Manure nutrient cycling in US animal agriculture basins-North Carolina case study.

Nutrient cycling in crop-animal production is impacted by changes in both systems, with imbalance hotspots in concentrated animal production regions severely impacting water quality. This study assesses manure-crop nutrient balances in five river basins in North Carolina and demonstrates a new approach for partial nutrient balances along hydrological boundaries. County-level crop production data were combined with crop-type spatial distribution data to derive spatially referenced nutrient uptake and removal. Similarly, spatially referred animal production inventory data were used to derive excreted and recovered manure nutrients. Partial nutrient balances were developed for both N and P in basins and hydrologic units. Excreted manure N and P were 139% and 159% of respective plant N and P removal at harvest across the five basins. Finer geographical scales revealed hotspots for manure surplus, particularly within the Cape Fear basin (up to 96% N and 97% P). Despite N hotspots, plant-available manure N met only 38% of crop N demand due to significant losses during storage. Plant-available manure P exceeded crop P removal by 54% over the entire area. Cape Fear showed the greatest P excess, 76% greater than crop removal. This study contributes to nutrient cycling improvements by connecting crop-animal nutrient budgets to hydrologic resources. Furthermore, we show the value of finer spatial scales to identify hotspots that play a significant role in nutrient losses. We conclude that nutrient-surplus basins require, in addition to manure nutrient conservation, a basin-wide redistribution and export strategies to address nutrient excesses and water quality impacts.

Beware the Unknown: Views on Genetic Technology in Conservation.

Artificial Gene Drive (GD) may offer a number of transformative impacts on society. Despite potential usage in the area of conservation, GD remains largely unfamiliar to the public and little is known about their views. In our study, participants from New Zealand were placed in groups based upon one of four worldviews. They had a brief free word association session before considering a concise, technical definition of GD and were asked to discuss their views. Overall, discussions made use of narrative devices that expressed caution and concern around large-scale technological intervention with the natural world. However, specific worldviews presented unique themes. While fears of human overstep causing uncontrollable feedback across wild species and environments were universally present, this differed according to the group's worldview. We conclude that conversations on such technologies, especially those relating to gene modification, provide insight into deep-rooted social, cultural and even metaphysical concerns that transcend the technology's stated purpose.

A Case of Acute Pulmonary Embolus after mRNA SARS-CoV-2 Immunization.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a critical strategy to overcome the COVID-19 pandemic. Multiple SARS-CoV-2 vaccines have been developed in a rapid timeframe to combat the pandemic. While generally safe and effective, rare cases of venous thromboembolism (VTE) have been reported after two adenovirus-based vaccines, the AstraZeneca ChAdOx1 nCoV-19 vaccine and the Janssen Ad.26.COV2.S vaccine, as well as after the Pfizer-BioNTech BNT162b2 mRNA vaccine. Here, we present the case of a patient who developed acute pulmonary emboli (PE) shortly after his second dose of the Moderna mRNA-1273 SARS-CoV-2 vaccine. We report the results of an extensive thrombophilia workup that was normal except for the identification of positive lupus anticoagulant (LA) signals. It is our goal to contribute to the body of knowledge regarding SARS-CoV-2 vaccines and encourage vaccine adverse event reporting so that clinicians can have a full appreciation and awareness of the possible adverse events related to these critical vaccines.

High spin-wave propagation length consistent with low damping in a metallic ferromagnet.

We report ultralow intrinsic magnetic damping in Co25Fe75 heterostructures, reaching the low 10-4 regime at room temperature. By using a broadband ferromagnetic resonance technique in out-of-plane geometry, we extracted the dynamic magnetic properties of several Co25Fe75-based heterostructures with varying ferromagnetic layer thicknesses. By measuring radiative damping and spin pumping effects, we found the intrinsic damping of a 26 nm thick sample to be α 0 ≲ 3.18 × 10-4. Furthermore, using Brillouin light scattering microscopy, we measured spin-wave propagation lengths of up to (21 ± 1) µm in a 26 nm thick Co25Fe75 heterostructure at room temperature, which is in excellent agreement with the measured damping.

Magnetoelasticity of Co25Fe75 thin films.

