Economic Evaluation of Wastewater Surveillance Combined with Clinical COVID-19 Screening Tests, Japan.

The COVID-19 pandemic has imposed substantial burdens on the global society. To find an optimal combination of wastewater surveillance and clinical testing for tracking COVID-19, we evaluated the economic efficiency of hypothetical screening options at a single facility in Japan. To conduct cost-benefit analyses, we developed standard decision models in which we assumed model parameters from literature and primary data, such as screening policies used at the Tokyo Olympic and Paralympic Village in 2021. We compared hypothetical 2-step screening options that used clinical PCR to diagnose COVID-19 after a positive result from primary screening using antigen tests (option 1) or wastewater surveillance (option 2). Our simulation results indicated that option 2 likely would be economically more justifiable than option 1, particularly at lower incidence levels. Our findings could help justify and promote the use of wastewater surveillance as a primary screening at a facility level for COVID-19 and other infectious diseases.

Economic Evaluation of Telemedicine Consultations to Reduce Unnecessary Neonatal Care Transfers.

OBJECTIVES: To perform an economic evaluation to estimate the return on investment (ROI) of making available telemedicine consultations from a healthcare payer perspective, and to estimate the economic impacts of telemedicine under a hypothetical scenario in which all rural hospitals providing level I neonatal care in California had access to telemedicine consultations from neonatologists at level III and level IV neonatal intensive care units (NICUs). STUDY DESIGN: We developed standard decision models with assumptions derived from primary data and the literature. Telemedicine costs included equipment installation and operation costs. Probabilistic analysis with Monte Carlo simulation was performed to address model uncertainties and to estimate 95% probabilistic confidence intervals (PCIs). All costs were adjusted to 2017 US dollars using the Consumer Price Index. RESULTS: Our probabilistic analysis estimated the ROI to have a mean value of 2.23 (95% PCI, -0.7 to 6.0). That is, a $1 investment in this telemedicine model would yield a net medical expenditure saving of $1.23. "Cost saving" was observed for 75% of the hypothetical 1000 Monte Carlo simulations. For the state of California, the estimated mean annual net savings was $661 000. CONCLUSIONS: Providing telemedicine and making available consultations to rural hospitals providing level I neonatal care are likely to reduce medical expenditures by reducing potentially avoidable transfers of newborns to level III and IV NICUs, offsetting all telemedicine-related costs.

Multiacquisition Variable-Resonance Image Combination Selective Can Improve Image Quality and Reproducibility for Metallic Implants in the Lumbar Spine.

The aim of this study is to evaluate how metallic artifacts in the lumbar spine can affect images obtained from magnetic resonance (MR) sequences. We performed a phantom experiment by scanning an agar containing an orthopedic metallic implant using 64-channel multidetector row computed tomography (CT) and a 3-tesla MR unit. We compared the reproducibility in each measurement, enlargement or reduction ratio of the CT and MR measurements, and signal deviation in each voxel from the control. The reproducibility on CT and multiacquisition variable-resonance image combination selective (MAVRIC SL) was good, but that on the other MR sequences showed either fixed bias or proportional bias. The reduction ratios of the distance between the nails were significantly smaller in MAVRIC SL than in the other MR sequences after CT measurements (p<0.001, respectively). MAVRIC SL was able to reduce the metallic artifact, permitting observation of the tissue surrounding the metal with good reproducibility.

Influence of anionic, neutral, and cationic polysaccharides on the in vitro digestibility of raw and gelatinized potato starch.

BACKGROUND: Polysaccharides have been expected to have a suppressive effect on starch digestibility by blending. The objective of this study was to investigate the effects of anionic (xanthan gum), neutral (guar gum), and cationic (chitosan) polysaccharides on the in vitro digestibility of raw and gelatinized starch using six potato cultivars differing in phosphorus content. RESULTS: By comparing the starch digestibility between potato cultivars, a significant difference was observed for the raw starches, and 'Benimaru', which is a potato cultivar containing a higher proportion of short-chain amylopectin and the lowest phosphorus content in starch, showed a distinctly faster rate of starch hydrolysis. The added polysaccharides decreased the extent of digestion of both raw and gelatinized starches. No significant correlation between phosphorus content and the extent of starch digestion was observed in mixed systems, whereas significant correlations were noted between the extent of starch digestion and Rapid Visco Analyser parameters. The extent of raw and gelatinized starch digestion negatively correlated with pasting temperature, initial viscosity before heating, and peak viscosity (P < 0.01). CONCLUSION: The added polysaccharides were observed to decrease the starch digestibility, and their suppressive effects were mainly dependent on the increase of viscosity rather than chemical interactions. A combination of potato cultivar and type of polysaccharide was proved to be important for nutritional value of potato starch. © 2020 Society of Chemical Industry.

