response to PH. One week post-MMC treatment, dipeptidyl peptidase IV negative (DPPIV−) host rats were given a PH followed by injection of late gestation, newborn or adult total liver isolates from DPPIV+ rats. For allogeneic transplantation, host rats received injections of anti-CD3 antibody before and after PH. Results Host liver staining 2–9 weeks post-transplantation revealed well-defined donor hepatocyte colonies with strong canalicular DPPIV activity. At the same cell dose, fetal and newborn isolates produced more colonies than adult liver isolates. Hepatocyte colonies also co-expressed marker proteins characteristic of adult hepatocytes and showed polarized localization of plasma membrane proteins. Host livers contained large clusters of sinusoids lined by DPPIV+ endothelial cells co-expressing the endothelial cell marker, RECA-1 but lacked the canalicular marker leucine aminopeptidase. Colonies containing donor hepatocytes, endothelial cells and bile ducts, were also observed. Similar levels of engraftment and expansion were achieved with allogeneic liver cell isolates by using anti-CD3 antibody treatment. Conclusions The MMC transplantation model provides a rapid method for engraftment and expansion of hepatocytes, endothelial cells and cholangiocytes and should be applicable to investigations centering on the role of endothelial cells in liver regeneration and the identification and characterization of putative endothelial, hepatocyte and cholangiocyte progenitors. PMID:19696631

  10. Antitumor immunomodulatory activity of allogenic bone marrow cells on TiNi scaffold

    NASA Astrophysics Data System (ADS)

    Kokorev, O. V.; Hodorenko, V. N.; Cherdyntseva, N. V.; Gunther, V. E.

    2016-08-01

    The present study was undertaken to evaluate the feasibility of modulation of anti-tumor response by allogenic bone marrow cell transplantation into porous TiNi-based scaffold. Transplantation of bone marrow cells into porous TiNi-based scaffold leads to antitumor (35%) and antimetastatic (55%) effects. The lifetime of tumor-bearing animals and implanted allogenic bone marrow cells in incubator of TiNi increases up to 60%. The possible mechanisms of the effect of allogenic cells on tumor process are the stimulation of endogenous effectors of antitumor immunity.

  11. Post-radiation changes in oral tissues - An analysis of cancer irradiation cases

    PubMed Central

    Pandya, Jay Ashokkumar; Srikant, N.; Boaz, Karen; Manaktala, Nidhi; Kapila, Supriya Nikita; Yinti, Shanmukha Raviteja

    2014-01-01

    Introduction: Radiation, commonly employed as neoadjuvant, primary, and adjuvant therapy for head and neck cancer causes numerous epithelial and stromal changes, prominent among which is fibrosis with its early and late consequences. Very little is known about the true nature of the fibrosed tissue and the type of fibers accumulated. Radiotherapy affects the supporting tumor stroma often resulting in a worsening grade of tumor post-radiation. Aim: To study epithelial, neoplastic, stromal, and glandular changes in oral cavity induced by radiation therapy for oral squamous cell carcinoma (OSCC) using special stains. Materials and Methods: The study included 27 samples of recurrent OSCC following completion of radiotherapy (recurrence within an average span of 11 months), and 26 non-irradiated cases of OSCC. Patients with a history of combined radiotherapy and chemotherapy were not included in the study. The epithelial changes assessed included epithelial atrophy, apoptosis, necrosis, dysplasia, and neoplasia. The connective tissue was evaluated for amount of fibrosis, quality of fibers (using picrosirius red staining), fibrinous exudate, necrosis, pattern of invasion, vessel wall thickening, and salivary gland changes. The aforementioned changes were assessed using light and polarizing microscopy and tabulated. Statistical Analysis: Epithelial and connective tissue parameters were compared between the irradiated and non-irradiated cases using chi square and t-tests. Results: Epithelial and connective tissue parameters were found to be increased in irradiated patients. Pattern of invasion by tumor cells varied from strands and  cords between the two groups studied. The effect of radiation was seen to reflect on the maturity of fibers and the regularity of their distribution. PMID:25136522

  12. Building, Testing, and Post Test Analysis of Durability Heat Pipe No.6

    SciTech Connect

    MOSS, TIMOTHY A.

    2002-03-01

    The Solar Thermal Program at Sandia supports work developing dish/Stirling systems to convert solar energy into electricity. Heat pipe technology is ideal for transferring the energy of concentrated sunlight from the parabolic dish concentrators to the Stirling engine heat tubes. Heat pipes can absorb the solar energy at non-uniform flux distributions and release this energy to the Stirling engine heater tubes at a very uniform flux distribution thus decoupling the design of the engine heater head from the solar absorber. The most important part of a heat pipe is the wick, which transports the sodium over the heated surface area. Bench scale heat pipes were designed and built to more economically, both in time and money, test different wicks and cleaning procedures. This report covers the building, testing, and post-test analysis of the sixth in a series of bench scale heat pipes. Durability heat pipe No.6 was built and tested to determine the effects of a high temperature bakeout, 950 C, on wick corrosion during long-term operation. Previous tests showed high levels of corrosion with low temperature bakeouts (650-700 C). Durability heat pipe No.5 had a high temperature bakeout and reflux cleaning and showed low levels of wick corrosion after long-term operation. After testing durability heat pipe No.6 for 5,003 hours at an operating temperature of 750 C, it showed low levels of wick corrosion. This test shows a high temperature bakeout alone will significantly reduce wick corrosion without the need for costly and time consuming reflux cleaning.

  13. Post-Flight Analysis of Dynamic Data Acquired During the ATV-2 Johannes Kepler Launch

    NASA Astrophysics Data System (ADS)

    Meitzner, R.; Abdoly, K.; Newerla, A.

    2012-07-01

    An in-flight data acquisition system called TeleMesure Autonome (TMA) has been implemented on ATV-1 Jules Verne (launched in March 2008) and ATV-2 Johannes Kepler (launched in February 2011). The TMA served the main objective to measure dynamic responses on the ATV spacecraft for comparison with coupled load analysis predictions and to verify that the ATV mechanical flight environment has been sufficiently covered by the respective ATV design specifications. The acquired flight data included low frequency sinusoidal, random vibration and shock measurements. Whereas the TMA on ATV-1 Jules Verne failed to properly work after 17 seconds after liftoff the improved TMA on ATV-2 Johannes Kepler performed its tasks successfully for all flight phases. The flight data have been subsequently evaluated by the ATV prime contractor Astrium. As first step of the performed analyses a correction of the acquired data was necessary to remove any artificial content (spikes, mean truncation, offset correction) followed by a visual inspection of the corrected data to ensure data quality. Then standard post processing methods were applied to the data consisting of generating equivalent sinusoidal responses and transfer functions for the low frequency data, power spectral densities for the random data and shock responses for the high frequency shock data. Although it was noted that the quality of the data was limited by the available transmission bandwidth and the amplitude resolution of the data acquisition system the implementation of the TMA on ATV-2 Johannes Kepler has nevertheless turned out successful and valuable data have been acquired for all relevant flight phases.

  14. Radial-Velocity Analysis of the Post-AGB Star, HD101584

    NASA Astrophysics Data System (ADS)

    Díaz, F.; Hearnshaw, J.; Rosenzweig, P.; Guzman, E.; Sivarani, T.; Parthasarathy, M.

    2007-08-01

    This project concerns the analysis of the periodicity of the radial velocity of the peculiar emission-line supergiant star HD 101584 (F0 Ia), and also we propose a physical model to account for the observations. From its peculiarities, HD 101584 is a star that is in the post-AGB phase. This study is considered as a key to clarify the multiple aspects related with the evolution of the circum-stellar layer associated with this star's last phase. The star shows many lines with P Cygni profiles, including H-alpha, Na D lines in the IR Ca triplet, indicating a mass outflow. For HD 101584 we have performed a detailed study of its radial-velocity variations, using both emission and absorption lines over a wide range of wavelength. We have analyzed the variability and found a periodicity for all types of lines of 144 days, which must arise from the star's membership in a binary system. The data span a period of five consecutive years and were obtained using the 1-m telescope of Mt John Observatory, in New Zealand., with the echelle and Hercules high resolution spectrographs and CCD camera. HD101584 is known to be an IRAS source, and our model suggests it is a proto-planetary nebula, probably with a bipolar outflow and surrounded by a dusty disk as part of a binary system. We have found no evidence for HD101584 to contain a B9 star as found by Bakker et al (1996). A low resolution IUE spectrum shows the absence of any strong UV continuum that would be expected for a B star to be in this system.

  15. Allogeneic Splenocyte Transfer and Lipopolysaccharide Inhalations Induce Differential T Cell Expansion and Lung Injury: A Novel Model of Pulmonary Graft-versus-Host Disease

    PubMed Central

    Sun, Jesse; Kelly, Francine L.; Nelson, Margaret E.; Garantziotis, Stavros; Foster, W. Michael; Palmer, Scott M.

    2014-01-01

    Background Pulmonary GVHD (pGVHD) is an important complication of hematopoietic cell transplant (HCT) and is thought to be a consequence of the HCT conditioning regimen, allogeneic donor cells, and posttransplant lung exposures. We have previously demonstrated that serial inhaled lipopolysaccharide (LPS) exposures potentiate the development of pGVHD after murine allogeneic HCT. In the current study we hypothesized that allogeneic lymphocytes and environmental exposures alone, in the absence of a pre-conditioning regimen, would cause features of pGVHD and would lead to a different T cell expansion pattern compared to syngeneic cells. Methods Recipient Rag1−/− mice received a transfer of allogeneic (Allo) or syngeneic (Syn) spleen cells. After 1 week of immune reconstitution, mice received 5 daily inhaled LPS exposures and were sacrificed 72 hours after the last LPS exposure. Lung physiology, histology, and protein levels in bronchoalveolar lavage (BAL) were assessed. Lung cells were analyzed by flow cytometry. Results Both Allo and Syn mice that undergo LPS exposures (AlloLPS and SynLPS) have prominent lymphocytic inflammation in their lungs, resembling pGVHD pathology, not seen in LPS-unexposed or non-transplanted controls. Compared to SynLPS, however, AlloLPS have significantly increased levels of BAL protein and enhancement of airway hyperreactivity, consistent with more severe lung injury. This injury in AlloLPS mice is associated with an increase in CD8 T cells and effector CD4 T cells, as well as a decrease in regulatory to effector CD4 T cell ratio. Additionally, cytokine analysis is consistent with a preferential Th1 differentiation and upregulation of pulmonary CCL5 and granzyme B. Conclusions Allogeneic lymphocyte transfer into lymphocyte-deficient mice, followed by LPS exposures, causes features of pGVHD and lung injury in the absence of a pre-conditioning HCT regimen. This lung disease associated with an expansion of allogeneic effector T cells

  16. Factors affecting long-term outcome after allogeneic haematopoietic stem cell transplantation for acute myelogenous leukaemia: a retrospective study of 172 adult patients reported to the Austrian Stem Cell Transplantation Registry.

    PubMed

    Greinix, Hildegard T; Nachbaur, David; Krieger, Otto; Eibl, Margit; Knöbl, Paul; Kalhs, Peter; Lutz, Dieter; Linkesch, Werner; Niederwieser, Dietger; Hinterberger, Wolfgang; Lechner, Klaus; Rosenmayr, Agathe; Gritsch, Beate

    2002-06-01

    Between 1982 and 2000, 172 patients with acute myelogenous leukaemia (AML) received haematopoietic stem cell transplants (SCT) from related (n = 132) or unrelated (n = 40) donors at four Austrian transplant centres and their results were reported to the Austrian Stem Cell Transplantation Registry. Conditioning for SCT consisted of cyclophosphamide and total body irradiation in 156 (91%) patients. Graft-versus-host disease (GVHD) prophylaxis was with standard cyclosporine and methotrexate in 95 (55%) patients. Median post-transplant follow-up was 5.6 years (range, 0.2--16.7). Multivariate analysis of transplant-related mortality (TRM) identified four variables associated with a lower risk: disease status of first complete remission (CR) at SCT, patient age of 45 years and younger, transplant performed during or after 1995, and lack of acute GVHD. Variables associated with significantly improved leukaemia-free survival were: bone marrow as the stem cell source, disease status of first CR at SCT, and occurrence of chronic GVHD. In multivariate analysis, transplantation performed during or after 1995, first CR at SCT, occurrence of limited chronic GVHD and lack of acute GVHD grades III to IV were associated with increased overall survival. Based on these analyses, options for the improvement of results obtained with allogeneic SCT in patients with AML could be defined. PMID:12060131

  17. An overview of infectious complications after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Sahin, Ugur; Toprak, Selami Kocak; Atilla, Pinar Ataca; Atilla, Erden; Demirer, Taner

    2016-08-01

    Infections are the most common and significant cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The presence of neutropenia and mucosal damage are the leading risk factors in the early pre-engraftment phase. In the early post-engraftment phase, graft versus host disease (GvHD) induced infection risk is increased in addition to catheter related infections. In the late phase, in which reconstitution of cellular and humoral immunity continues, as well as the pathogens seen during the early post-engraftment phase, varicella-zoster virus and encapsulated bacterial infections due to impaired opsonization are observed. An appropriate vaccination schedule following the cessation of immunosuppressive treatment after transplantation, intravenous immunoglobulin administration, and antimicrobial prophylaxis with penicillin or macrolide antibiotics during immunosuppressive treatment for GvHD might decrease the risk of bacterial infections. Older age, severe mucositis due to toxicity of chemotherapy, gastrointestinal tract colonization, prolonged neutropenia, unrelated donor and cord blood originated transplantations, acute and chronic GvHD are among the most indicative clinical risk factors for invasive fungal infections. Mold-active anti-fungal prophylaxis is suggested regardless of the period of transplantation among high risk patients. The novel serological methods, including Aspergillus galactomannan antigen and beta-D-glucan detection and computed tomography are useful in surveillance. Infections due to adenovirus, influenza and respiratory syncytial virus are encountered in all phases after allo-HSCT, including pre-engraftment, early post-engraftment and late phases. Infections due to herpes simplex virus-1 and -2 are mostly seen during the pre-engraftment phase, whereas, infections due to cytomegalovirus and human herpes virus-6 are seen in the early post-engraftment phase and Epstein-Barr virus and varicella

  18. Post-treatment of molasses wastewater by electrocoagulation and process optimization through response surface analysis.

    PubMed

    Tsioptsias, C; Petridis, D; Athanasakis, N; Lemonidis, I; Deligiannis, A; Samaras, P

    2015-12-01

    Molasses wastewater is a high strength effluent of food industry such as distilleries, sugar and yeast production plants etc. It is characterized by a dark brown color and exhibits a high content in substances of recalcitrant nature such as melanoidins. In this study, electrocoagulation (EC) was studied as a post treatment step for biologically treated molasses wastewater with high nitrogen content obtained from a baker's yeast industry. Iron and copper electrodes were used in various forms; the influence and interaction of current density, molasses wastewater dilution, and reaction time, on COD, color, ammonium and nitrate removal rates and operating cost were studied and optimized through Box Behnken's response surface analysis. Reaction time varied from 0.5 to 4 h, current density varied from 5 to 40 mA/cm(2) and dilution from 0 to 90% (v/v expressed as water concentration). pH, conductivity and temperature measurements were also carried out during each experiment. From preliminary experiments, it was concluded that the application of aeration and sample dilution, considerably influenced the kinetics of the process. The obtained results showed that COD removal varied between 10 and 54%, corresponding to an operation cost ranging from 0.2 to 33 euro/kg COD removed. Significant removal rates were obtained for nitrogen as nitrate and ammonium (i.e. 70% ammonium removal). A linear relation of COD and ammonium to the design parameters was observed, while operation cost and nitrate removal responded in a curvilinear function. A low ratio of electrode surface to treated volume was used, associated to a low investment cost; in addition, iron wastes could be utilized as low cost electrodes i.e. iron fillings from lathes, aiming to a low operation cost due to electrodes replacement. In general, electrocoagulation proved to be an effective and low cost process for biologically treated molasses-wastewater treatment for additional removal of COD and nitrogen content and

  19. Post-treatment of molasses wastewater by electrocoagulation and process optimization through response surface analysis.

    PubMed

    Tsioptsias, C; Petridis, D; Athanasakis, N; Lemonidis, I; Deligiannis, A; Samaras, P

    2015-12-01

    Molasses wastewater is a high strength effluent of food industry such as distilleries, sugar and yeast production plants etc. It is characterized by a dark brown color and exhibits a high content in substances of recalcitrant nature such as melanoidins. In this study, electrocoagulation (EC) was studied as a post treatment step for biologically treated molasses wastewater with high nitrogen content obtained from a baker's yeast industry. Iron and copper electrodes were used in various forms; the influence and interaction of current density, molasses wastewater dilution, and reaction time, on COD, color, ammonium and nitrate removal rates and operating cost were studied and optimized through Box Behnken's response surface analysis. Reaction time varied from 0.5 to 4 h, current density varied from 5 to 40 mA/cm(2) and dilution from 0 to 90% (v/v expressed as water concentration). pH, conductivity and temperature measurements were also carried out during each experiment. From preliminary experiments, it was concluded that the application of aeration and sample dilution, considerably influenced the kinetics of the process. The obtained results showed that COD removal varied between 10 and 54%, corresponding to an operation cost ranging from 0.2 to 33 euro/kg COD removed. Significant removal rates were obtained for nitrogen as nitrate and ammonium (i.e. 70% ammonium removal). A linear relation of COD and ammonium to the design parameters was observed, while operation cost and nitrate removal responded in a curvilinear function. A low ratio of electrode surface to treated volume was used, associated to a low investment cost; in addition, iron wastes could be utilized as low cost electrodes i.e. iron fillings from lathes, aiming to a low operation cost due to electrodes replacement. In general, electrocoagulation proved to be an effective and low cost process for biologically treated molasses-wastewater treatment for additional removal of COD and nitrogen content and

  20. Reproducible Analysis of Post-Translational Modifications in Proteomes—Application to Human Mutations

    PubMed Central

    Holehouse, Alex S.; Naegle, Kristen M.

    2015-01-01

    Background Protein post-translational modifications (PTMs) are an important aspect of protein regulation. The number of PTMs discovered within the human proteome, and other proteomes, has been rapidly expanding in recent years. As a consequence of the rate in which new PTMs are identified, analysis done in one year may result in different conclusions when repeated in subsequent years. Among the various functional questions pertaining to PTMs, one important relationship to address is the interplay between modifications and mutations. Specifically, because the linear sequence surrounding a modification site often determines molecular recognition, it is hypothesized that mutations near sites of PTMs may be more likely to result in a detrimental effect on protein function, resulting in the development of disease. Methods and Results We wrote an application programming interface (API) to make analysis of ProteomeScout, a comprehensive database of PTMs and protein information, easy and reproducible. We used this API to analyze the relationship between PTMs and human mutations associated with disease (based on the ‘Clinical Significance’ annotation from dbSNP). Proteins containing pathogenic mutations demonstrated a significant study bias which was controlled for by analyzing only well-studied proteins, based on their having at least one pathogenic mutation. We found that pathogenic mutations are significantly more likely to lie within eight amino acids of a phosphoserine, phosphotyrosine or ubiquitination site when compared to mutations in general, based on a Fisher’s Exact test. Despite the skew of pathogenic mutations occurring on positively charged arginines, we could not account for this relationship based only on residue type. Finally, we hypothesize a potential mechanism for a pathogenic mutation on RAF1, based on its proximity to a phosphorylation site, which represents a subtle regulation difference that may explain why its biochemical effect has failed to

  1. Analysis of Solar Wind Samples Returned by Genesis Using Laser Post Ionization Secondary Neutral Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Veryovkin, I. V.; Calaway, W. F.; Tripa, C. E.; Pellin, M. J.; Burnett, D. S.

    2005-12-01

    A new secondary neutral mass spectrometry (SNMS) instrument implementing laser post ionization (LPI) of ion sputtered and laser desorbed neutral species has been developed and constructed for the specific purpose of quantitative analysis of metallic elements at ultra trace levels in solar wind collector samples returned to Earth by the Genesis Discovery mission. The first LPI SNMS measurements are focusing on determining Al, Ca, Cr, and Mg in these samples. These measurements provide the first concentration and isotopic abundances determinations for several key metallic elements and also elucidate possible fractionation effects between the photosphere and the solar wind compositions. It is now documented that Genesis samples suffered surface contamination both during flight and during the breach of the Sample Return Capsule when it crashed. Since accurate quantitative analysis is compromised by sample contamination, several features have been built into the new LPI SNMS instrument to mitigate this difficulty. A normally-incident, low-energy (<500 eV) ion beam combined with a keV energy ion beam and a desorbing laser beam (both microfocused) enables dual beam analyses. The low-energy ion beam can be used to remove surface contaminant by sputtering with minimum ion beam mixing. This low-energy beam also will be used to perform ion beam milling, while either the microfocused ion or laser beam probes the solar wind elemental compositions as a function of sample depth. Because of the high depth resolution of dual beam analyses, such depth profiles clearly distinguish between surface contaminants and solar wind implanted atoms. In addition, in-situ optical and electron beam imaging for observing and avoiding particulates and scratches on solar wind sample surfaces is incorporated in the new LPI SNMS instrument to further reduce quantification problems. The current status of instrument tests and analyses will be presented. This work is supported by the U. S. Department of

  2. Allogeneic peripheral blood hematopoietic stem cell transplantation: guidelines for red blood cell immuno-hematological assessment and transfusion practice.Société Française de Greffe de Moelle.

