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.

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.

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.

Design validation and labeling comprehension study for a new epinephrine autoinjector.

BACKGROUND: To facilitate the correct use of epinephrine autoinjectors (EAIs) by patients and caregivers, a novel EAI (Auvi-Q) was designed to help minimize use-related hazards. OBJECTIVE: To support validation of Auvi-Q final design and assess whether the instructions for use in the patient information leaflet (PIL) are effective in training participants on proper use of Auvi-Q. METHODS: Healthy participants, 20 adult and 20 pediatric, were assessed for their ability to complete a simulated injection by following the Auvi-Q instructions for use. Participants relied only on the contents of the PIL and other labeling features (device labeling and its instructions for use, electronic voice instructions and visual prompts). RESULTS: The mean ± SD age of the adult and pediatric participants was 39.4 ± 11.6 and 10.9 ± 2.3 years, respectively. In total, 80% of adult and 35% of pediatric participants had prior experience with EAIs. All adults and 95% of pediatric participants completed a simulated injection on the first attempt; 1 pediatric participant required parental training and a second attempt. Three adult and 4 pediatric participants exhibited a noncritical issue while successfully completing the simulated injection. Most participants agreed that the injection steps were easy to follow and the PIL facilitated understanding on using Auvi-Q safely and effectively. CONCLUSION: The PIL and other labeling features were effective in communicating instructions for successful use of Auvi-Q. This study provided validation support for the final design and anticipated instructions for use of Auvi-Q.

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.

Estimating the economic burden of food-induced allergic reactions and anaphylaxis in the United States.

BACKGROUND: Food allergy is reported to affect 4% to 6% of children and 1% to 2% of adults in the United States. Every year, allergic reactions result in visits to physicians, emergency departments, and hospitals. However, the economic burden of food-induced allergic reactions is unknown. OBJECTIVE: We sought to estimate the direct medical costs and indirect costs of food-induced allergic reactions and anaphylaxis in the United States. METHODS: Costs were estimated with a bottom-up approach from a societal perspective: the average cost of illness per patient was calculated and multiplied by reported prevalence estimates. Patients with an inpatient admission, emergency department admission, office-based physician visit, or outpatient visit for a food-induced allergic reaction were identified from a list of federally administered 2006 and 2007 databases by using International Classification of Diseases, ninth revision, codes. Indirect costs were quantified by estimating lost productivity in terms of lost earnings caused by absenteeism and mortality of patients or caregivers. Sensitivity analyses were conducted to measure the robustness of the estimates. RESULTS: For 2007, direct medical costs were $225 million, and indirect costs were $115 million. Office visits accounted for 52.5% of costs, and the remainder was split between emergency visits (20%), inpatient hospitalizations (11.8%), outpatient visits (3.9%), ambulance runs (3%), and epinephrine devices (8.7%). Simulations from probabilistic sensitivity analyses suggested mean direct medical costs were $307 million and indirect costs were $203 million. CONCLUSIONS: The economic burden of allergic reactions caused by food and anaphylaxis was an estimated half a billion dollars in 2007. Ambulatory visits accounted for more than half of the costs.

Conservation pest control with new technologies: public perceptions.

New genetic tools can potentially mitigate the decline of biodiversity. Democratisation of science mandates public opinion be considered while new technologies are in development. We conducted eleven focus groups in New Zealand to explore three questions about novel technologies (gene drive and two others for comparison of pest control tools): (1) what are the risks/benefits? (2) how do they compare to current methods? and (3) who should be represented on a panel that evaluates the tools and what factors should they consider? Findings from the content analysis of the risks/benefits revealed three main considerations that were of social concern - Environmental, Practical, and Ethical. Most participants were self-aware of their insufficient knowledge to compare the different technologies. Unanimously, respondents wanted the available information provided throughout the tool development process and saw multi-sector panel oversight as essential. Scientists and policy makers should match the public's willingness to engage collaboratively.

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.

Voluntarily reported unintentional injections from epinephrine auto-injectors.

BACKGROUND: Epinephrine auto-injectors provide life-saving prehospital treatment for individuals experiencing anaphylaxis in community settings. OBJECTIVE: To determine the number, demographics, and associated circumstances and outcomes of unintentional injections from epinephrine auto-injectors. METHODS: We searched the databases of the American Association of Poison Control Centers and the Food and Drug Administration's Safety Information and Adverse Event Report System for these incidents as reported by members of the public and by health care professionals. RESULTS: From 1994 to 2007, a total of 15,190 unintentional injections from epinephrine auto-injectors were reported to US Poison Control Centers, 60% of them from 2003 to 2007. Those unintentionally injected had a median age of 14 years (interquartile range, 8-35), 55% were female, and 85% were injected in a home or other residence. Management was documented in only 4101 cases (27%), of whom 53% were observed without intervention, 29% were treated, 13% were neither held for observation nor treated, and 4% refused treatment. In contrast, from 1969 to 2007, only 105 unintentional injections from epinephrine auto-injectors were reported to MedWatch. Forty percent of these occurred during attempts to treat allergic reactions. Injuries resulting in permanent sequelae were rarely reported to either US Poison Control Centers or to MedWatch. CONCLUSION: The number of reported unintentional injections from epinephrine auto-injectors increased annually from 1994 to 2007. To prevent these unintentional injections, improved epinephrine auto-injector design is needed, along with increased vigilance in training the trainers and in training and coaching the users, as well as efforts to increase public awareness of the role of epinephrine auto-injectors in the first-aid treatment of anaphylaxis in the community.

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.

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).

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.

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.

Postherniorrhaphy groin pain and how to avoid it.

