Model Analysis of Time Reversal Symmetry Test in the Caltech Fe-57 Gamma-Transition Experiment

The CALTECH gamma-transition experiment testing time reversal symmetry via the E2/M1 mulipole mixing ratio of the 122 keV gamma-line in Fe-57 has already been performed in 1977. Extending an earlier analysis in terms of an effective one-body potential, this experiment is now analyzed in terms of effective one boson exchange T-odd P-even nucleon nucleon potentials. Within the model space considered for the Fe-57 nucleus no contribution from isovector rho-type exchange is possible. The bound on the coupling strength phi_A from effective short range axial-vector type exchange induced by the experimental bound on sin(eta) leads to phi_A < 10^{-2}.Comment: 5 pages, RevTex 3.

Acute graft versus host disease

Acute graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. About 35%–50% of hematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD. The exact risk is dependent on the stem cell source, age of the patient, conditioning, and GVHD prophylaxis used. Given the number of transplants performed, we can expect about 5500 patients/year to develop acute GVHD. Patients can have involvement of three organs: skin (rash/dermatitis), liver (hepatitis/jaundice), and gastrointestinal tract (abdominal pain/diarrhea). One or more organs may be involved. GVHD is a clinical diagnosis that may be supported with appropriate biopsies. The reason to pursue a tissue biopsy is to help differentiate from other diagnoses which may mimic GVHD, such as viral infection (hepatitis, colitis) or drug reaction (causing skin rash). Acute GVHD is staged and graded (grade 0-IV) by the number and extent of organ involvement. Patients with grade III/IV acute GVHD tend to have a poor outcome. Generally the patient is treated by optimizing their immunosuppression and adding methylprednisolone. About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line) immunosuppressive therapy for which there is currently no standard-of-care. Well-organized clinical trials are imperative to better define second-line therapies for this disease. Additional management issues are attention to wound infections in skin GVHD and fluid/nutrition management in gastrointestinal GVHD. About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD

Late Effects in Hematopoietic Cell Transplant Recipients with Acquired Severe Aplastic Anemia: A Report from the Late Effects Working Committee of the Center for International Blood and Marrow Transplant Research

