Technical efficiency in the use of health care resources: a comparison of OECD countries

Our paper analyzes technical efficiency in the production of aggregate health outcomes of reduced infant mortality and increased life expectancy, using Organization for Economic Cooperation and Development (OECD) health data. Application of data envelopment analysis (DEA) reveals that some countries achieve relative efficiency advantages, including those with good health outcomes (Japan, Sweden, Norway, and Canada) and those with modest health outcomes (Mexico and Turkey). We conclude the USA may learn from countries more economical in their allocation of healthcare resources that more is not necessarily better. Specifically, we find that the USA can substantially reduce inputs while maintaining the current level of life expectancy.     

"Good Old" clinical markers have similar power in breast cancer prognosis as microarray gene expression profilers

We compared the power of gene expression measurements with that of conventional prognostic markers, i.e., clinical, histopathological, and cell biological parameters, for predicting distant metastases in breast cancer patients using both established prognostic indices (e.g., the Nottingham Prognostic Index (NPI)) and novel combinations of conventional markers. We used publicly available data on 97 patients, and the performance of metastasis prediction was represented by receiver operating characteristic (ROC) areas and Kaplan-Meier plots. The gene expression profiler did not perform noticeably better than indices constructed from the clinical variables, e.g., the well established NPI. When analysing separately subgroups, according to the oestrogen receptor (ER) status both approaches could predict clinical outcome more easily for the ER-positive than for the ER-negative cohort. Given the time it may take before microarray processing is used worldwide, particularly due to the costs and the lack of standards, it is important to pursue research using conventional markers. Our analysis suggests that it might be possible to improve the combination of different conventional prognostic markers into one prognostic index.     

Greater antibody responses to an eleven valent mixed carrier diphtheria- or tetanus-conjugated pneumococcal vaccine in Filipino than in Finnish or Israeli infants

BACKGROUND: Antibody responses to pneumococcal conjugate vaccines may vary when administered in different populations or epidemiologic settings. Understanding the causes and significance of this variation could help to determine the number of doses and timing required for protection against pneumococcal diseases in each country. METHODS: This report compares antibody responses to aluminum-adjuvanted and nonadjuvanted mixed carrier 11-valent diphtheria- or tetanus-conjugated pneumococcal vaccine (11-PncTD) formulations when given at 6, 10 and 14 weeks and 9 months of age to Filipino infants (n = 51) and at 2, 4, 6 and 12 months of age to Finnish (n = 127) and Israeli (n = 124) infants. The study populations differ in their natural exposure to pneumococcus and risk factors for pneumococcal carriage and disease. RESULTS: Filipino and Israeli infants had slightly but significantly higher prevaccination geometric mean concentration (GMC) of antibodies than did the Finnish infants. After three doses of aluminum-adjuvanted 11-PncTD vaccine, the Filipino infants had 1.8 to 6.7 and 1.5 to 5.0 times higher GMC than the Finnish and Israeli infants, respectively, against pneumococcal serotypes conjugated to tetanus protein. The GMC of serotypes conjugated to diphtheria toxoid was 1.3 to 3.0 and 0.7 to 2.0 times the GMC in Finnish and Israeli infants, respectively. The nonadjuvanted vaccine formulation induced generally lower GMCs. CONCLUSIONS: The antibody responses to the tetanus-conjugated polysaccharides were considerably higher in the Filipino than in the Finnish or Israeli infants. This may be a result of several factors including the priming effect of tetanus toxoid given to pregnant women, early pneumococcal nasopharyngeal acquisition and genetic differences among populations.     

Voltage-gated Na+ channels enhance the temporal filtering properties of electrosensory neurons in the torus

Regenerative processes enhance postsynaptic potential (PSP) amplitude and behaviorally relevant temporal filtering in more than one-third of electrosensory neurons in the torus semicircularis of Eigenmannia. Data from in vivo current-clamp intracellular recordings indicate that these "regenerative PSPs" can be divided in two groups based on their half-amplitude durations: constant duration (CD) and variable duration (VD) PSPs. CD PSPs have half-amplitude durations of between 20 and 60 ms that do not vary in relation to stimulus periodicity. In contrast, the half-amplitude durations of VD PSPs vary in relation to stimulus periodicity and range from approximately 10 to 500 ms. Injection of 0.1 nA sinusoidal current through the recording electrode demonstrated that CD PSPs and not VD PSPs can be elicited by voltage fluctuations alone. In addition, CD PSPs were blocked by intracellular application of either QX-314 or QX-222, whereas VD PSPs were not. These in vivo data suggest, therefore, that CD PSPs are mediated by voltage-dependent Na+ conductances.     

An investigation of apoptosis in androgenetic alopecia

While the androgens, including dihydrotestosterone (DHT), have been implicated in the development of androgenetic alopecia (AGA), the exact mechanism by which they exert their effect(s) is unknown. Since apoptosis is an integral component of the normal cycling of human hair, we investigated individuals clinically affected by AGA to assess whether objective differences in the expression of apoptosis-related immunohistochemical markers could be observed in scalp biopsies. Specimens from 16 alopecic male patients were stained with bd-2 and the terminal deoxynucleotidyltransferase dUTP fluorescein nick end-labeling (TUNEL) method was used to assess apoptotic activity in affected and unaffected areas ofthe scalp. Immunoreactivity was analyzed by quantifying staining differences within the same individual. Sections from 3 human volunteers were used to establish the method validity. Significant differences in the bcl-2 staining index (0.67 versus 0.42, p < 0.05) and TUNEL expression (5.7 versus 10.2, p < 0.05) were observed between the areas of the scalp that were clinically affected (frontal) and unaffected (occipital) by AGA. The Gaussian distributions of bcl-2 and TUNEL staining suggest that a relatively uniform population of follicles exists at the frontal hairline and/or that synchrony of follicular cycling occurs in AGA. The apoptosis "hot spot" revealed by TUNEL staining in the bulge-isthmus region of the murine follicle is also identifiable in the human follicle.     

RXRalpha-regulated liver SAMe and GSH levels influence susceptibility to alcohol-induced hepatotoxicity

Retinoids influence the pathogenesis of alcohol liver disease (ALD). To analyze the impact of retinoid X receptor alpha (RXRalpha) on ALD, alcohol-induced hepatotoxicity was studied using mice fed ethanol intragastrically for 25 days. Alcohol-induced microvesicular fat around the central vein and drug-induced morphological changes (loss of rough endoplasmic reticulum, pinkish cytoplasm, and enlarged hepatocyte) in the pericentral area were observed in the liver of wild-type mice. In the hepatocyte RXRalpha-deficient mouse liver, alcohol induced fat accumulation, mitosis, acute inflammation, and necrosis. The histology score after alcohol treatment was significantly higher in mutant mice than in wild-type mice. However, drug-induced morphological changes were not apparent in alcohol-treated hepatocyte RXRalpha-deficient mice. Northern analysis showed that the basal and alcohol-induced CYP2B, CYP2A, and CYP3A mRNA levels were lower in hepatocyte RXRalpha-deficient mice than in wild-type mice, which in turn may protect mutant mice from morphological changes. Compared with wild-type mice, hepatocyte RXRalpha-deficient mice have significant lower levels of S-adenosylmethionine and glutathione, which is further reduced after alcohol treatment, and that may account for severe liver injury induced by alcohol. The overall result suggests an important role of RXRalpha in preventing alcohol-induced liver injury.