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A field study was carried out on the year-long residual activity of the insect growth regulator (IGR) pyriproxyfen (Nylar 0.5G) in comparison with methoprene (Altosid® XRP Pellets) against mosquito developmental stages in catch basins in northwestern Riverside County, southern California. Pyriproxyfen was applied at 75, 100, 125, 150, 175 g per catch basin and methoprene at 3.5 g per catch basin. A total of 80 catch basins (10 per each treatment and 20 for control) were used. Posttreatment observations of catch basins were carried out at weekly intervals, with all pupal collections reared to adults. Mosquito species composition in this study, consisting mostly of Culex species (693), was predominated by Cx. quinquefasciatus (92.8%), followed by Cx. erythrothorax (5.5%), Cx. tarsalis (1.2%), Cx. stigmatosoma (0.3%), and Cx. thriambus (0.2%). Activity of both IGRs was expressed as percent inhibition of adult emergence (% IAE). Data generated on % IAE showed that, like methoprene, pyriproxyfen provided complete control of mosquitoes at 75, 125, and 175 g per catch basin up to 50 wk posttreatment at the Riverside amusement park, whereas its activity against mosquitoes in catch basins treated with 100 g and 150 g at the Eastvale site was short-lived, up to 48 wk. Water samples, bioassayed against laboratory-reared, 4th-stage larvae of Cx. quinquefasciatus 1–2 wk after the 50-wk-long study, showed evidence of significant % IAE (∼50) by pyriproxyfen at the 2 higher rates (125 g, 175 g) used at the amusement park. In conclusion, pyriproxyfen can be used to effectively control mosquitoes in catch basins for 48–50 wk, depending on the rate of application.

The ability to filter sensory information into relevant versus irrelevant stimuli is a fundamental, conserved property of the central nervous system and is accomplished in part through habituation learning. Synaptic plasticity that underlies habituation learning has been described at the cellular level, yet the genetic regulators of this plasticity remain poorly understood, as do circuits that mediate sensory filtering. A forward genetic screen for zebrafish genes that control habituation learning identified a mutant allele doryp177 that caused reduced habituation of the acoustic startle response. Whole-genome sequencing identified the calcium voltage-gated channel auxiliary subunit alpha-2/delta-3 (cacna2d3) as a candidate gene affected in doryp177 mutants. Behavioral characterization of larvae homozygous for two additional, independently derived mutant alleles of cacna2d3, together with failure of these alleles to complement doryp177, confirmed a critical role for cacna2d3 in habituation learning. Notably, detailed analyses of the acoustic response in mutant larvae also revealed increased startle sensitivity to acoustic stimuli, suggesting a broader role for cacna2d3 in controlling innate response thresholds to acoustic stimuli. Taken together, our data demonstrate a critical role for cacna2d3 in sensory filtering, a process that is disrupted in human CNS disorders, e.g. ADHD, schizophrenia, and autism.

Large lakes provide a variety of ecological services to surrounding cities and communities. Many of these services are supported by ecological processes that are threatened by the increasing prevalence of cyanobacterial blooms which occur as aquatic ecosystems experience cultural eutrophication. Over the past 10 yr, Lake Erie experienced cyanobacterial blooms of increasing severity and frequency, which have resulted in impaired drinking water for the surrounding communities. Cyanobacterial blooms may impact ecological processes that support other services, but many of these impacts have not been documented. Secondary production (production of primary consumers) is an important process that supports economically important higher trophic levels. Cyanobacterial blooms may influence secondary production because cyanobacteria are a poor-quality food resource and cyanotoxins may be harmful to consumers. Over 3 yr at 34 sites across the western basin of Lake Erie, we measured three indices of secondary production that focus on the dominant bivalve taxa: (1) growth of a native unionid mussel, (2) the size of young-of-year dreissenid mussels, and (3) the mass of colonizing animals on a Hester-Dendy sampler. Associations between these indices and cyanobacterial data were estimated to assess whether cyanobacteria are associated with variation in secondary production in the western basin of Lake Erie. The results suggest cyanobacterial abundance alone is only weakly associated with secondary production, but that cyanotoxins have a larger effect on secondary production. Given recurring late-summer cyanobacterial blooms, this impact on secondary production has the potential to undermine Lake Erie's ability to sustain important ecosystem services.

Invasion of North American waters by nonnative Dreissena polymorpha and D. rostriformis bugensis has resulted in declines of the Unionidae family of native North American mussels. Dreissenid mussels biofoul unionid mussels in large numbers and interfere with unionid movement, their acquisition of food, and the native mussels' ability to open and close their shells. Initial expectations for the Great Lakes included extirpation of unionids where they co-occurred with dreissenids, but recently adult and juvenile unionids have been found alive in several apparent refugia. These unionid populations may persist due to reduced dreissenid biofouling in these areas, and/or due to processes that remove biofoulers. For example locations inaccessible to dreissenid veligers may reduce biofouling and habitats with soft substrates may allow unionids to burrow and thus remove dreissenids. We deployed caged unionid mussels (Lampsilis siliquoidea) at 36 sites across the western basin of Lake Erie to assess spatial...

Dissolved organic matter (DOM) influences the physical, chemical, and biological properties of aquatic ecosystems. We hypothesized that controls over spatial variation in DOM quantity and composition (measured with DOM optical properties) differ based on the source of DOM to aquatic ecosystems. DOM quantity and composition should be better predicted by land cover in aquatic habitats with allochthonous DOM and related more strongly to nutrients in aquatic habitats with autochthonous DOM. Three habitat types [rivers (R), rivermouths (RM), and the nearshore zone (L)] associated with 23 tributaries of the Laurentian Great Lakes were sampled to test this prediction. Evidence from optical indices suggests that DOM in these habitats generally ranged from allochthonous (R sites) to a mix of allochthonous-like and autochthonous-like (L sites). Contrary to expectations, DOM properties such as the fluorescence index, humification index, and spectral slope ratio were only weakly related to land cover or nutrient data (Bayesian R 2 values were indistinguishable from zero). Strongly supported models in all habitat types linked DOM quantity (that is, dissolved organic carbon concentration [DOC]) to both land cover and nutrients (Bayesian R 2 values ranging from 0.55 to 0.72). Strongly supported models predicting DOC changed with habitat type: The most important predictor in R sites was wetlands whereas the most important predictor at L sites was croplands. These results suggest that as the DOM pool becomes more autochthonous-like, croplands become a more important driver of spatial variation in DOC and wetlands become less important.