    PubMed

    Lapierre, V; Kuentz, M; Tiberghien, P

    2000-03-01

    Allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) is presently being evaluated in a French randomized study comparing peripheral blood vs bone marrow. Cases of potentially lethal acute hemolysis have recently been reported after allogeneic PBSCT in the presence of a 'minor' ABO incompatibility. Patients were frequently transfused with recipient-compatible and donor-incompatible RBC and usually did not receive methotrexate in addition to cyclosporin A for graft-versus-host disease (GVHD) prophylaxis. In order to homogenize immuno-hematological (IH) assessment and transfusion practices within our protocol, we made proposals to 25 allo-transplant French centers on the following aspects: pre-inclusion IH assessment, IH exclusion criteria, transfusion rules, post-transplant IH surveillance and treatment of hemolysis. Analysis of responses to our proposals led to the elaboration of guidelines which were approved and implemented by the French Bone Marrow Transplantation Society (SFGM). Pre-inclusion IH testing includes mandatory detection and titration of anti-RBC allo-Ab, as well as titration of anti-A and anti-B Ab. The presence in the donor of an anti-A (group A or AB recipients), anti-B (group B or AB recipients) Ab with a titer >1/32 or the presence of allo-Ab against Rh, Kell, Fya, Fyb, Jka, Jkb, Ss Ag present on recipient RBC is an exclusion criterion for the protocol. ABO and RhD compatibility of RBC blood products with both HSC donor and recipient is mandatory. A similar compatibility is also required for Rh (other than D) and Kell Ag. If not possible, compatibility of RBC blood products with the HSC donor is mandatory. Lastly, guidelines regarding post-transplantation IH follow-up as well as acute hemolysis treatment have been elaborated. The implementation of these guidelines should contribute to enhancing the quality of transfusion practice after PBSCT. Such an approach will be applied to other aspects of transfusion medicine in the

  3. [Immunosuppressives to prevent rejection reactions after allogeneic corneal transplantation].

    PubMed

    Lapp, T; Maier, P; Birnbaum, F; Schlunck, G; Reinhard, T

    2014-03-01

    In order to prevent rejection of an allogeneic corneal transplant after perforating (high risk) keratoplasty, active agents from different classes of pharmacological substances are used, as with solid organ transplantation. In addition to glucocorticoids, antiproliferative agents, small molecule inhibitors and antibodies, those belonging to the group of macrolides with their many derivatives represent an interesting class of substances in this context. As a supplement to cyclosporin A (CSA) the most successful macrolide in transplantation medicine, animal experiments are currently being carried out to test newer macrolide derivatives, such as sanglifehrin A (SFA). This overview describes the classes of drugs and modes of action of currently administered standard medications in the clinical routine and new developments are presented.

  4. REDUCED INTENSITY CONDITIONING FOR ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION: CURRENT PERSPECTIVES

    PubMed Central

    Sandmaier, Brenda M.; Mackinnon, Stephen; Childs, Richard W.

    2007-01-01

    Allogeneic hematopoietic cell transplantation after myeloablative conditioning is an effective therapy for patients with hematologic malignancies. In an attempt to extend this therapy to older patients or those with comorbidities, reduced intensity or truly nonmyeloablative regimens have been developed over the last decade. The principle underlying reduced intensity regimens is to provide some tumor kill with lessened regimen-related morbidity and mortality, then rely on graft-versus-tumor (GVT) effects to eradicate remaining malignant cells, while nonmyeloablative regimens rely primarily on GVT effects. In this article, three representative approaches are described, demonstrating the clinical application for both hematopoietic and non-hematopoietic malignancies. Current challenges include controlling graft-versus-host disease while allowing GVT to occur. In the future, clinical trials using reduced intensity and nonmyeloablative conditioning will be compared to myeloablative conditioning in selected malignancies to extend the application to standard risk patients. PMID:17222778

  5. A Unique Case of Allogeneic Fat Grafting Between Brothers

    PubMed Central

    Kim, Samuel; Edelson, Richard L.; Sumpio, Brandon; Kwei, Stephanie

    2016-01-01

    Summary: We present a case of a 65-year-old man with cutaneous T-cell lymphoma treated with radiation therapy and an allogeneic hematopoietic stem cell transplant from his human leukocyte antigen-matched brother. Engraftment was successful, but the patient went on to develop painful, radiation-induced ulcers. The ulcers were fat-allografted using liposuctioned fat from his brother because of the patient’s unique chimeric state. Postprocedure follow-up revealed epithelialization of the ulcer sites and significant improvement in neuropathic pain. Our unique case study supports the use of fat grafting for its restorative purposes and for its ability to alleviate chronic neuropathic pain. Additionally, it appears that our case provides a basis of a general approach to the treatment of radiation-induced ulcers in chimeric patients with lymphoid malignancies. PMID:27757347

  6. Bullous pemphigoid after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Kato, Keisuke; Koike, Kazutoshi; Kobayashi, Chie; Iijima, Shigeruko; Hashimoto, Takashi; Tsuchida, Masahiro

    2015-06-01

    Bullous pemphigoid (BP) is an autoimmune skin disorder characterized by subepidermal blisters due to deposit of autoantibody against dermal basement membrane protein. It has been reported that BP can occur after allogeneic hematopoietic stem cell transplantation (HSCT). We describe a patient with BP having autoantibody against BP180 after unrelated-donor HSCT against T lymphoblastic leukemia. The patient was treated with steroid leading to complete resolution of BP, but T lymphoblastic leukemia progressed rapidly after steroid hormone treatment. Given that immunosuppressant may reduce graft-versus-tumor effect, immunomodulatory agents such as nicotinamide and tetracycline, erythromycin, and immunoglobulin may be appropriate as soon as typical blister lesions are seen after HSCT. PMID:26113316

  7. Allogeneic transplantation in the UK: an aggregation of marginal gains?

    PubMed

    Thomson, Kirsty J; Peggs, Karl S

    2013-10-01

    A number of advances in clinical practice that are considered routine in modern allogeneic transplant programmes lack definitive supporting evidence, partly because they may offer modest incremental benefits that are difficult to demonstrate in a statistically robust manner given the relatively small cohorts of patients who undergo such procedures. Nevertheless, these marginal gains probably contribute therapeutically meaningful overall benefit, particularly when aggregated. We review the evidence for a number of these practices in terms of impact on transplant outcomes, with particular reference to the setting of T cell depletion as widely practiced in the United Kingdom, including high resolution tissue typing, surveillance for and therapy of infectious complications, chimerism-directed immune modulation and more sensitive monitoring for residual or progressive disease.

  8. Harnessing Reconsolidation to Weaken Fear and Appetitive Memories: A Meta-Analysis of Post-Retrieval Extinction Effects

    PubMed Central

    Kredlow, M. Alexandra; Unger, Leslie D.; Otto, Michael W.

    2015-01-01

    A new understanding of the mechanisms of memory retrieval and reconsolidation holds the potential for improving exposure-based treatments. Basic research indicates that following fear extinction, safety and fear memories may compete, raising the possibility of return of fear. One possible solution is to modify original fear memories through reconsolidation interference, reducing the likelihood of return of fear. Post-retrieval extinction is a behavioral method of reconsolidation interference that has been explored in the context of conditioned fear and appetitive memory paradigms. This meta-analysis examines the magnitude of post-retrieval extinction effects and potential moderators of these effects. A PubMed and PsycINFO search was conducted through June 2014. Sixty-three comparisons examining post-retrieval extinction for preventing the return of fear or appetitive responses in animals or humans met inclusion criteria. Post-retrieval extinction demonstrated a significant, small-to-moderate effect (g = .40) for further reducing the return of fear in humans and a significant, large effect (g = 0.89) for preventing the return of appetitive responses in animals relative to standard extinction. For fear outcomes in animals, effects were small (g = 0.21) and non-significant, but moderated by the number of animals housed together and the duration of time between post-retrieval extinction/extinction and test. Across paradigms, these findings support the efficacy of this pre-clinical strategy for preventing the return of conditioned fear and appetitive responses. Overall, findings to date support the continued translation of post-retrieval extinction research to human and clinical applications, with particular application to the treatment of anxiety, traumatic stress, and substance use disorders. PMID:26689086

  9. Allogeneic versus xenogeneic immune reaction to bioengineered skin grafts.

    PubMed

    Erdag, Gulsun; Morgan, Jeffrey R

    2004-01-01

    There are conflicting reports on the survival and immune reaction to allografts and xenografts of cultured skin substitutes (CSS). In this study, we investigated the allogeneic and xenogeneic responses to CSS of human keratinocytes and genetically engineered CSS expressing keratinocyte growth factor (KGF) that forms a hyperproliferative epidermis. CSS (control and KGF modified) and neonatal human foreskins were evaluated by immunohistochemistry for the expression of MHC class I and II. To study allograft rejection, grafts were transplanted to human peripheral blood mononuclear cell (huPBMC)-reconstituted SCID mice. To study xenograft rejection, grafts were transplanted to immunocompetent mice. Graft survival and immune reaction were assessed visually and microscopically. After transplantation, control CSS formed a normal differentiated epidermis, whereas KGF CSS formed a hyperproliferative epidermis. Control and KGF CSS expressed class I similar to neonatal foreskin, but did not express class II. In the allograft model, rejection of neonatal foreskins was between 5 and 9 days. In contrast, neither control nor KGF CSS was rejected by huPBMC-SCID mice. Histology showed dense mononuclear cell infiltration in human foreskins, with few, if any, mononuclear cells in control or KGF CSS. In contrast to the allogeneic reaction, CSS (control and KGF) were rejected in the xenograft model, but rejection was delayed (9-21 days) compared with neonatal skin (5-8 days). Humanized SCID mice rejected allografts of human neonatal foreskins, but did not reject control CSS or KGF CSS, even though the KGF CSS formed a hyperproliferative epidermis. Rejection of control and KGF CSS by immunocompetent mice in a xenograft model was comparable and their survival was significantly prolonged compared with neonatal skin. These results demonstrate that control CSS and hyperproliferative KGF CSS are less immunogenic than normal human skin and that sustained hyperproliferation of the epidermis

  10. Survival prolongation of microencapsulated allogeneic islet by nanosized nordihydroguaiaretic acid.

    PubMed

    Yang, T-Y; Chen, J-P; Ku, K-W; Fu, S-H; Hsu, B R-S

    2005-05-01

    Immunoisolation such as alginate-poly-L-lysine-alginate (APA) microencapsulation may protect entrapped islet graft cells from destruction by cellular and humoral immunities, but cannot avoid aggregation of macrophages and fibroblasts around microcapsules, which has been known to cause late dysfunction. Nordihydroguaiaretic acid (NDGA) is a lipoxygenase inhibitor that prevents the activation and chemotaxis of macrophages. In this study, we used the dialysis method without surfactant to prepare poly (DL-lactide-co-glycolide) (PLGA) nanoparticles to entrap NDGA. We determined the formulation conditions suitable for sustained release when coencapsulated with the islets. Nanoparticle sizes of 0.2-0.3 microm were suitable for sustained release in electromagnetic driven APA microcapsules. In the toxicity study, we coincubated islets with PLGA-NDGA nanoparticles in vitro for 2 and 4 weeks. The glucose stimulated insulin secretion and insulin contents of islets were not influenced significantly. To test whether nanosized NDGA provides extra protection for APA islets, about 160-200 allogeneic islets of C57BL/6 mice were either encapsulated alone using APA or coencapsulated with PLGA-NDGA. At 2 and 4 weeks after implantation into the peritoneal cavities of healthy BALB/c mice, the intraperitoneal islet grafts were recovered using lavage. Mice that received islets of APA-PLGA-NDGA preparations showed a higher recovery rate of functioning grafts than those that received islets prepared using APA alone (10.1%, n = 4 vs 5.2%, n = 3). In conclusion, nanosized NDGA prolonged the graft survival of APA microencapsulated allogeneic islets.

  11. New insights into the electrode mechanism of lithium sulfur batteries via air-free post-test analysis.

    PubMed

    Chen, Lin; Dietz Rago, Nancy L; Bloom, Ira D; Shaw, Leon L

    2016-08-01

    Effects of the volume expansion and shrinkage of Li2S cathodes on electrochemical cycle life are investigated via post-test analysis without exposure to air. The engineered electrodes that confine volume changes within micro-reactors have significantly longer life than the electrodes without the micro-reactor structure, providing the first unambiguous evidence of the importance of confining volume changes for improved battery performance. PMID:27430393

  12. A Post Hoc Analysis of D-Threo-Methylphenidate Hydrochloride (Focalin) Versus D,l-Threo-Methylphenidate Hydrochloride (Ritalin)

    ERIC Educational Resources Information Center

    Weiss, Margaret; Wasdell, Michael; Patin, John

    2004-01-01

    Objective: To evaluate clinical measures of the benefit/risk ratio in a post hoc analysis of a clinical trial of d-threo-methylphenidate hydrochloride (d-MPH) and d,l-threo-methylphenidate hydrochloride (d,l-MPH). Method: Data from a phase III clinical trial was used to compare equimolar doses of d-MPH and d,l-MPH treatment for…

  13. Thermal Analysis of Post-eruption Loops from 80,000 to 1.6 million K

    NASA Technical Reports Server (NTRS)

    Kucera, T.; Landi, E.

    2006-01-01

    We analyze the thermal properties of a set of post eruptive loops which appeared after a prominence eruption on April 30, 2004. The event was observed by TRACE and SOHO/SUMER. The SUMER data was taken from a single slit location with a 90 second cadence and included a number of lines spanning the temperature range 80,000 to 1.6 million K. We perform a differential emission measure analysis of the loops in order to study their thermal evolution.

  14. Allogeneic bone marrow transplantation for postpolycythemic myeloid metaplasia with myelofibrosis: a case report.

    PubMed

    de Revel, T; Giraudier, S; Nedellec, G; Joussemet, M; Bourin, P; Schill, H; Gaillard, J F; Auzanneau, G

    1995-07-01

    Myeloid metaplasia with myelofibrosis develops in about 10% of patients with polycythemia vera. We report a case of a 48-year-old female with postpolycythemic myelofibrosis successfully treated with allogeneic HLA-matched bone marrow transplantation.

  15. Experimental validation of finite element model analysis of a steel frame in simulated post-earthquake fire environments

    NASA Astrophysics Data System (ADS)

    Huang, Ying; Bevans, W. J.; Xiao, Hai; Zhou, Zhi; Chen, Genda

    2012-04-01

    During or after an earthquake event, building system often experiences large strains due to shaking effects as observed during recent earthquakes, causing permanent inelastic deformation. In addition to the inelastic deformation induced by the earthquake effect, the post-earthquake fires associated with short fuse of electrical systems and leakage of gas devices can further strain the already damaged structures during the earthquakes, potentially leading to a progressive collapse of buildings. Under these harsh environments, measurements on the involved building by various sensors could only provide limited structural health information. Finite element model analysis, on the other hand, if validated by predesigned experiments, can provide detail structural behavior information of the entire structures. In this paper, a temperature dependent nonlinear 3-D finite element model (FEM) of a one-story steel frame is set up by ABAQUS based on the cited material property of steel from EN 1993-1.2 and AISC manuals. The FEM is validated by testing the modeled steel frame in simulated post-earthquake environments. Comparisons between the FEM analysis and the experimental results show that the FEM predicts the structural behavior of the steel frame in post-earthquake fire conditions reasonably. With experimental validations, the FEM analysis of critical structures could be continuously predicted for structures in these harsh environments for a better assistant to fire fighters in their rescue efforts and save fire victims.

  16. Radar rainfall estimation in the context of post-event analysis of flash-flood events

    NASA Astrophysics Data System (ADS)

    Delrieu, G.; Bouilloud, L.; Boudevillain, B.; Kirstetter, P.-E.; Borga, M.

    2009-09-01

    This communication is about a methodology for radar rainfall estimation in the context of post-event analysis of flash-flood events developed within the HYDRATE project. For such extreme events, some raingauge observations (operational, amateur) are available at the event time scale, while few raingauge time series are generally available at the hydrologic time steps. Radar data is therefore the only way to access to the rainfall space-time organization, but the quality of the radar data may be highly variable as a function of (1) the relative locations of the event and the radar(s) and (2) the radar operating protocol(s) and maintenance. A positive point: heavy rainfall is associated with convection implying better visibility and lesser bright band contamination compared with more current situations. In parallel with the development of a regionalized and adaptive radar data processing system (TRADHy; Delrieu et al. 2009), a pragmatic approach is proposed here to make best use of the available radar and raingauge data for a given flash-flood event by: (1) Identifying and removing residual ground clutter, (2) Applying the "hydrologic visibility" concept (Pellarin et al. 2002) to correct for range-dependent errors (screening and VPR effects for non-attenuating wavelengths, (3) Estimating an effective Z-R relationship through a radar-raingauge optimization approach to remove the mean field bias (Dinku et al. 2002) A sensitivity study, based on the high-quality volume radar datasets collected during two intense rainfall events of the Bollène 2002 experiment (Delrieu et al. 2009), is first proposed. Then the method is implemented for two other historical events occurred in France (Avène 1997 and Aude 1999) with datasets of lesser quality. References: Delrieu, G., B. Boudevillain, J. Nicol, B. Chapon, P.-E. Kirstetter, H. Andrieu, and D. Faure, 2009: Bollène 2002 experiment: radar rainfall estimation in the Cévennes-Vivarais region, France. Journal of Applied

  17. Statistical analysis of eruptive vent distribution from post-subduction monogenetic fields in Baja California, Mexico

    NASA Astrophysics Data System (ADS)

    Germa, A.; Cañon-Tapia, E.; Connor, L.; Le Corvec, N.

    2012-04-01

    Volcanism in Baja California (BC, Mexico) was active from the end of the subduction of the Farallon plate (12.5Ma) until recently (< 1Ma). Most of this volcanism formed twelve volcanic fields, seven of them being monogenetic, delineating a ~600-km-long array parallel to the Gulf of California. Previous studies on these fields have focused on the compositional diversity of magmatic products. Although geochemistry and ages of few lava flows are constrained, only two studies investigated the spatial distribution of the eruptive vents of San Borja. Within a monogenetic volcanic field, cone alignments and linear arrays are considered to reflect the geometry of feeder dikes formed either parallel to the maximum principal stress (σ1) in the lithosphere or using pre-existing crustal fractures. These intrinsic local structures will be compared with the shape of the field, which could reflect the shape of the source at depth. Using satellite imagery to define the location of eruptive centres on four monogenetic volcanic fields from central Baja California (Jaraguay, San Borja, Santa Clara, and San Ignacio), we completed statistical analyses of their spatial distribution. Using commercially available GIS software, spatial density analysis, and statistical scripts, each volcanic field was analysed for the number and density of vents, clustering, vent spacing and alignment azimuths. Our preliminary results reveal that vent densities are within the range of 0.001 to 0.2 vents / 100 km2. Eruptive vents are generally clustered, with density higher than 0.1 vents/100 km2. A common elongation direction trends N135° to N152° in most clusters and fields. We thus propose a NW-SE direction as the preferred orientation of the maximum principal stress (σ1), direction that needs to be confirmed by azimuths of the vents alignments. Using a combination of different computational methods, this study allows to quantify the influence of tectonic stresses at the deep and shallow level within

  18. [Medicolegal experiences in external post-mortem examinations before cremation--a retrospective analysis of the years 1998-2008].

    PubMed

    Eckstein, Philipp; Schyma, Christian; Madea, Burkhard

    2010-01-01

    The paper presents a retrospective analysis of 16,541 external post-mortem examinations carried out before cremation by the Institute of Forensic Medicine of the University of Bonn between 1998 and 2008 with regard to different variables (age, sex, place of death, cause of death etc.). In more than 50 % of cases, the individuals had died in a hospital followed by their apartment or a nursing home. The first post-mortem examination was mainly performed by hospital doctors followed by emergency doctors and office practitioners. As to the age distribution, the 6th to 8th decade of life was prevalent. In 99.8 %, a natural death was certified in the first external post-mortem and only in 0.2 % the manner of death was determined to be non-natural or unclear. In more than half of the cases, the non-natural deaths were determined by emergency doctors. Deaths wrongly classified in the first external post-mortem were mostly accidents and deaths associated with medical procedures. Although the second external examination before cremation is very useful in detecting previously overlooked signs of homicide, it is only of limited value in homicides with few external traces or for detecting underlying diseases and causes of death. In this respect, the second external examination before cremation can only check the plausibility of the cause of death given by the attending physician. The gold standard for a reliable certification of the manner and cause of death remains the autopsy.

