From research to practice: the effects of the jointly sponsored dissemination of an arthritis self-care nursing intervention

Various educational programs have been developed and found to be effective in the self-management of arthritis. This study reexamined the effectiveness of one such program, "Bone Up On Arthritis" (BUOA), when the program was delivered by a community-based service organization to a sample of persons (N = 154) who differed widely in disease type and demographic characteristics. Arthritis Foundation staff implemented BUOA at four national sites; data were collected and analyzed by University of Michigan nurse researchers. Investigators found improved scores on all outcome measures (self-care behavior, helplessness, pain, dysfunction, and depression). These findings suggest that "Bone Up" is an effective nursing intervention in multiple organizational and community environments and for diverse patient populations.     

Feedstock powder processing research needs for additive manufacturing development

Additive manufacturing (AM) promises to redesign traditional manufacturing by enabling the ultimate in agility for rapid component design changes in commercial products and for fabricating complex integrated parts. By significantly increasing quality and yield of metallic alloy powders, the pace for design, development, and deployment of the most promising AM approaches can be greatly accelerated, resulting in rapid commercialization of these advanced manufacturing methods. By successful completion of a critical suite of processing research tasks that are intended to greatly enhance gas atomized powder quality and the precision and efficiency of powder production, researchers can help promote continued rapid growth of AM. Other powder-based or spray-based advanced manufacturing methods could also benefit from these research outcomes, promoting the next wave of sustainable manufacturing technologies for conventional and advanced materials.     

Duration of treatment with progesterone and regression of persistent ovarian follicles in cattle

The objective of the present study was to determine the duration of elevated concentrations of progesterone necessary to induce atresia of persistent ovarian follicles. Heifers were administered 25 mg of PGF2alpha on d 6 and 7 (d 0 = d of synchronized estrus) and a norgestomet implant from d 6 to 14. Ovaries were monitored by ultrasonography, and blood samples were collected on d 3, 5, 7, 9, 11, and 12 and daily from d 14 until ovulation. On d 12, heifers received either two progesterone-releasing intravaginal devices (PRID) for 6 h (6-h; n = 5), two PRID for 24 h (24-h; n = 5), or no treatment (CON; n = 5). Blood samples were collected at 15-min intervals from h -6 to 30 (PRID insertion = h 0) and analyzed for concentrations of LH. Characteristics of LH secretion were determined for consecutive 6-h periods (Period 0 to 5). Hourly blood samples, collected from h 0 to 29, were analyzed for concentrations of 17beta-estradiol (estradiol) and progesterone. The dominant ovarian follicles present on d 7 increased in size to 15.4+/-.3 mm on d 12 ("persistent follicle"). Following removal of the PRID and norgestomet implants, atresia of persistent follicles and ovulation of new follicles were induced in one of five and in four of five heifers in the 6-h and 24-h treatments, respectively. Persistent follicles ovulated after withdrawal of norgestomet in all other heifers. Concentrations of progesterone were increased from h 1 to 7 in the 6-h and h 1 to 26 in the 24-h treatment. Frequency of LH pulses was reduced (P < .05) during Periods 1 to 2 in the 6-h and Periods 1 to 5 in the 24-h treatment relative to the CON treatment. By h 10, concentrations of estradiol in the 6-h and 24-h treatments were lower (P < . 05) than in the CON treatment. This suppression continued through h 29 in the 24-h treatment (P < .05), whereas concentrations in the 6-h treatment were intermediate to those of the CON and 24-h treatments after h 14. Suppression of pulsatile LH release and estradiol secretion was evident with 6 and 24 h of treatment with progesterone, but only the 24-h treatment induced atresia of persistent follicles in a majority of the heifers.     

Genetic effects of 1,3-butadiene and associated risk for heritable damage

A summary of the results of the studies conducted in the EU Project "Multi-endpoint analysis of genetic damage induced by 1,3-butadiene and its major metabolites in somatic and germ cells of mice, rats and man" is presented. Results of the project are summarized on the detection of DNA and hemoglobin adducts, on the cytotoxic and clastogenic effects in somatic and germinal cells of mice and rats, on the induction of somatic mutations at the hprt locus of experimental rodents and occupationally exposed workers, on the induction of dominant lethal mutations in mice and rats, and on heritable translocations induced in mice, after exposure to butadiene (BD) or its major metabolites, butadiene monoepoxide (BMO), diepoxybutane (DEB) and butadiene diolepoxide (BDE). The primary goal of this project was to collect experimental data on the genetic effects of BD in order to estimate the germ cell genetic risk to humans of exposure to BD. To achieve this, the butadiene exposure are based on data for heritable translocations and bone marrow micronuclei induced in mice and chromosome aberrations observed in lymphocytes of exposed workers. A doubling dose for heritable translocations in human germ cells of 4900 ppm/h is estimated, which, assuming cumulative BD exposure over the sensitive period of spermatogenesis, corresponds to 5-6 weeks of continuous exposure at the workplace to 20-25 ppm. Alternatively, the rate of heritable translocation induction per ppm/h of BD exposure is estimated to be approximately 0.8 per million live born, compared to a spontaneous incidence of balanced translocations in humans of approximately 800 per million live born. These estimates have large confidence intervals and are only intended to indicate orders of magnitude of human genetic risk. These risk estimates are based on data from germ cells of BD-exposed male mice. The demonstration that clastogenic damage was induced by DEB in preovulatory oocytes at doses which were not ovotoxic implies that additional studies on the response of mammalian female germ cells to BD and its metabolites are needed. The basic assumption of the above genetic risk estimates is that experimental mouse data obtained after BD exposure can be extrapolated to humans. Several points exist in the present report and in the literature which contradict this assumption: (1) the level of BMO-hemoglobin adducts was significantly elevated in BD-exposed workers; however, it was considerably lower than would have been predicted from comparable rat and mouse exposures; (2) the concentrations of the metabolites DEB and BMO were significantly higher in mouse than in rat blood after BD exposure. Thus, while metabolism of BD is qualitatively similar in the two species, it is quantitatively different; (3) no increase of HPRT mutations was shown in 19 workers exposed on average to 1.8 ppm of BD, while in a different population of workers from a US plant exposed on average to 3.5 ppm of BD, a significant increase of HPRT variants was detected; and (4) data from cancer bioassays and cancer epidemiology suggest that rat is a more appropriate model than mouse for human cancer risk from BD exposure. However, the dominant lethal study in rats gave a negative result. At present, we do not know which BD metabolite(s) may be responsible for the genetic effects even though the bifunctional alkylating agent DEB is the most likely candidate for the induction of clastogenic events. Unfortunately, methods to measure DEB adducts in hemoglobin or DNA are only presently being developed. Despite these several uncertainties the use of the mouse genetic data is regarded as a justifiable and conservative approach to human genetic risk estimation given the considerable heterogeneity observed in the biotransformation of BD in humans.     

