Genetic architecture of disease resistance and tolerance in Douglas-fir trees.

Understanding the genetic basis of how plants defend against pathogens is important to monitor and maintain resilient tree populations. Swiss needle cast (SNC) and Rhabdocline needle cast (RNC) epidemics are responsible for major damage of forest ecosystems in North America. Here we investigate the genetic architecture of tolerance and resistance to needle cast diseases in Douglas-fir (Pseudotsuga menziesii) caused by two fungal pathogens: SNC caused by Nothophaeocryptopus gaeumannii, and RNC caused by Rhabdocline pseudotsugae. We performed case-control genome-wide association analyses and found disease resistance and tolerance in Douglas-fir to be polygenic and under strong selection. We show that stomatal regulation as well as ethylene and jasmonic acid pathways are important for resisting SNC infection, and secondary metabolite pathways play a role in tolerating SNC once the plant is infected. We identify a major transcriptional regulator of plant defense, ERF1, as the top candidate for RNC resistance. Our findings shed light on the highly polygenic architectures underlying fungal disease resistance and tolerance and have important implications for forestry and conservation as the climate changes.

Nontuberculous Mycobacterial Musculoskeletal Infection Cases from a Tertiary Referral Center, Colorado, USA.

Nontuberculous mycobacteria represent an uncommon but important cause of infection of the musculoskeletal system. Such infections require aggressive medical and surgical treatment, and cases are often complicated by delayed diagnosis. We retrospectively reviewed all 14 nonspinal cases of nontuberculous mycobacterial musculoskeletal infections treated over 6 years by orthopedic surgeons at a university-affiliated tertiary referral center. All patients required multiple antimicrobial agents along with aggressive surgical treatment; 13 of 14 patients ultimately achieved cure. Four patients required amputation to control the infection. Half these patients were immunosuppressed by medications or other medical illness when they sought care at the referral center. Six cases involved joint prostheses; all ultimately required hardware removal and placement of an antimicrobial spacer for eradication of infection. Our findings highlight the importance of vigilance for nontuberculous mycobacterial musculoskeletal infection, particularly in patients who are immunosuppressed or have a history of musculoskeletal surgery.

Quantitative lymph node burden as a 'very-high-risk' factor identifying head and neck cancer patients benefiting from postoperative chemoradiation.

Background: Adjuvant chemoradiation (CRT) is standard for head and neck squamous cell carcinoma (HNSCC) patients with positive margins or extranodal extension (ENE) following surgery. However, emerging evidence suggests the number of positive lymph nodes (LNs) is the dominant determinant of survival in non-oropharyngeal HNSCC and thus may better identify those benefiting from treatment intensification. Patients and methods: Patients from the National Cancer Database diagnosed with non-oropharyngeal HNSCC (oral cavity, larynx, hypopharynx) between 2004 and 2014 and undergoing surgical resection, neck dissection, and postoperative radiotherapy (RT) were included. Multivariable regression with first-order interaction terms was used to model the interaction between postoperative CRT and continuous number of positive LNs with respect to overall survival. Results: In total, 7144 patients met inclusion criteria. In multivariable analysis, increasing number of positive LNs was associated with both increasing mortality (P < 0.001) and increasing benefit from postoperative CRT versus RT alone (interaction P < 0.001). While there was no benefit from postoperative CRT in patients with 0-2 LN+ [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.86-1.07, P = 0.47], increased benefit was seen in those with 3-5 LN+ (HR 0.84, 95% CI 0.70-1.00, P = 0.05) and those with ≥6 LN+ (HR 0.65, 95% CI 0.51-0.82, P < 0.001) in multivariable models. By contrast, margin status and ENE did not reliably identify patients benefitting from postoperative CRT based on statistical tests of interaction. Even in patients with ENE, positive margins, or both, only those with ≥6 LN+ had improved survival with postoperative CRT. Conclusion: Increasing metastatic nodal burden was associated with increased benefit from CRT compared with RT alone, surpassing conventional high-risk factors in identifying patients benefiting from CRT. Stratification by metastatic LN number may characterize a very-high-risk patient cohort best suited for treatment intensification.