  19. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion

    PubMed Central

    Henry, David A; Carless, Paul A; Moxey, Annette J; O’Connell, Dianne; Stokes, Barrie J; Fergusson, Dean A; Ker, Katharine

    2014-01-01

    Background Concerns regarding the safety of transfused blood have led to the development of a range of interventions to minimise blood loss during major surgery. Anti-fibrinolytic drugs are widely used, particularly in cardiac surgery, and previous reviews have found them to be effective in reducing blood loss, the need for transfusion, and the need for re-operation due to continued or recurrent bleeding. In the last few years questions have been raised regarding the comparative performance of the drugs. The safety of the most popular agent, aprotinin, has been challenged, and it was withdrawn from world markets in May 2008 because of concerns that it increased the risk of cardiovascular complications and death. Objectives To assess the comparative effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) on blood loss during surgery, the need for red blood cell (RBC) transfusion, and adverse events, particularly vascular occlusion, renal dysfunction, and death. Search methods We searched: the Cochrane Injuries Group’s Specialised Register (July 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 3), MEDLINE (Ovid SP) 1950 to July 2010, EMBASE (Ovid SP) 1980 to July 2010. References in identified trials and review articles were checked and trial authors were contacted to identify any additional studies. The searches were last updated in July 2010. Selection criteria Randomised controlled trials (RCTs) of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. Eligible trials compared anti-fibrinolytic drugs with placebo (or no treatment), or with each other. Data collection and analysis Two authors independently assessed trial quality and extracted data. This version of the review includes a sensitivity analysis excluding trials authored by Prof. Joachim Boldt. Main results This review summarises data from 252 RCTs that recruited over 25,000 participants. Data from

  20. Mouse host unlicensed NK cells promote donor allogeneic bone marrow engraftment

    PubMed Central

    Alvarez, Maite; Sun, Kai

    2016-01-01

    Natural killer (NK) cells exist as subsets based on expression of inhibitory receptors that recognize major histocompatibility complex I (MHCI) molecules. NK cell subsets bearing MHCI binding receptors for self-MHCI have been termed as “licensed” and exhibit a higher ability to respond to stimuli. In the context of bone marrow transplantation (BMT), host licensed-NK (L-NK) cells have also been demonstrated to be responsible for the acute rejection of allogeneic and MHCI-deficient BM cells (BMCs) in mice after lethal irradiation. However, the role of recipient unlicensed-NK (U-NK) cells has not been well established with regard to allogeneic BMC resistance. After NK cell stimulation, the prior depletion of host L-NK cells resulted in a marked increase of donor engraftment compared with the untreated group. Surprisingly, this increased donor engraftment was reduced after total host NK cell depletion, indicating that U-NK cells can actually promote donor allogeneic BMC engraftment. Furthermore, direct coculture of U-NK cells with allogeneic but not syngeneic BMCs resulted in increased colony-forming unit cell growth in vitro, which was at least partially mediated by granulocyte macrophage colony-stimulating factor (GM-CSF) production. These data demonstrate that host NK cell subsets exert markedly different roles in allogeneic BMC engraftment where host L- and U-NK cells reject or promote donor allogeneic BMC engraftment, respectively. PMID:26738538

  1. Principles of Leading Change: An Inductive Analysis from Post-Katrina New Orleans

    ERIC Educational Resources Information Center

    Beabout, Brian R.

    2014-01-01

    Despite over forty years of research on theories of educational change, little is known of the change theories-in-use of school-based administrators, often tasked with implementing externally imposed reform mandates. Capitalizing on the unique case of post-Katrina schooling, this qualitative study examines the ways in which ten principals spoke…

  2. Transformation or Continuation? A Critical Analysis of the Making of the Post-2015 Education Agenda

    ERIC Educational Resources Information Center

    Enns, Charis

    2015-01-01

    As the target date of 2015 draws near for both the Education for All and Millennium Development Goals, consultations are well-underway to begin defining the shape and scope of the post-2015 development agenda. Between September 2012 and March 2013, UN Member States, private sector representatives, multilateral development agencies, epistemic…

  3. Educational Participation Post-16: A Longitudinal Analysis of Intentions and Outcomes

    ERIC Educational Resources Information Center

    Croll, Paul

    2009-01-01

    The issue of levels of participation in post-compulsory education has been emphasised by the current policy initiatives to increase the age to which some form of participation is compulsory. One of the acknowledged weaknesses of research in the field of children's intentions with regard to participation is the lack of longitudinal data. This paper…

  4. Integrated Education and Black Development in Post-apartheid South Africa: A Critical Analysis.

    ERIC Educational Resources Information Center

    Abdi, Ali A.

    2001-01-01

    Focuses on the problems of education and development in post-apartheid South Africa. Argues that there must be a focus on the uneven terrain of educational attainment and long term socio-economic development. Discusses factors hindering educational development. Calls for reconstitution of South Africa's educational programs for all citizens. (CAJ)

  5. Supportive Distortions: An Analysis of Posts on a Pedophile Internet Message Board

    ERIC Educational Resources Information Center

    Malesky, L. Alvin, Jr.; Ennis, Liam

    2004-01-01

    A covert observation of posts on a pro-pedophile Internet message board investigated evidence of distorted cognitions that were supportive of sexually abusive behavior. Implications for the treatment and supervision of members of online communities that support pedophilic interests and behaviors are discussed. The purpose of the present study was…

  6. The Overlap between Emotional Intelligence and Post-Industrial Leadership Capacity: A Construct Validity Analysis

    ERIC Educational Resources Information Center

    Rosch, David M.; Joseph, Dana L.; Newman, Daniel A.

    2011-01-01

    A sample of 276 students enrolled in campus leadership programs completed the Emotional Competence Inventory-University Edition (ECI-U) and the Socially Responsible Leadership Scale (SRLS) as a means to determine the relatedness in college students of emotional intelligence (EI) to the practice of post-industrial leadership skills. Confirmatory…

  7. E3 10C compressor test analysis of high-speed post-stall data

    NASA Technical Reports Server (NTRS)

    Dvorak, S. D.; Hosny, W. M.; Steenken, W. G.

    1986-01-01

    In-stall characteristics from high-speed post-stall transients are determined. The transient, surge-cycle nature of high-speed post-stall operation precludes the possibility of obtaining in-stall characteristics in a steady-state manner, as is possible during low-speed post-stall operation, which is characterized by quasi-steady rotating-stall behavior. Maximum likelihood parameter estimation techniques were used to obtain the quasi-steady high-speed characteristics from transient data. The necessary data was first obtained from a specially instrumented compressor that was tested well beyond its limits of normal operation. The unsteady, post-stall data thus obtained was then digitized and processed through a simplified analytical model to construct the input-output relationship necessary for estimation. In-stall characteristics were determined using this estimation procedure at two different high-speed conditions, 90 and 98.5 percent corrected speed. The estimated characteristics were found to be robust in the presence of measurement noise and unmodelled system dynamics, but the compressor response-time constants, also estimated, were more sensitive to these same disturbances. The experimentally determined low-speed in-stall characteristics and the estimated high-speed in-stall characteristics were then incorporated into a one-dimensional compressor simulation model developed as a parallel effort to the compressor testing and data reduction effort, which yielded predictable results.

  8. Adoption and guardianship: A moderated mediation analysis of predictors of post-permanency continuity.

    PubMed

    Testa, Mark F; Snyder, Susan M; Wu, Qi; Rolock, Nancy; Liao, Minli

    2015-03-01

    The original thinking behind permanency planning for foster children was to secure a caregiver's intention to provide a permanent home, not to guarantee it. Little is known, however, about how intentions change after permanence or what effect this change has on post-permanency continuity of care. This study examined the mediating effects of caregivers' thoughts about ending an adoption or guardianship, and how this mechanism may be contingent on primordial and bureaucratic factors that child welfare agencies rely on to ensure family continuity after legal permanence. In 2006, a sample of 346 Illinois caregivers who finalized an adoption or guardianship between 1998 and 2002 completed surveys about child behavior problems, the adequacy of financial assistance, and thoughts about maintaining the permanency relationship. Responses were linked to administrative data that tracked continuity of care through 2012. Simple mediation and moderated mediation hypotheses of the effects of caregiver thoughts on post-permanency continuity were tested. At last observation, 8% of caregivers were no longer living with the child or stopped receiving subsidies on the child's behalf. Thoughts expressed at survey time about ending the permanency relationship mediated the effect of child behavior problems on post-permanency discontinuity rates. This indirect effect was more pronounced among distantly related kin, lone caregivers, and caregivers who felt the subsidy was inadequate to cover their expenses. Our findings suggest that post-permanency services should target a narrow segment of caregivers who express weakened permanency commitments that arise from the challenges of parenting a child with multiple behavioral problems.

  9. Evaluation of an Innovative Post-Arrest Diversion Program: 12-Month Recidivism Analysis

    ERIC Educational Resources Information Center

    Dembo, Richard; Walters, Wansley; Wareham, Jennifer; Burgos, Catherimarty; Schmeidler, James; Hoge, Robert; Underwood, Lee

    2008-01-01

    We report the results of an evaluation study of a diversion program, operated by the Miami-Dade County Juvenile Assessment Center in Florida. The Post-Arrest Diversion (PAD) program represents an innovative approach to treatment and intervention within the juvenile justice system that utilizes standardized psychosocial risks and needs assessment…

  10. Factor Analysis of Aviation Training Measures and Post-Training Performance Evaluations.

    ERIC Educational Resources Information Center

    Booth, Richard F.; Berkshire, James R.

    The purpose of this study was to relate the factor structure of naval air training measures to the performance of Marine pilots in operational squadrons. Five post-training criteria were developed; four were Commanding Officer (C.O.) nominations of junior officers for hypothetical special assignments, and the fifth was a general…

  11. ORNL ADCP POST-PROCESSING GUIDE AND MATLAB ALGORITHMS FOR MHK SITE FLOW AND TURBULENCE ANALYSIS

    SciTech Connect

    Gunawan, Budi; Neary, Vincent S

    2011-09-01

    Standard methods, along with guidance for post-processing the ADCP stationary measurements using MATLAB algorithms that were evaluated and tested by Oak Ridge National Laboratory (ORNL), are presented following an overview of the ADCP operating principles, deployment methods, error sources and recommended protocols for removing and replacing spurious data.

  12. Slovak Preschool Curriculum Reform and Teachers' Emotions: An Analysis of Facebook Posts

    ERIC Educational Resources Information Center

    Kascak, O.; Pupala, B.; Mbugua, T.

    2016-01-01

    The school system in the Slovak Republic, as in other post-communist countries, was first reformed at the beginning of the 1990s. It was not until 2008, when an education law was adopted to set out new parameters for creating a national curriculum at all levels, that fundamental curricular reforms were made. Thus the law also meant that preschool…

  13. Decolonizing Education: A Critical Discourse Analysis of Post-Secondary Humanities Textbooks

    ERIC Educational Resources Information Center

    Harper, Kimberly C.

    2012-01-01

    This dissertation examines nine post-secondary humanities textbooks published between 2001 and 2011 using an approach that includes both qualitative and quantitative methodology to analyze the written and visual content of humanities textbooks. This dissertation engages in current debates that address bias in humanities textbooks and contributes…

  14. Pre-treatment of allogeneic bone marrow recipients with the CXCR4 antagonist AMD3100 transiently enhances hematopoietic chimerism without promoting donor-specific skin allograft tolerance.

    PubMed

    Li, Zhanzhuo; Xu, Xin; Weiss, Ido D; Jacobson, Orit; Murphy, Philip M

    2015-10-01

    Hematopoietic chimerism established by allogeneic bone marrow transplantation is known to promote donor-specific organ allograft tolerance; however, clinical application is limited by the need for toxic host conditioning and "megadoses" of donor bone marrow cells. A potential solution to this problem has been suggested by the observation that recipient bone marrow mobilization by the CXCR4 antagonist AMD3100 promotes chimerism in congenic bone marrow transplantation experiments in mice. Here we report that a single subcutaneous dose of 10 mg/kg AMD3100 in recipient C57BL/6 mice was able to enhance hematopoietic chimerism when complete MHC-mismatched BALB/c donor bone marrow cells were transplanted 1h after drug dosing. However, levels of chimerism measured 30 days post-transplantation were not sustained when mice were reexamined on day 90 post-transplantation. Moreover, transient chimerism induced by this protocol did not support robust donor-specific skin allograft tolerance. Using the same transient immunosuppression protocol, we confirmed that "megadoses" of donor bone marrow cells could induce durable chimerism associated with donor-specific skin allograft tolerance without AMD3100 pre-treatment. We conclude that in this protocol AMD3100 pretreatment may empty bone marrow niches that become reoccupied by allogeneic donor hematopoietic progenitor cells but not by true long-lived donor hematopoietic stem cells, resulting in short-lived chimerism and failure to support durable donor-specific allograft tolerance.

  15. T-cell receptor excision circle levels after allogeneic stem cell transplantation are predictive of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome.

    PubMed

    Uzunel, Mehmet; Sairafi, Darius; Remberger, Mats; Mattsson, Jonas; Uhlin, Michael

    2014-07-15

    In this retrospective study, 209 patients with malignant disease were analyzed for levels of T-cell receptor excision circles (TRECs) for the first 24 months after allogeneic stem cell transplantation. CD3(+) cells were separated by direct antibody-coupled magnetic beads, followed by DNA extraction according to a standard protocol. The δRec-ψJα signal joint TREC was measured with real-time quantitative PCR. Patients were grouped based on malignant disease: chronic myeloid leukemia, chronic lymphatic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndrome (MDS). Patients were further subdivided based on TREC levels below (low-TREC) or above (high-TREC) median at each time point. TREC levels were then correlated to relapse incidence and relapse-free survival (RFS). For patients with AML, low TREC levels 2 months post-transplantation were correlated to high relapse incidence at 5 years (P<0.05). In patients with chronic leukemia, high TREC levels were correlated with improved RFS (P<0.05). For patients with MDS, high TREC levels at 9 months post-transplantation were associated with higher RFS at 5 years (P<0.02) and lower relapse incidence (P<0.02). This study shows the potential use of TREC measurement in blood to predict relapse in patients with AML and MDS after allogeneic hematopoietic stem cell transplantation. PMID:24617310

  16. DNA profiling in peripheral blood, buccal swabs, hair follicles and semen from a patient following allogeneic hematopoietic stem cells transplantation

    PubMed Central

    LI, YA-TING; XIE, MING-KUN; WU, JIN

    2014-01-01

    Allogeneic peripheral blood stem cells transplantation (allo-PBSCT) or allogeneic bone marrow transplantation (allo-BMT) have been widely used to treat patients exhibiting certain severe illnesses. However, previous studies have shown that the biological materials of allo-PBSCT or allo-BMT recipients may not constitute credible materials for personal identification. In the present study, four types of commonly used samples were collected from a male individual following gender-matched allo-BMT. Autosomal short tandem repeat (STR) and Y-STR markers analysis, based on polymerase chain reaction, were used to evaluate the chimerism status. The results showed that the blood sample were all donor type, the buccal swab sample were mixed chimerism, and the sperm and hair follicle samples maintained a recipient origin of 100%. In conclusion, identical results were obtained by the two methods and it was confirmed that DNA extracted from hair follicles and sperm can be used as a reference for the pre-transplant genotype DNA profile of the recipient in the gender-match allo-BMT or -PBSCT. PMID:25279149

  17. Human tonsil-derived mesenchymal stromal cells enhanced myelopoiesis in a mouse model of allogeneic bone marrow transplantation

    PubMed Central

    Ryu, Jung-Hwa; Park, Minhwa; Kim, Bo-Kyung; Kim, Yu-Hee; Woo, So-Youn; Ryu, Kyung-Ha

    2016-01-01

    Mesenchymal stromal cells (MSCs) have therapeutic potential for repairing tissue damage and are involved in immune regulation. MSCs are predominantly isolated from bone marrow (BM), adipose tissue or placental tissue. Further to these well-known sources, the isolation of MSCs from human tonsils was previously reported. The aim of the present study was to investigate a potential role for tonsil-derived MSCs (T-MSCs) in BM reconstitution and application towards supplementing hematopoiesis in a mouse model of BM transplantation (BMT). Eight-week-old BALB/c female mice received 80 mg/kg busulfan (Bu)/200 mg/kg cyclophosphamide (Cy) conditioning chemotherapy for BM ablation. Subsequently, human T-MSCs were injected into the Bu/Cy-treated mice with or without BM cells (BMCs) obtained from allogeneic C57BL/6 male mice. After 3 weeks, peripheral blood and BM was collected for analysis. The red blood cell count in the group that received BMCs had almost returned to normal, whereas mononuclear cell counts and BM cellularity were most improved in the T-MSCs + BMCs group. These results indicate that the T-MSCs enhanced myelopoiesis in the allogeneic BMT mouse model, as evidenced by the restoration of BM with hematopoietic cells, as well as increased myeloid colony formation in vitro. Therefore, T-MSCs may provide a source of MSCs to facilitate myelopoiesis and megakaryocytosis following BMT. PMID:27511380

  18. Slowly Delivered Icariin/Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells to Promote the Healing of Calvarial Critical-Size Bone Defects

    PubMed Central

    Liu, Tianlin; Luo, Yuan

    2016-01-01

    Bone tissue engineering technique is a promising strategy to repair large-volume bone defects. In this study, we developed a 3-dimensional construct by combining icariin (a small-molecule Chinese medicine), allogeneic bone marrow-derived mesenchymal stem cells (BMSCs), and a siliceous mesostructured cellular foams-poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (SMC-PHBHHx) composite scaffold. We hypothesized that the slowly released icariin could significantly promote the efficacy of SMC-PHBHHx/allogeneic BMSCs for repairing critical-size bone defects in rats. In in vitro cellular experiments, icariin at optimal concentration (10−6 mol/L) could significantly upregulate the osteogenesis- and angiogenesis-related genes and proteins, such as Runx2, ALP, osteocalcin, vascular endothelial growth factors, and fibroblast growth factors, as well as the mineralization of BMSCs. Icariin that was adsorbed onto the SMC-PHBHHx scaffold showed a slow release profile within a 2-week monitoring span. Eight weeks after implantation in calvarial critical-size bone defects, the constructs with icariin were associated with significantly higher bone volume density, trabecular thickness, trabecular number, and significantly lower trabecular separation than the constructs without icariin. Histomorphometric analysis showed that icariin was also associated with a significantly higher density of newly formed blood vessels. These data suggested a promising application potential of the icariin/SMC-PHBHHx/allogeneic BMSCs constructs for repairing large-volume bone defects in clinic. PMID:27721833

  19. Comparative classification analysis of post-harvest growth detection from terrestrial LiDAR point clouds in precision agriculture

    NASA Astrophysics Data System (ADS)

    Koenig, Kristina; Höfle, Bernhard; Hämmerle, Martin; Jarmer, Thomas; Siegmann, Bastian; Lilienthal, Holger

    2015-06-01

    In precision agriculture, detailed geoinformation on plant and soil properties plays an important role, e.g., in crop protection or the application of fertilizers. This paper presents a comparative classification analysis for post-harvest growth detection using geometric and radiometric point cloud features of terrestrial laser scanning (TLS) data, considering the local neighborhood of each point. Radiometric correction of the TLS data was performed via an empirical range-correction function derived from a field experiment. Thereafter, the corrected amplitude and local elevation features were explored regarding their importance for classification. For the comparison, tree induction, Naive Bayes, and k-Means-derived classifiers were tested for different point densities to distinguish between ground and post-harvest growth. The classification performance was validated against highly detailed RGB reference images and the red edge normalized difference vegetation index (NDVI705), derived from a hyperspectral sensor. Using both geometric and radiometric features, we achieved a precision of 99% with the tree induction. Compared to the reference image classification, the calculated post-harvest growth coverage map reached an accuracy of 80%. RGB and LiDAR-derived coverage showed a polynomial correlation to NDVI705 of degree two with R2 of 0.8 and 0.7, respectively. Larger post-harvest growth patches (>10 × 10 cm) could already be detected by a point density of 2 pts./0.01 m2. The results indicate a high potential of radiometric and geometric LiDAR point cloud features for the identification of post-harvest growth using tree induction classification. The proposed technique can potentially be applied over larger areas using vehicle-mounted scanners.

