944 resultados para Expected and observed heterozygosity


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Currently more than half of Electronic Health Record (EHR) projects fail. Most of these failures are not due to flawed technology, but rather due to the lack of systematic considerations of human issues. Among the barriers for EHR adoption, function mismatching among users, activities, and systems is a major area that has not been systematically addressed from a human-centered perspective. A theoretical framework called Functional Framework was developed for identifying and reducing functional discrepancies among users, activities, and systems. The Functional Framework is composed of three models – the User Model, the Designer Model, and the Activity Model. The User Model was developed by conducting a survey (N = 32) that identified the functions needed and desired from the user’s perspective. The Designer Model was developed by conducting a systemic review of an Electronic Dental Record (EDR) and its functions. The Activity Model was developed using an ethnographic method called shadowing where EDR users (5 dentists, 5 dental assistants, 5 administrative personnel) were followed quietly and observed for their activities. These three models were combined to form a unified model. From the unified model the work domain ontology was developed by asking users to rate the functions (a total of 190 functions) in the unified model along the dimensions of frequency and criticality in a survey. The functional discrepancies, as indicated by the regions of the Venn diagrams formed by the three models, were consistent with the survey results, especially with user satisfaction. The survey for the Functional Framework indicated the preference of one system over the other (R=0.895). The results of this project showed that the Functional Framework provides a systematic method for identifying, evaluating, and reducing functional discrepancies among users, systems, and activities. Limitations and generalizability of the Functional Framework were discussed.

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This project develops K(bin), a relatively simple, binomial based statistic for assessing interrater agreement in which expected agreement is calculated a priori from the number of raters involved in the study and number of categories on the rating tool. The statistic is logical in interpretation, easily calculated, stable for small sample sizes, and has application over a wide range of possible combinations from the simplest case of two raters using a binomial scale to multiple raters using a multiple level scale.^ Tables of expected agreement values and tables of critical values for K(bin) which include power to detect three levels of the population parameter K for n from 2 to 30 and observed agreement $\ge$.70 calculated at alpha =.05,.025, and.01 are included.^ An example is also included which describes the use of the tables for planning and evaluating an interrater reliability study using the statistic, K(bin). ^

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Context. The Rosetta encounter with comet 67P/Churyumov-Gerasimenko provides a unique opportunity for an in situ, up-close investigation of ion-neutral chemistry in the coma of a weakly outgassing comet far from the Sun. Aims. Observations of primary and secondary ions and modeling are used to investigate the role of ion-neutral chemistry within the thin coma. Methods. Observations from late October through mid-December 2014 show the continuous presence of the solar wind 30 km from the comet nucleus. These and other observations indicate that there is no contact surface and the solar wind has direct access to the nucleus. On several occasions during this time period, the Rosetta/ROSINA/Double Focusing Mass Spectrometer measured the low-energy ion composition in the coma. Organic volatiles and water group ions and their breakup products (masses 14 through 19), CO2+ (masses 28 and 44) and other mass peaks (at masses 26, 27, and possibly 30) were observed. Secondary ions include H3O+ and HCO+ (masses 19 and 29). These secondary ions indicate ion-neutral chemistry in the thin coma of the comet. A relatively simple model is constructed to account for the low H3O+/H2O+ and HCO+/CO+ ratios observed in a water dominated coma. Results from this simple model are compared with results from models that include a more detailed chemical reaction network. Results. At low outgassing rates, predictions from the simple model agree with observations and with results from more complex models that include much more chemistry. At higher outgassing rates, the ion-neutral chemistry is still limited and high HCO+/CO+ ratios are predicted and observed. However, at higher outgassing rates, the model predicts high H3O+/H2O+ ratios and the observed ratios are often low. These low ratios may be the result of the highly heterogeneous nature of the coma, where CO and CO2 number densities can exceed that of water.

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Background: A small pond, c. 90 years old, near Bern, Switzerland contains a population of threespine stickleback (Gasterosteus aculeatus) with two distinct male phenotypes. Males of one type are large, and red, and nest in the shallow littoral zone. The males of the other are small and orange, and nest offshore at slightly greater depth. The females in this population are phenotypically highly variable but cannot easily be assigned to either male type. Question: Is the existence of two sympatric male morphs maintained by substrate-associated male nest site choice and facilitated by female mate preferences? Organisms: Male stickleback caught individually at their breeding sites. Females caught with minnow traps. Methods: In experimental tanks, we simulated the slope and substrate of the two nesting habitats. We then placed individual males in a tank and observed in which habitat the male would build his nest. In a simultaneous two-stimulus choice design, we gave females the choice between a large, red male and a small, orange one. We measured female morphology and used linear mixed effect models to determine whether female preference correlated with female morphology. Results: Both red and orange males preferred nesting in the habitat that simulated the slightly deeper offshore condition. This is the habitat occupied by the small, orange males in the pond itself. The proportion of females that chose a small orange male was similar to that which chose a large red male. Several aspects of female phenotype correlated with the male type that a female preferred.

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CONTEXT The autosomal dominant form of GH deficiency (IGHD II) is characterized by markedly reduced GH secretion combined with low concentrations of IGF-1 leading to short stature. OBJECTIVE Structure-function analysis of a missense mutation in the GH-1 gene converting codon 76 from leucine (L) to proline (P) yielding a mutant GH-L76P peptide. DESIGN, SETTINGS, AND PATIENTS Heterozygosity for GH-L76P/wt-GH was identified in a nonconsanguineous Spanish family. The index patients, two siblings, a boy and a girl, were referred for assessment of their short stature (-3.2 and -3.8 SD). Their grandmother, father, and aunt were also carrying the same mutation and showed severe short stature; therefore, IGHD II was diagnosed. INTERVENTIONS AND RESULTS AtT-20 cells coexpressing both wt-GH and GH-L76P showed a reduced GH secretion (P < .001) after forskolin stimulation when compared with the cells expressing only wt-GH. In silico mutagenesis and molecular dynamics simulations presented alterations of correct folding and mutant stability compared with wt-GH. Therefore, further structural analysis of the GH-L76P mutant was performed using expressed and purified proteins in Escherichia coli by thermofluor assay and fast degradation proteolysis assay. Both assays revealed that the GH-L76P mutant is unstable and misfolded compared to wt-GH confirming the bioinformatic model prediction. CONCLUSIONS This is the first report of a family suffering from short stature caused by IGHD II, which severely affects intracellular GH folding and stability as well as secretion, highlighting the necessity of functional analysis of any GH variant for defining new mechanisms as a cause for IGHD II.

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Accurate rainfall data are the key input parameter for modelling river discharge and soil loss. Remote areas of Ethiopia often lack adequate precipitation data and where these data are available, there might be substantial temporal or spatial gaps. To counter this challenge, the Climate Forecast System Reanalysis (CFSR) of the National Centers for Environmental Prediction (NCEP) readily provides weather data for any geographic location on earth between 1979 and 2014. This study assesses the applicability of CFSR weather data to three watersheds in the Blue Nile Basin in Ethiopia. To this end, the Soil and Water Assessment Tool (SWAT) was set up to simulate discharge and soil loss, using CFSR and conventional weather data, in three small-scale watersheds ranging from 112 to 477 ha. Calibrated simulation results were compared to observed river discharge and observed soil loss over a period of 32 years. The conventional weather data resulted in very good discharge outputs for all three watersheds, while the CFSR weather data resulted in unsatisfactory discharge outputs for all of the three gauging stations. Soil loss simulation with conventional weather inputs yielded satisfactory outputs for two of three watersheds, while the CFSR weather input resulted in three unsatisfactory results. Overall, the simulations with the conventional data resulted in far better results for discharge and soil loss than simulations with CFSR data. The simulations with CFSR data were unable to adequately represent the specific regional climate for the three watersheds, performing even worse in climatic areas with two rainy seasons. Hence, CFSR data should not be used lightly in remote areas with no conventional weather data where no prior analysis is possible.

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Objective. The prevalence of overweight and obesity differs substantially among children of different ethnic origin in the United States. The objective of this project is to estimate to what extent changes in ethnic composition since 1980 have contributed to the current general “obesity epidemic” in the childhood population of the United States.^ Methods. Populations by single year of age, 0 to 19, male and female, for Hispanics, non-Hispanic whites, and non-Hispanic blacks, from the US Census’ July estimates for 1985, 1990, 1995, 2000 and 2005 were taken and compared to the population and percentage of those groups from 1980. Age, sex, and ethnicity specific prevalence rates for overweight in 1980 were then applied to the populations by age for the specified year and differences in expected and actual overweight populations were assessed.^ Result. The results from this investigation provide estimates of the contribution that different ethnic groups have made to the overall prevalence of overweight and obesity in the childhood population of the United States. Assuming that the 1976-1980 prevalence rates had remained unchanged, and then comparing the population had there been no change in ethnic composition with the population given the actual change in ethnicity, the percentage increase was 1.06% in 1985, 1.72% in 1990, 2.57% in 1995, 3.95% in 2000, and 4.39% in 2005.^ Conclusion. The changes in ethnic composition of the population, independent of changes in ethnicity-specific prevalence, have contributed substantially to the current overall prevalence of obesity in the United States childhood population. There are a number of factors that may be responsible for the apparent susceptibility of Mexican-Americans and non-Hispanic blacks to overweight and obesity. Further research is needed on specific characteristics of those populations.^