Suppressive effect of ethanol extract from mango (Mangifera indica L.) peel on IgE production in vitro and in vivo.

Immunoglobulin E (IgE) is involved in the onset of allergic reaction, and the suppression of IgE production leads to alleviation of allergic symptoms. We found that mango peel ethanol extract (MPE) significantly suppresses IgE production by human myeloma cell line U266 cells, suggesting that MPE has an anti-allergic effect by inhibiting the production of IgE. Although mangiferin is contained in mango, which suppresses IgE production by U266 cells, it was not contained in MPE. We investigated the suppressive effect of MPE in 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis model mice. The elevation of serum IgE level was significantly suppressed by oral administration of MPE. Intake of MPE also suppressed the expression level of IL-4 in the DNFB-challenged ears, suggesting that MPE suppresses the IL-4-mediated maturation into IgE-producing cells. Our findings indicate that MPE has a potential to alleviate the increase in serum IgE level that is feature of type I allergy.

Selected Use of Telemedicine in Intensive Care Units Based on Severity of Illness Improves Cost-Effectiveness.

BACKGROUND: Telemedicine in the intensive care unit (tele-ICU) is expected to address geographic health disparities through more efficient resource allocation. Our previous economic evaluation demonstrated tele-ICU to be cost-effective in most cases and cost saving in some cases, compared to conventional intensive care unit (ICU) care without adequate intensivist coverage. INTRODUCTION: This study's objective is to examine how to optimize the cost-effectiveness of tele-ICU use by selecting highest risk (i.e., both highest mortality and highest cost) subpopulations. We also explore potential cost savings. MATERIALS AND METHODS: We conducted simulation analyses among a hypothetical adult ICU patient cohort defined by the literature, distinguishing four types of hospitals: urban tertiary (primary analysis), urban community, rural tertiary, and rural community. The selected tele-ICU use was assumed to affect per-patient ICU cost and hospital mortality among highest risk subpopulations (10-100% of all ICU patients), defined by an established illness-severity measure. RESULTS: We found a U-shaped relationship between the economic efficiency and selected tele-ICU use among all 4 hospital types. Optimal cost-effectiveness was achieved when tele-ICU was applied to the 30-40% highest risk patients among all ICU patients (incremental cost-effectiveness ratio = $25,392 [2014 U.S. dollars] per extending a quality-adjusted life year) in urban tertiary hospitals (primary analysis). Our break-even analyses indicated that cost saving seems more feasible when reducing ICU medical care cost, rather than lowering the cost to operate telemedicine alone. DISCUSSION AND CONCLUSIONS: A selected use of tele-ICU based on severity of illness is likely to improve tele-ICU cost-effectiveness. To achieve cost saving, tele-ICU must reduce more than just telemedicine-related cost.

An enzymatic method for the production of 6-oxohexanoic acid from 6-aminohexanoic acid by an enzyme oxidizing ω-amino compounds from Phialemonium sp. AIU 274.

An enzymatic method for 6-oxohexanoic acid production was developed using 6-aminohexanoic acid and an ω-amino group-oxidizing enzyme (ω-AOX) from Phialemonium sp. AIU 274. 6-Oxohexanoic acid was produced from 6-aminohexanoic acid with 100% yield by incubation with 0.3 U of the ω-AOX and 20 U of catalase at 30 °C for 30 h in 0.1 M potassium phosphate buffer (pH 7.0).

Program Evaluation of a Nursing Workforce Intervention: The Maryland Nurse Support Program II.