Transcription through the eye of a needle: daily and annual cyclic gene expression variation in Douglas-fir needles.

BACKGROUND: Perennial growth in plants is the product of interdependent cycles of daily and annual stimuli that induce cycles of growth and dormancy. In conifers, needles are the key perennial organ that integrates daily and seasonal signals from light, temperature, and water availability. To understand the relationship between seasonal cycles and seasonal gene expression responses in conifers, we examined diurnal and circannual needle mRNA accumulation in Douglas-fir (Pseudotsuga menziesii) needles at diurnal and circannual scales. Using mRNA sequencing, we sampled 6.1 × 109 reads from 19 trees and constructed a de novo pan-transcriptome reference that includes 173,882 tree-derived transcripts. Using this reference, we mapped RNA-Seq reads from 179 samples that capture daily and annual variation. RESULTS: We identified 12,042 diurnally-cyclic transcripts, 9299 of which showed homology to annotated genes from other plant genomes, including angiosperm core clock genes. Annual analysis revealed 21,225 circannual transcripts, 17,335 of which showed homology to annotated genes from other plant genomes. The timing of maximum gene expression is associated with light intensity at diurnal scales and photoperiod at annual scales, with approximately half of transcripts reaching maximum expression +/- 2 h from sunrise and sunset, and +/- 20 days from winter and summer solstices. Comparisons with published studies from other conifers shows congruent behavior in clock genes with Japanese cedar (Cryptomeria), and a significant preservation of gene expression patterns for 2278 putative orthologs from Douglas-fir during the summer growing season, and 760 putative orthologs from spruce (Picea) during the transition from fall to winter. CONCLUSIONS: Our study highlight the extensive diurnal and circannual transcriptome variability demonstrated in conifer needles. At these temporal scales, 29% of expressed transcripts show a significant diurnal cycle, and 58.7% show a significant circannual cycle. Remarkably, thousands of genes reach their annual peak activity during winter dormancy. Our study establishes the fine-scale timing of daily and annual maximum gene expression for diverse needle genes in Douglas-fir, and it highlights the potential for using this information for evaluating hypotheses concerning the daily or seasonal timing of gene activity in temperate-zone conifers, and for identifying cyclic transcriptome components in other conifer species.

Photoperiod cues and patterns of genetic variation limit phenological responses to climate change in warm parts of species' range: Modeling diameter-growth cessation in coast Douglas-fir.

The phenology of diameter-growth cessation in trees will likely play a key role in mediating species and ecosystem responses to climate change. A common expectation is that warming will delay cessation, but the environmental and genetic influences on this process are poorly understood. We modeled the effects of temperature, photoperiod, and seed-source climate on diameter-growth-cessation timing in coast Douglas-fir (an ecologically and economically vital tree) using high-frequency growth measurements across broad environmental gradients for a range of genotypes from different seed sources. Our model suggests that cool temperatures or short photoperiods can induce cessation in autumn. At cool locations (high latitude and elevation), cessation seems to be induced primarily by low temperatures in early autumn (under relatively long photoperiods), so warming will likely delay cessation and extend the growing season. But at warm locations (low latitude or elevation), cessation seems to be induced primarily by short photoperiods later in autumn, so warming will likely lead to only slight extensions of the growing season, reflecting photoperiod limitations on phenological shifts. Trees from seed sources experiencing frequent frosts in autumn or early winter tended to cease growth earlier in the autumn, potentially as an adaptation to avoid frost. Thus, gene flow into populations in warm locations with little frost will likely have limited potential to delay mean cessation dates because these populations already cease growth relatively late. In addition, data from an abnormal heat wave suggested that very high temperatures during long photoperiods in early summer might also induce cessation. Climate change could make these conditions more common in warm locations, leading to much earlier cessation. Thus, photoperiod cues, patterns of genetic variation, and summer heat waves could limit the capacity of coast Douglas-fir to extend its growing season in response to climate change in the warm parts of its range.