  20. The Impact of a Science Qualification Emphasising Scientific Literacy on Post-compulsory Science Participation: An analysis using national data

    NASA Astrophysics Data System (ADS)

    Homer, Matt; Ryder, Jim

    2015-06-01

    In 2006 in England an innovative suite of science qualifications for 14-16-year-olds called Twenty-First Century Science (21CS) was introduced. These qualifications have a strong focus on developing scientific literacy in all students whilst simultaneously providing preparation for the study of post-compulsory science for a smaller proportion of students. Claims have been made that such an innovative qualification would impact significantly on post-compulsory science participation-either positively or negatively. Using national data in England to track one cohort of students over 2007-2011, this study compares progression rates to post-compulsory science qualifications in England between 21CS qualifications and more traditional non-21CS qualifications. Methods employed include simple comparisons of proportions progressing from each qualification, and more complex multi-level modelling approaches that take account of both students clustered in schools, and potentially differing demographic and achievement profiles of students in the 2 groups of qualifications. A simple descriptive analysis shows that there is very little difference in overall progression rates between the 2 types of 14-16 science qualification. More fine-grained descriptive analyses show that there are some important differences, based in particular on the interaction between the amount of science studied at ages 14-16, and on the post-16 science qualification chosen (biology, chemistry or physics). Furthermore, sophisticated modelling analyses indicate a consistently negative small to moderate impact on progression from the 21CS qualification. Overall, our findings suggest that the emphasis on scientific literacy within the 21CS qualification suite has not had a major impact on the uptake of post-compulsory science qualifications.

  1. Analysis of error introduced during end-user post-processing of airborne laser data (lidar)

    NASA Astrophysics Data System (ADS)

    Smith, Sarah Louise

    The primary aims and objectives of this thesis are to identify the sources and operation of the errors which are introduced during end-user post-processing of airborne laser scanning data. Previous research has concentrated on the errors incorporated during data capture and preliminary supplier processing. The errors which are introduced by the end-users have been largely neglected. As a result, data users cannot currently estimate the errors within, and therefore the quality of, the models they produce. Laser scanning is a remote sensing technique for the capture of height data of the surface of the Earth. It offers competitive capture costs, high accuracy, and is particularly suited to capturing information in complex urban areas. As a result the commercial value of laser scanning data is high. However, in order to realise the potential of this technique, the quality of the datasets derived from the data must be assessed and the errors introduced during modelling understood. For users to make informed decisions regarding the design of their post-processing workflow it is fundamental that they know how and where errors may be introduced. The characteristics of these errors are investigated in this thesis using a range of approaches. End-user post-processing is divided into three techniques in the thesis: data structuring, filtering and segmentation. Each process is investigated hi terms of accuracy and sensitivity, through the comparison of several methods with reference models. New algorithms for filtering and segmenting laser data are presented. The errors created by each process are identified and analysed. The location of errors across the elevation surface are also investigated. It is shown how this information could be used to aid end-users design their post-processing methodology. The methodology for analyzing the errors is presented as a framework which could be used as a standard for ALS models. This thesis shows that the choice of post

  2. Allogeneic Articular Chondrocyte Transplantation Down Regulates IL-8 Gene Expression in the Degenerating Rabbit Intervertebral Disc in Vivo

    PubMed Central

    Zhang, Yejia; Chee, Ana; Shi, Peng; Wang, Rui; Moss, Isaac; Chen, Er-Yun; He, Tong-Chuan; An, Howard S.

    2014-01-01

    Objective To investigate if repopulating the degenerating intervertebral disc (IVD) with articular chondrocytes (ACs) will decrease inflammation and restore disc structure. In this study, we aimed to determine if well-differentiated AC alone or transduced with adenovirus overexpressing BMP-7 gene may survive and inhibit inflammation or repair disc structure in the degenerating rabbit IVD. Design This was a biological study in a rabbit IVD-injury model in vivo. Dual cell tracking methods (IR dye-labeling and adenovirus transduction) were used to demonstrate the viability of allogeneic AC injected into degenerating rabbit IVDs. Interleukin (IL)-8 gene expression was determined via real-time PCR. Infiltrating inflammatory cells (macrophages, T-cells or neutrophils) were examined with immunohistochemistry. The IVDs were also examined by routine histology. Results ACs labeled with infrared (IR) dye were detected in the degenerating IVDs at both 2 and 8 weeks after injection. At the 2-week time point, IL-8 gene expression was comparable in IVDs injected with chondrocytes and in intact discs as control (P=0.647), while its expression in IVDs injected with saline increased 50fold (p=0.028). Transgene expression of red fluorescent protein, β-galactosidase, and BMP-7 diminished at 8 weeks post injection. IVDs injected with chondrocytes overexpressing hBMP-7 did not show lower IL-8 gene expression or improved histology. Macrophages were consistently detected by immunohistochemistry in the cartilage formation around the needle insertion sites in both the saline and chondrocyte groups, while neither T cells nor neutrophils were detected. Conclusions Allogeneic rabbit AC survived in the degenerating rabbit IVDs for at least 8 weeks. Cell treatment resulted in reduced IVD inflammation, but did not significantly improve IVD structure. PMID:25133623

  3. Key molecular processes of the diapause to post-diapause quiescence transition in the alfalfa leafcutting bee Megachile rotundata identified by comparative transcriptome analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insect diapause (dormancy) synchronizes an insect’s life cycle to seasonal changes in the abiotic and biotic resources required for development and reproduction. Transcription analysis of Megachile rotundata diapause termination identified 399 post-diapause upregulated and 144 post-diapause down-reg...

  4. The effect of cochlear implantation and post-operative rehabilitation on acoustic voice analysis in post-lingual hearing impaired adults.

    PubMed

    Hassan, Sabah M; Malki, Khalid H; Mesallam, Tamer A; Farahat, Mohamad; Bukhari, Manal; Murry, Thomas

    2011-10-01

    Post-lingual deaf adults can develop some vocal abnormalities similar to those developed in pre-lingual deaf individuals. The aim of this work was to study the effect of cochlear implantation followed by post-operative rehabilitation on voice acoustics in post-lingual hearing impaired adults with different durations of hearing loss. The study included 35 post-lingual hearing impaired adults who underwent cochlear implantation. Patients were divided into two groups according to the duration of their hearing loss. Each group was further divided into two subgroups according to whether they received auditory rehabilitation or not. Using the Multi-Dimensional Voice Program (MDVP) parameters, comparisons were made between each subgroup of patients and the normal MDVP Saudi database, and between subgroups of patients. Most of the patients in the two groups reported significant improvement in their MDVP results post-implantation. Further, significantly deviant MDVP parameters were reported in the group of patients with longer duration of hearing loss. Patients who received rehabilitation significantly improved more than those who did not. In conclusion, it appears that cochlear implantation improves the auditory control of voice production in post-lingual deaf adults. Also, it is obvious that cochlear implantation at an early stage of hearing loss gives better results on voice control, especially if augmented with auditory rehabilitation. PMID:21331786

  5. Chemical analysis of post explosion samples obtained as a result of model field experiments.

    PubMed

    Borusiewicz, Rafal; Zadora, Grzegorz; Zieba-Palus, Janina

    2013-11-15

    Five different explosives were detonated in a series of field experiments. Each experiment (detonation of the charge of each specific explosive) was repeated three times. The experiments were conducted under controlled conditions, exceeding those of research published so far. Detonated charges were uniform in size and, as far as possible, in shape. The explosives used originated from the same batch. Additionally, the same kind of electric detonators were used. Witness plates (sheets of galvanised steel 100 cm × 90 cm × 0.5 mm) were used to collect post-blast residues in a reproducible way. They were placed relatively close to the charge to minimise the influence of the wind. Samples were collected by systematic swabbing of the surface of the plate by acetone moistened cotton swabs. Samples were packed tight, transferred to the laboratory, and extracted with methanol. Extracts were concentrated by solvent evaporation, cleaned by centrifugation, and analysed using HPLC-DAD. Each extract was analysed three times and the mean value of the amount of the given explosive within the extract was calculated. For each of the explosive materials used the results of the repetition of the experiments proved them to be irreproducible. After each detonation of a specific charge different amounts of given explosives were found in post-blast samples. Also, the intuitively expected relationship between the distance from the charge and amount of post-blast residues were not observed. These results are consistent with previously published results of field experiments. The lack of reproducibility may be explained by differences in efficiency of detonation. The efficiency of a detonation may be influenced even by small differences in the shape of the charge as well as by the position and properties of the detonator. The lack of dependency between the amount of the explosive in the post-blast samples and the distance from the charge may be explained by the fact that during detonation

  6. Reproductive history and post-reproductive mortality: A sibling comparison analysis using Swedish register data.

    PubMed

    Barclay, Kieron; Keenan, Katherine; Grundy, Emily; Kolk, Martin; Myrskylä, Mikko

    2016-04-01

    A growing body of evidence suggests that reproductive history influences post-reproductive mortality. A potential explanation for this association is confounding by socioeconomic status in the family of origin, as socioeconomic status is related to both fertility behaviours and to long-term health. We examine the relationship between age at first birth, completed parity, and post-reproductive mortality and address the potential confounding role of family of origin. We use Swedish population register data for men and women born 1932-1960, and examine both all-cause and cause-specific mortality. The contributions of our study are the use of a sibling comparison design that minimizes residual confounding from shared family background characteristics and assessment of cause-specific mortality that can shed light on the mechanisms linking reproductive history to mortality. Our results were entirely consistent with previous research on this topic, with teenage first time parents having higher mortality, and the relationship between parity and mortality following a U-shaped pattern where childless men and women and those with five or more children had the highest mortality. These results indicate that selection into specific fertility behaviours based upon socioeconomic status and experiences within the family of origin does not explain the relationship between reproductive history and post-reproductive mortality. Additional analyses where we adjust for other lifecourse factors such as educational attainment, attained socioeconomic status, and post-reproductive marital history do not change the results. Our results add an important new level of robustness to the findings on reproductive history and mortality by showing that the association is robust to confounding by factors shared by siblings. However it is still uncertain whether reproductive history causally influences health, or whether other confounding factors such as childhood health or risk-taking propensity could

  7. Post-natal growth of the gastrointestinal tract of the Siberian hamster: morphometric analysis.

    PubMed

    Wołczuk, K; Kobak, J

    2014-12-01

    Post-natal growth of the gastrointestinal tract of the Siberian hamster was studied in newborn and 3-, 7-, 14-, 21-, 42- and 90-day-old animals. Morphometric measurements and calculations were carried out: length and internal surface of gastrointestinal tract segments, size (height, width, surface) and density of villi as well as allometric growth rate of the length and internal surface of the segments with respect to the body mass. The fastest growth rate of the gastrointestinal tract segments was noticed during the first 3 days of the post-natal life. Nevertheless, significant regional differences in their growth rate were found. The increase in the length and internal surface of the large intestine was fastest, while the smallest increase was observed in the oesophagus. All segments of the gastrointestinal tract except oesophagus exhibited a positive allometric relationship to the body mass from birth till final weaning, whereas during the post-weaning period, the increase was isometric. Thus, at birth, the gastrointestinal tract segments were relatively smaller compared with those observed in adults, but then, the gastrointestinal tract grew faster than the rest of the body and reached its adult proportions just before the transition to solid food. Most probably, reaching the adult structure of the gastrointestinal tract before the final weaning is an essential condition for the proper growth of an organism after the weaning.

  8. Digital PCR Panel for Sensitive Hematopoietic Chimerism Quantification after Allogeneic Stem Cell Transplantation.

    PubMed

    Stahl, Tanja; Rothe, Caroline; Böhme, Manja U; Kohl, Aloisa; Kröger, Nicolaus; Fehse, Boris

    2016-01-01

    Accurate and sensitive determination of hematopoietic chimerism is a crucial diagnostic measure after allogeneic stem cell transplantation to monitor engraftment and potentially residual disease. Short tandem repeat (STR) amplification, the current "gold standard" for chimerism assessment facilitates reliable accuracy, but is hampered by its limited sensitivity (≥1%). Digital PCR (dPCR) has been shown to combine exact quantification and high reproducibility over a very wide measurement range with excellent sensitivity (routinely ≤0.1%) and thus represents a promising alternative to STR analysis. We here aimed at developing a whole panel of digital-PCR based assays for routine diagnostic. To this end, we tested suitability of 52 deletion/insertion polymorphisms (DIPs) for duplex analysis in combination with either a reference gene or a Y-chromosome specific PCR. Twenty-nine DIPs with high power of discrimination and good performance were identified, optimized and technically validated. We tested the newly established assays on retrospective patient samples that were in parallel also measured by STR amplification and found excellent correlation. Finally, a screening plate for initial genotyping with DIP-specific duplex dPCR assays was designed for convenient assay selection. In conclusion, we have established a comprehensive dPCR system for precise and high-sensitivity measurement of hematopoietic chimerism, which should be highly useful for clinical routine diagnostics. PMID:27618030

  9. Digital PCR Panel for Sensitive Hematopoietic Chimerism Quantification after Allogeneic Stem Cell Transplantation

    PubMed Central

    Stahl, Tanja; Rothe, Caroline; Böhme, Manja U.; Kohl, Aloisa; Kröger, Nicolaus; Fehse, Boris

    2016-01-01

    Accurate and sensitive determination of hematopoietic chimerism is a crucial diagnostic measure after allogeneic stem cell transplantation to monitor engraftment and potentially residual disease. Short tandem repeat (STR) amplification, the current “gold standard” for chimerism assessment facilitates reliable accuracy, but is hampered by its limited sensitivity (≥1%). Digital PCR (dPCR) has been shown to combine exact quantification and high reproducibility over a very wide measurement range with excellent sensitivity (routinely ≤0.1%) and thus represents a promising alternative to STR analysis. We here aimed at developing a whole panel of digital-PCR based assays for routine diagnostic. To this end, we tested suitability of 52 deletion/insertion polymorphisms (DIPs) for duplex analysis in combination with either a reference gene or a Y-chromosome specific PCR. Twenty-nine DIPs with high power of discrimination and good performance were identified, optimized and technically validated. We tested the newly established assays on retrospective patient samples that were in parallel also measured by STR amplification and found excellent correlation. Finally, a screening plate for initial genotyping with DIP-specific duplex dPCR assays was designed for convenient assay selection. In conclusion, we have established a comprehensive dPCR system for precise and high-sensitivity measurement of hematopoietic chimerism, which should be highly useful for clinical routine diagnostics. PMID:27618030

  10. Digital PCR Panel for Sensitive Hematopoietic Chimerism Quantification after Allogeneic Stem Cell Transplantation.

    PubMed

    Stahl, Tanja; Rothe, Caroline; Böhme, Manja U; Kohl, Aloisa; Kröger, Nicolaus; Fehse, Boris

    2016-01-01

    Accurate and sensitive determination of hematopoietic chimerism is a crucial diagnostic measure after allogeneic stem cell transplantation to monitor engraftment and potentially residual disease. Short tandem repeat (STR) amplification, the current "gold standard" for chimerism assessment facilitates reliable accuracy, but is hampered by its limited sensitivity (≥1%). Digital PCR (dPCR) has been shown to combine exact quantification and high reproducibility over a very wide measurement range with excellent sensitivity (routinely ≤0.1%) and thus represents a promising alternative to STR analysis. We here aimed at developing a whole panel of digital-PCR based assays for routine diagnostic. To this end, we tested suitability of 52 deletion/insertion polymorphisms (DIPs) for duplex analysis in combination with either a reference gene or a Y-chromosome specific PCR. Twenty-nine DIPs with high power of discrimination and good performance were identified, optimized and technically validated. We tested the newly established assays on retrospective patient samples that were in parallel also measured by STR amplification and found excellent correlation. Finally, a screening plate for initial genotyping with DIP-specific duplex dPCR assays was designed for convenient assay selection. In conclusion, we have established a comprehensive dPCR system for precise and high-sensitivity measurement of hematopoietic chimerism, which should be highly useful for clinical routine diagnostics.

  11. Transcranial direct current stimulation facilitates motor learning post-stroke: a systematic review and meta-analysis.

    PubMed

    Kang, Nyeonju; Summers, Jeffery J; Cauraugh, James H

    2016-04-01

    Transcranial direct current stimulation (tDCS) is an attractive protocol for stroke motor recovery. The current systematic review and meta-analysis investigated the effects of tDCS on motor learning post-stroke. Specifically, we determined long-term learning effects by examining motor improvements from baseline to at least 5 days after tDCS intervention and motor practise. 17 studies reported long-term retention testing (mean retention interval=43.8 days; SD=56.6 days) and qualified for inclusion in our meta-analysis. Assessing primary outcome measures for groups that received tDCS and motor practise versus sham control groups created 21 valid comparisons: (1) 16 clinical assessments and (2) 5 motor skill acquisition tests. A random effects model meta-analysis showed a significant overall effect size=0.59 (p<0.0001; low heterogeneity, T(2)=0.04; I(2)=22.75%; and high classic fail-safe N=240). 4 moderator variable analyses revealed beneficial effects of tDCS on long-term motor learning: (1) stimulation protocols: anodal on the ipsilesional hemisphere, cathodal on the contralesional hemisphere, or bilateral; (2) recovery stage: subacute or chronic stroke; (3) stimulation timing: tDCS before or during motor practise; and (4) task-specific training or conventional rehabilitation protocols. This robust meta-analysis identified novel long-term motor learning effects with tDCS and motor practise post-stroke. PMID:26319437

  12. Transcranial direct current stimulation facilitates motor learning post-stroke: a systematic review and meta-analysis.

    PubMed

    Kang, Nyeonju; Summers, Jeffery J; Cauraugh, James H

    2016-04-01

    Transcranial direct current stimulation (tDCS) is an attractive protocol for stroke motor recovery. The current systematic review and meta-analysis investigated the effects of tDCS on motor learning post-stroke. Specifically, we determined long-term learning effects by examining motor improvements from baseline to at least 5 days after tDCS intervention and motor practise. 17 studies reported long-term retention testing (mean retention interval=43.8 days; SD=56.6 days) and qualified for inclusion in our meta-analysis. Assessing primary outcome measures for groups that received tDCS and motor practise versus sham control groups created 21 valid comparisons: (1) 16 clinical assessments and (2) 5 motor skill acquisition tests. A random effects model meta-analysis showed a significant overall effect size=0.59 (p<0.0001; low heterogeneity, T(2)=0.04; I(2)=22.75%; and high classic fail-safe N=240). 4 moderator variable analyses revealed beneficial effects of tDCS on long-term motor learning: (1) stimulation protocols: anodal on the ipsilesional hemisphere, cathodal on the contralesional hemisphere, or bilateral; (2) recovery stage: subacute or chronic stroke; (3) stimulation timing: tDCS before or during motor practise; and (4) task-specific training or conventional rehabilitation protocols. This robust meta-analysis identified novel long-term motor learning effects with tDCS and motor practise post-stroke.

  13. [Kinetic study of splenocytes after allogeneic murine bone marrow transplantation].

    PubMed

    Liu, Jing-Hua; Zhou, Fan; Dou, Li-Ping; Wang, Li-Li; Wang, Xin-Rong; Li, Li; Yu, Li

    2010-08-01

    The study was purposed to understand immunological reconstitution of peripheral immune organs after transplantation, through establishing allogeneic murine bone marrow transplantation model and detecting the kinetic change of splenocytes after transplantation. C57BL/6 mice were donors, BALB/c mice were recipients. Recipient mice were divided into irradiation group (R), irradiation plus inoculating bone marrow mononuclear cells (MNC) group (B), and irradiation plus inoculating bone marrow mononuclear cells and spleno-MNC group (S). After transplantation, the mice were examined daily for the symptoms such as weight, hunched posture, activity, ruffled fur, diarrhea, and survival. Blood routine test was done once a week, splenocyte was counted and CD3, CD4, CD8, B220, CD11c positive cell relative count was detected by FACS on day 2, 7, 14, 27, 60 after transplantation, Liver, skin and intestine were biopsied for histopathological examination before dying. The results indicated that 89% mice in S group died of acute graft-versus-host disease (aGVHD) during day 6 to 78. The spleno-mononuclear cell count quickly decreased and reached to lowest level on day 2, then gradually recovered to level of pretransplantation on day 14; CD8 and B220 positive cells decreased to lowest level on day 12, in which CD8(+) cells quickly recovered and reached to level of pretransplantation, but the B220(+) recovered most slowly and sustained to be with low level, then gradually recovered to level of pretransplantation on day 60; CD3 and CD4 positive cells decreased relatively slowly, and reached to lowest level on day 14, then both gradually recovered to level of pretransplantation on day 60; CD11c positive cell count changed unstrikingly except day 14. It is concluded that when C57BL/6 mice are donors, and BALB/c mice are recipients treated with irradiation of 7.5 Gy and inoculated with 1 x 10⁷ bone marrow MNC and 1 x 10⁷ spleno-MNC, allogeneic murine bone marrow transplantation model

  14. Role of acute graft-versus-host disease in the risk of bacteremia and invasive fungal disease after allogeneic hemopoietic stem cell transplantation in children. Results from a single-center observational study.

