Editorial

No aspect of the practice of pediatric anesthesia is more essential than airway management. Pediatric anesthesiologists are the ‘go to’ specialists when infants and children with difficult airways present anywhere in the hospital. To our advantage, rapid technical advances have taken place during the past decades and the number of tools available to assist us in providing and maintaining a secure and stable airway has increased significantly. Until the 1970s tracheal intubation with a conventional laryngoscope or blind nasal intubation were the mainstays of establishing an artificial airway. The choice of endotracheal tubes was limited. During the past 20 years a remarkable assortment of equipment and novel techniques to facilitate optimal airway management have been developed. These include supraglottic airways, direct and fiberoptic laryngoscopes and transtracheal devices. Improved imaging of the airway prior to initiation of airway management, with CT and MRI, for example, and during airway manipulation and instrumentation, using fiberoptic cameras and portable video displays, is now widely used. While new developments in airway management have helped us improve the quality of care of our patients, new challenges have also arisen. Which techniques should we learn, teach and employ? Which endotracheal tubes should be utilized – uncuffed or cuffed, old or new design? Which of our patients need preoperative imaging of the airway and/or sleep studies? What are the risks of newer interventions, including novel airway devices and laser instruments

ATHENA: A Phase 3, Open-Label Study Of The Safety And Effectiveness Of Oliceridine (TRV130), A G-Protein Selective Agonist At The µ-Opioid Receptor, In Patients With Moderate To Severe Acute Pain Requiring Parenteral Opioid Therapy.

Background:Pain management with conventional opioids can be challenging due to dose-limiting adverse events (AEs), some of which may be related to the simultaneous activation of β-arrestin (a signaling pathway associated with opioid-related AEs) and G-protein pathways. The investigational analgesic oliceridine is a G-protein-selective agonist at the µ-opioid receptor with less recruitment of β-arrestin. The objective of this phase 3, open-label, multi-center study was to evaluate the safety and tolerability, of IV oliceridine for moderate to severe acute pain in a broad, real-world patient population, including postoperative surgical patients and non-surgical patients with painful medical conditions. Methods:Adult patients with a score ≥4 on 11-point NRS for pain intensity received IV oliceridine either by bolus or PCA; multimodal analgesia was permitted. Safety was assessed using AE reports, study discontinuations, clinical laboratory and vital sign measures. Results:A total of 768 patients received oliceridine. The mean age (SD) was 54.1 (16.1) years, with 32% ≥65 years of age. Most patients were female (65%) and Caucasian (78%). Surgical patients comprised the majority of the study population (94%), most common being orthopedic (30%), colorectal (15%) or gynecologic (15%) procedures. Multimodal analgesia was administered to 84% of patients. Oliceridine provided a rapid reduction in NRS pain score by 2.2 ± 2.3 at 30 mins from a score of 6.3 ± 2.1 (at baseline) which was maintained to the end of treatment. No deaths or significant cardiorespiratory events were reported. The incidence of AEs leading to early discontinuation and serious AEs were 2% and 3%, respectively. Nausea (31%), constipation (11%), and vomiting (10%) were the most common AEs. AEs were mostly of mild (37%) or moderate (25%) severity and considered possibly or probably related to oliceridine in 33% of patients. Conclusion:Oliceridine IV for the management of moderate to severe acute pain was generally safe and well tolerated in the patients studied. ClinicalTrialsgov identifier:NCT02656875

Dissecting and modelling the comparative adaptation to water limitation of sorghum and maize: role of transpiration efficiency, transpiration rate and height

