Although contemporary fire regimes in fire-prone Australian savannas are recognised as having major impacts on an array of biodiversity and environmental values, a number of studies have observed ...significant monsoon rainforest expansion in recent decades. Here we assess the status of a locally extensive endemic monsoon rainforest type, dominated by Allosyncarpia ternata (Myrtaceae), restricted to sandstone terrain including in the World Heritage property, Kakadu National Park. We undertook assessments of: (1) geographic correlates of Allosyncarpia forest distribution; (2) change in canopy cover at 40 representative forest patches at topographically exposed sites with reference to a 60-year aerial photo and fine-scale image archive, and fire mapping data; and (3) structural characteristics associated with sites exhibiting stable, contracting, and increasing canopy cover. Mean canopy cover at sampled forest patches declined by 9.5% over the study period. Most canopy loss occurred at the most fire-susceptible patches. Assessment of structural characteristics at sampled sites illustrated that canopy expansion represented vegetative recovery rather than expansion de novo. The study (1) confirms the vulnerability of exposed margins of this forest type to fire incursions; (2) illustrates the magnitude of, and describes solutions for addressing, the regional conservation management challenge; and (3) serves as a reminder that, in savanna environments, severe fire regimes can substantially outweigh the woody growth-enhancing effects of other regional (e.g., increased rainfall) and global-scale (e.g., atmospheric CO2 fertilisation) drivers.
In the context of Australia's developing carbon economy, fire management helps to abate emissions of greenhouse gases and is an important means of generating carbon credits. The vast high-rainfall ...savannas of northern Australia are one of the world's most flammable landscapes. Management of fires in this region has the potential to assist with meeting emissions reduction targets, as well as conserving biodiversity and providing employment for Indigenous people in remote parts of Australia's north. This comprehensive volume brings together recent research from northern Australian savannas to provide an internationally relevant case study for applying greenhouse gas accounting methodologies to the practice of fire management. It provides scientific arguments for enlarging the area of fire- prone land managed for emissions abatement. The book also charts the progress towards development of a savanna fire bio-sequestration methodology. The future of integrated approaches to emissions abatement and bio-sequestration is also discussed.
The 2015 European Society of Cardiology/European Respiratory Society treatment guidelines recommend frequent risk assessment in pulmonary arterial hypertension utilizing risk variables. Our ...objectives were: (1) to investigate the impact of inhaled treprostinil on risk stratification using the French noninvasive approach and REVEAL 2.0, and (2) to analyze the prognostic utility of both risk stratification methods in the predominantly New York Heart Association/World Health Organization functional class III/IV cohorts of TRIUMPH and BEAT. A post hoc analysis was performed to assess risk at baseline and follow-up at Week 12 in the TRIUMPH cohort (n = 148) and at Week 16, 21, and 30 in the inhaled treprostinil naïve placebo BEAT cohort (n = 73). Overall survival, clinical worsening-free survival, and pulmonary arterial hypertension-related hospitalization-free survival were all assessed in the pooled TRIUMPH and inhaled treprostinil naïve placebo BEAT cohorts based on risk group/strata at Week 12/16 follow-up. Inhaled treprostinil improved REVEAL 2.0 risk stratum (OR: 2.38, 95% CI: 1.09–5.19, p = 0.0298) and REVEAL 2.0 score (p = 0.0008) compared to placebo in the TRIUMPH cohort at Week 12. REVEAL 2.0 risk stratum and the number of low-risk criteria by the French approach improved at Weeks 16, 21, and 30 in the inhaled treprostinil naïve placebo BEAT cohort. Combining cohorts, REVEAL 2.0 risk stratification at follow-up was prognostic for clinical worsening-free, pulmonary arterial hypertension hospitalization-free, and overall survival, whereas the number of low-risk criteria was not. These post-hoc pooled analyses suggest inhaled treprostinil improves risk status and indicates that the REVEAL 2.0 calculator may be more suitable than the French noninvasive method for evaluating short-term clinical change in the New York Heart Association/World Health Organization functional class III/IV population.
Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest ...in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of nerve agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerve agent poisoning.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The hydrology of near‐surface glacier ice remains a neglected aspect of glacier hydrology despite its role in modulating meltwater delivery to downstream environments. To elucidate the hydrological ...characteristics of this near‐surface glacial weathering crust, we describe the design and operation of a capacitance‐based piezometer that enables rapid, economical deployment across multiple sites and provides an accurate, high‐resolution record of near‐surface water‐level fluctuations. Piezometers were employed at 10 northern hemisphere glaciers, and through the application of standard bail–recharge techniques, we derive hydraulic conductivity (K) values from 0.003 to 3.519 m day−1, with a mean of 0.185 ± 0.019 m day−1. These results are comparable to those obtained in other discrete studies of glacier near‐surface ice, and for firn, and indicate that the weathering crust represents a hydrologically inefficient aquifer. Hydraulic conductivity correlated positively with water table height but negatively with altitude and cumulative short‐wave radiation since the last synoptic period of either negative air temperatures or turbulent energy flux dominance. The large range of K observed suggests complex interactions between meteorological influences and differences arising from variability in ice structure and crystallography. Our data demonstrate a greater complexity of near‐surface ice hydrology than hitherto appreciated and support the notion that the weathering crust can regulate the supraglacial discharge response to melt production. The conductivities reported here, coupled with typical supraglacial channel spacing, suggest that meltwater can be retained within the weathering crust for at least several days. Not only does this have implications for the accuracy of predictive meltwater run‐off models, but we also argue for biogeochemical processes and transfers that are strongly conditioned by water residence time and the efficacy of the cascade of sediments, impurities, microbes, and nutrients to downstream ecosystems. Because continued atmospheric warming will incur rising snowline elevations and glacier thinning, the supraglacial hydrological system may assume greater importance in many mountainous regions, and consequently, detailing weathering crust hydraulics represents a research priority because the flow path it represents remains poorly constrained.
Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with ...the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex with the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the P(R) enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the P(S) isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic P(S) isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification.
BackgroundMethamphetamine is a growing drug of abuse in America. Patients with recent methamphetamine use pose potential complications to general anesthesia due to changes in hemodynamics and ...arrhythmias. Limited data exists on the incidence of intraoperative complications on methamphetamine-intoxicated patients requiring urgent or emergent trauma surgery. This study aims to describe intraoperative complications observed in methamphetamine and amphetamine-intoxicated patients requiring emergent surgery.MethodsUsing the Trauma Registry at our ACS-verified level I trauma center, we completed a single-center, descriptive, retrospective cohort review between July 1, 2012 and June 30, 2016, of adult patients requiring emergent surgery with a positive urine-drug screen for methamphetamines or amphetamines. The objective was to evaluate vasopressor utilization during surgical operation.ResultsA total of 92 patients were identified with a positive UDS for amphetamine and/or methamphetamine who went to the operating room within 24 hours of admission. Thirty-two (34%) patients received one or more (≥1) doses of vasopressor, while 60 patients (66%) received no vasopressor. Changes in mean arterial pressure (MAP) were noted in 64%, while only 3% experienced an EKG change. A binomial logistic regression showed age, base deficit and change in MAP to be predictive of vasopressor use (p<0.002). No intraoperative cardiac events or anesthetic complications were seen.DiscussionHemodynamic instability in the amphetamine and methamphetamine-intoxicated population may be more directly related to degree of resuscitation required, than the presence of a positive UDS.Level of evidenceIV
Valid and reliable biomarkers can play an important role in clinical trials as indicators of biological or pathogenic processes or as a signal of treatment response. Currently, there are no ...biomarkers for pain qualified by the U.S. Food and Drug Administration or the European Medicines Agency for use in clinical trials. This article summarizes an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting in which 3 potential biomarkers were discussed for use in the development of analgesic treatments: 1) sensory testing, 2) skin punch biopsy, and 3) brain imaging. The empirical evidence supporting the use of these tests is described within the context of the 4 categories of biomarkers: 1) diagnostic, 2) prognostic, 3) predictive, and 4) pharmacodynamic. Although sensory testing, skin punch biopsy, and brain imaging are promising tools for pain in clinical trials, additional evidence is needed to further support and standardize these tests for use as biomarkers in pain clinical trials.
The applicability of sensory testing, skin biopsy, and brain imaging as diagnostic, prognostic, predictive, and pharmacodynamic biomarkers for use in analgesic treatment trials is considered. Evidence in support of their use and outlining problems is presented, as well as a call for further standardization and demonstrations of validity and reliability.
Savannas are the most fire-prone of the earth's major biomes. The availability of various broad-scale satellite-derived fire mapping and regional datasets provides a framework with which to examine ...the seasonality, extent and implications of large fires with particular reference to biodiversity values in the tropical savannas of northern Australia. We document the significance of savanna fires in the fire-prone 'Top End' region of the Northern Territory, Australia, using 9 years (1997-2005) of National Oceanic and Atmospheric Administration (NOAA)-Advanced Very High Resolution Radiometer (AVHRR)-, Landsat Thematic Mapper (TM)- and Enhanced Thematic Mapper (ETM+)-derived fire mapping. Fire (patch) sizes from both AVHRR- and Landsat-scale mapping increased through the calendar year associated with progressive curing of grass and litter fuels. Fire frequency data at both satellite sensor scales indicate that regional fire regimes in higher rainfall regions are dominated by large (>1000 km²) fires occurring typically at short (~2-3 years) fire return intervals. In discussion, we consider the ecological implications of these patch size distributions on regional fire-sensitive biota. Collectively, assembled data illustrate that many northern Australian savanna flora, fauna and habitats embedded within the savanna matrix are vulnerable to extensive and frequent fires, especially longer-lived obligate seeder plant taxa and relatively immobile vertebrate fauna with small home ranges.
Background
The success of coronary artery bypass grafting surgery (CABG) is dependent on long‐term graft patency, which is negatively related to early wall thickening. Avoiding high‐pressure ...distension testing for leaks and preserving the surrounding pedicle of fat and adventitia during vein harvesting may reduce wall thickening.
Methods
A single‐centre, factorial randomized controlled trial was carried out to compare the impact of testing for leaks under high versus low pressure and harvesting the vein with versus without the pedicle in patients undergoing CABG. The primary outcomes were graft wall thickness, as indicator of medial‐intimal hyperplasia, and lumen diameter assessed using intravascular ultrasound after 12 months.
Results
Ninety‐six eligible participants were recruited. With conventional harvest, low‐pressure testing tended to yield a thinner vessel wall compared with high‐pressure (mean difference MD; low minus high −0.059 mm, 95% confidence interval (CI) −0.12, +0.0039, p = .066). With high pressure testing, veins harvested with the pedicle fat tended to have a thinner vessel wall than those harvested conventionally (MD pedicle minus conventional −0.057 mm, 95% CI: −0.12, +0.0037, p = .066, test for interaction p = .07). Lumen diameter was similar across groups (harvest comparison p = .81; pressure comparison p = .24). Low‐pressure testing was associated with fewer hospital admissions in the 12 months following surgery (p = .0008). Harvesting the vein with the pedicle fat was associated with more complications during the index admission (p = .0041).
Conclusions
Conventional saphenous vein graft preparation with low‐pressure distension and harvesting the vein with a surrounding pedicle yielded similar graft wall thickness after 12 months, but low pressure was associated with fewer adverse events.
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