A nursing workforce initiative in Maryland sought to graduate additional nursing students to become registered nurses and to increase the number and preparation levels of nursing faculty. Between FY 2006 and FY 2015, nearly $100 million was awarded through 109 competitive institutional grants at 27 nursing programs across the state; 950 faculty received awards through fellowships, scholarships, and grants. Maryland's nursing workforce intervention increased the number of graduates by 27% through this decade-long program. Although Maryland outperformed the nation in the rate of increase of registered nurses, there is still a projected state shortfall of 12,100 nurses by 2025. It is imperative for nurse researchers and nurse leaders to address the future nursing and nurse faculty workforce shortage using effective strategies based on empirical evidence and evaluation of outcomes. This program evaluation informed the decision to continue investments in the nursing and faculty workforce (up to $75 million) for an additional 5 years.

The Impact of Economic Recession On Registered Nurse Workforce Supply in California.

The severe economic recession from December 2007 to December 2010 substantially affected registered nurse (RN) employment. The objective of this study was to determine if the association between RN workforce supply and its potential determinants differed during the period from 2008 to 2012. Older, experienced RNs were more likely to work in 2010, compared to 2008, but less likely to work in 2012 compared to 2010. RNs were less sensitive to financial factors in 2010 than in 2008, but were more sensitive in 2012 than in 2010. These recession-driven changes in employment may have had impacts on the labor market for newly graduating RNs.

A comparison of the effects of heat moisture treatment (HMT) on rheological properties and amylopectin structure in sago (Metroxylon sago) and arenga (Arenga pinnata) starches.

The objective of this study was to study and compare the impact of HMT on rheology and textural properties observed between sago and arenga starces, and then related to structural change of amylopectin. The HMT were conducted using the autoclaving method at 20% moisture content and heated to 120 C for 60 min for sago and 90 min for arenga starch as optimum condition. The HMT shifted gelatinization temperature higher and reduced the enthalpy of both starches. The HMT sago starch paste exhibited an exceptionally strong shear thinning behavior as shown by a rapid decrease of viscosity and an increase of shear rate. The HMT clearly made the texture of starch gels more fragile compared to their native form and reduced their breaking point to a lower strain. The HMT effect on the rheological properties and texture of the sago starch was greater than the changes observed with the arenga starch. Major changes in rheological properties after HMT was not followed by changes in amylopectin structure. The HMT process did not significantly affect the amylopectin chain-length distribution in Arenga starch. In the sago starch, HMT affect to long chain amylopectin with DP ≥ 37. The HMT effect on rheology and textural properties was higher in sago starch than arenga starch. This study demonstrated that long chain amylopectin with DP ≥ 37 plays an important role in contributing to the rheological change caused by the HMT.

Economic Evaluation of Telemedicine for Patients in ICUs.

OBJECTIVE: Despite telemedicine's potential to improve patients' health outcomes and reduce costs in the ICU, hospitals have been slow to introduce telemedicine in the ICU due to high up-front costs and mixed evidence on effectiveness. This study's first aim was to conduct a cost-effectiveness analysis to estimate the incremental cost-effectiveness ratio of telemedicine in the ICU, compared with ICU without telemedicine, from the healthcare system perspective. The second aim was to examine potential cost saving of telemedicine in the ICU through probabilistic analyses and break-even analyses. DESIGN: Simulation analyses performed by standard decision models. SETTING: Hypothetical ICU defined by the U.S. literature. PATIENTS: Hypothetical adult patients in ICU defined by the U.S. literature. INTERVENTIONS: The intervention was the introduction of telemedicine in the ICU, which was assumed to affect per-patient per-hospital-stay ICU cost and hospital mortality. Telemedicine in the ICU operation costs included the telemedicine equipment-installation (start-up) costs with 5-year depreciation, maintenance costs, and clinician staffing costs. Telemedicine in the ICU effectiveness was measured by cumulative quality-adjusted life years for 5 years after ICU discharge. MEASUREMENTS AND MAIN RESULTS: The base case cost-effectiveness analysis estimated telemedicine in the ICU to extend 0.011 quality-adjusted life years with an incremental cost of $516 per patient compared with ICU without telemedicine, resulting in an incremental cost-effectiveness ratio of $45,320 per additional quality-adjusted life year (= $516/0.011). The probabilistic cost-effectiveness analysis estimated an incremental cost-effectiveness ratio of $50,265 with a wide 95% CI from a negative value (suggesting cost savings) to $375,870. These probabilistic analyses projected that cost saving is achieved 37% of 1,000 iterations. Cost saving is also feasible if the per-patient per-hospital-stay operational cost and physician cost were less than $422 and less than $155, respectively, based on break-even analyses. CONCLUSIONS: Our analyses suggest that telemedicine in the ICU is cost-effective in most cases and cost saving in some cases. The thresholds of cost and effectiveness, estimated by break-even analyses, help hospitals determine the impact of telemedicine in the ICU and potential cost saving.

