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Abstract Background Ischaemic strokes are medical emergencies, and reperfusion treatment, most commonly intravenous thrombolysis, is time-critical. Thrombolysis administration relies on well-organised pathways of care with highly skilled and efficient clinicians. Simulation training is a widespread teaching modality, but results from studies on the impact of this intervention have yet to be synthesised. This systematic review and meta-analysis aimed to synthesise the evidence and provide a recommendation regarding the effects of simulation training for healthcare professionals on door-to-needle time in the emergency thrombolysis of patients with ischaemic stroke. Methods Seven electronic databases were systematically searched (last updated 12th July 2023) for eligible full-text articles and conference abstracts. Results were screened for relevance by two independent reviewers. The primary outcome was door-to-needle time for recombinant tissue plasminogen activator administration in emergency patients with ischaemic stroke. The secondary outcomes were learner-centred, improvements in knowledge and communication, self-perceived usefulness of training, and feeling ‘safe’ in thrombolysis-related decision-making. Data were extracted, risk of study bias assessed, and analysis was performed using RevMan™ software (Web version 5.6.0, The Cochrane Collaboration). The quality of the evidence was assessed using the Medical Education Research Study Quality Instrument. Results Eleven studies were included in the meta-analysis and nineteen in the qualitative synthesis (n = 20,189 total patients). There were statistically significant effects of simulation training in reducing door-to-needle time; mean difference of 15 min [95% confidence intervals (CI) 8 to 21 min]; in improving healthcare professionals’ acute stroke care knowledge; risk ratio (RR) 0.42 (95% CI 0.30 to 0.60); and in feeling ‘safe’ in thrombolysis-related decision-making; RR 0.46 (95% CI 0.36 to 0.59). Furthermore, simulation training improved healthcare professionals' communication and was self-perceived as useful training. Conclusion This meta-analysis showed that simulation training improves door-to-needle times for the delivery of thrombolysis in ischaemic stroke. However, results should be interpreted with caution due to the heterogeneity of the included studies.

Summary: Background: Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury. Methods: In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.3 or 0.65 mg/kg) or placebo (1:1) for 2 days (5 intravenous infusions), stratified by region and renal function. Eligible patients had at least one pre-defined AKI risk factor. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR]

Objectives: The Prospective Randomized On-X Mechanical Prosthesis Versus St Jude Medical Mechanical Prosthesis Evaluation (PROSE) trial purpose was to investigate whether a current-generation mechanical prosthesis (On-X; On-X Life Technologies/Artivion Inc) reduced the incidence of thromboembolic-related complications compared with a previous-generation mechanical prosthesis (St Jude Medical Mechanical Prosthesis; Abbott/St Jude Medical). This second report documents the valve-related complications by individual prostheses and by Western and Developing populations. Methods: The PROSE trial study was conducted in 28 worldwide centers and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The study protocol, and analyses of 10 demographic variables and 24 risk factors were published in detail in 2021. Results: The total patient population (N = 855) included patients receiving an On-X valve (n = 462) and a St Jude Medical valve (n = 393). The overall freedom evaluation showed no differences at 5 years between the prostheses for thromboembolism or for valve thrombosis. There were also no differences in mortality. There were several differences between Developing and Western populations. The freedom relations at 5 years for mortality favored Western over Developing populations. Valve thrombosis was differentiated by position and site: aortic

Abstract Objectives The PROSE trial purpose is to investigate whether the incidence of thromboembolic—related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.—On-X) compared with a previous generation mechanical prosthesis (St Jude Medical—SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. Methods The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. Results The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. Conclusions The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

