ABSTRACT
Movement of resources was essential to the survival and success of early complex societies. The sources and destinations of goods and the means of transportation - be it by boats, carts and/or foot - can often be inferred, but the logistics of these movements are inherently more difficult to ascertain. Here, we use strontium isotopic analysis to test hypotheses about the role of animal and animal-powered transport in medium and long-distance movement and exchange, using the Indus Civilization as a case study. Across the wide geographical spread of the Indus Civilisation, there is strong evidence for long-distance exchange of raw materials and finished objects and this process is presumed to involve boats and animal-driven transport, although there is little evidence as to the relative importance of each mode of movement. Strontium isotopic analysis of animal remains from four sites analysed for this study combined with results from nine other sites indicates limited long-distance animal movement between different geological zones within the Indus Civilisation. These findings suggest that individual animals primarily moved short- or medium-distances, though there are several significant exceptions seen in some pigs and cattle found at two large urban sites. We infer that long-distance transport of goods, be it raw materials, finished objects, other goods, or the animals themselves, could have occurred through the use of boats and waterways, by traction animals moving over long distances that did not end up in the archaeological record, and/or by different animals participating in many short to medium-distance movements.
Subject(s)
Hoof and Claw , Animals , Cattle , Swine , Strontium Isotopes , Archaeology , Transportation , Civilization , MovementABSTRACT
Partial nephrectomy (PN) for small renal masses is common, but outcomes are not reported in a standard manner. Traditionally, parameters such as 90-day mortality, blood loss, transfusion rates, length of stay, nephrometry scoring and complications are published but their collective impact on warm ischemia time (WIT) and post-surgery GFR is rarely determined. Thus, our aim was to assess if "Trifecta" and "Pentafecta" outcomes could be used as useful surgical outcome markers. A prospective database of 252 Robotic-Assisted PN (RAPN) cases (2008-2019) was analysed. "Pentafecta" was defined as achievement of "Trifecta" (negative surgical margin, no postoperative complications and WIT of < 25 min) plus over 90% estimated GFR preservation and no CKD stage upgrading at 1 year. Binary logistic regression analysis was conducted to predict factors which may prevent achieving a Trifecta/Pentafecta. Median tumour size was 3 cm and mean WIT was 15 min. Positive surgical margins (PSM) occurred in 2 cases. Overall, the intra-operative complication rate was 7%. One recurrence conferred 5-year cancer-free survival of 97%. Trifecta outcome was achieved in 169 (67%) and Pentafecta in 141 (56%) of cases. At logistic regression analysis, intraoperative blood loss was the only factor to affect Trifecta achievement (p = 0.018). Advanced patient age negatively impacted Pentafecta achievement (p = 0.010). The Trifecta and Pentafecta outcomes are easily applicable to PN data, and offer an internationally comparable PN outcome, quality measure. We recommend applying this standardization to national data collection to improve the quality of reporting and ease of interpretation of surgeon/centres' outcomes.
Subject(s)
Kidney Neoplasms , Robotic Surgical Procedures , Humans , Kidney Neoplasms/surgery , Neoplasm Recurrence, Local , Nephrectomy , Reference Standards , Retrospective Studies , Robotic Surgical Procedures/methods , Treatment OutcomeABSTRACT
Namaqualand, South Africa, is a global biodiversity hotspot but local populations are affected by challenging economic conditions largely because of poor access to water. In this study groundwater types are characterised and sources of salts and salinisation processes are identified using hydrochemistry and δ18O, δ2H and 87Sr/86Sr data. Analysis of δ18O and δ2H data suggests that evaporation does not play a major role in salinisation of the groundwater. However, major ion chemistry and 87Sr/86Sr ratios indicate that salts present in the groundwater are linked to dry deposition of marine aerosols and ion-exchange reactions in soils in the alluvial aquifer systems. The hydrochemical variability of the groundwater in the basement aquifer system suggests that there are strong local controls linked to weathering processes in individual basement rock types. The region is also notable for the high density of heuweltjies, biophysical features associated with increased nutrient levels, associated with termite activity. Electromagnetic scanning as well as measurement of water-soluble soil electrical conductivity values on and off heuweltjies, show that heuweltjies are saline with salinity increasing with depth. The level of groundwater salinity correlates with the level of heuweltjie salinity. Precipitation records from the last 150 years provide support for the hypothesis that accumulated salts, and in particular, heuweltjie salts are flushed into the groundwater system during sporadic large volume precipitation events. Thus, heuweltjies and hence termite activity, could potentially represent a previously unrecognized contributor to groundwater salinisation across Namaqualand and in other parts of the world.