    PubMed

    Castagnola, Elio; Bagnasco, Francesca; Bandettini, Roberto; Caviglia, Ilaria; Morreale, Giuseppe; Lanino, Edoardo; Giardino, Stefano; Moroni, Cristina; Haupt, Riccardo; Faraci, Maura

    2014-07-01

    Data on epidemiology of severe infectious complications, ie, bacteremia or invasive fungal disease (IFD), in children with acute graft-versus-host disease (aGVHD) after allogeneic hemopoietic stem cell transplantation (HSCT) are scarce. In a retrospective, single-center study, we analyzed the risk (hazard ratio [HR]) and the rate (episodes/1000 patients days at risk) of bacteremias and IFD in children receiving allogeneic HSCT, according to the type of donor (matched related [MRD] or alternative [AD]) and presence and grade of aGVHD. From 2000 to 2009, 198 children receiving 217 allogeneic HSCT developed 134 severe infectious episodes (103 bacteremias and 31 IFD). The type of donor (AD versus MRD) was the most important risk factor for the severe infections (P = .0052). In separate multivariable analysis for bacteremia and IFD, children receiving an AD HSCT had increased HR and rate of bacteremia compared with those receiving a MRD transplantation (P = .0171 and P = .0001, respectively), whereas the HR and the rate of IFD were significantly influenced by the grade of aGVHD (P = .0002 and P < .0001, respectively). Finally, infectious episodes occurred late after HSCT, especially in presence of severe aGVHD, and bacteremias were 3 to 6 times more frequent than IFD. These data may be important to design management strategies of infections in pediatric allogeneic HSCT.

  15. Reconstruction of Beagle Hemi-Mandibular Defects with Allogenic Mandibular Scaffolds and Autologous Mesenchymal Stem Cells

    PubMed Central

    Luo, JinChao; Liu, HuaWei; Hu, Min; Yue, Wen

    2014-01-01

    Objective Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs) can increase the integration of massive allografts (hemi-mandible) in a large animal model. Methods Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at4 (n = 4), 12 (n = 4), 24 (n = 4) or 48 weeks (n = 3) postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD) of transplants were used to evaluate defect reconstruction outcomes. Results Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05), and all micro-architectural parameters were significantly different between groups (p<0.05). Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed. Conclusions Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a

  16. Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats.

    PubMed

    Zhang, Jun; Bai, Xiaozhi; Zhao, Bin; Wang, Yunchuan; Su, Linlin; Chang, Peng; Wang, Xujie; Han, Shichao; Gao, Jianxin; Hu, Xiaolong; Hu, Dahai; Liu, Xiaoyan

    2016-05-01

    Autologous adipose-derived stem cells (ADSCs) can protect fat grafts in cell-assisted lipotransfer (CAL). However, diabetes alters the intrinsic properties of ADSCs and impairs their function so that they lack these protective effects. We investigate whether allogeneic ADSCs from healthy donors could protect fat grafts in immunocompetent diabetic rats. Syngeniec adipose tissues and ADSCs were derived from diabetic Lewis (LEW) rats, whereas allogeneic ADSCs were from healthy brown-Norway rats. A grafted mixture containing 0.7 ml granule fat and 0.3 ml 6 × 10(6) allogeneic/syngeneic ADSCs was injected subcutaneously on the skulls of diabetic LEW rats. Fat samples were harvested to evaluate the levels of injury and vascularization as shown by perilipin A, CD34 and VEGF at 14 days. The immune response was evaluated with a lymphocytotoxicity test and the CD4/CD8 ratio in peripheral blood at 14 days. The volume retention of fat grafts was measured at 3 months. Healthy allogeneic ADSCs increased the expression levels of perilipin A, CD34 and VEGF at 14 days. The volume retention of fat grafts was improved by allogeneic ADSCs at 3 months. ADSCs were demonstrated to have low immunogenicity by the lymphocyte proliferation test and immunophenotype including MHC and co-stimulatory markers. The lymphocytotoxicity test and CD4/CD8 ratio indicated no obvious immune response elicited by allogeneic ADSCs. Thus, healthy allogeneic ADSCs can promote the survival of fat grafts in this immunocompetent diabetic rat model, with little or no obvious immune rejection.

  17. Allogeneic IgG combined with dendritic cell stimuli induce antitumour T-cell immunity.

    PubMed

    Carmi, Yaron; Spitzer, Matthew H; Linde, Ian L; Burt, Bryan M; Prestwood, Tyler R; Perlman, Nicola; Davidson, Matthew G; Kenkel, Justin A; Segal, Ehud; Pusapati, Ganesh V; Bhattacharya, Nupur; Engleman, Edgar G

    2015-05-01

    Whereas cancers grow within host tissues and evade host immunity through immune-editing and immunosuppression, tumours are rarely transmissible between individuals. Much like transplanted allogeneic organs, allogeneic tumours are reliably rejected by host T cells, even when the tumour and host share the same major histocompatibility complex alleles, the most potent determinants of transplant rejection. How such tumour-eradicating immunity is initiated remains unknown, although elucidating this process could provide the basis for inducing similar responses against naturally arising tumours. Here we find that allogeneic tumour rejection is initiated in mice by naturally occurring tumour-binding IgG antibodies, which enable dendritic cells (DCs) to internalize tumour antigens and subsequently activate tumour-reactive T cells. We exploited this mechanism to treat autologous and autochthonous tumours successfully. Either systemic administration of DCs loaded with allogeneic-IgG-coated tumour cells or intratumoral injection of allogeneic IgG in combination with DC stimuli induced potent T-cell-mediated antitumour immune responses, resulting in tumour eradication in mouse models of melanoma, pancreas, lung and breast cancer. Moreover, this strategy led to eradication of distant tumours and metastases, as well as the injected primary tumours. To assess the clinical relevance of these findings, we studied antibodies and cells from patients with lung cancer. T cells from these patients responded vigorously to autologous tumour antigens after culture with allogeneic-IgG-loaded DCs, recapitulating our findings in mice. These results reveal that tumour-binding allogeneic IgG can induce powerful antitumour immunity that can be exploited for cancer immunotherapy.

  18. Acute GVHD after allogeneic hematopoietic transplantation affects early marrow reconstitution and speed of engraftment.

    PubMed

    Milone, Giuseppe; Camuglia, Maria Grazia; Avola, Giuseppe; Di Marco, Annalia; Leotta, Salvatore; Cupri, Alessandra; Spina, Paolo; Romano, Alessandra; Spina, Eleonora; Azzaro, Maria Pia; Berritta, Deja; Parisi, Marina; Tripepi, Giovanni

    2015-06-01

    Our aim was to study the influence of acute graft-versus-host disease (a-GVHD) on primary engraftment times after allogeneic transplantation. Primary engraftment and frequency of marrow granulocyte-macrophage colony-forming units and erythroid burst-forming units, at day +18, were studied in 126 allogeneic transplants. Patients were grouped according to the time when a-GVHD treatment with corticosteroids was started. The no-a-GVHD group are those who, during the first 3 months, had no need for a-GVHD treatment; the early-a-GVHD group are those who needed a-GVHD treatment within 19 days; and the postengraftment-a-GVHD group are those who were not on corticosteroid treatment at the time of engraftment but needed it after day +19. The no-a-GVHD group reached a neutrophil count (N) > 0.5 × 10(9)/L in a median of 17.8 days. The postengraftment-a-GVHD group reached N > 0.5 × 10(9)/L in a median of 21.4 days (p = 0.0003). The early-a-GVHD group had N > 0.5 × 10(9)/L in a median of +17.0 days (p = 0.23). When factors important for engraftment were studied in a multivariate analysis, postengraftment a-GVHD was a significant factor in delayed neutrophil and platelet engraftment. Both the early-a-GVHD and postengraftment-a-GVHD groups showed a significant reduction in frequency of granulocyte-macrophage colony-forming units and erythroid burst-forming units found in marrow at day +18. In conclusion, a-GVHD may influence early marrow reconstitution and is a relevant factor for primary myeloid and platelet engraftment. PMID:25704053

  19. Reduced-intensity conditioning allogeneic stem cell transplantation in malignant lymphoma: current status

    PubMed Central

    Zhang, Le; Zhang, Yi-Zhuo

    2013-01-01

    Allogeneic stem cell transplantation (allo-SCT) is a potential cure for patients with malignant lymphoma that is based on the graft-versus-lymphoma (GVL) effect. Myeloablative conditioning allo-SCT is associated with high mortality and morbidity, particularly in patients older than 45 years, heavily pretreated patients (prior hematopoietic stem cell transplantation or more than two lines of conventional chemotherapy) or patients affected by other comorbidities. Therefore, conventional allo-SCT is restricted to younger patients (<50 to 55 years) in good physical condition. Over the last decade, allo-SCT with reduced-intensity conditioning (RIC-allo-SCT) has been increasingly used to treat patients with lymphoma. This treatment is associated with lower toxicity and substantial decrease in the incidence of transplant-related mortality, and has the potential to lead to long-term remissions. Therefore, patients who are not suitable to undergo conventional allo-SCT can benefit from the potentially curative GVL effects of allo-SCT. Although RIC-allo-SCT has improved the survival of lymphoma patients, high post-transplant relapse rates or disease progression mainly results in treatment failure. Thus, further improvement is clearly needed. The role and timing of RIC-allo-SCT in the treatment of lymphoma remains unclear. Therefore, more prospective studies should clarify the effectiveness of this method. In this article, we review the recent literature on RIC-allo-SCT as a treatment for major lymphoma subtypes. Areas that require further investigation in the context of clinical trials are also highlighted. PMID:23691438

  20. Maintenance Therapy with Decitabine after Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndrome.

    PubMed

    Pusic, Iskra; Choi, Jaebok; Fiala, Mark A; Gao, Feng; Holt, Matthew; Cashen, Amanda F; Vij, Ravi; Abboud, Camille N; Stockerl-Goldstein, Keith E; Jacoby, Meghan A; Uy, Geoffrey L; Westervelt, Peter; DiPersio, John F

    2015-10-01

    Decitabine is a hypomethylating agent that irreversibly inhibits DNA methyltransferase I, inducing leukemic differentiation and re-expression of epigenetically silenced putative tumor antigens. We assessed safety and efficacy of decitabine maintenance after allogeneic transplantation for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Decitabine maintenance may help eradicate minimal residual disease, decrease the incidence of graft-versus-host disease (GVHD), and facilitate a graft-versus-leukemia effect by enhancing the effect of T regulatory lymphocytes. Patients with AML/MDS in complete remission (CR) after allotransplantation started decitabine between day +50 and +100. We investigated 4 decitabine doses in cohorts of 4 patients: 5, 7.5, 10, and 15 mg/m(2)/day × 5 days every 6 weeks, for a maximum 8 cycles. The maximum tolerated dose (MTD) was defined as the maximum dose at which ≤ 25% of people experience dose-limiting toxicities during the first cycle of treatment. Twenty-four patients were enrolled and 22 were evaluable. All 4 dose levels were completed and no MTD was reached. Overall, decitabine maintenance was well tolerated. Grade 3 and 4 hematological toxicities were experienced by 75% of patients, including all patients treated at the highest dose level. Nine patients completed all 8 cycles and 8 of them remain in CR. Nine patients died from relapse (n = 4), infectious complications (n = 3), and GVHD (n = 2). Most occurrences of acute GVHD were mild and resolved without interruption of treatment; 1 patient died of acute gut GVHD. Decitabine maintenance did not clearly impact the rate of chronic GVHD. Although there was a trend of increased FOXP3 expression, results were not statistically significant. In conclusion, decitabine maintenance is associated with acceptable toxicities when given in the post-allotransplantation setting. Although the MTD was not reached, the dose of 10 mg/m(2) for 5 days every 6 weeks appeared to be the

  1. Effects of pharmacological concentrations of dietary zinc oxide on growth of post-weaning pigs: a meta-analysis.

    PubMed

    Sales, James

    2013-06-01

    Pharmacological dietary zinc (Zn) concentrations of 1,000 to 3,000 mg/kg diet from Zn oxide have been found to increase growth in post-weaning pigs. However, results were inconsistent among studies. A frequentist meta-analysis, in which effects were numerically described with standardized effect sizes (Hedges's g), was conducted in order to identify and quantify the responses in average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G/F) in post-weaning pigs upon dietary Zn supplementation from Zn oxide. The inability of independent continuous variables to explain significant heterogeneity obtained with fixed effect models necessitated the use of random effects models to calculate summary statistics. Dietary Zn supplementation increased (P < 0.05) ADG (mean effect size = 1.086, 95 % confidence intervals = 0.905-1.266, 26 studies, 72 comparisons), ADFI (mean effect size = 0.794, 95 % confidence intervals = 0.616-0.971, 25 studies, 71 comparisons), and G/F (mean effect size = 0.566, 95 % confidence intervals = 0.422-0.710, 24 studies, 70 comparisons). Zinc oxide provided a feasible alternative to in-feed antibiotics to improve growth in post-weaning pigs, and its reduction in diets due to potential environmental pollution will have to be negated by alternative feed additives and management strategies in order to prevent economic losses.

  2. Genomic Convergence Analysis of Schizophrenia: mRNA Sequencing Reveals Altered Synaptic Vesicular Transport in Post-Mortem Cerebellum

    PubMed Central

    Mudge, Joann; Miller, Neil A.; Khrebtukova, Irina; Lindquist, Ingrid E.; May, Gregory D.; Huntley, Jim J.; Luo, Shujun; Zhang, Lu; van Velkinburgh, Jennifer C.; Farmer, Andrew D.; Lewis, Sharon; Beavis, William D.; Schilkey, Faye D.; Virk, Selene M.; Black, C. Forrest; Myers, M. Kathy; Mader, Lar C.; Langley, Ray J.; Utsey, John P.; Kim, Ryan W.; Roberts, Rosalinda C.; Khalsa, Sat Kirpal; Garcia, Meredith; Ambriz-Griffith, Victoria; Harlan, Richard; Czika, Wendy; Martin, Stanton; Wolfinger, Russell D.; Perrone-Bizzozero, Nora I.; Schroth, Gary P.; Kingsmore, Stephen F.

    2008-01-01

    Schizophrenia (SCZ) is a common, disabling mental illness with high heritability but complex, poorly understood genetic etiology. As the first phase of a genomic convergence analysis of SCZ, we generated 16.7 billion nucleotides of short read, shotgun sequences of cDNA from post-mortem cerebellar cortices of 14 patients and six, matched controls. A rigorous analysis pipeline was developed for analysis of digital gene expression studies. Sequences aligned to approximately 33,200 transcripts in each sample, with average coverage of 450 reads per gene. Following adjustments for confounding clinical, sample and experimental sources of variation, 215 genes differed significantly in expression between cases and controls. Golgi apparatus, vesicular transport, membrane association, Zinc binding and regulation of transcription were over-represented among differentially expressed genes. Twenty three genes with altered expression and involvement in presynaptic vesicular transport, Golgi function and GABAergic neurotransmission define a unifying molecular hypothesis for dysfunction in cerebellar cortex in SCZ. PMID:18985160

  3. Post-crisis analysis of an ineffective tsunami alert: the 2010 earthquake in Maule, Chile.

    PubMed

    Soulé, Bastien

    2014-04-01

    Considering its huge magnitude and its location in a densely populated area of Chile, the Maule seism of 27 February 2010 generated a low amount of victims. However, post-seismic tsunamis were particularly devastating on that day; surprisingly, no full alert was launched, not at the national, regional or local level. This earthquake and associated tsunamis are of interest in the context of natural hazards management as well as crisis management planning. Instead of focusing exclusively on the event itself, this article places emphasis on the process, systems and long-term approach that led the tsunami alert mechanism to be ineffectual. Notably, this perspective reveals interrelated forerunner signs of vulnerability.

  4. Hazard Analysis for Post-Fire Debris-Flow Potential in Arizona

    NASA Astrophysics Data System (ADS)

    Youberg, A.; Koestner, K. A.; Schiefer, E.; Neary, D. G.

    2011-12-01

    Several large, devastating wildfires occurred in Arizona during the past 2 years, after a 4-year period without any large wildfires. In June, 2010, the human-caused Schultz Fire near Flagstaff burned 6,100 ha of mostly steep terrain. Subsequent rains from the 4th wettest monsoon on record produced numerous debris flows, significant erosion, and substantial flooding of the downslope residential areas. In May and June of 2011, 3 very large human-caused wildfires (Wallow, Horseshoe 2, and Monument Fires) burned over 320,000 ha, posing serious threats to communities below burned slopes. The Burned Area Emergency Response (BAER) teams, in need of a rapid method to assess the potential for post-fire debris flows, turned to models developed by the USGS for this purpose [Cannon and others, 2010, GSA Bull, 122(1-2), 127-144]. These models, while providing quick results, have not been evaluated for use in Arizona's varied physiographic provinces. Here we use data from the Schultz Fire to compare basin responses with those predicted by the USGS post-fire debris-flow models. Data from the Schultz Fire includes detailed field documentation of debris-flow occurrence and runout distances, 1:12,000 stereo aerial photographs, high-resolution digital elevation models (DEMs) and tipping-bucket rainfall data. These data document debris-flow producing storms, basin response, and the extent of debris-flow runout, and provide estimates of debris-flow volumes. The hydrologic responses from 30 small, steep, upper basins burned by the Schultz Fire were assessed for debris or flood flow occurrences. Nineteen basins produced debris flows during a July 20th storm that had a peak 10-minute intensity of 24 mm. A second storm on August 16th, with a peak 10-minute intensity of 15 mm, produced additional debris flows in several of the same basins. Of the 30 basins assessed, 19 were completely burned; four at high severity and 12 at moderate to high severity. The basin with the smallest burned area

  5. Practice variation in physician referral for allogeneic hematopoietic cell transplantation.

    PubMed

    Pidala, J; Craig, B M; Lee, S J; Majhail, N; Quinn, G; Anasetti, C

    2013-01-01

    Hematological malignancy patients not referred by their primary hematologist/medical oncologist suffer disparate access to allogeneic hematopoietic cell transplantation (HCT). However, investigation into physician, system and patient factors relevant to this decision making is lacking. We surveyed a national randomized sample of practicing hematologists/medical oncologists identified through the AMA (American Medical Association) masterfile. A modified Dillman approach was utilized to encourage survey response. From 1200 surveyed, a total of 113 physicians responded. In all, 68% were male, 62% identified as White/non-Hispanic, 79% practiced in non-academic settings and 80% reported spending 75-100% of their professional effort in clinical care. Using clinical vignettes, we detected significantly increased odds for HCT non-referral according to age (age 60 vs 30, odds ratio (OR) 8.3, 95% confidence interval (CI): 5.9-11.7, P<0.0001), insurance coverage (no coverage vs coverage, OR 6.9, 95% CI: 5.2-9.1, P<0.0001) and race (African-American vs Caucasian, OR 2.4, 95% CI: 1.9-2.9, P<0.0001). Physician (perception of HCT risks), system (insurance coverage) and patient (age, social support and co-morbid illness) factors were strongly endorsed by respondents as important determinants of their HCT referral practices. These data speak to important factors relevant to HCT referral practices, and highlight several opportunities for education and intervention to reduce current disparities.

