Long-term human hematopoiesis in the SCID-hu mouse.

Coimplantation of small fragments of human fetal thymus and fetal liver into immunodeficient SCID mice resulted in the formation of a unique structure (Thy/Liv). Thereafter, the SCID-hu mice showed reproducible and long-term reconstitution of human hematopoietic activity. For periods lasting 5-11 mo after transplantation, active T lymphopoiesis was observed inside the grafts and cells that were negative for T cell markers were found to have colony-forming units for granulocyte/macrophage (CFU-GM) and erythroid burst-forming unit (BFU-E) activity in the methylcellulose colony assay. In addition, structures similar to normal human bone marrow were observed inside the Thy/Liv grafts, consisting of blast cells, mature and immature forms of myelomonocytic cells, and megakaryocytes. These data indicate long-term maintenance, in vivo, of human progenitor cells for the T lymphoid, myelomonocytic, erythroid, and megakaryocytic lineages. The role of the implanted fetal liver fragments was analyzed using HLA-mismatched Thy/Liv implants. The HLA type of the liver donor was found on T cells and macrophages in the graft. In addition, cells grown in the methylcellulose colony assay and cells in a bone marrow-like structure, the thymic isle, expressed the HLA type of the liver donor. Thus, the Thy/Liv implants provided a microenvironment in which to follow human hematopoietic progenitor cells for multiple lineages. The formation of the Thy/Liv structures also results in a continuous source of human T cells in the peripheral circulation of the SCID-hu mouse. Though present for 5-11 mo, these cells did not engage in a xenograft (graft-versus-host) reaction. This animal model, the first in which multilineage human hematopoietic activity is maintained for long periods of time, should be useful for the analysis of human hematopoiesis in vivo

A method for finding new sets of axioms for classes of semigroups

We introduce a general technique for finding sets of axioms for a given class of semigroups. To illustrate the technique, we provide new sets of defining axioms for groups of exponent n, bands, and semilattices

Population pharmacokinetics of cyclophosphamide and metabolites in children with neuroblastoma: a report from the children's oncology group.

Cyclophosphamide-based regimens are front-line treatment for numerous pediatric malignancies; however, current dosing methods result in considerable interpatient variability in tumor response and toxicity. In this pediatric population, the authors' objectives were (1) to quantify and explain the pharmacokinetic variability of cyclophosphamide and 2 of its metabolites, hydroxycyclophosphamide (HCY) and carboxyethylphosphoramide mustard (CEPM), and (2) to apply a population pharmacokinetic model to describe the disposition of cyclophosphamide and these metabolites. A total of 196 blood samples were obtained from 22 children with neuroblastoma receiving intravenous cyclophosphamide (400 mg/m2/d) and topotecan. Blood samples were quantitated for concentrations of cyclophosphamide, HCY, and CEPM using liquid chromatography-mass spectrometry and analyzed using nonlinear mixed-effects modeling with the NONMEM software system. After model building was complete, the area under the concentration-time curve (AUC) was computed using NONMEM. Cyclophosphamide elimination was described by noninducible and inducible routes, with the latter producing HCY. Glomerular filtration rate was a covariate for the fractional elimination of HCY and its conversion to CEPM. Considerable interpatient variability was observed in the AUC of cyclophosphamide, HCY, and CEPM. These results represent a critical first step in developing pharmacokinetic-linked pharmacodynamic studies in children receiving cyclophosphamide to determine the clinical relevance of the pharmacokinetic variability in cyclophosphamide and its metabolites

