Explaining the efficiency of local health departments in the U.S.: an exploratory analysis.

No study to date has analyzed the efficiency at which local health departments (LHDs) produce public health services. As a result, this study employs data envelopment analysis (DEA) to explore the relative technical efficiency of LHDs operating in the United States using 2005 data. The DEA indicates that the typical LHD operates with about 28% inefficiency although inefficiency runs as high as 69% for some LHDs. Multiple regression analysis reveals that more centralized and urban LHDs are less efficient at producing local public health services. The findings also suggest that efficiency is higher for LHDs that produce a greater variety of services internally and rely more on internal funding. However, because this is the first study of LHD efficiency and some shortcomings exist with the available data, we are reluctant to draw strong policy conclusions from the analysis.

Co-expression of 9-O-acetylated sialoglycoproteins and their binding proteins on lymphoblasts of childhood acute lymphoblastic leukemia: an anti-apoptotic role.

Enhanced levels of 9-O-acetylated sialoglycoproteins (Neu5,9Ac(2)GPs) as disease-associated molecules was reported to act as signaling molecules for promoting survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL). Here, we searched for potential physiological ligands for Neu5,9Ac(2)GPs that could be involved in modulating the survival of lymphoblasts. Accordingly, we examined the presence of binding proteins for Neu5,9Ac(2)GPs on cell lines and primary cells of patients with B- and T-ALL, at presentation of the disease. Peripheral blood mononuclear cells from normal healthy donors and cells from myeloid leukemia patients were used for comparison. Neu5,9Ac(2)GPs-binding proteins (BPs) were specifically detected on the surface of both T- and B-ALL-lymphoblasts and ALL-cell lines along with the consistent presence of Neu5,9Ac(2)GPs. The Neu5,9Ac(2)GPs and BPs also co-localized on the cell surface and interacted specifically in vitro. Apoptosis of lymphoblasts, induced by serum starvation, was reversed in the presence of purified Neu5,9Ac(2)GPs due to possible engagement of BPs, and the anti-apoptotic role of this interaction was established. This is the first report of the presence of potential physiological ligands for disease-associated molecules like Neu5,9Ac(2)GPs, the interaction of which is able to trigger an anti-apoptotic signal conferring a survival advantage to leukemic cells in childhood ALL.

O-acetylation of GD3 prevents its apoptotic effect and promotes survival of lymphoblasts in childhood acute lymphoblastic leukaemia.

We have previously demonstrated induction of O-acetylated sialoglycoproteins on lymphoblasts of childhood acute lymphoblastic leukaemia (ALL). These molecules promote survival of lymphoblasts by preventing apoptosis. Although O-acetylated sialoglycoproteins are over expressed, the status of O-acetylation of gangliosides and their role in lymphoblasts survival remains to be explored in ALL patients. Here, we have observed enhanced levels of 9-O-acetylated GD3 (9-O-AcGD3) in the lymphoblasts of patients and leukaemic cell line versus disialoganglioside GD3 in comparison to the normal cells. Localization of GD3 and 9-O-AcGD3 on mitochondria of patient's lymphoblasts has been demonstrated by immuno-electron microscopy. The exogenous administration of GD3-induced apoptosis in lymphoblasts as evident from the nuclear fragmentation and sub G0/G1 apoptotic peak. In contrast, 9-O-AcGD3 failed to induce such apoptosis. We further explored the mitochondria-dependent pathway triggered during GD3-induced apoptosis in lymphoblasts. GD3 caused a time-dependent depolarization of mitochondrial membrane potential, release of cytochrome c and 7.4- and 8-fold increased in caspase 9 and caspase 3 activity respectively. However, under identical conditions, an equimolar concentration of 9-O-AcGD3 failed to induce similar effects. Interestingly, 9-O-AcGD3 protected the lymphoblasts from GD3-induced apoptosis when administered in equimolar concentrations simultaneously. In situ de-O-acetylation of 9-O-AcGD3 with sodium salicylate restores the GD3-responsiveness to apoptotic signals. Although both GD3 and 9-O-acetyl GD3 localize to mitochondria, these two structurally related molecules may play different roles in ALL-disease biology. Taken together, our results suggest that O-acetylation of GD3, like that of O-acetylated sialoglycoproteins, might be a general strategy adopted by leukaemic blasts towards survival in ALL.

9-O-acetylated GD3 triggers programmed cell death in mature erythrocytes.