Rivermouth ecosystems are areas where tributary waters mix with lentic near-shore waters and provide habitat for many Laurentian Great Lakes fish and wildlife species. Rivermouths are the interface between terrestrial activities that influence rivers and the ecologically important nearshore. Stable isotopes of nitrogen (N) and carbon (C) in consumers were measured from a range of rivermouths systems to address two questions: 1) What is the effect of rivermouth ecosystems and land cover on the isotopic composition of N available to rivermouth consumers? 2) Are rivermouth consumers composed of lake-like or river-like C? For question 1, data suggest that strong relationships between watershed agriculture and consumer N are weakened or eliminated at the rivermouth, in favor of stronger relationships between consumer N and depositional areas that may favor denitrification. For question 2, despite apparently large riverine inputs, consumers only occasionally appear river-like. More often consumers seem to incorporate large amounts of C from either the nearshore or primary production within the rivermouth itself. Rivermouths appear to be active C and N processing environments, thus necessitating their explicit incorporation into models estimating nearshore loading and possibly contributing to their importance to Great Lakes biota.

The inability to compare different measures of species abundance (such as density and percent cover) or different metrics of species biomass (such as wet mass and ash-free dry mass) hampers quantitative studies of community dynamics, trophic interactions, energy flow and biodiversity. This has been especially problematic for the dynamic and highly productive communities inhabiting shallow reefs in temperate seas where varied metrics are commonly used to characterize the abundance and biomass of different suites of species. To facilitate the conversion of abundance data into common metrics of biomass, we developed quantitative relationships between wet mass and length and wet mass and percent cover, and conversion factors for transforming wet mass into dry mass, shell-free and decalcified dry mass, and ash-free dry mass for 84 species of benthic macroinvertebrates common to giant kelp forests in southern California. Regressions for all 84 species were highly significant, and regression fits were very good for most species. Interspecific differences between regression slopes and in the ratios used to convert one metric of mass into another varied by as much as an order of magnitude among species within the same taxonomic group indicating that caution should be used when attempting to estimate biomass using generic relationships or ratios that were developed for other species, even if those species are closely related.

This study provides one historical and two alternative future contexts for evaluating land cover modifications within the Upper Mississippi River (UMR) floodplain. Given previously documented changes in land use, river engineering, restoration efforts and hydro-climatic changes within the UMR basin and floodplain, we wanted to know which of these changes are the most important determinants of current and projected future floodplain land cover. We used Geographic Information System data covering approximately 37% of the UMR floodplain (3232 km2) for ca 1890 (pre-lock and dam) and three contemporary periods (1975, 1989 and 2000) across which river restoration actions have increased and hydro-climatic changes have occurred. We further developed two 50-year future scenarios from the spatially dependent land cover transitions that occurred from 1975 to 1989 (scenario A) and from 1989 to 2000 (scenario B) using Markov models. Land cover composition of the UMR did not change significantly from 1975 to 2000, indicating that current land cover continues to reflect historical modifications that support agricultural production and commercial navigation despite some floodplain restoration efforts and variation in river discharge. Projected future land cover composition based on scenario A was not significantly different from the land cover for 1975, 1989 or 2000 but was different from the land cover of scenario B, which was also different from all other periods. Scenario B forecasts transition of some forest and marsh habitat to open water by the year 2050 for some portions of the northern river and projects that some agricultural lands will transition to open water in the southern portion of the river. Future floodplain management and restoration planning efforts in the UMR should consider the potential consequences of continued shifts in hydro-climatic conditions that may occur as a result of climate change and the potential effects on floodplain land cover. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

Laboratory observations and computational results for the response of bedform fields to rapid variations in discharge are compared and discussed. The simple case considered here begins with a relatively low discharge over a flat bed on which bedforms are initiated, followed by a short high-flow period with double the original discharge, during which the morphology of the bedforms adjusts, followed in turn by a relatively long period of the original low discharge. For the grain size and hydraulic conditions selected, the Froude number remains subcritical during the experiment, and sediment moves predominantly as bedload. Observations show rapid development of quasi-two-dimensional bedforms during the initial period of low flow with increasing wavelength and height over the initial low-flow period. When the flow increases, the bedforms rapidly increase in wavelength and height, as expected from other empirical results. When the flow decreases back to the original discharge, the height of the bedforms quickly decreases in response, but the wavelength decreases much more slowly. Computational results using an unsteady two-dimensional flow model coupled to a disequilibrium bedload transport model for the same conditions simulate the formation and initial growth of the bedforms fairly accurately and also predict an increase in dimensions during the high-flow period. However, the computational model predicts a much slower rate of wavelength increase, and also performs less accurately during the final low-flow period, where the wavelength remains essentially constant, rather than decreasing. In addition, the numerical results show less variability in bedform wavelength and height than the measured values; the bedform shape is also somewhat different. Based on observations, these discrepancies may result from the simplified model for sediment particle step lengths used in the computational approach. Experiments show that the particle step length varies spatially and temporally over the bedforms during the evolution process. Assuming a constant value for the step length neglects the role of flow alterations in the bedload sediment-transport process, which appears to result in predicted bedform wavelength changes smaller than those observed. However, observations also suggest that three-dimensional effects play at least some role in the decrease of bedform wavelength, so incorporating better models for particle hop lengths alone may not be sufficient to improve model predictions. Published in 2011. This article is a US Government work and is in the public domain in the USA.

Lake Erie is a large lake straddling the border of the USA and Canada that has become increasingly eutrophic in recent years. Eutrophication is particularly focused in the shallow western basin. The western basin of Lake Erie is hydrodynamically similar to a large estuary, with riverine inputs from the Detroit and Maumee Rivers mixing together and creating gradients in chemical and physical conditions. This study was driven by two questions: (1) How does secondary production and food quality for consumers vary across this large mixing zone? and (2) Are there correlations between cyanobacterial abundance and secondary production or food quality for consumers? Measuring spatial and temporal variation in secondary production and food quality is difficult for a variety of logistical reasons, so here a common consumer approach was used. In a common consumer approach, individuals of a single species are raised under similar conditions until placed in the field across environmental gradients of interest. After some period of exposure, the response of that common consumer is measured to provide an index of spatial variation in conditions. Here, a freshwater mussel (Lampsilis siliquoidea) was deployed at 32 locations that spanned habitat types and a gradient in cyanobacterial abundance in the western basin of Lake Erie to measure spatial variation in growth (an index of secondary production) and fatty acid (FA) content (an index of food quality). We found secondary production was highest within the Maumee river mouth and lowest in the open waters of the lake. Mussel tissues in the Maumee river mouth also included more eicosapentaenoic and docosapentaenoic fatty acids (EPA and DPA, respectively), but fewer bacterial FAs, suggesting more algae at the base of the food web in the Maumee river mouth compared to open lake sites. The satellite-derived estimate of cyanobacterial abundance was not correlated to secondary production, but was positively related to EPA and DPA content in the mussels, suggesting more of these important FAs in locations with more cyanobacteria. These results suggest that growth of secondary consumers and the availability of important fatty acids in the western basin are centered on the Maumee river mouth.

