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Abstract Normal pressure hydrocephalus (NPH) is associated with a reduction in cerebral blood flow and an ischemic metabolic state. Ischemia should exhaust the available autoregulation in an attempt to correct the metabolic imbalance. There is evidence of some retained autoregulation reserve in NPH. The aim of this study is to model the cerebral autoregulation in NPH to discover a solution to this apparent paradox. A lumped parameter model was developed utilizing the known limits of autoregulation in man. The model was tested by predicting the cerebral blood volume changes which would be brought about by changes in resistance. NPH and the post shunt state were then modeled using the known constraints provided from the literature. The model successfully predicted the cerebral blood volume changes brought about by altering the cerebral perfusion pressure to the limit of autoregulation. The model suggests that NPH is associated with a balanced increase in resistance within the arterial and venous outflow segments. The arterial resistance decreased after modelling shunt insertion. The model suggests that the cerebral blood flow is actively limited in NPH by arteriolar constriction. This may occur to minimize the rise in ICP by reducing the apparent CSF formation rate.

AbstractThe entrepreneurship field is increasingly interlaced with diverse disciplines, tackling complex societal issues from sustainability to digitalization and family business dynamics. Recognizing the necessity to steer future research, the editorial team of Cogent Business and Management’s Entrepreneurship and Innovation section present ten research domains identified through collective expertise. These areas, ranging from corporate innovation to entrepreneurship education and transitional entrepreneurship, are critical for academic investigation and hold potential for significant societal impact. These domains are not intended to constitute a ‘top 10’ list, nor are they exhaustive; rather, they are intended to help guide scholars toward research domains we believe are ripe for exploration and with the potential to be highly impactful. These domains embody the field’s ever-evolving nature, encapsulating the entrepreneurial spirit as a quilt of interconnected patches rather than isolated pieces. They encourage an interdisciplinary approach, highlighting the need for a comprehensive understanding of entrepreneurial activity. As the entrepreneurship literature grows, its adaptability will be crucial for theoretical advancement and practical applications. The proposed research roadmap aims to ignite cross-disciplinary dialogue, driving the impact of entrepreneurship research beyond academic circles and into the realms of policy and practice.

Abstract Spaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. Previously, the current authors have discussed the similarities and differences between SANS and idiopathic intracranial hypertension to try to elucidate a possible pathophysiology. Recently, a theory has been advanced that SANS may occur secondary to failure of the glymphatic system caused by venous dilatation within the brain and optic nerves. There is recent evidence to suggest glymphatic obstruction occurs in childhood hydrocephalus, multiple sclerosis and syringomyelia due to venous outflow dilatation similar to that proposed in SANS. The purpose of the current paper is to discuss the similarities and differences between the known CSF and venous pathophysiology in SANS with these other terrestrial diseases, to see if they can shed any further light on the underlying cause of this microgravity-induced disease.

Abstract Senecavirus A (SVA) causes vesicular disease in swine and has been responsible for a rampant increase in the yearly number of foreign animal disease investigations conducted in the United States. Diagnostic investigations for SVA are typically performed by sampling animals individually, which is labor-intensive and stressful. Developing an alternative aggregate sampling method would facilitate the detection of this virus at the population level. In a preliminary study, SVA was detected in processing fluids (PF) collected in a breeding herd before and after outbreak detection. The objective of this study was to estimate the average number of weeks PF remain SVA-positive after an SVA outbreak. Ten farrow-to-wean breeding herds volunteered to participate in this studyby longitudinally collecting PF samples after an SVA outbreak was detected and submitting samples for RT-rtPCR testing. The PF samples from the 10 farms were SVA-positive for an average of 11.8 weeks after the outbreak. Here, we show that testing of PF may be a cost-effective method to detect SVA and help halt its spread in SVA-endemic regions.

A comprehensive aircraft survey of onshore oil and gas infrastructure in British Columbia finds that methane emissions may be 1.7 times higher than the official inventory and introduces a framework for compiling measurement-led regional greenhouse gas emissions data.

Abstract The cross-sectional area of the superior sagittal sinus (SSS) is larger in multiple sclerosis than normal and correlates with disease severity and progression. The sinus could be enlarged due to a decrease in the pressure difference between the lumen and the subarachnoid space, an increase in wall thickness or increased wall stiffness. The cross-sectional area of the SSS and straight sinus (ST) were measured in 103 patients with multiple sclerosis and compared to 50 controls. The cross-sectional area of the SSS and ST were increased by 20% and 13% compared to the controls (p = 0.005 and 0.02 respectively). The deflection of the wall of the sinus was estimated. The change in pressure gradient, wall thickness or elastic modulus between groups was calculated by modelling the walls as simply supported beams. To account for these findings, the modelling suggests either a 70% reduction in transmural venous pressure or a 2.4 fold increase in SSS wall stiffness plus an 11% increase in wall thickness or a combination of changes. An increase in sinus pressure, although the most straight forward possibility to account for the change in sinus size may exist in only a minority of patients. An increase in sinus wall stiffness and thickness may need further investigation.

Abstract Spaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. There is controversy regarding SANS being similar to patients with idiopathic intracranial hypertension (IIH). IIH has been shown to be due to an elevation in venous sinus pressure. The literature suggests an increase in jugular vein pressure secondary to a headward shift of fluid occurs in SANS but this may not be enough to significantly alter the intracranial pressure (ICP). The literature regarding cardiac output and cerebral blood flow (CBF) in long-duration spaceflight is contradictory, however, more recent data suggests increased flow. Recent modelling has shown that an increase in CBF can significantly increase sinus pressure. The purpose of the present paper is to review the SANS vascular dynamics literature and through mathematical modelling suggest the possible underlying cause of SANS as an elevation in venous sinus pressure, secondary to the redistribution of fluids towards the head, together with a significant increase in pressure drop across the venous system related to the CBF.

