Measuring the effect of commuting on the performance of the Bayesian Aerosol Release Detector.

Background: Early detection of outdoor aerosol releases of anthrax is an important problem. The Bayesian Aerosol Release Detector (BARD) is a system for detecting releases of aerosolized anthrax and characterizing them in terms of location, time and quantity. Modelling a population's exposure to aerosolized anthrax poses a number of challenges.

New-onset lymphopenia assessed during routine follow-up is a risk factor for relapse postautologous peripheral blood hematopoietic stem cell transplantation in patients with diffuse large B-cell lymphoma.

A specific predictor during routine follow-up to ascertain risk for postautologous peripheral blood hematopoietic stem cell transplantation (post-APHSCT) relapse in non-Hodgkin lymphoma (NHL) has not been identified. Thus, we studied if new-onset lymphopenia measured by the absolute lymphocyte count (ALC) was a marker of post-APHSCT NHL relapse. ALC was obtained at the time of confirmed relapse, and at last follow-up with no relapse.

Outcome of transplantation for myelofibrosis.

Myelofibrosis is a myeloproliferative disorder incurable with conventional strategies. Several small series have reported long-term disease-free survival (DSF) after allogeneic hematopoietic cell transplantation (HCT). In this study, we analyze the outcomes of 289 patients receiving allogeneic transplantation for primary myelofibrosis between 1989 and 2002, from the database of the Center for International Bone Marrow Transplant Research (CIBMTR).

JAK2 germline genetic variation affects disease susceptibility in primary myelofibrosis regardless of V617F mutational status: nullizygosity for the JAK2 46/1 haplotype is associated with inferior survival.

A common JAK2 germline haplotype (46/1) has been associated with JAK2V617F (VF)-positive myeloproliferative neoplasms. The rs12343867 SNP (C/T) tags this haplotype. A total of 130 patients (77 VF-positive) with primary myelofibrosis (PMF) were analyzed for this informative SNP, using bone marrow-derived DNA.

Knowledge-based variable selection for learning rules from proteomic data.

Background: The incorporation of biological knowledge can enhance the analysis of biomedical data. We present a novel method that uses a proteomic knowledge base to enhance the performance of a rule-learning algorithm in identifying putative biomarkers of disease from high-dimensional proteomic mass spectral data. In particular, we use the Empirical Proteomics Ontology Knowledge Base (EPO-KB) that contains previously identified and validated proteomic biomarkers to select m/zs in a proteomic dataset prior to analysis to increase performance.

Kinetics of interferon-gamma producing cytomegalovirus (CMV)-specific CD4+ and CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic hematopoietic stem cell transplantation.

Background: Deficiencies in cytomegalovirus (CMV)-specific T lymphocytes impair the immunologic response against CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT).

Methods: A time-dependent analysis was conducted to determine the association between the percentages and kinetics of interferon-gamma-producing CMV-specific CD4+ and CD8+ T lymphocytes and CMV viremia among 30 allogeneic HSCT recipients.

Results: Higher percentages of CD4+ T lymphocytes activated with CMVpp65 (hazard ratio [HR]: 2.

Mining aggregates of over-the-counter products for syndromic surveillance.

There has recently been a surge of research efforts aimed at very early detection of disease outbreaks. An important strategy for improving the timeliness of outbreak detection is to identify signals that occur early in the epidemic process. We have developed a novel algorithm to identify aggregates of "similar" over-the-counter products that have strong association with a given disease.

Using a novel resource to decrease proteomic biomarker identification time.

The Empirical Proteomic Ontology Knowledge Base (EPO-KB) is an online database that represents current knowledge of biomarkers and contains associations between mass-to-charge (m/z) ratios of mass-spectrometry peaks to proteins. Such a database is a useful tool for identifying putative proteins associated with a m/z ratio. At present, EPO-KB contains data that have been extracted from 120 published research papers.

Adoptive immunotherapy against allogeneic kidney grafts in dogs with stable hematopoietic trichimerism.

Dogs given nonmyeloablative conditioning and marrow grafts from 2 dog leukocyte antigen (DLA)-identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. In this study, we used trichimeras to evaluate strategies for adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from 2 DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy of total body irradiation (TBI) and given a short course of postgraft immunosuppression.

Autologous stem cell transplant in 716 patients with multiple myeloma: low treatment-related mortality, feasibility of outpatient transplant, and effect of a multidisciplinary quality initiative.

We report on the feasibility of outpatient transplant in 716 patients undergoing autologous stem cell transplant for multiple myeloma at Mayo Clinic's site in Rochester, MN, from January 1, 2000, through October 31, 2007. We also report on the development and effect of a multidisciplinary quality initiative implemented by the Mayo Clinic Blood and Marrow Transplant Program involving physicians, nurses, pharmacists, dietitians, and financial specialists for outpatient management of patients undergoing stem cell transplant. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors.