Will changes in phenology track climate change? A study of growth initiation timing in coast Douglas-fir.

Under climate change, the reduction of frost risk, onset of warm temperatures and depletion of soil moisture are all likely to occur earlier in the year in many temperate regions. The resilience of tree species will depend on their ability to track these changes in climate with shifts in phenology that lead to earlier growth initiation in the spring. Exposure to warm temperatures ('forcing') typically triggers growth initiation, but many trees also require exposure to cool temperatures ('chilling') while dormant to readily initiate growth in the spring. If warming increases forcing and decreases chilling, climate change could maintain, advance or delay growth initiation phenology relative to the onset of favorable conditions. We modeled the timing of height- and diameter-growth initiation in coast Douglas-fir (an ecologically and economically vital tree in western North America) to determine whether changes in phenology are likely to track changes in climate using data from field-based and controlled-environment studies, which included conditions warmer than those currently experienced in the tree's range. For high latitude and elevation portions of the tree's range, our models predicted that warming will lead to earlier growth initiation and allow trees to track changes in the onset of the warm but still moist conditions that favor growth, generally without substantially greater exposure to frost. In contrast, toward lower latitude and elevation range limits, the models predicted that warming will lead to delayed growth initiation relative to changes in climate due to reduced chilling, with trees failing to capture favorable conditions in the earlier parts of the spring. This maladaptive response to climate change was more prevalent for diameter-growth initiation than height-growth initiation. The decoupling of growth initiation with the onset of favorable climatic conditions could reduce the resilience of coast Douglas-fir to climate change at the warm edges of its distribution.

Climate-related genetic variation in drought-resistance of Douglas-fir (Pseudotsuga menziesii).

There is a general assumption that intraspecific populations originating from relatively arid climates will be better adapted to cope with the expected increase in drought from climate change. For ecologically and economically important species, more comprehensive, genecological studies that utilize large distributions of populations and direct measures of traits associated with drought-resistance are needed to empirically support this assumption because of the implications for the natural or assisted regeneration of species. We conducted a space-for-time substitution, common garden experiment with 35 populations of coast Douglas-fir (Pseudotsuga menziesii var. menziesii) growing at three test sites with distinct summer temperature and precipitation (referred to as 'cool/moist', 'moderate', or 'warm/dry') to test the hypotheses that (i) there is large genetic variation among populations and regions in traits associated with drought-resistance, (ii) the patterns of genetic variation are related to the native source-climate of each population, in particular with summer temperature and precipitation, (iii) the differences among populations and relationships with climate are stronger at the warm/dry test site owing to greater expression of drought-resistance traits (i.e., a genotype × environment interaction). During midsummer 2012, we measured the rate of water loss after stomatal closure (transpiration(min)), water deficit (% below turgid saturation), and specific leaf area (SLA, cm(2) g(-1)) on new growth of sapling branches. There was significant genetic variation in all plant traits, with populations originating from warmer and drier climates having greater drought-resistance (i.e., lower transpiration(min), water deficit and SLA), but these trends were most clearly expressed only at the warm/dry test site. Contrary to expectations, populations from cooler climates also had greater drought-resistance across all test sites. Multiple regression analysis indicated that Douglas-fir populations from regions with relatively cool winters and arid summers may be most adapted to cope with drought conditions that are expected in the future.

Impact of climate change on cold hardiness of Douglas-fir (Pseudotsuga menziesii): environmental and genetic considerations.

