Shifting the focus: Addressing breast cancer disparities at the health care organization level

The purpose of this study was to understand the scope of breast cancer disparities within the Texas Medical Center. The goal was to increase the awareness of breast cancer disparities at the health care organization level, and to foster the development of organizational interventions to reduce breast cancer disparities. The study seeks to answer the following questions: 1. Are hospitals in the Texas Medical Center implementing interventions to reduce breast cancer disparities? 2. What are their interventions for reducing the effects of non clinical factors on breast cancer treatment disparities? 3. What are their measures for monitoring, continuously improving, and evaluating the success of their interventions? ^ This research project was designed as a mixed methods case study. Quantitative breast cancer data for the years 2000-2009 was obtained from the Texas Cancer Registry (TCR). Qualitative data collection and analysis was done by conducting a total of 20 semi-structured interviews of administrators, physicians and nurses at five hospitals (A, B, C, D and E) in the Texas Medical Center (TMC). For quantitative analysis, the study was limited to early stage breast cancer patients: local and regional. The dependent variable was receipt of standard treatment: Surgery (Yes/No), BCS vs Mastectomy, Chemotherapy (Yes/No) and Radiation after BCS (Yes/No). The main independent variable was race: non-Hispanic White (NHW) , non-Hispanic Black (NHB), and Hispanic. Other covariates included age at diagnosis, diagnosis date, percent poverty, grade, stage, and regional nodes. Multivariate logistic regression was used to test the adjusted association between receipt of standard care and race. Qualitative data was analyzed with the Atlas.ti7 software (ATLAS.ti GmbH, Berlin). ^ Though there were significant differences by race for all dependent variables when the data was analyzed as a single group of all hospitals; at the level of the individual hospitals the results were not consistent by race/ethnicity across all dependent variables for hospitals A, B, and E. There were no racial differences in adjusted analysis for receipt of chemotherapy for the individual hospitals of interest in this study. For hospitals C and D, no racial disparities in treatment was observed in adjusted multivariable analysis. All organizations in this study were aware of the body of research which shows that there are disparities in breast cancer outcomes for patient population groups. However, qualitative data analysis found that there were differences in interest among hospitals in addressing breast cancer disparities in their patient population groups. Some organizations were actively implementing directed measures to reduce the breast cancer disparity gap in outcomes for patients, and others were not. Despite the differences in levels of interest, quantitative data analysis showed that organizations in the Texas Medical Center were making progress in reducing the burden of breast cancer disparities in the patient populations being served.^

Evaluation of PRESAGE® dosimeters for brachytherapy sources and the 3D dosimetry and characterization of the new AgX100 125I seed model

With continuous new improvements in brachytherapy source designs and techniques, method of 3D dosimetry for treatment dose verifications would better ensure accurate patient radiotherapy treatment. This study was aimed to first evaluate the 3D dose distributions of the low-dose rate (LDR) Amersham 6711 OncoseedTM using PRESAGE® dosimeters to establish PRESAGE® as a suitable brachytherapy dosimeter. The new AgX100 125I seed model (Theragenics Corporation) was then characterized using PRESAGE® following the TG-43 protocol. PRESAGE® dosimeters are solid, polyurethane-based, 3D dosimeters doped with radiochromic leuco dyes that produce a linear optical density response to radiation dose. For this project, the radiochromic response in PRESAGE® was captured using optical-CT scanning (632 nm) and the final 3D dose matrix was reconstructed using the MATLAB software. An Amersham 6711 seed with an air-kerma strength of approximately 9 U was used to irradiate two dosimeters to 2 Gy and 11 Gy at 1 cm to evaluate dose rates in the r=1 cm to r=5 cm region. The dosimetry parameters were compared to the values published in the updated AAPM Report No. 51 (TG-43U1). An AgX100 seed with an air-kerma strength of about 6 U was used to irradiate two dosimeters to 3.6 Gy and 12.5 Gy at 1 cm. The dosimetry parameters for the AgX100 were compared to the values measured from previous Monte-Carlo and experimental studies. In general, the measured dose rate constant, anisotropy function, and radial dose function for the Amersham 6711 showed agreements better than 5% compared to consensus values in the r=1 to r=3 cm region. The dose rates and radial dose functions measured for the AgX100 agreed with the MCNPX and TLD-measured values within 3% in the r=1 to r=3 cm region. The measured anisotropy function in PRESAGE® showed relative differences of up to 9% with the MCNPX calculated values. It was determined that post-irradiation optical density change over several days was non-linear in different dose regions, and therefore the dose values in the r=4 to r=5 cm regions had higher uncertainty due to this effect. This study demonstrated that within the radial distance of 3 cm, brachytherapy dosimetry in PRESAGE® can be accurate within 5% as long as irradiation times are within 48 hours.

The role of suppressor factors in the regulation of immune responses by ultraviolet radiation -induced suppressor T lymphocytes

The purpose of these studies was to determine the role of suppressor factors (TsF) in the regulation of immune responses by ultraviolet radiation-induced suppressor T lymphocytes (Ts). The Ts were induced following epicutaneous sensitization with contact allergens to an unirradiated site on mice irradiated five days earlier with 40 kJ/m$\sp2$ UVB (280-320 nm) radiation. The spleens of such mice contain afferent, hapten-specific, Thy-1$\sp+$, Lyt-1$\sp+$,2$\sp-$ Ts that suppress in vivo contact hypersensitivity (CHS) and antibody responses and the in vitro generation of cytotoxic T lymphocytes (CTL). Four approaches were used to determine the role of TsF. First, lysates produced from sonically-disrupted Ts were injected i.v. into normal animals; they inhibited CHS in vivo in a nonspecific manner. The lysates suppressed the induction and elicitation of CHS, and they inhibited the in vitro generation of CTL. Lysates prepared from splenocytes obtained from unirradiated mice or UV-irradiated, unsensitized mice failed to inhibit either response. Second, supernatants from cultures containing Ts, normal syngeneic responder lymphocytes, and hapten-modified stimulator cells were injected i.v. into normal recipients. They inhibited the induction of CHS and did so in a hapten-specific manner. Cellular and kinetic requirements were observed for the generation of suppressive activity. Splenocytes from mice treated with Ts supernatants suppressed CHS when transferred into normal animals. The supernatants also suppressed the in vitro generation of specific CTL. Third, the TsF-specific B16G monoclonal antibody was tested for its ability to modulate the effects of UV radiation in vivo. The i.v. injection of B16G into UV-irradiated mice reduced the suppression of CHS. Splenocytes of B16G-treated mice transferred into normal recipients, and they suppressed CHS, indicating that the Ts were not depleted. Fourth, B16G was used to isolate a putative TsF by antibody immunoadsorbance. When the B16G-bound fraction was eluted and injected i.v. into normal animals, it suppressed CHS and represented a 900-fold enrichment of activity over the starting material, based on specific activity. By SDS-PAGE, the B16G-bound material contained nondisulfide-linked 45- and 50-kDa components. These results suggest that TsF may play an immunoregulatory role in CHS. The isolation of a UV radiation-induced TsF lends credence to the involvement of such molecules. ^

Immunologic characteristics of immunogenic variants generated by {\it in vitro\/} treatment of a methylcholanthrene-induced murine fibrosarcoma MCA-F with 1 methyl-3-nitro-1-nitrosoguanidine, 5 -aza-2$\sp\prime$-deoxycytidine, or ultraviolet radiation