COVID-19 has led to an unprecedented disruption in tourism spending. This has propagated through the whole economy, however the scale of these system-wide consequences can be hard to quantify. We calculate direct reductions in spending across domestic and inbound tourism categories and then use a computable general equilibrium model to quantify their economic impacts. The results – illustrated using a model for Scotland and focusing on 2021 - demonstrate the scale of the losses in the tourism industry and the economy as a whole that are attributable to changes in both domestic and inbound tourism demand. We find that the extent to which domestic tourism demand can mitigate the losses in inbound spending depends on the composition of demand.

Abstract As well as their role in contributing towards emissions reductions targets, it is increasingly relevant for policymakers to understand the contribution that renewable energy technologies make to the economy. Various methods have been used to quantify impacts, such as job counts, surveys and measures based on economic statistics. Economic modelling approaches on the other hand appear to offer an ability to both provide metrics of interest to policymakers and crucially an understanding of the activities which support that contribution. In this paper, we implement a new method for estimating the activity supported by renewable energy activities; applying a ‘hypothetical extraction’ of offshore wind—to identify the contribution that such activities make to U.K. economic activity, job quality and national emissions. By undertaking the partial extraction of offshore wind from an aggregated input–output (IO) table and then subsequently from one in which we have separated out the offshore wind electricity sector, we highlight the value of more disaggregation and technology‐specific detail in economic accounts. The results from our fullest extraction suggest that in 2010, offshore wind in the United Kingdom supported 10 240 jobs, with 9 in 10 of these jobs either medium or high skill, and contributed £780 million to gross domestic product (GDP). In addition, a significant portion of activity supported by offshore wind is attributable to expansions in capacity rather than operational activities.

Abstract Background It has been shown that idiopathic intracranial hypertension (IIH) in children is associated with cerebral hyperemia, which induces an increase in cerebral venous pressure. The current literature suggests venous pressure scales with blood flow in a linear fashion, however, a linear relationship would not raise the pressure high enough to induce IIH. There is, however, some evidence to suggest that this relationship could be quadratic in nature. The purpose of this paper is to characterize the relationship between cerebral blood flow and the pressure drop across the cerebral venous system. Methods 10 CT venogram data sets were collected for this study, with 5 useable geometries created. Computational fluid dynamics (CFD) models were generated using these geometries, with 10 simulations conducted per patient. The flow rates tested ranged from 200 mL/min to 2000 mL/min. 3D pressure and velocity streamline distributions were created and analyzed for each CFD model, with pressure drops across the cerebral venous system determined. The effective and hydraulic diameters were determined at the superior sagittal sinus, transverse sinus and both proximal and distal sigmoid sinuses. Results A quadratic relationship between blood flow and sinus pressure was found, with correlations of 0.99 or above in all five patients. The presence of vortical blood flow was found to explain this trend, with fluid curl and pressure drop correlations being above 0.97. This suggests that the presence of high blood flow should be considered in the diagnostic workup of IIH. Conclusions The cerebral venous sinus blood flow and pressure response relationship are quadratic in nature, with the major cause of this being the degree of rotation induced in the flow. The elevated blood flow found in children with IIH can explain the increased ICP that is found, secondary to the increase in venous pressure that develops.

The female perspective of implementing failure learning orientation is explored through the analysis of interviews with Canadian female executives of technology firms. The results of this study established several strategies for executives to use for creating an organizational culture that learns from failure. The strategies include, reimagine failure to mitigate negative emotions, focus on the root of the issue, openly discuss strategies and failures, be proactive, encourage risk-taking in experimentation, and finally, provide a calming presence.

Abstract Background Children referred to a tertiary hospital for the indication, “rule out idiopathic intracranial hypertension (IIH)” may have an increased risk of raised venous sinus pressure. An increase in sinus pressure could be due to obesity, venous outflow stenosis or cerebral hyperemia. The purpose of this paper is to define the incidence of each of these variables in these children. Methods Following a data base review, 42 children between the ages of 3 and 15 years were found to have been referred over a 10 year period. The body mass index was assessed. The cross sectional areas and circumferences of the venous sinuses were measured at 4 levels to calculate the hydraulic and effective diameters. The arterial inflow, sagittal and straight sinus outflows were measured. Automatic cerebral volumetry allowed the brain volume and cerebral blood flow (CBF) to be calculated. The optic nerve sheath diameter was used as a surrogate marker of raised intracranial pressure (ICP). The sagittal sinus percentage venous return was used as a surrogate marker of elevated venous pressure. Age and sex matched control groups were used for comparison. Results Compared to controls, the obesity rates were not significantly different in this cohort. Compared to controls, those at risk for IIH had a 17% reduction in transverse sinus and 14% reduction in sigmoid sinus effective cross sectional area (p = 0.005 and 0.0009). Compared to controls, the patients at risk for IIH had an arterial inflow increased by 34% (p

Abstract Background Symptomatic or active hydrocephalus in children is linked to an elevation in intracranial pressure (ICP), which is likely to be multifactorial in origin. The CSF outflow resistance, venous sinus resistance and total cerebral blood flow are likely factors in the ICP elevation. The purpose of this paper is to define the incidence, site and significance of venous sinus stenosis and/or cerebral hyperemia in a cohort of children diagnosed with hydrocephalus at a tertiary referral hospital. Methods The imaging database was reviewed over a 10 year period and the index MRI of all children between the ages of 4 months and 15 years, who were diagnosed with treatment naive hydrocephalus of any type (excluding secondary to tumor) and had magnetic resonance venography (MRV) and flow quantification were selected. Patients were compared with children undergoing an MRI with MRV and flow quantification who were subsequently shown to have no abnormality. The cross-sectional area and circumference of the sinuses were measured at 4 levels. The hydraulic and effective diameters were calculated. An area stenosis of 65% or greater was deemed significant. A total cerebral blood flow greater than two standard deviations above the mean for controls was taken to be abnormal. Results There were a total of 55 children with hydrocephalus compared to 118 age matched control MRV’s and 35 control flow quantification studies. A high grade stenosis occurred in 56% of patients but in none of the controls (p