ABSTRACT
Clinopyroxene is a major host mineral for lithophile elements in the mantle lithosphere, and therefore, its origin is vital for constraints on mantle evolution and melt generation. In situ Sr isotopic measurement of clinopyroxene has been available since the recent development of laser ablation multicollector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) in the 2000s. Therefore, there is an increasing demand for natural clinopyroxene reference materials for Sr isotope microanalysis. In this contribution, we present six natural clinopyroxene reference materials from South Africa (JJG1424) and China (YY09-47, YY09-04, YY09-24, YY12-01, and YY12-02) for Sr isotope microanalysis. The Sr content of these clinopyroxenes ranges from 50 to 340 µg g-1, which covers most natural clinopyroxene compositions. Homogeneity of these potential reference materials were investigated and evaluated in detail over a 2-year period using 193-nm nanosecond and 257-nm femtosecond laser systems coupled to either a Neptune or Neptune Plus MC-ICP-MS. Additionally, the major and trace element of these clinopyroxenes were examined by electron probe microanalyzer (EPMA) as well as solution and laser ICP-MS. The in situ 87Sr/86Sr values obtained for the six natural clinopyroxene reference materials agree well with data obtained using the thermal ionization mass spectrometer (TIMS) method. The Sr isotopic stability and homogeneity of these clinopyroxenes make them potential reference materials for in situ Sr microanalysis to correct instrumental fractionation or as quality control materials for analytical sessions. The new Sr isotope data provided here might be beneficial for microbeam analysis in the geochemical community.
ABSTRACT
The impacts of ecosystem engineers may be expected to vary along environmental gradients. Due to some resources being more limited in arid than in mesic environments, disturbances created by burrowing mammals are expected to have a greater ameliorating effect in arid environments, with larger differences in microhabitat conditions expected between burrows and undisturbed areas. The aim of this study was to test if the impacts of a medium-sized burrowing mammal, the aardvark, on soil properties (soil temperature, moisture and compaction) and vegetation characteristics (plant cover, species richness and species composition) are consistent across three biomes that differ strongly in annual rainfall. Burrowing affected soil and vegetation attributes, but the direction and magnitude of these biogeomorphological impacts were not consistent across the different biomes. For example, plant species composition was altered by burrowing in the arid scrubland and in the mesic grassland, but not in the semi-arid savannah. Contrary to expectations, the difference in the impacts of burrowing between biomes were not related to rainfall, with burrowing having strong, albeit different, impacts in both the arid scrubland and the mesic grassland, but weaker effects in the semi-arid savannah. It appears, therefore, that the impacts of these biogeomorphic agents may be site-specific and that it may be difficult to predict variation in their biotic and abiotic effects across environmental gradients. As a result, forecasting the impacts of ecosystem engineers under different conditions remains a challenge to management, restoration and conservation strategies related to these types of species.
