Denitrification and nitrous oxide emissions from riparian forests soils exposed to prolonged nitrogen runoff

Compared to upland forests, riparian forest soils have greater potential to remove nitrate (NO3) from agricultural run-off through denitrification. It is unclear, however, whether prolonged exposure of riparian soils to nitrogen (N) loading will affect the rate of denitrification and its end products. This research assesses the rate of denitrification and nitrous oxide (N2O) emissions from riparian forest soils exposed to prolonged nutrient run-off from plant nurseries and compares these to similar forest soils not exposed to nutrient run-off. Nursery run-off also contains high levels of phosphate (PO4). Since there are conflicting reports on the impact of PO4 on the activity of denitrifying microbes, the impact of PO4 on such activity was also investigated. Bulk and intact soil cores were collected from N-exposed and non-exposed forests to determine denitrification and N2O emission rates, whereas denitrification potential was determined using soil slurries. Compared to the non-amended treatment, denitrification rate increased 2.7- and 3.4-fold when soil cores collected from both N-exposed and non-exposed sites were amended with 30 and 60 μg NO3-N g-1 soil, respectively. Net N2O emissions were 1.5 and 1.7 times higher from the N-exposed sites compared to the non-exposed sites at 30 and 60 μg NO3-N g-1 soil amendment rates, respectively. Similarly, denitrification potential increased 17 times in response to addition of 15 μg NO3-N g-1 in soil slurries. The addition of PO4 (5 μg PO4–P g-1) to soil slurries and intact cores did not affect denitrification rates. These observations suggest that prolonged N loading did not affect the denitrification potential of the riparian forest soils; however, it did result in higher N2O emissions compared to emission rates from non-exposed forests

Challenges of Profile Likelihood Evaluation in Multi-Dimensional SUSY Scans

Statistical inference of the fundamental parameters of supersymmetric theories is a challenging and active endeavor. Several sophisticated algorithms have been employed to this end. While Markov-Chain Monte Carlo (MCMC) and nested sampling techniques are geared towards Bayesian inference, they have also been used to estimate frequentist confidence intervals based on the profile likelihood ratio. We investigate the performance and appropriate configuration of MultiNest, a nested sampling based algorithm, when used for profile likelihood-based analyses both on toy models and on the parameter space of the Constrained MSSM. We find that while the standard configuration is appropriate for an accurate reconstruction of the Bayesian posterior, the profile likelihood is poorly approximated. We identify a more appropriate MultiNest configuration for profile likelihood analyses, which gives an excellent exploration of the profile likelihood (albeit at a larger computational cost), including the identification of the global maximum likelihood value. We conclude that with the appropriate configuration MultiNest is a suitable tool for profile likelihood studies, indicating previous claims to the contrary are not well founded.Comment: 21 pages, 9 figures, 1 table; minor changes following referee report. Matches version accepted by JHE

The what and where of adding channel noise to the Hodgkin-Huxley equations

One of the most celebrated successes in computational biology is the Hodgkin-Huxley framework for modeling electrically active cells. This framework, expressed through a set of differential equations, synthesizes the impact of ionic currents on a cell's voltage -- and the highly nonlinear impact of that voltage back on the currents themselves -- into the rapid push and pull of the action potential. Latter studies confirmed that these cellular dynamics are orchestrated by individual ion channels, whose conformational changes regulate the conductance of each ionic current. Thus, kinetic equations familiar from physical chemistry are the natural setting for describing conductances; for small-to-moderate numbers of channels, these will predict fluctuations in conductances and stochasticity in the resulting action potentials. At first glance, the kinetic equations provide a far more complex (and higher-dimensional) description than the original Hodgkin-Huxley equations. This has prompted more than a decade of efforts to capture channel fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of these approaches, while intuitively appealing, produce quantitative errors when compared to kinetic equations; others, as only very recently demonstrated, are both accurate and relatively simple. We review what works, what doesn't, and why, seeking to build a bridge to well-established results for the deterministic Hodgkin-Huxley equations. As such, we hope that this review will speed emerging studies of how channel noise modulates electrophysiological dynamics and function. We supply user-friendly Matlab simulation code of these stochastic versions of the Hodgkin-Huxley equations on the ModelDB website (accession number 138950) and http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl

Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate ligament reconstruction: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The efficacy of selective cox-2 inhibitors in postoperative pain reduction were usually compared with conventional non-selective conventional NSAIDs or other types of medicine. Previous studies also used selective cox-2 inhibitors as single postoperative dose, in continued mode, or in combination with other modalities. The purpose of this study was to compare analgesic efficacy of single preoperative administration of etoricoxib versus celecoxib for post-operative pain relief after arthroscopic anterior cruciate ligament reconstruction.</p> <p>Methods</p> <p>One hundred and two patients diagnosed as anterior cruciate ligament injury were randomized into 3 groups using opaque envelope. Both patients and surgeon were blinded to the allocation. All of the patients were operated by one orthopaedic surgeon under regional anesthesia. Each group was given either etoricoxib 120 mg., celecoxib 400 mg., or placebo 1 hour prior to operative incision. Post-operative pain intensity, time to first dose of analgesic requirement and numbers of analgesic used for pain control and adverse events were recorded periodically to 48 hours after surgery. We analyzed the data according to intention to treat principle.</p> <p>Results</p> <p>Among 102 patients, 35 were in etoricoxib, 35 in celecoxib and 32 in placebo group. The mean age of the patients was 30 years and most of the injury came from sports injury. There were no significant differences in all demographic characteristics among groups. The etoricoxib group had significantly less pain intensity than the other two groups at recovery room and up to 8 hours period but no significance difference in all other evaluation point, while celecoxib showed no significantly difference from placebo at any time points. The time to first dose of analgesic medication, amount of analgesic used, patient's satisfaction with pain control and incidence of adverse events were also no significantly difference among three groups.</p> <p>Conclusions</p> <p>Etoricoxib is more effective than celecoxib and placebo for using as preemptive analgesia for acute postoperative pain control in patients underwent arthroscopic anterior cruciate ligament reconstruction.</p> <p>Trial registration number</p> <p>NCT01017380</p

Concurrent acute illness and comorbid conditions poorly predict antibiotic use in upper respiratory tract infections: a cross-sectional analysis

<p>Abstract</p> <p>Background</p> <p>Inappropriate antibiotic use promotes resistance. Antibiotics are generally not indicated for upper respiratory infections (URIs). Our objectives were to describe patterns of URI treatment and to identify patient and provider factors associated with antibiotic use for URIs.</p> <p>Methods</p> <p>This study was a cross-sectional analysis of medical and pharmacy claims data from the Pennsylvania Medicaid fee-for-service program database. We identified Pennsylvania Medicaid recipients with a URI office visit over a one-year period. Our outcome variable was antibiotic use within seven days after the URI visit. Study variables included URI type and presence of concurrent acute illnesses and chronic conditions. We considered the associations of each study variable with antibiotic use in a logistic regression model, stratifying by age group and adjusting for confounders.</p> <p>Results</p> <p>Among 69,936 recipients with URI, 35,786 (51.2%) received an antibiotic. In all age groups, acute sinusitis, chronic sinusitis, otitis, URI type and season were associated with antibiotic use. Except for the oldest group, physician specialty and streptococcal pharyngitis were associated with antibiotic use. History of chronic conditions was not associated with antibiotic use in any age group. In all age groups, concurrent acute illnesses and history of chronic conditions had only had fair to poor ability to distinguish patients who received an antibiotic from patients who did not.</p> <p>Conclusion</p> <p>Antibiotic prevalence for URIs was high, indicating that potentially inappropriate antibiotic utilization is occurring. Our data suggest that demographic and clinical factors are associated with antibiotic use, but additional reasons remain unexplained. Insight regarding reasons for antibiotic prescribing is needed to develop interventions to address the growing problem of antibiotic resistance.</p

Neonatal hypothermia and associated risk factors among newborns of southern Nepal

<p>Abstract</p> <p>Background</p> <p>Neonatal hypothermia is associated with an increased mortality risk for 28 days. There are few community-based data on specific risk factors for neonatal hypothermia. Estimates of association between neonatal hypothermia in the community and risk factors are needed to guide the design of interventions to reduce exposure.</p> <p>Methods</p> <p>A cohort of 23,240 babies in rural southern Nepal was visited at home by field workers who measured axillary temperatures for 28 days (213,316 temperature measurements). The cumulative incidence of hypothermia (defined as < 35.0°C based on an analysis of the hypothermia-mortality risk relationship) was examined for any association with infant characteristics, care practices and parental, household, socioeconomic and demographic factors. Estimates were adjusted for age and ambient temperature.</p> <p>Results</p> <p>Ten percent of the babies (<it>n </it>= 2342) were observed with temperatures of < 35.0°C. Adjusted prevalence ratios (Adj PR) were increased among those who weighed < 2000 g [Adj PR = 4.32 (3.73, 5.00)] or < 1500 g [Adj PR = 11.63 (8.10, 16.70)] compared to those of normal weight (> 2500 g). Risk varied inversely along the entire weight spectrum: for every 100 g decrement hypothermia risk increased by 7.4%, 13.5% and 31.3%% for babies between 3000 g and 2500 g, 2500 g and 2000 g and < 2000 g, respectively. Preterm babies (< 34 weeks), females, those who had been first breastfed after 24 h and those with hypothermic mothers were at an increased risk. In the hot season the risk disparity between smaller and larger babies increased. Hypothermia was not associated with delayed bathing, hat wearing, room warming or skin-to-skin contact: they may have been practiced reactively and thereby obscured any potential benefit.</p> <p>Conclusions</p> <p>In addition to season in which the babies were born, weight is an important risk factor for hypothermia. Smaller babies are at higher relative risk of hypothermia during the warm period and do not receive the protective seasonal benefit apparent among larger babies. The need for year-round thermal care, early breastfeeding and maternal thermal care should be emphasized. Further work is needed to quantify the benefits of other simple neonatal thermal care practices.</p

The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study

<p>Abstract</p> <p>Background</p> <p>Tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) are the three components of the once-daily, single tablet regimen (Atripla) for treatment of HIV-1 infection. Previous cell culture studies have demonstrated that the double combination of tenofovir (TFV), the parent drug of TDF, and FTC were additive to synergistic in their anti-HIV activity, which correlated with increased levels of intracellular phosphorylation of both compounds.</p> <p>Results</p> <p>In this study, we demonstrated the combinations of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV synergistically inhibit HIV replication in cell culture and synergistically inhibit HIV-1 reverse transcriptase (RT) catalyzed DNA synthesis in biochemical assays. Several different methods were applied to define synergy including median-effect analysis, MacSynergy^®II and quantitative isobologram analysis. We demonstrated that the enhanced formation of dead-end complexes (DEC) by HIV-1 RT and TFV-terminated DNA in the presence of FTC-triphosphate (TP) could contribute to the synergy observed for the combination of TFV+FTC, possibly through reduced terminal NRTI excision. Furthermore, we showed that EFV facilitated efficient formation of stable, DEC-like complexes by TFV- or FTC-monophosphate (MP)-terminated DNA and this can contribute to the synergistic inhibition of HIV-1 RT by TFV-diphosphate (DP)+EFV and FTC-TP+EFV combinations.</p> <p>Conclusion</p> <p>This study demonstrated a clear correlation between the synergistic antiviral activities of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV combinations and synergistic HIV-1 RT inhibition at the enzymatic level. We propose the molecular mechanisms for the TFV+FTC+EFV synergy to be a combination of increased levels of the active metabolites TFV-DP and FTC-TP and enhanced DEC formation by a chain-terminated DNA and HIV-1 RT in the presence of the second and the third drug in the combination. This study furthers the understanding of the longstanding observations of synergistic anti-HIV-1 effects of many NRTI+NNRTI and certain NRTI+NRTI combinations in cell culture, and provides biochemical evidence that combinations of anti-HIV agents can increase the intracellular drug efficacy, without increasing the extracellular drug concentrations.</p

Protein C anticoagulant system—anti-inflammatory effects

Activated protein C (APC) plays active roles in preventing progression of a number of disease processes. These include thrombosis due to its direct anticoagulant activity which is likely augmented by its cytoprotective activity, thereby limiting exposure of procoagulant cellular membrane surfaces on cells. Beyond that, the pathway signals the cells to prevent apoptosis, to dampen inflammation, to increase endothelial barrier function, and to selectively downregulate some genes implicated in disease progression. Most of these functions are manifested to APC binding to endothelial protein C receptor (EPCR) allowing PAR1 activation, but activation of other PARS is also implicated in some cases. In addition to EPCR orchestrating these changes, CD11b is also capable of supporting APC signaling. Selective control of these pathways offers potential in new therapeutic approaches to disease

Functional assessment of coronary artery flow using adenosine stress dual-energy CT: a preliminary study

We attempted to assess coronary artery flow using adenosine-stress and dual-energy mode with dual-source CT (DE-CT). Data of 18 patients with suspected coronary arteries disease who had undergone cardiac DE-CT were retrospectively analyzed. The patients were divided into two groups: 10 patients who performed adenosine stress CT, and 8 patients who performed rest CT as controls. We reconstructed an iodine map and composite images at 120 kV (120 kV images) using raw data with scan parameters of 100 and 140 kV. We measured mean attenuation in the coronary artery proximal to the distal portion on both the iodine map and 120 kV images. Coronary enhancement ratio (CER) was calculated by dividing mean attenuation in the coronary artery by attenuation in the aortic root, and was used as an estimate of coronary enhancement. Coronary stenosis was identified as a reduction in diameter of >50% on CT angiogram, and myocardial ischemia was diagnosed by adenosine-stress myocardial perfusion scintigraphy. The iodine map showed that CER was significantly lower for ischemic territories (0.76 ± 0.06) or stenosed coronary arteries (0.77 ± 0.06) than for non-ischemic territories (0.95 ± 0.21, P = 0.02) or non-stenosed coronary arteries (1.07 ± 0.33, P < 0.001). The 120 kV images showed no difference in CER between these two groups. Use of CER on the iodine map separated ischemic territories from non-ischemic territories with a sensitivity of 86% and a specificity of 75%. Our quantification is the first non-invasive analytical technique for assessment of coronary artery flow using cardiac CT. CER on the iodine map is a candidate method for demonstration of alteration in coronary artery flow under adenosine stress, which is related to the physiological significance of coronary artery disease

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher