Calcium diffusion in transient and steady states in muscle.

Rates of diffusion through the extracellular space of thin sheets of myocardium from the right ventricular outflow tract of kittens were estimated at 23 degrees C for 45Ca2+ and an inert reference tracer, [14C]sucrose. The myocardial sheets were mounted in an Ussing chamber and equilibrated with Tyrode solution with varied calcium concentrations, Cao. The tracers were added to one side and their concentrations on the other side measured at 5-15-min intervals for 6 h. The apparent tracer diffusion coefficient for sucrose was 1.11 +/- 0.06 X 10(-6) cm2s-1 (mean +/- SEM, n = 74), 22% of the free diffusion coefficient; the lag time before reaching a steady state provided estimates of the intratissue volume of distribution or diffusion space of 0.41 +/- 0.15 ml/ml tissue (n = 74), a value compatible with expectations for extracellular fluid space. Over the range of Cao from 0.02 to 9.0 mM, the intratissue apparent diffusion coefficient for Ca, DCa, averaged 1.65 +/- 0.10 X 10(-6) cm2s-1, n = 74, which is 21% of the free DoCa, and was not influenced by Cao. Because transsarcolemmal Ca permeation is slow, DCa is the diffusion coefficient in the extracellular region. The paired ratios DCa/Ds averaged 1.32 +/- 0.05 (n = 67) for all levels of Cao but at physiologic or higher Cao averaged 1.45 +/- 0.07 (n = 39), close to the ratio of free diffusion coefficients, 1.53. Equations distinguishing transient from steady state diffusion were fitted to the data, showing that the apparent distribution volume of "binding sites" external to the diffusion pathway diminished at higher Cao in a fashion suggesting that a least two different Ca2+ binding sites were present.     

Effects of thromboxane analog U46619 on endothelial damaged canine coronary arteries in vivo

We studied the effects of the thromboxane analog, U46619, infused into the left anterior descending (LAD) artery of intact dogs before and after producing endothelial denudation of the mid portion of the LAD. Proximal artery cross-sectional area (CSA) decreased by 47% with 0.1 microgram/min infusion of U46619 with intact and denuded endothelium, while resting CSA reduced spontaneously following denudation. Coronary resistance vessels demonstrated a marked constrictor response to U46619 with a rise in resistance and a fall in flow and myocardial O2 consumption. U46619 produces significant narrowing of proximal epicardial coronary arteries as well as resistance coronary vessels. This effect could cause ischemia in patients with moderate coronary atherosclerosis.     

Aspen (<Emphasis Type="Italic">Populus tremuloides</Emphasis>) stands and their contribution to plant diversity in a semiarid coniferous landscape

We conducted a field study to determine the relative contributions of aspen (Populus tremuloides), meadow, and conifer communities to local and landscape-level plant species diversity in the Sierra Nevada and southern Cascade Range, northeastern California, USA. We surveyed plant assemblages at 30 sites that included adjacent aspen, conifer, and meadow communities across a 10,000-km² region. We statistically investigated patterns in local and landscape-scale plant diversity within and among the three vegetation types. Summing across sites, aspen stands supported more plant species overall and more unique plant species than either meadow or conifer communities. Local richness and diversity did not differ between aspen and meadow plots; conifer forest plots were significantly lower in both measures. Heterogeneity in species composition was higher for aspen forest than for meadows or conifer forest, both within sites and between sites. Plant communities in aspen stands shared less than 25% of their species with adjacent vegetation in conifer and meadow plots. Within aspen forest, we found a negative relationship between total canopy cover and plant diversity. Our results strongly support the idea that plant communities of aspen stands are compositionally distinct from adjacent meadows and conifer forest, and that aspen forests are a major contributor to plant species diversity in the study region. Current patterns of aspen stand succession to conifer forest on many sites in the semiarid western US are likely to reduce local and landscape-level plant species diversity, and may also have negative effects on other ecosystem functions and services provided by aspen forest.     

The delivery of evidence-based preventive care for older Americans with arthritis

Introduction  

Previous research suggests patients with rheumatoid arthritis (RA) may receive suboptimal care with respect to preventive tests and services. We evaluated the proportion of older Americans with RA, psoriatic arthritis (PsA), and osteoarthritis (OA) receiving these services and the specialty of the providers delivering this care.     