Abstract Diabetic retinopathy (DR) is a form of microangiopathy. Reducing oxidative stress in the mitochondria and cell membranes decreases ischemic injury and end-organ damage to the retina. New approaches are needed, which reduce the risk and improve the outcomes of DR while complementing current therapeutic approaches. Homocysteine (Hcy) elevation and oxidative stress are potential therapeutic targets in DR. Common genetic polymorphisms such as those of methylenetetrahydrofolate reductase (MTHFR), increase Hcy and DR risk and severity. Patients with DR have high incidences of deficiencies of crucial vitamins, minerals, and related compounds, which also lead to elevation of Hcy and oxidative stress. Addressing the effects of the MTHFR polymorphism and addressing comorbid deficiencies and insufficiencies reduce the impact and severity of the disease. This approach provides safe and simple strategies that support conventional care and improve outcomes. Suboptimal vitamin co-factor availability also impairs the release of neurotrophic and neuroprotective growth factors. Collectively, this accounts for variability in presentation and response of DR to conventional therapy. Fortunately, there are straightforward recommendations for addressing these issues and supporting traditional treatment plans. We have reviewed the literature for nutritional interventions that support conventional therapies to reduce disease risk and severity. Optimal combinations of vitamins B1, B2, B6, L-methylfolate, methylcobalamin (B12), C, D, natural vitamin E complex, lutein, zeaxanthin, alpha-lipoic acid, and n-acetylcysteine are identified for protecting the retina and choroid. Certain medical foods have been successfully used as therapy for retinopathy. Recommendations based on this review and our clinical experience are developed for clinicians to use to support conventional therapy for DR. DR from both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have similar retinal findings and responses to nutritional therapies.

Abstract By using risk-adjusted price signals to transfer responsibility for property-level flood protection and recovery from governments to property owners, flood insurance represents a key tenet of the flood risk management (FRM) paradigm. The Government of Canada has worked with insurers to introduce flood insurance for the first time as a part of a broader shift towards FRM to limit the growing costs of flooding. The viability of flood insurance in Canada, however, has been questioned by research that disputes the utility of purchasing coverage by property owners. This study tested this assumption by drawing on public opinion survey data to assess factors that influence decisions about the utility of insurance. The findings reveal that Canadians have limited knowledge of flood insurance coverage, exhibit a low willingness-to-pay for both insurance and property-level flood protection measures, and expect governments to shoulder much of the financial burden of flood recovery through disaster assistance.

Abstract Background Homocysteine and vitamin D may play a role in the development of diabetic and hypertensive retinopathy in patients with diabetes mellitus (DM) and hypertension. Supplementing food with L-methylfolate and vitamin D theoretically may improve diabetic and hypertensive retinopathy, however, the outcome of these nutritional approaches has not been fully examined. A retrospective case review was done of cases of retinopathy reversal in patients on Ocufolin™ and a similar nonprescription multivitamin, Eyefolate™. In this study, they were administered L-methylfolate (2.7 mg and 3.0 mg, respectively) and vitamin D3 (4500 IU each). These dosages are significantly above the RDA but well below levels associated with toxicity. Case presentation Seven patients had nonproliferative diabetic retinopathy (NPDR) and some of them had hypertension. One patient had only hypertensive retinopathy. All patients were instructed to take Ocufolin™ medical food as a food supplement. Baseline genetic testing for MTHFR polymorphisms was conducted. Fundus photography was used to document the fundus condition of the enrolled eyes in 8 NPDR patients at the initial and follow-up visits. Microaneurysms (MA) and exudates were observed to be improved in some trial patients. All subjects had one or more MTHFR polymorphisms. All had diabetic retinopathy, hypertensive retinopathy, or both. MAs were resolved, and exudates were decreased in 8/8 cases after taking the medical food. Retinal edema was found in 2/8 cases and improved or resolved in both cases after taking the medical food or the supplement. The best corrected visual activity was stable or improved in 8/8 cases. Conclusion We report a series of diabetic and hypertensive retinopathy cases with MTHFR polymorphisms and the improvement of retinal microvasculature (mainly MAs) in serial fundus photography after taking a medical food or supplement containing L-methylfolate and vitamin D. It appears that the use of nutritional supplements and medical foods containing L-methylfolate and vitamin D may be effective in facilitating the improvement of diabetic and hypertensive retinopathy.