The success of conifers over much of the world's terrestrial surface is largely attributable to their tolerance to cold stress (i.e., cold hardiness). Due to an increase in climate variability, climate change may reduce conifer cold hardiness, which in turn could impact ecosystem functioning and productivity in conifer-dominated forests. The expression of cold hardiness is a product of environmental cues (E), genetic differentiation (G), and their interaction (G × E), although few studies have considered all components together. To better understand and manage for the impacts of climate change on conifer cold hardiness, we conducted a common garden experiment replicated in three test environments (cool, moderate, and warm) using 35 populations of coast Douglas-fir (Pseudotsuga menziesii var. menziesii) to test the hypotheses: (i) cool-temperature cues in fall are necessary to trigger cold hardening, (ii) there is large genetic variation among populations in cold hardiness that can be predicted from seed-source climate variables, (iii) observed differences among populations in cold hardiness in situ are dependent on effective environmental cues, and (iv) movement of seed sources from warmer to cooler climates will increase risk to cold injury. During fall 2012, we visually assessed cold damage of bud, needle, and stem tissues following artificial freeze tests. Cool-temperature cues (e.g., degree hours below 2 °C) at the test sites were associated with cold hardening, which were minimal at the moderate test site owing to mild fall temperatures. Populations differed 3-fold in cold hardiness, with winter minimum temperatures and fall frost dates as strong seed-source climate predictors of cold hardiness, and with summer temperatures and aridity as secondary predictors. Seed-source movement resulted in only modest increases in cold damage. Our findings indicate that increased fall temperatures delay cold hardening, warmer/drier summers confer a degree of cold hardiness, and seed-source movement from warmer to cooler climates may be a viable option for adapting coniferous forest to future climate.

Generalized provisional seed zones for native plants.

Deploying well-adapted and ecologically appropriate plant materials is a core component of successful restoration projects. We have developed generalized provisional seed zones that can be applied to any plant species in the United States to help guide seed movement. These seed zones are based on the intersection of high-resolution climatic data for winter minimum temperature and aridity (as measured by annual heat : moisture index), each classified into discrete bands. This results in the delineation of 64 provisional seed zones for the continental United States. These zones represent areas of relative climatic similarity, and movement of seed within these zones should help to minimize maladaptation. Superimposing Omernik's level III ecoregions over these seed zones distinguishes areas that are similar climatically yet different ecologically. A quantitative comparison of provisional seed zones with level III ecoregions and provisional seed zones within ecoregions for three species showed that provisional seed zone within ecoregion often explained the greatest proportion of variation in a suite of traits potentially related to plant fitness. These provisional seed zones can be considered a starting point for guidelines for seed transfer, and should be utilized in conjunction with appropriate species-specific information as well as local knowledge of microsite differences.

Differences in branch hydraulic architecture related to the aridity of growing sites and seed sources of coastal Douglas-fir saplings.

To better understand hydraulic adaptations of coastal Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) to local climate, we examined genetic (G) and environmental (E) responses of branch hydraulic architecture of 7-year-old saplings from dry and wet climates of origin grown at a relatively dry and a relatively wet common garden site in western Oregon. We sampled 2 years of branch growth from three dry-source and three wet-source families grown at both sites (72 branches, total). Overall, only 4 of the 11 traits had significant genetic (G) effects, whereas 9 traits had significant environmental (E) effects (P < 0.05). Both dry and wet sources had higher leaf-specific conductance (kl) at the dry than the wet site, but the values were achieved by different mechanisms and driven by G × E effects for leaf area/sapwood area (Al/As), shoot length (L), specific conductivity (Ks) and leaf-specific conductivity (Kl). Dry sources achieved higher kl in the dry site through higher Kl (via a lower Al/As and no change in Ks) with no difference in L. Wet sources achieved higher kl at the dry site through no difference in Kl (via no effect on Al/As, despite decreases in Al and As, and lower Ks) with lower L. Vulnerability to embolism (measured as percentage loss of conductivity at 4 MPa) had no G effect but an E effect, with slightly lower values at the dry site. Specific leaf area had G and E effects, with lower values for the dry sources and site. There were no G or E effects on wood density. The different responses of dry and wet sources to site aridity suggest that populations are differentially adapted to the aridity of growing sites. Population variation in response to aridity should be considered when selecting seed sources for establishing forests for future climates.

Genetic variation of piperidine alkaloids in Pinus ponderosa: a common garden study.

