Detection of increased pyruvate dehydrogenase flux in the human heart during adenosine stress test using hyperpolarized [1-13C]pyruvate cardiovascular magnetic resonance imaging.

BACKGROUND: Hyperpolarized (HP) [1-13C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1-13C]pyruvate to either [1-13C]lactate or 13C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine stress test with HP [1-13C]pyruvate CMR to detect cardiac metabolism in the healthy human heart at rest and during moderate stress. METHODS: A prospective descriptive study was performed between October 2019 and August 2020. Healthy human subjects underwent cine CMR and HP [1-13C]pyruvate CMR at rest and during adenosine stress. HP [1-13C]pyruvate CMR images were acquired at the mid-left-ventricle (LV) level. Semi-quantitative assessment of first-pass myocardial [1-13C]pyruvate perfusion and metabolism were assessed. Paired t-tests were used to compare mean values at rest and during stress. RESULTS: Six healthy subjects (two female), age 29 ± 7 years were studied and no adverse reactions occurred. Myocardial [1-13C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2 ± 2.8 to 2.7 ± 1.3 s, p = 0.02. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (kPL) for lactate increased from 11 ± 9 *10-3 to 20 ± 10 * 10-3 s-1, p = 0.04. The pyruvate oxidation rate (kPB) increased from 4 ± 4 *10-3 to 12 ± 7 *10-3 s-1, p = 0.008. This increase in carbohydrate metabolism was positively correlated with heart rate (R2 = 0.44, p = 0.02). CONCLUSIONS: Adenosine stress testing combined with HP [1-13C]pyruvate CMR is feasible and well-tolerated in healthy subjects. We observed an increased pyruvate oxidation during cardiac stress. The present study is an important step in the translation of HP [1-13C]pyruvate CMR into clinical cardiac imaging. Trial registration EUDRACT, 2018-003533-15. Registered 4th of December 2018, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-003533-15.

Leveraging the blue economy to transform marine forest restoration.

The UN Decade of Ecosystem Restoration is a response to the urgent need to substantially accelerate and upscale ecological restoration to secure Earth's sustainable future. Globally, restoration commitments have focused overwhelmingly on terrestrial forests. In contrast, despite a strong value proposition, efforts to restore seaweed forests lag far behind other major ecosystems and continue to be dominated by small-scale, short-term academic experiments. However, seaweed forest restoration can match the scale of damage and threat if moved from academia into the hands of community groups, industry, and restoration practitioners. Connecting two rapidly growing sectors in the Blue Economy-seaweed cultivation and the restoration industry-can transform marine forest restoration into a commercial-scale enterprise that can make a significant contribution to global restoration efforts.

Reconciling the temperature dependence of respiration across timescales and ecosystem types.

Ecosystem respiration is the biotic conversion of organic carbon to carbon dioxide by all of the organisms in an ecosystem, including both consumers and primary producers. Respiration exhibits an exponential temperature dependence at the subcellular and individual levels, but at the ecosystem level respiration can be modified by many variables including community abundance and biomass, which vary substantially among ecosystems. Despite its importance for predicting the responses of the biosphere to climate change, it is as yet unknown whether the temperature dependence of ecosystem respiration varies systematically between aquatic and terrestrial environments. Here we use the largest database of respiratory measurements yet compiled to show that the sensitivity of ecosystem respiration to seasonal changes in temperature is remarkably similar for diverse environments encompassing lakes, rivers, estuaries, the open ocean and forested and non-forested terrestrial ecosystems, with an average activation energy similar to that of the respiratory complex (approximately 0.65 electronvolts (eV)). By contrast, annual ecosystem respiration shows a substantially greater temperature dependence across aquatic (approximately 0.65 eV) versus terrestrial ecosystems (approximately 0.32 eV) that span broad geographic gradients in temperature. Using a model derived from metabolic theory, these findings can be reconciled by similarities in the biochemical kinetics of metabolism at the subcellular level, and fundamental differences in the importance of other variables besides temperature­such as primary productivity and allochthonous carbon inputs­on the structure of aquatic and terrestrial biota at the community level.

Partitioning of the diffuse attenuation coefficient for photosynthetically available irradiance in a deep dendritic tropical lake.