This article is concerned with providing empirical evidence relating to the use of digital media and resistance during the so-called Arab Spring events. These events have been widely acknowledged as a case where digital media significantly contributed to the successful attainment of movements’ objectives. The use of such innovative technologies has been tied to the characteristics and, ultimately, the ends of these movements, with their ‘youthful’, ‘leaderless’ and ‘spontaneous’ nature reflecting Western-orientated practices. However, the analysis presented here utilises interview data obtained from participants in the 2010/11 Tunisian Revolution, detailing their perspectives and explanations of digital media’s role. The data and analysis show that while such technologies were a useful tool, their prominence has been exaggerated and offers a flawed understanding of the events. Rather, the social change being pursued during the Tunisian revolution was profound. Therefore, the deeper implications of the common emphasis on digital media in the literature is explored, with Rosa’s (2015) assessment of social acceleration being informative for elaborating on the nuances of these technologies’ use during the 2010/11 events.

Abstract Background Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a significant problem for livestock industries in many countries worldwide including Northern Ireland, where a test and slaughter regime has utilised the Single Intradermal Comparative Cervical Tuberculin (SICCT) test since 1959. We investigated the variation in post-mortem confirmation based on bTB visible lesion (VL) presence during herd breakdowns using two model suites. We investigated animal-level characteristics, while controlling for herd-level factors and clustering. We were interested in potential impacts of concurrent infection, and therefore we assessed whether animals with evidence of liver fluke infection (Fasciola hepatica; post-mortem inspection), M. avium reactors (animals with negative M. bovis-avium (b-a) tuberculin reactions) or Bovine Viral Diarrhoea Virus (BVDV; RT-PCR tested) were associated with bTB confirmation. Results The dataset included 6242 animals removed during the 14 month study period (2013–2015). bTB-VL presence was significantly increased in animals with greater b-a reaction size at the disclosing SICCT test (e.g. b-a = 5-9 mm vs. b-a = 0 mm, adjusted Odds ratio (aOR): 14.57; p 0.1). Conclusions Our results suggest that neither co-infection of liver fluke nor BVDV had a significant effect on the presence of VLs in this high-risk cohort. M. avium tuberculin reactors had a significantly increased risk of disclosing with a bTB lesion, which could be related to the impact of co-infection with M. avium subsp. paratuberculosis (MAP) affecting the performance of the SICCT however further research in this area is required. Movements, test history, breed and age were important factors influencing confirmation in high-risk animals.

Purpose: The OSCE is regarded as the gold standard of competence assessment in many healthcare programs, however, there are numerous internal and external sources of variation contributing to checklist marks. There is concern amongst organisers that candidates may be unfairly disadvantaged if they follow an "excellent" preceding candidate. This study assessed if average checklist scores differed depending on who a candidate follows accounted for different sources of variation. Design/methodology/approach: This study examined assessment data from final year MBChB OSCEs at the University of Aberdeen and categorised candidates into three levels dependent on examiner awarded global scores of preceding candidates for each station. Data were modelled using a linear mixed model incorporating fixed and random effects. Findings: A total of 349 candidates sat the OSCEs. The predicted mean (95% CI) score for students following an "excellent" candidate was 21.6 (20.6, 22.6), followed "others" was 21.5 (20.5, 22.4) and followed an "unsatisfactory" student was 22.2 (21.1, 23.3). When accounted for individual, examiner and station levels variabilities, students following an "excellent" candidate did not have different mean scores compared to those who followed "other" (p = 0.829) or "unsatisfactory" candidates (p = 0.162), however, students who followed an "unsatisfactory" student scored slightly higher on average compared to those who followed "other" (p = 0.038). Originality/value: There was weak evidence that candidate's checklist variations could be attributed to who they followed, particularly those following unsatisfactory students; the difference in predicted mean scores may be of little practical relevance. Further studies with multiple centres may be warranted assuring perceived fairness of the OSCE to candidates and educators.

