Oxidative stress mediates associations between preoperative psychosocial phenotype and pain-related outcomes at 6 months following total knee arthroplasty: a longitudinal cohort study.

OBJECTIVE: Greater preoperative depression, anxiety, and pain catastrophizing are associated with more severe long-term pain following total knee arthroplasty (TKA). In a secondary analysis of previously reported data, we tested the hypothesis that these associations are mediated by oxidative stress (OS). DESIGN: A mixed between/within-subjects longitudinal cohort design. SETTING: A single academic medical center. SUBJECTS: Osteoarthritis patients (n = 91; 62.6% female) undergoing unilateral TKA. METHODS: We assessed depression, anxiety, and catastrophizing, as well as markers of central sensitization (widespread pain, temporal summation of pain) preoperatively. Blood samples were then obtained immediately prior to intraoperative tourniquet placement for quantification of in vivo biomarkers of systemic OS, F2-isoprostanes and isofurans. Post-TKA pain intensity (numeric rating scale worst pain [NRS], McGill Pain Questionnaire-2 [MPQ-2]) and function (PROMIS Pain Interference) were assessed at 6 months following TKA. RESULTS: Greater preoperative depression, catastrophizing, and widespread pain were associated with higher intraoperative combined OS (F2-isoprostanes+isofurans/2), which was in turn associated with higher post-TKA pain intensity and worse function (P < .05). All preoperative phenotype predictors except anxiety were correlated positively with post-TKA pain and/or function (P < .05). Bootstrapped mediation analyses revealed significant (P < .05) indirect (mediated) effects of depression (NRS Worst Pain, MPQ-2, PROMIS Pain Interference), anxiety (MPQ-2, PROMIS Pain Interference), and catastrophizing (PROMIS Pain Interference) on adverse long-term post-TKA outcomes via elevated OS. Central sensitization-related predictors demonstrated only direct effects (P < .05) on post-TKA outcomes that were independent of OS mechanisms. CONCLUSIONS: Results suggest that the adverse impact of depression, anxiety, and pain catastrophizing on post-TKA pain and functional outcomes are mediated in part by elevated OS.

Preoperative Predictors of Prolonged Opioid Use in the 6 Months After Total Knee Arthroplasty.

OBJECTIVES: Prolonged postoperative opioid use increases the risk for new postsurgical opioid use disorder. We evaluated preoperative phenotypic factors predicting prolonged postoperative opioid use. METHODS: We performed a secondary analysis of a prospective observational cohort (n=108) undergoing total knee arthroplasty (TKA) for osteoarthritis with 6-week and 6-month follow-up. Current opioid use and psychosocial, pain, and opioid-related characteristics were assessed at preoperative baseline. Primary outcomes were days/week of opioid use at follow-up. RESULTS: At 6 weeks, preoperative opioid use and greater cumulative opioid exposure, depression, catastrophizing, anxiety, pain interference, sleep disturbance, and central sensitization were significantly associated with more days/week of opioid use after controlling for contemporaneous pain intensity. Prior euphoric response to opioids were also significant predictors at 6 months. All 6-week predictors except anxiety remained significant after controlling for preoperative opioid use; at 6 months, cumulative opioid exposure, catastrophizing, pain interference, and sleep disturbance remained significant after this adjustment ( P <0.05). In multivariable models, a psychosocial factor reflecting negative affect, sleep, and pain accurately predicted 6-week opioid use (area under the curve=0.84). A combined model incorporating psychosocial factor scores, opioid-related factor scores, and preoperative opioid use showed near-perfect predictive accuracy at 6 months (area under the curve=0.97). DISCUSSION: Overall, preoperative psychosocial, pain-related, and opioid-related phenotypic characteristics predicted prolonged opioid use after total knee arthroplasty.

Genetics of evolved load resistance in the skeletons of unusually large mice from Gough Island.