This study addresses the questions of whether the frequency of generation and in vivo cross-reactivity of highly immunogenic tumor clones induced in a single parental murine fibrosarcoma cell line MCA-F is more closely related to the agent used to induce the Imm$\sp{+}$ clone or whether these characteristics are independent of the agents used. These questions were addressed by treating the parental tumor cell line MCA-F with UV-B radiation (UV-B), 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), or 5-aza-2$\sp\prime$-deoxycytidine (5-azaCdR). The frequency of Imm$\sp{+}$ variant generation was similarly high for the three different agents, suggesting that the frequency of Imm$\sp{+}$ generation was related more closely to the cell line than to the inducing agent used. Cross-reactivity was tested with two Imm$\sp{+}$ clones from each treatment group in a modified immunoprotection assay that selectively engendered antivariant, but not antiparental immunity. Under these conditions each clone, except one, immunized against itself. The MNNG-induced clones engendered stronger antivariant immunity but a weaker variant cross-reactive immunity could also be detected.^ This study also characterized the lymphocyte populations responsible for antivariant and antiparental immunity in vivo. Using the local adoptive transfer assay (LATA) and antibody plus complement depletion of T-cell subsets, we showed that immunity induced by the Imm$\sp{+}$ variants against the parent MCA-F was transferred by the Thy1.2$\sp{+}$, L3T4a$\sp{+}$, Lyt2.1$\sp{-}$ (CD4$\sp{+}$) population, without an apparent contribution by Thy1.2$\sp{+}$, L3T4a$\sp{-}$, Lyt2.1$\sp{+}$ (CD8$\sp{+}$) cells. A role for Lyt2.1$\sp{+}$T lymphocytes in antivariant, but not antiparent immunity was supported by the results of LATA and CTL assays. Immunization with low numbers of viable Imm$\sp{+}$ cells, or with high numbers of non viable Imm$\sp{+}$ cells engendered only antivariant immunity without parental cross-protection. The associative recognition of parental antigens and variant neoantigens resulting in strong antiparent immunity was investigated using somatic cells hybrids of Imm$\sp{+}$ variants of MCA-F and an antigenically distinct tumor MCA-D. An unexpected result of these latter experiments was the expression of a unique tumor-specific antigen by the hybrid cells. These studies demonstrate that the parental tumor-specific antigen and the variant neoantigen must be coexpressed on the cell surface to engender parental cross-protective immunity. (Abstract shortened with permission of author.) ^

Alterations in the ras oncogene and the p53 tumor suppressor gene in ultraviolet radiation-induced skin carcinogenesis

A rapid increase of the ultraviolet radiation (UVR)-related skin cancer incidence has attracted more and more public attention during the last few decades. Prevention and treatment of UVR-related skin cancer has become an important public health issue in the United States. Recent studies indicate that mutations in ras and/or p53 genes may be involved in UVR-induced skin tumor development but the precise molecular mechanism remains unclear. In this study, alterations of H-ras and p53 genes were investigated in different stages of carcinogenesis in a chronic UVR (solar simulator) exposure-induced Sencar mouse skin carcinogenesis model in order to clarify the role of the alterations of these genes during the skin carcinogenesis process and to further understand the mechanisms by which UVR causes skin cancer.^ Positive ras-p21 staining in cell membranes and cytosol were detected in 18/33 (55%) of squamous cell carcinomas (SCCs), but were not detected in UV-exposed skin, papillomas, or spindle cell tumors (SCTs). Positive staining of the malignant progression marker K13 was found in 17/33 (52%) of SCCs only. A significant positive correlation was observed between the K13 and the ras-p21 expression. Polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis and gene sequencing analysis revealed three point mutations, one (codon 56) in UV-exposed non-tumor bearing skin and the other two (codons 21 and 13) in SCCs. No UV-specific mutation patterns were found.^ Positive p53 nuclear staining was found in 10/37 (27%) of SCCs and 12/24 (50%) of SCTs, but was not detected in normal skin or papillomas. PCR-based SSCP and sequencing analysis revealed eight point mutations in exons 5 and 6 (four in SCTs, two in SCCs, and two in UV-exposed skin) including six C-T or C-A transitions. Four of the mutations occurred at a dipyrimidine (CC) sequence. The pattern of the mutations indicated that the mutagenic lesions were induced by UVR.^ These results indicate that overexpression of ras-p21 in conjunction with aberrant expression of K13 occurred frequently in UVR-induced SCCs in Sencar mouse skin. The point mutation in the H-ras gene appeared to be a rare event in UVR skin carcinogenesis and may not be responsible for overexpression of ras-p21. UVR-induced P53 gene alteration is a frequent event in UVR-induced SCCs and later stage SCT tumors in Sencar mice skin, suggesting the p53 gene mutation plays an important role in skin tumor malignant progression. ^

Investigation of mechanisms involved in ultraviolet B radiation-induced, T cell -mediated immune suppression

