Educating the next generation of cancer researchers: Evaluation of a cancer research partnership training program.

African American, American Indian and Alaska Native, Hispanic (or Latinx), Native Hawaiian, and other Pacific Islander groups are underrepresented in the biomedical workforce, which is one of the barriers to addressing cancer disparities among minority populations. The creation of a more inclusive biomedical workforce dedicated to reducing the burden of cancer health disparities requires structured, mentored research and cancer-related research exposure during the earlier stages of training. The Summer Cancer Research Institute (SCRI) is a multicomponent 8-week intensive summer program funded under the Partnership between a Minority Serving Institute and a National Institutes of Health-designated Comprehensive Cancer Center. In this survey study, we found that students who participated in the SCRI Program reported greater knowledge and interest in pursuing careers in cancer-related fields than their counterparts who did not participate in SCRI. Successes, challenges, and solutions in providing training in cancer and cancer health disparities research to improve diversity in the biomedical fields were also discussed.

Educating the Next Generation of Cancer Researchers: Evaluation of A Cancer Research Partnership Training Program.

African American, American Indian and Alaska Native, Hispanic (or Latinx), Native Hawaiian, and other Pacific Islander groups are underrepresented in the biomedical workforce, which is one of the barriers to addressing cancer disparities among minority populations. The creation of a more inclusive biomedical workforce dedicated to reducing the burden of cancer health disparities requires structured, mentored research and cancer-related research exposure during the earlier stages of training. The Summer Cancer Research Institute (SCRI), a multicomponent 8-week intensive summer program funded under the Partnership between a Minority Serving Institute and a National Institutes of Health-designated Comprehensive Cancer Center. This study assessed whether students who participated in the SCRI Program report greater knowledge and interest in pursuing careers in cancer-related fields than their counterparts who did not participate in SCRI. Successes, challenges, and solutions in providing training in cancer and cancer health disparities research to improve diversity in the biomedical fields were also discussed.

EVALUATION OF A TRANSDISCIPLINARY CANCER RESEARCH TRAINING PROGRAM FOR UNDER-REPRESENTED MINORITY STUDENTS.

AIM/PURPOSE: This paper will describe the initial development of systems to evaluate research education activities of a U.S. academic Partnership to train minority students as cancer researchers and provide preliminary data from monitoring Partnership activities during the first six months. BACKGROUND: There is increased focus on multidisciplinary/transdisciplinary research training programs. However, few training programs have included detailed evaluations to assess their outcomes and effectiveness. METHODOLOGY: The Temple University/Fox Chase Cancer Center and Hunter College Regional Comprehensive Cancer Health Disparity Partnership (TUFCCC/HC Cancer Partnership, or the Partnership) is a recently-initiated center focused on training individuals from under-represented minorities (URMs) as cancer researchers. Evaluation of the training activities involves detailed specification of goals for each of the Partnership's Cores; objectives for addressing each goal; measures and indicators to determine progress towards each objective; and data sources to provide information for the measures/indicators. CONTRIBUTUION: This paper will provide important information for evaluation of training programs focused on students from URM populations and development of trans-disciplinary research education programs. FINDINGS: Goals, objectives, measures, and data sources for evaluation of the Partnership's Research Education Core (REC) were developed jointly by personnel from the REC and the Planning Evaluation Core (PEC) in an iterative process. These measures capture the training activities led by the REC (e.g., number of seminars and workshops), scientific output by trainees (e.g., papers and grants), and ability of the program to meet trainees' goals and expectations. RECOMMENDATIONS FOR PRACTITIONERS AND RESEARCHES: Evaluation plans for transdisciplinary training programs need to be developed prior to program initiation. Evaluation measures should be jointly specified by training and evaluation personnel, then reviewed and revised in an iterative process. IMPACT ON SOCIETY: This program is intended to enhance diversity among cancer researchers and increase studies to address disparities in cancer care. FUTURE RESEARCH: The PEC will oversee the evaluation of Partnership training activities over the five year period and assist Partnership leaders in ensuring successful outcomes.

Reviving a Positive Discourse on Sexuality within Social Work.

