•We model Eisenia fetida populations using an agent-based framework.•Individual energy budgets follow the basic principles of physiological ecology.•Methods are developed to show how chemicals ...achieve their physiological effects.•The model realistically captures sublethal effects under variable feeding conditions.•Energy budget ABMs have potential for refining chemical risk assessment.
Earthworms are important organisms in soil communities and so are used as model organisms in environmental risk assessments of chemicals. However current risk assessments of soil invertebrates are based on short-term laboratory studies, of limited ecological relevance, supplemented if necessary by site-specific field trials, which sometimes are challenging to apply across the whole agricultural landscape. Here, we investigate whether population responses to environmental stressors and pesticide exposure can be accurately predicted by combining energy budget and agent-based models (ABMs), based on knowledge of how individuals respond to their local circumstances. A simple energy budget model was implemented within each earthworm Eisenia fetida in the ABM, based on a priori parameter estimates. From broadly accepted physiological principles, simple algorithms specify how energy acquisition and expenditure drive life cycle processes. Each individual allocates energy between maintenance, growth and/or reproduction under varying conditions of food density, soil temperature and soil moisture. When simulating published experiments, good model fits were obtained to experimental data on individual growth, reproduction and starvation. Using the energy budget model as a platform we developed methods to identify which of the physiological parameters in the energy budget model (rates of ingestion, maintenance, growth or reproduction) are primarily affected by pesticide applications, producing four hypotheses about how toxicity acts. We tested these hypotheses by comparing model outputs with published toxicity data on the effects of copper oxychloride and chlorpyrifos on E. fetida. Both growth and reproduction were directly affected in experiments in which sufficient food was provided, whilst maintenance was targeted under food limitation. Although we only incorporate toxic effects at the individual level we show how ABMs can readily extrapolate to larger scales by providing good model fits to field population data. The ability of the presented model to fit the available field and laboratory data for E. fetida demonstrates the promise of the agent-based approach in ecology, by showing how biological knowledge can be used to make ecological inferences. Further work is required to extend the approach to populations of more ecologically relevant species studied at the field scale. Such a model could help extrapolate from laboratory to field conditions and from one set of field conditions to another or from species to species.
Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is that the analgesic effect lasts ...only a few hours, after which moderate to severe pain at the surgical site may result in the need for alternative analgesic therapy. Several adjuvants have been used to prolong the analgesic duration of peripheral nerve block, including perineural or intravenous dexamethasone.
To evaluate the comparative efficacy and safety of perineural dexamethasone versus placebo, intravenous dexamethasone versus placebo, and perineural dexamethasone versus intravenous dexamethasone when added to peripheral nerve block for postoperative pain control in people undergoing surgery.
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, DARE, Web of Science and Scopus from inception to 25 April 2017. We also searched trial registry databases, Google Scholar and meeting abstracts from the American Society of Anesthesiologists, the Canadian Anesthesiologists' Society, the American Society of Regional Anesthesia, and the European Society of Regional Anaesthesia.
We included all randomized controlled trials (RCTs) comparing perineural dexamethasone with placebo, intravenous dexamethasone with placebo, or perineural dexamethasone with intravenous dexamethasone in participants receiving peripheral nerve block for upper or lower limb surgery.
We used standard methodological procedures expected by Cochrane.
