Gout as a risk factor for osteoporosis: epidemiologic evidence from a population-based longitudinal study involving 108,060 individuals.

Is gout a risk factor for future osteoporosis? This large population-based study comprising two matched groups of individuals with and without gout demonstrates that patients with gout have a 20% increase in the risk of developing osteoporosis in future through an 8-year follow-up. INTRODUCTION: To examine if gout is associated with an increased risk of osteoporosis. METHODS: We conducted a nationwide population-based retrospective matched-cohort study. Two matched cohorts (n = 36,458 with gout and 71,602 without gout) assembled and recruited from the Longitudinal Health Insurance Dataset containing 1 million subjects. Exclusion criteria were missing data, age < 20 years, short follow-up period, and pre-existing osteoporosis. Both cohorts were followed up until incident osteoporosis, death, or the end of the study. Person-year data and incidence rates were evaluated. A multivariable Cox model was used to derive an adjusted hazard ratio (aHR) after controlling for socioeconomic proxy, geographical difference, glucocorticoid and allopurinol exposure, various prespecified medical conditions, and comorbidities. RESULTS: Men comprised 72.8% of the cohorts. With a follow-up of 183,729 and 359,900 person-years for the gout and non-gout cohorts, 517 and 811 incidents of osteoporosis occurred, respectively, after excluding osteoporosis incidents in the first 3 years of follow-up. The cumulative incidence of osteoporosis was statistically higher in the gout cohort than in the non-gout cohort, at 3.3 versus 2.1% (P = 0.0036, log-rank). Our Cox model showed a 1.2-fold increase in the incidence of osteoporosis in the gout cohort, with an aHR of 1.2 (95% confidence interval, 1.06-1.35). CONCLUSIONS: This first population-based epidemiologic study supports the hypothesis that compared with individuals without gout; those with gout have a modest increase in the risk of developing osteoporosis in future.

3D Parylene sheath neural probe for chronic recordings.

OBJECTIVE: Reliable chronic recordings from implanted neural probes remain a significant challenge; current silicon-based and microwire technologies experience a wide range of biotic and abiotic failure modes contributing to loss of signal quality. APPROACH: A multi-prong alternative strategy with potential to overcome these hurdles is introduced that combines a novel three dimensional (3D), polymer-based probe structure with coatings. Specifically, the Parylene C sheath-based neural probe is coated with neurotrophic and anti-inflammatory factors loaded onto a Matrigel carrier to encourage the ingrowth of neuronal processes for improved recording quality, reduce the immune response, and promote improved probe integration into brain tissue for reliable, long-term implementation compared to its rigid counterparts. MAIN RESULTS: The 3D sheath structure of the probe was formed by thermal molding of a surface micromachined Parylene C microchannel, with electrode sites lining the interior and exterior regions of the lumen. Electrochemical characterization of the probes via cyclic voltammetry and electrochemical impedance spectroscopy was performed and indicated suitable electrode properties for neural recordings (1 kHz electrical impedance of ∼200 kΩ in vitro). A novel introducer tool for the insertion of the compliant polymer probe into neural tissue was developed and validated both in vitro using agarose gel and in vivo in the rat cerebral cortex. In vivo electrical functionality of the Parylene C-based 3D probes and their suitability for recording the neuronal activity over a 28-day period was demonstrated by maintaining the 1 kHz electrical impedance within a functional range (<400 kΩ) and achieving a reasonably high signal-to-noise ratio for detection of resolvable multi-unit neuronal activity on most recording sites in the probe. Immunohistochemical analysis of the implant site indicated strong correlations between the quality of recorded activity and the neuronal/astrocytic density around the probe. SIGNIFICANCE: The provided electrophysiological and immunohistochemical data provide strong support to the viability of the developed probe technology. Furthermore, the obtained data provide insights into further optimization of the probe design, including tip geometry, use of neurotrophic and anti-inflammatory drugs in the Matrigel coating, and placement of the recording sites.

Optimization and risk analyses for rule curves of reservoir operation: application to Tien-Hua-Hu Reservoir in Taiwan.

Tien-Hua-Hu Reservoir is currently under planning by the Water Resources Agency, Taiwan to meet the increasing water demands of central Taiwan arising from rapid growth of domestic water supply, and high-tech industrial parks. This study develops a simulation model for the ten-day period reservoir operation to calculate the ten-day water shortage index under varying rule curves. A genetic algorithm is coupled to the simulation model to find the optimal rule curves using the minimum ten-day water shortage index as an objective function. This study generates many sets of synthetic streamflows for risk, reliability, resiliency, and vulnerability analyses of reservoir operation. ARMA and disaggregation models are developed and applied to the synthetic streamflow generation. The optimal rule curves obtained from this study perform better in the ten-day shortage index when compared to the originally designed rule curves from a previous study. The optimal rule curves are also superior to the originally designed rule curves in terms of vulnerability. However, in terms of reliability and resiliency, the optimal rule curves are inferior to the those originally designed. Results from this study have provided in general a set of improved rule curves for operation of the Tien-Hua-Hu Reservoir. Furthermore, results from reliability, resiliency and vulnerability analyses offer much useful information for decision making in reservoir operation.

Identification of rat Gas7 isoforms differentially expressed in brain and regulated following kainate-induced neuronal injury.