A low-temperature synthesis coupled with mild activation produces zeolite films exhibiting low dielectric constant (low-k) matching the theoretically predicted and experimentally measured values for single crystals. This synthesis and activation method allows for the fabrication of a device consisting of a b-oriented film of the pure-silica zeolite MFI (silicalite-1) supported on a gold-coated silicon wafer. The zeolite seeds are assembled by a manual assembly process and subjected to optimized secondary growth conditions that do not cause corrosion of the gold underlayer, while strongly promoting in-plane growth. The traditional calcination process is replaced with a nonthermal photochemical activation to ensure preservation of an intact gold layer. The dielectric constant (k), obtained through measurement of electrical capacitance in a metal–insulator–metal configuration, highlights the ultralow k ≈ 1.7 of the synthetized films, which is among the lowest values reported for an MFI film. There is large improvement in elastic modulus of the film (E ≈ 54 GPa) over previous reports, potentially allowing for integration into silicon wafer processing technology.

Although all bipolar cells in the retina probably use the excitatory transmitter glutamate, approximately half of the cone bipolar cells also contain elevated levels of the inhibitory transmitter glycine. Some types of cone bipolar cells make heterologous gap junctions with rod amacrine cells, which contain elevated levels of glycine, leading to the hypothesis that the bipolar cells obtain their glycine from amacrine cells. Experimental support for this hypothesis is now provided by three independent lines of evidence. First, the glycine transporter GLYT1 is expressed by the glycine-containing amacrine cells but not by the glycine-containing bipolar cells, suggesting that only the amacrine cells are functionally glycinergic. Second, the gap-junction blocker carbenoxolone greatly reduces exogenous3H-glycine accumulation into the bipolar cells but not the amacrine cells. Moreover, when the endogenous glycine stores in both cell classes are depleted by incubating the retina with a glycine-uptake inhibitor, carbenoxolone blocks the subsequent glycine replenishment of the bipolar cells but not the amacrine cells. Third, intracellular injection of rod amacrine cells with the gap-junction permeant tracer Neurobiotin secondarily labels a heterogenous population of cone bipolar cells, all of which show glycine immunoreactivity. Taken together, these findings indicate that the elevated glycine in cone bipolar cells is not derived by high-affinity uptake orde novosynthesis but is obtained by neurotransmitter coupling through gap junctions with glycinergic amacrine cells. Thus transmitter content may be an unreliable indicator of transmitter function for neurons that make heterologous gap junctions.

Using a simplified version of Johnson’s core model analysis of the plastic zone, one may determine the plastic zone size around a contact or, alternatively, determine the yield strength by measuring the plastic zone. The theoretical model contains three parameters: indentation load, yield strength and zone size so that knowing any two gives the third. This is experimentally demonstrated for a series of single crystals (Fe–3wt%Si, tungsten, zinc) and polycrystals (1100-0 Al, copper and 2024-T6 aluminum). In addition, two of these are evaluated in several work-hardened states. Plastic zone sizes are estimated principally by atomic force microscopy and Zygo interferometry imaging with some verification by transmission electron microscopy. On the theoretical side, verification of the relationship is obtained by elastic–plastic numerical analysis of a bi-material system based upon an Fe–3wt%Si single crystal with a thin oxide film. It is shown that in general predictions are reasonable down to nanometer level contacts except for two cases where an indentation size effect may dominate. The proposed relationship is suggested to be an alternative measure of yield strength compared to the often cited value of H /3, particularly at light contacts.

Active-passive potential steps have been applied during continuous microindentation into 300 μ m thick Fe3%Si sheets exposed to 1 M H 2 SO 4 . First, samples were allowed to deflect in the indentation direction whereby the indenter penetration changed due to local metal dissolution and sample deflection resulting from passive film stress induced bending. Samples were then constrained to eliminate stress induced deflection. A distinct difference between the indentation curves for the above two types of tests allowed separation of the effects of film stress and local dissolution. Indenter tip displacement correlated with the current behavior and was consistent with the salt film evolution and resulting electrostrictive film stress. A theoretical model allows estimates of the time dependent film thickness (3.5 μ m at maximum) and electrostrictive film stress (330 MPa at maximum).

We have modified the microscratch test to create a near plane strain loading condition. In the Microwedge Scratch Test (MWST), a wedge-shaped diamond indenter tip is drawn along a fine line (i.e., narrow strip of film), while simultaneously being driven into the line. We compare microwedge scratching of zone 1 (voided grain boundaries) and zone T (metallurgical grain boundaries) thin film specimens of sputtered tungsten on thermally grown SiO2. Symptomatic of its weak grain boundaries, the zone 1 film displays three separate crack systems. Because of its superior grain boundary strength, the zone T film displayed only one of these—an interfacial crack system. By correlating fracture phenomena to signature events in the load-displacement curve, we develop governing equations for propagating interfacial cracks, including expressions for strain energy release rate, bending strain, and mode mixity. Grain boundary fracture causes zone 1 films to spall before a stable crack is formed. Zone T films survive the bending strains, and hence adhesions may be inferred from stable crack growth mechanics. We conclude by contrasting and comparing experimental results for plane strain indentation versus plane strain scratching.

A new method for evaluating modulus and hardness from nanoindentation load/ displacement curves is presented. As a spherical indenter penetrates an elastoplastic half-space, the elastic displacement above the contact line is presumed to diminish in proportion to the total elastic displacement under the indenter. Applying boundary conditions on the elastic and plastic displacements for elastic and rigid plastic contacts leads to an expression that can be best fit to the entire unloading curve to determine E*, the reduced modulus. Justification of the formulation is presented, followed by the results of a preliminary survey conducted on three predominantly isotropic materials: fused quartz, polycrystalline Al, and single crystal W. Diamond tips with radii ranging from 130 nm to 5 μm were used in combination with three different nanoindentation devices. Results indicate that the method gives property values consistent with accepted values for modulus and hardness. The importance of surface roughness and indentation depth are also considered.