With improvements in hematopoietic cell transplant (HCT) outcomes for severe aplastic anemia (SAA), there is a growing population of SAA survivors after HCT. However, there is a paucity of information regarding late effects that occur after HCT in SAA survivors. This study describes the malignant and nonmalignant late effects in survivors with SAA after HCT. A descriptive analysis was conducted of 1718 patients post-HCT for acquired SAA between 1995 and 2006 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). the prevalence and cumulative incidence estimates of late effects are reported for 1-year HCT survivors with SAA. of the HCT recipients, 1176 (68.5%) and 542 (31.5%) patients underwent a matched sibling donor (MSD) or unrelated donor (URD) HCT, respectively. the median age at the time of HCT was 20 years. the median interval from diagnosis to transplantation was 3 months for MSD HCT and 14 months for URD HCT. the median follow-up was 70 months and 67 months for MSD and URD HCT survivors, respectively. Overall survival at I year, 2 years, and 5 years for the entire cohort was 76% (95% confidence interval [CI]: 74-78), 73% (95% CI: 71-75), and 70% (95% CI: 68-72). Among 1-year survivors of MSD HCT, 6% had 1 late effect and 1% had multiple late effects. for 1-year survivors of URD HCT, 13% had 1 late effect and 2% had multiple late effects. Among survivors of MSD HCT, the cumulative incidence estimates of developing late effects were all <3% and did not increase over time. in contrast, for recipients of URD HCT, the cumulative incidence of developing several late effects exceeded 3% by 5 years: gonadal dysfunction 10.5% (95% CI: 7.3-14.3), growth disturbance 7.2% (95% CI: 4.4-10.7), avascular necrosis 6.3% (95% CI: 3.6-9.7), hypothyroidism 5.5% (95% CI: 2.8-9.0), and cataracts 5.1% (95% CI: 2.9-8.0). Our results indicated that all patients undergoing HCT for SAA remain at risk for late effects, must be counseled about, and should be monitored for late effects for the remainder of their lives.Public Health Service Grant from the National Cancer InstituteNational Heart, Lung, and Blood InstituteNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteHealth Resources and Services Administration/Department of Health and Human ServicesOffice of Naval ResearchAllosAmgenAngioblastChildrens Hosp Orange Cty, Dept Hematol, Orange, CA 92668 USACIBMTR Med Coll Wisconsin, Dept Biostat, Milwaukee, WI USAMed Coll Wisconsin, CIBMTR Stat Ctr, Milwaukee, WI 53226 USAKing Faisal Specialist Hosp & Res Ctr, Dept Oncol, Riyadh 11211, Saudi ArabiaNew York Med Coll, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Valhalla, NY 10595 USAStemcyte, Covina, CA USADana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USAUniv Florida, Dept Hematol Oncol, Gainesville, FL USAPrincess Margaret Hosp, Dept Med, Toronto, ON M4X 1K9, CanadaUniv S Florida, All Childrens Hosp, Dept Pediat Hematol & Oncol, St Petersburg, FL 33701 USAUniv Basel Hosp, Dept Hematol, CH-4031 Basel, SwitzerlandOregon Hlth & Sci Univ, Dept Hematol & Oncol, Portland, OR 97201 USAChildrens Natl Med Ctr, Dept Blood & Marrow Transplantat, Washington, DC 20010 USABaylor Coll Med, Ctr Cell Therapy, Dept Hematol & Oncol, Houston, TX 77030 USAUniv N Carolina Hosp, Dept Pediat, Chapel Hill, NC USAUniv Hosp Case, Med Ctr, Dept Med, Cleveland, OH USAUniv Arkansas Med Sci, Dept Hematol & Oncol, Little Rock, AR 72205 USACincinnati Childrens Hosp Med Ctr, Dept Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH USATufts Med Ctr, Dept Med & Pediat, Boston, MA USAUniv S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hematol & Oncol, Tampa, FL 33612 USAFlorida Ctr Cellular Therapy, Dept Med, Orlando, FL USAUniv Fed Parana, Dept Bone Marrow Transplantat, BR-80060000 Curitiba, Parana, BrazilVanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USAInst Oncol Pediat, Dept Pediat, São Paulo, BrazilFred Hutchinson Canc Res Ctr, Dept Clin Res & Transplantat, Seattle, WA 98104 USAMt Sinai Med Ctr, Dept Bone Marrow & Stem Cell Transplantat, New York, NY 10029 USAUniv N Carolina Hosp, Dept Hematol & Oncol, Chapel Hill, NC USAUniv Manitoba, CancerCare Manitoba, Dept Manitoba Blood & Marrow Transplant Program, Winnipeg, MB, CanadaKarolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Dept Pediat, Stockholm, SwedenLouisiana State Univ, Hlth Sci Ctr, Childrens Hosp, Dept Pediat, New Orleans, LA USADept Natl Marrow Donor Program, Minneapolis, MN USAPublic Health Service Grant from the National Cancer Institute: U24-CA76518National Heart, Lung, and Blood Institute: 5U01HL069294Office of Naval Research: N00014-06-1-0704Office of Naval Research: N00014-08-1-0058HHSH234200637015CWeb of Scienc

Late effects in hematopoietic cell transplant recipients with acquired severe aplastic anemia: a report from the late effects working committee of the center for international blood and marrow transplant research (CIBMTR)