Bioaerosols often contain human pathogens and allergens affecting public health. However, relatively little attention has been given to bioaerosols compared with non-biological aerosols. In this study, we aimed to identify bioaerosol compositions in Manchester, UK by applying high throughput sequencing methods and to find potential sources. Samples were collected at Manchester Air Quality Super Site at the Firs Environmental Research Station in November 2019 and in February 2020. Total DNA has been extracted and sequenced targeting the 16S rRNA gene of prokaryotes, ITS region of fungal DNA and 18S rRNA gene of eukaryotes. We found marine environment-associated bacteria and archaea were relatively more abundant in the February 2020 samples compared with the November 2019 samples, consistent with the North West marine origin based on wind back-trajectory analysis. In contrast, an OTU belonging to Methylobacterium, which includes many species resistant to heavy metals, was relatively more abundant in November 2019 when there were higher metal concentrations. Fungal taxa that fruit all year were relatively more abundant in the February 2020 samples while autumn fruiting species generally had higher relative abundance in the November 2019 samples. There were higher relative abundances of land plants and algae in the February 2020 samples based on 18S rRNA gene sequencing. One of the OTUs belonging to the coniferous yew genus Taxus was more abundant in the February 2020 samples agreeing with the usual pollen season of yews in the UK which is from mid-January until late April. The result from this study suggests a potential application of bioaerosol profiling for tracing the source of atmospheric particles.

Resistive switching is of the key phenomena for applications such as nonvolatile memories or neuromorphic computing. V_{3}O_{5}, a compound of the vanadium oxide Magnéli series, is one of the rare materials to exhibit an insulator-metal transition above room temperature (T_{c}∼415 K). The switching mechanisms in this material are still not clear. Here, we demonstrate both static dc volatile resistive switching and fast oscillatory spiking regimes in V_{3}O_{5} devices at room temperature (120 K below the phase transition temperature) by applying an electric field. We couple electrical measurements, operando optical imaging, and infrared measurements to track the reflectivity change and the temperature of a device during the resistive switching. We find that the resistive switching starts via thermal runaway deep in the insulating state and triggers the phase transition with the formation of a filament of the high-temperature phase. Furthermore, we capture optically and thermally the spiking oscillations that we link to the negative differential resistance regime and find the filament forms and dissolves via a periodic spatiotemporal instability that we describe by numerical simulations. Our studies play an important role in understanding the volatile resistive switching mechanisms and demonstrate that V_{3}O_{5} can be a key vanadium oxide for neuromorphic computing.

Abstract Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late onset Alzheimer’s disease (AD). Studies have shown that apoE, apoE4 in particular, binds to amyloid-β (Aβ) peptides at residues 12-28 of Aβ and this binding modulates Aβ accumulation and disease progression. We have previously shown in several AD transgenic mice lines that blocking the apoE/Aβ interaction with Aβ12-28 P reduced Aβ and tau-related pathology, leading to cognitive improvements in treated AD mice. Recently, we have designed a small peptoid library derived from the Aβ12-28 P sequence to screen for new apoE/Aβ binding inhibitors with higher efficacy and safety. Peptoids are better drug candidates than peptides due to their inherently more favorable pharmacokinetic properties. One of the lead peptoid compounds, CPO_Aβ17–21 P, diminished the apoE/Aβ interaction and attenuated the apoE4 pro-fibrillogenic effects on Aβ aggregation in vitro as well as apoE4 potentiation of Aβ cytotoxicity. CPO_Aβ17–21 P reduced Aβ-related pathology coupled with cognitive improvements in an AD APP/PS1 transgenic mouse model. Our study suggests the non-toxic, non-fibrillogenic peptoid CPO_Aβ17–21 P has significant promise as a new AD therapeutic agent which targets the Aβ related apoE pathway, with improved efficacy and pharmacokinetic properties.

Astroviruses (AstVs) cause disease in a wide variety of species. Porcine AstVs are highly genetically diverse and conventionally assigned to five genetic lineages (PoAstV1-5). Due to the increasing evidence that porcine astrovirus type 3 (PoAstV3) is a cause of encephalomyelitis in swine and to elucidate important ecologic characteristics, the infection dynamics and environmental distribution of PoAstV3 were investigated in a herd with PoAstV3-associated neurologic disease. Over a 22 week period, the frequency of PoAstV3 fecal shedding varied by pig and age. The peak detection by RT-qPCR of PoAstV3 on fecal swabs (95%; 61 of 64) occurred at 3 weeks of age. The lowest frequency of detection was at 21 weeks of age (4%; 2 of 47); however, the frequency increased to 41% (19 of 46) at the final sampling time point (25 weeks of age). Viremia was rare (0.9%: 4 of 433). Detection in oral fluid was consistent with 75% to 100% of samples positive at each time point. Pens and feeders also had a high rate of detection with a majority of samples positive at a majority of sampling time points. Based on the data presented, PoAstV3 can be consistently detected in the environment with a majority of pigs being infected and a subset intermittently shedding the virus in feces out to 25 weeks of age. These findings suggest the importance of as-yet unidentified risk factors associated with the development of PoAstV3-associated polioencephalomyelitis.

Primary biological aerosols often include allergenic and pathogenic microorganisms posing potential risks to human health. Moreover, there are airborne plant and animal pathogens that may have ecological and economic impact. In this study, we used high-throughput sequencing techniques (Illumina, MiSeq) targeting the 16S rRNA genes of bacteria and the 18S rRNA genes of eukaryotes, to characterize airborne primary biological aerosols. We used a filtration system on the UK Facility for Airborne Atmospheric Measurements (FAAM) research aircraft to sample a range of primary biological aerosols across southern England overflying surface measurement sites from Chilbolton to Weybourne. We identified 30 to 60 bacterial operational taxonomic units (OTUs) and 108 to 224 eukaryotic OTUs per sample. Moreover, 16S rRNA gene sequencing identified significant numbers of genera that have not been found in atmospheric samples previously or only been described in limited number of atmospheric field studies, which are rather old or published in local journals. This includes the genera Gordonia, Lautropia, and Psychroglaciecola. Some of the bacterial genera found in this study include potential human pathogens, for example, Gordonia, Sphingomonas, Chryseobacterium, Morganella, Fusobacterium, and Streptococcus. 18S rRNA gene sequencing showed Cladosporium to be the major genus in all of the samples, which is a well-known allergen and often found in the atmosphere. There were also genetic signatures of potentially allergenic taxa; for example, Pleosporales, Phoma, and Brassicales. Although there was no significant clustering of bacterial and eukaryotic communities depending on the sampling location, we found meteorological factors explaining significant variations in the community composition. The findings in this study support the application of DNA-based sequencing technologies for atmospheric science studies in combination with complementary spectroscopic and microscopic techniques for improved identification of primary biological aerosols.