An acetylated modification of a tumor-associated ganglioside GD3 (9-O-AcGD3) is expressed in certain tumors and present during early stages of development in different tissues. However, the status and the role of 9-O-AcGD3 in the erythroid progenitor cells remain unexplored. Here, we report the level of 9-O-AcGD3 during erythropoiesis in bone marrow is down regulated during maturation. Signaling via 9-O-AcGD3 induces alteration of morphology and membrane characteristics of mature erythrocytes. This process also induces, a cell death program in these erythrocytes even in the absence of nucleus, mitochondria and other cell organelles sharing features of apoptosis in nucleated cells like membrane alterations, vesicularization, phosphatidyl serine exposure, activation of cysteine proteases like caspase-3. This is the first report of a programmed cell death pathway in mature erythrocytes, triggered by 9-O-AcGD3 contrary to their anti-apoptotic role in lymphoblasts, which suggests a cell specific role of this O-acetyl ester of GD3.

O-acetylation of sialic acids is required for the survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL).

Exploiting the selective affinity of Achatinin-H towards 9-O-acetylneuraminic acid(alpha2-6)GalNAc, we have demonstrated the presence of 9-O-acetylated sialoglycoproteins (Neu5,9Ac(2)-GPs) on hematopoietic cells of children suffering from acute lymphoblastic leukemia (ALL), indicative of defective sialylation associated with this disease. The carbohydrate epitope of Neu5,9Ac(2)-GPs(ALL) was confirmed by using several synthetic sialic acid analogues. They are functionally active signaling molecules as demonstrated by their role in mediating lymphoproliferative responses and consequential increased production of IFN-gamma due to specific stimulation of Neu5,9Ac(2)-GPs on PBMC(ALL) with Achatinin-H. Cells devoid of 9-O-acetylations (9-O-AcSA(-)) revealed decreased nitric oxide production as compared to 9-O-AcSA(+) cells on exposure to IFN-gamma. Under this condition, a decrease in viability of 9-O-AcSA(-) cells as compared to 9-O-AcSA(+) cells was also observed which was reflected from increased caspase 3 activity and apoptosis suggesting the protective role of this glycotope. These Neu5,9Ac(2)-GPs are also capable of inducing disease-specific anti-Neu5,9Ac(2)-GPs antibodies in ALL children. Additionally, we have observed that disease-specific anti-Neu5,9Ac(2)-GPs have altered glycosylation profile, and they are incapable of exerting a few Fc-glycosylation-sensitive effector functions. These observations hint toward a disbalanced homeostasis, thereby enabling the cancer cells to escape host defense. Taken together, it may be hypothesized that Neu5,9Ac(2)-GPs and their antibodies play a prominent role in promoting the survival of lymphoblasts in ALL.

Market structure and technical efficiency in the hospital services industry: a DEA approach.

This article uses data envelopment analysis and multiple regression analysis to examine empirically the impact of various market-structure elements on the technical efficiency of the hospital services industry in various metropolitan areas of the United States. Market-structure elements include the degree of rivalry among hospitals, extent of HMO activity, and health insurer concentration. The DEA results show the typical hospital services industry experienced 11 percent inefficiency in 1999. Moreover, multiple regression analysis indicates the level of technical efficiency varied directly across metropolitan hospital services industries in response to greater HMO activity and private health insurer concentration in the state. The analysis suggests the degree of rivalry among hospitals had no marginal effect on technical efficiency at the industry level. Evidence also implies that the presence of a state Certificate of Need law was not associated with a greater degree of inefficiency in the typical metropolitan hospital services industry.

Detection of immune-complexed 9-O-acetylated sialoglycoconjugates in the sera of patients with pediatric acute lymphoblastic leukemia.

Although childhood acute lymphoblastic leukemia (ALL) is highly responsive to chemotherapy, reliable techniques are needed to determine treatment outcome. Over expression of 9-O-acetylated sialoglycoconjugates (9-OAcSGs) on lymphoblasts and concomitant anti-9-OAcSGs was found to have a diagnostic and prognostic potential. However, the presence of circulatory immune-complexed antigens remains unknown. The present study was aimed to evaluate whether immune-complexed 9-OAcSGs can be harnessed for better disease management. Immune-complexed antigens were evaluated in ALL sera (n=262) by a Dot-blot using a 9-OAcSAalpha2-6GalNAc-specific lectin, Achatinin-H. Using three serum samples, the inter- and intra-assay imprecision was evaluated as 11-13% and 7-11%, respectively. The recovery of spiked 9-OAcSGs was 84.2-95.4%. The central 95% reference interval for immune-complexed 9-OAcSGs in normal human sera (NHS, n=144) was 2.9-3.4 mug/ml irrespective of sex and age. At disease presentation, the immune-complexed 9-OAcSGs were fivefold higher than NHS, decreased with remission induction and importantly, reappeared with clinical relapse. Sera from patients with other hematological disorders (n=86) showed negligible levels. The Dot-blot demonstrated the potential application of immune-complexed antigen as a disease-specific marker and its efficacy as a sensitive and specific method that could serve as an economical yet effective index for monitoring disease status.