We studied the effects of particulate and dissolved optically active components on the attenuation of photosynthetic active radiation (PAR) in a tropical lake. The temporal and spatial distribution of tripton, Chl-a and aCDOM(440) and their relative contribution to the diffuse PAR attenuation coefficient (Kd) was investigated at 21 sites (dry and wet seasons and two intermediate periods) and at monthly interval at 1 pelagic site. Higher values of ​​ Kd were observed during the mixing period, characterized by a higher concentration of tripton and Chl-a compared to the stratified rainy season. In the spatial sampling PAR attenuation was dominated by tripton absorption/scattering (average relative contribution of 79%), followed by Chl-a (average 11.6%). In the monthly sampling tripton and Chl-a accounted for most of the Kd with relative contributions of 47.8% and 35.6%, respectively. Multiple linear regression analysis showed that Chl-a and tripton in combination explained 97% of the monthly variation in Kd (p<0.001), but Chl-a had more influence (higher regression coefficient). Thus, although most of light attenuation was due to tripton, seasonal variations in phytoplankton abundance were responsible for most of the temporal fluctuations in Kd.

A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial.

BACKGROUND: Despite rapid dissemination of an everolimus-eluting bioresorbable scaffold for treatment for coronary artery disease, no data from comparisons with its metallic stent counterpart are available. In a randomised controlled trial we aimed to compare an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent. Here we report secondary clinical and procedural outcomes after 1 year of follow-up. METHODS: In a single-blind, multicentre, randomised trial, we enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients in a 2:1 ratio to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb, Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience, Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. The co-primary endpoints of this study are vasomotion (change in mean lumen diameter before and after nitrate administration at 3 years) and difference between minimum lumen diameter (after nitrate administration) after the index procedure and at 3 years. Secondary endpoints were procedural performance assessed by quantitative angiography and intravascular ultrasound; composite clinical endpoints based on death, myocardial infarction, and coronary revascularisation; device and procedural success; and angina status assessed by the Seattle Angina Questionnaire and exercise testing at 6 and 12 months. Cumulative angina rate based on adverse event reporting was analysed post hoc. This trial is registered at ClinicalTrials.gov, number NCT01425281. FINDINGS: Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the bioresorbable scaffold group (335 patients, 364 lesions) or the metallic stent group (166 patients, 182 lesions). Dilatation pressure and balloon diameter at the highest pressure during implantation or postdilatation were higher and larger in the metallic stent group, whereas the acute recoil post implantation was similar (0.19 mm for both, p=0.85). Acute lumen gain was lower for the bioresorbable scaffold by quantitative coronary angiography (1.15 mm vs 1.46 mm, p<0.0001) and quantitative intravascular ultrasound (2.85 mm(2)vs 3.60 mm(2), p<0.0001), resulting in a smaller lumen diameter or area post procedure. At 1 year, however, cumulative rates of first new or worsening angina from adverse event reporting were lower (72 patients [22%] in the bioresorbable scaffold group vs 50 [30%] in the metallic stent group, p=0.04), whereas performance during maximum exercise and angina status by SAQ were similar. The 1-year composite device orientated endpoint was similar between the bioresorbable scaffold and metallic stent groups (16 patients [5%] vs five patients [3%], p=0.35). Three patients in the bioresorbable scaffold group had definite or probable scaffold thromboses (one definite acute, one definite sub-acute, and one probable late), compared with no patients in the metallic stent group. There were 17 (5%) major cardiac adverse events in the bioresorbable scaffold group compared with five (3%) events in the metallic stent group, with the most common adverse events being myocardial infarction (15 cases [4%] vs two cases [1%], respectively) and clinically indicated target-lesion revascularisation (four cases [1%] vs three cases [2%], respectively). INTERPRETATION: The everolimus-eluting bioresorbable scaffold showed similar 1-year composite secondary clinical outcomes to the everolimus-eluting metallic stent. FUNDING: Abbott Vascular.

Automatic High Frequency Monitoring for Improved Lake and Reservoir Management.