Because lithium is difficult to use, divalproex may be an effective alternative for elderly manic patients. In this study, the authors retrospectively assessed outcome of 21 patients, age 60 to 82 years, hospitalized for a manic episode and treated with divalproex. The mean final divalproex dose was 1,405 mg/day, and the mean serum level was 72 micrograms/ml; 20 patients also received concomitant neuroleptic medication. Overall, 19 of the 21 patients (90%) were rated as Much or Very Much Improved. The only remarkable side effect, sedation, occurred in two patients and improved with dose reduction. Although the study suggests that divalproex is an effective and well tolerated treatment for elderly manic patients, the retrospective nature of the study and the concomitant administration of neuroleptic medication suggest caution in interpreting the findings.

Continuous microindentation has been carried out on an iron–3% silicon single crystal in 1 M sulfuric acid. The ability of the material to support elastic loading is directly linked to the presence of thermally grown oxide films and passive films applied through potentiostatic control of the sample. When the passive film is removed, either by chemical or electrochemical means, the iron alloy can no longer sustain pressures on the order of the theoretical shear strength of iron. Instead, the metal behaves in a traditional elastic-plastic manner when no film is present. The oxide film at the edges of the indentation can sustain applied tensile stresses up to 1.2 GPa prior to failure. Indentation in materials undergoing dissolution must account for the rate of material removal over the remote surface and the resulting plastic deformation around the contact of the indentation.

Terrestrial agricultural activities strongly influence riverine nitrogen (N) dynamics, which is reflected in the δ(15)N of riverine consumer tissues. However, processes within aquatic ecosystems also influence consumer tissue δ(15)N. As aquatic processes become more important terrestrial inputs may become a weaker predictor of consumer tissue δ(15)N. In a previous study, this terrestrial-consumer tissue δ(15)N connection was very strong at river sites, but was disrupted by processes occurring in rivermouths (the 'rivermouth effect'). This suggested that watershed indicators of N loading might be accurate in riverine settings, but could be inaccurate when considering N loading to the nearshore of large lakes and oceans. In this study, the rivermouth effect was examined on twenty-five sites spread across the Laurentian Great Lakes. Relationships between agriculture and consumer tissue δ(15)N occurred in both upstream rivers and at the outlets where rivermouths connect to the nearshore zone, but agriculture explained less variation and had a weaker effect at the outlet. These results suggest that rivermouths may sometimes be significant sources or sinks of N, which would cause N loading estimates to the nearshore zone that are typically made at discharge gages further upstream to be inaccurate. Identifying definitively the controls over the rivermouth effect on N loading (and other nutrients) will require integration of biogeochemical and hydrologic models.

Yield points have been detected in both GaAs and Fe3wt%Si single crystals when contacting the surface with sharp diamond tips. The present study concentrates mostly on Fe3wt%Si and demonstrates that a unique point in the load-displacement curve can be associated with the first dislocation nucleated. This occurs at loads in the vicinity of 100 μN for a 66 nm radius tip. Subsequently, this produces an avalanche of dislocations estimated to range from about 15 to 74 in number depending on the magnitude of the yield point load. A model, based upon discretized dislocations is proposed for both the initiation of yielding at an upper yield point (UYP) and the arrest of the indenter at a lower yield point (LYP). The UYP is interpreted in terms of Rice's unstable stacking energy concept, previously applied to crack tips, and accounts for tip radius, oxide film thickness and image force effects. The LYP is interpreted in terms of the back forces provided by previously emitted shielding dislocations. These two approaches provide first order solutions of the upper and lower yield points which both vary from test to test by as much as a factor of four. The large variation in nucleation load is proposed to be due to point to point differences in oxide thickness which might range from 4.5 to 8.5 nm.

Conventionally, the genetics of species of the family Gramineae have been studied separately. Comparative mapping using DNA markers offers a method of combining the research efforts in each species. In this study, we developed consensus maps for members of the Triticeae tribe (Triticum aestivum, T. tauschii, and Hordeum spp.) and compared them to rice, maize and oat. The aneuploid stocks available in wheat are invaluable for comparative mapping because almost every DNA fragment can be allocated to a chromosome arm, thus preventing erroneous conclusions about probes that could not be mapped due to a lack of polymorphism between mapping parents. The orders of the markers detected by probes mapped in rice, maize and oat were conserved for 93, 92 and 94% of the length of Triticeae consensus maps, respectively. The chromosome segments duplicated within the maize genome by ancient polyploidization events were identified by homoeology of segments from two maize chromosomes to regions of one Triticeae chromosome. Homoeologous segments conserved across Triticeae species, rice, maize, and oat can be identified for each Triticeae chromosome. Putative orthologous loci for several simply inherited and quantitatively inherited traits in Gramineae species were identified.

Nanomechanical devices constitute an important and growing field, as they allow for new understanding of the mechanical properties at interfaces and surfaces. As an example, a newly developed nanoindentation device has been used to accomplish μN load indents into GaAs. First, it is shown that a plastic zone can be measured and is comparable to theory. Also, it is shown that the rate of indentation affects both the depth and upset zone of low load indents, implying a strain-rate sensitivity effect at room temperature. This is reinforced by observation of what appears to be a glide-based relaxation process.

The purpose of environmental monitoring is to promote the early identification of, and response to, potential adverse environmental impacts associated with Lawrence Livermore National Laboratory (LLNL) operations. Environmental monitoring supports the Integrated Safety Management System (ISMS), International Organization for Standardization (ISO) 14001 Environmental Management Systems standard, and U. S. Department of Energy (DOE) Order 458.1, Radiation Protection of the Public and the Environment. Specifically, environmental monitoring enables LLNL to detect, characterize, and respond to releases from LLNL activities; assess impacts; estimate dispersal patterns in the environment; characterize the pathways of exposure to members of the public; characterize the exposures and doses to individuals and to the population; and to evaluate the potential impacts to the biota in the vicinity of LLNL. Environmental monitoring is also a major component of compliance demonstration for permits and other regulatory requirements. The Environmental Monitoring Plan (EMP) addresses the sample collection and analytical work supporting environmental monitoring to ensure the following: (1) A consistent system for collecting, assessing, and documenting environmental data of known and documented quality; (2) A validated and consistent approach for sampling and analysis of samples to ensure laboratory data meets program-specific needs and requirements within the framework of a performance-based approach for analytical laboratory work; and (3) An integrated sampling approach to avoid duplicative data collection. LLNL prepares the EMP because it provides an organizational framework for ensuring that environmental monitoring work, which is integral to the implementation of LLNL's Environmental Management System, is conducted appropriately. Furthermore, the Environmental Monitoring Plan helps LLNL ensure compliance with DOE Order 231.1 Change 2, Environment, Safety and Health Reporting, which require the publication of an annual report that characterizes the site's environmental management performance. To summarize, the general regulatory drivers for this environmental monitoring plan are ISO 14001, DOE Order 458.1, and DOE Order 231.1. The environmental monitoring addressed by this plan includes preoperational characterization and assessment, effluent and surveillance monitoring, and permit and regulatory compliance monitoring. Additional environmental monitoring is conducted at LLNL as part of compliance with the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA, also known as Superfund). LLNL coordinates its ground water surveillance monitoring program with the CERCLA monitoring program to gain sampling efficiencies.

Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although the functional relationship of the decline of the GH-IGF-I system and catabolism is recognized, the biological role of DHEA in human aging remains undefined. To test the hypothesis that the decline in DHEA may contribute to the shift from anabolism to catabolism associated with aging, we studied the effect of a replacement dose of DHEA in 13 men and 17 women, 40-70 yr of age. A randomized placebo-controlled cross-over trial of nightly oral DHEA administration (50 mg) of 6-month duration was conducted. During each treatment period, concentrations of androgens, lipids, apolipoproteins, IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, insulin sensitivity, percent body fat, libido, and sense of well-being were measured. A subgroup of men (n = 8) and women (n = 5) underwent 24-h sampling at 20-min intervals for GH determinations. DHEA and DS serum levels were restored to those found in young adults within 2 weeks of DHEA replacement and were sustained throughout the 3 months of the study. A 2-fold increase in serum levels of androgens (androstenedione, testosterone, and dihydrotestosterone) was observed in women, with only a small rise in androstenedione in men. There was no change in circulating levels of sex hormone-binding globulin, estrone, or estradiol in either gender. High density lipoprotein levels declined slightly in women, with no other lipid changes noted for either gender. Insulin sensitivity and percent body fat were unaltered. Although mean 24-h GH and IGFBP-3 levels were unchanged, serum IGF-I levels increased significantly, and IGFBP-1 decreased significantly for both genders, suggesting an increased bioavailability of IGF-I to target tissues. This was associated with a remarkable increase in perceived physical and psychological well-being for both men (67%) and women (84%) and no change in libido. In conclusion, restoring DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These observations together with improvement of physical and psychological well-being in both genders and the absence of side-effects constitute the first demonstration of novel effects of DHEA replacement in age-advanced men and women.

The synaptic input of six spiny stellate neurons in sublamina 4A of cat area 17 was assessed by electron microscopy. The neurons were physiologically characterized and filled with horseradish peroxidase in vivo. After processing the neurons were reconstructed at the light microscopic level using computer-assisted methods and analyzed quantitatively. The extensive branching of the dendritic tree about 50 microns from the soma meant that the distal branches constituted five times the length of proximal dendrite. Proximal and distal portions of a single dendrite from each neuron were examined in series of ultrathin sections (1,456 sections) in the electron microscope. The majority (79%) of the 263 synapses examined were asymmetric; the remainder (21%) were symmetric. Symmetric synapses formed 35% of synapses sampled on proximal dendrites and were usually located on the shaft. They formed only 4% of synapses sampled on distal dendrites. Spines accounted for less than half of the total asymmetric synapses (45%); the remainder were on shafts. Symmetric synapses formed with four of 92 spines. Nine spines formed no synapses. Spiny stellate neurons in cat visual cortex appear to differ considerably from pyramidal neurons in having a significant asymmetric (excitatory) synaptic input to the dendritic shaft.

Our hypothesis was that spiny stellate neurons in layer 4 of cat visual cortex receive polyneuronal innervation. We characterised the synapses of four likely sources of innervation by three simple criteria: the type of synapse, the target (spine, dendritic shaft), and the area of the presynaptic bouton. The layer 6 pyramids had the smallest boutons and formed asymmetric synapses mainly with the dendritic shaft. The thalamic afferents had the largest boutons and formed asymmetric synapses mainly with spines. The spiny stellates had medium-sized boutons and formed asymmetric synapses mainly with spines. We used these to make a "template" to match against the boutons forming synapses with the spiny stellate dendrite. Of the asymmetric synapses, 45% could have come from layer 6 pyramidal neurons, 28% from spiny stellate neurons, and 6% from thalamic afferents. The remaining 21% of asymmetric synapses could not be accounted for without assuming some additional selectivity of the presynaptic axons. Additional asymmetric synapses may come from a variety of sources, including other cortical neurons and subcortical nuclei such as the claustrum. Of the symmetric synapses, 84% could have been provided by clutch cells, which form large boutons. The remainder, formed by small boutons, probably come from other smooth neurons in layer 4, e.g., neurogliaform and bitufted neurons. Our analysis supports the hypothesis that the spiny stellate receives polyneuronal innervation, perhaps from all the sources of boutons in layer 4. Although layer 4 is the major recipient of thalamic afferents, our results show that they form only a few percent of the synapses of layer 4 spiny stellate neurons.

The in situ mechanical properties of the fibers, matrices and interfaces in an Al2O3 fiber-reinforced β-21S Ti alloy have been evaluated by using two nanoscale indentation tests. The Al2O3 fibers were coated with a refractory metal and Y2O3 duplex coating which served as a diffusion barrier during the HIPing used to produce the metal matrix composites. The hardness of the fibers, interfaces and matrix were obtained by performing a series of indentations across the fiber/matrix interface. The hardness decreases from the Al2O3 fiber to the Ti matrix. Additionally, by doing fiber pushout tests, the interfacial shear strength, interfacial frictional stress and mode II interfacial fracture energy were obtained. Scanning electron microscopy and X-ray mapping were used for microstructural and chemical analysis. The mechanical properties of the interfaces were related to their chemical composition. The interfacial fracture was found to occur at the interface between the refractory metal and the Y2O3. The mode II interfacial fracture energy in this system is more than two orders of magnitude lower than the interfacial fracture energy of Ti/Al2O3 without the diffusion barrier.