ABSTRACT
BACKGROUND: There is little research on the prevalence and characteristics of home and recreational injuries in infants under 12months of age. However, domestic accidents result in an average of 50 infant deaths in France every year. METHODS: A descriptive and retrospective study was conducted, based on data from the permanent investigation on home and recreational injuries in infants under 12months of age (EPAC) published by the Institute for Public Health. Data were collected from 2004 to 2013 in the pediatric emergency department of Le Havre hospital. A global quantitative analysis was carried out, as well as age-group-based analyses (groups of infants of similar age within a specific range of 3months of age). RESULTS: A total of 3708 infants under 1year of age were victims of home and recreational injuries. The incidence of domestic accidents was found to be an average of one case per day (gender ratio, 1.12). Up to 85% of reported injuries were found to occur in the home. Falls were the leading cause of home accidents or injuries (73% of the total number of reported accidents), 7% of which resulted from a fall from stairs. Children frequently suffered from concussion or contusions (65%). The neck and head were affected in 73% of cases. A higher proportion of foreign body injuries occurred after 6months of age (RR=2.9, p<0.001). The number of hospitalizations decreased with age: 21% of accidents occurred before 3 months of age; 7% occurred between 9 and 11 months of age (RR=0.32, p<0.001). Falling from a changing table accounted for 9% of fall-related hospitalizations. CONCLUSIONS: This survey characterized for the first time the occurrence of home and recreational injuries in infants under 12months of age in France.
Subject(s)
Accidental Falls/statistics & numerical data , Accidents, Home/statistics & numerical data , Contusions/epidemiology , Emergency Service, Hospital , Foreign Bodies/epidemiology , Female , France/epidemiology , Hospitals, Pediatric , Humans , Incidence , Infant , Infant, Newborn , Male , Prevalence , Retrospective Studies , Walking , Wounds and Injuries/epidemiologyABSTRACT
Salmonellosis is a leading cause of bacterial gastroenteritis, responsible for invasive infections especially in young children. Reptiles are salmonella reservoirs, and the indirect contact via parents' hands may be responsible for contamination. We report on two cases of Salmonella-rotavirus coinfection secondary to the presence of turtles in the home.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Ceftriaxone/administration & dosage , Rotavirus Infections/complications , Rotavirus/isolation & purification , Salmonella Infections/complications , Salmonella enterica/isolation & purification , Animals , Animals, Exotic , Coinfection , Gastroenteritis/microbiology , Gastroenteritis/virology , Humans , Infant , Male , Rotavirus Infections/diagnosis , Rotavirus Infections/transmission , Salmonella Infections/diagnosis , Salmonella Infections/transmission , Treatment Outcome , Turtles/microbiology , Turtles/virologyABSTRACT
Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data
Subject(s)
Humans , Brain Diseases , Neurophysiological Monitoring , Brain Diseases/diagnosis , Brain Diseases/therapy , Health Personnel , Critical CareABSTRACT
BACKGROUND: Guidelines recommend regular assessment of asthma control. The Childhood Asthma Control Test (C-ACT) is a clinically validated tool. AIM: To evaluate asthma control according to GINA2006, NAEPP, pediatrician's assessment (PA), and C-ACT in asthmatic children visiting their ambulatory pediatrician or tertiary care pediatric pulmonologist. METHODS: Demographic data, treatment, and number of severe exacerbations during the previous year were collected. Control was assessed using (i) strict GINA 2006 criteria, (ii) GINA without taking into account the exacerbation item, (iii) NAEPP criteria, and (iv) PA. Children and parents filled out the C-ACT. RESULTS: Five hundred and twenty-five children completed the survey (mean age: 7.7 years; 28% ≤ 6 years). 78% had a controller treatment. 58% reported ≥ 1 severe exacerbation. C-ACT was ≤ 19 in 29.5%. Control was not achieved in 76.5%, 55%, 40%, and 34% according to GINA 2006 guidelines, NAEPP guidelines, GINA 2006 without exacerbation criteria, and PA, respectively. C-ACT was significantly lower in children ≤ 6 years old (P = 0.002) or with severe exacerbations (P < 0.0001). According to PA, 89% of patients with a C-ACT > 21 were controlled and 85% of patients with a C-ACT < 17 not controlled. CONCLUSION: We observed discrepancies between the different tools applied to assess asthma control in children, and the impact of age and exacerbations. Cutoff point of 19 of C-ACT was not associated with the best performance compared to PA. Assessment of control should take into account symptoms and lung function as suggested by the latest GINA guidelines as well as exacerbation over a long period.