Recent technological developments have increased the number of variables being monitored in lakes and reservoirs using automatic high frequency monitoring (AHFM). However, design of AHFM systems and posterior data handling and interpretation are currently being developed on a site-by-site and issue-by-issue basis with minimal standardization of protocols or knowledge sharing. As a result, many deployments become short-lived or underutilized, and many new scientific developments that are potentially useful for water management and environmental legislation remain underexplored. This Critical Review bridges scientific uses of AHFM with their applications by providing an overview of the current AHFM capabilities, together with examples of successful applications. We review the use of AHFM for maximizing the provision of ecosystem services supplied by lakes and reservoirs (consumptive and non consumptive uses, food production, and recreation), and for reporting lake status in the EU Water Framework Directive. We also highlight critical issues to enhance the application of AHFM, and suggest the establishment of appropriate networks to facilitate knowledge sharing and technological transfer between potential users. Finally, we give advice on how modern sensor technology can successfully be applied on a larger scale to the management of lakes and reservoirs and maximize the ecosystem services they provide.

A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan.

AIMS: Theoretically, bioresorbable vascular scaffolds (BVSs) may provide superior long-term results compared with permanent metallic drug-eluting stents (DESs). However, whether BVSs are as safe and effective as metallic DESs prior to complete bioresorption is unknown. METHODS AND RESULTS: ABSORB Japan was a single-blind, multicentre, active-controlled, randomized trial designed to support regulatory approval of the Absorb BVS in Japan. Eligible patients with one or two de novo lesions in different epicardial vessels were randomized at 38 Japanese sites in a 2:1 ratio to Absorb BVS vs. cobalt-chromium everolimus-eluting stents (CoCr-EESs). The primary endpoint was target lesion failure [TLF: a composite of cardiac death, myocardial infarction attributable to target vessel, or ischaemia-driven target lesion revascularization (ID-TLR)] at 12 months, powered for non-inferiority. The major secondary endpoint was angiographic in-segment late lumen loss (LLL) at 13 months. A total of 400 patients were randomized to BVSs (266 patients and 275 lesions) or CoCr-EESs (134 patients and 137 lesions). TLF through 12 months was 4.2% with BVSs and 3.8% with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.39% (3.95%); Pnon-inferiority < 0.0001]. Definite/probable stent/scaffold thrombosis at 12 months occurred in 1.5% of the patients with both devices (P = 1.0), and ID-TLR for restenosis was infrequent (1.1% with BVSs and 1.5% with CoCr-EESs, P = 1.0). With 96.0% angiographic follow-up, in-segment LLL at 13 months was 0.13 ± 0.30 mm with BVSs and 0.12 ± 0.32 mm with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.01 (0.07); Pnon-inferiority < 0.0001). CONCLUSION: In the ABSORB Japan randomized trial, 12-month clinical and 13-month angiographic outcomes of BVSs were comparable to CoCr-EESs. CLINICAL REGISTRATION: ClinicalTrials.gov, number NCT01844284.

A phase I thorough QT/QTc study evaluating therapeutic and supratherapeutic doses of avacopan in healthy participants.

This phase I thorough QTc, double-blind, randomized, placebo- and positive-controlled, parallel group, multiple-dose study evaluated avacopan's effect on cardiac repolarization using concentration-QTc (C-QTc) as the primary analysis. Avacopan 30 mg b.i.d. (therapeutic dose) was administered orally on days 1 through 7 followed by avacopan 100 mg b.i.d. (supratherapeutic dose) on days 8 through 14 in 29 healthy participants. Moxifloxacin 400 mg and placebo were administered on days 1 and 15 in a nested crossover design for assay sensitivity in separate cohorts to 28 participants. Time-matched plasma concentrations and up to 10 replicate ECGs were obtained on prespecified days at baseline and postdose on days 1, 7, 14, and 15. The mean change from baseline on QTcF for avacopan (-5.5 to 3.5 ms) was similar to placebo (-6.9 to 1.4 ms) across days 1, 7, and 14. The mean effect on ΔΔQTcF (90% CI) was estimated as 1.5 ms (-0.17 to 3.09) and 0.8 ms (-2.41 to 4.05) for 30 and 100 mg avacopan b.i.d. treatments, respectively. Based on the C-QTc analysis, avacopan's effect on ΔΔQTcF >10 ms can be excluded within the observed plasma concentration range of up to ~1220 and ~335 ng/mL for avacopan and active major metabolite, M1, respectively. The estimated population slopes showed a shallow relationship, which was not statistically significant. There was no clinically meaningful effect of avacopan on heart rate or cardiac conduction (PR and QRS intervals). Avacopan appeared to be generally well tolerated in this study population.