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This paper defines and compares several models for describing excess influenza pneumonia mortality in Houston. First, the methodology used by the Center for Disease Control is examined and several variations of this methodology are studied. All of the models examined emphasize the difficulty of omitting epidemic weeks.^ In an attempt to find a better method of describing expected and epidemic mortality, time series methods are examined. Grouping in four-week periods, truncating the data series to adjust epidemic periods, and seasonally-adjusting the series y(,t), by:^ (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)^ is the best method examined. This new series w(,t) is stationary and a moving average model MA(1) gives a good fit for forecasting influenza and pneumonia mortality in Houston.^ Influenza morbidity, other causes of death, sex, race, age, climate variables, environmental factors, and school absenteeism are all examined in terms of their relationship to influenza and pneumonia mortality. Both influenza morbidity and ischemic heart disease mortality show a very high relationship that remains when seasonal trends are removed from the data. However, when jointly modeling the three series it is obvious that the simple time series MA(1) model of truncated, seasonally-adjusted four-week data gives a better forecast.^

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Mixture modeling is commonly used to model categorical latent variables that represent subpopulations in which population membership is unknown but can be inferred from the data. In relatively recent years, the potential of finite mixture models has been applied in time-to-event data. However, the commonly used survival mixture model assumes that the effects of the covariates involved in failure times differ across latent classes, but the covariate distribution is homogeneous. The aim of this dissertation is to develop a method to examine time-to-event data in the presence of unobserved heterogeneity under a framework of mixture modeling. A joint model is developed to incorporate the latent survival trajectory along with the observed information for the joint analysis of a time-to-event variable, its discrete and continuous covariates, and a latent class variable. It is assumed that the effects of covariates on survival times and the distribution of covariates vary across different latent classes. The unobservable survival trajectories are identified through estimating the probability that a subject belongs to a particular class based on observed information. We applied this method to a Hodgkin lymphoma study with long-term follow-up and observed four distinct latent classes in terms of long-term survival and distributions of prognostic factors. Our results from simulation studies and from the Hodgkin lymphoma study demonstrated the superiority of our joint model compared with the conventional survival model. This flexible inference method provides more accurate estimation and accommodates unobservable heterogeneity among individuals while taking involved interactions between covariates into consideration.^

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An integrated instrument package for measuring and understanding the surface radiation budget of sea ice is presented, along with results from its first deployment. The setup simultaneously measures broadband fluxes of upwelling and downwelling terrestrial and solar radiation (four components separately), spectral fluxes of incident and reflected solar radiation, and supporting data such as air temperature and humidity, surface temperature, and location (GPS), in addition to photographing the sky and observed surface during each measurement. The instruments are mounted on a small sled, allowing measurements of the radiation budget to be made at many locations in the study area to see the effect of small-scale surface processes on the large-scale radiation budget. Such observations have many applications, from calibration and validation of remote sensing products to improving our understanding of surface processes that affect atmosphere-snow-ice interactions and drive feedbacks, ultimately leading to the potential to improve climate modelling of ice-covered regions of the ocean. The photographs, spectral data, and other observations allow for improved analysis of the broadband data. An example of this is shown by using the observations made during a partly cloudy day, which show erratic variations due to passing clouds, and creating a careful estimate of what the radiation budget along the observed line would have been under uniform sky conditions, clear or overcast. Other data from the setup's first deployment, in June 2011 on fast ice near Point Barrow, Alaska, are also shown; these illustrate the rapid changes of the radiation budget during a cold period that led to refreezing and new snow well into the melt season.

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A mass budget was constructed for organic carbon on the upper slope of the Middle Atlantic Bight, a region thought to serve as a depocenter for fine-grained material exported from the adjacent shelf. Various components of the budget are internally consistent, and observed differences can be attributed to natural spatial variability or to the different time scales over which measurements were made. The flux of organic carbon to the sediments in the core of the depocenter zone, at a water depth of 1000 m, was measured with sediment traps to be 65 mg C m**-2 day**-1, of which 6-24 mg C m**-2 day**-1 is buried. Oxygen fluxes into the sediments, measured with incubation chambers attached to a free vehicle lander, correspond to total carbon remineralization rates of 49-70 mg C m**-2 day**-1. Carbon remineralization rates estimated from gradients of Corg within the mixed layer, and from gradients of dissolved ammonia and phosphate in pore waters, sum to only 4-6 mg C m**-2 day**-1. Most of the Corg remineralization in slope sediments is mediated by bacteria and takes place within a few mm of the sediment-water interface. Most of the Corg deposited on the upper slope sediments is supplied by lateral transport from other regions, but even if all of this material were derived from the adjacent shelf, it represents <2% of the mean annual shelf productivity. This value is further lowered by recognizing that as much as half of the Corg deposited on the slope is refractory, having originated by reworking from older deposits. Refractory Corg arrives at the sea bed with an average 14C age 600-900 years older than the pre-bomb 14C age of DIC in seawater, and has a mean life in the sediments with respect to biological remineralization of at least 1000 years. Labile carbon supplied to the slope, on the other hand, is rapidly and (virtually) completely remineralized, with a mean life of < 1 year. Carbon-14 ages of fine-grained carbonate and organic carbon present within the interstices of shelf sands are consistent with this material acting as a source for the old carbon supplied to the slope. Winnowing and export of reworked carbon may contribute to the often-described relationship between organic carbon preservation and accumulation rate of marine sediments.