Long-term outcome of allogeneic stem cell transplantation in chronic lymphocytic leukemia: analysis after a minimum follow-up of 5 years.

In order to evaluate the long-term results of allogeneic stem cell transplantation (ASCT) in B-cell chronic lymphocytic leukemia (CLL), we reviewed the outcome of 12 consecutive CLL patients, who underwent ASCT at the Mayo Clinic prior to July, 2004. Median age was 44 years (range 18-55) and median time from diagnosis to transplant 58.5 months.

Copper deficiency in celiac disease.

Copper deficiency is an uncommonly reported complication of celiac disease that has not received much attention in recent years. Copper deficiency may result in anemia and thrombocytopenia and also irreversible myeloneuropathy if it is not detected and treated appropriately. The prevalence of copper deficiency in patients with celiac disease is unknown.

Intensified postgrafting immunosuppression failed to assure long-term engraftment of dog leukocyte antigen-identical canine marrow grafts after 1 gray total body irradiation.

Background: Late graft rejection after conditioning with 1 Gy of total body irradiation (TBI) was consistently seen in historical dogs given two postgrafting immunosuppressive drugs.

Methods: Here, 16 dogs were given four different three-drug combinations of cyclosporine, mycophenolate mofetil, sirolimus, or methotrexate after 1 Gy TBI and dog leukocyte antigen-identical marrow grafts. In addition, we assessed the effects of TBI doses of 0.

EPO-KB: a searchable knowledge base of biomarker to protein links.

Unlabelled: The knowledge base EPO-KB (Empirical Proteomic Ontology Knowledge Base) is based on an OWL ontology that represents current knowledge linking mass-to-charge (m/z) ratios to proteins on multiple platforms including Matrix Assisted Laser/Desorption Ionization (MALDI) and Surface Enhanced Laser/Desorption Ionization (SELDI)--Time of Flight (TOF). At present, it contains information on m/z ratio to protein links that were extracted from 120 published research papers. It has a web interface that allows researchers to query and retrieve putative proteins that correspond to a user-specified m/z ratio.

Hematological manifestations of copper deficiency: a retrospective review.

Copper deficiency is an established cause of hematological abnormalities but is frequently misdiagnosed. Copper deficiency can present as a combination of hematological and neurological abnormalities and it may masquerade as a myelodysplastic syndrome. We reviewed the records of patients with hypocupremia and hematologic abnormalities identified between 1970 and 2005.

Peripheral blood stem cell transplant for POEMS syndrome is associated with high rates of engraftment syndrome.

Polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome is a devastating syndrome, characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis and high vascular endothelial growth factor (VEGF). High-dose chemotherapy with autologous peripheral blood stem cell transplantation (ASCT) ultimately yields excellent clinical responses, but there can be considerable peritransplant morbidity. We have treated 30 POEMS patients with ASCT at Mayo Clinic, Rochester.

The Bayesian aerosol release detector: an algorithm for detecting and characterizing outbreaks caused by an atmospheric release of Bacillus anthracis.

Early detection and characterization of outdoor aerosol releases of Bacillus anthracis is an important problem. As health departments and other government agencies address this problem with newer methods of surveillance such as environmental surveillance through the BioWatch program and enhanced medical surveillance, they increasingly have newer types of surveillance data available. However, existing methods for the statistical analysis of surveillance data do not account for recent meteorological conditions, as human analysts did in the case of the Sverdlovsk anthrax outbreak of 1979 to determine whether the locations of victims were consistent with meteorological conditions in the week preceding their onset of illness.

Graft vs. host disease after liver transplantation: a new approach is needed.

Graft-vs.-host disease (GVHD) is a rare, serious complication of orthotopic liver transplantation (OLT). We have treated 5 patients to date with GVHD after OLT.

Extending Jak2V617F and MplW515 mutation analysis to single hematopoietic colonies and B and T lymphocytes.

JAK2V617F and MPLW515L/K are myeloproliferative disorder (MPD)-associated mutations. We genotyped 552 individual hematopoietic colonies obtained by CD34+ cell culture from 16 affected patients (13 JAK2V617F and 3 MPLW515L/K) to determine (a) the proportion of colonies harboring a particular mutation in the presence or absence of cytokines, (b) the lineage distribution of endogenous colonies for each mutation, and (c) the differences (if any) in the pattern of mutation among the various MPDs, as established by genotyping of individual colonies. Genotyping analysis revealed cohabitation of mutation-negative and mutation-positive endogenous colonies in polycythemia vera as well as other MPDs.

Unsupervised clustering of over-the-counter healthcare products into product categories.

A general problem in biosurveillance is finding appropriate aggregates of elemental data to monitor for the detection of disease outbreaks. We developed an unsupervised clustering algorithm for aggregating over-the-counter healthcare (OTC) products into categories. This algorithm employs MCMC over hundreds of parameters in a Bayesian model to place products into clusters.