Exploratory study of the Sentinel-3 level 2 product for monitoring chlorophyll-a and assessing ecological status in Danish seas.

In situ Chl-a data were used to perform empirical calibration and validation of Sentinel-3 level 2 product in Danish marine waters. Comparing in situ data with both same-day and ±5 days moving averaged Sentiel-3 Chl-a values yielded two similar positive correlations (p > 0.05) with rpearson values of 0.56 and 0.53, respectively. However, as the moving averaged values resulted in significantly more available data than daily matchups (N = 392 vs. N = 1292) at a similar quality of correlation with similar model parameters (slope (1.53 and 1.7) and intercept (-0.28 and -0.33) respectively), which were not significantly different (p > 0.05), the further analyses were focused on ±5 days moving averaged values. A thorough comparison of seasonal and growing season averages (GSA) also showed a very good agreement, except for a few stations characterized by very shallow depth. Overestimation by the Sentinel-3 occurred in shallow coastal areas and was attributed to the interferences from benthic vegetation and high levels of Colored Dissolved Organic matter (CDOM) interfering with the Chl-a signals. Underestimation observed in the inner estuaries with shallow Chl-a rich waters, however, seen as a result of self-shading at high Chl-a concentrations, reducing effective absorption by phytoplankton. Besides the observed minor disagreements, there was no significant difference when the GSA values from in situ and Sentinel-3 were compared for all three water types (p > 0.05, N = 110). Analyzing Chl-a estimates along a depth gradient showed significant (p < 0.001) non-linear trends of declining concentrations from shallow to deeper waters for both in situ (explaining 15.2 % of the variance (N = 109)) and Sentinel-3 data (explaining 36.3 % of the variance (N = 110)), with higher variability in shallow waters. Furthermore, Sentinel-3 enabled full spatial coverage of all 102 monitored water bodies providing GSA data at much higher spatial and temporal resolutions for good ecological status (GES) assessment compared to only 61 through in situ sampling. This underlines the potential of Sentinel-3 for substantially extending the geographical coverage of monitoring and assessment. However, the systematic over- and underestimation of Chl-a in shallow nutrient rich inner estuaries through Sentinel-3 requires further attention to enable routine application of the Sentinel-3 level 2 standard product in the operational Chl-a monitoring in Danish coastal waters. We provide methodological recommendations on how to improve the Sentinel-3 products' representation of in situ Chl-a conditions. Continued frequent in situ sampling remains important for monitoring as these measurements provide essential data for empirical calibration and validation of satellite based estimates to reduce possible systematic bias.

Modelled dispersal pathways of non-indigenous species in the Danish Wadden Sea.

The introduction-rate of non-indigenous species (NIS) to coastal water bodies has accelerated over the last century. We present a model study assessing the fate of NIS released in likely point sources of the Danish Wadden Sea. We show that NIS-particles released in the deep North Sea are generally transported away from the Wadden Sea, while those released in the coastal North Sea and the Wadden Sea show large variability in track pattern and settlement location. Consequently, the introduction of NIS from ships entering the port of Esbjerg pose a threat to the Wadden Sea through primary and secondary spreading, while transport of species from sources in the south likely causes a slow and steady settling of NIS in the Wadden Sea and coastal North Sea. The study points to the importance of enforcing an efficient monitoring system to ensure early detection of changes to the species composition of the Wadden Sea.

High-resolution hydrodynamics of coral reefs and tracing of pollutants from hotel areas along the west coast of Unguja Island, Zanzibar.