Lichen traits and species as indicators of vegetation and environment

Lichens in the Arctic play important ecological roles. They also face the threats of increasing fire and shrub and tree expansion, exacerbated or caused by climate change. These forces may lead to changes not only in lichen community composition but also in the abundance, diversity and distribution of lichen functional traits. We sought to connect landscape-scale patterns of lichen community composition and traits to environmental gradients to both monitor lichen communities and clarify community-trait-environment relationships. We measured lichens throughout one of the largest and most remote U.S. National Parks within the Arctic. We then analyzed lichen community composition and species richness within ecologically informative lichen trait groups along environmental and vascular vegetation gradients. Macrolichen species richness in 0.4 ha plots averaged 41 species with a total landscape level observed gamma diversity of 262 macrolichen species. Jackknife estimators placed the landscape level macrolichen diversity at 307 to 331 species. A gradient from low-elevation forests to high elevation rocky areas was the dominant ecological gradient as expressed by the lichen community, representing 68% of the variation in species composition. Low-elevation forests hosted more epiphytic lichens characteristic of boreal forests, whereas high-elevation lichen communities were characterized by saxicolous lichens, varying between siliceous, basic or mafic rock types. Along this gradient, species reproducing vegetatively and lichens with filamentous growth form were more frequent in forests while the diversity of traits was highest in alpine habitats. Simple cladoniiform, as opposed to erectly branched fruticose lichens in the genus Cladonia, were the only functional group associated with tussock tundra. Vegetation types differed significantly in lichen species composition and richness and trait richness; characteristic suites of lichen species and traits are associated with the particular vegetation types in the Arctic. We also extended the range of Fuscopannaria abscondita reported new to North America and Zahlbrucknerella calcarea new to Alaska.Keywords: growth-form, Alaska, vegetative dispersal, Gates of the Arctic National Park and Preserve, photobion

Plasmas and Controlled Nuclear Fusion

Contains reports on twelve research projects split into three sections.National Science Foundation (Grant GK-57)National Science Foundation (Grant GK-1165

Plasma Magnetohydrodynamics and Energy Conversion

Contains reports on seven research projects.U. S. Air Force (Aeronautical Systems Division) under Contract AF33 (615)-1083 with the Air Force Aero Propulsion Laboratory, Wright-Patterson Air Force Base, OhioNational Science Foundation (Grant GK-57

A model to predict cardiovascular events in patients with newly diagnosed Wegener's granulomatosis and microscopic polyangiitis

Objective To create a prognostic tool to quantify the 5-year cardiovascular (CV) risk in patients with newly diagnosed Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) without premorbid CV disease. Methods We reviewed CV outcomes during the long-term followup of patients in the first 4 European Vasculitis Study Group (EUVAS) trials of WG and MPA. CV events were defined as CV death, stroke, myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention. Logistic regression was performed to create a model to predict the absolute risk of a CV event. The model was tested using the Wegener's Granulomatosis Etanercept Trial (WGET) cohort. Results Seventy-four (13.8%) of 535 patients with 5 years of followup from the EUVAS trials had at least 1 CV event: 33 (11.7%) of 281 WG versus 41 (16.1%) of 254 MPA. The independent determinants of CV outcomes were older age (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.11–1.90), diastolic hypertension (OR 1.97, 95% CI 0.98–3.95), and positive proteinase 3 (PR3) antineutrophil cytoplasmic antibody (ANCA) status (OR 0.39, 95% CI 0.20–0.74). The model was validated using the WGET cohort (area under the receiver operating characteristic curve of 0.80). Conclusion Within 5 years of diagnosis of WG or MPA, 14% of patients will have a CV event. We have constructed and validated a tool to quantify the risk of a CV event based on age, diastolic hypertension, and PR3 ANCA status in patients without prior CV disease. In patients with vasculitis, PR3 ANCA is associated with a reduced CV risk compared to myeloperoxidase ANCA or negative ANCA status.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83751/1/20433_ftp.pd

Wigs, disguises and child's play : solidarity in teacher education

It is generally acknowledged that much contemporary education takes place within a dominant audit culture, in which accountability becomes a powerful driver of educational practices. In this culture both pupils and teachers risk being configured as a means to an assessment and target-driven end: pupils are schooled within a particular paradigm of education. The article discusses some ethical issues raised by such schooling, particularly the tensions arising for teachers, and by implication, teacher educators who prepare and support teachers for work in situations where vocational aims and beliefs may be in in conflict with instrumentalist aims. The article offers De Certeau’s concept of ‘la perruque’ to suggest an opening to playful engagement for human ends in education, as a way of contending with and managing the tensions generated. I use the concept to recover a concept of solidarity for teacher educators and teachers to enable ethical teaching in difficult times