The "Living Loving Dying" research project aimed to improve end of life and bereavement care for people caring and dying in rural areas. The data were provided by people who had experienced caring for someone until his/her death, while living in an area of low population and geographical isolation. Undertaking data collection on such a sensitive topic, from people still vulnerable from the impacts of death and grief, requires the use of particularly sensitive research methods. It is also important that participants feel their voices are heard and that they are contributing to positive change for others. In view of this we positioned people to participate as community-partners and utilized a descriptive qualitative design with participatory elements in the data collection method of in-depth, semi structured interviewing. The non-hierarchical relationship between researchers and community-partners were key influences for using participatory elements in this research with a vulnerable population. In this article we reflect on the pragmatic and ethical considerations that the application of this method has for rural end-of-life research.

Although the importance of urban infrastructure resilience can be inferred, its terminology remains convoluted within the literature due to a lack of systematic review from a sustainable development planning perspective. This review paper was designed to elucidate connected research themes, scientific popularity, and conceptual boundaries of the term infrastructure resilience in an urban context. Three guiding research questions were asked: What does urban infrastructure resilience really mean? What are the most common research topics connected to urban infrastructure resilience? How can humanity further improve urban infrastructure resilience from a sustainable development planning perspective? To answer these research questions, a two-step literature analysis was adopted consisting of: (i) a scoping review to select relevant publications based on a specific search query; and (ii) a content analysis to reduce and synthesize the scoping review findings further based on the three most applicable publishing outlets. The scoping review reduced articles to 535, while content analysis further condensed it to 84 across three key journals. With North America and Europe leading, the findings corroborated that eight connected subject areas establish the conceptual boundaries of urban infrastructure resilience. The eight related research topics in decreasing abundance were: (1) climate change, (2) floods, (3) disasters, (4) environmental policy, (5) ecosystems, (6) risk assessment, (7) emergency preparedness, and (8) adaptation. In conclusion, these research topics should be pursued when creating urban infrastructure resilience strategies for moving towards sustainability.

Dance Dance Revolution is a pioneering exergame which has attracted considerable interest for its potential to promote regular exercise and its associated health benefits. The advent of a range of different consumer body motion tracking video game console peripherals raises the question whether their different technological affordances (i.e., variations in the type and number of body limbs that they can track) influence the user experience while playing dance-based exergames both in terms of the level of physical exertion and the nature of the play experience. To investigate these issues a group of subjects performed a total of six comparable dance routines selected from commercial dance-based exergames (two routines from each game) on three different consoles. The subjects’ level of physical exertion was assessed by measuring oxygen consumption and heart rate. They also reported their perceived level of exertion, difficulty, and enjoyment ratings after completing each dance routine. No differences were found in the physiological measures of exertion between the peripherals/consoles. However, there were significant variations in the difficulty and enjoyment ratings between peripherals. The design implications of these results are discussed including the tension between helping to guide and coordinate player movement versus offering greater movement flexibility.

Abstract Colorectal cancer is one of the top contributors to cancer-related deaths in the United States, with over 100,000 estimated cases in 2020 and over 50,000 deaths. The most common screening technique is minimally invasive colonoscopy using either reflected white light endoscopy or narrow-band imaging. However, current imaging modalities have only moderate sensitivity and specificity for lesion detection. We have developed a novel fluorescence excitation-scanning hyperspectral imaging (HSI) approach to sample image and spectroscopic data simultaneously on microscope and endoscope platforms for enhanced diagnostic potential. Unfortunately, fluorescence excitation-scanning HSI datasets pose major challenges for data processing, interpretability, and classification due to their high dimensionality. Here, we present an end-to-end scalable Artificial Intelligence (AI) framework built for classification of excitation-scanning HSI microscopy data that provides accurate image classification and interpretability of the AI decision-making process. The developed AI framework is able to perform real-time HSI classification with different speed/classification performance trade-offs by tailoring the dimensionality of the dataset, supporting different dimensions of deep learning models, and varying the architecture of deep learning models. We have also incorporated tools to visualize the exact location of the lesion detected by the AI decision-making process and to provide heatmap-based pixel-by-pixel interpretability. In addition, our deep learning framework provides wavelength-dependent impact as a heatmap, which allows visualization of the contributions of HSI wavelength bands during the AI decision-making process. This framework is well-suited for HSI microscope and endoscope platforms, where real-time analysis and visualization of classification results are required by clinicians.