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1. Identifying plant communities that are resistant to climate change will be critical for developing accurate, wide-scale vegetation change predictions. Most northern plant communities, especially tundra, have shown strong responses to experimental and observed warming. 2. Experimental warming is a key tool for understanding vegetation responses to climate change. We used open-top chambers to passively warm an evergreen-shrub heath by 1.0-1.3 °C for 15 years at Alexandra Fiord, Nunavut, Canada (79 °N). In 1996, 2000 and 2007, we measured height, plant composition and abundance with a point-intercept method. 3. Experimental warming did not strongly affect vascular plant cover, canopy height or species diversity, but it did increase bryophyte cover by 6.3% and decrease lichen cover by 3.5%. Temporal changes in plant cover were more frequent and of greater magnitude than changes due to experimental warming. 4. Synthesis. This evergreen-shrub heath continues to exhibit community-level resistance to long-term experimental warming, in contrast to most Arctic plant communities. Our findings support the view that only substantial climatic changes will alter unproductive ecosystems.

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The physical (temperature, salinity, velocity) and biogeochemical (oxygen, nitrate) structure of an oxygen depleted coherent, baroclinic, anticyclonic mode-water eddy (ACME) is investigated using high-resolution autonomous glider and ship data. A distinct core with a diameter of about 70 km is found in the eddy, extending from about 60 to 200 m depth and. The core is occupied by fresh and cold water with low oxygen and high nitrate concentrations, and bordered by local maxima in buoyancy frequency. Velocity and property gradient sections show vertical layering at the flanks and underneath the eddy characteristic for vertical propagation (to several hundred-meters depth) of near inertial internal waves (NIW) and confirmed by direct current measurements. A narrow region exists at the outer edge of the eddy where NIW can propagate downward. NIW phase speed and mean flow are of similar magnitude and critical layer formation is expected to occur. An asymmetry in the NIW pattern is seen that possible relates to the large-scale Ekman transport interacting with ACME dynamics. NIW/mean flow induced mixing occurs close to the euphotic zone/mixed layer and upward nutrient flux is expected and supported by the observations. Combing high resolution nitrate (NO3-) data with the apparent oxygen utilization (AOU) reveals AOU:NO3- ratios of 16 which are much higher than in the surrounding waters (8.1). A maximum NO3- deficit of 4 to 6 µmol kg-1 is estimated for the low oxygen core. Denitrification would be a possible explanation. This study provides evidence that the recycling of NO3-, extracted from the eddy core and replenished into the core via the particle export, may quantitatively be more important. In this case, the particulate phase is of keys importance in decoupling the nitrogen from the oxygen cycling.

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In order to assess the effects of ocean acidification and warming on the Mediterranean mussel (Mytilus galloprovincialis), specimens were reared in aquarium tanks and exposed to elevated conditions of temperature (+3°C) and acidity (-0.3 pH units) for a period of 10 months. The whole system comprised a factorial experimental design with 4 treatments (3 aquaria per treatment): control, lowered pH, elevated temperature, and lowered pH/elevated temperature. Mortality was estimated on a weekly basis and every 2 months, various biometrical parameters and physiological processes were measured: somatic and shell growth, metabolic rates and body fluid acid-base parameters. Mussels were highly sensitive to warming, with 100% mortality observed under elevated temperature at the end of our experiment in October. Mortality rates increased drastically in summer, when water temperature exceeded 25°C. In contrast, our results suggest that survival of this species will not be affected by a pH decrease of 0.3 in the Mediterranean Sea. Somatic and shell growth did not appear very sensitive to ocean acidification and warming during most of the experiment, but were reduced, after summer, in the lowered pH treatment. This was consistent with measured shell net dissolution and observed loss of periostracum, as well as uncompensated extracellular acidosis in the lowered pH treatment indicating a progressive insufficiency in acid-base regulation capacity. However, based on the present dataset, we cannot elucidate if these decreases in growth and regulation capacities after summer are a consequence of lower pH levels during that period or a consequence of a combined effect of acidification and warming. To summarize, while ocean acidification will potentially contribute to lower growth rates, especially in summer when mussels are exposed to sub-optimal conditions, ocean warming will likely pose more serious threats to Mediterranean mussels in this region in the coming decades.