Cutaneous exposure to ultraviolet-B radiation (UVR) results in the suppression of cell-mediated immune responses such as contact hypersensitivity (CHS) and delayed-type hypersensitivity (DTH). This modulation of immune responses is mediated by local or systemic mechanisms, both of which are associated with the generation of antigen-specific suppressor T lymphocytes (Ts). UV-induced Ts have been shown to be CD3+CD4+CD8 − T cells that control multiple immunological pathways. However, the precise mechanisms involved in the generation and function of these immunoregulatory cells remain unclear. We investigated the cellular basis for the generation of UV-induced Ts lymphocytes in both local and systemic models of immune suppression, and further examined the pleiotrophic function of these immunoregulatory cells. ^ We used Thy1.1 and Thy1.2 congenic mice in a draining lymph node (DLN) cell transfer model to analyze the role played by epidermal Langerhans cells in the generation of Ts cells. We demonstrate that T cells tightly adhered to antigen-presenting cells (APC) from UV-irradiated skin are the direct progenitors of UV-induced Ts lymphocytes. Our studies also reveal that UV-induced DNA-damage in the form of cyclobutyl pyrimidine dimers (CPD) in the epidermal APC is crucial for the altered maturation of these adherent T cells into Ts. ^ We used TCR transgenic mice in an adoptive transfer model and physically tracked the antigen-specific clones during immune responses in unirradiated versus UV-irradiated mice. We demonstrate that UV-induced Ts and effector TDTH cells share the same epitope specificity, indicating that both cell populations arise from the same clonal progenitors. UVR also causes profound changes in the localization and proliferation of antigen-specific T cells during an immune response. Antigen-specific T cells are not detectable in the DLNs of UV-irradiated mice after 3 days post-immunization, but are found in abundance in the spleen. In contrast, these clones continue to be found in the DLNs and spleens of normal animals several days post-immunization. Our studies also reveal that a Th2 cytokine environment is essential for the generation of Ts in UV-irradiated mice. ^ The third part of our study examined the pleiotrophic nature of UV-induced Ts. We used a model for the induction of both cellular and humoral responses to human gamma-globulin (HGG) to demonstrate that UV-induced Ts lymphocytes can suppress DTH as well as antibody responses. (Abstract shortened by UMI.) ^

The role of p53 in skin cancer induction by UV radiation and as a potential tumor antigen in UV-induced murine skin tumors

Carcinoma of the skin is the most common type of human cancer in the United States. Ultraviolet radiation (UVR) present in the sunlight is thought to be the major carcinogen responsible for induction of skin cancer. In UV-associated skin carcinogenesis, mutations in p53 are not only present with very high frequency, but occur early in the course of tumor development. In addition, UV-induced skin tumors in mice exhibit unique immunological characteristics. They are highly antigenic and express both individually-specific tumor transplantation antigens recognized by effector T cells and the UV-associated common antigen recognized by UV-induced suppressor T cells. ^ To examine the hypothesis that p53 plays a critical role in preventing skin cancer induction by UVR, mice constitutively lacking one or two functional p53 alleles were compared to wild-type mice for their susceptibility to UV carcinogenesis. Both p53 +/– and –/– mice showed greater susceptibility to skin cancer induction than wild-type mice, and –/– mice were the most susceptible, Accelerated tumor development in the p53 +/– mice was not associated with loss of the remaining wild-type allele of p53 , but in many cases was associated with UV-induced mutations in p53. Our studies clearly demonstrate the essential role of p53 in protection against UV carcinogenesis, particularly in the eye and epidermis. ^ The role of p53 in the antigenicity of UV-induced murine skin tumors was also addressed. Primary UV-induced tumors from p53 –/–, +/– and +/+ mice were transplanted into both normal and immunosuppressed mice, and rates of tumor rejection were compared. Tumors from mice with only one or no functional p53 alleles were less antigenic than those from mice with two functional p53 alleles. Moreover, tumors with no functional p53 also failed to grow well in chronically UV-irradiated mice. These results indicate that p53 contributes to the strong antigenicity of UV-induced murine skin tumors, and suggest that it may play a critical role in expression of the UV-associated common antigen recognized by suppressor T cells. ^ In this study we also monitored the effect of UVR on the development of lymphoid malignancies in p53 deficient mice. The incidence of lymphoid malignancies in UV-irradiated p53 +/– mice was drastically enhanced compared to that in unirradiated counterparts. The immune responses of the mice were identical and were suppressed to the same extent by UV irradiation regardless of the p53 genotype. These data provide the first experimental evidence that exposure to UVR can contribute to the development of lymphoid neoplasms in genetically susceptible hosts. ^

