Early intranasal medication administration in out-of-hospital cardiac arrest: Two randomized simulation trials.

Objective: Intranasal medications have been proposed as adjuncts to out-of-hospital cardiac arrest (OHCA) care. We sought to quantify the effects of intranasal medication administration (INMA) in OHCA workflows. Methods: We conducted separate randomized OHCA simulation trials with lay rescuers (LRs) and first responders (FRs). Participants were randomized to groups performing hands-only cardiopulmonary resuscitation (CPR)/automated external defibrillator with or without INMA during the second analysis phase. Time to compression following the second shock (CPR2) was the primary outcome and compression quality (chest compression rate (CCR) and fraction (CCF)) was the secondary outcome. We fit linear regression models adjusted for CPR training in the LR group and service years in the FR group. Results: Among LRs, INMA was associated with a significant increase in CPR2 (mean diff. 44.1 s, 95% CI: 14.9, 73.3), which persisted after adjustment (p = 0.005). We observed a significant decrease in CCR (INMA 95.1 compressions per min (cpm) vs control 104.2 cpm, mean diff. -9.1 cpm, 95% CI -16.6, -1.6) and CCF (INMA 62.4% vs control 69.8%, mean diff. -7.5%, 95% CI -12.0, -2.9). Among FRs, we found no significant CPR2 delays (mean diff. -2.1 s, 95% CI -15.9, 11.7), which persisted after adjustment (p = 0.704), or difference in quality (CCR INMA 115.5 cpm vs control 120.8 cpm, mean diff. -5.3 cpm, 95% CI -12.6, 2.0; CCF INMA 79.6% vs control 81.2% mean diff. -1.6%, 95% CI -7.4, 4.3%). Conclusions: INMA in LR resuscitation was associated with diminished resuscitation performance. INMA by FR did not impede key times or quality.

How do current police practices impact trauma care in the prehospital setting? A scoping review.

Objective: In the United States, police are often important co-responders to 911 calls with emergency medical services for medical emergencies. To date, there remains a lack of a comprehensive understanding of the mechanisms by which police response modifies time to in-hospital medical care for traumatically injured patients. Further, it remains unclear if differentials exist within or between communities. A scoping review was performed to identify studies evaluating prehospital transport of traumatically injured patients and the role or impact of police involvement. Methods: PubMed, SCOPUS, and Criminal Justice Abstracts databases were utilized to identify articles. English-language, US-based, peer-reviewed articles published on or prior to March 30, 2022 were eligible for inclusion. Results: Of 19,437 articles initially identified, 70 articles were selected for full review and 17 for final inclusion. Key findings included (1) current law enforcement practices involving scene clearance introduce the potential for delayed patient transport but to date there is little research quantifying delays; (2) police transport protocols may decrease transport times; and (3) there are no studies examining the potential impact of scene clearance practices at the patient or community level. Conclusions: Our results highlight that police are often the first on scene when responding to traumatic injuries and have an active role via scene clearance or, in some systems, patient transport. Despite the significant potential for impact on patient well-being, there remains a paucity of data examining and driving current practices.

2D-Hexagonal Boron Nitride Screen-Printed Bulk-Modified Electrochemical Platforms Explored towards Oxygen Reduction Reactions.

A low-cost, scalable and reproducible approach for the mass production of screen-printed electrode (SPE) platforms that have varying percentage mass incorporations of 2D hexagonal boron nitride (2D-hBN) (2D-hBN/SPEs) is demonstrated herein. These novel 2D-hBN/SPEs are explored as a potential metal-free electrocatalysts towards oxygen reduction reactions (ORRs) within acidic media where their performance is evaluated. A 5% mass incorporation of 2D-hBN into the SPEs resulted in the most beneficial ORR catalysis, reducing the ORR onset potential by ca. 200 mV in comparison to bare/unmodified SPEs. Furthermore, an increase in the achievable current of 83% is also exhibited upon the utilisation of a 2D-hBN/SPE in comparison to its unmodified equivalent. The screen-printed fabrication approach replaces the less-reproducible and time-consuming drop-casting technique of 2D-hBN and provides an alternative approach for the large-scale manufacture of novel electrode platforms that can be utilised in a variety of applications.

Improving Emergency Medical Services Information Exchange: Methods for Automating Entity Resolution.