CHOC Children’s Hospital - UC Irvine, Orange, CAMedical College of Wisconsin, Milwaukee, WIMedical College of Wisconsin, Milwaukee, WIKing Faisal Specialist Hospital and Research Center, Riyadh, TX, Saudi ArabiaNew York Medical College, Valhalla, NYStemcyte, Covina, CADana Farber Cancer Institute, Boston, MAUniversity of Florida, Gainesville, FLPrincess Margaret Hospital, Toronto, ON, CanadaAll Children’s Hospital, St. Petersburg, FLUniversity Hospital Basel, Basel, SwitzerlandOregon Health and Science University, Portland, ORChildren’s National Medical Center, Washington, DCBaylor College of Medicine Center for Cell Therapy, Houston, TXUniversity of North Carolina Hospitals, Chapel Hill, NCUniversity Hospitals Case Medical Center, Cleveland, OHUniversity of Arkansas for Medical Sciences, Little Rock, ARCincinnati Children’s Hospital Medical Center, Cincinnati, OHTufts Medical Center, Boston, MAH Lee Moffitt Cancer Center and Research Institute, Tampa, FLFlorida Center for Cellular Therapy, Orlando, FLUniversidade Federal de Parana, Curitiba, BrazilVanderbilt University Medical Center, Nashville, TNInstituto de Oncologia Pediatrica, Sao Paulo, BrazilFred Hutchinson Cancer Research Center, Seattle, WAMount Sinai Medical Center, New York, NYUniversity of North Carolina, Chapel Hill, NCCancerCare Manitoba, University of Manitoba, Winnipeg, CanadaKarolinska University Hospital, Center for Allogeneic Stem Cell Transplantation, Stockholm, SwedenChildrens Hospital LSU Health Sciences Center, New Orleans, LANational Marrow Donor Program, Minneapolis, MNWeb of Scienc

Outcomes of pediatric patients with therapy-related myeloid neoplasms

Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs

Minimization and management of wastes from biomedical research.

Several committees were established by the National Association of Physicians for the Environment to investigate and report on various topics at the National Leadership Conference on Biomedical Research and the Environment held at the 1--2 November 1999 at the National Institutes of Health in Bethesda, Maryland. This is the report of the Committee on Minimization and Management of Wastes from Biomedical Research. Biomedical research facilities contribute a small fraction of the total amount of wastes generated in the United States, and the rate of generation appears to be decreasing. Significant reductions in generation of hazardous, radioactive, and mixed wastes have recently been reported, even at facilities with rapidly expanding research programs. Changes in the focus of research, improvements in laboratory techniques, and greater emphasis on waste minimization (volume and toxicity reduction) explain the declining trend in generation. The potential for uncontrolled releases of wastes from biomedical research facilities and adverse impacts on the general environment from these wastes appears to be low. Wastes are subject to numerous regulatory requirements and are contained and managed in a manner protective of the environment. Most biohazardous agents, chemicals, and radionuclides that find significant use in research are not likely to be persistent, bioaccumulative, or toxic if they are released. Today, the primary motivations for the ongoing efforts by facilities to improve minimization and management of wastes are regulatory compliance and avoidance of the high disposal costs and liabilities associated with generation of regulated wastes. The committee concluded that there was no evidence suggesting that the anticipated increases in biomedical research will significantly increase generation of hazardous wastes or have adverse impacts on the general environment. This conclusion assumes the positive, countervailing trends of enhanced pollution prevention efforts by facilities and reductions in waste generation resulting from improvements in research methods will continue

Functional Characterization of N297A, A Murine Surrogate for low-Fc Binding Anti-Human CD3 Antibodies

Several low- or non-FcR binding anti-human CD3 monoclonal antibodies have been under investigation for the treatment of autoimmune diseases. To model the mechanism of action of these anti-human CD3 mAbs in the murine system, an Fc-modified anti-mouse CD3 antibody (N297A) was generated. N297A exhibited similar biological effects as Fc-modified anti-human CD3 antibodies including rapid, reversible reduction in peripheral leukocyte numbers, differential modulation of activated versus resting T cells, and reduced levels of induced cytokine release compared to the non-Fc-modified parent antibody. In an in vivo model of colitis induced by adoptive transfer of IL–10-deficient cells, administration of N297A significantly reduced body weight loss. As N297A shared many functional characteristics of non-FcR binding anti-human CD3 mAbs both in vitro and in vivo, it provides a means to model the mechanisms of action of Fc-modified anti-human CD3 antibodies in mouse