Low current performance of the Bern medical cyclotron down to the pA range

A medical cyclotron accelerating H- ions to 18 MeV is in operation at the Bern University Hospital (Inselspital). It is the commercial IBA 18/18 cyclotron equipped with a specifically conceived 6 m long external beam line ending in a separate bunker. This feature is unique for a hospital-based facility and makes it possible to conduct routine radioisotope production for PET diagnostics in parallel with multidisciplinary research activities, among which are novel particle detectors, radiation biophysics, radioprotection, radiochemistry and radiopharmacy developments. Several of these activities, such as radiobiology experiments for example, require low current beams down to the pA range, while medical cyclotrons are designed for high current operation above 10 μA. In this paper, we present the first results on the low current performance of a PET medical cyclotron obtained by ion source, radio-frequency and main coil tuning. With this method, stable beam currents down to (1.5+/- 0.5 ) pA were obtained and measured with a high-sensitivity Faraday cup located at the end of the beam transport line.

Moving from medical to health systems classifications of deaths : extending verbal autopsy to collect information on the circumstances of mortality

Funding A Health Systems Research Initiative Development Grant from the UK Department for International Development (DFID), Economic and Social Research Council (ESRC), Medical Research Council (MRC (and the Wellcome Trust (MR/N005597/1) funds the research presented in this paper. Support for the Agincourt HDSS including verbal autopsies was provided by The Wellcome Trust, UK (grants 058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z), and the University of the Witwatersrand and Medical Research Council, South Africa.

Prospective case review of a global e-health system for doctors in developing countries

The Swinfen Charitable Trust has managed email consultations for doctors in developing countries since 1999. The process was handled manually for the first three years and then subsequently using an automatic message-handling system. We conducted a prospective review of email consultations between referring doctors and consulting specialists during six months of automatic operation (December 2003 to May 2004). During the study period 125 consultations took place. These concerned a wide range of specialties (e.g. orthopaedics 17%, dermatology 16%, obstetrics and gynaecology 11%, radiology 10%). Of these referrals, 33% (41) were for paediatric cases. Consulting specialists, who were based in five countries, were volunteers. Referring doctors were from 24 hospitals in 12 developing countries. The median time from referral to definitive reply was 1.5 days (interquartile range 0.6-4.9). There was an 85% response rate (n = 106) to a survey concerning the value of the consultation to the referring doctor. All the referring doctors who responded made positive comments about the service and half said that it improved their management of the case. The second-opinion consultation system operated by the Swinfen Charitable Trust represents an example of a global e-health system operated for altruistic, rather than commercial, reasons.

An e-health needs assessment of medical residents in Cameroon

Medical residents from Yaounde I University in Cameroon are required to spend periods of time in rural or remote locations to complete their training. To determine if e-health might lessen their isolation and enhance patient care, a needs assessment of the residents was performed using a brief questionnaire (five items) about the situation in which residents found themselves outside their medical school environment. We gave the questionnaires to 45 residents. Seventeen questionnaires had been returned at the time of the site visit, a response rate of 38%. Most residents indicated that the ability to contact a mentor would have either made them feel more confident (16, or 94%) or altered their handling of recent cases (15, or 88%). All residents had access to a mobile phone, and many (11, or 65%) had used it to contact a medical colleague for guidance. A low-cost and technologically simple telemedicine solution that maximized use of mobile phone capability, provided access to medical and health-care information, and permitted exchange of images would be an appropriate response to the identified needs.

Managerial work roles of health care executives in the changing environment of academic medical centers