We investigate the magnetoelastic properties of Co25Fe75 and Co10Fe90 thin films by measuring the mechanical properties of a doubly clamped string resonator covered with multilayer stacks containing these films. For the magnetostrictive constants, we find λ Co25 Fe75 = (-20.68 ± 0.25) × 10-6 and λ Co10 Fe90 = (-9.80 ± 0.12) × 10-6 at room temperature, in contrast to the positive magnetostriction previously found in bulk CoFe crystals. Co25Fe75 thin films unite low damping and sizable magnetostriction and are thus a prime candidate for micromechanical magnonic applications, such as sensors and hybrid phonon-magnon systems.

Characterization of Uniformity in Nb/NbxSi1-x/Nb Josephson Junctions.

The uniformity of the barriers in Josephson junctions (JJs) is a critical parameter in determining performance and operating margins for a wide variety of superconducting electronic circuits. We present an automated measurement system capable of measuring individual JJs across a 1 × 1 cm die at both ambient temperature and 4 K. This technique allows visualization of the spatial variation over a large area of the critical electrical properties of the junctions and allows for the direct correlation between room-temperature (RT) resistance and low temperature properties. The critical current variation of NbxSi1-x (x = 15%) barriers is found to be about 2.6% (one standard deviation) for 1024 junctions across an individual die and only weakly correlates with RT resistance measurements.

The cost of addressing saline lake level decline and the potential for water conservation markets.

The world's saline lakes are shrinking and human water diversions are a significant contributor. While there is increased interest in protecting the ecosystem services provided by these lakes, the cost of protecting water levels has not been estimated. To explore this question we consider the case of Great Salt Lake (Utah, USA) where human diversions from three rivers have caused the lake level to decline during the last century. Recent work has suggested the restoration of inflows is necessary to maintain a target elevation consistent with well-functioning ecosystems. We construct cost estimates of increasing water inflows using conservation cost curves for each river basin. We then compare the cost of uniform cutbacks to cap-and-trade systems which allow intra- and inter-basin trading. The cost of water to permanently implement uniform water right cutbacks to increase inflows by 20% above current levels is $37.4 million. Costs and cost-savings are sensitive to alternative allocation, inflow, and cost assumptions, and we estimate significant cost reductions from intra-basin water conservation markets (5-54% cost decrease) and inter-basin water conservation markets (22-57% cost decrease).

Non-detection of honeybee hive contamination following Vespula wasp baiting with protein containing fipronil.

Introduced wasps (Vespula germanica and V. vulgaris) are costly invertebrate pests in New Zealand, with large impacts on the local ecology and economy. Wasps eat honeybees (Apis mellifera), which has potentially devastating effects on hive health, as well as agricultural and horticultural industries. Vespex bait, which contains fipronil in a proteinaceous carrier, has recently been introduced for wasp control. In over a decade of reported trials, honeybees have never been observed foraging on Vespex, likely because the bait contains no sugars to serve as a bee food source. However, the potential for the control agent fipronil to enter beehives has not been tested. Therefore, here, we investigated this using a liquid chromatography-mass spectrometry assay of fipronil and two of its environmental breakdown and metabolic derivatives, fipronil desulfinyl and fipronil sulfone. We did not detect fipronil in any of the worker bee, bee larva, honey or pollen samples (n = 120 per product) collected from 30 hives over a 2-year period. Furthermore, although we detected fipronil desulfinyl in one honeybee sample, this is thought to have originated from a single individual, representing a rare occurrence of intoxication, and there was no evidence that Vespex was the toxicant source. There was also no evidence of trophallactic transfer of fipronil or its derivatives in any of the hives sampled. Previous studies have reported the impairment of individual bee performance at fipronil doses similar to the detection limit of our study. However, our results provide confidence that if undetectable intoxication was occurring, it would involve an acute exposure for those few individuals affected, with minimal impairment to colonies. Therefore, we conclude that the use of Vespex in the vicinity of honeybees does not result in significant hive uptake while effectively reducing wasp pressure on honeybee colonies.

Observation of spin-orbit effects with spin rotation symmetry.

The spin-orbit interaction enables interconversion between a charge current and a spin current. It is usually believed that in a nonmagnetic metal (NM) or at a NM/ferromagnetic metal (FM) bilayer interface, the symmetry of spin-orbit effects requires that the spin current, charge current, and spin orientation are all orthogonal to each other. Here we demonstrate the presence of spin-orbit effects near the NM/FM interface that exhibit a very different symmetry, hereafter referred to as spin-rotation symmetry, from the conventional spin Hall effect while the spin polarization is rotating about the magnetization. These results imply that a perpendicularly polarized spin current can be generated with an in-plane charge current simply by use of a FM/NM bilayer with magnetization collinear to the charge current. The ability to generate a spin current with arbitrary polarization using typical magnetic materials will benefit the development of magnetic memories.Converting charge to spin currents using spin-orbit interactions has useful applications in spintronics but symmetry constraints can limit the control over spin polarization. Here the authors demonstrate spin-orbit effects with a different symmetry, which could help generate arbitrary spin polarizations.