  6. Allogeneic anorectal transplantation in rats: technical considerations and preliminary results

    PubMed Central

    Galvão, Flavio H. F.; Waisberg, Daniel R.; Seid, Victor E.; Costa, Anderson C. L.; Chaib, Eleazar; Baptista, Rachel Rossini; Capelozzi, Vera Luiza; Lanchotte, Cinthia; Cruz, Ruy J.; Araki, Jun; D’Albuquerque, Luiz Carneiro

    2016-01-01

    Fecal incontinence is a challenging condition with numerous available treatment modalities. Success rates vary across these modalities, and permanent colostomy is often indicated when they fail. For these cases, a novel potential therapeutic strategy is anorectal transplantation (ATx). We performed four isogeneic (Lewis-to-Lewis) and seven allogeneic (Wistar-to-Lewis) ATx procedures. The anorectum was retrieved with a vascular pedicle containing the aorta in continuity with the inferior mesenteric artery and portal vein in continuity with the inferior mesenteric vein. In the recipient, the native anorectal segment was removed and the graft was transplanted by end-to-side aorta-aorta and porto-cava anastomoses and end-to-end colorectal anastomosis. Recipients were sacrificed at the experimental endpoint on postoperative day 30. Surviving animals resumed normal body weight gain and clinical performance within 5 days of surgery. Isografts and 42.9% of allografts achieved normal clinical evolution up to the experimental endpoint. In 57.1% of allografts, signs of immunological rejection (abdominal distention, diarrhea, and anal mucosa inflammation) were observed three weeks after transplantation. Histology revealed moderate to severe rejection in allografts and no signs of rejection in isografts. We describe a feasible model of ATx in rats, which may allow further physiological and immunologic studies. PMID:27488366

  7. Allogenic banking of dental pulp stem cells for innovative therapeutics.

    PubMed

    Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

    2015-08-26

    Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

  8. Twisting immune responses for allogeneic stem cell therapy

    PubMed Central

    Li, Shengwen Calvin; Zhong, Jiang F

    2009-01-01

    Stem cell-derived tissues and organs have the potential to change modern clinical science. However, rejection of allogeneic grafts by the host’s immune system is an issue which needs to be addressed before embryonic stem cell-derived cells or tissues can be used as medicines. Mismatches in human leukocyte class I antigens and minor histocompatibility antigens are the central factors that are responsible for various graft-versus-host diseases. Traditional strategies usually involve suppressing the whole immune systems with drugs. There are many side effects associated with these methods. Here, we discuss an emerging strategy for manipulating the central immune tolerance by naturally “introducing” donor antigens to a host so a recipient can acquire tolerance specifically to the donor cells or tissues. This strategy has two distinct stages. The first stage restores the thymic function of adult patients with sex steroid inhibitory drugs (LHRH-A), keratinocyte growth factor (KGF), interleukin 7 (IL-7) and FMS-like tyrosine kinase 3 (FLT3). The second stage introduces hematopoietic stem cells and their downstream progenitors to the restored thymus by direct injection. Hematopoietic stem cells are used to introduce donor antigens because they have priority access to the thymus. We also review several clinical cases to explain this new strategy. PMID:20975985

  9. Dyslipidemia after allogeneic hematopoietic stem cell transplantation: evaluation and management.

    PubMed

    Griffith, Michelle L; Savani, Bipin N; Boord, Jeffrey B

    2010-08-26

    Currently, approximately 15,000 to 20,000 patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) annually throughout the world, with the number of long-term survivors increasing rapidly. In long-term follow-up after transplantation, the focus of care moves beyond cure of the original disease to the identification and treatment of late effects after HSCT. One of the more serious complications is therapy-related cardiovascular disease. Long-term survivors after HSCT probably have an increased risk of premature cardiovascular events. Cardiovascular complications related to dyslipidemia and other risk factors account for a significant proportion of late nonrelapse morbidity and mortality. This review addresses the risk and causes of dyslipidemia and impact on cardiovascular complications after HSCT. Immunosuppressive therapy, chronic graft-versus-host disease, and other long-term complications influence the management of dyslipidemia. There are currently no established guidelines for evaluation and management of dyslipidemia in HSCT patients; in this review, we have summarized our suggested approach in the HSCT population.

  10. [Human Herpesvirus-6 Encephalitis in Allogeneic Hematopoietic Stem Cell Transplantation].

    PubMed

    Ogata, Masao

    2015-07-01

    The reactivation of human herpesvirus-6B (HHV-6B) is common after allogeneic hematopoietic cell transplantation (allo-HCT), and it is sporadically associated with the development of HHV-6 encephalitis. HHV-6 encephalitis typically develops around 2-6 weeks after allo-HCT, and it is characterized by short-term memory loss. Magnetic resonance imaging typically shows bilateral signal abnormalities in the limbic system. The incidence of HHV-6 encephalitis is reportedly 0-11.6% after bone marrow or peripheral blood stem cell transplantation and 4.9-21.4% after cord blood transplantation. The mortality of HHV-6 encephalitis is high, and survivors are often left with serious sequelae. Antiviral therapy using foscarnet or ganciclovir is recommended for the treatment of HHV-6 encephalitis, but the efficacy of the currently available treatment is insufficient once HHV-6 encephalitis has developed. The elucidation of the pathogenesis of HHV-6 encephalitis and the establishment of preventative therapy are needed to overcome this disease.

  11. Allogenic banking of dental pulp stem cells for innovative therapeutics

    PubMed Central

    Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

    2015-01-01

    Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat. PMID:26328017

  12. Effective strategies for weight loss in post-partum women: a systematic review and meta-analysis.

    PubMed

    Lim, S; O'Reilly, S; Behrens, H; Skinner, T; Ellis, I; Dunbar, J A

    2015-11-01

    Post-partum weight loss is critical to preventing and managing obesity in women, but the results from lifestyle interventions are variable and the components associated with successful outcomes are not yet clearly identified. This study aimed to identify lifestyle intervention strategies associated with weight loss in post-partum women. MEDLINE, EMBASE, PubMed, CINAHL and four other databases were searched for lifestyle intervention studies (diet or exercise or both) in post-partum women (within 12 months of delivery) published up to July 2014. The primary outcome was weight loss. Subgroup analyses were conducted for self-monitoring, individual or group setting, intervention duration, intervention types, the use of technology as a support, and home- or centre-based interventions. From 12,673 studies, 46 studies were included in systematic review and 32 randomized controlled trials were eligible for meta-analysis (1,892 women, age 24-36 years). Studies with self-monitoring had significantly greater weight lost than those without (-4.61 kg [-7.08, -2.15] vs. -1.34 kg [-1.66, -1.02], P = 0.01 for subgroup differences). Diet and physical activity when combined were significantly more effective on weight loss compared with physical activity alone (-3.24 kg [-4.59, -1.90] vs. -1.63 kg [-2.16, -1.10], P < 0.001 for subgroup differences). Lifestyle interventions that use self-monitoring and take a combined diet-and-exercise approach have significantly greater weight loss in post-partum women.

  13. Stress distribution on dentin-cement-post interface varying root canal and glass fiber post diameters. A three-dimensional finite element analysis based on micro-CT data

    PubMed Central

    LAZARI, Priscilla Cardoso; de OLIVEIRA, Rodrigo Caldeira Nunes; ANCHIETA, Rodolfo Bruniera; de ALMEIDA, Erika Oliveira; FREITAS JUNIOR, Amilcar Chagas; KINA, Sidney; ROCHA, Eduardo Passos

    2013-01-01

    Objective The aim of the present study was to analyze the influence of root canal and glass fiber post diameters on the biomechanical behavior of the dentin/cement/post interface of a root-filled tooth using 3D finite element analysis. Material and Methods Six models were built using micro-CT imaging data and SolidWorks 2007 software, varying the root canal (C) and the glass fiber post (P) diameters: C1P1-C=1 mm and P=1 mm; C2P1-C=2 mm and P=1 mm; C2P2-C=2 mm and P=2 mm; C3P1-C=3 mm and P=1 mm; C3P2-C=3 mm and P=2 mm; and C3P3-C=3 mm and P=3 mm. The numerical analysis was conducted with ANSYS Workbench 10.0. An oblique force (180 N at 45º) was applied to the palatal surface of the central incisor. The periodontal ligament surface was constrained on the three axes (x=y=z=0). Maximum principal stress (σmax) values were evaluated for the root dentin, cement layer, and glass fiber post. Results: The most evident stress was observed in the glass fiber post at C3P1 (323 MPa), and the maximum stress in the cement layer occurred at C1P1 (43.2 MPa). The stress on the root dentin was almost constant in all models with a peak in tension at C2P1 (64.5 MPa). Conclusion The greatest discrepancy between root canal and post diameters is favorable for stress concentration at the post surface. The dentin remaining after the various root canal preparations did not increase the stress levels on the root. PMID:24473716

  14. Whole proteome analysis of post-translational modifications: applications of mass-spectrometry for proteogenomic annotation

    SciTech Connect

    Gupta, Nitin; Tanner, Stephen; Jaitly, Navdeep; Adkins, Joshua N.; Lipton, Mary S.; Edwards, Robert; Romine, Margaret F.; Osterman, Andrei; Bafna, Vineet; Smith, Richard D.; Pevzner, Pavel A.

    2007-09-04

    While bacterial genome annotations have significantly improved in recent years, techniques for bacterial proteome annotation (including post-translational chemical modifications, signal peptides, proteolytic events, etc.) are still in their infancy. At the same time, the number of sequenced bacterial genomes is rising sharply, far outpacing our ability to validate the predicted genes, let alone annotate bacterial proteomes. In this study, we use tandem mass spectrometry (MS/MS) to annotate the proteome of Shewanella oneidensis MR-1, an important microbe for bioremediation. In particular, we provide the first comprehensive map of post-translational modifications in a bacterial genome, including a large number of chemical modifications, signal peptide cleavages and cleavage of N-terminal methionine residues. We also detect multiple genes that were missed or assigned incorrect start positions by gene prediction programs and suggest corrections to improve the gene annotation. This study demonstrates that complementing every genome sequencing project by an MS/MS project would significantly improve both genome and proteome annotations for a reasonable cost.

  15. Transcriptome analysis of differentiating trypanosomes reveals the existence of multiple post-transcriptional regulons

    PubMed Central

    Queiroz, Rafael; Benz, Corinna; Fellenberg, Kurt; Hoheisel, Jörg D; Clayton, Christine

    2009-01-01

    Background Trypanosome gene expression is regulated almost exclusively at the post-transcriptional level, with mRNA degradation playing a decisive role. When trypanosomes are transferred from the blood of a mammal to the midgut of a Tsetse fly, they transform to procyclic forms: gene expression is reprogrammed, changing the cell surface and switching the mode of energy metabolism. Within the blood, trypanosomes can pre-adapt for Tsetse transmission, becoming growth-arrested stumpy forms. We describe here the transitions in gene expression that occur during differentiation of in-vitro cultured bloodstream forms to procyclic forms. Results Some mRNAs showed changes within 30 min of cis-aconitate addition, whereas others responded 12-24 hours later. For the first 12 h after addition of cis-aconitate, cells accumulated at the G1 phase of the cell cycle, and showed decreases in mRNAs required for proliferation, mimicking the changes seen in stumpy forms: many mRNAs needed for ribosomal and flagellar biogenesis showed striking co-regulation. Other mRNAs encoding components of signal transduction pathways and potential regulators were specifically induced only during differentiation. Messenger RNAs encoding proteins required for individual metabolic pathways were often co-regulated. Conclusion Trypanosome genes form post-transcriptional regulons in which mRNAs with functions in particular pathways, or encoding components of protein complexes, show almost identical patterns of regulation. PMID:19857263

  16. Post-Buckling Analysis of Curved Honeycomb Sandwich Panels Containing Interfacial Disbonds

    NASA Technical Reports Server (NTRS)

    Pineda, Evan J.; Bednarcyk, Brett A.; Krivanek, Thomas K.

    2016-01-01

    A numerical study on the effect of facesheet-core disbonds on the post-buckling response of curved honeycomb sandwich panels is presented herein. This work was conducted as part of the development of a damage tolerance plan for the next-generation Space Launch System heavy lift launch vehicle payload fairing. As such, the study utilized full-scale fairing barrel segments as the structure of interest. The panels were composed of carbon fiber reinforced polymer facesheets and aluminum honeycomb core. The panels were analyzed numerically using the finite element method incorporating geometric nonlinearity. In a predetermined circular region, facesheet and core nodes were detached to simulate a disbond, between the outer mold line facesheet and honeycomb core, induced via low-speed impact. Surface-to-surface contact in the disbonded region was invoked to prevent interpenetration of the facesheet and core elements and obtain realistic stresses in the core. The diameter of this disbonded region was varied and the effect of the size of the disbond on the post-buckling response was observed. Significant changes in the slope of the edge load-deflection response were used to determine the onset of global buckling and corresponding buckling load. Finally, several studies were conducted to determine the sensitivity of the numerical predictions to refinement in the finite element mesh.

  17. Haploidentical Natural Killer Cells Infused before Allogeneic Stem Cell Transplantation for Myeloid Malignancies: A Phase I Trial.

    PubMed

    Lee, Dean A; Denman, Cecele J; Rondon, Gabriela; Woodworth, Glenda; Chen, Julianne; Fisher, Tobi; Kaur, Indreshpal; Fernandez-Vina, Marcelo; Cao, Kai; Ciurea, Stefan; Shpall, Elizabeth J; Champlin, Richard E

    2016-07-01

    Allogeneic stem cell transplantation is an effective treatment for high-risk myeloid malignancies, but relapse remains the major post-transplantation cause of treatment failure. Alloreactive natural killer (NK) cells mediate a potent antileukemic effect and may also enhance engraftment and reduce graft-versus-host disease (GVHD). Haploidentical transplantations provide a setting in which NK cell alloreactivity can be manipulated, but they are associated with high rates of GVHD. We performed a phase I study infusing escalating doses of NK cells from an HLA haploidentical-related donor-selected for alloreactivity when possible-as a component of the preparative regimen for allotransplantation from a separate HLA-identical donor. The goal of infusing third-party alloreactive NK cells was to augment the antileukemic effect of the transplantation without worsening GVHD and, thus, improve the overall outcome of hematopoietic transplantation. Twenty-one patients with high-risk acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia refractory or beyond first remission received a preparative regimen with busulfan and fludarabine followed by infusion of apheresis-derived, antibody-selected, and IL-2-activated NK cells. Doses were initially based on total nucleated cell (TNC) content and later based on CD56(+) cells to reduce variability. CD56(+) content ranged from .02 to 8.32 × 10(6)/kg. IL-2, .5 × 10(6) units/m(2) subcutaneously was administered daily for 5 days in the final cohort (n = 10). CD3(+) cells in the NK cell product were required to be < 10(5)/kg. Median relapse-free, overall, and GVHD-free/relapse-free survival for all patients enrolled was 102, 233, and 89 days, respectively. Five patients are alive, 5 patients died of transplantation-related causes, and 11 patients died of relapse. Despite the small sample size, survival was highly associated with CD56(+) cells delivered (P = .022) and development of

  18. Quantitative chimerism: an independent acute leukemia prognosis indicator following allogeneic hematopoietic SCT.

    PubMed

    Qin, X-Y; Li, G-X; Qin, Y-Z; Wang, Y; Wang, F-R; Liu, D-H; Xu, L-P; Chen, H; Han, W; Wang, J-Z; Zhang, X-H; Li, J-L; Li, L-D; Liu, K-Y; Huang, X-J

    2014-10-01

    This study evaluates the prognostic significance of quantitative chimerism to monitor minimal residual disease and predict relapse in acute leukemia (AL) patients following allogeneic hematopoietic SCT (HSCT). The quantitative chimerism levels of 129 AL patients were measured using RQ-PCR based on 29 sequence polymorphisms. Receiver-operating characteristic curve indicated that the optimal cutoff point to predict an inevitable relapse was 1.0%, which results in 100.0% sensitivity and 79.6% specificity.The relapse rate of patients with chimerism >1.0% at 2 years was 55.0%, whereas that for patients with chimerism <1.0% was 0%(P=0.000). Quantitative chimerism >1.00% indicated a higher probability of relapse. Cox multivariate analysis indicated that quantitative chimerism >1.00% was associated with lower disease-free survival (hazard ratio (HR)=10.825; 95% confidence interval (CI) =4.704-24.912, P=0.000) and lower OS (HR=8.681; 95% CI=3.728-20.212, P=0.000). Patients (24/47 with quantitative chimerism >1.00%) who received preemptive modified DLI immunotherapy had significantly lower relapse rate (37.5%) than those (n=9) who did not (100%; P=0.001). Thus, quantitative chimerism is an independent prognostic factor that predicts clinical outcomes after HSCT and provides a guide for suitable interventions.

  19. Prognostic utility of routine chimerism testing at 2 to 6 months after allogeneic hematopoietic cell transplantation.

    PubMed

    Mossallam, Ghada I; Kamel, Azza M; Storer, Barry; Martin, Paul J

    2009-03-01

    The utility of routine chimerism analysis as a prognostic indicator of subsequent outcomes after allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning regimens remains controversial. To address this controversy, routine chimerism test results at 2 to 6 months after HCT with myeloablative conditioning regimens were evaluated for association with subsequent risk of chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, and overall mortality. Only 70 of 1304 patients (5%) had < 95% donor-derived cells in the marrow. Low donor chimerism in the marrow occurred more often in patients with low-risk diseases compared with those with higher-risk diseases and was significantly associated with a reduced risk of chronic GVHD. Among 673 patients evaluated, 164 (24%) had < 85% donor-derived T cells in the blood. Low donor T cell chimerism was more frequent in patients with low-risk diseases compared with those with higher-risk diseases, in those who received conditioning with busulfan compared with those who received conditioning with total body irradiation, and in those with lower-grade acute GVHD. Low donor T cell chimerism in the blood was significantly associated with a reduced risk of chronic GVHD but not with a reduced risk of relapse, NRM, or overall mortality. Routine testing of chimerism in the marrow and blood at 2 to 6 months after HCT with myeloablative conditioning regimens may be helpful in documenting engraftment in clinical trials, but provides only limited prognostic information in clinical practice.

  20. Risk factors for recurrent Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients.

    PubMed

    Mani, S; Rybicki, L; Jagadeesh, D; Mossad, S B

    2016-05-01

    Clostridium difficile infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Hematopoietic stem cell transplantation (HSCT) confers increased risk for CDI because of prolonged hospital stay, immunosuppression, the need to use broad-spectrum antibiotics and a complex interplay of preparative regimen and GvHD-induced gut mucosal damage. Our study evaluated risk factors (RF) for recurrent CDI in HSCT recipients given the ubiquity of traditional RF for CDI in this population. Of the 499 allogeneic HSCT recipients transplanted between 2005 and 2012, 61 (12%) developed CDI within 6 months before transplant or 2 years after transplant and were included in the analysis. Recurrent CDI occurred in 20 (33%) patients. One year incidence of CDI recurrence was 31%. Multivariable analyses identified the number of antecedent antibiotics other than those used to treat CDI as the only significant RF for recurrence (hazard ratio 1.96, 95% confidence interval 1.09-3.52, P=0.025). Most recurrences occurred within 6 months of the first CDI, and the recurrence of CDI was associated with a trend for increased risk of mortality. This prompts the need for further investigation into secondary prophylaxis to prevent recurrent CDI. PMID:26726944

  1. Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

    PubMed

    Avery, R K; Bolwell, B J; Yen-Lieberman, B; Lurain, N; Waldman, W J; Longworth, D L; Taege, A J; Mossad, S B; Kohn, D; Long, J R; Curtis, J; Kalaycio, M; Pohlman, B; Williams, J W

    2004-12-01

    Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined. PMID:15489872

  2. Antitumor effects of HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation.

    PubMed

    Ciceri, Fabio; Bonini, Chiara; Marktel, Sarah; Zappone, Elisabetta; Servida, Paolo; Bernardi, Massimo; Pescarollo, Alessandra; Bondanza, Attilio; Peccatori, Jacopo; Rossini, Silvano; Magnani, Zulma; Salomoni, Monica; Benati, Claudia; Ponzoni, Maurilio; Callegaro, Luciano; Corradini, Paolo; Bregni, Marco; Traversari, Catia; Bordignon, Claudio

    2007-06-01

    The extensive exploitation of the antitumor effect of donor lymphocytes infused after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is limited by the risk of graft-versus-host disease (GvHD). To overcome this limitation, we investigated the therapeutic potential of donor lymphocytes engineered with the suicide gene thymidine kinase of herpes simplex virus (TK) in 23 patients experiencing recurrence of hematologic malignancies after allo-HSCT. Long-term follow-up of infused patients included analysis of engraftment of genetically engineered lymphocytes, in vivo assessment of antitumor effect, and control of GvHD by ganciclovir. All 17 patients evaluable for engraftment and graft-versus-leukemia (GvL) had circulating TK(+) cells detectable beginning at a median time of 18 days. Eleven patients (65%) experienced a substantial clinical benefit resulting in 6 (35%) complete remissions and 5 (29%) partial responses. The antitumor effect tightly correlated with the in vivo expansion of TK(+) cells. Seven patients received ganciclovir, resulting in elimination of TK(+) cells and effective and selective treatment of GvHD. Immunization against HSV-TK was observed in 7 patients but did not preclude an effective GvL. These data validate the feasibility, safety, and efficacy of TK(+) cells in the context of allografting and represent the basis for a broader application of this technology. PMID:17327416

  3. Spinal fluid lymphocytes responsive to autologous and allogeneic cells in multiple sclerosis and control individuals.

    PubMed Central

    Birnbaum, G; Kotilinek, L; Schwartz, M; Sternad, M

    1984-01-01

    Spinal fluid lymphocytes from multiple sclerosis (MS) patients and controls were stimulated with either autologous non-T cells or with allogeneic non-T cells followed by stimulation with autologous non-T lymphocytes. Cells responding to these stimuli were cloned and their proliferative responses to autologous and allogeneic MS and normal non-T cells were measured. Large numbers of clones with specific patterns of reaction to both autologous and allogeneic cells were obtained from lymphocytes in MS cerebrospinal fluid (CSF), but only occasionally from cells in control CSF. Patterns of responses among clones from a particular CSF were similar and often identical, which suggested that cells in MS CSF were relatively restricted in their specificities. Surface antigen phenotyping of the clones showed them to be predominantly OKT4+, with 13% OKT8+ and 11% OKT4+8+. Peripheral T cells that were stimulated and cultured in parallel with CSF cells were different in that they usually did not give rise to as many clones nor were their patterns of response similar. Many CSF clones were heteroclitic, that is they responded to particular allogeneic cells but not autologous cells. Lymphocytes in MS CSF thus appear to represent a selected population of cells with a high frequency of responsiveness to autologous and allogeneic antigens. Such responses may be evidence for immune regulation within the central nervous system or could represent responses to altered-self antigens. PMID:6237121