BACKGROUND AND AIMS: Previous measurements of conifer alkaloids have revealed significant variation attributable to many sources, environmental and genetic. The present study takes a complementary and intensive, common garden approach to examine genetic variation in Pinus ponderosa var. ponderosa alkaloid production. Additionally, this study investigates the potential trade-off between seedling growth and alkaloid production, and associations between topographic/climatic variables and alkaloid production. METHODS: Piperidine alkaloids were quantified in foliage of 501 nursery seedlings grown from seed sources in west-central Washington, Oregon and California, roughly covering the western half of the native range of ponderosa pine. A nested mixed model was used to test differences among broad-scale regions and among families within regions. Alkaloid concentrations were regressed on seedling growth measurements to test metabolite allocation theory. Likewise, climate characteristics at the seed sources were also considered as explanatory variables. KEY RESULTS: Quantitative variation from seedling to seedling was high, and regional variation exceeded variation among families. Regions along the western margin of the species range exhibited the highest alkaloid concentrations, while those further east had relatively low alkaloid levels. Qualitative variation in alkaloid profiles was low. All measures of seedling growth related negatively to alkaloid concentrations on a natural log scale; however, coefficients of determination were low. At best, annual height increment explained 19.4 % of the variation in ln(total alkaloids). Among the climate variables, temperature range showed a negative, linear association that explained 41.8 % of the variation. CONCLUSIONS: Given the wide geographic scope of the seed sources and the uniformity of resources in the seedlings' environment, observed differences in alkaloid concentrations are evidence for genetic regulation of alkaloid secondary metabolism in ponderosa pine. The theoretical trade-off with seedling growth appeared to be real, however slight. The climate variables provided little evidence for adaptive alkaloid variation, especially within regions.

Maternal effects mediated by maternal age: from life histories to population dynamics.

1. Maternal effects describe how mothers influence offspring life histories. In many taxa, maternal effects arise by differential resource allocation to young, often identified by variation in propagule size, and which affects individual traits and population dynamics. 2. Using a laboratory model system, the soil mite Sancassania berlesei, we show that, controlling for egg size, older mothers lay eggs that hatch later, develop more slowly, and mature at larger body sizes. 3. Such differences in life histories lead to marked population dynamical effects lasting for multiple generations, as evidenced by an experiment initiated with similarly sized eggs that came from young or old mothers. Differences in maturation from the initial cohort led to differences in population structure and life history that propagated the initial differences over time. 4. Maternal-age effects, which are not related to gross provisioning of the egg and are therefore phenotypically cryptic, can have profound implications for population dynamics, especially if environmental variation can affect the age structure of the adult population.

A new photolysis laser-induced fluorescence instrument for the detection of H2O and HDO in the lower stratosphere.

We present a new instrument, Hoxotope, for the in situ measurement of H(2)O and its heavy deuterium isotopologue (HDO) in the upper troposphere and lower stratosphere aboard the NASA WB-57. Sensitive measurements of deltaD are accomplished through the vacuum UV photolysis of water followed by laser-induced fluorescence detection of the resultant OH and OD photofragments. The photolysis laser-induced fluorescence technique can obtain S/N>20 for 1 ppbv HDO and S/N>30 for 5 ppmv H(2)O for 10 s data, providing the sensitivity required for deltaD measurements in the tropopause region. The technique responds rapidly to changing water concentrations due to its inherently small sampling volume, augmented by steps taken to minimize water uptake on instrument plumbing. Data from the summer 2005 Aura Validation Experiment Water Isotope Intercomparison Flights (AVE-WIIF) out of Houston, TX show agreement for H(2)O between Hoxotope and the Harvard water vapor instrument and for HDO between Hoxotope and the Harvard ICOS water isotope instrument, to within stated instrument uncertainties. The successful intercomparison validates Hoxotope as a credible source of deltaD data in the upper troposphere and lower stratosphere.

Viral factors associated with cytokine expression during HCV/HIV co-infection.