A primary function of the skeleton is to resist the loads imparted by body weight. Genetic analyses have identified genomic regions that contribute to differences in skeletal load resistance between laboratory strains of mice, but these studies are usually restricted to 1 or 2 bones and leave open the question of how load resistance evolves in natural populations. To address these challenges, we examined the genetics of bone structure using the largest wild house mice on record, which live on Gough Island (GI). We measured structural traits connected to load resistance in the femur, tibia, scapula, humerus, radius, ulna, and mandible of GI mice, a smaller-bodied reference strain from the mainland, and 760 of their F2s. GI mice have bone geometries indicative of greater load resistance abilities but show no increase in bone mineral density compared to the mainland strain. Across traits and bones, we identified a total of 153 quantitative trait loci (QTL) that span all but one of the autosomes. The breadth of QTL detection ranges from a single bone to all 7 bones. Additive effects of QTL are modest. QTL for bone structure show limited overlap with QTL for bone length and width and QTL for body weight mapped in the same cross, suggesting a distinct genetic architecture for load resistance. Our findings provide a rare genetic portrait of the evolution of load resistance in a natural population with extreme body size.

Perioperative oxidative stress predicts subsequent pain-related outcomes in the 6 months after total knee arthroplasty.

ABSTRACT: Total knee arthroplasty (TKA) is effective for pain reduction in most patients, but 15% or more report unsatisfactory long-term pain outcomes. We tested whether oxidative stress (OS) related to extended tourniquet application during TKA and subsequent ischemic reperfusion (IR) contributed to adverse post-TKA pain outcomes. Blood samples were obtained in 91 patients with osteoarthritis (63% female) undergoing TKA before tourniquet placement (T1), 45 minutes after tourniquet inflation (T2), and 15 minutes after tourniquet removal (T3). Plasma levels of F 2 -isoprostanes and isofurans, the most specific measures of in vivo OS, were quantified. Pain intensity and function were assessed at baseline and again at 6 weeks and 6 months after TKA. Results indicated that higher Combined OS (F 2 -isoprostanes + isofurans/2) at T1 baseline and larger increases in Combined OS from T1 to T2 were associated with higher baseline-corrected past 24-hour worst and average pain intensity (numeric rating scale) and higher past week McGill Pain Questionnaire-2 total scores at 6-month follow-up ( P 's < 0.05). Increases in Combined OS from T1 to T3, which should most directly capture OS and IR injury related to tourniquet use, were not associated with short-term or long-term post-TKA pain outcomes. Longer ischemia duration was unexpectedly associated with lower baseline-corrected pain intensity at 6-month follow-up. Combined OS was not linked to functional outcomes at either follow-up. Elevated perioperative OS seems to exert small but significant adverse effects on long-term post-TKA pain outcomes, although this OS seems unrelated to IR injury associated with extended tourniquet use.

Is Female Representation Increasing in Society and Journal Editorial Boards in Oral and Maxillofacial Surgery?

PURPOSE: Surgical specialties, including oral and maxillofacial surgery (OMS), are traditionally male-dominated fields. This study aimed to analyze the proportions of female surgeons on specialty society boards and journal editorial boards in OMS in the United States and to assess whether they were proportionate with female representation in OMS academic faculty between 2011 and 2020. METHODS: A retrospective cohort study was performed using information obtained from the websites of two major OMS journals and information obtained directly from six American specialty societies for OMS. The predictor variable was time. The outcome variable was gender. Temporal changes in the proportion of women on society and journal editorial boards were compared with those amongst full-time board-certified faculty. Chi-squared test and simple linear regression were used for statistical analyses. RESULTS: Between 2011 and 2020, the proportion of women on editorial and society boards was 6.7% (31 women among 463 editorial board members) and 7.8% (43 women among 553 society board members), respectively. The proportion of women on editorial boards increased from 4.5% in 2011 to 10.6% in 2020 (ß = 0.656 [95% confidence interval, 0.336-0.975], P = .001) and that of women on society boards increased from 4.3% in 2011 to 10.3% in 2020 (ß = 0.645 [95% confidence interval, 0.252-1.037], P = .005). The proportion of women on editorial boards in 2011-2012 was significantly lower than that in full-time board-certified faculty positions (4.3% vs 11.0%, P = .045), whereas by 2019-2020, there was no difference between the 2 groups (9.8% vs 12.5%, P = .454). Similarly, the proportion of women on society boards in 2011-2012 tended to be lower than that in full-time board-certified faculty positions (5.6% vs 11.0%, P = .111), while in 2019-2020, no difference was observed between the 2 groups (10.4% vs 12.5%, P = .531). CONCLUSION: The proportion of women on society and journal editorial boards in OMS remains low but has progressively increased from 2011 to 2020, resulting in proportionate female representation in these positions compared with the gender composition of academic faculty in recent years. The current upward trend of female representation in leadership positions will hopefully present more diverse opportunities and mentorship/role models for trainees.