Astroviruses cause disease in a variety of species. Yet, little is known about the epidemiology of a majority of astroviruses including porcine astrovirus type 3 (PoAstV3), which is a putative cause of polioencephalomyelitis in swine. Accordingly, a cross-sectional study was conducted on sow farms with or without reported PoAstV3-associated neurologic disease in growing pigs weaned from those farms. Additionally, a conveniently selected subset of piglets from one farm was selected for gross and histologic evaluation. The distribution of PoAstV3 in the enteric system was evaluated through in situ hybridization. PoAstV3, as detected by RT-qPCR on fecal samples, was frequently detected across sows and piglets (66−90%) on all farms (65−85%). PoAstV3 was detected subsequently at a similar detection frequency (77% vs 85%) on one farm after three months. Viral shedding, as determined by the cycle quantification value, suggests that piglets shed higher quantities of virus than adult swine. No link between gastrointestinal disease and PoAstV3 was found. However, PoAstV3 was detected by in situ in myenteric plexus neurons of piglets elucidating a possible route of spread of the virus from the gastrointestinal tract to the central nervous system. These data suggest PoAstV3 has endemic potential, is shed in the feces at greater quantities by suckling piglets when compared to sows, and infection is widespread on farms in which it is detected.

Point-source methane emission flux quantification is required to help constrain the global methane budget. Facility-scale fluxes can be derived using in situ methane mole fraction sampling, near-to-source, which may be acquired from an unmanned aerial vehicle (UAV) platform. We test a new non-dispersive infrared methane sensor by mounting it onto a small UAV, which flew downwind of a controlled methane release. Nine UAV flight surveys were conducted on a downwind vertical sampling plane, perpendicular to mean wind direction. The sensor was first packaged in an enclosure prior to sampling which contained a pump and a recording computer, with a total mass of 1.0 kg. The packaged sensor was then characterised to derive a gain factor of 0.92 ± 0.07, independent of water mole fraction, and an Allan deviation precision (at 1 Hz) of ±1.16 ppm. This poor instrumental precision and possible short-term drifts made it non-trivial to define a background mole fraction during UAV surveys, which may be important where any measured signal is small compared to sources of instrumental uncertainty and drift. This rendered the sensor incapable of deriving a meaningful flux from UAV sampling for emissions of the order of 1 g s−1. Nevertheless, the sensor may indeed be useful when sampling mole fraction enhancements of the order of at least 10 ppm (an order of magnitude above the 1 Hz Allan deviation), either from stationary ground-based sampling (in baseline studies) or from mobile sampling downwind of sources with greater source flux than those observed in this study. While many methods utilising low-cost sensors to determine methane flux are being developed, this study highlights the importance of adequately characterising and testing all new sensors before they are used in scientific research.

The accurate quantification of methane emissions from point sources is required to better quantify emissions for sector-specific reporting and inventory validation. An unmanned aerial vehicle (UAV) serves as a platform to sample plumes near to source. This paper describes a near-field Gaussian plume inversion (NGI) flux technique, adapted for downwind sampling of turbulent plumes, by fitting a plume model to measured flux density in three spatial dimensions. The method was refined and tested using sample data acquired from eight UAV flights, which measured a controlled release of methane gas. Sampling was conducted to a maximum height of 31 m (i.e. above the maximum height of the emission plumes). The method applies a flux inversion to plumes sampled near point sources. To test the method, a series of random walk sampling simulations were used to derive an NGI upper uncertainty bound by quantifying systematic flux bias due to a limited spatial sampling extent typical for short-duration small UAV flights (less than 30 min). The development of the NGI method enables its future use to quantify methane emissions for point sources, facilitating future assessments of emissions from specific source-types and source areas. This allows for atmospheric measurement-based fluxes to be derived using downwind UAV sampling for relatively rapid flux analysis, without the need for access to difficult-to-reach areas.

Computation is a central aspect of 21st century physics practice; it is used to model complicated systems, to simulate impossible experiments, and to analyze mountains of data. Physics departments and their faculty are increasingly recognizing the importance of teaching computation to their students. We recently completed a national survey of faculty in physics departments to understand the state of computational instruction and the factors that underlie that instruction. The data collected from the faculty responding to the survey included a variety of scales, binary questions, and numerical responses. We then used random forest, a supervised learning technique, to explore the factors that are most predictive of whether a faculty member decides to include computation in their physics courses. We find that experience using computation with students in their research, or lack thereof and various personal beliefs to be most predictive of a faculty member having experience teaching computation. Interestingly, we find demographic and departmental factors to be less useful factors in our model. The results of this study inform future efforts to promote greater integration of computation into the physics curriculum as well as comment on the current state of computational instruction across the United States.

This study presents the first gaseous formic acid (HC(O)OH) concentration measurements collected over the Fenno-Scandinavian wetlands (67.9–68.0° N, 22.1–27.8° E) as part of the MAMM (Methane and other greenhouse gases in the Arctic-Measurements, process studies and Modelling) aircraft campaigns conducted in August and September 2013. A boundary layer box model approach has been used to calculate a regionally representative (~240 km2) surface flux for HC(O)OH of 0.0098 (±0.0057) mg[HCOOH]·m−2·h−1. A surface-type classification map was used to estimate proportional source contributions to the observed HC(O)OH flux over the measurement region. The removal of expected source contributions (using available literature parameterisations) from the calculated surface flux identified that 75% remained unaccounted for. This may suggest that HC(O)OH emission from wetland within the Fenno-Scandinavian region could contribute up to 29 times higher per unit area than previous theoretical HC(O)OH globally-averaged wetland estimates, highlighting a need for further constrained wetland studies of HC(O)OH emission to better understand its potentially significant impact on the Arctic HC(O)OH budget and consequent impacts on oxidative capacity.

Variations in postmortem metabolism in muscle impact pork quality development. Curiously, some genetic lines are more refractile to adverse pork quality development than others and may regulate energy metabolism differently. The aim of this study was to challenge pork carcasses from different genetic populations with electrical stimulation (ES) to determine how postmortem metabolism varies with genetic line and explore control points that reside in glycolysis in dying muscle. Three genetic populations (GP) were subjected to ES (100 V or 200 V, 13 pulses, 2 s on/2 s off) at 15- or 25-min post-exsanguination, or no stimulation (NS). Genetic population affected relative muscle relative abundance of different myosin heavy chains, glycogen, G6P, and lactate concentrations. Genetic lines responded similarly to ES, but a comparison of ES treatment groups revealed a trend for an interaction between voltage, time of ES, and time postmortem. Higher voltage accelerated pH decline at 20 min up to 60 min postmortem. Trends in color and firmness scores and L* values were consistent with pH and metabolite data. These data show that genetic populations respond differently to postmortem perturbation by altering glycolytic flux and suggest differences in postmortem glycolysis may be partially responsible for differences in meat quality between genetic populations, though not entirely.

The objective of this study was to determine if ractopamine (RAC) impacts postmortem muscle metabolism and subsequent pork quality in Halothane (HAL) and Rendement Napole (RN) mutant pigs. All RAC fed pigs had increased (P < 0.04) L* values. HAL and RN mutants muscle had lower (P < 0.01) pH values but RAC feeding had no effect. RN mutants had higher and lower (P < 0.05) muscle pH and temperatures, respectfully at 15 min and RN mutant pigs had greater (P < 0.0001) glycogen initially but lactate levels similar to wild type (WT) pigs at 24 h. RAC lowered (P < 0.05) glycogen in RN mutants but not in HAL mutated or WT pig muscle. These data show RAC feeding changes postmortem energy metabolism but does not change pH and pork quality hallmark of two major pig gene mutations and supports our contention that ultimate meat quality traits and their biochemical drivers may be more complex than originally reasoned., (Published by Elsevier Ltd.)

Objectives: Academic surgeons manage their role as intraoperative educators in a variety of ways. Such variability is neither idiosyncratic nor is there a single best approach. This study sought to explore the practices of surgeons deemed influential by their residents, allowing insight into a variety of potentially effective practices., Participants: Constructivist grounded theory guided data collection and analysis. Data sources included surveys from senior surgical residents (PGY3-6) and recent graduates from an academic hospital in Canada (36% response rate), intraoperative observations of teaching interactions, and semi-structured interviews with observed surgeons. Rigour was supported by data triangulation, constant comparison, and collection to theoretical sufficiency., Design: We developed a framework grouping effective teaching into three overlapping approaches: exacting, empowering, and fostering. The approaches differ based on the level of independence granted and the degree of expectation placed on individual residents. Each demonstrates different strategies for balancing the multiple supervisory roles and patient care obligations faced by academic surgeons. We also identified strategies that could be used across approaches to enhance learning., Conclusions: For surgical educators seeking to improve upon the quality of the intraoperative supervision they provide, frameworks such as this may serve as models of effective supervision. Enhancing surgeons' knowledge of proven strategies, combined with reflecting on how they teach and how they balance responsibilities to patients and trainees, may allow them to broaden their educational practice., Competing Interests: Declaration of Competing Interest This project was partially funded by the Schulich School of Medicine and Dentistry Department of Surgery Internal Research Fund and the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario (AMOSO)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Postnatal muscle growth is accompanied by increases in fast fiber type compositions and hypertrophy, raising the possibility that a slow to fast transition may be partially requisite for increases in muscle mass. To test this hypothesis, we ablated the Myh4 gene, and thus myosin heavy chain IIB protein and corresponding fibers in mice, and examined its consequences on postnatal muscle growth. Wild-type and Myh4 -/- mice had the same number of muscle fibers at 2 weeks postnatal. However, the gastrocnemius muscle lost up to 50% of its fibers between 2 and 4 weeks of age, though stabilizing thereafter. To compensate for the lack of functional IIB fibers, type I, IIA, and IIX(D) fibers increased in prevalence and size. To address whether slowing the slow-to-fast fiber transition process would rescue fiber loss in Myh4 -/- mice, we stimulated the oxidative program in muscle of Myh4 -/- mice either by overexpression of PGC-1α, a well-established model for fast-to-slow fiber transition, or by feeding mice AICAR, a potent AMP kinase agonist. Forcing an oxidative metabolism in muscle only partially protected the gastrocnemius muscle from loss of fibers in Myh4 -/- mice. To explore whether traditional means of stimulating muscle hypertrophy could overcome the muscling deficits in postnatal Myh4 -/- mice, myostatin null mice were bred with Myh4 -/- mice, or Myh4 -/- mice were fed the growth promotant clenbuterol. Interestingly, both genetic and pharmacological stimulations had little impact on mice lacking a functional Myh4 gene suggesting that the existing muscle fibers have maximized its capacity to enlarge to compensate for the lack of its neighboring IIB fibers. Curiously, however, cell signaling events responsible for IIB fiber formation remained intact in the tissue. These findings further show disrupting the slow-to-fast transition of muscle fibers compromises muscle growth postnatally and suggest that type IIB myosin heavy chain expression and its corresponding fiber type may be necessary for fiber maintenance, transition and hypertrophy in mice. The fact that forcing muscle metabolism toward a more oxidative phenotype can partially compensates for the lack of an intact Myh4 gene provides new avenues for attenuating the loss of fast-twitch fibers in aged or diseased muscles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zeng, Shi, Kirkpatrick, Ricome, Park, Scheffler, Hannon, Grant and Gerrard.)