The 21st century has seen an enormous growth in emergency medical services (EMS) information technology systems, with corresponding accumulation of large volumes of data. Despite this growth, integration efforts between EMS-based systems and electronic health records, and public-sector databases have been limited due to inconsistent data structure, data missingness, and policy and regulatory obstacles. Efforts to integrate EMS systems have benefited from the evolving science of entity resolution and record linkage. In this chapter, we present the history and fundamentals of record linkage techniques, an overview of past uses of this technology in EMS, and a look into the future of record linkage techniques for integrating EMS data systems including the use of machine learning-based techniques.

Simulating partial vaccine protection: BCG in badgers.

In wildlife disease management there are few diseases for which vaccination is a viable option. The human vaccine BCG has been used for the control of bovine tuberculosis in badgers since 2010 and is expected to increase. Understanding the long-term effects of repeated vaccination campaigns on disease prevalence is vital, but modelling thus far has generally assumed that a vaccine provides perfect protection to a proportion of the population, and that animals exposed to a repeated vaccination have a second independent chance of becoming protected. We held a workshop with experts in the field to obtain consensus over the main pathways for partial protection in the badger, and then simulated these using an established model. The available data supported the possibility that some individuals receive no benefit from the BCG vaccine, others may result in a delayed disease progression and in the remaining animals, vaccine protected the individual from any onward transmission. Simulating these pathways using different levels of overall efficacy demonstrated that partial protection leads to a reduced effect of vaccination, but in all of the identified scenarios it was still possible to eradicate disease in an isolated population with no disease introduction. We also identify those potential vaccination failures that require further investigation to determine which of our proposed pathways is the more likely.

Detection of a local Mycobacterium bovis reservoir using cattle surveillance data.

The incidence of bovine tuberculosis (TB, caused by Mycobacterium bovis) in cattle has been associated with TB in badgers (Meles meles) in parts of England. The aim was to identify badger-associated M. bovis reservoirs in the Edge Area, between the High- and Low-Risk Areas for cattle TB. Data from badger TB surveys were sparse. Therefore, a definition for a local M. bovis reservoir potentially shared by cattle and badgers was developed using cattle TB surveillance data. The performance of the definition was estimated through Latent Class Analysis using badger TB survey data. Spatial units (25 km2 ) in the Edge Area were classified as having a reservoir if they had (i) at least one TB incident in at least three of the previous 7 years, (ii) at least one TB incident in a cattle herd confirmed by post-mortem tests as due to M. bovis infection and not attributable to cattle movements in the previous 2 years and (iii) more confirmed TB incidents than un-confirmed in the previous 2 years. Approximately 20% of the Edge Area was classified as having a local M. bovis reservoir using the cattle-based definition. Assuming 15% TB prevalence in Edge Area badgers, sensitivity for the local M. bovis reservoir definition varied from 25.7% [95% credible interval (CrI): 10.7%-85.1%] to 64.8% (95% CrI: 48.1%-88.0%). Specificity was 91.9% (CrI: 83.6%-97.4%). Over 90% of the local reservoir was in stable endemic TB areas identified through previous work and its spatial distribution was largely consistent with local veterinary knowledge. Uncertainty in the reservoir spatial distribution was explored through its recalculation in spatial units shifted in different directions. We recommend that the definition is re-evaluated as further data on badger infection with M. bovis become available.

Simulating the next steps in badger control for bovine tuberculosis in England.

Industry-led culling of badgers has occurred in England to reduce the incidence of bovine tuberculosis in cattle for a number of years. Badger vaccination is also possible, and a move away from culling was "highly desirable" in a recent report to the UK government. Here we used an established simulation model to examine badger control option in a post-cull environment in England. These options included no control, various intermittent culling, badger vaccination and use of a vaccine combined with fertility control. The initial simulated cull led to a dramatic reduction in the number of infected badgers present, which increased slowly if there was no further badger management. All three approaches led to a further reduction in the number of infected badgers, with little to choose between the strategies. We do note that of the management strategies only vaccination on its own leads to a recovery of the badger population, but also an increase in the number of badgers that need to be vaccinated. We conclude that vaccination post-cull, appears to be particularly effective, compared to vaccination when the host population is at carrying capacity.

UK national study of barriers to renal transplantation in children.

AIMS: To investigate access to paediatric renal transplantation and examine potential barriers within the process. METHODS: Cross-sectional, multicentre, observational study where paediatric nephrology centres in the UK were requested to provide data on transplantation plans for all children (<18 years) with end-stage kidney disease (ESKD). RESULTS: 308 children with ESKD were included in this study from 12 out of 13 UK paediatric nephrology centres. 139 (45%) were being prepared for living donor transplantation and 82 (27%) were listed for deceased donor transplantation. The most common cited factors delaying transplantation from occurring in children were disease factors (36%), donor availability (27%) and size of the child (20%). Psychosocial factors were listed as a barrier in 19% of children. CONCLUSIONS: In this study we have documented the main barriers to renal transplantation in children. Some identified factors may be modifiable through local or national intervention, including donor availability and patient psychosocial factors.

Versailles Project on Advanced Materials and Standards interlaboratory study on intensity calibration for x-ray photoelectron spectroscopy instruments using low-density polyethylene.

We report the results of a Versailles Project on Advanced Materials and Standards interlaboratory study on the intensity scale calibration of x-ray photoelectron spectrometers using low-density polyethylene (LDPE) as an alternative material to gold, silver, and copper. An improved set of LDPE reference spectra, corrected for different instrument geometries using a quartz-monochromated Al Kα x-ray source, was developed using data provided by participants in this study. Using these new reference spectra, a transmission function was calculated for each dataset that participants provided. When compared to a similar calibration procedure using the NPL reference spectra for gold, the LDPE intensity calibration method achieves an absolute offset of ∼3.0% and a systematic deviation of ±6.5% on average across all participants. For spectra recorded at high pass energies (≥90 eV), values of absolute offset and systematic deviation are ∼5.8% and ±5.7%, respectively, whereas for spectra collected at lower pass energies (<90 eV), values of absolute offset and systematic deviation are ∼4.9% and ±8.8%, respectively; low pass energy spectra perform worse than the global average, in terms of systematic deviations, due to diminished count rates and signal-to-noise ratio. Differences in absolute offset are attributed to the surface roughness of the LDPE induced by sample preparation. We further assess the usability of LDPE as a secondary reference material and comment on its performance in the presence of issues such as variable dark noise, x-ray warm up times, inaccuracy at low count rates, and underlying spectrometer problems. In response to participant feedback and the results of the study, we provide an updated LDPE intensity calibration protocol to address the issues highlighted in the interlaboratory study. We also comment on the lack of implementation of a consistent and traceable intensity calibration method across the community of x-ray photoelectron spectroscopy (XPS) users and, therefore, propose a route to achieving this with the assistance of instrument manufacturers, metrology laboratories, and experts leading to an international standard for XPS intensity scale calibration.

Modified magnetic core-shell mesoporous silica nano-formulations with encapsulated quercetin exhibit anti-amyloid and antioxidant activity.

Targeted tissue drug delivery is a challenge in contemporary nanotechnologically driven therapeutic approaches, with the interplay interactions between nanohost and encapsulated drug shaping the ultimate properties of transport, release and efficacy of the drug at its destination. Prompted by the need to pursue the synthesis of such hybrid systems, a family of modified magnetic core-shell mesoporous silica nano-formulations was synthesized with encapsulated quercetin, a natural flavonoid with proven bioactivity. The new nanocarriers were produced via the sol-gel process, using tetraethoxysilane as a precursor and bearing a magnetic core of surface-modified monodispersed magnetite colloidal superparamagnetic nanoparticles, subsequently surface-modified with polyethylene glycol 3000 (PEG3k). The arising nano-formulations were evaluated for their textural and structural properties, exhibiting enhanced solubility and stability in physiological media, as evidenced by the loading capacity, entrapment efficiency results and in vitro release studies of their load. Guided by the increased bioavailability of quercetin in its encapsulated form, further evaluation of the biological activity of the magnetic as well as non-magnetic core-shell nanoparticles, pertaining to their anti-amyloid and antioxidant potential, revealed interference with the aggregation of ß-amyloid peptide (Aß) in Alzheimer's disease, reduction of Aß cellular toxicity and minimization of Aß-induced Reactive Oxygen Species (ROS) generation. The data indicate that the biological properties of released quercetin are maintained in the presence of the host nanocarriers. Collectively, the findings suggest that the emerging hybrid nano-formulations can function as efficient nanocarriers of hydrophobic natural flavonoids in the development of multifunctional nanomaterials toward therapeutic applications.