The growth arrest-specific gene 7 (Gas7) is expressed primarily in the brain and is necessary for the formation of neurite in cultured cerebellar preneurons. The endogenous rat Gas7 (rGas7) is transiently elevated before nerve growth factor-promoted neurite outgrowths emerge in cultured PC12 cells. We report three Gas7 isoforms (a, b, and c) in rat tissues. Peptide microsequencing identified two Gas7 forms, rGas7-a (38 kDa) and rGas7-b (47 kDa). rGas7-c can be predicted from a transcription variant by alternative splicing. Although two open reading frames were predicted, a cloned rGas7 cDNA encoded mostly rGas7-a in mammalian cells. The overexpression of the rGas7 cDNA in PC12 cells sufficed to promote small lamellipodia- and filopodia-like cell processes that resemble the initial stages of neurite formation. Three rGas7 isoforms were differentially expressed in all of the brain subregions. Only rGas7-a was detected in rat cerebellum, as in mouse cerebellum. Kainate injury did not affect the level of rGas7-b, but the level of isoform c was substantially suppressed in the hippocampus. Immunohistochemistry reveals that Gas7 was expressed primarily in the pyramidal neurons of the hippocampus and was quickly attenuated before recovery in the CA3 area after kainate was administered. These results suggest that differential expression and unique regulation of Gas7 isoforms in brain subregions may be important in specialized brain functions. Conservation of Gas7 isoforms by alternative splicing in mammals is also considered.

Multiobjective water resources systems analysis using genetic algorithms--application to Chou-Shui River Basin, Taiwan.

Multipurpose operation is adopted by most reservoirs in Taiwan in order to maximize the benefits of power generation, water supply, irrigation and recreational purposes. A multiobjective approach can be used to obtain trade-off curves among these multipurpose targets. The weighting method, in which different weighting factors are used for different purposes, was used in this research work. In Taiwan, most major reservoirs are operated by rule curves. Genetic algorithms with characteristics of artificial intelligence were applied to obtain the optimal rule curves of the multireservoir system under multipurpose operation in Chou-Shui River Basin in central Taiwan. The model results reveal that different shapes of rule curves under different weighting factors on targets can be efficiently obtained by genetic algorithms. Pareto optimal solutions for a trade-off between water supply and hydropower were obtained and analyzed.

The influence of artificial cutoff on a monitoring system and the water quality of the Keelung River.

The purpose of this study was to design a water quality monitoring network for the Keelung River in order to evaluate the effects of artificial cutoff across two bend channels. A steady-state water quality model was used to simulate the BOD and DO curves. The Kriging theory was applied to select the optimal locations for a water quality monitoring network. The sampling frequency was determined by the coefficients of variation of water quality and by considering the significance level and confidence interval. After calibration and verification of the water quality model, the model was applied and the simulation results indicated that the values of DO in the new channel would be higher than those of the old channel reaches. The critical point of the oxygen sag curve would shift to the mouth of river under O75 low-flow conditions, and the BOD values in the new channel would also slightly increase. The results further indicated that more monitoring stations would be needed in the downstream reaches.

Oxygen- and growth rate-dependent regulation of Escherichia coli fumarase (FumA, FumB, and FumC) activity.

Escherichia coli contains three biochemically distinct fumarases which catalyze the interconversion of fumarate to L-malate in the tricarboxylic acid cycle. Batch culture studies indicated that fumarase activities varied according to carbon substrate and cell doubling time. Growth rate control of fumarase activities in the wild type and mutants was demonstrated in continuous culture; FumA and FumC activities were induced four- to fivefold when the cell growth rate (k) was lowered from 1.2/h to 0.24/h at 1 and 21% O(2), respectively. There was a twofold induction of FumA and FumC activities when acetate was utilized instead of glucose as the sole carbon source. However, these fumarase activities were still shown to be under growth rate control. Thus, the activity of the fumarases is regulated by the cell growth rate and carbon source utilization independently. Further examination of FumA and FumC activities in a cya mutant suggested that growth rate control of FumA and FumC activities is cyclic AMP dependent. Although the total fumarase activity increased under aerobic conditions, the individual fumarase activities varied under different oxygen levels. While FumB activity was maximal during anaerobic growth (k = 0.6/h), FumA was the major enzyme under anaerobic cell growth, and the maximum activity was achieved when oxygen was elevated to 1 to 2%. Further increase in the oxygen level caused inactivation of FumA and FumB activities by the high oxidized state, but FumC activity increased simultaneously when the oxygen level was higher than 4%. The same regulation of the activities of fumarases in response to different oxygen levels was also found in mutants. Therefore, synthesis of the three fumarase enzymes is controlled in a hierarchical fashion depending on the environmental oxygen that the cell encounters.

Transcontinental Tidal Gravity Profile across the United States.

Data obtained from a transcontinental tidal gravity profile across the United States were analyzed. Results for the principal tidal constituents M(2) and O(1) have shed light on the long-standing problem of the indirect influence of ocean tides on the solid-earth tide. The profile consists of nine observational stations distributed almost evenly around latitudes 39 to 41 degrees north across the United States. The observed values of the gravimetric factor and the phase were found to depend on the tidal characteristics of the Atlantic and Pacific oceans. There is no observable correlation between tidal gravity parameters and the regional geology. When the influence of ocean tides is taken into account, it is possible for the first time to bring the gravimetric factors and phases for all the stations of a transcontinental network into a consistent system within the framework of the earth tidal theory.