Solving environmental odor issues can be confounded by many analytical, technological, and socioeconomic factors. Considerable know-how and technologies can fail to properly identify odorants responsible for the downwind nuisance odor and, thereby, focus on odor mitigation strategies. We propose enabling solutions to environmental odor issues utilizing troubleshooting techniques developed for the food, beverage, and consumer products industries. Our research has shown that the odorant impact-priority ranking process can be definable and relatively simple. The initial challenge is the prioritization of environmental odor character from the perspective of the impacted citizenry downwind. In this research, we utilize a natural model from the animal world to illustrate the rolling unmasking effect (RUE) and discuss it more systematically in the context of the proposed environmental odorant prioritization process. Regardless of the size and reach of an odor source, a simplification of odor character and composition typically develops with increasing dilution downwind. An extreme odor simplification-upon-dilution was demonstrated for the prehensile-tailed porcupine (P.T. porcupine); its downwind odor frontal boundary was dominated by a pair of extremely potent character-defining odorants: (1) 'onion'/'body odor' and (2) 'onion'/'grilled' odorants. In contrast with the outer-boundary simplicity, the near-source assessment presented considerable compositional complexity and composite odor character difference. The ultimate significance of the proposed RUE approach is the illustration of naturally occurring phenomena that explain why some environmental odors and their sources can be challenging to identify and mitigate using an analytical-only approach (focused on compound identities and concentrations). These approaches rarely move beyond comprehensive lists of volatile compounds emitted by the source. The novelty proposed herein lies in identification of those few compounds responsible for the downwind odor impacts and requiring mitigation focus.

Background: Total hip arthroplasty is a successful treatment for hip osteoarthritis. Primary and secondary implant fixation is dependent on implant design and plays an important role in the longevity of an implant. In this study, we assessed the self-locking cementless Master SL femoral stem., Materials and Methods: In this single-centre prospective study, 50 consecutive hips with the indication for total hip arthroplasty, who met the inclusion criteria, received the Master SL stem from LIMA Corporate. Patients had pre- and post-operative clinical and radiological assessment and completed patient-reported outcome measures [Oxford Hip Score (OHS), Harris Hip Score (HHS) and Forgotten Joint Score (FJS)] at the 6-week and 6-, 12- and 24-month mark. Post-operative X-rays were assessed for osteointegration (Engh Score), alignment and subsidence., Results: After 2 years, aseptic survival was 100%. One hip had to be explanted due to early deep infection and was excluded from the study. At 2 years, the patients reported a significant improved HHS and OHS of 95.3 ± 5.8 and 46.1 ± 3.6 (mean ± standard deviation), respectively, compared to preoperatively. The mean ± standard deviation for the FJS was 86.4 ± 18.7 with two-thirds of the patients reporting a score above 85. The mean Engh score is 15.1 ± 5.9 (mean ± standard deviation) with no patient scoring below 1 which suggests good osteointegration in all femoral stems., Conclusions: The Master SL femoral stem performed well in this short-term follow-up study, with high patient satisfaction and good signs of osteointegration. Long-term follow-up will be necessary to evaluate longevity., Level of Evidence: Level 3, Prospective cohort study., Trial Registration: The study was registered on the 30.03.2016 with Australia New Zealand Clinical Trials Registry (ACTRN12617000550303)., (© 2020. The Author(s).)

Pork quality is a product of the rate and extent of muscle pH decline paced by carbohydrate metabolism postmortem. The beta-adrenergic agonist ractopamine (RAC) alters muscle metabolism but has little impact on pork quality. The objective of this study was to determine how feeding RAC alters postmortem carbohydrate metabolism in muscle. Muscle pH was higher early postmortem in pigs fed RAC for 2 wks compared to control, while other time points and temperatures were largely unaffected. Early postmortem, muscle lactate levels were reduced (P < 0.05) after feeding RAC for 1 and 2 wks. Similarly, pigs fed RAC for 4 wks had reduced (P < 0.05) glycogen levels early postmortem compared to control pigs, but unexpectedly, L* values (lightness) increased (P < 0.05) after inclusion of RAC in the diet for 4 wk. These data show RAC feeding reduces glycogen content and changes lactate accumulation postmortem, but raise questions about the role glycolytic flux has in driving pork quality development., (Published by Elsevier Ltd.)