The effect of prior healthcare employment on the wages of registered nurses.

BACKGROUND: The proportion of registered nurses (RNs) with employment in health-related positions before their initial RN education has increased in the past two decades. Previous research found that prior health-related employment is positively associated with RN workforce supply, potentially due to the wage differences based on different career paths. This study's objective is to test the hypotheses that prior health-related employment is associated with differences in starting wages and with different rates of wage growth for experience as an RN. METHODS: We conducted a cross-sectional analysis using the 2008 National Sample Survey of Registered Nurses (NSSRN) linked with county-level variables from the Area Health Resource File. We estimated a Heckman model where the second-stage equation's outcome variable was the logarithm of the RN hourly wage, accounting for the self-selection of working or not working as an RN (i.e., the first-stage equation's outcome variable). Key covariates included interaction terms between years of experience, experience squared, and six categories of prior health-related employment (manager, LPN/LVN, allied health, nursing aide, clerk, and all other healthcare positions). Additional covariates included demographics, weekly working hours, marital status, highest nursing degree, and county-level variables (e.g., unemployment rate). We estimated the marginal effect of experience on wage for each type of prior health-related employment, conducting separate analyses for RNs whose initial education was a Bachelor of Science in Nursing (BSN) (unweighted N = 10,345/weighted N = 945,429), RNs whose initial education was an Associate degree (unweighted N = 13,791/weighted N = 1,296,809), and total population combining the former groups (unweighted N = 24,136/weighted N = 2,242,238). RESULTS: Prior health-related employment was associated with higher wages, with the strongest wage differences among BSN-educated RNs. Among BSN-educated RNs, previous employment as a health care manager, LPN/LVN, or nursing aide produced statistically higher starting wages ($1.72-$3.86 per hour; $3400-$7700 per year; p = 0.006-0.08). However, experience-based wage growth was lower for BSN-educated RNs previously employed as allied health workers, LPN/LVNs, or nursing aides. Among Associate degree-educated RNs, wage difference was not observed except for higher initial wage for RNs with previous employment as LPN/LVNs. CONCLUSIONS: Prior employment in health-related positions was associated with both starting salary and experience-based wage growth among BSN-educated RNs. The higher wage return for those with a BSN may motivate non-RN healthcare workers to seek a BSN in their transition to RN jobs, which could help advancement toward the 80 % BSN workforce recommended by the U.S. Institute of Medicine.

Effect of Prior Health-Related Employment on the Registered Nurse Workforce Supply.

Registered nurses (RN) who held prior health-related employment in occupations other than licensed practical or vocational nursing (LPN/LVN) are reported to have increased rapidly in the past decades. Researchers examined whether prior health-related employment affects RN workforce supply. A cross-sectional bivariate probit model using the 2008 National Sample Survey of Registered Nurses was esti- mated. Prior health-related employment in relatively lower-wage occupations, such as allied health, clerk, or nursing aide, was positively associated with working s an RN. ~>Prior health-related employ- ment in relatively higher-wage categories, such as a health care manager or LPN/LVN, was positively associated with working full-time as an RN. Policy implications are to promote an expanded career ladder program and a nursing school admission policy that targets non-RN health care workers with an interest in becoming RNs.

Printability of Nixtamalized Corn Dough during Screw-Based Three-Dimensional Food Printing.

This study aimed to analyze the printability of corn-based dough during screw-based three-dimensional (3D) food printing (3DFP) by relating its rheological and mechanical properties to its screw-based 3DFP performance, with the objective of providing insights into the utilization of corn-based dough to produce 3D-printed foods. Screw-based 3DFP was performed using seven corn-based doughs with different nixtamalized corn flour (NCF) and water contents. Afterward, their rheological and mechanical properties were analyzed and associated with their screw-based 3DFP performance. The results showed that stable printability was obtained within a specific range of NCF content in the dough (30-32.5 wt%). Below this range, the 3D-printed foods flattened, while above it, the extrudability of the dough was affected. The printability of the dough was influenced by different rheological and mechanical properties, depending on the stage of the screw-based 3DFP process. During the extrusion stage, the loss tangent at nozzle strain, yield stress, apparent viscosity, and adhesiveness mainly affected the extrudability of the dough. In contrast, the loss tangent at minimum strain, elastic modulus, Young's modulus, and hardness influenced the self-supporting stage. Therefore, it is important to find a balance between all of these properties, where stable extrudability and self-supporting of the 3D structure are achieved.