  4. Regenerative stromal cell therapy in allogeneic hematopoietic stem cell transplantation: Current impact and future directions

    PubMed Central

    Auletta, Jeffery J.; Cooke, Kenneth R.; Solchaga, Luis A.; Deans, Robert J.; Hof, Wouter van’t

    2014-01-01

    Regenerative stromal cell therapy (RSCT) has the potential to become a novel therapy for preventing and treating acute graft-versus-host disease (GVHD) in the allogeneic hematopoietic stem cell transplant (HSCT) recipient. However, enthusiasm for using RSCT in allogeneic HSCT has been tempered by limited clinical data and poorly-defined in vivo mechanisms of action. As a result, the full clinical potential of RSCT in supporting hematopoietic reconstitution and as treatment for GVHD remains to be determined. This manuscript reviews the immunomodulatory activity of regenerative stromal cells in pre-clinical models of allogeneic HSCT and emphasizes an emerging literature suggesting that microenvironment influences RSC activation and function. Understanding this key finding may ultimately define the proper niche for RSCT in allogeneic HSCT. In particular, mechanistic studies are needed to delineate the in vivo effects of RSCT in response to inflammation and injury associated with allogeneic HSCT and to define the relevant sites of RSC interaction with immune cells in the transplant recipient. Furthermore, development of in vivo imaging technology to correlate biodistribution patterns, desired RSC effect, and clinical outcome will be crucial to establishing dose-response effects and minimal biologic-dose thresholds needed to advance translational treatment strategies for complications like GVHD. PMID:20018250

  5. Effect of different adhesion strategies on fiber post cementation: Push-out test and scanning electron microscopy analysis

    PubMed Central

    Saraiva, Letícia Oliveria; Aguiar, Thaiane Rodrigues; Costa, Leonardo; Correr-Sobrinho, Lourenço; Muniz, Leonardo; Mathias, Paula

    2013-01-01

    Aim: The aim of this study was to investigate the effect of phosphoric acid etching and the dentin pre-treatment with sodium hypochlorite (NaOCl) on the push-out bond strength between fiber post and root canal dentin. Materials and Methods: Root canals of 48 human incisors were selected, post spaces were prepared and assigned to four groups: G1-37% phosphoric acid (15 s); G2-5.25% NaOCl (2 min) +37% phosphoric acid (15 s); G3-37% phosphoric acid (60 s); and G4-5.25% NaOCl (2 min) +37% phosphoric acid (60 s). Fiber post cementation was performed with two-step etch-and-rinse adhesive system/dual-cured resin cement according to the manufacturer's recommendation. After 24 h, each root was sectioned transversally into three slices (cervical, middle and apical) and the bond strength of each section was determined using a push-out bond strength test. Morphology analysis of the bonded interface was evaluated using a scanning electron microscopy. Push-out strength data (MPa) were analyzed by Analysis of Variance and Tukey-Kramer (α = 0.05). Results: Considering the NaOCl pre-treatment, no statistically significant differences were observed among groups; however, when the phosphoric acid was applied during 60 s in the apical portion without NaOCl pre-treatment, the bond strength was statistically significant increased. Conclusion: The NaOCl pre-treatment did not improve the bond strength of adhesive luting cement to root canal dentin. The findings suggest that the use of 37% phosphoric acid for 60 s may have a beneficial effect on bond strength in the apical root third. PMID:24403786

  6. Combined Use of Post-Ion Mobility/Collision-Induced Dissociation and Chemometrics for b Fragment Ion Analysis

    NASA Astrophysics Data System (ADS)

    Zekavat, Behrooz; Miladi, Mahsan; Becker, Christopher; Munisamy, Sharon M.; Solouki, Touradj

    2013-09-01

    Although structural isomers may yield indistinguishable ion mobility (IM) arrival times and similar fragment ions in tandem mass spectrometry (MS), it is demonstrated that post-IM/collision-induced dissociation MS (post-IM/CID MS) combined with chemometrics can enable independent study of the IM-overlapped isomers. The new approach allowed us to investigate the propensity of selected b type fragment ions from AlaAlaAlaHisAlaAlaAla-NH2 (AAA(His)AAA) heptapeptide to form different isomers. Principle component analysis (PCA) of the unresolved post-IM/CID profiles indicated the presence of two different isomer types for b4 +, b5 +, and b6 + and a single isomer type for b7 + fragments of AAA(His)AAA. We employed a simple-to-use interactive self-modeling mixture analysis (SIMPLISMA) to calculate the total IM profiles and CID mass spectra of b fragment isomers. The deconvoluted CID mass spectra showed discernible fragmentation patterns for the two isomers of b4 +, b5 +, and b6 + fragments. Under our experimental conditions, calculated percentages of the "cyclic" isomers (at the 95 % confidence level for n = 3) for b4 +, b5 +, and b6 + were 61 (± 5) %, 36 (± 5) %, and 48 (± 2) %, respectively. Results from the SIMPLISMA deconvolution of b5 + species resembled the CID MS patterns of fully resolved IM profiles for the two b5 + isomers. The "cyclic" isomers for each of the two-component b fragment ions were less susceptible to ion fragmentation than their "linear" counterparts.

  7. Application of response surface methodology (RSM) to the optimization of a post-column luminol chemiluminescence analysis of silyl peroxides.

    PubMed

    Baj, Stefan; Słupska, Roksana; Krawczyk, Tomasz

    2013-01-15

    The possibility of the utilization of chemiluminescence post-column luminol oxidation (CL) in a HPLC system for silyl peroxides analysis has been investigated. The conditions of HPLC separation for 12 silyl peroxides, representing bissilyl and alkyl-silyl peroxides, as well as their potential impurities, were established. Optimal chemiluminescent post-column reaction conditions were found using central composite design (CCD) and response surface methodology (RSM). The interaction effects of four of the most important operating variables - the concentrations of luminol, hemin, sodium hydroxide and the post-column solution flow rate - on the light intensity were evaluated. The optimized conditions for analysis were the same for bissilyl and alkyl-silyl peroxides for the base concentration (0.03 M), the luminol concentration (0.4 g L(-1)) and the hemin concentration (0.3 g L(-1)). The only differences occurred in a reagent flow rate (for bissilyl peroxide -0.3 mL min(-1) and for alkyl-silyl peroxides -0.9 mL min(-1)). Under optimal conditions, the detection limits were in the 0.07-0.16 nM range for bissilyl, and 0.53-1.01 for alkyl-silyl peroxides. The calibration curves were linear in the 0.25-3 nM range for bissilyl and the 2.5-25 range for alkyl-silyl peroxides. Intra-day and inter-day precision was lower than 5.5% for each tested concentration level. A mechanism of luminol oxidation by silyl peroxides involving a hydrolysis step with the formation of hydrogen peroxide or hydroperoxide was proposed.

  8. Risk factors of Ganciclovir-related neutropenia after allogeneic stem cell transplantation: a retrospective monocentre study on 547 patients.

    PubMed

    Venton, G; Crocchiolo, R; Fürst, S; Granata, A; Oudin, C; Faucher, C; Coso, D; Bouabdallah, R; Berger, P; Vey, N; Ladaique, P; Chabannon, C; le Merlin, M; Blaise, D; El-Cheikh, J

    2014-02-01

    Cytomegalovirus (CMV) infection is a serious complication that may occur in the weeks or months following bone marrow transplantation. However, both Ganciclovir and the CMV infection itself can cause marrow toxicity, notably neutropenia, that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. The aim of this retrospective study was to identify factors associated with the occurrence of grade III-IV neutropenia among patients receiving pre-emptive Ganciclovir therapy after allogeneic stem cell transplantation at our Institution. We identified 547 consecutive patients transplanted from January 2005 to June 2011 at our Institution. In all, 190 patients (35%) presented with CMV reactivation of whom 30 patients (5%) were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally, 160 (29%) patients were analysed. According to multivariate analysis, at the time of treatment initiation, the risk factors significantly associated with a grade III-IV Ganciclovir-related neutropenia included a high viral load (hazard ratio (HR) = 2.68, 95% CI 1.25-5.737, p 0.01); an absolute neutrophil count >3000 was a protective factor (HR = 0.26, 95% CI 0.125-0.545, p <0001) whereas serum creatinine >2 mg/dL was associated with higher Ganciclovir-related neutropenia (HR = 2.4, 95% CI 1.11-5.17, p 0.002). This large analysis revealed three risk factors for Ganciclovir-related neutropenia among patients with CMV reactivation after allogeneic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, so reducing the morbidity and mortality associated with CMV reactivation.

  9. Non-Occupational Post-Exposure Prophylaxis for HIV: 10-Year Retrospective Analysis in Seattle, Washington

    PubMed Central

    McDougal, Sarah J.; Alexander, Jeremiah; Dhanireddy, Shireesha; Harrington, Robert D.; Stekler, Joanne D.

    2014-01-01

    Despite treatment guidelines in place since 2005, non-occupational post-exposure HIV prophylaxis (nPEP) remains an underutilized prevention strategy. We conducted a retrospective chart review of patients presenting to a publicly-funded HIV clinic in Seattle, Washington for nPEP between 2000 and 2010 (N = 360). nPEP prescriptions were provided for 324 (90%) patients; 83% of prescription decisions were appropriate according to Centers for Disease Control and Prevention guidelines, but only 31% (N = 111/360) of patients were considered “high risk.” In order to use limited resources most efficiently, public health agencies should target messaging for this high-cost intervention to individuals with high-risk HIV exposures. PMID:25140868

  10. Phase-retrieval analysis of pre- and post-repair Hubble Space Telescope images.

    PubMed

    Krist, J E; Burrows, C J

    1995-08-01

    Phase-retrieval measurements of point-spread functions from the pre- and post-repair Hubble Space Telescope are presented. The primary goal was to determine the aberrations present in the second wide-field and planetary camera (WFPC2) to align and validate its corrective optics. With both parametric model-fitting techniques and iterative (Gerchberg-Saxton) methods, accurate measurements have been obtained of the WFPC2 and Hubble Space Telescope optics, including improved maps of the zonal errors in the mirrors. Additional phase-retrieval results were obtained for the aberrated, prerepair cameras and the corrected faint-object camera. The information has been used to improve models produced by point-spread-function simulation programs. On the basis of the measurements a conic constant for the primary mirror of κ = -1.0144 has been derived.

  11. Linear MHD stability analysis of post-disruption plasmas in ITER

    NASA Astrophysics Data System (ADS)

    Aleynikova, K.; Huijsmans, G. T. A.; Aleynikov, P.

    2016-05-01

    Most of the plasma current can be replaced by a runaway electron (RE) current during plasma disruptions in ITER. In this case the post-disruption plasma current profile is likely to be more peaked than the pre-disruption profile. The MHD activity of such plasma will affect the runaway electron generation and confinement and the dynamics of the plasma position evolution (Vertical Displacement Event), limiting the timeframe for runaway electrons and disruption mitigation. In the present paper, we evaluate the influence of the possible RE seed current parameters on the onset of the MHD instabilities. By varying the RE seed current profile, we search for subsequent plasma evolutions with the highest and the lowest MHD activity. This information can be applied to a development of desirable ITER disruption scenario.

  12. Space shuttle post-entry and landing analysis. Volume 1: Candidate system evaluations

    NASA Technical Reports Server (NTRS)

    Crawford, B. S.; Duiven, E. M.

    1973-01-01

    The general purpose of this study is to aid in the evaluation and design of multi-sensor navigation schemes proposed for the orbiter. The scope of the effort is limited to the post-entry, energy management, and approach and landing mission phases. One candidate system based on conventional navigation aids is illustrated including two DME (Distance Measuring Equipment) stations and ILS (Instrument Landing System) glide slope and localizer antennas. Some key elements of the system not shown are the onboard IMUs (Inertial Measurement Units), altimeters, and a computer. The latter is programmed to mix together (filter) the IMU data and the externally-derived data. A completely automatic, all-weather landing capability is required. Since no air-breathing engines will be carried on orbital flights, there will be no chance to go around and try again following a missed approach.

  13. Post-flight Analysis of Mars Science Laboratory Entry Aerothermal Environment and Thermal Protection System Response

    NASA Technical Reports Server (NTRS)

    White, Todd Richard; Mahazari, Milad; Bose, Deepak; Santos, Jose Antonio

    2013-01-01

    The Mars Science Laboratory successfully landed on the Martian surface on August 5th, 2012. The rover was protected from the extreme heating environments of atmospheric entry by an ablative heatshield. This Phenolic Impregnated Carbon Ablator heatshield was instrumented with a suite of embedded thermocouples, isotherm sensors, and pressure transducers. The sensors monitored the in-depth ablator response, as well as the surface pressure at discrete locations throughout the hypersonic deceleration. This paper presents a comparison of the flight data with post-entry estimates. An assessment of the aerothermal environments, as well as the in-depth response of the heatshield material is made, and conclusions regarding the overall performance of the ablator at the suite locations are presented.

  14. Contraband tobacco on post-secondary campuses in Ontario, Canada: analysis of discarded cigarette butts

    PubMed Central

    2013-01-01

    Background No studies to date have assessed young adults’ use of First Nations/Native tobacco, a common form of contraband tobacco in Canada. This study examined the proportion of First Nations/Native cigarette butts discarded on post-secondary campuses in the province of Ontario, and potential differences between colleges and universities and across geographical regions. Methods In 2009, discarded cigarette butts were collected from high-traffic smoking locations at 12 universities and 13 colleges purposively selected to represent a variety of institutions from all 7 health service regions across Ontario. Cigarette butts were identified as First Nations/Native tobacco if they were: known First Nations/Native brands; had names not matching domestic and international legally-manufactured cigarettes; had no visible branding or logos. Results Of 36,355 butts collected, 14% (95% CI = 9.75–19.04) were First Nations/Native. Use of this tobacco was apparent on all campuses, accounting for as little as 2% to as much as 39% of cigarette consumption at a particular school. Proportions of First Nations/Native butts were not significantly higher on colleges (M = 17%) than universities (M = 12%), but were significantly higher in the North region. Conclusions The presence of cheap First Nations/Native (contraband) tobacco on post-secondary campuses suggests the need for regulation and public education strategies aimed to reduce its use. Strategies should account for regional variations, and convey messages that resonate with young adults. Care must be taken to present fair messages about First Nations/Native tobacco, and avoid positioning regulated tobacco as a healthier option than contraband. PMID:23577796

  15. The cost of post-abortion care in developing countries: a comparative analysis of four studies.

    PubMed

    Vlassoff, Michael; Singh, Susheela; Onda, Tsuyoshi

    2016-10-01

    Over the last five years, comprehensive national surveys of the cost of post-abortion care (PAC) to national health systems have been undertaken in Ethiopia, Uganda, Rwanda and Colombia using a specially developed costing methodology-the Post-abortion Care Costing Methodology (PACCM). The objective of this study is to expand the research findings of these four studies, making use of their extensive datasets. These studies offer the most complete and consistent estimates of the cost of PAC to date, and comparing their findings not only provides generalizable implications for health policies and programs, but also allows an assessment of the PACCM methodology. We find that the labor cost component varies widely: in Ethiopia and Colombia doctors spend about 30-60% more time with PAC patients than do nurses; in Uganda and Rwanda an opposite pattern is found. Labor costs range from I$42.80 in Uganda to I$301.30 in Colombia. The cost of drugs and supplies does not vary greatly, ranging from I$79 in Colombia to I$115 in Rwanda. Capital and overhead costs are substantial amounting to 52-68% of total PAC costs. Total costs per PAC case vary from I$334 in Rwanda to I$972 in Colombia. The financial burden of PAC is considerable: the expense of treating each PAC case is equivalent to around 35% of annual per capita income in Uganda, 29% in Rwanda and 11% in Colombia. Providing modern methods of contraception to women with an unmet need would cost just a fraction of the average expenditure on PAC: one year of modern contraceptive services and supplies cost only 3-12% of the average cost of treating a PAC patient. PMID:27045001

  16. The cost of post-abortion care in developing countries: a comparative analysis of four studies

    PubMed Central

    Vlassoff, Michael; Singh, Susheela; Onda, Tsuyoshi

    2016-01-01

    Over the last five years, comprehensive national surveys of the cost of post-abortion care (PAC) to national health systems have been undertaken in Ethiopia, Uganda, Rwanda and Colombia using a specially developed costing methodology—the Post-abortion Care Costing Methodology (PACCM). The objective of this study is to expand the research findings of these four studies, making use of their extensive datasets. These studies offer the most complete and consistent estimates of the cost of PAC to date, and comparing their findings not only provides generalizable implications for health policies and programs, but also allows an assessment of the PACCM methodology. We find that the labor cost component varies widely: in Ethiopia and Colombia doctors spend about 30–60% more time with PAC patients than do nurses; in Uganda and Rwanda an opposite pattern is found. Labor costs range from I$42.80 in Uganda to I$301.30 in Colombia. The cost of drugs and supplies does not vary greatly, ranging from I$79 in Colombia to I$115 in Rwanda. Capital and overhead costs are substantial amounting to 52–68% of total PAC costs. Total costs per PAC case vary from I$334 in Rwanda to I$972 in Colombia. The financial burden of PAC is considerable: the expense of treating each PAC case is equivalent to around 35% of annual per capita income in Uganda, 29% in Rwanda and 11% in Colombia. Providing modern methods of contraception to women with an unmet need would cost just a fraction of the average expenditure on PAC: one year of modern contraceptive services and supplies cost only 3–12% of the average cost of treating a PAC patient. PMID:27045001

  17. Structure-Function Analysis of CCL28 in the Development of Post-viral Asthma*

    PubMed Central

    Thomas, Monica A.; Buelow, Becky J.; Nevins, Amanda M.; Jones, Stephanie E.; Peterson, Francis C.; Gundry, Rebekah L.; Grayson, Mitchell H.; Volkman, Brian F.

    2015-01-01

    CCL28 is a human chemokine constitutively expressed by epithelial cells in diverse mucosal tissues and is known to attract a variety of immune cell types including T-cell subsets and eosinophils. Elevated levels of CCL28 have been found in the airways of individuals with asthma, and previous studies have indicated that CCL28 plays a vital role in the acute development of post-viral asthma. Our study builds on this, demonstrating that CCL28 is also important in the chronic post-viral asthma phenotype. In the absence of a viral infection, we also demonstrate that CCL28 is both necessary and sufficient for induction of asthma pathology. Additionally, we present the first effort aimed at elucidating the structural features of CCL28. Chemokines are defined by a conserved tertiary structure composed of a three-stranded β-sheet and a C-terminal α-helix constrained by two disulfide bonds. In addition to the four disulfide bond-forming cysteine residues that define the traditional chemokine fold, CCL28 possesses two additional cysteine residues that form a third disulfide bond. If all disulfide bonds are disrupted, recombinant human CCL28 is no longer able to drive mouse CD4+ T-cell chemotaxis or in vivo airway hyper-reactivity, indicating that the conserved chemokine fold is necessary for its biologic activity. Due to the intimate relationship between CCL28 and asthma pathology, it is clear that CCL28 presents a novel target for the development of alternative asthma therapeutics. PMID:25556652

  18. Functional analysis of Scr during embryonic and post-embryonic development in the cockroach, Periplaneta americana.

    PubMed

    Hrycaj, Steven; Chesebro, John; Popadić, Aleksandar

    2010-05-01

    The cockroach, Periplaneta americana represents a basal insect lineage that undergoes the ancestral hemimetabolous mode of development. Here, we examine the embryonic and post-embryonic functions of the hox gene Scr in Periplaneta as a way of better understanding the roles of this gene in the evolution of insect body plans. During embryogenesis, Scr function is strictly limited to the head with no role in the prothorax. This indicates that the ancestral embryonic function of Scr was likely restricted to the head, and that the posterior expansion of expression in the T1 legs may have preceded any apparent gain of function during evolution. In addition, Scr plays a pivotal role in the formation of the dorsal ridge, a structure that separates the head and thorax in all insects. This is evidenced by the presence of a supernumerary segment that occurs between the labial and T1 segments of RNAiScr first nymphs and is attributed to an alteration in engrailed (en) expression. The fact that similar Scr phenotypes are observed in Tribolium but not in Drosophila or Oncopeltus reveals the presence of lineage-specific variation in the genetic architecture that controls the formation of the dorsal ridge. In direct contrast to the embryonic roles, Scr has no function in the head region during post-embryogenesis in Periplaneta, and instead, strictly acts to provide identity to the T1 segment. Furthermore, the strongest Periplaneta RNAiScr phenotypes develop ectopic wing-like tissue that originates from the posterior region of the prothoracic segment. This finding provides a novel insight into the current debate on the morphological origin of insect wings.