Student Attitudes Contribute to the Effectiveness of a Genomics CURE.

The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student's epistemic beliefs to achieving positive learning outcomes.

When a school is more than just a school: Improving school-based health in the wake of COVID-19.

The ongoing COVID-19 pandemic has posed tremendous challenges for economies and individuals around the world. At the same time, it has also laid bare the blatant and growing inequities that many individuals, particularly children, are confronted with on a daily basis. With communities in lockdowns and schools going virtual in many parts of the United States, the important role that schools and school-based services play in the lives of many children have gained new attention. Nonetheless, only 3% of American schools have school-based health centers on campus, and they remain relegated to the fringes of both health care and education. One key limitation has been the lack of appropriately trained health-care professionals. Over the past 2 years, we have interviewed dozens of individuals about their experiences in school-based health centers. Based on this study, we explore what it means for a health-care professional to work in school-based health care and how it differs from more traditional health-care settings. Our analysis particularly focuses on training and education, work environments, and their unique demands that come from being embedded within the educational setting. We conclude by addressing the important role that governmental policies could play in augmenting this crucial workforce.

Preoperative Predictors of Complex Regional Pain Syndrome Outcomes in the 6 Months Following Total Knee Arthroplasty.

This prospective observational study evaluated preoperative predictors of complex regional pain syndrome (CRPS) outcomes in the 6 months following total knee arthroplasty (TKA). Participants were n = 110 osteoarthritis patients (64.5% female) undergoing unilateral TKA with no prior CRPS history. Domains of negative affect (depression, anxiety, catastrophizing), pain (intensity, widespread pain, temporal summation of pain [TSP]), pain interference, sleep disturbance, and pro-inflammatory status (tumor necrosis factor-alpha [TNF-a]) were assessed preoperatively. CRPS outcomes at 6-week and 6-month follow-up included the continuous CRPS Severity Score (CSS) and dichotomous CRPS diagnoses (2012 IASP criteria). At 6 months, 12.7% of participants met CRPS criteria, exhibiting a "warm CRPS" phenotype. Six-week CSS scores were predicted by greater preoperative depression, anxiety, catastrophizing, TSP, pain intensity, sleep disturbance, and TNF-a (P's < .05). Provisional CRPS diagnosis at 6 weeks was predicted by higher preoperative TSP, sleep disturbance, and TNF-a (P's < .05). CSS scores at 6 months were predicted by more widespread and intense preoperative pain, and higher preoperative TSP, pain interference, and TNF-a (P's < .01). CRPS diagnosis at 6 months was predicted only by more widespread and intense pain preoperatively (P's < .05). Risk for CRPS following TKA appears to involve preoperative central sensitization and inflammatory mechanisms. Preoperative negative affect is unlikely to directly influence long-term CRPS risk. PERSPECTIVE: This article identifies preoperative predictors of CRPS features at 6 months following total knee arthroplasty, including more widespread pain and higher pain intensity, temporal summation of pain, pain interference, and tumor necrosis factor-alpha levels. Findings suggest the importance of central sensitization and inflammatory mechanisms in CRPS risk following tissue trauma.

Oxidative stress is associated with characteristic features of the dysfunctional chronic pain phenotype.

