Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles

Notch is a highly conserved transmembrane protein that is involved in cell fate decisions and is found in organisms ranging from Drosophila to humans. A human homologue of Notch, TAN1, was initially identified at the chromosomal breakpoint of a subset of T-cell lymphoblastic leukemias/lymphomas containing a t(7;9) chromosomal translocation; however, its role in oncogenesis has been unclear. Using a bone marrow reconstitution assay with cells containing retrovirally transduced TAN1 alleles, we analyzed the oncogenic potential of both nuclear and extranuclear forms of truncated TAN1 in hematopoietic cells. Although the Moloney leukemia virus long terminal repeat drives expression in most hematopoietic cell types, retroviruses encoding either form of the TAN1 protein induced clonal leukemias of exclusively immature T cell phenotypes in approximately 50% of transplanted animals. All tumors overexpressed truncated TAN1 of the size and subcellular localization predicted from the structure of the gene. These results show that TAN1 is an oncoprotein and suggest that truncation and overexpression are important determinants of transforming activity. Moreover, the murine tumors caused by TAN1 in the bone marrow transplant model are very similar to the TAN1-associated human tumors and suggest that TAN1 may be specifically oncotropic for T cells

Likelihood of recurrent high Emergency Department utilization by Indigent Patients

Recurrent utilization of emergency medical services by certain patient populations is a challenge at the University of New Mexico Emergency Department (UNM ED) and at other institutions. Data suggest that a significant percentage of patients treated in the UNM ED could be treated in other, less costly outpatient settings. Existing data were used to analyze trends in UNM ED utilization among four distinct populations — managed uninsured patients (UNM Care), unmanaged uninsured patients (Self-pay), managed Medicaid patients (Salud), and unmanaged Medicaid patients (Medicaid). We hypothesized that those who previously had high usage of the Emergency Department (ED) in the index year would continue high use of the ED in the next year. In addition, we hypothesized that patients in managed programs, UNM Care and Salud, would likely have a lower recurrent use of the ED than patients in unmanaged programs, Self-pay and Medicaid, patients. Our data included 19,461 adult patients, with 1,104 having 653 visits in Fiscal Year 2004 (FY04). Of those patients, 145 (13.1%) patients had 653 visits in Fiscal Year 2005 (FY05). Unmanaged Medicaid patients who had 653 visits in FY04 were 17.80 times as likely to have 653 visits in FY05 (p\u3c0.001) compared to unmanaged Medicaid patients with 1-2 visits in FY04. The next highest recurrent high utilization pattern was the Self-pay group with 653 visits in FY04, who were 9.37 times as likely to have 653 visits in 2005 as the Self-pay patients with 1-2 visits in FY04. The managed groups also showed that patients with high utilization in the index year continued high use in the next year, but to a lesser extent than the unmanaged groups. Salud patients with 653 visits in 2004 were 6.69 times more likely to have 653 visits in 2005, while the UNM Care group shows significantly less recurrent ED use at 4.28 times as likely to have 653 visits in 2005, compared to patients from the respective groups with 1-2 visits in FY04, which is also lower than the other three groups (p\u3c0.05)

Individual, Neighborhood, and Situational Factors Associated with Violent Victimization and Offending

The criminological literature presents substantial evidence that victims and offenders in violent crimes share demographic characteristics, engage in similar lifestyles and activities, and reside in socially disorganized neighborhoods. However, research has examined these relationships separately using either victimization or offending data, and prior studies have not examined these relationships by comparing victims and offenders within the same incidents. This limits the effect of examining whether these factors are associated with victimization and offending in similar or distinct ways. Using a law enforcement database of victims (n = 1,248) and offenders (n = 1,735) involved within the same aggravated battery incidents (n = 1,015) in Bernalillo County, New Mexico, this research explores whether victims and offenders involved in non-lethal violence share certain individual, neighborhood and situational characteristics. Results suggest that victims and offenders live in socially disorganized neighborhoods and engage in risky lifestyles and violent offending behaviors in similar proportions. These findings highlight the overlapping factors associated with victimization and offending in non-lethal violent personal crimes. The implications of these findings are discussed

Care of HIV-Infected Pregnant Women in Maternal–Fetal Medicine Programs

Objective: To survey the evolution over the past decade of attitudes and practices of obstetricians in maternal–fetal medicine fellowship programs regarding the management of human immunodeficiency virus (HIV)-infected pregnant women. Methods: Directors of all 65 approved maternal–fetal medicine training programs were sent questionnaires, responses to which were to reflect the consensus among members of their faculties. Programs were stratified based upon the number of HIV-infected pregnant patients cared for in the previous year. Results: Responses reflect experience with over 1000 infected pregnantwomen per year, nearly one-quarter with advanced disease. Combination antiretroviral therapy was prescribed by all respondents, universally in the 2nd and 3rd trimesters. A three-drug regimen (often containing a protease inhibitor) was used more often by those who treated at least 20 HIV-infected pregnant patients per year than by those programs seeing a lower number of patients (80 vs 59%).Despite the known and unknown risks of the use of antiretrovirals during pregnancy, only half of all responding programs report adverse events to the Antiretroviral Pregnancy Registry; reporting was more common among the institutions seeing a higher number of patients (61 vs 45%). Seventy-eight percent of higher volume programs enroll their patients in clinical studies, usually multicenter, versus 35% of lower volume programs. Conclusions: Care for HIV² pregnant women has dramatically changed over the past decade. Antiretroviral therapy is now universally prescribed by physicians involved in maternal–fetal medicine training programs. Given limited experience with these agents in the setting of pregnancy, it is essential for maternal–fetal medicine practitioners to actively report on adverse events and participate in clinical trials