A rapid increase in population size along with expansion in hotel investment have been identified as key drivers of marine pollution in Zanzibar coastal waters. A validated high-resolution hydrodynamic tracer model was used to estimate the dispersal and impact range of pollutants from the main hotel areas along the western coastline of Unguja Island. The model showed the highest impact of pollutants from land during the northeast monsoon season due to the weakening of the main current. Marine protected areas with short distances to hotel areas and weak tidal currents were more likely to be impacted by pollutants from land than the more remote areas with higher flushing in agreement with water quality and seagrass health measurements. Cumulative effects of pollutants instead of single sources are important to consider for integrated wastewater treatment plans and management strategies to reduce pollution for the protection of biodiversity and guide future monitoring.

Contribution of boulder reef habitats to oxygen dynamics of a shallow estuary.

We assessed the importance of boulder reefs to the oxygen dynamics of a shallow estuary during two growing seasons in 2017 and 2018. Using open-system diel oxygen measurements and benthic and pelagic incubations, we evaluated the relative contribution of pelagic and benthic habitats to the ecosystem metabolism along a depth gradient in two areas, with (Reef) and without (Bare) boulder reefs in the Limfjorden, Denmark. System integrated areal rates of gross primary production (GPP) and ecosystem respiration (ER) both increased with depth in both areas. Benthic contribution to system GPP and ER was highest at shallow depth where it represented 47 and 53% respectively. However, with increasing depth pelagic processes dominated GPP and ER (98 and 94%) even in the Reef area. Although the Reef area had higher biomass of auto- and heterotrophic organisms (macroalgae and macrofauna), benthic GPP was at similar level in both areas, due to a significant contribution from micro-phytobenthic organisms. The Reef area had lower sediment pools of organic matter, nitrogen and phosphorous and was slightly more oxygenated compared to the nearby Bare area. Extreme temperatures and higher levels of nutrients in 2018 caused a marked increase in benthic ER rates resulting in net heterotrophy (NEM = GPP - ER < 0) in 2018 compared to net autotrophy (NEM > 0) in 2017. Under current eutrophic conditions, boulder reefs do not contribute positively to the oxygen dynamics in the estuary. Reoccurring blooms of phytoplankton with high organic matter decomposition combined with high temperatures and dominance of fauna stimulate depletion of oxygen around the reefs. Significant improvements in water clarity are needed to regrow perennial macroalgae and induce net autotrophy. Under current turbid conditions, it is only recommended to establish boulder reefs in shallow (<3 m) parts of the estuary.

Submerged aquatic vegetation: Overview of monitoring techniques used for the identification and determination of spatial distribution in European coastal waters.

Coastal waters are highly productive and diverse ecosystems, often dominated by marine submerged aquatic vegetation (SAV) and strongly affected by a range of human pressures. Due to their important ecosystem functions, for decades, both researchers and managers have investigated changes in SAV abundance and growth dynamics to understand linkages to human perturbations. In European coastal waters, monitoring of marine SAV communities traditionally combines diver observations and/or video recordings to determine, for example, spatial coverage and species composition. While these techniques provide very useful data, they are rather time consuming, labor-intensive, and limited in their spatial coverage. In this study, we compare traditional and emerging remote sensing technologies used to monitor marine SAV, which include satellite and occupied aircraft operations, aerial drones, and acoustics. We introduce these techniques and identify their main strengths and limitations. Finally, we provide recommendations for researchers and managers to choose the appropriate techniques for future surveys and monitoring programs. Integr Environ Assess Manag 2022;18:892-908. © 2021 SETAC.

Impact of socioeconomic position on initiation of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes - a Danish nationwide observational study.