Co-infection with human immunodeficiency virus (HIV) is associated with reduced hepatitis C virus (HCV) treatment response and accelerated HCV disease. Cytokines, as mediators of immune responses, inflammation, and fibrogenesis, may underlie important differences in HCV pathogenesis during HIV co-infection. We previously found that serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) increased after HCV therapy with interferon (IFN) in HCV/HIV co-infected patients; however, cytokine levels were not predictive of HCV therapeutic response. Here, we examined viral factors associated with expression of IL-8, TNF-alpha, and transforming growth factor-beta1 (TGF-beta1) in uninfected, HCV mono-infected, HIV mono-infected, and HCV/HIV co-infected persons. HIV co-infection was associated with decreased IL-8 detection but not TNF-alpha detection. A significant interaction effect demonstrated that HIV infection was associated with elevated TGF-beta1 in HCV-positive individuals but not in HCV-negative individuals. The induction of a sustained profibrotic signal, such as TGF-beta1, by HIV may cause accelerated liver fibrosis during HCV/HIV co-infection and may hinder the host's ability to mount an effective HCV-specific immune response. Further studies are warranted to identify noninvasive markers of liver disease for the clinical management of HCV disease, particularly when liver biopsies have not been performed or are contraindicated.

Immunogenicity of Isogenic IgG in Aggregates and Immune Complexes.

A paradox in monoclonal antibody (mAb) therapy is that despite the well-documented tolerogenic properties of deaggregated IgG, most therapeutic IgG mAb induce anti-mAb responses. To analyze CD4 T cell reactions against IgG in various physical states, we developed an adoptive transfer model using CD4+ T cells specific for a Vκ region-derived peptide in the hapten-specific IgG mAb 36-71. We found that heat-aggregated or immune complexes (IC) of mAb 36-71 elicited anti-idiotypic (anti-Id) antibodies, while the deaggregated form was tolerogenic. All 3 forms of mAb 36-71 induced proliferation of cognate CD4+ T cells, but the aggregated and immune complex forms drove more division cycles and induced T follicular helper cells (TFH) development more effectively than did the deaggregated form. These responses occurred despite no adjuvant and no or only trace levels of endotoxin in the preparations. Physical analyses revealed large differences in micron- and nanometer-sized particles between the aggregated and IC forms. These differences may be functionally relevant, as CD4+ T cell proliferation to aggregated, but not IC mAb 36-71, was nearly ablated upon peritoneal injection of B cell-depleting antibody. Our results imply that, in addition to denatured aggregates, immune complexes formed in vivo between therapeutic mAb and their intended targets can be immunogenic.

An examination of the elastic properties of tissue-mimicking phantoms using vibro-acoustography and a muscle motor system.

Tissue hardness, often quantified in terms of elasticity, is an important differentiating criterion for pathological identity and is extensively used by surgeons for tumor localization. Delineation of malignant regions from benign regions is typically performed by visual inspection and palpation. Although practical, this method is highly subjective and does not provide quantitative metrics. We have previously reported on Vibro-Acoustography (VA) for tumor delineation. VA is unique in that it uses the specific, non-linear properties of tumor tissue in response to an amplitude modulated ultrasound beam to generate spatially resolved, high contrast maps of tissue. Although the lateral and axial resolutions (sub-millimeter and sub-centimeter, respectively) of VA have been extensively characterized, the relationship between static stiffness assessment (palpation) and dynamic stiffness characterization (VA) has not been explicitly established. Here we perform a correlative exploration of the static and dynamic properties of tissue-mimicking phantoms, specifically elasticity, using VA and a muscle motor system. Muscle motor systems, commonly used to probe the mechanical properties of materials, provide absolute, quantitative point measurements of the elastic modulus, analogous to Young's modulus, of a target. For phantoms of varying percent-by-weight concentrations, parallel VA and muscle motor studies conducted on 18 phantoms reveal a negative correlation (p < - 0.85) between mean signal amplitude levels observed with VA and calculated elastic modulus values from force vs. indentation depth curves. Comparison of these elasticity measurements may provide additional information to improve tissue modeling, system characterization, as well as offer valuable insights for in vivo applications, specifically surgical extirpation of tumors.

Organic nitrate chemistry and its implications for nitrogen budgets in an isoprene- and monoterpene-rich atmosphere: constraints from aircraft (SEAC4RS) and ground-based (SOAS) observations in the Southeast US.