Maize is considered less drought-tolerant than sorghum, but sorghum is commonly grown as a short triple dwarf (3dwarf) type, so difference in plant height confounds the species comparison. The objectives of this study were to experimentally determine effects of species and plant height differences on transpiration efficiency (TE) and transpiration rate per unit green leaf area (TGLA) and use findings to explain input parameters in a simulation study on the comparative adaptation of 3dwarf sorghum and maize in environments with contrasting water availability. Maize, tall double dwarf (2dwarf) and short 3dwarf sorghum genotypes were grown in two lysimeter experiments in 2011 in SE Queensland, Australia. Each plant was harvested after anthesis and total transpiration, shoot and root dry mass were measured to estimate TE. Daily TGLA was used to compare transpiration rates. Species and height had limited effect on TE, but significantly affected TGLA. This was associated with differences in biomass allocation. The similar TE but higher TGLA in maize compared with 3dwarf sorghum meant it potentially produces more biomass, consistent with published differences in biomass accumulation and radiation use efficiency (RUE). The simulation study, which used similar TE for maize and 3dwarf sorghum, but captured differences in TGLA through differences in RUE, predicted crossover interactions for grain yield between species and total water use. The greater TGLA of maize decreased grain yield in water-limited environments, but increased yields in well-watered situations. Results highlight that similarity in TE and differences in TGLA can influence comparative adaptation to water limitation

Wildland-urban interface maps vary with purpose and context

Maps of the Wildland-Urban Interface (WUI) are both pragmatic policy tools and powerful visual images with broad appeal. While the growing number of WUI maps serve the same general purpose, this paper demonstrates that WUI maps based on the same data can differ in ways related to their purpose, and discusses the use of ancillary data in modifying census data. A comparison of two methods suggests GIS methods used for mapping the WUI be tailored to specific questions. Dasymetric mapping to improve census data precision is useful but dependent on data quality, and land ownership datasets suffer problems that argue for caution in their use. No single mapping approach is “best,” and analysts must be clear about the problem addressed, the methods used, and data quality. These considerations should apply to any analysis, but are especially important to analyses of the WUI upon which public-sector decisions will be made

Pharmacy Refill Adherence Compared with CD4 Count Changes for Monitoring HIV-Infected Adults on Antiretroviral Therapy

Analyzing pharmacy and laboratory records from 1,982 patients beginning HIV therapy in southern Africa, Gregory Bisson and colleagues find medication adherence superior to CD4 count changes in identifying treatment failure

Pharmacokinetics and pharmacodynamics of fenoldopam mesylate for blood pressure control in pediatric patients

<p>Abstract</p> <p>Background</p> <p>Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children.</p> <p>Methods</p> <p>Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints.</p> <p>Results</p> <p>Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0–1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined.</p> <p>Conclusion</p> <p>Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8–1.2 mcg/kg/min) than as labeled for adults (0.05–0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar.</p

Catching the future : Applying Bayesian belief networks to exploratory scenario storylines to assess long‐term changes in Baltic herring (Clupea harengus membras, Clupeidae) and salmon (Salmo salar, Salmonidae) fisheries

Fisheries management aims to ensure that the fishing activities are environmentally sustainable in the long term, while also achieving the economic, social and food security related management objectives. To facilitate this, both the ecological and human dimensions of sustainability need to be included in fisheries assessment. In addition, assessing long-term sustainability calls for taking into account plausible changes in the surrounding societal conditions that shape the characteristics of the fisheries governance system, as well as the ecological conditions. The paper uses a combination of qualitative exploratory scenario storylines (ESS) and Bayesian belief networks (BBN) to integrate the environmental, economic, social and food security dimensions in an interdisciplinary assessment of the future sustainability of Baltic herring (Clupea harengus membras, Clupeidae) and salmon (Salmo salar, Salmonidae) fisheries. First, four alternative ESS were created based on plausible changes in societal drivers. The ESS were then formulated into a BBN to (a) visualize the assumed causalities, and (b) examine quantitatively how changes in the societal drivers affect the social-ecological fisheries system and ultimately the fisheries management objectives. This type of probabilistic scenario synthesis can help in thinking qualitative scenarios in a quantitative way. Moreover, it can increase understanding on the causal links between societal driving forces and the complex fisheries system and on how the management objectives can be achieved, thereby providing valuable information for strategic decision-making under uncertainty.Peer reviewe

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure