COVID-19 and Well-Being of Non-local Students: Implications for International Higher Education Governance.

Non-local students have been one of the worst affected groups during the COVID-19 pandemic. Many of them live in foreign countries/regions with limited social and economic support. This study examines the effects of the COVID-19 pandemic and its control measures on the well-being of non-local students globally. It also examines the effectiveness of university support for the well-being of non-local students. Data were derived from a global survey on non-local students' knowledge, experiences, and well-being amidst the COVID-19 Pandemic, which was conducted in April 2020 (n = 583). A significant proportion (42.6%) of the students had low well-being. We found that being worried about COVID-19 (B = - 0.206, p = 0.048), perceived disruption of academic activities (B = - 0.155, p = 0.024), perceived disruption of social activities (B = - 0.153, p = 0.044), and feeling lonely (B = - 0.340, p = 0.000) were negatively associated with the students' well-being. However, informational support from universities was positively associated with their well-being (B = 0.225, p = 0.004). These findings are discussed in the context of higher education governance and practical changes necessary to promote non-local students' well-being during and after the pandemic.

Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells.

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and FcεRIα for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5-CD163+CD14+ cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies.

Metformin Monotherapy Downregulates Diabetes-Associated Inflammatory Status and Impacts on Mortality.

Aging is the main risk factor for developing diabetes and other age-related diseases. One of the most common features of age-related comorbidities is the presence of low-grade chronic inflammation. This is also the case of metabolic syndrome and diabetes. At the subclinical level, a pro-inflammatory phenotype was shown to be associated with Type-2 diabetes mellitus (T2DM). This low to mid-grade inflammation is also present in elderly individuals and has been termed inflammaging. Whether inflammation is a component of aging or exclusively associated with age-related diseases in not entirely known. We used clinical data and biological readouts in a group of individuals stratified by age, diabetes status and comorbidities to investigate this aspect. While aging is the main predisposing factor for several diseases there is a concomitant increased level of pro-inflammatory cytokines. DM patients show an increased level of sTNFRll, sICAM-1, and TIMP-1 when compared to Healthy, Non-DM and Pre-DM individuals. These inflammatory molecules are also associated with insulin resistance and metabolic syndrome in Non-DM and pre-DM individuals. We also show that metformin monotherapy was associated with significantly lower levels of inflammatory molecules, like TNFα, sTNFRI, and sTNFRII, when compared to other monotherapies. Longitudinal follow up indicates a higher proportion of death occurs in individuals taking other monotherapies compared to metformin monotherapy. Together our finding shows that chronic inflammation is present in healthy elderly individuals and exacerbated with diabetes patients. Likewise, metformin could help target age-related chronic inflammation in general, and reduce the predisposition to comorbidities and mortality.

Hallmarks of improved immunological responses in the vaccination of more physically active elderly females.

Physical inactivity is one of the leading contributors to worldwide morbidity and mortality. The elderly are particularly susceptible since the features of physical inactivity overlap with the outcomes of natural aging - including the propensity to develop cardiovascular diseases, cancer, diabetes mellitus, sarcopenia and cognitive impairment. The age-dependent loss of immune function, or immunosenescence, refers to the progressive depletion of primary immune resources and is linked to the development of many of these conditions. Immunosenescence is primarily driven by chronic immune activation and physical activity interventions have demonstrated the potential to reduce the risk of complications in the elderly by modulating inflammation and augmenting the immune system. Since poor vaccination outcome is a hallmark of immunosenescence, the assessment of vaccine efficacy provides a window to study the immunological effects of regular physical activity. Using an accelerator-based study, we demonstrate in a Singaporean Chinese cohort that elderly women (n=56) who walk more after vaccination display greater post-vaccination expansion of monocytes and plasmablasts in peripheral blood. Active elderly female participants also demonstrated lower baseline levels of IP-10 and Eotaxin, and the upregulation of genes associated with monocyte/macrophage phagocytosis. We further describe postive correlations between the monocyte response and the post-vaccination H1N1 HAI titres of participants. Finally, active elderly women reveal a higher induction of antibodies against Flu B in their 18-month second vaccination follow-up. Altogether, our data are consistent with better immunological outcomes in those who are more physically active and highlight the pertinent contribution of monocyte activity.

Mapping of γ/δ T cells reveals Vδ2+ T cells resistance to senescence.

BACKGROUND: Immune adaptation with aging is a major of health outcomes. Studies in humans have mainly focus on αß T cells while γδ T cells have been neglected despite their role in immunosurveillance. We investigated the impact of aging on γδ T cell subsets phenotypes, functions, senescence and their molecular response to stress. METHODS: Peripheral blood of young and old donors in Singapore have been used to assess the phenotype, functional capacity, proliferation capacity and gene expression of the various γδ T cell subsets. Peripheral blood mononuclear cells from apheresis cones and young donors have been used to characterize the telomere length, epigenetics profile and DNA damage response of the various γδ T cell subsets phenotype. FINDINGS: Our data shows that peripheral Vδ2+ phenotype, functional capacity (cytokines, cytotoxicity, proliferation) and gene expression profile are specific when compared against all other αß and γδ T cells in aging. Hallmarks of senescence including telomere length, epigenetic profile and DNA damage response of Vδ2+ also differs against all other αß and γδ T cells. INTERPRETATION: Our results highlight the differential impact of lifelong stress on γδ T cells subsets, and highlight possible mechanisms that enable Vδ2+ to be resistant to cellular aging. The new findings reinforce the concept that Vδ2+ have an "innate-like" behavior and are more resilient to the environment as compared to "adaptive-like" Vδ1+ T cells.

Influenza Vaccine-Induced Antibody Responses Are Not Impaired by Frailty in the Community-Dwelling Elderly With Natural Influenza Exposure.

Background: Elderly adults over 65 years of age are recommended to receive seasonal influenza vaccination as they are at a higher risk of infection and its complications than the younger community. The elderly are often stratified according to frailty status where frail individuals are more susceptible to adverse health outcomes than their non-frail counterparts, however, it is not known whether immunity induced by influenza vaccination is impaired in the frail elderly. Study Design: Two hundred and five elderly subjects of Chinese ethnicity in Singapore (mean age 73.3 ± 5.3 years, 128 females and 77 males) were administered the recommended trivalent inactivated 2013-14 seasonal influenza vaccine (Vaxigrip™) containing A/H1N1, A/H3N2, and B strains. The elderly subjects were stratified into three groups according to Fried's frailty criteria (59 frail, 85 pre-frail, 61 robust) and were also ranked by Rockwood's frailty index (RFI). Statistical associations were evaluated between frailty status and pre- and post-vaccination antibody titres in sera measured by Hemagglutination inhibition (HAI) and microneutralization (MN) assays. Immunological responses across frailty strata were also studied in terms of leukocyte cellular distribution, cytokine levels and gene expression. Results: Post-vaccination, 83.4% of the subjects seroconverted for A/H1N1, 80.5% for A/H3N2, and 81% for the B strain. The seroconversion rates were comparable across frailty groups (A/H1N1, ANOVA, p = 0.7910; A/H3N2, ANOVA, p = 0.8356, B, ANOVA, p = 0.9741). Geometric mean titres of HAI and MN as well as seroprotection rates were also similar in all three frailty groups and uncorrelated with RFI (Spearman, r = 0.023, p = 0.738). No statistically significant differences were observed between the frailty groups in vaccine-induced modulation of leukocyte populations, cytokine responses, and gene expression profiles of peripheral blood mononuclear cells (PBMCs). Whereas, post- and pre-vaccination HAI titres were positively correlated after adjusting for age and gender (A/H1N1, R2 = 0.216, p = 9.1e-11; A/H3N2, R2 = 0.166, p = 3.4e-8; B, R2 = 0.104, p = 3.1e-5). With most subjects lacking previous history of influenza vaccination, the pre-vaccination titres were likely due to natural exposure and seen to match the pattern of influenza subtype prevalence in the time period of vaccination. Conclusion: The majority of the elderly subjects seroconverted for seasonal influenza upon vaccination, and importantly, influenza vaccination-induced humoral immune responses and seroprotection were similar across the frailty strata, indicating that frail individuals may also benefit from influenza vaccination. Pre-existing antibodies due to natural exposure appeared to positively influence vaccine-induced antibody responses.

Dysregulated homeostatic pathways in sarcopenia among frail older adults.

Sarcopenia, a core feature of the physical frailty syndrome, is characterized by multisystem physiological dysregulation. No study has explored qualitatively the hierarchical network of relationships among different dysregulated pathways involved in the pathogenesis of sarcopenia. We used 40 blood biomarkers belonging to community-dwelling prefrail and frail older persons to derive measures of multiple physiological pathways, and structural equation modeling to generate path network models of the multisystem physiological dysregulations associated with muscle mass and function (MMF). Insulin-leptin signaling and energy regulation, anabolic sex steroid regulation (testosterone, leptin), and tissue oxygenation (hemoglobin, red cell count) appear to be primary mediating factors exerting direct influences on MMF. There was additionally secondary mediatory involvement of myocyte- and adipocyte-derived cytokines, hypothalamic pituitary adrenal (HPA) stress hormones (cortisol, DHEAS), glomerular function, and immune cell regulatory and inflammatory cytokines and glycoproteins. We conclude that within a hierarchical network of multisystem physiological dysregulations in sarcopenia, dysregulated anabolic and catabolic pathways via sex steroids and insulin-leptin dual signaling and tissue hypoxemia are primary physiological dysregulations responsible for sarcopenia and frailty.

Longitudinal Study of Cellular and Systemic Cytokine Signatures to Define the Dynamics of a Balanced Immune Environment During Disease Manifestation in Zika Virus-Infected Patients.

Background: Since its unexpected reemergence, Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection. Methods: Patient samples were collected longitudinally during the acute, convalescence and recovery phases of ZIKV infection over 6 months during the Singapore outbreak in late 2016. Plasma immune mediators were profiled via multiplex microbead assay, while changes in blood cell numbers were determined with immunophenotyping. Results: Data showed the involvement of various immune mediators during acute ZIKV infection accompanied by a general reduction in blood cell numbers for all immune subsets except CD14+ monocytes. Importantly, viremic patients experiencing moderate symptoms had significantly higher quantities of interferon γ-induced protein 10, monocyte chemotactic protein 1, interleukin 1 receptor antagonist, interleukin 8, and placental growth factor 1, accompanied by reduced numbers of peripheral CD8+ T cells, CD4+ T cells, and double-negative T cells. Levels of T-cell associated mediators, including interferon γ-induced protein 10, interferon γ, and interleukin 10, were high in recovery phases of ZIKV infection, suggesting a functional role for T cells. The identification of different markers at specific disease phases emphasizes the dynamics of a balanced cytokine environment in disease progression. Conclusions: This is the first comprehensive study that highlights specific cellular changes and immune signatures during ZIKV disease progression, and it provides valuable insights into ZIKV immunopathogenesis.

Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies.

Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2.

During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.

Inflammatory and immune markers associated with physical frailty syndrome: findings from Singapore longitudinal aging studies.

Chronic systematic inflammation and reduced immune system fitness are considered potential contributing factors to the development of age-related frailty, but the underlying mechanisms are poorly defined. This exploratory study aimed to identify frailty-related inflammatory markers and immunological phenotypes in a cohort of community-dwelling adults aged ≥ 55 years. Frailty was assessed using two models, a Frailty Index and a categorical phenotype, and correlated with levels of circulating immune biomarkers and markers of senescence in immune cell subsets. We identified eight serological biomarkers that were associated with frailty, including sgp130, IL-2Rα, I-309, MCP-1, BCA-1, RANTES, leptin, and IL-6R. Frailty Index was inversely predicted by the frequency of CD3+, CD45RA+, and central memory CD4 cells, and positively predicted by the loss of CD28 expression, especially in CD8+ T cells, while frailty status was predicted by the frequency of terminal effector CD8+ T cells. In γ/δ T cells, frailty was negatively associated with CD27, and positively associated with IFNγ+TNFα- secretion by γ/δ2+ cells and IFNγ-TNFα+ secretion by γ/δ2- cells. Increased numbers of exhausted and CD38+ B cells, as well as CD14+CD16+ inflammatory monocytes, were also identified as frailty-associated phenotypes. This pilot study supports an association between inflammation, cellular immunity, and the process of frailty. These findings have significance for the early identification of frailty using circulating biomarkers prior to clinical manifestations of severe functional decline in the elderly.

Quality-of-life concerns of Chinese patients with advanced cancer.

This study aimed to examine the quality of life (QOL) of patients with advanced cancer in Hong Kong. Ninety participants were recruited from the oncology ward of the study hospital. They responded to a 28-item, 8-subscale multidimensional questionnaire and a single-item scale that measured QOL in a face-to-face interview. Participation in health care decisions, food-related concerns, and existential distress were some QOL concerns that require health care professionals' attention. Walking ability predicted the level of QOL in certain QOL domains that surfaces patients' need for rehabilitation. That the QOL domain value of life was the most important domain that predicted overall QOL calls for meaning-of-life interventions for palliative care.

Effect of a life review program for Chinese patients with advanced cancer: a randomized controlled trial.

BACKGROUND: Empirical data suggest that life review is an effective psychospiritual intervention. However, it has not been applied to Chinese patients with advanced cancer, and its effects on this population remain unknown. OBJECTIVE: The aim of the study was to determine the effect of a life review program on quality of life among Chinese patients with advanced cancer. METHODS: In this prospective randomized controlled trial, a total of 80 patients were randomly assigned to the life review program group and the control group. The 3-weekly life review program included reviewing a life and formulating a life review booklet. Outcome data were assessed by a collector who was blinded to group assignment before and immediately after the program and at a 3-week follow-up. RESULTS: Significantly better scores in overall quality of life, support, negative emotions, sense of alienation, existential distress, and value of life were found in the life review group immediately after the program and at the 3-week follow-up. CONCLUSION: This study provides additional data on the potential role of a life review in improving quality of life, particularly psychospiritual well being; it also indicates that the life review program could enable Chinese patients with advanced cancer to express their views on life and death. IMPLICATIONS FOR PRACTICE: The life review program offers advanced cancer patients an opportunity to integrate their whole life experiences and discuss end-of-life issues, which lays the ground for further active intervention in their psychospiritual distress. The program could be integrated into daily home care to enhance the psychospiritual well-being of Chinese patients with advanced cancer.

The meaning of life intervention for patients with advanced-stage cancer: development and pilot study.

PURPOSE/OBJECTIVES: To develop the Meaning of Life Intervention in response to the need for brief and meaning-focused interventions in palliative care and to establish potential effect sizes for future full-scale randomized, controlled trials. DESIGN: A randomized, controlled trial conducted to pilot test the Meaning of Life Intervention. SETTING: A 68-bed oncology inpatient ward in an urban acute general hospital in Hong Kong. SAMPLE: 84 patients with advanced-stage cancer. Fifty-eight completed the study. METHODS: Assessments of outcome variables were conducted at baseline and one day and two weeks after the intervention. Patients were randomly allocated to the intervention group or the control group. Repeated measures analysis of covariance were conducted to assess the impact of the Meaning of Life Intervention on participants' quality of life. MAIN RESEARCH VARIABLES: The primary outcome was quality of life and was measured by the Quality-of-Life Concerns in the End-of-Life (QOLC-E) questionnaire and with a single-item scale on global quality of life. The eight subscales of the QOLC-E served as secondary outcomes. FINDINGS: Statistically significant main effects were noted for the group in the QOLC-E questionnaire total score, the single-item scale on global quality of life, and the existential distress subscale of the QOLC-E questionnaire. The effects represented a medium effect size. CONCLUSIONS: The results of this pilot study show that the Meaning of Life Intervention can improve quality of life, particularly existential distress. IMPLICATIONS FOR NURSING: The Meaning of Life Intervention represents a potentially effective and efficient intervention that is feasible for implementation by nursing staff for patients with advanced-stage cancer in a palliative care setting.

Perceptions of a life review programme among Chinese patients with advanced cancer.

AIMS: The aim of this study was to elicit patients' perceptions of their participation in a life review programme for Chinese patients with advanced cancer. BACKGROUND: Empirical data have supported the suggestion that a life review is an effective psycho-spiritual intervention, particularly with older people. However, no life review programmes have been specifically designed for Chinese patients with advanced cancer, and their views on the life review therefore remain unknown. DESIGN: This study was a descriptive qualitative design. METHOD: In-depth individual interviews were conducted with a sample of 26 patients with advanced cancer receiving home-based palliative care from a hospice after the completion of the programme. RESULTS: The six categories identified in the analysis were as follows: (1) accepting one's unique life; (2) feelings of emotional relief; (3) bolstering a sense of meaning in life; (4) leaving a personal legacy; (5) making future orientations; and (6) barriers to a life review. CONCLUSION: Our life review programme is non-invasive care intervention for improving the psycho-spiritual well-being of Chinese patients with advanced cancer and helping them to prepare for death. This programme not only provides Chinese nurses with a new approach to meeting the unique needs of patients approaching death but also poses a challenge to customary beliefs about death, which is considered a social taboo in China. RELEVANCE TO CLINICAL PRACTICE: The life review programme can be integrated into the usual care arrangements to enhance the psycho-spiritual well-being of Chinese patients with advanced cancer. Nurses should be aware of the challenges involved in the process of conducting a life review.

Evaluation of the psychometric properties of a modified Chinese version of the Caregiver Task Inventory--refinement and psychometric testing of the Chinese Caregiver Task Inventory: a confirmatory factor analysis.

AIM: To test the reliability and validity of the modified Chinese version of the Caregiver Task Inventory. BACKGROUND: The original Caregiver Task Inventory was developed in 1983 by Clark and Rakowski in the USA. It was used to measure Chinese family caregivers' needs in Hong Kong. Its failure to evaluate the psychometric properties of the instrument measuring the needs of family caregivers across cultures limited its scientific rigor. DESIGN: A quantitative study method was used to test the psychometrics of the modified Chinese version of the Caregiver Task Inventory. METHODS: A convenience sample of 114 family caregivers completed the Caregiver Task Inventory in 2005 to test different aspects of the validity and reliability and confirm items of the short form of the Chinese Caregiver Task Inventory-25. RESULTS: The content validity of the 25 items of the Chinese Caregiver Task Inventory was validated by six experts, who assessed the correlation between caregiving tasks and the five refined sub-scales. The construct validity was determined by confirmatory factor analysis (CFA). The χ(2) goodness-of-fit, χ(2): df ratio, goodness-of-fit index (GFI), adjusted GFI and root mean square residual were obtained and used to assess the fit of the model. The internal consistency and stability of the Chinese Caregiver Task Inventory-25 were determined by Cronbach's method (0·93) and the internal reliability (item total correlation) for the five refined sub-scales ranged from 0·67-0·86. CFA and internal consistency analysis showed a strong degree of fit between the conceptualisation and the development of the measurement. CONCLUSIONS: The Chinese Caregiver Task Inventory-25 is a relevant and culturally appropriate research instrument to measure the needs of Chinese family caregivers. RELEVANCE TO CLINICAL PRACTICE: This study reveals that stroke nurses should assess the impacts of caregiving tasks on caregivers' physical and psychological stress levels prior to planning relevant interventions.

Holistic concerns of Chinese stroke survivors during hospitalization and in transition to home.

AIM: This article is a report of a study conducted to explore the phenomenon of concerns as experienced by Chinese stroke survivors during hospitalization and in transition to home. BACKGROUND: Stroke is characterized by its sudden onset and prolonged residual problems, which affect survivors' holistic well-being. Many studies have focused on stroke consequences and their correlates with psychosocial outcomes. Very little is known about holistic concerns of stroke survivors, particularly in the transition from hospital to home. METHOD: We used purposive sampling of 15 stroke survivors who participated in semi-structured interviews after being discharged from stroke wards of a general hospital in Hong Kong from November 2008 to February 2009. The interviews were transcribed verbatim and analysed using Giorgi's phenomenological techniques. FINDINGS: Stroke survivors' physical, psychological, socio-cultural and spiritual concerns in hospital and transition to home emerged from the data analysis. The four major themes identified were: (a) dynamic interplay of holistic concerns, (b) cultural expression of illness experiences, (c) social support 'paradox' and (d) caring gaps in clinical management. CONCLUSION: Understanding the interwoven holistic concerns for the stroke survivors in hospital and after discharged home can help nurses to identify their health needs and plan for appropriate nursing interventions. The findings provide guidance for the development of culture-sensitive holistic care interventions with family involvement in Chinese stroke populations.

Advance directives and life-sustaining treatment: attitudes of Hong Kong Chinese elders with chronic disease.

OBJECTIVE: To examine the attitudes of Hong Kong Chinese elders with chronic disease with regard to advance directives and life-sustaining treatment. DESIGN: Cross-sectional questionnaire survey. SETTING: Medical unit of a regional teaching hospital in Hong Kong. PARTICIPANTS: In-patients aged 60 years or above with chronic disease. MAIN OUTCOME MEASURES: Demographic profiles and attitudes towards advance directives and life-sustaining treatment. RESULTS: A total of 219 elderly patients completed the questionnaire. Their mean age was 73 (standard deviation, 8) years; 133 (61%) were female. The majority had neither heard about advance directives (81%), nor discussed the issue with others (73%) before participating in this study. After they were informed of the concept of advance directives, about half (49%) said they would consider using it if it is legislated in Hong Kong. The respondents generally supported the withholding or withdrawing of life-sustaining treatment in medically futile situations. In all, 55% of them believed that the patient alone should make the decision on withholding or withdrawing life-sustaining treatment, if competent to do so. If the patient became not competent, 44% believed that the individual's family alone should make such a decision. CONCLUSION: The fact that most of the respondents had never heard about advance directives or discussed the concept with others points to a lack of knowledge and to the necessity to step up public education about such issues.