Application of human factors engineering (HFE) to the design of a naloxone auto-injector for the treatment of opioid emergencies.

The increased use of opioids for chronic treatment of pain and the resulting epidemic of opioid overdoses have created a major public health challenge. Parenteral naloxone has been used since the 1970's to treat opioid overdose. Recently, a novel naloxone auto-injector device (EVZIO, kaleo, Inc., Richmond, VA) was approved by the Food and Drug Administration. In this article, we review the Human Factors Engineering (HFE) process used in the development and testing of this novel naloxone auto-injector currently used in nonmedical settings for the emergency treatment of known or suspected opioid overdose. HFE methods were employed throughout the product development process for the naloxone auto-injector including formative and summative studies in order to optimize the auto-injector's user interface, mitigate use-related hazards and increase reliability during an opioid emergency use scenario. HFE was also used to optimize the product's design and user interface in order to reduce or prevent user confusion and misuse. The naloxone auto-injector went through a rigorous HFE process that included perceptual, cognitive, and physical action analysis; formative usability evaluations; use error analysis and summative design validation studies. Applying HFE resulted in the development of a product that is safe, fast, easy and predictably reliable to deliver a potentially life-saving dose of naloxone during an opioid overdose emergency. The naloxone auto-injector may be considered as a universal precaution option for at-risk patients prescribed opioids or those who are at increased risk for an opioid overdose emergency.

Take-home naloxone treatment for opioid emergencies: a comparison of routes of administration and associated delivery systems.

INTRODUCTION: Naloxone reversal of opioid-induced respiratory depression outside of medical facilities has become more prevalent because of the escalating opioid epidemic in the USA. Take-home naloxone for treatment of opioid emergencies is now being recommended by numerous federal, state, and professional organizations. Areas covered: The scope of the opioid overdose epidemic is reviewed along with practical, clinical, regulatory, and usability considerations for take-home naloxone routes of administration currently available and associated delivery systems. Specific opioid-related factors are discussed in detail with emphasis placed on life-threatening respiratory depression and naloxone antagonism. A clinical overview, including pharmacokinetic and FDA approval information for each take-home naloxone product is discussed in detail as well as the impact of take-home naloxone in the community. Finally, given these products are to be used in a panic-stricken, life-threatening opioid emergency, an analysis of available usability data is provided with proposed directions for further study. Expert opinion: Based on the available clinical evidence, auto-injectable naloxone should be the preferred administration route for take-home naloxone treatment until additional safety, efficacy, and comparative outcomes data are available for unconventional routes of administration that unequivocally provide equal or superior results.

Patient Characteristics and Outcomes in Unintentional, Non-fatal Prescription Opioid Overdoses: A Systematic Review.

BACKGROUND: Opioid overdose continues to be a significant and growing cause of preventable mortality and morbidity. Studies suggest that unintentional, non-fatal overdose from prescription opioid analgesics constitutes a large portion of total overdose events. The societal burden associated with these events is a frequently overlooked public health concern. OBJECTIVES: To evaluate unintentional, non-fatal prescription opioid overdoses, including the identification of risk factors, societal burden, and knowledge gaps where further study is warranted. STUDY DESIGN: Systematic review of the literature for unintentional, non-fatal opioid overdose. METHODS: Preferred reporting items for systematic reviews and meta-analyses guidelines were used in constructing this systematic review. To determine the scope of the existing literature, a systematic search was conducted using the MEDLINE, CINAHL, PsycINFO, and Web of Science databases. RESULTS: This systematic review analyzes 24 articles (21 retrospective descriptive analyses, 2 prospective analyses, one phase III trial, and one meta-analysis). Articles were reviewed by authors and relevant data examined. Results show that opioid overdose morbidity is significantly more prevalent than mortality and sequelae of non-fatal events should be studied in more detail. LIMITATIONS: The limitations of this systematic review include the range of study populations and opioids discussed and the broad and variable definitions of "opioid overdose" in the literature. CONCLUSIONS: Opioid overdose morbidity and mortality is seen across the entire spectrum of inpatient and outpatient use with significant numbers of adverse events occurring in population segments not identified by high risk indicators. Increased physician awareness and a multi-modal approach could help mitigate the overdose epidemic while maintaining effective pain control for patients. KEY WORDS: Prescription, opioid, accidental drug overdose, unintentional overdose, drug poisoning, fentanyl, oxycodone, hydrocodone, methadone, oxymorphone, hydromorphone.