Neurons are one of the few cell types in the human body that do not support HIV type-1 (HIV-1) replication. Although the lack of key receptors is a major obstacle to infection, studies suggest that additional functions inhibit virus replication to explain the exquisite resistance of neurons to HIV-1. However, specific neuronal factors that may explain this resistance remain to be discovered. In a screen for antiviral factors using a fibroblast line chemically mutagenized and selected for resistance to retroviral infection, we recently identified induction of rat FEZ1 (fasciculation and elongation protein zeta-i), a brain-specific protein, as the cause of this resistance. When exogenously expressed in nonneuronal cell lines rat FEZ1 blocked nuclear entry of retroviral DNA. Here, we demonstrate that among human brain cells, neurons naturally express high levels of FEZ1 compared to astrocytes or microglia cells and are correspondingly less susceptible to infection with pseudotyped HIV-1 that bypasses receptor-mediated viral entry. Demonstrating that endogenous FEZ1 was functionally important in the resistance of neurons to HIV-i infection, siRNA-mediated knockdown of endogenous FEZ1 increased the infectivity of neurons while sensitive brain cell types like microglia became more resistant upon FEZ1 overexpression. In addition, FEZ1 expression was not induced in response to IFN treatment. As such, in contrast to other widely expressed, IFN-inducible antiviral factors, FEZ1 appears to represent a unique neuron-specific determinant of cellular susceptibility to infection in a cell type that is naturally resistant to HIV-1. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) DNA is found in virtually all cervical cancers, strongly suggesting that these viruses are necessary to initiate this disease. The HPV E2 protein is required for viral replication, but E2 expression is usually lost in HPV-transformed cells because of the integration of viral DNA into the host chromosome. Several studies have shown that the reintroduction of E2 into HPV-transformed cells can induce growth arrest and apoptotic cell death. This raises the possibility that E2 could be useful in the treatment of HPV-induced disease. However, the effects of E2 on cell proliferation are not limited to HPV-transformed cells. The E2 protein from HPV type 16 can induce apoptosis via at least two pathways. One pathway involves the binding of E2 to p53 and operates in HPV-transformed cells, many non-HPV-transformed cell lines, and untransformed normal cells. The second pathway requires the binding of E2 to the viral genome and operates only in HPV-transformed cells. A mutation in E2 that significantly reduces the binding of this protein to p53 abrogates the induction of apoptosis in non-HPV-transformed cells and normal cells, but has no effect on the ability of the mutated protein to induce apoptosis in HPV-transformed cells. Here we show that a chimeric protein consisting of this mutant of E2, fused to the herpes simplex virus type 1 VP22 protein, can traffic between cells in a three-dimensional tumor model and induce apoptosis in HPV-transformed cells with high specificity. This cancer cell-specific inducer of apoptosis may be useful in the treatment of cervical cancer and other HPV-induced diseases. [ABSTRACT FROM AUTHOR]