Subject(s)
Asthma/prevention & control , Asthma/therapy , Age Factors , Asthma/diagnosis , Child , Child, Preschool , Disease Progression , Female , France , Humans , Male , Outcome Assessment, Health Care , Pediatrics , Practice Guidelines as Topic , Prospective Studies , Severity of Illness Index , Surveys and QuestionnairesABSTRACT
Recommendations for the use of diagnostic testing in low respiratory infection in children older than 3 months were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP(2)A). The Haute Autorité de santé (HAS) methodology, based on formalized consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text is available on the SP(2)A website.
Subject(s)
Diagnostic Tests, Routine , Lung Diseases/diagnosis , Chlamydial Pneumonia/diagnosis , Diagnostic Tests, Routine/methods , Evidence-Based Medicine , France , Humans , Infant , Lung Diseases/therapy , Pneumonia, Bacterial/diagnosis , Pneumonia, Mycoplasma/diagnosis , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Viral/diagnosis , Pulmonary Aspergillosis/diagnosisABSTRACT
Sarcoidosis, a chronic multisystem inflammatory granulomatous disorder of unknown origin, is a rare disease in children. Two distinct clinical presentations of sarcoidosis in childhood are known. Older children usually show multisystem disease, close to the adult manifestation, with lung infiltration and frequent hilar lymphadenopathy. Prior to the age of 5, sarcoidosis reveals more frequently with the classical triad of rash, arthritis, and uveitis. Due to non-specific clinical features and the lack of a specific test, recognizing sarcoidosis can be difficult in the pediatric population. Moreover, unlike in adults, lung involvement is rare in pediatric sarcoidosis. Given the lack of a definitive blood test, the World Association of Sarcoidosis and Other Granulomatous disorders (WASOG) only recommends dosing the serum angiotensin-converting enzyme (ACE). Its level is usually higher in children than in adults, but an increased ACE may help in the diagnosis. The gold standard is a biopsy specimen with typical epithelioid gigantocellular granuloma without caseating necrosis granuloma, after other disorders known to cause granulomatous disease have been reasonably excluded. We report here the case of a 4.5-year-old male with the history of polyarthritis and uveitis, considered first as juvenile rheumatoid arthritis, followed 5 years later by cutaneous involvement, which led to reconsidering the diagnosis. There were no pulmonary clinical findings. Histology provided the diagnosis of sarcoidosis. He then developed dependence on steroids. The lack of the classical triad delayed the diagnosis several years. This case shows the pediatric singularity of sarcoidosis, which needs to be known so that early and appropriate follow-up can be conducted.
Subject(s)
Sarcoidosis/diagnosis , Age of Onset , Child, Preschool , Humans , MaleABSTRACT
Macropores play an important role in the rapid transport of water, solutes and pollutants through the soil. Transport through these pores (>0.5 mm) is dominated by gravitational forces (i.e. matrix forces have low impact) resulting in flow rates orders of magnitude higher than rates that would be predicted, posing problems for modelling and understanding water and solute transport through soils. This study aimed to quantify the water conducting macroporosity (WCM) in a range of soils in South Africa and to develop three pedotransfer functions (PTFs) able to predict WCM. Saturated (K(s)) and unsaturated (K30) conductivities were measured in situ on 120 soil profiles using double ring and tension infiltrometers methods. Differences between K(s) and K30 in conjunction with Poiseuille's law and the capillary rise equation were used to calculate WCM. The first two multiple regression functions made use of all available soil properties influencing WCM using a 'best model' and 'backward' analysis approach respectively. The third model used only easily observable soil properties to predict the WCM. The functions were validated using a double-cross method. Results are encouraging with R² values of 0.78, 0.74 and 0.69 for functions 1, 2 and 3 respectively.