Optimization of anti-wear and anti-bacterial properties of beta TiNb alloy via controlling duty cycle in open-air laser nitriding.

A multifunctional beta TiNb surface, featuring wear-resistant and antibacterial properties, was successfully created by means of open-air fibre laser nitriding. Beta TiNb alloy was selected in this study as it has low Young's modulus, is highly biocompatible, and thus can be a promising prosthetic joint material. It is, however, necessary to overcome intrinsically weak mechanical properties and poor wear resistance of beta TiNb in order to cover the range of applications to load-bearing and/or shearing parts. To this end, open-air laser nitriding technique was employed. A control of single processing parameter, namely duty cycle (between 5% and 100%), led to substantially different structural and functional properties of the processed beta TiNb surfaces as analyzed by an array of analytical tools. The TiNb samples nitrided at the DC condition of 60% showed a most enhanced performance in terms of improving surface hardness, anti-friction, anti-wear and anti-bacterial properties in comparison with other conditions. These findings are expected to be highly important and useful when TiNb alloys are considered as materials for hip/knee articular joint implants.

Estimating wildlife vaccination coverage using genetic methods.

Vaccination is a useful approach for the control of disease in wildlife populations. However, its effectiveness is dependent in part on delivery to a sufficient proportion of the target population. Measuring the proportions of wild animal populations that have been vaccinated is challenging and so there is a need to develop robust approaches that can contribute to our understanding of the likely efficacy of wildlife vaccination campaigns. We used a modified capture mark recapture technique to estimate vaccine coverage in a wild population of European badgers (Meles meles) vaccinated by live-trapping and injecting with Bacillus Calmette-Guérin as part of a bovine tuberculosis control initiative in Wales, United Kingdom. Our approach used genetic matching of vaccinated animals to a sample of the wider population to estimate the percentage of badgers that had been vaccinated. Individual-specific genetic profiles were obtained using microsatellite genotyping of hair samples, which were collected directly from trapped and vaccinated badgers and non-invasively from the wider population using hair traps deployed at badger burrows (setts). With two nights of trapping at each sett in an annual campaign, an estimated 50 % (95 % confidence interval 40-60 %) of the badger population received at least one dose of vaccine in a single year. Using a simple population model this suggested that the proportion of the population that would have received at least one dose of vaccine over the course of the four year vaccination campaign was between 67 % and 83 %. This is the first attempt, outside of field trials, to quantify the level of vaccine coverage achieved by trapping and injecting badgers, which is currently the only option for delivering BCG vaccine to this species. The results therefore have specific application to bTB control policy and the novel approach may have wider value in wildlife management and research.

Modelling Spatial and Temporal Patterns of African Swine Fever in an Isolated Wild Boar Population to Support Decision-Making.

African swine fever (ASF) is a highly contagious disease affecting all suids including wild boar. As the disease can damage commercial pig production and its circulation can threaten international trade, understanding the risks produced by free-living wild boar (as a wildlife reservoir) is important to ensure proportionate policies to exclude the disease, as well as an effective contingency response. The recent spread of the virus into Western Europe has produced concerns in many stakeholders including pig producers and national governments. Unlike in mainland Europe, where wild boar are widespread, in Britain, free-living populations have only recently re-established, and whilst these are still relatively small and isolated, they may provide a sufficient reservoir capable of sustaining disease and may thus present a continual source of infection risk to domestic pigs. This study focuses on one component of the risk produced by wild boar, specifically the distribution and persistence of virus in a landscape produced by the natural circulation of disease within wild boar. We used a spatial individual-based model run across a representation of a real landscape to explore the epidemiological consequences of an introduction of ASF into the Forest of Dean, currently hosting the largest population of wild boar in England. We explore various scenarios including variations in the prophylactic management of boar, as well as variations in reactive management (contingency response) following the detection of disease to evaluate their value in reducing this specific risk (presence of ASF virus of wild boar origin in the landscape). The abundance and distribution of wild boar is predicted to increase across our study extent over the next 20 years. Outbreaks of ASF are not predicted to be self-sustaining, with the median time to disease "burn-out" (no new infections) being 14 weeks. Carcass removal, as a tool in a package of reactive management, was of limited value in reducing the duration of outbreaks in this study. We suggest that useful predictions of some of the risks produced by ASF might be possible using only the distribution of the boar, rather than more difficult abundance or density measures.

Between roost contact is essential for maintenance of European bat lyssavirus type-2 in Myotis daubentonii bat reservoir: 'The Swarming Hypothesis'.

Many high-consequence human and animal pathogens persist in wildlife reservoirs. An understanding of the dynamics of these pathogens in their reservoir hosts is crucial to inform the risk of spill-over events, yet our understanding of these dynamics is frequently insufficient. Viral persistence in a wild bat population was investigated by combining empirical data and in-silico analyses to test hypotheses on mechanisms for viral persistence. A fatal zoonotic virus, European Bat lyssavirus type 2 (EBLV-2), in Daubenton's bats (Myotis daubentonii) was used as a model system. A total of 1839 M. daubentonii were sampled for evidence of virus exposure and excretion during a prospective nine year serial cross-sectional survey. Multivariable statistical models demonstrated age-related differences in seroprevalence, with significant variation in seropositivity over time and among roosts. An Approximate Bayesian Computation approach was used to model the infection dynamics incorporating the known host ecology. The results demonstrate that EBLV-2 is endemic in the study population, and suggest that mixing between roosts during seasonal swarming events is necessary to maintain EBLV-2 in the population. These findings contribute to understanding how bat viruses can persist despite low prevalence of infection, and why infection is constrained to certain bat species in multispecies roosts and ecosystems.

Modeling current and potential distributions of mammal species using presence-only data: A case study on British deer.

AIM: Decisions on wildlife conservation, management, and epidemiological risk are best based on robust evidence. The continual improvement of species distributions, such that they can be relied upon in decision-making, is important. Here we seek to refine aspects of a generic modelling approach and improve the utility of species distribution maps. LOCATION: Great Britain (GB). METHODS: We applied a modeling framework based on hierarchical Bayesian species distribution models exploiting opportunistic occurrence records from citizen science datasets to predict both current and potential distributions for each of the six deer species known to be present in GB. Using the resulting maps, we performed a simple analysis of the overlap between species to illustrate possible contact, which we interpret as the relative risk of potential disease spread given an introduction. RESULTS: Predicted distribution maps showed good agreement with the broader scale occurrence reported by a recent national deer survey with an average True Skill Statistics and AUC of 0.69 and 0.89, respectively. Aggregation of the maps for all species highlighted regions of central and eastern England as well as parts of Scotland where extensive areas of range overlap could result in interspecific contact with consequences for risk assessments for diseases of deer. However, if populations are allowed to expand to their predicted potential, then areas of overlap, and therefore disease interspecific transmission risk, will become extensive and widespread across all of mainland Britain. MAIN CONCLUSIONS: The generic modeling approach outlined performed well across all of the deer species tested, offering a robust and reliable tool through which current and potential animal distributions can be estimated and presented. Our application, intended to inform quantitative risk assessments, demonstrates the practical use of such outputs to generate the valuable evidence required to inform policy decisions on issues such as management strategy.

Magnetic cationic liposomal nanocarriers for the efficient drug delivery of a curcumin-based vanadium complex with anticancer potential.

In this work novel magnetic cationic liposomal nanoformulations were synthesized for the encapsulation of a crystallographically defined ternary V(IV)-curcumin-bipyridine (VCur) complex with proven bioactivity, as potential anticancer agents. The liposomal vesicles were produced via the thin film hydration method employing N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium (DOTAP) and egg phosphatidylcholine lipids and were magnetized through the addition of citric acid surface-modified monodispersed magnetite colloidal magnetic nanoparticles. The obtained nanoformulations were evaluated for their structural and textural properties and shown to have exceptional stability and enhanced solubility in physiological media, demonstrated by the entrapment efficiency and loading capacity results and the in vitro release studies of their cargo. Furthermore, the generated liposomal formulations preserved the superparamagnetic behavior of the employed magnetic core maintaining the physicochemical and morphological requirements for targeted drug delivery applications. The novel nanomaterials were further biologically evaluated for their DNA interaction potential and were found to act as intercalators. The findings suggest that the positively charged magnetic liposomal nanoformulations can generate increased concentration of their cargo at the DNA site, offering a further dimension in the importance of cationic liposomes as nanocarriers of hydrophobic anticancer metal ion complexes for the development of new multifunctional pharmaceutical nanomaterials with enhanced bioavailability and targeted antitumor activity.

The risk of foot-and-mouth disease becoming endemic in a wildlife host is driven by spatial extent rather than density.

In the past 20 years, free living populations of feral wild boar have re-established in several locations across the UK. One of the largest populations is in the Forest of Dean where numbers have been steadily increasing since monitoring began in 2008, with estimates from 2016 reporting a population of more than 1500. Feral wild boar have significant ecological and environmental impacts and may present a serious epidemiological risk to neighbouring livestock as they are a vector for a number of important livestock diseases. This includes foot-and-mouth disease (FMD) which is currently absent from the UK. We developed an individual-based spatially explicit modelling approach to simulate feral wild boar populations in the Forest of Dean (England, UK) and use it to explore whether current or future populations might be sufficient to produce long-lived outbreaks of FMD in this potential wildlife reservoir. Our findings suggest that if you exclude the spread from feral wild boar to other susceptible species, the current population of boar is insufficient to maintain FMD, with 95% of unmanaged simulations indicating disease burn-out within a year (not involving boar management specifically for disease). However, if boar are allowed to spread beyond their current range into the adjacent landscape, they might maintain a self-sustaining reservoir of infection for the disease.

A novel 'bottom-up' synthesis of few- and multi-layer graphene platelets with partial oxidation via cavitation.

The transient cavitation of diaromatic components such as 1-methylnaphthalene has been used to produce graphene platelets in a 'bottom-up' synthesis via the high temperature (>5000 K) conditions that are generated inside collapsing bubbles. Acoustic cavitation produced yields of 5.7 × 10-11 kgJ-1 at a production rate of 2.2 × 10-9 kgs-1. This can be improved by generating cavitation hydrodynamically, thus making commercial scale production viable. Hydrodynamic cavitation produced platelets with larger lateral dimensions (≥2 µm) than those formed by acoustic cavitation (10-200 nm). The partially oxidised nature of the platelets enables their covalent chemical functionalisation, which was achieved by combining suitable molecules in the reaction medium to affect a one-pot formation and functionalisation of graphene.

Nanodiamond based surface modified screen-printed electrodes for the simultaneous voltammetric determination of dopamine and uric acid.

The electroanalytical detection of the neurotransmitter dopamine (DA) in the presence of uric acid (UA) is explored for the first time using commercially procured nanodiamonds (NDs). These are electrically wired via surface modification upon screen-printed graphite macroelectrodes (SPEs). The surface coverage of the NDs on the SPEs was explored in order to optimize electroanalytical outputs to result in well-resolved signals and in low limits of detection. The (electro)analytical outputs are observed to be more sensitive than those achieved at bare (unmodified) SPEs. Such responses, previously reported in the academic literature have been reported to be electrocatalytic and have been previously attributed to the presence of surface sp2 carbon and oxygenated species on the surface of the NDs. However, XPS analysis reveals the commercial NDs to be solely composed of nonconductive sp3 carbon. The low/negligible electroconductivity of the NDs was further confirmed when ND paste electrodes were fabricated and found to exhibit no electrochemical activity. The electroanalytical enhancement, when using NDs electronically wired upon SPEs, is attributed not to the NDs themselves being electrocatalytic, as reported previously, but rather changes in mass transport where the inert NDs block the underlying electroactive SPEs and create a random array of graphite microelectrodes. The electrode was applied to simultaneous sensing of DA and UA at pH 5.5. Figures of merit include (a) low working potentials of around 0.27 and 0.35 V (vs. Ag/AgCl); and (b) detection limits of 5.7 × 10-7 and 8.9 × 10-7 M for DA and UA, respectively. Graphical abstract The electroanalytical enhancement of screen-printed electrodes modified with inert/non-conductive nanodiamonds is due to a change in mass transfer where the inert nanodiamonds facilitate the production of a random microelectrode array.