BACKGROUND: Low socioeconomic position may affect initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucacon-like-peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D). We examined the association between socioeconomic position and initiation of SGLT-2i or GLP-1RA in patients with T2D at time of first intensification of antidiabetic treatment. METHODS: Through nationwide registers, we identified all Danish patients on metformin who initiated second-line add-on therapy between December 10, 2012, and December 31, 2020. For each time period (2012-2014, 2015-2017, and 2018-2020), we used multivariable multinomial logistic regression to associate disposable income, as proxy for socioeconomic position, with the probability of initiating a specific second-line treatment at time of first intensification. We reported probabilities standardised to the distribution of demographics and comorbidities of patients included in the last period (2018-2020). FINDINGS: We included 48915 patients (median age 62 years; 61·7% men). In each time period, high-income patients were more often men and had less comorbidities as compared with low income-patients. In each time period, the standardised probability of initiating a SGLT-2i or a GLP-1RA was significantly higher in the highest income group compared with the lowest: 11·4% vs. 9·5% (probability ratio [PR] 1·21, 95 % confidence interval [CI] 1·01-1·44) in 2012-2014; 22·6% vs. 19.6% (PR 1·15, CI 1·05-1·27) in 2015-2017; and 65·8% vs. 54·8% (PR 1·20, CI 1·16-1·24) in 2018-2020. The differences by income were consistent across multiple subgroups. INTERPRETATION: Despite a universal healthcare system, low socioeconomic position was consistently associated with a lower probability of initiating a SGLT-2i or a GLP-1RA. These disparities may widen the future socioeconomic gap in cardiovascular outcomes. FUNDING: The work was funded by unrestricted grants from 'Region Sjaelland Den Sundhedsvidenskabelige Forskningsfond' and 'Murermester Lauritz Peter Christensen og hustru Kirsten Sigrid Christensens Fond'.

Socioeconomic position and first-time major cardiovascular event in patients with type 2 diabetes: a Danish nationwide cohort study.

AIMS: The association between socioeconomic position and cardiovascular disease has not been well studied in patients with type 2 diabetes. We aimed to examine the association between socioeconomic position and first-time major adverse cardiovascular events (MACE) in patients with type 2 diabetes. METHODS AND RESULTS: Through the Danish nationwide registers, we identified all residents with newly diagnosed type 2 diabetes between 2012 and 2017. Based on sex-stratified multivariable cause-specific Cox regression models, we calculated the standardized absolute 5-year risk of the composite outcome of first-time myocardial infarction, stroke, or cardiovascular mortality (MACE) according to income quartiles. A total of 57 106 patients with type 2 diabetes were included. During 155 989 person years, first-time MACE occurred in 2139 patients. Among both men and women, income was inversely associated with the standardized absolute 5-year risk of MACE. In men, the 5-year risk of MACE increased from 5.7% [95% confidence interval (CI) 4.9-6.5] in the highest income quartile to 9.3% (CI 8.3-10.2) in the lowest income group, with a risk difference of 3.5% (CI 2.4-4.7). In women, the risk of MACE increased from 4.2% (CI 3.4-5.0) to 6.1% (CI 5.2-7.0) according to income level, with a risk difference of 1.9% (CI 0.8-2.9). CONCLUSION: Despite free access to medical care in Denmark, low-socioeconomic position was associated with a higher 5-year risk of first-time MACE in patients with incident type 2 diabetes. Our results suggest prevention strategies could be developed specifically for patients with low-socioeconomic position.

Effect of body mass index on the efficacy, side effect profile, and plasma concentration of fixed-dose regadenoson for myocardial perfusion imaging.

BACKGROUND: There are limited data on the effect of body mass index (BMI) on the actions of fixed-dose regadenoson. The purpose of this study was to determine the effect of BMI on the efficacy, side effects, and plasma concentration of regadenoson for Myocardial Perfusion Imaging (MPI). METHODS AND RESULTS: The study included 2,015 subjects from the ADVANCE MPI trials. Initial adenosine MPI was followed by randomization to regadenoson (400-µg bolus injection) or adenosine (6-minute infusion) MPI. Subjects were classified according to BMI into six categories from underweight (<20 kg/m(2)) to extremely obese (≥40 kg/m(2)). PK modeling was used to predict the effect of BMI on plasma regadenoson concentration (PRC). Adenosine-regadenoson agreement rates for the presence and extent of reversibility were similar across BMI categories (P > .05). The incidence of side effects was also similar across BMIs (P ≥ .06). Subjects were less likely to feel very or extremely uncomfortable after regadenoson vs adenosine in all groups with BMI ≥ 25 kg/m(2), but this trend was not statistically significant in subjects with BMI 20-24 kg/m(2) (P > .05). PRC was inversely related to BMI with 19% higher PRC in the underweight and 36% lower PRC in the extremely obese compared with a normal weight subject. CONCLUSIONS: BMI does not alter the efficacy of regadenoson MPI despite lower PRC in high BMI subjects, or its side effect profile despite higher PRC in low BMI subjects. Regadenoson is better tolerated than adenosine but this benefit seems to lose statistical significance in subjects with BMI < 25 kg/m(2).