Altered fire regimes cause long‐term lichen diversity losses

Many global ecosystems have undergone shifts in fire regimes in recent decades, such as changes in fire size, frequency, and/or severity. Recent research shows that increases in fire size, frequency, and severity can lead to long‐persisting deforestation, but the consequences of shifting fire regimes for biodiversity of other vegetative organisms (such as understory plants, fungi, and lichens) remain poorly understood. Understanding lichen responses to wildfire is particularly important because lichens play crucial roles in nutrient cycling and supporting wildlife in many ecosystems. Lichen responses to fire have been little studied, and most previous research has been limited to small geographic areas (e.g. studies of a single fire), making it difficult to establish generalizable patterns. To investigate long‐term effects of fire severity on lichen communities, we sampled epiphytic lichen communities in 104 study plots across California's greater Sierra Nevada region in areas that burned in five wildfires, ranging from 4 to 16 years prior to sampling. The conifer forest ecosystems we studied have undergone a notable increase in fire severity in recent decades, and we sample across the full gradient of fire severity to infer how shifting fire regimes may influence landscape‐level biodiversity. We find that low‐severity fire has little to no effect on lichen communities. Areas that burned at moderate and high severities, however, have significantly and progressively lower lichen richness and abundance. Importantly, we observe very little postfire lichen recolonization on burned substrates even more than 15 years after fire. Our multivariate model suggests that the hotter, drier microclimates that occur after fire removes forest canopies may prevent lichen reestablishment, meaning that lichens are not likely to recolonize until mature trees regenerate. These findings suggest that altered fire regimes may cause broad and long‐persisting landscape‐scale biodiversity losses that could ultimately impact multiple trophic levels.     

Production of very-high-amylose potato starch by inhibition of SBE A and B

High-amylose starch is in great demand by the starch industry for its unique functional properties. However, very few high-amylose crop varieties are commercially available. In this paper we describe the generation of very-high-amylose potato starch by genetic modification. We achieved this by simultaneously inhibiting two isoforms of starch branching enzyme to below 1% of the wild-type activities. Starch granule morphology and composition were noticeably altered. Normal, high-molecular-weight amylopectin was absent, whereas the amylose content was increased to levels comparable to the highest commercially available maize starches. In addition, the phosphorus content of the starch was increased more than fivefold. This unique starch, with its high amylose, low amylopectin, and high phosphorus levels, offers novel properties for food and industrial applications.     

Large-scale causes of variation in the serpentine vegetation of California

Serpentine vegetation in California ranges from forest to shrubland and grassland, harbors many rare and endemic species, and is only moderately altered by invasive exotic species at the present time. To better understand the factors regulating the distribution of common/representative species, endemic/rare species, and the threat of exotics in this important flora, we analyzed broad-scale community patterns and environmental conditions in a geographically stratified set of samples from across the state. We considered three major classes of environmental influences: climate (especially precipitation), soils (especially the Mg²⁺/Ca²⁺ ratio), and the indirect influences of climate on soils. We used ordination to identify the major axes of variation in common species abundances, structural equation models to analyze the relationship of community axes and endemic and exotic species richness to the environment, and group analysis techniques to identify consistent groupings of species and characterize their properties. We found that community variation could be explained by a two-axis ordination. One axis ranged from conifer forest to grassland and was strongly related to precipitation. The second axis ranged from chaparral to grassland and had little relationship to current environmental conditions, suggesting a possible role for successional history. Precipitation and elevation were respectively the largest influences on endemic and exotic richness, followed by Mg²⁺/Ca²⁺. The results also support the idea that long-term precipitation patterns have altered the Mg²⁺/Ca²⁺ ratio via selective leaching, resulting in indirect influences on endemics (positive) and exotics (negative) but not affecting the abundances of common species. We discuss implications of these findings for the conservation of the California serpentine flora.     

Derivation and preliminary validation of an administrative claims-based algorithm for the effectiveness of medications for rheumatoid arthritis

Introduction

Administrative claims data have not commonly been used to study the clinical effectiveness of medications for rheumatoid arthritis (RA) because of the lack of a validated algorithm for this outcome. We created and tested a claims-based algorithm to serve as a proxy for the clinical effectiveness of RA medications.

Methods

We linked Veterans Health Administration (VHA) medical and pharmacy claims for RA patients participating in the longitudinal Department of Veterans Affairs (VA) RA registry (VARA). Among individuals for whom treatment with a new biologic agent or nonbiologic disease-modifying agent in rheumatic disease (DMARD) was being initiated and with registry follow-up at 1 year, VARA and administrative data were used to create a gold standard for the claims-based effectiveness algorithm. The gold standard outcome was low disease activity (LDA) (Disease Activity Score using 28 joint counts (DAS28) ≤ 3.2) or improvement in DAS28 by > 1.2 units at 12 ± 2 months, with high adherence to therapy. The claims-based effectiveness algorithm incorporated biologic dose escalation or switching, addition of new disease-modifying agents, increase in oral glucocorticoid use and dose as well as parenteral glucocorticoid injections.

Results

Among 1,397 patients, we identified 305 eligible biologic or DMARD treatment episodes in 269 unique individuals. The patients were primarily men (94%) with a mean (± SD) age of 62 ± 10 years. At 1 year, 27% of treatment episodes achieved the effectiveness gold standard. The performance characteristics of the effectiveness algorithm were as follows: positive predictive value, 76% (95% confidence interval (95% CI) = 71% to 81%); negative predictive value, 90% (95% CI = 88% to 92%); sensitivity, 72% (95% CI = 67% to 77%); and specificity, 91% (95% CI = 89% to 93%).

Conclusions

Administrative claims data may be useful in evaluating the effectiveness of medications for RA. Further validation of this effectiveness algorithm will be useful in assessing its generalizability and performance in other populations.     

Pulse Decomposition Analysis of the digital arterial pulse during hemorrhage simulation

Background

Markers of temporal changes in central blood volume are required to non-invasively detect hemorrhage and the onset of hemorrhagic shock. Recent work suggests that pulse pressure may be such a marker. A new approach to tracking blood pressure, and pulse pressure specifically is presented that is based on a new form of pulse pressure wave analysis called Pulse Decomposition Analysis (PDA). The premise of the PDA model is that the peripheral arterial pressure pulse is a superposition of five individual component pressure pulses, the first of which is due to the left ventricular ejection from the heart while the remaining component pressure pulses are reflections and re-reflections that originate from only two reflection sites within the central arteries. The hypothesis examined here is that the PDA parameter T13, the timing delay between the first and third component pulses, correlates with pulse pressure. T13 was monitored along with blood pressure, as determined by an automatic cuff and another continuous blood pressure monitor, during the course of lower body negative pressure (LBNP) sessions involving four stages, -15 mmHg, -30 mmHg, -45 mmHg, and -60 mmHg, in fifteen subjects (average age: 24.4 years, SD: 3.0 years; average height: 168.6 cm, SD: 8.0 cm; average weight: 64.0 kg, SD: 9.1 kg).

Results

Statistically significant correlations between T13 and pulse pressure as well as the ability of T13 to resolve the effects of different LBNP stages were established. Experimental T13 values were compared with predictions of the PDA model. These interventions resulted in pulse pressure changes of up to 7.8 mmHg (SE = 3.49 mmHg) as determined by the automatic cuff. Corresponding changes in T13 were a shortening by -72 milliseconds (SE = 4.17 milliseconds). In contrast to the other two methodologies, T13 was able to resolve the effects of the two least negative pressure stages with significance set at p < 0.01.

Conclusions

The agreement of observations and measurements provides a preliminary validation of the PDA model regarding the origin of the arterial pressure pulse reflections. The proposed physical picture of the PDA model is attractive because it identifies the contributions of distinct reflecting arterial tree components to the peripheral pressure pulse envelope. Since the importance of arterial pressure reflections to cardiovascular health is well known, the PDA pulse analysis could provide, beyond the tracking of blood pressure, an assessment tool of those reflections as well as the health of the sites that give rise to them.