ABSTRACT: The dysfunctional chronic pain (Dysfunctional CP) phenotype is an empirically identifiable CP subtype with unclear pathophysiological mechanisms that cuts across specific medical CP diagnoses. This study tested whether the multidimensional pain and psychosocial features that characterize the dysfunctional CP phenotype are associated broadly with elevated oxidative stress (OS). Measures of pain intensity, bodily extent of pain, catastrophizing cognitions, depression, anxiety, sleep disturbance, pain interference, and function were completed by 84 patients with chronic osteoarthritis before undergoing total knee arthroplasty. Blood samples were obtained at the initiation of surgery before incision or tourniquet placement. Plasma levels of F2-isoprostanes and isofurans, the most highly specific measures of in vivo OS, were quantified using gas chromatography/negative ion chemical ionization mass spectrometry. The results indicated that controlling for differences in age, sex, and body mass index, higher overall OS (mean of isoprostanes and isofurans) was associated with significantly (P < 0.05) greater pain intensity, more widespread pain, greater depressive symptoms and pain catastrophizing, higher pain interference, and lower function. OS measures were not significantly associated with sleep disturbance or anxiety levels (P >0.10). The results build on prior case-control findings suggesting that presence of a CP diagnosis is associated with elevated OS, highlighting that it may specifically be individuals displaying characteristics of the dysfunctional CP phenotype who are characterized by elevated OS. Clinical implications of these findings remain to be determined.

Olmsted Syndrome: Case Report of Nursing Management of Premature Twins.

BACKGROUND: Olmsted syndrome is a rare and complex skin disorder affecting 46 (published) infants as of 2012. The infants affected in this case were born premature at 28 weeks' gestation. Infants affected by this syndrome demonstrate numerous plaques on several specific areas of the skin. Common treatments include exfoliation in addition to psoriasis treatments. The extremely fragile nature of the premature infants' skin complicates treatment modalities. CLINICAL FINDINGS: The progression of the infants' dermatologic findings and plaque formation is discussed in this case study. PRIMARY DIAGNOSIS: The primary diagnosis of Olmsted syndrome was made with the assistance of a multidisciplinary team to work through several differential diagnoses presenting with severe forms of palmoplantar keratoderma. INTERVENTIONS: The management of skin plaques in twin premature infants is presented in this case study. An evidence-based approach, utilizing the model of family-centered care, is presented with multidisciplinary involvement and an outline of the specific plan of care for the extensive skin care regimen used. OUTCOMES: An interdisciplinary skin care regimen was created to provide consistency in transition from hospital to home. Using a consistent approach, the plaques were able to be softened and many removed. Continual maintenance is required to manage continual buildup of skin plaques. PRACTICE RECOMMENDATIONS: Premature infants are at increased risk for infection due to the immaturity of their skin. The complexity of their skin complicates the ability to recognize and care for rare skin disorders. This case study illuminates the practicality of a consistent and evidence-based approach to a complex and rare skin disorder.

Work-Life Balance for Oral and Maxillofacial Surgeons.

Oral and maxillofacial surgeons experience high levels of stress and work-home conflict, which predispose them to burnout. There is emerging evidence in support of work-life integration to prevent burnout; interventional strategies exist on an individual and organizational level. This article explores the current evidence on promoting work-life integration for improved surgeon satisfaction, performance, and efficiency. Work-life integration initiatives can help promote the recruitment and retention of a diverse surgical workforce in oral and maxillofacial surgery.

Trainee Wellness and Safety in the Context of COVID-19: The Experience of One Institution.

The COVID-19 pandemic has had significant ramifications for provider well-being. During these unprecedented and challenging times, one institution's Department of Surgery put in place several important initiatives for promoting the well-being of trainees as they were redeployed to provide care to COVID-19 patients. In this article, the authors describe these initiatives, which fall into 3 broad categories: redeploying faculty and trainees, ensuring provider safety, and promoting trainee wellness. The redeployment initiatives are the following: reframing the team mindset, creating a culture of grace and forgiveness, establishing a multidisciplinary wellness committee, promoting centralized leadership, providing clear communication, coordinating between departments and programs, implementing phased restructuring of the department's services, establishing scheduling flexibility and redundancy, adhering to training regulations, designating a trainee ombudsperson, assessing physical health risks for high-risk individuals, and planning for structured deimplementation. Initiatives specific to promoting provider safety are appointing a trainee safety advocate, guaranteeing personal protective equipment and relevant information about these materials, providing guidance regarding safe practices at home, and offering alternative housing options when necessary. Finally, the initiatives put in place to directly promote trainee wellness are establishing an environment of psychological safety, providing mental health resources, maintaining the educational missions, solidifying a sense of community by showing appreciation, being attentive to childcare, and using social media to promote community morale. The initiatives to carry out the department's strategy presented in this article, which were well received by both faculty and trainee members of the authors' community, may be employed in other departments and even outside the context of COVID-19. The authors hope that colleagues at other institutions and departments, independent of specialty, will find the initiatives described here helpful during, and perhaps after, the pandemic as they develop their own institution-specific strategies to promote trainee wellness.