Spiny stellate neurons of area 17 of the cat's visual cortex were physiologically characterised and injected intracellularly with horseradish peroxidase. Six neurons from sublamina 4A were selected. Five had the S-type of simple receptive fields; one had a complex receptive field. Their axons formed boutons mainly in layers 3 and 4. An electron microscopic examination of 45 boutons showed that each bouton formed one asymmetric synapse on average. Spines were the most frequent synaptic target (74%); dendritic shafts formed the remainder (26%). On the basis of ultrastructural characteristics, 8% of the target dendrites were characterised as originating from smooth gamma-aminobutyrate-ergic (GABAergic) neurons. Thus the major output of spiny stellate neurons is to other spiny neurons, probably pyramidal neurons in layer 3 and spiny stellates in layer 4.

The mechanical properties of the interfaces in an Al2O3 fiber reinforced β-21S Ti alloy have been evaluated by using fiber pushout tests. The Al2O3 fibers were coated with a refractory metal and Y2O3 which served as a diffusion barrier during the HIPing used to produce the metal matrix composites. By doing fiber pushout tests, the interfacial fracture was found to occur at the interface between the refractory metal and the Y2O3. The interfacial shear strength and interfacial frictional stress were measured to be 323 and 312 ± 2 MPa, respectively. The interfacial frictional stress, which is due to asperity interlocking during the fiber sliding, was correlated to the surface roughness of the coated Al2O3 fiber obtained with the aid of an atomic force microscope. The measured surface roughness of 18.8 ± 2.2 nm was related to the frictional stress through Hutchinson's model.9 The frictional coefficient between the Al2O3 fiber and the Ti matrix is calculated to be 0.32 ± 0.02.

Metal-reinforced diamond composite films produced by a three-step process are studied by examining the nature and interaction of the three types of interfaces present in the composite: diamond-substrate, binder-substrate and diamond-binder. Diamond composites were deposited on tungsten substrates with nickel or CuTiAg alloy binders. It is found that a diffusion bond formed between the binder and the substrate. In addition, carbide-forming elements are found to segregate to the diamond-binder interface. The binding state of the diffused elements was studied by examining the fine structure of the Auger spectra. Carbon at the interface between the binder and the diamond is found to have carbide-type bonding which should improve the adherence of the binder to the diamond.

The purposes of the Lawrence Livermore National Laboratory Environmental Report 2010 are to record Lawrence Livermore National Laboratory's (LLNL's) compliance with environmental standards and requirements, describe LLNL's environmental protection and remediation programs, and present the results of environmental monitoring at the two LLNL sites - the Livermore site and Site 300. The report is prepared for the U.S. Department of Energy (DOE) by LLNL's Environmental Protection Department. Submittal of the report satisfies requirements under DOE Order 231.1A, Environmental Safety and Health Reporting, and DOE Order 5400.5, Radiation Protection of the Public and Environment. The report is distributed electronically and is available at https://saer.llnl.gov/, the website for the LLNL annual environmental report. Previous LLNL annual environmental reports beginning in 1994 are also on the website. Some references in the electronic report text are underlined, which indicates that they are clickable links. Clicking on one of these links will open the related document, data workbook, or website that it refers to. The report begins with an executive summary, which provides the purpose of the report and an overview of LLNL's compliance and monitoring results. The first three chapters provide background information: Chapter 1 is an overview of the location, meteorology, and hydrogeologymore » of the two LLNL sites; Chapter 2 is a summary of LLNL's compliance with environmental regulations; and Chapter 3 is a description of LLNL's environmental programs with an emphasis on the Environmental Management System including pollution prevention. The majority of the report covers LLNL's environmental monitoring programs and monitoring data for 2010: effluent and ambient air (Chapter 4); waters, including wastewater, storm water runoff, surface water, rain, and groundwater (Chapter 5); and terrestrial, including soil, sediment, vegetation, foodstuff, ambient radiation, and special status wildlife and plants (Chapter 6). Complete monitoring data, which are summarized in the body of the report, are provided in Appendix A. The remaining three chapters discuss the radiological impact on the public from LLNL operations (Chapter 7), LLNL's groundwater remediation program (Chapter 8), and quality assurance for the environmental monitoring programs (Chapter 9). The report uses System International units, consistent with the federal Metric Conversion Act of 1975 and Executive Order 12770, Metric Usage in Federal Government Programs (1991). For ease of comparison to environmental reports issued prior to 1991, dose values and many radiological measurements are given in both metric and U.S. customary units. A conversion table is provided in the glossary.« less

A sphere in air will roll down a plane that is tilted away from the vertical. The only couple acting about the point of contact between the sphere and the plane is due to the component of the weight of the sphere along the plane, provided that air friction is negligible. If on the other hand the sphere is immersed in a liquid, hydrodynamic forces will enter into the couples that turn the sphere, and the rotation of the sphere can be anomalous, i.e., as if rolling up the plane while it falls. In this paper we shall show that anomalous rolling is a characteristic phenomenon that can be observed in every viscoelastic liquid tested so far. Anomalous rolling is normal for hydrodynamically levitated spheres, both in Newtonian and viscoelastic liquids. Normal and anomalous rolling are different names for dry and hydrodynamic rolling. Spheres dropped at a vertical wall in Newtonian liquids are forced into anomalous rotation and are pushed away from the wall while in viscoelastic liquids, they are forced into anomalous rotation, but are pushed toward the wall. If the wall is inclined and the fluid is Newtonian, the spheres will rotate normally for dry rolling, but the same spheres rotate anomalously in viscoelastic liquids when the angle of inclination from the vertical is less than some critical value. The hydrodynamic mechanisms underway in the settling of circular particles in a Newtonian fluid at a vertical wall are revealed by an exact numerical simulation based on a finite-element solution of the Navier-Stokes equations and Newton's equations of motion for a rigid body.

Water-soluble 3H-labeled arsenic compounds were phenol-extracted from mussels (Mytilus edulis) and seawater after exposure to [3H]monomethylarsonate (MMAA) and [3H]dimethylarsinate (DMAA). Varying amounts of [3H] arsenobetaine were found in mussels and seawater, depending upon the experimental conditions. The results indicate that arsenobetaine is principally biosynthesized by microscopic organisms in the seawater and that it is bioaccumulated by mussels. Total arsenic concentrations in mussel flesh, byssal threads and shells were also determined, showing concentration increases in all three compartments.