  19. Top-Down Analysis of Highly Post-Translationally Modified Peptides by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Guerrero, Andres; Lerno, Larry; Barile, Daniela; Lebrilla, Carlito B.

    2015-03-01

    Bovine κ-caseinoglycomacropeptide (GMP) is a highly modified peptide from κ-casein produced during the cheese making process. The chemical nature of GMP makes analysis by traditional proteomic approaches difficult, as the peptide bears a strong net negative charge and a variety of post-translational modifications. In this work, we describe the use of electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) for the top-down analysis of GMP. The method allows the simultaneous detection of different GMP forms that result from the combination of amino acid genetic variations and post-translational modifications, specifically phosphorylation and O-glycosylation. The different GMP forms were identified by high resolution mass spectrometry in both negative and positive mode and confirmation was achieved by tandem MS. The results showed the predominance of two genetic variants of GMP that occur as either mono- or bi-phosphorylated species. Additionally, these four forms can be modified with up to two O-glycans generally sialylated. The results demonstrate the presence of glycosylated, bi-phosphorylated forms of GMP never described before.

  20. Effect of precut sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis: A systematic review and meta-analysis

    PubMed Central

    Choudhary, Abhishek; Winn, Jessica; Siddique, Sameer; Arif, Murtaza; Arif, Zainab; Hammoud, Ghassan M; Puli, Srinivas R; Ibdah, Jamal A; Bechtold, Matthew L

    2014-01-01

    AIM: To conduct a systemic review and meta-analysis to investigate the role of early precut technique. Multiple randomized controlled trails (RCTs) have reported conflicting results of the early precut sphincterotomy. METHODS: MEDLINE/PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and recent abstracts from major conference proceedings were searched (June 2013). Randomized and non-randomized studies comparing early precut technique with prolonged standard methods were included. Pooled estimates of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP), cannulation and adverse events were analyzed by using odds ratio (OR). Random and fixed effects models were used as appropriate. Publication bias was assessed by funnel plots. Heterogeneity among studies was assessed by calculating I2 measure of inconsistency. RESULTS: Seven randomized and seven non-randomized trials met inclusion criteria. Meta-analysis of RCTs showed a decrease trend for PEP with early precut sphincterotomy but was not statistically significant (OR = 0.58; 95%CI: 0.32-1.05; P = 0.07). No heterogeneity was noted among the studies with I2 of 0%. CONCLUSION: Early precut technique for common bile duct cannulation decreases the trend of post-ERCP pancreatitis. PMID:24744601

  1. Altered post-mortem metabolism identified in very fast chilled lamb M. longissimus thoracis et lumborum using metabolomic analysis.

    PubMed

    Warner, Robyn D; Jacob, Robin H; Rosenvold, Katja; Rochfort, Simone; Trenerry, Craige; Plozza, Tim; McDonagh, Matthew B

    2015-10-01

    The aim of this experiment was to use metabolomic techniques to investigate the energy metabolism in lamb M. longissimus thoracis et lumborum subjected to very fast chilling (VFC) post-mortem. The tissue was prepared by 2 different operators and subjected to very fast chilling (less than 0°C within 1.5h of slaughter) or typical chilling regimes (Control; 0°C within 22h of slaughter). Non-targeted metabolomic analysis ((1)H NMR) and targeted analysis ((31)P NMR, HPLC-PDA and HPLC-MS/MS) were used to examine the change in muscle metabolites post-mortem. One VFC treatment, which resulted in a colder core temperature and more tender meat, had higher levels of glycolytic intermediate metabolites pre-rigor as well as more of the end-products of adenosine and nicotine nucleotide metabolism pre-rigor, relative to conventionally chilled treatments. In conclusion, VFC to less than 0°C within 1.5h of slaughter causes considerable changes in metabolism and rigor onset, which are associated with tender meat. PMID:26163181

  2. Mass-spectrometry analysis of histone post-translational modifications in pathology tissue using the PAT-H-MS approach.

    PubMed

    Noberini, Roberta; Pruneri, Giancarlo; Minucci, Saverio; Bonaldi, Tiziana

    2016-06-01

    Aberrant histone post-translational modifications (hPTMs) have been implicated with various pathologies, including cancer, and may represent useful epigenetic biomarkers. The data described here provide a mass spectrometry-based quantitative analysis of hPTMs from formalin-fixed paraffin-embedded (FFPE) tissues, from which histones were extracted through the recently developed PAT-H-MS method. First, we analyzed FFPE samples from mouse spleen and liver or human breast cancer up to six years old, together with their corresponding fresh frozen tissue. We then combined the PAT-H-MS approach with a histone-focused version of the super-SILAC strategy-using a mix of histones from four breast cancer cell lines as a spike-in standard- to accurately quantify hPTMs from breast cancer specimens belonging to different subtypes. The data, which are associated with a recent publication (Pathology tissue-quantitative mass spectrometry analysis to profile histone post-translational modification patterns in patient samples (Noberini, 2015) [1]), are deposited at the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD002669. PMID:27408908

  3. Analysis of post-blasting source mechanisms of mining-induced seismic events in Rudna copper mine, Poland.

    NASA Astrophysics Data System (ADS)

    Caputa, Alicja; Rudzinski, Lukasz; Talaga, Adam

    2016-04-01

    Copper ore exploitation in the Lower Silesian Copper District, Poland (LSCD), is connected with many specific hazards. The most hazardous one is induced seismicity and rockbursts which follow strong mining seismic events. One of the most effective method to reduce seismic activity is blasting in potentially hazardous mining panels. This way, small to moderate tremors are provoked and stress accumulation is substantially reduced. This work presents an analysis of post-blasting events using Full Moment Tensor (MT) inversion at the Rudna mine, Poland using signals dataset recorded on underground seismic network. We show that focal mechanisms for events that occurred after blasts exhibit common features in the MT solution. The strong isotropic and small Double Couple (DC) component of the MT, indicate that these events were provoked by detonations. On the other hand, post-blasting MT is considerably different than the MT obtained for common strong mining events. We believe that seismological analysis of provoked and unprovoked events can be a very useful tool in confirming the effectiveness of blasting in seismic hazard reduction in mining areas.

  4. del Nido versus St. Thomas Cardioplegia Solutions: A Single-Center Retrospective Analysis of Post Cross-Clamp Defibrillation Rates.

    PubMed

    Buel, Shane T; Striker, Carrie Whittaker; O'Brien, James E

    2016-06-01

    There are many cardioplegia solutions currently in use for pediatric cardiopulmonary bypass (CPB). The most common being del Nido solution. Another common cardioplegia solution used for pediatric CPB is St. Thomas. In October 2014, Children's Mercy Kansas City changed from the use of modified St. Thomas to del Nido. This study compared rates of post cross-clamp fibrillation requiring defibrillation between del Nido solution and modified St. Thomas solution stratified by weight at Children's Mercy Kansas City. This retrospective study consisted of 394 patients who underwent cardiac surgery requiring cardioplegia between January 1, 2014 and July 31, 2015. The outcome measured was defibrillation upon cross-clamp removal. Statistical significance was determined using Fishers exact test with a two-sided significance level of .05. Incidence of defibrillation post cross-clamp removal was 4.4% in the del Nido group and 26.8% in the St. Thomas group (p < .0001). Analysis by weight stratifications displays a reduction in post cross-clamp defibrillation rates in groups using the del Nido solution. The 0- to 6-kg category had an incidence of fibrillation of 1.23% in the del Nido group and 17.5% in the St. Thomas group (p < .0003). The 6- to 15-kg category had an incidence of defibrillation of 1.82% in the del Nido group and 14% in the St. Thomas group (p < .0198). The 15- to 60-kg category had an incidence of defibrillation of 8.9% in the del Nido group and 61% in the St. Thomas group (p < .0001). The >60-kg category had an incidence of defibrillation of 16.7% in the del Nido group and 63% in the St. Thomas group (p < .0623). This study demonstrates a 6-fold decrease in the overall rate of defibrillation post cross-clamp removal between St. Thomas and del Nido cardioplegia solutions. Analyses of weight stratifications demonstrate a decrease in the rate of defibrillation post cross-clamp removal in all categories within the del Nido group. PMID:27578896

  5. Younger women's experiences of deciding against delayed breast reconstruction post-mastectomy following breast cancer: An interpretative phenomenological analysis.

    PubMed

    Holland, Fiona; Archer, Stephanie; Montague, Jane

    2016-08-01

    Most women do not reconstruct their breast(s) post-mastectomy. The experiences of younger women who maintain this decision, although important to understand, are largely absent in the research literature. This interview-based study uses interpretative phenomenological analysis to explore the experiences of six women, diagnosed with primary breast cancer in their 30s/40s, who decided against delayed reconstruction. Findings reported here focus on one superordinate theme (decision-making) from a larger analysis, illustrating that the women's drive to survive clearly influenced their initial decision-making process. Their tenacity in maintaining their decision is highlighted, despite non-reconstruction sometimes being presented negatively by medical teams. Patient-centred support recommendations are made.

  6. Finite Element Analysis of the Stability (Buckling and Post-Buckling) of Composite Laminated Structures: Well Established Procedures and Challenges

    NASA Astrophysics Data System (ADS)

    Pietropaoli, Elisa; Riccio, Aniello

    2012-02-01

    Finite element procedures for the analysis of composite structures under compressive loads (buckling and post-buckling) generally are not deployed in books because they are still considered object of research whereas they are deemed as assessed by researchers that focus their papers on restricted audience topics. Therefore, regarding these procedures, a gap exists in literature between what researchers consider as well established and what has been already published. The aim of this paper is to contribute to close this gap by providing an insight in linear and non-linear buckling analyses and in their use with composite structures. Both modelling and analysis considerations are presented and discussed, focusing on what can be considered as best practice when dealing with this kind of problems. Applications (to a stiffened panel and to a wing box) are provided for demonstrating the effectiveness of the procedures presented.

  7. Analysis of Amphiphilic Lipids and Hydrophobic Proteins Using Nonresonant Femtosecond Laser Vaporization with Electrospray Post-Ionization

    NASA Astrophysics Data System (ADS)

    Brady, John J.; Judge, Elizabeth J.; Levis, Robert J.

    2011-04-01

    Amphiphilic lipids and hydrophobic proteins are vaporized at atmospheric pressure using nonresonant 70 femtosecond (fs) laser pulses followed by electrospray post-ionization prior to being transferred into a time-of-flight mass spectrometer for mass analysis. Measurements of molecules on metal and transparent dielectric surfaces indicate that vaporization occurs through a nonthermal mechanism. The molecules analyzed include the lipids 1-monooleoyl-rac-glycerol, 1,2-dihexanoyl- sn-glycero-3-phosphocholine, 1,2-dimyristoyl- sn-glycero-3-phosphocholine, and the hydrophobic proteins gramicidin A, B, and C. Vaporization of lipids from blood and milk are also presented to demonstrate that lipids in complex systems can be transferred intact into the gas phase for mass analysis.

  8. NCI 1st International Workshop on the Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Summary and Recommendations from the Organizing Committee

    PubMed Central

    Bishop, Michael R.; Alyea, Edwin P.; Cairo, Mitchell S.; Falkenburg, J.H. Frederik; June, Carl H.; Kröger, Nicolaus; Little, Richard F.; Miller, Jeffrey S.; Pavletic, Steven Z.; Porter, David L.; Riddell, Stanley R.; van Besien, Koen; Wayne, Alan S.; Weisdorf, Daniel J.; Wu, Roy S.; Giralt, Sergio

    2011-01-01

    The First International Workshop on The Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation was organized and convened to identify, prioritize, and coordinate future research activities related to relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT). Each of the Workshop’s six working committees have published individual reports of ongoing basic, translational and clinical research and recommended areas for future research related to the areas of relapse biology, epidemiology, prevention and treatment. This document summarizes each of the committees’ recommendations and suggests three major initiatives for a coordinated research effort to address the problem of relapse after alloHSCT. The first is the need to establish multi-center correlative and clinical trials networks for basic/translational, epidemiological, and clinical research. Second, there is a need for a network of biorepositories for the collection of samples pre- and post-alloHSCT to aid in laboratory and clinical studies. Third, there should be further refinement, implementation, and study of the proposed Workshop disease-specific response and relapse definitions and the recommendations for monitoring of minimal residual disease. These recommendations, in coordination with ongoing research initiatives and transplant organizations, provide a research framework to rapidly and efficiently address the significant problem of relapse following alloHSCT. PMID:21224011

  9. Partitioning the Proteome: Phase Separation for Targeted Analysis of Membrane Proteins in Human Post-Mortem Brain

    PubMed Central

    Scaife, Caitriona; Cotter, David R.; Dunn, Michael J.

    2012-01-01

    Neuroproteomics is a powerful platform for targeted and hypothesis driven research, providing comprehensive insights into cellular and sub-cellular disease states, Gene × Environmental effects, and cellular response to medication effects in human, animal, and cell culture models. Analysis of sub-proteomes is becoming increasingly important in clinical proteomics, enriching for otherwise undetectable proteins that are possible markers for disease. Membrane proteins are one such sub-proteome class that merit in-depth targeted analysis, particularly in psychiatric disorders. As membrane proteins are notoriously difficult to analyse using traditional proteomics methods, we evaluate a paradigm to enrich for and study membrane proteins from human post-mortem brain tissue. This is the first study to extensively characterise the integral trans-membrane spanning proteins present in human brain. Using Triton X-114 phase separation and LC-MS/MS analysis, we enriched for and identified 494 membrane proteins, with 194 trans-membrane helices present, ranging from 1 to 21 helices per protein. Isolated proteins included glutamate receptors, G proteins, voltage gated and calcium channels, synaptic proteins, and myelin proteins, all of which warrant quantitative proteomic investigation in psychiatric and neurological disorders. Overall, our sub-proteome analysis reduced sample complexity and enriched for integral membrane proteins by 2.3 fold, thus allowing for more manageable, reproducible, and targeted proteomics in case vs. control biomarker studies. This study provides a valuable reference for future neuroproteomic investigations of membrane proteins, and validates the use Triton X-114 detergent phase extraction on human post mortem brain. PMID:22745773

  10. Chimerism in DNA of buccal swabs from recipients after allogeneic hematopoietic stem cell transplantations: implications for forensic DNA testing.

    PubMed

    Berger, Burkhard; Parson, Roswitha; Clausen, Johannes; Berger, Cordula; Nachbaur, David; Parson, Walther

    2013-01-01

    We attempted to quantitatively determine the chimeric state in a total of 162 buccal swabs from 77 adult recipients aged 19-74 (median 50 years) after allogeneic hematopoietic cell transplantation by estimating the chimeric recipient/donor DNA ratios through analysis of 15 autosomal short tandem repeat markers. From each individual between one and nine, buccal swabs were taken at known time intervals after transplantation, ranging from 17 to 3,361 days (median 394 days). In buccal cells, the determined recipient/donor DNA ratios turned out to be highly variable between individuals and also within an individual. Relative donor chimerism levels (%Ch) between 0 and 100 % were detected with maximal frequencies between 10 and 30 %. Blood was always found to show the donor's genotype while hair samples in all cases gave the recipient's genotype. We examine chimerism levels with respect to age, gender, and posttransplantation period and discuss the results in the context of forensic identity testing.

  11. Transplantation tolerance in primates after total lymphoid irradiation and allogeneic bone marrow injection

    SciTech Connect

    Smit, J.A.; Hill, R.R.H.; Myburgh, J.A.; Browde, S.

    1980-08-01

    After total lymphoid irradiation (TLI), allogeneic bone marrow (BM) injection, and organ transplantation in baboons, there is a prolonged period of reduced lymphocyte proliferative responsiveness to polyclonal mitogens and allogeneic lymphocytes. The effect observed is greater with the use of fractionated TLI than after single doses of irradiation. Suppressor cell activity can be demonstrated in vitro in most animals by inhibition of mixed lymphocyte reactivity (MLR) by mitomycin-treated recipient lymphocytes harvested after TLI, with or without allogeneic BM injection, and organ transplantation. Preliminary data suggest the presence of both donor-specific and nondonor-specific suppression, although other interpretations are possible, and suppressor phenomena may not be responsible for the transplantation tolerance observed.

  12. Allogeneic hematopoietic stem cell transplantation for Leukocyte Adhesion Deficiency

    PubMed Central

    Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E.Graham; Davis, Jeffery; Duval, Michel; Eames, Gretchen; Farinha, Nuno; Filopovich, Alexandra; Fischer, Alain; Friedrich, Wilhelm; Gennery, Andrew; Heilmann, Carsten; Landais, Paul; Horwitz, Mitchell; Porta, Fulvio; Sedlacek, Petr; Seger, Reinhard; Slatter, Mary; Teague, Lochie; Eapen, Mary; Veys, Paul

    2012-01-01

    OBJECTIVES Leukocyte Adhesion Deficiency (LAD) is a rare primary immune disorder caused by defects of the CD18 β-integrin molecule on immune cells. The condition usually presents in early infancy and is characterised by deep tissue infections, leukocytosis with impaired formation of pus and delayed wound healing. Allogeneic haematopoietic stem cell transplantation (HSCT) offers the possibility of curative therapy, and with patient numbers at any individual centre being limited, we surveyed the transplant experience at 14 centres worldwide. PATIENTS & METHODS The course of 36 children with a confirmed diagnosis of LAD who underwent HSCT between 1993 and 2007 was retrospectively analysed. Data was collected by the registries of the European Society for Immunodeficiencies (ESID)/European Group for Blood and Marrow Transplantation (EBMT), and the Center for International Blood and Marrow Transplant Research (CIBMTR) RESULTS At median followup of 62 months (extending to 14 years) overall survival was 75%. Myeloablative conditioning regimens were used in 28 patients, and reduced intensity conditioning (RIC) in 8 patients, with no deaths in this subgroup. Survival after matched family donor and unrelated donor transplants was similar, with 11/14 matched family donor and 12/14 unrelated donor recipients alive; mortality was greatest following haplo-identical transplants, where 4/8 children did not survive. Twenty seven transplant recipients are alive, with full donor engraftment in 17 cases, mixed multi-lineage chimerism in 7 patients, and mononuclear cell restricted chimerism in a further 3 cases. CONCLUSIONS HSCT offers long term benefit in LAD and should be considered as an early therapeutic option if a suitable HLA-matched stem cell donation is available. Reduced intensity conditioning was particularly safe, and mixed donor chimersim appears sufficient to prevent significant symptoms, although careful long term monitoring will be required for these patients. PMID

  13. Allogenic sedimentary components of Bear Lake, Utah and Idaho

    USGS Publications Warehouse

    Rosenbaum, J.G.; Dean, W.E.; Reynolds, R.L.; Reheis, M.C.

    2009-01-01

    Bear Lake is a long-lived lake filling a tectonic depression between the Bear River Range to the west and the Bear River Plateau to the east, and straddling the border between Utah and Idaho. Mineralogy, elemental geochemistry, and magnetic properties provide information about variations in provenance of allogenic lithic material in last-glacial-age, quartz-rich sediment in Bear Lake. Grain-size data from the siliciclastic fraction of late-glacial to Holocene carbonate-rich sediments provide information about variations in lake level. For the quartz-rich lower unit, which was deposited while the Bear River fl owed into and out of the lake, four source areas are recognized on the basis of modern fluvial samples with contrasting properties that reflect differences in bedrock geology and in magnetite content from dust. One of these areas is underlain by hematite-rich Uinta Mountain Group rocks in the headwaters of the Bear River. Although Uinta Mountain Group rocks make up a small fraction of the catchment, hematite-rich material from this area is an important component of the lower unit. This material is interpreted to be glacial fl our. Variations in the input of glacial flour are interpreted as having caused quasi-cyclical variations in mineralogical and elemental concentrations, and in magnetic properties within the lower unit. The carbonate-rich younger unit was deposited under conditions similar to those of the modern lake, with the Bear River largely bypassing the lake. For two cores taken in more than 30 m of water, median grain sizes in this unit range from ???6 ??m to more than 30 ??m, with the coarsest grain sizes associated with beach or shallow-water deposits. Similar grain-size variations are observed as a function of water depth in the modern lake and provide the basis for interpreting the core grain-size data in terms of lake level. Copyright ?? 2009 The Geological Society of America.

  14. Immune Reconstitution after Allogeneic Hematopoietic Cell