Background: Emergency front of neck airway access by anaesthetists carries a high failure rate and it is recommended to identify the cricothyroid membrane before induction of anaesthesia in patients with a predicted difficult airway. We have investigated whether a marking of the cricothyroid membrane done in the extended neck position remains correct after the patient's neck has been manipulated and subsequently repositioned., Methods: The subject was first placed in the extended head and neck position and had the cricothyroid membrane identified and marked with 3 methods, palpation, 'laryngeal handshake' and ultrasonography and the distance from the suprasternal notch to the cricothyroid membrane was measured. The subject then moved off the table and sat on a chair and subsequently returned to the extended neck position and examinations were repeated., Results: Skin markings of all 11 subjects lay within the boundaries of the cricothyroid membrane when the subject was repositioned back to the extended neck position and the median difference between the two measurements of the distance from the suprasternal notch was 0 mm (range 0-2 mm)., Conclusion: The cricothyroid membrane can be identified and marked with the subject in the extended neck position. Then the patient's position can be changed as needed, for example to the 'sniffing' neck position for conventional intubation. If a front of neck airway access is required during subsequent airway management, the patient can be returned expediently to the extended-neck position, and the marking of the centre of the membrane will still be in the correct place., (© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Feeding ractopamine (RAC), a β-adrenergic agonist (BAA), to pigs increases type IIB muscle fiber type-specific protein and mRNA expression. However, increases in the abundance of these fast-twitch fiber types occur with other forms of muscle hypertrophy and thus BAA-induced changes in myosin heavy chain (MyHC) composition may simply be associated with increased muscle growth known to occur in response to BAA feeding. The objective of this study was to determine whether RAC feeding could change the MyHC gene expression in the absence of maximal muscle growth. Pigs were fed either an adequate diet that supported maximal muscle hypertrophy or a low nutrient diet that limited muscle growth. RAC was included in diets at 0 or 20 mg/kg for 1, 2, or 4 wk. Backfat depth was less (P < 0.05) in pigs fed the low nutrient diet compared with the adequate diet but was not affected by RAC. Loin eye area was greater (P < 0.05) in pigs fed an adequate diet plus RAC at 1 wk but did not differ among remaining pigs. At 2 and 4 wk, however, pigs fed the adequate diet had greater loin eye areas (P < 0.05) than pigs fed the low nutrient diet regardless of RAC feeding. Gene expression of the MyHC isoforms, I, IIA, IIX, and IIB, as well as glycogen synthase, citrate synthase, β 1-adrenergic receptor (AR), and β 2-AR were determined in longissimus dorsi (LD) and red (RST) and white (WST) portions of the semitendinosus muscles. MyHC type I gene expression was not altered by RAC or diet. Feeding RAC decreased (P < 0.01) MyHC type IIA gene expression in all muscles, but to a greater extent in WST and LD. MyHC type IIX gene expression was lower (P < 0.05) in WST and LD muscles in response to RAC but was not altered in RST muscles. RAC increased (P < 0.05) MyHC type IIB gene expression in all muscles, but to a greater extent in RST. β 1-AR gene expression was unaffected by RAC or diet, whereas the expression of the β 2-AR gene was decreased (P < 0.001) by RAC. No significant RAC * diet interactions were observed in gene expression in this study, indicating that RAC altered MyHC and β 2-AR gene expression in porcine skeletal muscles independent of growth., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To describe ocular clinical findings, gross/histopathologic findings, and treatment regimens in a series of migratory chuck-will's-widows (Antrostomus carolinensis) (CWW) with corneal epithelial defects., Methods: Seven CWW were presented to the South Florida Wildlife Center (SFWC). Four presented with bilateral (OU) corneal ulceration; two developed corneal ulceration OU; one had no ocular lesions. Treatment protocols for patients with corneal ulcers included the following: medical therapy only or medical therapy combined with an additional procedure. Four patients including the bird with no ocular lesions were euthanized, and one patient died. Their globes were submitted for histopathology. Two patients were released., Results: Clinical findings prior to enucleation included superficial corneal ulceration with redundant epithelium persisting weeks to >1 month. On histopathology, epithelium in nonulcerated globes was remarkably thin; this was considered normal. Common histopathologic findings of ulcerated globes revealed epithelial and conjunctival attenuation with an acellular superficial stromal layer and hypercellular mid-stromal layer. One globe healed with medical therapy and cotton tip applicator debridement. Four globes healed by combination of medical therapy, equine amnion, nictitating membrane (NM) flap, and temporary tarsorrhaphy. No globes healed with diamond burr debridement or grid keratotomy., Conclusions: Factors that may be contributing to these corneal epithelial defects include, but are not limited to, normally thin epithelium, exposure keratopathy, neurotrophic disease, epithelial turnover and inadequate stem cell recruitment, inherited/genetic causes, and unidentified infectious agents (eg, viral etiologies). Of the 12 eyes treated, one healed with medical therapy/cotton tip applicator debridement, and four healed with medical therapy/equine amnion/nictitating membrane flap/temporary tarsorrhaphy., (© 2020 American College of Veterinary Ophthalmologists.)

Insufficient acidification results in dark, firm, and dry beef. While this defect is often indicative of a stress event antemortem, muscle tissue may change in response to feeding regime. Longissimus dorsi muscle samples from 10 grain-fed and 10 grass-fed market weight, angus-crossbred beef cattle were collected postmortem. Lower (P < .05) L* and a* values were recorded for steaks from grass-fed cattle. Higher (P < .05) ultimate pH values were noted in lean of grass-fed cattle compared to grain-fed cattle, yet differences in lactate, glycogen and glucose were not detected. Further, increased (P < .05) ultimate pH values and lower (P < .05) lactate accumulations were noted when samples from grass-fed cattle were subjected to an in vitro glycolysis system. Muscle from grass-fed beef possessed nearly two-fold more (P < .05) succinate dehydrogenase and (P < .001) myoglobin than that of grain-fed cattle. These data show lean from grass-fed beef has greater enzymes reflective of oxidative metabolism and suggest dark lean from grass-fed cattle may be a function of more oxidative metabolism rather than a stress-related event antemortem., (Copyright © 2019. Published by Elsevier Ltd.)

Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to sham-treated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: LE, is employed as the Director of AusPhage Pty Ltd. LE provided intellectual input to experimental design in terms of phage therapy delivery and scheduling, however LE was not directly involved in the conduct of experiments, data acquisition or data analysis. The Orthopaedic Research Institute of Queensland receives annual funding donations from Stryker to support the salary of AG. These affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: ALM solution, a combination of adenosine, lidocaine and Mg 2+ , is an emerging small volume therapy that has been shown to prevent and correct coagulopathy and surgery-related inflammation in preclinical models, though its application in orthopaedic surgery is yet to be demonstrated. The effect of ALM solution on chondrocytes is unknown. The aim of this preliminary study was to investigate the effect of ALM solution on viability and inflammatory responses of chondrogenically-differentiated human bone marrow-derived mesenchymal stem cells (chondro-MSC), in vitro., Methods: Chondro-MSC were exposed to media only, saline (0.9% NaCl or 1.3% NaCl) only, or saline containing ALM (1 mM adenosine, 3 mM lidocaine, 2.5 mM Mg 2+ ) or tranexamic acid (TXA, 100 mg/ml) for 1 or 4 h. Responses to ALM solutions containing higher lidocaine concentrations were also compared. Chondrocyte viability was determined using WST-8 colorimetric assays and inflammatory cytokine (TNF-α, IL-1β, IL-8) and matrix metalloproteinases (MMP-3, MMP-12, MMP-13) concentrations using multiplex bead arrays., Results: The viability of chondro-MSC was significantly greater after 1 h treatment with ALM compared to saline (96.2 ± 7.9 versus 75.6 ± 7.3%). Extension of exposure times to 4 h had no significant adverse effect on cell viability after treatment with ALM (1 h, 85.4 ± 5.6 v 4 h, 74.0 ± 15.2%). Cytotoxicity was evident following exposure to solutions containing lidocaine concentrations greater than 30 mM. There were no significant differences in viability (80 ± 5.4 v 57.3 ± 16.2%) or secretion of IL-8 (60 ± 20 v 160 ± 50 pg/ml), MMP-3 (0.95 ± 0.6 v 3.4 ± 1.6 ng/ml), and MMP-13 (4.2 ± 2.4 v 9.2 ± 4.3 ng/ml) in chondro-MSC exposed to saline, ALM or TXA., Conclusions: Short-term, in vitro exposure to clinically-relevant concentrations of ALM solution had no adverse inflammatory or chondrotoxic effects on human chondro-MSC, with responses comparable to saline and TXA. These findings provide support for continued evaluation of ALM solution as a possible therapeutic to improve outcomes following orthopaedic procedures.

Background: Tranexamic acid (TXA) is commonly used in orthopedic surgery to reduce excessive bleeding and transfusion requirements. Our aim was to examine if TXA was required in all osteoarthritis patients undergoing TKA surgery, and its possible effects on systemic inflammation and coagulation properties., Methods: Twenty-three patients (Oxford Score 22-29) were recruited consecutively; 12 patients received TXA before (IV, 1.2 g/90 kg) and immediately after surgery (intra-articular, 1.4 g/90 kg). Inflammatory mediators and ROTEM parameters were measured in blood at baseline, after the first bone-cut, immediately after surgery, and postoperative days 1 and 2., Results: After the bone cut and surgery, TXA significantly increased MCP-1, TNF-α, IL-1β and IL-6 levels compared to non-TXA patients, which was further amplified postoperatively. During surgery, TXA significantly prolonged EXTEM clot times, indicating a thrombin-slowing effect, despite little or no change in clot amplitude or fibrinogen. TXA was associated with three- to fivefold increases in FIBTEM maximum lysis (ML), a finding counter to TXA's antifibrinolytic effect. Maximum lysis for extrinsic and intrinsic pathways was < 8%, indicating little or no hyperfibrinolysis. No significant differences were found in postoperative hemoglobin between the two groups., Conclusions: TXA was associated with increased systemic inflammation during surgery compared to non-TXA patients, with further amplification on postoperative days 1 and 2. On the basis of little or no change in viscoelastic clot strength, fibrinogen or clot lysis, there appeared to be no clinical justification for TXA in our group of patients. Larger prospective, randomized trials are required to investigate a possible proinflammatory effect in TKA patients.

Background: Unicompartmental knee arthroplasty (UKA) lacks history of patient satisfaction and research addressing technique validity. The aim of this study was to determine minimally invasive navigated kinematic UKA accuracy by comparing postoperative limb alignment with preoperative stress values., Methods: A single-center retrospective study was conducted on 53 consecutive patients (postoperative alignment: varus n = 51, valgus n = 2) who underwent computer navigation assisted UKA. Two patient groups (A and B) predetermined by joint deformity cut-off points (B included valgus deformity) underwent preoperative magnetic resonance imaging and x-ray evaluation to assess limb alignment and exclude lateral and patellofemoral osteoarthritis. Preoperative and postoperative joint alignment, stress value, and range of movement were recorded with navigation. Outcome measures include comparison of postoperative alignment to the preoperative stress values for varus and valgus postoperative alignment groups and preoperative and/or postoperative Western Ontario and McMaster Universities and Knee Society Score evaluations., Results: Minor systematic bias was found between stress value and postoperative alignment; however, the magnitude of difference was clinically acceptable. Score evaluations, prosthesis size or alignment didn't differ between groups. Furthermore, there was no significant increase in range of movement at 2 years. There was a high degree of agreement between stress value and postoperative alignment values suggesting strong validity for the surgical technique to determine optimal postoperative alignment., Conclusion: This study validates our surgical technique. Minimally invasive navigated UKA allows us to predict predisease alignment and recreates it with high accuracy. Our clinical results at 2 years are comparable with other published data., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study is to determine the utility of self-assessment in microsurgical training using a previously validated rating scale., Design: A prospective study of surgical residents taking a hands-on 5-day microsurgical training course. Learners completed multiple self-assessments of their technical skills using the University of Western Ontario Microsurgical Acquisition/Assessment instrument. Simultaneously, preceptors assessed the learners using the same scale. Self-assessment and preceptor scores were compared using the Pearson correlation coefficient (PCC)., Results: There was a significant agreement noted between the 32 preceptor assessments and 36 self-assessments that were completed. Correlation between scores for the knot-tying (PCC = 0.62) and anastomosis modules (PCC = 0.77) was good and excellent, respectively. Preceptor scores and self-scores improved over the duration of the course: for preceptors, knot-tying scores increased from 58% on day 1 to 78% on day 5 (p = 0.02) and anastomosis scores improved from 56% to 82% (p = 0.004); for self-scores, knot-tying scores increased from 44% to 81% (p = 0.001) and anastomosis scores from 49% to 84% (p = 0.001). Learners with greater experience (higher postgraduate year level) tended to have higher self as well as preceptor ratings, albeit not statistically significant., Conclusion: Self-assessment using the University of Western Ontario Microsurgical Acquisition/Assessment instrument has good to excellent agreement with preceptor-assessment scores suggesting good interrater reliability. Self-assessment using such tools may, therefore, be used along with preceptor supervision and assessment to potentially improve self-directed learning during these courses., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)