The adhesion properties of diamond coatings on cemented-carbide tools have been improved by two approaches: a novel substrate pre-treatment method and a three-step process for making metal-reinforced diamond composites. 1. (1) Diamond powders are rubbed into the voids created by cobalt removal from the cemented carbides. During subsequent diamond deposition these diamond powders consolidate to form the “anchoring roots” of the deposited diamond films, resulting in strong mechanical bonding between the films and substrates. 2. (2) The adhesion can also be improved by adding reinforcing phases using a three-step process. The above two methods have effectively overcome the film delamination problems due to the considerable thermal stress associated with curvature effects.

The adhesion strengths of metal/ceramic, metal/polymer, and polymer/polymer interfaces have been characterized using the continuous microscratch technique. In these experiments, a conical diamond indenter was driven simultaneously into a thin film at a rate of 15 nm/s and across the film surface at a rate of 0.5 μm/s until a load drop or other discontinuity occurred, indicating film failure. The critical load at failure of the thin film was taken as a measure of the adhesion strength. For metal/ ceramic systems such as Cr thin films on Al2O3, and for diamond-like-carbon (DLC) films on glass, clear load drops provided an accurate measure of the adhesion strengths. For metal/polymer systems such as Cu thin films on PET, a change in the loading pattern and periodic cracking events along the scratch track provided evidence of film delamination. For DLC films on polycarbonate substrates, the carbon thin film cracked before it delaminated. For bulk polymers such as polycarbonate and polystyrene/polypropylene, c...

The purpose of environmental monitoring is to promote the early identification of, and response to, potential adverse environmental impacts associated with Lawrence Livermore National Laboratory (LLNL) operations. Environmental monitoring supports the Integrated Safety Management System (ISMS), International Organization for Standardization (ISO) 14001 Environmental Management Systems standard, and U. S. Department of Energy (DOE) Order 450.1A, Environmental Protection Program. Specifically, in conformance with DOE Order 450.1A, Attachment 1, paragraph 1(b)(5), environmental monitoring enables LLNL to detect, characterize, and respond to releases from LLNL activities; assess impacts; estimate dispersal patterns in the environment; characterize the pathways of exposure to members of the public; characterize the exposures and doses to individuals and to the population; and to evaluate the potential impacts to the biota in the vicinity of LLNL. Environmental monitoring also serves to demonstrate compliance with permits and other regulatory requirements. The Environmental Monitoring Plan (EMP) addresses the sample collection and analytical work supporting environmental monitoring to ensure the following: (1) A consistent system for collecting, assessing, and documenting environmental data of known and documented quality. (2) A validated and consistent approach for sampling and analysis of samples to ensure laboratory data meets program-specific needs and requirements within the framework of amore » performance-based approach for analytical laboratory work. (3) An integrated sampling approach to avoid duplicative data collection. Until its cancellation in January 2003, DOE Order 5400.1 required the preparation of an environmental monitoring plan. Neither DOE Order 450.1A nor the ISO 14001 standard are as prescriptive as DOE Order 5400.1, in that neither expressly requires an EMP. However, LLNL continues to prepare the EMP because it provides an organizational framework for ensuring that this work, which is integral to the implementation of LLNL's Environmental Management System, is conducted appropriately. Furthermore, the Environmental Monitoring Plan helps LLNL ensure compliance with DOE Order 5400.5, Radiation Protection of the Public and the Environment, and DOE Order 231.1 Change 2, Environment, Safety and Health Reporting, which require the publication of an annual report that characterizes the site's environmental management performance. To summarize, the general regulatory drivers for this environmental monitoring plan are ISO 14001, DOE Order 450.1A, DOE Order 5400.5, and DOE Order 231.1. The environmental monitoring addressed by this plan includes preoperational characterization and assessment, effluent and surveillance monitoring, and permit and regulatory compliance monitoring. Additional environmental monitoring is conducted at LLNL as part of compliance with the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA, also known as Superfund). LLNL coordinates its ground water surveillance monitoring program with the CERCLA monitoring program to gain sampling efficiencies. (See LLNL [1992] and LLNL [2008] for information about LLNL's CERCLA activities).« less

The impact of chronic high volume athletic training on thyroid hormone economy has not been defined. We investigated the status of the hypothalamic-pituitary-thyroid axis (H-P-T) in women athletes with regular menstrual cycles (CA) and with amenorrhea (AA). Their data were compared with each other and with those derived from cyclic sedentary women (CS) matched for a variety of confounding factors including the intensity of exercise, caloric intake, and body weight. Alterations of the H-P-T axis were observed in women athletes compared to CS. While serum levels of T4, T3, free T4, free T3 and rT3 were substantially reduced (P less than 0.01) in AA, only serum T4 levels were significantly decreased in CA. Further, remarkable differences were found between CA and AA in that serum levels of free T4 (P less than 0.01), free T3 (P less than 0.01), and rT3 (P less than 0.05) were significantly lower in AA than in CA. Thyroid binding globulin and sex-hormone binding globulin concentrations were within their normal ranges for all groups of subjects. Both 24-h mean TSH levels and the circadian rhythm of TSH secretion were also comparable. However, the TSH response to TRH stimulation was blunted (P less than 0.01) in AA when compared to CA, but not to CS. Whereas the underlying mechanism(s) to account for the "global" reduction of circulating thyroid hormone in the face of normal TSH levels in AA is presently unknown, these observations provide information of clinical significance: 1) chronic high volume athletic training in women athletes with menstrual cyclicity is accompanied by an isolated T4 reduction; 2) an impaired H-P-T axis occurs selectively in athletic women in whom chronic high volume athletic training is associated with compromised hypothalamic-pituitary-ovarian function and amenorrhea.