Continued nursing education in low-income and middle-income countries: a narrative synthesis.

Introduction: Continued nursing education and development can reduce mortality and morbidity of patients and can alleviate the shortage of healthcare workers by training of nurses for high-demand skill sets. We reviewed patterns of educational interventions and strategies in initiating behaviour change, improving patient outcomes or knowledge for nurses in low- and middle-income countries (LMICs). Methods: The study searched the MEDLINE (PubMed), Embase, CINAHL, Google Scholar and Web of Science databases. The study included interventional studies on continued nursing education from 2007 to 2017. Of the 6216 publications retrieved, 98 articles were included and analysed by three independent reviewers. Results: Of the 98 studies that met inclusion criteria, five were randomised controlled trials, two were qualitative in design and the remaining 91 were quasi-experimental, before-and-after studies. Of these studies, the median sample size of participants was 64, and the majority were conducted in Asia (53.1%). During the 10-year study period, 20.4% was conducted in 2015, the highest proportion, with a general increase in number of studies over time from 2007 to 2017. Main themes that arose from the review included train-the-trainer models, low-dose/high-frequency models, use of multiple media for training, and emphasis on nurse empowerment, strong international partnerships, and the integration of cultural context. Overall, the studies were limited in quality and lacked rigorous study design. Conclusion: Continued nursing education in LMICs is essential and effective in improving nurses' knowledge base, and thus patient outcomes and quality of care. Long-term, randomised studies are needed to understand how training strategies compare in impact on nurses and patients.

Facilitating Growth through Frustration: Using Genomics Research in a Course-Based Undergraduate Research Experience.

A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-Based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students' learning experience is continuous and recursive, frequently beginning with frustration but eventually leading to success as they come up with defendable gene models. In order to explore our "formative frustration" hypothesis, we gathered data from faculty via a survey, and from students via both a general survey and a set of student focus groups. Upon analyzing these data, we found that all three datasets mentioned frustration and struggle, as well as learning and better understanding of the scientific process. Bioinformatics projects are particularly well suited to the process of iteration and refinement because iterations can be performed quickly and are inexpensive in both time and money. Based on these findings, we suggest that a dynamic of "formative frustration" is an important aspect for a successful CURE.

Differing, multiscale landscape effects on genetic diversity and differentiation in eastern chipmunks.

Understanding how habitat loss and fragmentation impact genetic variation is a major goal in landscape genetics, but to date, most studies have focused solely on the correlation between intervening matrix and genetic differentiation at a single spatial scale. Several caveats exist in these study designs, among them is the inability to include measures of genetic diversity in addition to differentiation. Both genetic metrics help predict population persistence, but are expected to function at differing spatial scales, which requires a multiscale investigation. In this study, we sampled two distinct spatial scales in 31 independent landscapes along a gradient of landscape context (i.e., forest amount, configuration, and types of intervening matrix) to investigate how landscape heterogeneity influences genetic diversity and differentiation in the forest-associated eastern chipmunk (Tamias striatus). Overall, quality of intervening matrix was correlated with genetic differentiation at multiple spatial scales, whereas only configuration was associated with regional scale genetic diversity. Habitat amount, in contrast, did not influence genetic differentiation or diversity at either spatial scale. Based on our findings, landscape effects on genetic variation appears to differ based on spatial scale, the type of genetic response variable, and random variation among landscapes, making extrapolation of results from single scale, unreplicated studies difficult. We encourage landscape geneticists to utilize multiscale, replicated landscapes with both genetic diversity, and differentiation to gain a more comprehensive understanding of how habitat loss and fragmentation influence genetic variation.