Evaluation of overexposure risk when there is a space between the subject and the couch in computed tomography: a phantom study.

The purpose of this study was to investigate the risk of overexposure associated with automatic tube current modulation (ATCM) and automatic couch height positioning compensation mechanism (AHC) in computed tomography (CT) systems, particularly in scenarios involving a gap between the subject and the couch. Results revealed that when AHC was enabled, CT dose index volume (CTDIvol) increased by approximately 10% at 2.5 cm, 20% at 5.0 cm, and 40% at 10.0 cm gaps compared to close contact conditions. While the AHC function ensures consistent exposure doses and image quality regardless of subject positioning relative to the CT gantry isocenter, the study highlights a potential risk of overexposure when a gap exists between the subject and the couch. These findings offer valuable insights for optimizing CT imaging protocols and underscore the importance of carefully considering subject positioning in clinical practice.

Genomic- and protein-based approaches for connectin (titin) identification in the ascidian Ciona intestinalis.

Determining the complete primary structure of large proteins is difficult because of the large sequence size and low sequence homology among animals, as is the case with connectin (titin)-like proteins in invertebrate muscles. Conventionally, large proteins have been investigated using immuno-screenings and plaque hybridization screenings that require significant time and labor. Recently, however, the genomic sequences of various invertebrates have been determined, leading to changes in the strategies used to elucidate the complete primary structures of large proteins. In this paper, we describe our methods for determining the sequences of large proteins by elucidating the primary structure of connectin from the ascidian Ciona intestinalis as an example. We searched for genes that encode connectin-like proteins in the C. intestinalis genome using the BLAST search program. Subsequently, we identified some domains present in connectin and connectin-like proteins, such as immunoglobulin (Ig), fibronectin type 3 (Fn) and kinase domains in C. intestinalis using the SMART program and manual estimation. The existence of these domains and the unique sequences between each domain were confirmed using RT-PCR. We also examined the localization of mRNA using whole-mount in situ hybridization (WISH) and protein expression using SDS-PAGE. These analyses indicate that the domain structure and molecular weight of ascidian connectin are similar to those of vertebrate connectin and that ascidian connectin is also expressed in heart muscle, similarly to vertebrate connectin. The methods described in this study can be used to determine the primary structures of large proteins, such as novel connectin-like proteins in invertebrates.

Endovascular Retrieval of a Fractured Tunneled Hemodialysis Central Venous Catheter Using the Loop Snare Technique.

The tunneled cuffed hemodialysis catheter is a valuable vascular access option for patients with end-stage renal disease (ESRD). Healthcare providers have become more familiar with the insertion of medical devices, including central venous catheters, in their daily practice. The occurrence of foreign body fragmentation is rare with these catheters. This article presents a case in which a fracture of the distal portion of the hemodialysis catheter was inadvertently identified during a coronary angiography. Percutaneous removal of the fractured venous catheter was performed successfully using a loop snare catheter, which prevented the patient from experiencing further complications.

Endogenous interleukin-22 prevents cardiac rupture after myocardial infarction in mice.