Decreasing resilience of kelp beds along a latitudinal temperature gradient: potential implications for a warmer future.

Successful mitigation of negative effects of global warming will depend on understanding the link between physiological and ecological responses of key species. We show that while metabolic adjustment may assist Australasian kelp beds to persist and maintain abundance in warmer waters, it also reduces the physiological responsiveness of kelps to perturbation, and suppresses canopy recovery from disturbances by reducing the ecological performance of kelp recruits. This provides a warning not to rely solely on inventories of distribution and abundance to evaluate ecosystem function. The erosion of resilience is mediated by a shift in adult-juvenile interactions from competitive under cool to facilitative under warm conditions, supporting the prediction that positive interactions may become increasingly important in a warmer future. Kelp beds may remain intact but with a lower threshold for where additional impacts (e.g., extreme storms or reduced water quality) will lead to persistent loss of habitat and ecological function.

Pharmacokinetic, pharmacodynamic, and electrocardiographic effects of dapoxetine and moxifloxacin compared with placebo in healthy adult male subjects.

Selective serotonin reuptake inhibitors (SSRIs) may be associated with electrocardiographic effects. The electrocardiographic pharmacodynamics of dapoxetine, a short-acting SSRI being developed for the treatment of premature ejaculation, are compared with those of placebo and moxifloxacin (positive control) in 2 single-center, randomized, crossover studies in healthy men. In study 1, subjects receive 2 doses of dapoxetine 120 mg, given 3 hours apart; a single dose of moxifloxacin 400 mg; and 2 doses of placebo, given 3 hours apart. In study 2, subjects receive single doses of dapoxetine 60 mg, dapoxetine 120 mg, moxifloxacin 400 mg, and placebo. Moxifloxacin significantly increases QT and corrects QT intervals (QTc) compared with placebo in both studies (eg, Bazett-corrected QTc of 11.90 milliseconds [95% confidence interval, 2.68 to 21.11] and 5.06 [95% confidence interval, -2.26 to 12.38]). Dapoxetine 60, 120, and 240 mg do not prolong the QT/QTc interval and have no clinically significant electrocardiographic effects. Dapoxetine and moxifloxacin pharmacokinetics are similar to previous reports. Adverse events are generally mild in severity; nausea is the most common. The results demonstrate that dapoxetine does not have electrocardiographic effects at doses of 60, 120, and 240 mg.

Adoption and consequences of new light-fishing technology (LEDs) on Lake Tanganyika, East Africa.

Maintaining sustainable fisheries requires understanding the influence of technological advances on catch efficiency, as technological creep can ultimately contribute to increased efficiency. Fisheries using light sources for attraction could be widely impacted by the shift to light emitting diode (LED) light systems. We studied the transition from kerosene lanterns to LED lamps in Lake Tanganyika, East Africa, examining factors that led to adoption as well as the impact of the new light sources on fish catch and composition. We used a combination of field experiments with catch assessments, fisher surveys, underwater light spectra measurements, and cost assessments to evaluate the impact of switching from kerosene to LED lamps. Overall, we found a very rapid rate of adoption of homemade outdoor LED light systems in Lake Tanganyika. Most of the batteries used to power these lamps were charged from the city power grid, rather than photovoltaic cells, although the potential exists for a reduction in greenhouse gas emissions. The LED light spectra was distinct from the kerosene light and penetrated much deeper into the water column. Regardless of light type, most of the fish caught within the two dominant species were below maturity. Although the LED lamps were associated with a slight increase in catch, environmental factors, particularly distance offshore, were generally more important in determining fish catch size and composition. The main advantages of the LED lamps were the lower operating costs and their robustness in bad weather. Thus, the primary effect of the use of battery-powered LED lighting systems to attract fish in Lake Tanganyika appears to reduce economic costs and increasing efficiency. However, overall the lake's fishery remains vulnerable to overfishing.