When neighborhoods matter: Developmental timing and youth reading achievement and problem behaviors.

Consistent evidence links neighborhood socioeconomic status with children's development outcomes. However, it is less clear precisely whether or when neighborhoods are most strongly associated with children's socioemotional functioning and achievement. Couched in bioecological and developmental theory, this study tests two models of neighborhood effects: childhood and adolescent exposure. We used the Project on Human Development in Chicago Neighborhoods, a longitudinal, multi-cohort study of children in Chicago in the 1990s and 2000s. We examined two cohorts of children, early childhood and adolescence, to compare the relative associations between neighborhood socioeconomic advantage and disadvantage, as measured by U.S. Census data. We conducted multilevel latent growth models (MLGMs), investigating children's initial status and growth in reading, internalizing and externalizing behaviors across the three developmental periods by neighborhood characteristics, controlling for a rich set of child- and family-level covariates. Results provided some support for the childhood and adolescent exposure models, but not precisely as hypothesized.

Youth-serving institutional resources and neighborhood safety: Ties with positive youth development.

Neighborhoods are critical contexts for adolescent development, but little attention has been paid to how neighborhood characteristics play a role in positive youth development (PYD), notably among predominantly African American youth. This study examined distinct features of the neighborhood, including youth-serving institutional resources (YSI) and safety, as they relate to PYD among adolescents from low-income neighborhoods in an urban setting (n = 491, 68.6% African American). Because neighborhood experiences during adolescence often differ based on gender, we also examined moderation by gender. Results from cross-sectional, multilevel data suggest that neighborhood safety, YSIs, and gender are differentially associated with indicators of PYD (i.e., hope, mastery, friend support). The pattern of results suggested that when associated with mastery, YSIs may compensate for low-safety neighborhoods for adolescent females but not males. In terms of associations with friend support, YSIs may foster the development of PYD in low-safety neighborhoods for males but not females. Limitations of the current study and implications for future research are discussed. (PsycINFO Database Record

Creation of Nepal's First Skin Bank: Challenges and Outcomes.

BACKGROUND: In Nepal, burn trauma causes more than 55,000 injuries each year. Burn-related mortality is high in Nepal, in part due to lack of allograft, leading to high infection rates. To address this challenge, our collaboration between Kirtipur Hospital, America Nepal Medical Foundation, Stanford University, and ReSurge International established Nepal's first skin bank. METHODS: We identified 3 major tasks to create a sustainable skin banking program: 1) identify and acquire the equipment and personnel needed to collect, process, store, and graft cadaveric skin for burn injuries; 2) develop safe donation protocols and documentation tools that remain feasible for low-resource settings; and 3) develop a long-term awareness program to educate the Nepali people on skin donation, a previously foreign concept. RESULTS: Kirtipur Hospital acquired the necessary equipment and materials for the skin bank through a combination of local and international fundraising efforts. Existing U.S. skin banking protocols were adapted for the Nepali setting and piloted on potential patients, donors, and physicians. For the first time in the hospital's history, patients with > 40% total body surface area burns were successfully treated with extensive allografts. CONCLUSIONS: It is feasible to create a skin bank in a country with no tradition of allograft skin use. Long-term sustainability now depends on spreading awareness and education in the Kathmandu Valley to overcome religious and cultural barriers that have hindered donor recruitment. Our low-cost and high-impact skin bank provides a model to expand this system to other hospitals both within Nepal and beyond.

Residential Mobility and Adolescent Achievement and Behavior: Understanding Timing and Extent of Mobility.

Residential mobility is generally viewed as an adverse event for adolescents' development. Less is known about whether moving during adolescence, childhood, or both periods explains this connection and whether the extent of mobility matters. Analytic shortcomings with much of the research call into question extant findings. We examined associations between childhood, adolescent, and child-adolescent mobility and adolescents' achievement (math and reading) and behavior problems (internalizing and externalizing). With a multisite, longitudinal sample (N = 1,056), we employed propensity score methods, which mitigate concerns about selection bias on observed variables, to investigate relationships. Results suggest that multiple, child-adolescent movers had more internalizing problems in adolescence than their stable peers, but did not differ on externalizing problems or achievement.