Sexuality is not an invisible dimension within social work. Social workers are constantly engaged with aspects of sexuality across virtually all practice domains. Indeed, some of the most fundamental and frequent concerns of social workers involve sexual abuse, sexual violence, and HIV and other sexually transmitted infections. However, conversations about healthy sexuality, positive sexuality, or sexual well-being that are well ensconced in many disciplines are all but absent from current social work literature, education, and practice. In this academic silence, social work is missing a significant opportunity to contribute to the larger conversation around healthy sexuality in a way that illuminates a more holistic perspective and that acknowledges desire and sexual satisfaction across the spectrum, including among marginalized and oppressed groups. In this article, authors make the case for shifting away from a pervasive focus on sexuality as solely risk based to one of balance, incorporating the normative nature and importance of sexuality, intimacy, pleasure, and desire within social work curricula, practice, and dialogue in general. They encourage social workers to recognize sexuality as a critical site of intersectionality and argue for the integration of a multidimensional approach to sexuality within social work education, practice, and research.

Investigating lipids as a source of chemical exchange-induced MRI frequency shifts.

While magnetic susceptibility is a major contributor to NMR resonance frequency variations in the human brain, a substantial contribution may come from the chemical exchange of protons between water and other molecules. Exchange-induced frequency shifts fe have been measured in tissue and protein solutions, but relatively lipid-rich white matter (WM) has a larger fe than gray matter, suggesting that lipids could contribute. Galactocerebrosides (GC) are a prime candidate as they are abundant in WM and susceptible to exchange. To investigate this, fe was measured in a model of WM lipid membranes in the form of multilamellar vesicles (MLVs), consisting of a 1:2 molar ratio of GC and phospholipids (POPC), and in MLVs with POPC only. Chemical shift imaging with 15% volume fraction of dioxane, an internal reference whose protons are assumed not to undergo chemical exchange, was used to remove susceptibility-induced frequency shifts in an attempt to measure fe in MLVs at several lipid concentrations. Initial analysis of these measurements indicated a necessity to correct for small unexpected variations in dioxane concentration due to its effect on the water frequency shift. To achieve this, the actual dioxane concentration was inferred from spectral analysis and its additional contribution to fe was removed through separate experiments which showed that the water-dioxane frequency shift depended linearly on the dioxane concentration at low concentrations with a proportionality constant of -0.021 ± 0.002 ppb/mM in agreement with published experiments. Contrary to expectations and uncorrected results, for GC + POPC vesicles, the dependence of the corrected fe on GC concentration was insignificant (0.023 ± 0.037 ppb/mM; r2 = 0.085, p > 0.57), whereas for the POPC-only vesicles a small but significant linear increase with POPC concentration was found: 0.044 ± 0.008 ppb/mM (r2 = 0.877, p < 0.01). These findings suggest that the exchange-induced contribution of lipids to frequency contrast in WM may be small. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Shape-changing magnetic assemblies as high-sensitivity NMR-readable nanoprobes.

Fluorescent and plasmonic labels and sensors have revolutionized molecular biology, helping visualize cellular and biomolecular processes. Increasingly, such probes are now being designed to respond to wavelengths in the near-infrared region, where reduced tissue autofluorescence and photon attenuation enable subsurface in vivo sensing. But even in the near-infrared region, optical resolution and sensitivity decrease rapidly with increasing depth. Here we present a sensor design that obviates the need for optical addressability by operating in the nuclear magnetic resonance (NMR) radio-frequency spectrum, where signal attenuation and distortion by tissue and biological media are negligible, where background interferences vanish, and where sensors can be spatially located using standard magnetic resonance imaging (MRI) equipment. The radio-frequency-addressable sensor assemblies presented here comprise pairs of magnetic disks spaced by swellable hydrogel material; they reversibly reconfigure in rapid response to chosen stimuli, to give geometry-dependent, dynamic NMR spectral signatures. The sensors can be made from biocompatible materials, are themselves detectable down to low concentrations, and offer potential responsive NMR spectral shifts that are close to a million times greater than those of traditional magnetic resonance spectroscopies. Inherent adaptability should allow such shape-changing systems to measure numerous different environmental and physiological indicators, thus providing broadly generalizable, MRI-compatible, radio-frequency analogues to optically based probes for use in basic chemical, biological, medical and engineering research.

The fabrication of uniform cylindrical nanoshells and their use as spectrally tunable MRI contrast agents.

A new form of tunable magnetic resonance imaging agent based on precisely dimensioned cylindrical magnetic nanoshells is introduced. Using top-down prepatterned substrates, the nanoshells are fabricated by exploiting what is usually regarded as a detrimental processing side-effect, namely the redeposition of material back-sputtered during ion-milling. The well-resolved nuclear magnetic resonance peaks of the resulting nanostructures attest to the nanoscale fabrication control and the general feasibility of such sputter redeposition for fabrication of a variety of self-supporting, highly monodisperse nanoscale structures.

Macrophage accumulation associated with rat cardiac allograft rejection detected by magnetic resonance imaging with ultrasmall superparamagnetic iron oxide particles.

BACKGROUND: Acute cardiac allograft rejection continues to be the cause of graft loss and contributes to the morbidity and mortality after cardiac transplantation. In this study, we report a new method for detecting organ rejection in transplantation with an MR-based technique using dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) particles. These particles ( approximately 27 nm in diameter) are known to shorten relaxation times in MRI experiments. METHODS AND RESULTS: A new rat model of heterotopic heart and lung transplantation has been developed for MRI experiments. Allotransplantations (DA-->BN) were performed (n=8), with syngeneic transplantations (BN-->BN) serving as controls (n=8). MR images were obtained with a gradient echo method. At postoperative day 7, allotransplants developed moderate rejection as determined histopathologically. A significant reduction in MR signal intensity was observed after USPIO injection into rats with allotransplanted hearts. Syngeneic transplants showed no differences in MR signal intensity before and after USPIO injections. After injection of USPIO particles at postoperative day 6, a group of allotransplanted rats was treated with cyclosporin A (3 mg/kg). Animals treated with cyclosporin A for 7 days showed no reduction in MR signal intensity after USPIO reinjection at day 14, whereas animals treated for 4 days showed a significant decrease in MR signal intensity in the transplanted hearts indicative of acute graft rejection. Pathological analysis of these animals revealed that dextran-coated USPIO particles were taken up by the infiltrating macrophages that accumulated within the rejecting cardiac graft. CONCLUSIONS: This MRI method offers promise as a noninvasive method for detecting transplant allograft rejection.

A novel approach with magnetic resonance imaging used for the detection of lung allograft rejection.

OBJECTIVE: Although various techniques have been explored for the detection and quantification of allograft transplant rejection, a practical and reliable method that is noninvasive is still elusive. METHODS: For our magnetic resonance imaging experiments, we have developed a new rat model of heterotopic lung transplantation to the inguinal region. Allogeneic transplants (DA to Brown Norway) were performed with and without cyclosporine A (INN: ciclosporin) treatment, with syngeneic transplants (Brown Norway to Brown Norway) serving as controls (n = 6 per group). Magnetic resonance images were obtained with a gradient echo method before and after injection of ultra-small superparamagnetic iron oxide particles. RESULTS: At day 5, allogeneic transplants without cyclosporine A treatment showed a grade 4 rejection histologically. A significantly lower magnetic resonance signal was seen 24 hours after injection of ultra-small superparamagnetic iron oxide particles compared with the preinjection image (346 +/- 7.6 vs 839 +/- 43.4 arbitrary units; P <. 05). Syngeneic transplants showed no evidence of rejection histologically and no differences in magnetic resonance imaging signals between the images before and after injection of ultra-small superparamagnetic iron oxide particles (863 +/- 18.8 vs 880 +/- 22.5). Allotransplants treated with cyclosporine A showed a grade 2 rejection histologically. The change in magnetic resonance signals in that group was small but showed a significant decrease in signal intensity after injection (646 +/- 10.5 vs 889 +/- 23.5, P <.05). Immunohistochemistry and iron staining of the allografts indicated that ultra-small superparamagnetic iron oxide particles were taken up by the infiltrating macrophages that accumulated at the rejection site. CONCLUSIONS: We have demonstrated a novel approach for the detection of acute lung allograft rejection using magnetic resonance imaging coupled with injection of ultra-small superparamagnetic iron oxide particles. Despite its limitations, our method might be a first step toward a potential clinical application.

Magnetic resonance imaging detection of rat renal transplant rejection by monitoring macrophage infiltration.