Formation of organic nitrates (RONO2) during oxidation of biogenic volatile organic compounds (BVOCs: isoprene, monoterpenes) is a significant loss pathway for atmospheric nitrogen oxide radicals (NOx), but the chemistry of RONO2 formation and degradation remains uncertain. Here we implement a new BVOC oxidation mechanism (including updated isoprene chemistry, new monoterpene chemistry, and particle uptake of RONO2) in the GEOS-Chem global chemical transport model with ∼25 × 25 km2 resolution over North America. We evaluate the model using aircraft (SEAC4RS) and ground-based (SOAS) observations of NOx, BVOCs, and RONO2 from the Southeast US in summer 2013. The updated simulation successfully reproduces the concentrations of individual gas- and particle-phase RONO2 species measured during the campaigns. Gas-phase isoprene nitrates account for 25-50% of observed RONO2 in surface air, and we find that another 10% is contributed by gas-phase monoterpene nitrates. Observations in the free troposphere show an important contribution from long-lived nitrates derived from anthropogenic VOCs. During both campaigns, at least 10% of observed boundary layer RONO2 were in the particle phase. We find that aerosol uptake followed by hydrolysis to HNO3 accounts for 60% of simulated gas-phase RONO2 loss in the boundary layer. Other losses are 20% by photolysis to recycle NOx and 15% by dry deposition. RONO2 production accounts for 20% of the net regional NOx sink in the Southeast US in summer, limited by the spatial segregation between BVOC and NOx emissions. This segregation implies that RONO2 production will remain a minor sink for NOx in the Southeast US in the future even as NOx emissions continue to decline.

Hemodynamic effects of intravenous digoxin in patients with severe heart failure initially treated with diuretics and vasodilators.

The purpose of this study was to assess the hemodynamic effects of intravenous digoxin in patients with New York Heart Association class IV heart failure, who had never previously been treated with digitalis drugs, and who were initially treated only with diuretics and systemic vasodilators to clinical end points of compensation. Eleven male patients, 5 with idiopathic and 6 with ischemic cardiomyopathy, had sinus rhythm and were hospitalized with congestive heart failure not precipitated by an acute ischemic event. All 11 patients were treated with intravenous furosemide and various vasodilators without invasive hemodynamic monitoring for a mean period of 4.3 +/- 2.1 days. This therapy resulted in subjective and objective improvement in all patients as reflected by a significant decrease in heart failure score from 9.5 +/- 2.2 to 2.7 +/- 2.3 (p less than 0.001). When compensation was achieved by clinical criteria, the patients were instrumented and hemodynamics obtained before and serially thereafter for 6 hours after the intravenous administration of digoxin given in two 0.5 mg doses 2 hours apart. In response to digoxin, cardiac index increased from 2.6 +/- 0.7 liters/min per m2 to a peak of 3.3 +/- 0.6 liters/min per m2 (p less than 0.005); left ventricular stroke work index (g X m/m2) increased from 27 +/- 16 to 43 +/- 23 (p less than 0.005) and the ejection fraction (eight patients) increased from 21 +/- 13% to 29 +/- 11% (p less than 0.04). Mean pulmonary capillary wedge pressure decreased from 24 +/- 7 to a minimum of 17 +/- 4 mm Hg (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Geophysical imaging reveals topographic stress control of bedrock weathering.

Bedrock fracture systems facilitate weathering, allowing fresh mineral surfaces to interact with corrosive waters and biota from Earth's surface, while simultaneously promoting drainage of chemically equilibrated fluids. We show that topographic perturbations to regional stress fields explain bedrock fracture distributions, as revealed by seismic velocity and electrical resistivity surveys from three landscapes. The base of the fracture-rich zone mirrors surface topography where the ratio of horizontal compressive tectonic stresses to near-surface gravitational stresses is relatively large, and it parallels the surface topography where the ratio is relatively small. Three-dimensional stress calculations predict these results, suggesting that tectonic stresses interact with topography to influence bedrock disaggregation, groundwater flow, chemical weathering, and the depth of the "critical zone" in which many biogeochemical processes occur.