Economic impact of a novel naloxone autoinjector on third-party payers.

BACKGROUND: Patient overdoses on prescription opioid analgesics in the United States continue to rise, resulting in increased emergency department and hospitalization costs. Opioid overdose is readily reversible with naloxone, a fast-acting opioid antagonist. A new naloxone autoinjector (NAI), Evzio, which does not require medical training to use, was approved by the FDA in April 2014. Payers must decide on reimbursement policies for this product. PURPOSE: To demonstrate to payer decision makers the costs and potential medical resource cost offsets associated with the utilization of a new NAI. DESIGN: A deterministic model using matched controls. METHODOLOGY: An Excel-based cost model was developed for a hypothetical health plan with 1 million adult members. Costs of prescription opioid overdose events for patients appropriately dispensed NAI were compared with matched controls. RESULTS: NAI prescriptions increased from 218 in Year 1 to 2,527 in Year 3. In Year 3, 86 NAI patients (and their matched controls) experienced opioid overdose events. For this period, fatal overdoses in the NAI cohort totaled 11.1 vs. 14.7 for the control group. In Year 3, 2.5 deaths (10.1-7.6) were avoided. NAI acquisition costs rose from $125,000 in Year 1 (PMPM = $0.01) to nearly $1.5 million in Year 3 (PMPM = $0.12).This cost was offset by medical resource savings of approximately $84,000 in Year 1, increasing to $975,000 in Year 3. The total net cost (NAI less offsets) in Year 3, when NAI uptake was assumed to plateau, was $481,000 (PMPM = $0.04). CONCLUSION: A deterministic model demonstrated that NAI acquisition costs can be offset through medical cost reductions with improved timely access to naloxone.

Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery.

INTRODUCTION: The standard of care for reversal of opioid-induced respiratory depression associated with opioid overdose is injectable naloxone. This study compared the usability of two naloxone delivery devices, a naloxone auto-injector (NAI) and a naloxone intranasal delivery system (NXN), in the administration of naloxone during a simulated opioid overdose emergency. NAI (EVZIO (®) ; kaleo, Inc., Richmond, VA, USA) is a Food and Drug Administration approved single-use pre-filled auto-injector containing 0.4 mg of naloxone. METHODS: Study participants were randomly assigned to administer naloxone using NAI and NXN, sequentially. The primary endpoint was successful administration of a simulated dose of naloxone into a mannequin during a simulated opioid emergency, both before and after receiving training. Secondary endpoints included using the NAI or NXN in accordance with the instructions-for-use and the comparative measurement of successful completion time of administration for both NAI and NXN. RESULTS: A total of 42 healthy participants aged 18-65 years were enrolled in the study. The proportion of participants able to successfully administer a simulated dose of naloxone was significantly greater for NAI compared to NXN both before (90.5% vs. 0.0%, respectively, P < 0.0001) and after (100% vs. 57.1%, respectively, P < 0.0001) participant training. The proportion of participants able to administer a simulated dose of naloxone in accordance with the instructions-for-use was also significantly greater for NAI compared to NXN before (85.7% vs. 0.0%, respectively, P < 0.0001) and after (100% vs. 0.0%, respectively, P < 0.0001) participant training. The average time to task completion for administration attempt before training was 0.9 ± 0.25 min for NAI versus 6.0 ± 4.76 min for NXN and after training was 0.5 ± 0.15 min for NAI versus 2.0 ± 2.15 min for NXN. CONCLUSION: Laypersons experienced substantially greater success administering a simulated dose of naloxone, both before and after training, using NAI versus NXN during a simulated opioid overdose emergency. No participants correctly used NXN without training.

Drug-device combination products in the twenty-first century: epinephrine auto-injector development using human factors engineering.