The current U.S. health care system faces numerous environmental challenges. To compete and survive, health care organizations are developing strategies to lower costs and increase efficiency and quality. All of these strategies require rapid and precise decision making by top level managers. The purpose of this study is to determine the relationship between the environment, made up of unfavorable market conditions and limited resources, and the work roles of top level managers, specifically in the settings of academic medical centers. Managerial work roles are based on the ten work roles developed by Henry Mintzberg, in his book, The Nature of Managerial Work (1973). ^ This research utilized an integrated conceptual framework made up of systems theory in conjunction with role, attribution and contingency theories to illustrate that four most frequently performed Mintzberg's work roles are affected by the two environment dimensions. The study sample consisted of 108 chief executive officers in academic medical centers throughout the United States. The methods included qualitative methods in the form of key informants and case studies and quantitative in the form of a survey questionnaire. Research analysis involved descriptive statistics, reliability tests, correlation, principal component and multivariate analyses. ^ Results indicated that under the market condition of increased revenue based on capitation, the work roles increased. In addition, under the environment dimension of limited resources, the work roles increased when uncompensated care increased while Medicare and non-government funding decreased. ^ Based on these results, a typology of health care managers in academic medical centers was created. Managers could be typed as a strategy-formulator, relationship-builder or task delegator. Therefore, managers who ascertained their types would be able to use this knowledge to build their strengths and develop their weaknesses. Furthermore, organizations could use the typology to identify appropriate roles and responsibilities of managers for their specific needs. Consequently, this research is a valuable tool for understanding health care managerial behaviors that lead to improved decision making. At the same time, this could enhance satisfaction and performance and enable organizations to gain the competitive edge . ^

Medical advice, diabetes self-management, and health outcomes of a multi-ethnic population from the National Health and Nutrition Examination Survey 2007--2008

Diabetes self-management, an essential component of diabetes care, includes weight control practices and requires guidance from providers. Minorities are likely to have less access to quality health care than White non-Hispanics (WNH) (American College of Physicians-American Society of Internal Medicine, 2000). Medical advice received and understood may differ by race/ethnicity as a consequence of the patient-provider communication process; and, may affect diabetes self-management. ^ This study examined the relationships among participants’ report of: (1) medical advice given; (2) diabetes self-management, and; (3) health outcomes for Mexican-Americans (MA) and Black non-Hispanics (BNH) as compared to WNH (reference group) using data available through the National Health and Nutrition Examination Survey (NHANES) for the years 2007–2008. This study was a secondary, single point analysis. Approximately 30 datasets were merged; and, the quality and integrity was assured by analysis of frequency, range and quartiles. The subjects were extracted based on the following inclusion criteria: belonging to either the MA, BNH or WNH categories; 21 years or older; responded yes to being diagnosed with diabetes. A final sample size of 654 adults [MA (131); BNH (223); WNH (300)] was used for the analyses. The findings revealed significant statistical differences in medical advice reported given. BNH [OR = 1.83 (1.16, 2.88), p = 0.013] were more likely than WNH to report being told to reduce fat or calories. Similarly, BNH [OR = 2.84 (1.45, 5.59), p = 0.005] were more likely than WNH to report that they were told to increase their physical activity. Mexican-Americans were less likely to self-monitor their blood glucose than WNH [OR = 2.70 (1.66, 4.38), p<0.001]. There were differences among ethnicities for reporting receiving recent diabetes education. Black, non-Hispanics were twice as likely to report receiving diabetes education than WNH [OR = 2.29 (1.36, 3.85), p = 0.004]. Medical advice reported given and ethnicity/race, together, predicted several health outcomes. Having recent diabetes education increased the likelihood of performing several diabetes self-management behaviors, independent of race. ^ These findings indicate a need for patient-provider communication and care to be assessed for effectiveness and, the importance of ongoing diabetes education for persons with diabetes.^

Nursing and medical students as agents of change in health care: impact of schools core values and culture-a discussion paper

Within the UK the quality of care delivered in some hospitals, nursing homes and caring facilities has been the subject of significant enquiry, challenge and concern in recent years. There was need for a change in the culture of patient and client care. Traditionally a change in culture is seen as moving from an organisational head through to the organisation and in this case through to front-line care. This hasn’t necessarily achieved the desired effect and impact in terms of quality of care within the UK. Historically, certainly nurses have acted more as recipients of change, rather than agents of change
This paper suggests that schools of nursing and medicine with robust core values and a more consistently enacted culture of care, are better able and more likely to transfer this to nursing and medical students within their professional socialisation. In addition, and rather than the newly qualified nurse or doctor being absorbed into existing cultures of care delivery (which are not necessarily always reflecting high qualities of care), schools of nursing and medicine could better facilitate the development of more `agency’ within students and better equipping the students on qualification and stepping into practice, with a role and function as potential agents of change. Effective leadership within schools of nursing and medicine can both translate to quality and consistency, and enactment of organisational core values and working culture. The working culture of schools is intrinsic to developing students as agents of change