Restructuring and hospital care: Sub-national trends, differentials, and their impacts; New Zealand from 1981

An analysis of the "nation's health" is the central concern of this study. Its genesis was a detailed, technical, time-series research on regional and ethnic differentials in health in New Zealand. But as this work progressed it became increasingly evident that the results of this more narrow analysis could make a wider contribution to the development of a knowledge-base on health trends and on the impacts of policy on these. In a sense, the analysis provides a demographic audit of health trends over the last two decades. The focus here is different from that in most other studies on restructuring of the New Zealand health system as their concern was either to review in detail the rewriting of policy per se, and attendant structural and institutional changes (Fougere 2001), or to identify how these changes relate to changes in mortality (Blakely et al. 2008). The research question reported here was, instead, to analyse the most crucial of health outcomes, „how long we live and how often we end up in hospital‟, identified in the earlier quotation, to report patterns and trends in hospital use nationally and sub-nationally over the period under review, and to determine the degrees to which various sub-populations benefited, or did not benefit, from these changes. The analysis focuses on the hospital sector in the system, but it will also show relations between this and other sectors, formal (e.g. primary health) and less formal (notably the healthcare afforded sickness and invalid beneficiaries). Thus two questions are addressed: 1. whether or not the nation‟s population health improved over the period and; 2. whether or not there was a convergence in patterns of health gain across its constituent sub-populations defined geographically and ethnically. This monograph deals with sub-national differences in health in New Zealand over a period of substantial socio-economic restructuring and associated radical changes in health policy, health systems and their related information systems (see also, Text Appendix A). It complements the recently published analysis of national ethnic trends in mortality (Blakely et al. 2004), but differs in several critical respects. That study reviewed health status by emphasising aetiologies and causes of death. In contrast, the present analysis focuses on actuarial dimensions of both mortality and morbidity and on health as measured by functional capacity rather than the disease orientated „burden of disease‟. It goes beyond health status issues to look at the system itself, to assess whether health policy outcomes were generated more through efficiency-gain (economic or service delivery, such as those resulting in a convergence sub-nationally of supply and demand effects), or through health gains, or ideally, by both. To do this, and as a by-product to analyse changes in health status and the system in an era of restructuring, innovative methodologies and composite time-series indices combining the two dimensions of a „nation‟s health‟, needing hospital care and longevity, have had to be custom-designed. To achieve this objective, the ensuing analysis is often technical, and may introduce concepts that are unfamiliar to some readers. In order to look at possible inequalities of outcome, comparisons were made between regions and ethnic groups, as well as age-groups and genders, and as a result, in places the analysis becomes rather complex

Antihyperlipidemic Activity of Terminalia Chebula Retz Extract-Loaded Phytosomes: Development and Characterization

Ethnopharmacological evidence has demonstrated that Terminalia chebula Retz is traditionally employed for the management of hepatic ailments. Presently, a significant number of prevalent diseases and nutritional disorders are managed through the utilization of natural remedies. The efficacy of herbal medications relies on the administration of a sufficient dosage of the therapeutically active component. However, there is a significant constraint in terms of their bioavailability when taken via oral or topical routes. Phytosomes are a novel class of herbal formulations that have been recently introduced. These formulations exhibit enhanced absorption properties, leading to improved bioavailability and efficacy compared to traditional phyto compounds or botanical extracts. The objective of the current investigation was to assess the qualitative and quantitative phytochemical analysis, high-performance liquid chromatography, optical microscopic research, and in vitro antioxidant properties of Terminalia chebula Retz leaves obtained from the Bhopal region of Madhya Pradesh. The hydroalcoholic extract of phytosome was prepared using a mixture of phospholipids and cholesterol. The characterization of phytosome was conducted using various analytical techniques, including Fourier-transform infrared spectroscopy, determination of entrapment efficiency, measurement of particle size and size distribution, examination under an optical microscope, high-performance liquid chromatography analysis. The concurrent utilization of phospholipids and Terminalia chebula Retz has the potential to produce a synergistic outcome. This synergistic effect can be assessed by evaluating the free radical scavenging activity using the DPPH model

Connecting Research and Practice: An Experience Report on Research Infusion with SAVE

NASA systems need to be highly dependable to avoid catastrophic mission failures. This calls for rigorous engineering processes including meticulous validation and verification. However, NASA systems are often highly distributed and overwhelmingly complex, making the software portion of these systems challenging to understand, maintain, change, reuse, and test. NASA's systems are long-lived and the software maintenance process typically constitutes 60-80% of the total cost of the entire lifecycle. Thus, in addition to the technical challenges of ensuring high life-time quality of NASA's systems, the post-development phase also presents a significant financial burden. Some of NASA's software-related challenges could potentially be addressed by some of the many powerful technologies that are being developed in software research laboratories. Many of these research technologies seek to facilitate maintenance and evolution by for example architecting, designing and modeling for quality, flexibility, and reuse. Other technologies attempt to detect and remove defects and other quality issues by various forms of automated defect detection, architecture analysis, and various forms of sophisticated simulation and testing. However promising, most such research technologies nevertheless do not make the transition from the research lab to the software lab. One reason the transition from research to practice seldom occurs is that research infusion and technology transfer is difficult. For example, factors related to the technology are sometimes overshadowed by other types of factors such as reluctance to change and therefore prohibits the technology from sticking. Successful infusion might also take very long time. One famous study showed that the discrepancy between the conception of the idea and its practical use was 18 years plus or minus three. Nevertheless, infusing new technology is possible. We have found that it takes special circumstances for such research infusion to succeed: 1) there must be evidence that the technology works in the practitioner's particular domain, 2) there must be a potential for great improvements and enhanced competitive edge for the practitioner, 3) the practitioner has to have strong individual curiosity and continuous interest in trying out new technologies, 4) the practitioner has to have support on multiple levels (i.e. from the researchers, from management, from sponsors etc), and 5) to remain infused, the new technology has to be integrated into the practitioner's processes so that it becomes a natural part of the daily work. NASA IV&V's Research Infusion initiative sponsored by NASA's Office of Safety & Mission Assurance (OSMA) through the Software Assurance Research Program (SARP), strives to overcome some of the problems related to research infusion

Helicobacter Pylori's Plasticity Zones Are Novel Transposable Elements

BACKGROUND:Genes present in only certain strains of a bacterial species can strongly affect cellular phenotypes and evolutionary potentials. One segment that seemed particularly rich in strain-specific genes was found by comparing the first two sequenced Helicobacter pylori genomes (strains 26695 and J99) and was named a "plasticity zone". PRINCIPAL FINDINGS:We studied the nature and evolution of plasticity zones by sequencing them in five more Helicobacter strains, determining their locations in additional strains, and identifying them in recently released genome sequences. They occurred as discrete units, inserted at numerous chromosomal sites, and were usually flanked by direct repeats of 5'AAGAATG, a sequence generally also present in one copy at unoccupied sites in other strains. This showed that plasticity zones are transposable elements, to be called TnPZs. Each full length TnPZ contained a cluster of type IV protein secretion genes (tfs3), a tyrosine recombinase family gene ("xerT"), and a large (>or=2800 codon) orf encoding a protein with helicase and DNA methylase domains, plus additional orfs with no homology to genes of known function. Several TnPZ types were found that differed in gene arrangement or DNA sequence. Our analysis also indicated that the first-identified plasticity zones (in strains 26695 and J99) are complex mosaics of TnPZ remnants, formed by multiple TnPZ insertions, and spontaneous and transposable element mediated deletions. Tests using laboratory-generated deletions showed that TnPZs are not essential for viability, but identified one TnPZ that contributed quantitatively to bacterial growth during mouse infection and another that affected synthesis of proinflammatory cytokines in cell culture. CONCLUSIONS:We propose that plasticity zone genes are contained in conjugative transposons (TnPZs) or remnants of them, that TnPZ insertion is mediated by XerT recombinase, and that some TnPZ genes affect bacterial phenotypes and fitness

Initiation and maintenance of pluripotency gene expression in the absence of cohesin

Cohesin is implicated in establishing and maintaining pluripotency. Whether this is because of essential cohesin functions in the cell cycle or in gene regulation is unknown. Here we tested cohesin’s contribution to reprogramming in systems that reactivate the expression of pluripotency genes in the absence of proliferation (embryonic stem [ES] cell heterokaryons) or DNA replication (nuclear transfer). Contrary to expectations, cohesin depletion enhanced the ability of ES cells to initiate somatic cell reprogramming in heterokaryons. This was explained by increased c-Myc (Myc) expression in cohesin-depleted ES cells, which promoted DNA replication-dependent reprogramming of somatic fusion partners. In contrast, cohesin-depleted somatic cells were poorly reprogrammed in heterokaryons, due in part to defective DNA replication. Pluripotency gene induction was rescued by Myc, which restored DNA replication, and by nuclear transfer, where reprogramming does not require DNA replication. These results redefine cohesin’s role in pluripotency and reveal a novel function for Myc in promoting the replication-dependent reprogramming of somatic nuclei

Study Protocol: insulin and its role in cancer

<p>Abstract</p> <p>Background</p> <p>Studies have shown that metabolic syndrome and its consequent biochemical derangements in the various phases of diabetes may contribute to carcinogenesis. A part of this carcinogenic effect could be attributed to hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding proteins and hence increase levels of free IGF-1. It is well established that bioactivity of free insulin growth factor 1 (IGF-1) increases tumor turnover rate. The objective is to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying the relation between insulin resistance/sensitivity and IGF-1 levels in cancer patients. We postulate that hyperinsulinaemia which prevails during initial phases of insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-1, which may contribute to process of carcinogenesis.</p> <p>Methods/Design</p> <p>Based on our pilot study results and power analysis of the same, we have designed a two group case-control study. 800 proven untreated cancer patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200 healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1 levels shall be determined in all subjects. Association between the two parameters shall be tested using suitable statistical methods.</p> <p>Discussion</p> <p>Well controlled studies in humans are essential to study the link between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study could provide insights to the role of insulin, insulin resistance, IGF-1 in carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve around insulin and insulin resistance.</p

New Directions in the Development of Population Estimates in the United States?

The advent of a continuously updated Master Area File (MAF) following the 2000 census represents an information resource that can be tapped for purposes of developing timely, cost-effective, and precise population estimates for even the smallest of geographical units (e.g., census blocks). We argue that the MAF can be enhanced (EMAF) for these purposes. In support of our argument we describe a set of activities needed to develop EMAF, each of which is well within the current capabilities of the U.S. Census Bureau and discuss various costs and benefits of each. We also describe how EMAF would provide population estimates containing a wide range of demographic (e.g., age, race, and sex) and socio-economic characteristics (e.g., educational attainment, income, and employment). As such, it could largely negate and eliminate the need for many of the traditional demographic methods of population estimation and possibly reduce the number of sample surveys. We identify important challenges that must be surmounted in order to realize EMAF and make suggestions for doing so. We conclude by noting that the idea of the EMAF could be of interest to other countries with MAF files and strong administrative records systems that, like the United States, are facing the challenge of producing good population information in the face of increasing census costs

Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system

In multicellular organisms, duplicated genes can diverge through tissue-specific gene expression patterns, as exemplified by highly regulated expression of Runx transcription factor paralogs with apparent functional redundancy. Here we asked what cell type-specific biologies might be supported by the selective expression of Runx paralogs during Langerhans cell and inducible regulatory T cell differentiation. We uncovered functional non-equivalence between Runx paralogs. Selective expression of native paralogs allowed integration of transcription factor activity with extrinsic signals, while non-native paralogs enforced differentiation even in the absence of exogenous inducers. DNA-binding affinity was controlled by divergent amino acids within the otherwise highly conserved RUNT domain, and evolutionary reconstruction suggested convergence of RUNT domain residues towards sub-maximal strength. Hence, the selective expression of gene duplicates in specialized cell types can synergize with the acquisition of functional differences to enable appropriate gene expression, lineage choice and differentiation in the mammalian immune system