BACKGROUND: A rat renal transplantation model was studied by noninvasive magnetic resonance imaging (MRI) with an infusion of ultrasmall superparamagnetic iron oxide (USPIO) particles to test whether the accumulation of immune cells, such as macrophages, could be detected in vivo while the kidney transplant was being rejected. METHODS: Major histocompatibility disparate DA to BN male rat renal transplantation recipients were infused with USPIO particles, with magnetic resonance (MR) images acquired before, immediately after, and one day following infusion. RESULTS: When the USPIO infusion was on the fourth day post-transplantation, some rejecting allografts showed a decrease of MR signal intensity one day later. Isografts and allografts with triple immunosuppressant treatment had no MR signal reduction. Immunohistologic staining for ED1+ macrophages and CD4+ and CD8+ T cells in allogeneic transplanted kidneys indicated the accumulation of these immune cells as acute rejection occurred. Morphological studies by electron microscopy confirmed the existence of iron inside the lysosomes of macrophages of rejecting kidneys, while Prussian blue staining detected the presence of iron plaques in macrophages. Isografts and allografts with a triple immunosuppressant treatment exhibited smaller MR signal reductions with minimal histologic changes. CONCLUSIONS: The concurrence of MR signal reduction following USPIO infusion with pathological manifestation in a rat renal allograft model suggests the possibility that renal transplantation status may be assessed by MRI using USPIO particles as markers for the accumulation of immune cells, such as macrophages.

Cardiac function of transplanted rat hearts using a working heart model assessed by magnetic resonance imaging.

BACKGROUND: A direct correlation between graft rejection and cardiac contractile function in small-animal models has been difficult to establish because (i) the conventional non-working heart model is greatly different from the orthotopic heart in terms of left ventricular work and (ii) it is difficult to obtain hemodynamic data in situ. We have used magnetic resonance imaging (MRI) techniques to obtain noninvasive, in-situ quantitation of ventricular volume after heterotopic cardiac transplantation. METHODS: Infra-renal heterotopic cardiac transplantation was performed on rats using syngeneic and allogeneic untreated donors in both working and non-working left heart models. An occluding balloon catheter in the inferior vena cava was used to vary the pre-load to the graft. An arteriovenous fistula was created to raise inferior caval oxygen saturation. Magnetic resonance imaging measurements were carried out at day 3, 4, and 5 post-transplantation. Left ventricle end-diastolic and end-systolic volumes were calculated using a biplanar ellipsoid model. RESULTS: Stroke volume was significantly increased in the working heart model as compared to the non-working model. At day 4 post-transplant, the diastolic pressure-volume relationship in the allograft group was significantly shifted, indicative of decreased myocardial distensibility, whereas the indices of systolic function were preserved. CONCLUSIONS: We have developed a heterotopic transplant working rat heart model and have used it to assess in-situ cardiac function by MRI. Sensitive indices of diastolic contractile function can be obtained in this rodent transplant model that correlate well with histologic evidence of early rejection.

Detection of single mammalian cells by high-resolution magnetic resonance imaging.

This study reports the detection of single mammalian cells, specifically T cells (T lymphocytes) labeled with dextran-coated superparamagnetic iron oxide particles, using magnetic resonance microscopy. Size amplification due to sequestration of the superparamagnetic particles in vacuoles enhances contrast in localized areas in high-resolution magnetic resonance imaging. Magnetic resonance images of samples containing differing concentrations of T cells embedded in 3% gelatin show a number of dark regions due to the superparamagnetic iron oxide particles, consistent with the number predicted by transmission electron microscopy. Colabeling of T cell samples with a fluorescent dye leads to strong correlations between magnetic resonance and fluorescence microscopic images, showing the presence of the superparamagnetic iron oxide particles at the cell site. This result lays the foundation for our approach to tracking the movement of a specific cell type in live animals and humans.

Developing a social work research agenda on ethics in health care.

This article advocates greater empirical research on ethics in health care by social work researchers. Although an extensive theoretical literature exists, scant empirical research has been conducted on ethical issues by social work researchers since 1980, compared with physicians and other health care researchers. A theoretical framework is presented as a heuristic device to stimulate research on a range of topics, including the content and nature of ethical deliberations, contextual factors, and ethical outcomes. By demonstrating empirically that their interventions improve ethical outcomes, social work researchers can provide ammunition to support social work's role in ethical deliberations in health care settings.