We included 35 trials of 2702 participants aged 15 to 78 years; 33 studies enrolled participants undergoing upper limb surgery and two undergoing lower limb surgery. Risk of bias was low in 13 studies and high/unclear in 22. Perineural dexamethasone versus placeboDuration of sensory block was significantly longer in the perineural dexamethasone group compared with placebo (mean difference (MD) 6.70 hours, 95% confidence interval (CI) 5.54 to 7.85; participants1625; studies 27). Postoperative pain intensity at 12 and 24 hours was significantly lower in the perineural dexamethasone group compared with control (MD -2.08, 95% CI -2.63 to -1.53; participants 257; studies 5) and (MD -1.63, 95% CI -2.34 to -0.93; participants 469; studies 9), respectively. There was no significant difference at 48 hours (MD -0.61, 95% CI -1.24 to 0.03; participants 296; studies 4). The quality of evidence is very low for postoperative pain intensity at 12 hours and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the perineural dexamethasone group compared with placebo (MD 19.25 mg, 95% CI 5.99 to 32.51; participants 380; studies 6). Intravenous dexamethasone versus placeboDuration of sensory block was significantly longer in the intravenous dexamethasone group compared with placebo (MD 6.21, 95% CI 3.53 to 8.88; participants 499; studies 8). Postoperative pain intensity at 12 and 24 hours was significantly lower in the intravenous dexamethasone group compared with placebo (MD -1.24, 95% CI -2.44 to -0.04; participants 162; studies 3) and (MD -1.26, 95% CI -2.23 to -0.29; participants 257; studies 5), respectively. There was no significant difference at 48 hours (MD -0.21, 95% CI -0.83 to 0.41; participants 172; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the intravenous dexamethasone group compared with placebo (MD -6.58 mg, 95% CI -10.56 to -2.60; participants 287; studies 5). Perinerual versus intravenous dexamethasoneDuration of sensory block was significantly longer in the perineural dexamethasone group compared with intravenous by three hours (MD 3.14 hours, 95% CI 1.68 to 4.59; participants 720; studies 9). We found that postoperative pain intensity at 12 hours and 24 hours was significantly lower in the perineural dexamethasone group compared with intravenous, however, the MD did not surpass our pre-determined minimally important difference of 1.2 on the Visual Analgue Scale/Numerical Rating Scale, therefore the results are not clinically significant (MD -1.01, 95% CI -1.51 to -0.50; participants 217; studies 3) and (MD -0.77, 95% CI -1.47 to -0.08; participants 309; studies 5), respectively. There was no significant difference in severity of postoperative pain at 48 hours (MD 0.13, 95% CI -0.35 to 0.61; participants 227; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. There was no difference in cumulative postoperative 24-hour opioid consumption (MD -3.87 mg, 95% CI -9.93 to 2.19; participants 242; studies 4). Incidence of severe adverse eventsFive serious adverse events were reported. One block-related event (pneumothorax) occurred in one participant in a trial comparing perineural dexamethasone and placebo; however group allocation was not reported. Four non-block-related events occurred in two trials comparing perineural dexamethasone, intravenous dexamethasone and placebo. Two participants in the placebo group required hospitalization within one week of surgery; one for a fall and one for a bowel infection. One participant in the placebo group developed Complex Regional Pain Syndrome Type I and one in the intravenous dexamethasone group developed pneumonia. The quality of evidence is very low due to the sparse number of events.
Low- to moderate-quality evidence suggests that when used as an adjuvant to peripheral nerve block in upper limb surgery, both perineural and intravenous dexamethasone may prolong duration of sensory block and are effective in reducing postoperative pain intensity and opioid consumption. There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not apply to participants at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe.There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not be apply to participants who at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe. The nine ongoing trials registered at ClinicalTrials.gov may change the results of this review.
The marine environment is being increasingly modified by the construction of artificial structures, the impacts of which may be mitigated through eco-engineering. To date, eco-engineering has ...predominantly aimed to increase biodiversity, but enhancing other ecological functions is arguably of equal importance for artificial structures. Here, we manipulated complexity through habitat structure (flat, and 2.5 cm, 5 cm deep vertical and 5 cm deep horizontal crevices) and seeding with the native oyster (Saccostrea glomerata, unseeded and seeded) on concrete tiles (0.25 m × 0.25 m) affixed to seawalls to investigate whether complexity (both orientation and depth of crevices) influences particle removal rates by suspension feeders and colonisation by different functional groups, and whether there are any ecological trade-offs between these functions. After 12 months, complex seeded tiles generally supported a greater abundance of suspension feeding taxa and had higher particle removal rates than flat tiles or unseeded tiles. The richness and diversity of taxa also increased with complexity. The effect of seeding was, however, generally weaker on tiles with complex habitat structure. However, the orientation of habitat complexity and the depth of the crevices did not influence particle removal rates or colonising taxa. Colonisation by non-native taxa was low compared to total taxa richness. We did not detect negative ecological trade-offs between increased particle removal rates and diversity and abundance of key functional groups. Our results suggest that the addition of complexity to marine artificial structures could potentially be used to enhance both biodiversity and particle removal rates. Consequently, complexity should be incorporated into future eco-engineering projects to provide a range of ecological functions in urbanised estuaries.