The purposes of the Lawrence Livermore National Laboratory Environmental Report 2008 are to record Lawrence Livermore National Laboratory's (LLNL's) compliance with environmental standards and requirements, describe LLNL's environmental protection and remediation programs, and present the results of environmental monitoring at the two LLNL sites - the Livermore site and Site 300. The report is prepared for the U.S. Department of Energy (DOE) by LLNL's Environmental Protection Department. Submittal of the report satisfies requirements under DOE Order 231.1A, Environmental Safety and Health Reporting, and DOE Order 5400.5, Radiation Protection of the Public and Environment. The report is distributed electronically and is available at https://saer.lln.gov/, the website for the LLNL annual environmental report. Previous LLNL annual environmental reports beginning in 1994 are also on the website. Some references in the electronic report text are underlined, which indicates that they are clickable links. Clicking on one of these links will open the related document, data workbook, or website that it refers to. The report begins with an executive summary, which provides the purpose of the report and an overview of LLNL's compliance and monitoring results. The first three chapters provide background information: Chapter 1 is an overview of the location, meteorology, and hydrogeology more » of the two LLNL sites; Chapter 2 is a summary of LLNL's compliance with environmental regulations; and Chapter 3 is a description of LLNL's environmental programs with an emphasis on the Environmental Management System including pollution prevention. The majority of the report covers LLNL's environmental monitoring programs and monitoring data for 2008: effluent and ambient air (Chapter 4); waters, including wastewater, storm water runoff, surface water, rain, and groundwater (Chapter 5); and terrestrial, including soil, sediment, vegetation, foodstuff, ambient radiation, and special status wildlife and plants (Chapter 6). Complete monitoring data, which are summarized in the body of the report, are provided in Appendix A. The remaining three chapters discuss the radiological impact on the public from LLNL operations (Chapter 7), LLNL's groundwater remediation program (Chapter 8), and quality assurance for the environmental monitoring programs (Chapter 9). The report uses Systeme International units, consistent with the federal Metric Conversion Act of 1975 and Executive Order 12770, Metric Usage in Federal Government Programs (1991). For ease of comparison to environmental reports issued prior to 1991, dose values and many radiological measurements are given in both metric and U.S. customary units. A conversion table is provided in the glossary. The report is the responsibility of LLNL's Environmental Protection Department. Monitoring data were obtained through the combined efforts of the Environmental Protection Department; Environmental Restoration Department; Physical and Life Sciences Environmental Monitoring Radiation Laboratory; and the Hazards Control Department. « less

Plasma concentrations of desipramine (DMI) and its 2-hydroxy metabolite (OHDMI) were compared among 72 patients being treated with desipramine for either depression (n = 39) or cocaine abuse (n = 33). Eleven cocaine abusers who were concurrently maintained on methadone had a significantly lower ratio of DMI dose to plasma concentration (0.9) than the depressives (2.2) or nonmethadone cocaine abusers (2.0). Their OHDMI/DMI ratios were significantly lower (0.19) than for either the other 22 cocaine abusers (0.39) or the depressed (0.50) patients. This difference was not due to DMI dosage. Although the underlying mechanism cannot be determined from these plasma studies, possible reduced hydroxylation of DMI in methadone patients suggests the need for DMI plasma monitoring.

The principal target of lateral geniculate nucleus in the cat visual cortex is the stellate neurons of layer 4. In previously reported work with intracellular recording and extracellular stimulation in slices of visual cortex, three general classes of fast excitatory synaptic potentials (EPSPs) in layer 4a spiny stellate neurons were identified. One of these classes, characterized by large and relatively invariant amplitudes (mean 1.7 mV, average coefficient of variation (CV) 0.083) were attributed to the action of geniculate axons because, unlike the other two classes, they could not be matched by intracortical inputs, using paired recording. We have examined in detail the properties of this synaptic input in twelve examples, selecting for study those EPSPs where there was secure extracellular stimulation of the single fibre input to a pair of stimuli 50 ms apart. In our analysis, we conclude that the depression that these inputs show to the second stimulus is entirely postsynaptic, since the evidence strongly suggests that the probability of transmitter release at the synaptic site(s) remains 1.0 for both stimuli. We argue that the most plausible explanation for this postsynaptic depression is a reduction in the average probability of opening the synaptic channels. Using a simple biochemical analysis (c.f. Sigworth plot), it is then possible to calculate the number of synaptic channels and their probability of opening, for each of the 12 connections. The EPSPs had a mean amplitude of 1.91 mV (±1.3 mV SD) and a mean CV of 0.067 (± 0.022). The calculated number of channels ranged from 20 to 158 (59.4 ± 48.7) and their probability of opening to the first EPSP had an average of 0.83 (± 0.09), with an average depression of the probability to 0.60 for the second EPSP. Geniculate afferents also terminate in layer 6. Intracellular recordings were also made in the upper part of this layer and a total of 51 EPSPs were recorded from pyramidal cells of three principal types. Amongst this dataset we sought EPSPs with similar properties to those characterized in layer 4a. Three examples were found, which is a much lower percentage (6%) than the incidence of putative geniculate EPSPs found in layer 4a (42%).

As the population of people over 65 years of age increases, clinicians will see more cases of late-life depression. Currently, the rates of depression in the elderly are higher for nursing home patients and other medical inpatients and outpatients than for the noninstitutionalized, non-medically ill elderly. Depression in the elderly may be difficult to diagnose because of factors such as late onset, comorbid medical illness, dementia, and bereavement, but depression is not a natural part of aging. People who are depressed have increased suffering, impaired functioning, and increased mortality. Fortunately, antidepressants have been shown to effectively treat late-life depression. While monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) are efficacious for treating depression in the elderly, their side effect profiles may be difficult and even dangerous for some older patients. However, serotonin selective reuptake inhibitors (SSRIs) and other second generation antidepressants appear to be both effective and better tolerated in the elderly. Since elderly patients may be more sensitive to drugs, clinicians may need to closely monitor these patients for dosing, side effects, and drug-drug interactions.

T-axis shift has been reported to be an indicator of increased mortality risk. We evaluated the association of spatial T-axis deviation with incident coronary heart disease (CHD) events in older men and women free from clinically overt CHD. Spatial T-axis deviation was measured from the standard 12-lead electrocardiogram of a subgroup of 4,173 subjects considered free of CHD at baseline in the Cardiovascular Health Study, a prospective cohort study of risk factors for CHD and stroke in older men and women. Cox regression analysis was used to evaluate the association of altered repolarization with the risk of incident CHD events. The prevalence of marked T-axis deviation (or =45 degrees ) was 12%. During the median follow-up of 7.4 years, there were 161 CHD deaths, 743 deaths from all causes, and 679 incident CHD events. Adjusting for demographic and clinical risk factors, including other electrocardiographic abnormalities, there was a nearly twofold excess risk of CHD death, and approximately a 50% excess risk of incident CHD and all-cause mortality for those with marked T-axis deviation. From other electrocardiographic abnormalities, only QT prolongation was associated with excess risk for incident CHD comparable to that for abnormal T-axis deviation. These results suggest that T-axis deviation is an easily quantified marker for subclinical disease and an independent indicator for the risk of incident CHD events in older men and women free of CHD.