Myocardial infarction (MI) can result in fatal myocardial rupture or heart failure due to adverse remodeling and dysfunction of the left ventricle. Although recent studies have shown that exogenous interleukin (IL)-22 shows cardioprotective effect after MI, the pathophysiological significance of endogenous IL-22 is unknown. In this study, we investigated the role of endogenous IL-22 in a mouse model of MI. We produced MI model by permanent ligation of the left coronary artery in wild-type (WT) and IL-22 knock-out (KO) mice. The post-MI survival rate was significantly worse in IL-22KO mice than in WT mice due to a higher rate of cardiac rupture. Although IL-22KO mice exhibited a significantly greater infarct size than WT mice, there was no significant difference in left ventricular geometry or function between WT and IL-22KO mice. IL-22KO mice showed increase in infiltrating macrophages and myofibroblasts, and altered expression pattern of inflammation- and extracellular matrix (ECM)-related genes after MI. While IL-22KO mice showed no obvious changes in cardiac morphology or function before MI, expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were increased, whereas that of tissue inhibitor of MMPs (TIMP)-3 was decreased in cardiac tissue. Protein expression of IL-22 receptor complex, IL-22 receptor alpha 1 (IL-22R1) and IL-10 receptor beta (IL-10RB), were increased in cardiac tissue 3 days after MI, regardless of the genotype. We propose that endogenous IL-22 plays an important role in preventing cardiac rupture after MI, possibly by regulating inflammation and ECM metabolism.

"Nata Puree," a Novel Food Material for Upgrading Vegetable Powders, Made by Bacterial Cellulose Gel Disintegration in the Presence of (1,3)(1,4)-ß-Glucan.

Pulverization is a potentially powerful solution for the resource management of surplus- and non-standard agricultural products, maintaining their nutritional values for long and ensuring their homogeneity, whereas their original textures could disappear to narrow the application ranges. Therefore, new technologies should be developed for reconstructing the powders to provide them with new physical characteristics. Herein, we developed a novel food material, nata puree (NP), by nata de coco (bacterial cellulose gel) disintegration with a water-soluble polysaccharide using a household blender. The process worked well with (1,3)(1,4)-ß-glucan (BGL) as the polysaccharide, which could be substituted with barley extract. Lichenase treatment of the NP dramatically modified its physical properties, suggesting the importance of the BGL polymeric forms. NP exhibited distinct potato powder and starch binding activities, which would be attributed to its interactions with the cell wall components and a physical capture of powders by the NP network, respectively. NP supplementation into the potato paste improved its firmness and enabled its printable range shift for 3D food printing to a lower powder-concentration. NP also promoted the dispersion of powders in its suspension, and designed gelation could also be successfully performed by the laser irradiation of an NP suspension containing dispersed curdlan and turmeric powders. Therefore, NP could be applied as a powder modifier to a wide range of products in both conventional cooking, food manufacturing, and next generation processes such as 3D food printing.

SOCS3 deficiency in cardiomyocytes elevates sensitivity of ischemic preconditioning that synergistically ameliorates myocardial ischemia reperfusion injury.

Ischemic preconditioning (IPC) is the most powerful endogenous cardioprotective form of cellular adaptation. However, the inhibitory or augmenting mechanism underlying cardioprotection via IPC remains largely unknown. Suppressor of cytokine signaling-3 (SOCS3) is a cytokine-inducible potent negative feedback regulator of the signal transducer and activator of transcription-3 (STAT3) signaling pathway. Here, we aimed to determine whether cardiac SOCS3 deficiency and IPC would synergistically reduce infarct size after myocardial ischemia reperfusion injury. We evaluated STAT3 activation and SOCS3 induction after ischemic conditioning (IC) using western blot analysis and real-time PCR, and found that myocardial IC alone transiently activated myocardial STAT3 and correspondingly induced SOCS3 expression in wild-type mice. Compared with wild-type mice, cardiac-specific SOCS3 knockout (SOCS3-CKO) mice showed significantly greater and more sustained IC-induced STAT3 activation. Following ischemia reperfusion, IPC substantially reduced myocardial infarct size and significantly enhanced STAT3 phosphorylation in SOCS3-CKO mice compared to in wild-type mice. Real-time PCR array analysis revealed that SOCS3-CKO mice after IC exhibited significantly increased expressions of several anti-apoptotic genes and SAFE pathway-related genes. Moreover, real-time PCR analysis revealed that myocardial IC alone rapidly induced expression of the STAT3-activating cytokine erythropoietin in the kidney at 1 h post-IC. We also found that the circulating erythropoietin level was promptly increased at 1 h after myocardial IC. Myocardial SOCS3 deficiency and IPC exert synergistic effects in the prevention of myocardial injury after ischemia reperfusion. Our present results suggest that myocardial SOCS3 is a potent inhibitor of IPC-induced cardioprotection, and that myocardial SOCS3 inhibition augment IPC-mediated cardioprotection during ischemia reperfusion injury.