•Eco-engineering of seawalls often focuses on enhancement of biodiversity.•We manipulated seawall complexity to enhance other ecological functions.•Increased habitat structure and bivalve seeding enhanced particle removal rates.•Habitat structure did not facilitate non-native over native species.•Multifunctional eco-engineering is possible without negative ecological trade-offs.
Abstract
We have acquired radio-continuum data between 70 MHz and 48 GHz for a sample of 19 southern starburst galaxies at moderate redshifts (0.067 < z < 0.227) with the aim of separating ...synchrotron and free–free emission components. Using a Bayesian framework, we find the radio continuum is rarely characterized well by a single power law, instead often exhibiting low-frequency turnovers below 500 MHz, steepening at mid to high frequencies, and a flattening at high frequencies where free–free emission begins to dominate over the synchrotron emission. These higher order curvature components may be attributed to free–free absorption across multiple regions of star formation with varying optical depths. The decomposed synchrotron and free–free emission components in our sample of galaxies form strong correlations with the total-infrared bolometric luminosities. Finally, we find that without accounting for free–free absorption with turnovers between 90 and 500 MHz the radio continuum at low frequency (ν < 200 MHz) could be overestimated by upwards of a factor of 12 if a simple power-law extrapolation is used from higher frequencies. The mean synchrotron spectral index of our sample is constrained to be α = −1.06, which is steeper than the canonical value of −0.8 for normal galaxies. We suggest this may be caused by an intrinsically steeper cosmic ray distribution.
ABSTRACT
While pulsars possess exceptional rotational stability, large-scale timing studies have revealed at least two distinct types of irregularities in their rotation: red timing noise and ...glitches. Using modern Bayesian techniques, we investigated the timing noise properties of 300 bright southern-sky radio pulsars that have been observed over 1.0–4.8 yr by the upgraded Molonglo Observatory Synthesis Telescope (MOST). We reanalysed the spin and spin-down changes associated with nine previously reported pulsar glitches, report the discovery of three new glitches and four unusual glitch-like events in the rotational evolution of PSR J1825−0935. We develop a refined Bayesian framework for determining how red noise strength scales with pulsar spin frequency (ν) and spin-down frequency ($\dot{\nu }$), which we apply to a sample of 280 non-recycled pulsars. With this new method and a simple power-law scaling relation, we show that red noise strength scales across the non-recycled pulsar population as $\nu ^{a} |\dot{\nu }|^{b}$, where $a = -0.84^{+0.47}_{-0.49}$ and $b = 0.97^{+0.16}_{-0.19}$. This method can be easily adapted to utilize more complex, astrophysically motivated red noise models. Lastly, we highlight our timing of the double neutron star PSR J0737−3039, and the rediscovery of a bright radio pulsar originally found during the first Molonglo pulsar surveys with an incorrectly catalogued position.
Changes in seasonal climate patterns and decreasing sea ice cover have facilitated an increase in navigable waters throughout Arctic Canada and resulted in the urgent need for new approaches to ...ocean, coastal, and vessel management. Increased access has resulted in a significant expansion of Arctic shipping activity over the past decade with one of the fastest growing sectors being expedition cruising. This paper presents an assessment of the existing marine regulations and governance structures that manage the cruise sector in Arctic Canada and provides a critical evaluation of its effectiveness considering recent and rapid growth. Using a variety of sources, including interviews with community residents and key informant stakeholders, analysis of changing ship volumes over the past decade, and an inventory of institutional governance for the sector, the major governance challenges for the industry were identified. Also identified are potential strategies for mitigating these challenges. Results of the analysis raise concerns that there is no central authority to govern the growth of the industry, no specific sector or operator management plan, and no site guidelines for highly visited shore locations (other than in protected areas). Instead, governance occurs within the complex multi-jurisdictional regulatory frameworks that exist for all shipping in the region. The paper concludes that under current conditions there are significant barriers to supporting development of this sector while avoiding human, environmental and security problems in the near-to medium-term future.