Subject(s)
Soil/chemistry , Water/chemistry , Models, Theoretical , South Africa , Water MovementsABSTRACT
The science of nursing has long been discussed as a blending of the art and science of caring, and nursing research builds the evidence of support for nursing practice. Nurses and nursing care are key to successful neurocritical care research endeavors. Ideally nursing care should be evidence based and supported by solid research. The goal of nursing research is to expand the knowledge of caring for patients. Within the scope of nursing research, the priorities for research in neurocritical care should support this goal. In this manuscript, we discuss what we believe are the priorities of neurocritical care nursing research, the obstacles, and some possible solutions.
Subject(s)
Critical Care/trends , Nervous System Diseases/nursing , Nervous System Diseases/therapy , Nursing Research/trends , Research/trends , Critical Care/methods , Humans , Nursing Research/methods , Research DesignABSTRACT
Neurocritical care diseases carry a high morbidity and mortality. Therapeutic and technological advances in neurocritical care have greatly improved the outcome of a variety of life-threatening disorders including traumatic brain injury, acute ischemic stroke, intracerebral and subarachnoid hemorrhage, and anoxic injury following cardiac arrest. These advances have stemmed from a better understanding of the physiology of neurocritical care illnesses, improved neuromonitoring techniques, and the introduction of more efficacious treatments. Despite all the advances in neuromonitoring, diagnostic imaging, and emerging treatments, much research needs to be undertaken in neurocritical care. Many of the clinical trials carried out in the general critical care population have excluded neurocritical care patients. For instance, the landmark ARDSNET trial that demonstrated the beneficial effects of low tidal volume ventilation in patients with ARDS cannot be directly applied to neurocritical care patients who frequently may experience this pulmonary complication. There is a need for a more cohesive and integrated research system or network to establish a track record for high-quality, investigator-initiated clinical research in neurocritical care. Such a system may help us overcome potential impediments to the future advancement of neurocritical care research. We propose the creation of the neurocritical care research network. The mission of the Network is to facilitate multicenter and multidisciplinary collaboration and patient enrollment in clinical trials of specific neurocritical care diseases.
Subject(s)
Clinical Trials as Topic , Critical Care/methods , Nervous System Diseases/therapy , Patient Care Team , Clinical Trials as Topic/methods , Clinical Trials as Topic/trends , Critical Care/trends , Humans , Multicenter Studies as Topic/methods , Multicenter Studies as Topic/trends , Nervous System Diseases/mortality , Nervous System Diseases/physiopathology , Patient Care Team/trendsABSTRACT
Clinical trials provide a robust mechanism to advance science and change clinical practice across the widest possible spectrum. Fundamental in the Neurocritical Care Society's mission is to promote Quality Patient Care by identifying and implementing best medical practices for acute neurological disorders that are consistent with the current scientific knowledge. The next logical step will be to foster rapid growth of our scientific body of evidence, to establish and disseminate these best practices. In this manuscript, five invited experts were impaneled to address questions, identified by the conference organizing committee as fundamental issues for the design of clinical trials in the neurological intensive care unit setting.
Subject(s)
Clinical Trials as Topic , Critical Care/methods , Nervous System Diseases/therapy , Research Design/standards , Clinical Trials as Topic/economics , Clinical Trials as Topic/methods , Clinical Trials as Topic/standards , HumansABSTRACT
Neurocritical care is a subspecialty of critical care medicine, dedicated to the care and the advancement of care of critically ill patients with neurosurgical or neurological diseases. Neurocritical care patients are heterogeneous, in both their disease process and the therapies they receive, however, several studies demonstrate that care of these patients in dedicated NeuroIntensive Care Units (neuroICUs) by neurointensivists, who coordinate their care is associated with reduced mortality and resource utilization. NeuroICUs foster innovation, and yet despite all the recent advances, much research needs to be undertaken in neurocritical care to better understand the disease pathophysiology and to demonstrate improved outcome with the use of goal-directed therapy based on evolving techniques and therapies.