Groin pain following inguinal hernia repair remains a challenge to most general surgeons. Prevention of groin pain may be the most effective solution to this management problem and necessitates careful anatomic dissection and precise knowledge of surgical anatomy of the groin as well as potential pitfalls of surgical intervention. When complications arise, a period of watchful waiting is warranted, but surgical intervention with triple neurectomy offers the most definitive resolution of symptoms. This article aims to provide a thorough review of pertinent anatomic landmarks for the proper identification of the nerves that, if injured, result in chronic groin pain and to provide a treatment algorithm for patients suffering with this morbidity.

Experimental inoculation of house sparrows (Passer domesticus) with buggy creek virus.

We performed experimental inoculations of house sparrows (Passer domesticus) with Buggy Creek virus (BCRV), a poorly known alphavirus (Togaviridae) vectored primarily by the swallow bug (Hemiptera: Cimicidae: Oeciacus vicarius) that is an ectoparasite of the cliff swallow (Petrochelidon pyrrhonota) and house sparrow. Viremias were detected by plaque assay in two of six birds on days 1-3 postinoculation; viremia was highest on day 2. Viral RNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in blood of six of 12 birds ranging from day 1 to day 15 postinoculation. Infectious BCRV was detected in nasopharyngeal swab samples from two birds by plaque assay. Three control birds that were housed with viremic individuals showed evidence of BCRV RNA in blood (by RT-PCR), suggesting possible bird-to-bird transmission of this virus. Viral RNA also was detected by RT-PCR in brain and skin tissue of six birds on necropsy at the end of the 16-day experiment. Introduced house sparrows are apparently a competent amplifying host for BCRV, and their presence year-round at cliff swallow colonies may facilitate persistence of the virus locally, especially when cliff swallows abandon a site temporarily. The findings that BCRV can be shed orally, that it persists in bird skin, and that control birds could apparently be infected by conspecifics suggest that this virus may be transmitted from bird to bird in the crowded conditions of many cliff swallow colonies.

Lithium treatment prevents neurocognitive deficit resulting from cranial irradiation.

Curative cancer treatment regimens often require cranial irradiation, resulting in lifelong neurocognitive deficiency in cancer survivors. This deficiency is in part related to radiation-induced apoptosis and decreased neurogenesis in the subgranular zone of the hippocampus. We show that lithium treatment protects irradiated hippocampal neurons from apoptosis and improves cognitive performance of irradiated mice. The molecular mechanism of this effect is mediated through multiple pathways, including Akt/glycogen synthase kinase-3beta (GSK-3beta) and Bcl-2/Bax. Lithium treatment of the cultured mouse hippocampal neurons HT-22 induced activation of Akt (1.5-fold), inhibition of GSK-3beta (2.2-fold), and an increase in Bcl-2 protein expression (2-fold). These effects were sustained when cells were treated with lithium in combination with ionizing radiation. In addition, this combined treatment led to decreased expression (40%) of the apoptotic protein Bax. The additional genes regulated by lithium were identified by microarray, such as decorin and Birc1f. In summary, we propose lithium treatment as a novel therapy for prevention of deleterious neurocognitive consequences of cranial irradiation.

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.

Avian mortality surveillance for West Nile virus in Colorado.

We tested 1,549 avian carcasses of 104 species to identify targets for West Nile virus (WNV) surveillance in Colorado, determine species affected by WNV, compare virus isolation versus RNA detection applied to hearts and oral swabs from carcasses, and compare the VecTest WNV Antigen Assay (VecTest) to standard assays. Forty-two species tested positive. From June to September 2003, 86% of corvids, 34% of non-corvid passerines, and 37% of raptors tested positive. We developed the Target Species Index, which identified American crows as the most important avian indicator species. However, testing multiple species maximizes detection, which may be important early and late in the transmission season. This index may benefit surveillance for other zoonotic pathogens, such as highly pathogenic avian influenza H5N1 virus. VecTest using oral swabs was most sensitive for American crow, black-billed magpie, house finch, house sparrow, and American kestrel. Wildlife rehabilitation centers should be recruited to enhance WNV surveillance.

Protein synthesis inhibition as a potential strategy for metabolic down-regulation.

OBJECTIVE: This pilot study tested the potential of puromycin (PUR) to inhibit protein synthesis and reduce oxygen utilization in a non-hibernating, whole animal preparation. METHODS: After anesthesia and instrumentation, male rats received a single dose of PUR or 0.9% saline (control), followed 60 min later with [(35)S] methionine/cysteine radiolabeling. Thirty minutes after isotope injection, organ biopsies were taken for quantification of de novo protein synthesis. Arterial and central venous blood gases were obtained at baseline and 60 min after injection of PUR or 0.9% saline. Temperature, mean arterial pressure (MAP), and heart rate were recorded continuously. RESULTS: Animals receiving PUR demonstrated significant reductions in protein synthesis in all organ systems sampled (p<0.05). The overall reduction averaged 67.8%. Central venous oxygen saturations (S(cv)O(2)) were higher in the PUR group than the controls at 60 min (90+/-2% versus 80+/-4%, p<0.05). The oxygen extraction ratio (O(2)ER) decreased from 16.1+/-1.7% to 6.8+/-1.2% in the PUR group (p<0.05) and increased from 12.5+/-3.2% to 16.0+/-4.2% in the controls (p=0.44). There was no difference in temperature, MAP, heart rate or blood gas variables, other than S(cv)O(2), at baseline or 60 min between groups. CONCLUSIONS: These results demonstrate that PUR is capable of reducing whole body protein synthesis significantly within a relatively short duration of time. This appears to decrease whole body oxygen utilization as evidenced by an increase in S(cv)O(2) and a decrease in O(2)ER. Protein synthesis inhibition may reduce metabolic demands and should be tested for its potential to improve outcomes where oxygen demands exceed oxygen delivery.