INTRODUCTION: The systematic application of human factors engineering (HFE) principles to the development of drug-device combination products, including epinephrine auto-injectors (EAIs), has the potential to improve the effectiveness and safety of drug administration. AREAS COVERED: A PubMed search was performed to assess the role of HFE in the development of drug-device combination products. The following keywords were used in different combinations: 'human factors engineering,' 'human factors,' 'medical products,' 'epinephrine/adrenaline auto-injector,' 'healthcare' and 'patient safety.' This review provides a summary of HFE principles and their application to the development of drug-device combination products as advised by the US FDA. It also describes the HFE process that was applied to the development of Auvi-Q, a novel EAI, highlighting specific steps that occurred during the product-development program. EXPERT OPINION: For drug-device combination products, device labeling and usability are critical and have the potential to impact clinical outcomes. Application of HFE principles to the development of drug-delivery devices has the potential to improve product quality and reliability, reduce risk and improve patient safety when applied early in the development process. Additional clinical and real-world studies will confirm whether the application of HFE has helped to develop an EAI that better meets the needs of patients at risk of anaphylaxis.

Getting hip to vitamin D: a hospitalist project for improving the assessment and treatment of vitamin D deficiency in elderly patients with hip fracture.

BACKGROUND: Vitamin D deficiency is common in elderly patients with hip fracture, and clinical practice guidelines recommend screening this population. Our hospitalist group cares for all patients admitted with hip fracture, yet lacked a standardized approach to screening for and treating vitamin D deficiency in this population. OBJECTIVES: To standardize and improve the assessment and treatment of vitamin D deficiency in elderly patients with hip fracture. DESIGN: Quality improvement implementation. SETTING: Tertiary academic hospital. PATIENTS: Adults age >50 years with hip fracture. INTERVENTIONS: We implemented a computerized hip fracture order set with preselected orders for 25-OH vitamin D level and initial supplementation with 1000 IU/day of vitamin D. We presented a review of the literature and performance data to our hospitalist group. MEASUREMENTS: Percentage of patients with acute hip fracture screened for vitamin D deficiency and percentage of deficient or insufficient patients discharged on recommended dose of vitamin D (50,000 IU/wk if level <20 ng/mL). RESULTS: The percentage of patients screened for vitamin D deficiency improved from 37.2% (n = 196) before implementation to 93.5% (n = 107) after (P < 0.001). The percentage of deficient or insufficient patients discharged on the recommended vitamin D dose improved from 40.9% to 68.0% (P = 0.008). The prevalence of vitamin D deficiency or insufficiency (25-OH vitamin D level <30 ng/mL) was 50.0%. CONCLUSIONS: Simple interventions, consisting of a change in computerized order set and presentation of evidence and data from group practice, led to significant improvement in the assessment and treatment of vitamin D deficiency in elderly patients with hip fracture.

Bioavailability of epinephrine from Auvi-Q compared with EpiPen.

BACKGROUND: Epinephrine autoinjectors are underused for the treatment of anaphylaxis in community settings. Auvi-Q, a novel epinephrine autoinjector, was designed to be intuitive to use and reduce the potential for use-related errors. OBJECTIVE: To compare the bioavailability of 0.3 mg of epinephrine (adrenaline) injected with Auvi-Q and EpiPen in healthy adults. METHODS: In this randomized, single-blind, 2-treatment, 3-period, 3-sequence crossover study, healthy adults (18-45 years old) received a single injection of 0.3 mg of epinephrine with Auvi-Q in one period and with EpiPen in the other 2 periods. Blood samples were obtained before and 14 times during 6 hours after the dose. Outcomes included peak plasma concentration (Cmax), total epinephrine exposure (area under the concentration-time curve [AUC] from baseline to the last measurable concentration [AUC0-t] and extrapolated to infinity [AUCinf]), and adverse events. RESULTS: Seventy-one volunteers (53 male, 74.6%), with a mean age of 33.2 years and a mean body mass index of 25.4, were randomized. Epinephrine peak concentration and total exposure were similar between Auvi-Q (Cmax = 0.486 ng/mL; AUC0-t = 0.536 ng·h/mL; AUCinf = 0.724 ng·h/mL) and EpiPen (Cmax = 0.520 ng/mL; AUC0-t = 0.466 ng·h/mL; AUCinf = 0.583 ng·h/mL). Cmax and AUC analyses demonstrated bioequivalence between Auvi-Q and EpiPen. Most treatment-emergent adverse events were mild (98%), and all resolved spontaneously. Rates of injection-site pain and bleeding were 13% and 5%, respectively, for Auvi-Q vs 24% and 10%, respectively, for EpiPen. CONCLUSION: After a single injection of 0.3 mg of epinephrine, Auvi-Q and EpiPen had similar peak and total epinephrine exposure, were bioequivalent, and had similar safety profiles.