2,4-Diamino-5-(2'-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition

Dihydrofolate reductase (DHFR) has been a well-recognized target for the development of therapeutics for human cancers for several decades. Classical inhibitors of DHFR use an active transport mechanism to gain access to the cell; disabling this mechanism creates a pathway for resistance. In response, recent research focuses on nonclassical lipid-soluble DHFR inhibitors that are designed to passively diffuse through the membrane. Here, a new series of propargyl-linked antifolates are investigated as potential nonclassical human DHFR inhibitors. Several of these compounds exhibit potent enzyme inhibition with 50% inhibition concentration values under 500 nM. Molecular docking investigations show that the compounds maintain conserved hydrogen bonds between the pyrimidine ring and the enzyme as well as form van der Waals interactions with critical residues in the active site. Interestingly, the most potent compound, 2,4-diamino-5-(3-(3,4,5-trimethoxyphenyl)prop-1-ynyl)-6-ethylpyrimidine (compound 35), is 3500-fold more potent than trimethoprim, a potent inhibitor of bacterial DHFR but weak inhibitor of human DHFR. The two structural differences between compound 35 and trimethoprim show that the propargyl linkage and the substitution at C6 of the pyrimidine ring are critical to the formation of contacts with Thr 56, Ser 59, Ile 60, Leu 22, Phe 31 and Phe 34 and hence, to enhancing potency. The propargyl-linked antifolates are efficient ligands with a high ratio of potency to the number of non-hydrogen atoms and represent a potentially fruitful avenue for future development of antineoplastic agents.     

Implementing enterprise resource planning systems: organizational performance and the duration of the implementation

This paper examines the impact of the duration of ERP implementation on firm performance both during and after implementation. Organizations choose either an accelerated implementation approach or a traditional (longer) implementation approach. The former approach gives the organization the advantage of speed, but the disadvantage of fitting its processes to that of a packaged (thus, undifferentiated from competitors) ERP. The latter approach allows the organization to redesign strategy and processes, and thus, search for ways to be unique from its competition. The study uses a regression model to capture the changes in various performance measures during and after implementation between firms that implemented the ERP, using the performance measure of a matched group of firms that did not implement an ERP as a benchmark/control sample, on the basis of the duration of the implementation. Financial data from Compustat, and data on start date and end date of ERP implementation between 1990 and 2005 for firms in the Oil and Gas industry was collected from an ERP vendor. Results show that measures such as return on sales improved after implementation. However, measures such as inventory turnover, which reflect operational benefits, improve during implementation. We find that accelerated implementation confers both operational and strategic benefits. This study highlights the strategic consequences of the different choices of implementation.     

Using LiDAR and quickbird data to model plant production and quantify uncertainties associated with wetland detection and land cover generalizations

Spatiotemporal data from satellite remote sensing and surface meteorology networks have made it possible to continuously monitor global plant production, and to identify global trends associated with land cover/use and climate change. Gross primary production (GPP) and net primary production (NPP) are routinely derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) onboard satellites Terra and Aqua, and estimates generally agree with independent measurements at validation sites across the globe. However, the accuracy of GPP and NPP estimates in some regions may be limited by the quality of model input variables and heterogeneity at fine spatial scales. We developed new methods for deriving model inputs (i.e., land cover, leaf area, and photosynthetically active radiation absorbed by plant canopies) from airborne laser altimetry (LiDAR) and Quickbird multispectral data at resolutions ranging from about 30 m to 1 km. In addition, LiDAR-derived biomass was used as a means for computing carbon-use efficiency. Spatial variables were used with temporal data from ground-based monitoring stations to compute a six-year GPP and NPP time series for a 3600 ha study site in the Great Lakes region of North America. Model results compared favorably with independent observations from a 400 m flux tower and a process-based ecosystem model (BIOME-BGC), but only after removing vapor pressure deficit as a constraint on photosynthesis from the MODIS global algorithm. Fine-resolution inputs captured more of the spatial variability, but estimates were similar to coarse-resolution data when integrated across the entire landscape. Failure to account for wetlands had little impact on landscape-scale estimates, because vegetation structure, composition, and conversion efficiencies were similar to upland plant communities. Plant productivity estimates were noticeably improved using LiDAR-derived variables, while uncertainties associated with land cover generalizations and wetlands in this largely forested landscape were considered less important.