•The cruise industry in Arctic Canada has grown by over 115% between 2005 and 2013.•Climate change and a reduction of sea ice have increased accessibility to the region.•Many governance challenges exist in managing cruise industry development.•Potential strategies to address current governance challenges are outlined.
Summary
Background
Bile acid diarrhoea is a common cause of chronic diarrhoea, occurring as a primary condition or secondary to ileal disease or resection. Many patients have reduced levels of the ...ileal hormone fibroblast growth factor 19 (FGF19), an inhibitory regulator of hepatic bile acid synthesis, secreted in response to farnesoid X receptor (FXR) activation.
Aim
To investigate whether obeticholic acid, a potent FXR agonist, could increase FGF19 in patients with bile acid diarrhoea, and produce clinical benefits.
Methods
After a 2 week run‐in when bile acid sequestrants were discontinued, patients with previously diagnosed primary bile acid diarrhoea (n = 10), secondary bile acid diarrhoea (n = 10) or idiopathic chronic diarrhoea (n = 8), received oral obeticholic acid 25 mg daily for 2 weeks. Serum FGF19, total bile acids and 7α‐OH‐4‐cholesten‐3‐one (C4) were measured, symptoms recorded and a diarrhoea index calculated.
Results
In primary bile acid diarrhoea, obeticholic acid increased median fasting FGF19 (133–237 pg/mL, P = 0.007) and significantly reduced fasting C4 and bile acid responses. Improvements occurred in median stool frequency (−24% after 2 weeks treatment, P = 0.03), stool form (−14%, P = 0.05) and diarrhoea index (−34%, P = 0.005). In the secondary bile acid diarrhoea group, significant clinical improvements were found predominantly in patients with shorter ileal resections. Symptoms of abdominal pain and urgency improved. FGF19 and bile acids changed in the control group, without significant clinical improvement. Total and LDL‐cholesterol increased and triglycerides decreased. Obeticholic acid treatment was well tolerated.
Conclusions
This proof‐of‐concept study indicates that obeticholic acid stimulates FGF19, reduces bile acid synthesis and produces clinical benefits in bile acid diarrhoea. FXR agonists have therapeutic potential in chronic diarrhoea. EudraCT 2011‐003777‐28; Clinical Trials: NCT01585025
A pH-driven DNA nanomachine based on the human α-thrombin binding aptamer was designed for the specific catch-and-release of human α-thrombin at neutral and acidic pH, respectively. In neutral ...conditions, the thrombin aptamer component of the nanomachine is exposed and exists in the G-quadruplex conformation required to bind to the target protein. At slightly acidic pH, the polyadenine tail of the nanomachine becomes partially protonated and A+(anti)•G(syn) mispairing results in a conformational change, causing the target protein to be released. Förster resonance energy transfer (FRET) was used to monitor conformational switching over multiple pH cycles. Electrophoretic mobility shift assay (EMSA) and fluorescence anisotropy were used to show pH dependent protein binding and release by the nanomachine. This approach could be applied generally to existing G-rich aptamers to develop novel biosensors, theranostics, and nanoswitches.
We searched for radio pulsars in 25 of the non-variable, unassociated sources in the Fermi LAT Bright Source List with the Green Bank Telescope at 820 MHz. We report the discovery of three radio and ...Delta *g-ray millisecond pulsars (MSPs) from a high Galactic latitude subset of these sources. All of the pulsars are in binary systems, which would have made them virtually impossible to detect in blind Delta *g-ray pulsation searches. They seem to be relatively normal, nearby (<=2 kpc) MSPs. These observations, in combination with the Fermi detection of Delta *g-rays from other known radio MSPs, imply that most, if not all, radio MSPs are efficient Delta *g-ray producers. The Delta *g-ray spectra of the pulsars are power law in nature with exponential cutoffs at a few GeV, as has been found with most other pulsars. The MSPs have all been detected as X-ray point sources. Their soft X-ray luminosities of ~1030-1031 erg s--1 are typical of the rare radio MSPs seen in X-rays.
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