The application of a simple, fast and reliable volumetric microrespirometric method to assess respiration of bivalve larvae is discussed. As a model, C. gigas larvae of various sizes were used. Metabolic activity of veliger larvae was assessed by measuring respiratory rate for use in ecophysiological modelling. As an example of the application of this approach, additional measurements of veliger respiratory rates were carried out to assess the effect on larval metabolism of different concentrations of leachate from wood treated with chromated copper-arsenate (CCA). Veligers of Crassostrea gigas (length from 95 to 331 $\mu $m) were fed with a mixture of Isochrysis galbana and Chaetoceros pumilum cells. Experiments were performed in a 20 °C constant seawater temperature. The wet and dry weight of four length ($L$, in $\mu $m) classes of larvae were obtained from which the relationship between total dry weight and veliger length was derived $\{{\it DW} = e ^{(3.27+L \times 0.0154)}\}$ ($R^{2}= 99$%). Moreover, tissue dry weight (TDW; in ng) was calculated according to Gerdes ([CITE]). Since the mathematical model between larval length and respiratory rate explained 88% of the total variability, a more conservative approach using oyster larval dry meat weight (in ng) and respiratory rate (in $\mu $lO$_{2}$ h$^{-1})$ was developed to establish a linear model explaining 94.5% of the variability: ${\rm Resp.}= -3.849\times 10^{-4}+ 5.211\times 10^{-6 }\times {\it TDW}$. These experiments provided updated figures of C. gigas larval respiratory rates for use in ecophysiological models. The relationship between tissue dry weight and respiratory rate was close to previous estimates obtained by Gerdes ([CITE]) and Hoegh-Guldberg and Manahan ([CITE]) at 25 °C and 20 °C respectively. Our experiments demonstrate that volumetric microrespirometry is suitable for assessing larval respiratory rate and therefore can be used to assess impacts of pollutants on an early larval stage. Oysters exposed to leachates from chromated copper arsenate (CCA) treated timber at 5 kg m$^{-3 }$ showed initially highly variable respiratory rates while those rates decreased drastically for a 15 kg m$^{-3 }$ CCA treatment exposure. Among bioindicators using physiological response to assess pollutant effects, swimming activity and respiratory rates can be compared, the later showing a significant response at a lower pollutant concentration. [ABSTRACT FROM AUTHOR]

Collision sports, such as Rugby Union (“Rugby”) have a particularly high risk of injury. Of all injuries common to collision sports, concussions have received the most attention due to the potentially negative cognitive effects in the short- and long-term. Despite non-professional Rugby players comprising the majority of the world’s playing population, there is relatively little research in this population. Stellenbosch Rugby Football Club (“Maties”), the official rugby club of Stellenbosch University, represents one of the world’s largest non-professional Rugby clubs, making this an ideal cohort for community-level injury surveillance. The aim of this study was to describe the incidence and events associated with concussion in this cohort. Baseline demographics were obtained on the 807 male student Rugby non-professional players who registered for the 10-week long 2018 season, which comprised 101 matches and 2,915 of exposure hours. All match-related injuries were captured by the medical staff of Stellenbosch Campus Health Service on an electronic form developed from the consensus statement for injury recording in Rugby. The mean age, height and weight of this cohort were 20 ± 2 years, 182 ± 7 cm and 88 ± 14 kg, respectively. Overall, there were 89 time-loss injuries, which equated to an injury rate of 30.6 per 1,000 match hours [95% confidence intervals (CIs): 24.2–36.9], or about one injury per match. The most common injury diagnosis was “concussion” (n = 27 out of 90 injuries, 30%), at a rate of 9.3 per 1,000 match hours (95% CIs: 5.8–12.8). The three most common mechanisms of concussion in the present study were performing a tackle (33%), accidental collision (30%) and being tackled (11%). Concussion was the most common injury in this population, at a rate that was six times higher than the most comparable study from the UK, which had far more exposure time over six seasons and wider range of player ability, from recreational to semi-professional. This might be explained by the training and vigilance of the club’s first aiders observing all matches for concussion. Future studies should try to explain this high rate and subsequently reduce these concussions. The addition of video surveillance data would assist in identifying the etiology of these concussions injuries in order to develop specific targeted interventions.