Subject(s)
Clinical Trials as Topic , Critical Care/methods , Multicenter Studies as Topic , Nervous System Diseases/therapy , Critical Care/trends , Humans , Intensive Care Units/trends , Multicenter Studies as Topic/trends , Nervous System Diseases/diagnosisABSTRACT
The daily practice of neurointensivists focuses on the recognition of subtle changes in the neurological examination, interactions between the brain and systemic derangements, and brain physiology. Common alterations such as fever, hyperglycemia, and hypotension have different consequences in patients with brain insults compared with patients of general medical illness. Various technologies have become available or are currently being developed. The session on "research and technology" of the first neurocritical care research conference held in Houston in September of 2009 was devoted to the discussion of the current status, and the research role of state-of-the art technologies in neurocritical patients including multi-modality neuromonitoring, biomarkers, neuroimaging, and "omics" research (proteomix, genomics, and metabolomics). We have summarized the topics discussed in this session. We have provided a brief overview of the current status of these technologies, and put forward recommendations for future research applications in the field of neurocritical care.
Subject(s)
Biomedical Technology/methods , Biomedical Technology/trends , Critical Care , Nervous System Diseases/therapy , Research Design , Critical Care/methods , Critical Care/trends , Genomics/methods , Genomics/trends , Humans , Metabolomics/methods , Metabolomics/trends , Nervous System Diseases/genetics , Nervous System Diseases/metabolism , Proteomics/methods , Proteomics/trends , Research Design/trendsABSTRACT
The nCPMG sequence is based on a particular phase modulation of the refocusing pulse train, and was originally designed for rendering the spin echo amplitude insensitive to the initial magnetization phase. This pulse sequence has the peculiarity of being easily invertible, which enables perfect driven equilibrium experiments, in the absence of relaxation. This magnetization 'realignment' is effective for all three components. Hence the overall operation is transparent. Supporting theory is presented here, together with the first direct experimental proof of the claim. The experiment shows that, with the present stabilization sequence, perfect realignment is indeed made possible for a range of refocusing pulse nutation angles from 130° to 230°.
Subject(s)
Algorithms , Electron Spin Resonance Spectroscopy/methods , Electromagnetic Fields , Indicators and Reagents , Signal Processing, Computer-AssistedABSTRACT
The vulnerability of brain neuronal cell subpopulations to neurologic insults varies greatly. Among cells that survive a pathological insult, for example ischemia or brain trauma, some may undergo morphological and/or biochemical changes that may compromise brain function. The present study is a follow-up of our previous studies that investigated the effect of glutamate-induced excitotoxicity on the GABA synthesizing enzyme glutamic acid decarboxylase (GAD65/67)'s expression in surviving DIV 11 cortical GABAergic neurons in vitro [Monnerie and Le Roux, (2007) Exp Neurol 205:367-382, (2008) Exp Neurol 213:145-153]. An N-methyl-D-aspartate receptor (NMDAR)-mediated decrease in GAD expression was found following glutamate exposure. Here we examined which NMDAR subtype(s) mediated the glutamate-induced change in GAD protein levels. Western blotting techniques on cortical neuron cultures showed that glutamate's effect on GAD proteins was not altered by NR2B-containing diheteromeric (NR1/NR2B) receptor blockade. By contrast, blockade of triheteromeric (NR1/NR2A/NR2B) receptors fully protected against a decrease in GAD protein levels following glutamate exposure. When receptor location on the postsynaptic membrane was examined, extrasynaptic NMDAR stimulation was observed to be sufficient to decrease GAD protein levels similar to that observed after glutamate bath application. Blocking diheteromeric receptors prevented glutamate's effect on GAD proteins after extrasynaptic NMDAR stimulation. Finally, NR2B subunit examination with site-specific antibodies demonstrated a glutamate-induced, calpain-mediated alteration in NR2B expression. These results suggest that glutamate-induced excitotoxic NMDAR stimulation in cultured GABAergic cortical neurons depends upon subunit composition and receptor location (synaptic vs. extrasynaptic) on the neuronal membrane. Biochemical alterations in surviving cortical GABAergic neurons in various disease states may contribute to the altered balance between excitation and inhibition that is often observed after injury.