Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses

Background: 18F-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of 18F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of 18F-FLT administered to human subjects, by: 1) performing an evaluation of the toxicity of 18F-FLT administered in radiotracer amounts for PET imaging, 2) comparing a radiotracer dose of FLT to clinical trial doses of FLT. Methods: Twenty patients gave consent to a 18F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after 18F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. 18F-FLT doses of 2.59 MBq/Kg with a maximal dose of 185 MBq (5 mCi) were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours (AUC12). Results: No side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations (p = 0.66). The blood samples-derived AUC12 values range from 0.232 ng*h/mL to 1.339 ng*h/mL with a mean of 0.802 � 0.303 ng*h/mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng*h/mL reported by Flexner et al (1994). This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner's twice daily trial. Conclusion: This study shows no evidence of toxicity or complications attributable to 18F-FLT injected intravenously.This study was supported by NIH grant R01 CA115559, 1R01 CA107264, and 1R01 CA80907

Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE'): study protocol

<p>Abstract</p> <p>Background</p> <p>Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction.</p> <p>Methods/Design</p> <p>Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m²) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin.</p> <p>Discussion</p> <p>While clinical data indicate that excess weight for height is associated with poor prognosis for long term survival, little attention is paid to weight control in the clinical management of breast cancer. This study will provide information that can be used to answer important patient questions about the effects of dietary pattern and magnitude of weight loss on long term survival following breast cancer treatment.</p> <p>Clinical Trial Registration</p> <p>CA125243</p

Towards sustainable urban development: the social acceptability of high-rise buildings in a Ghanaian city

Over the years, many city managers, policy makers and academics alike have turned to high-rise buildings as pathway to sustainable urban development. However, the sustainability of such types of development in various geographical contexts, especially in sub-Saharan Africa, is a subject less explored. Amidst the promotion of high-rise development in a rapidly urbanizing metropolis in Ghana, Kumasi, the research empirically examined the social acceptability of high-rise residential facilities and the institutional capacity for their effective management. By conducting face-to-face interviews with sampled households, and critical public service providers in the metropolis, the study uncovered that, contrary to the evidence from many Asian cities, there is generally low social acceptability of high-rise developments, and a weak institutional capacity for effective service delivery. The research concludes that, whilst it is tempting to embrace high-rise buildings as sustainable development pathway, it is crucial they are pursued with much circumspection. In addition to their design being tailored to the local needs of the people for whom they are built, the promotion of high-rise development should recognize the importance of effective service delivery, and general social acceptability

Migration-related detention centers : The challenges of an ecological perspective with a focus on justice

Background: In recent years, border control and migration-related detention have become increasingly widespread practices affecting the lives of undocumented migrants, their families, and communities at large. In spite of the concern within academia, few studies have directly witnessed the life and experiences of people confined to migration-related detention centers. In the medical and psychological fields, a considerable body of research has demonstrated the pathogenic nature of detention in terms of mental health, showing an association between length of detention and severity of distress. Nevertheless, it was limited to the assessment of individuals’ clinical consequences, mainly focusing on asylum seekers. There currently exists a need to adopt an ecological perspective from which to study detained migrants’ experiences as context-dependent, and influenced by power inequalities. This paper addresses this gap. Discussion: Drawing upon advances in community psychology, we illustrate an ecological framework for the study of migration-related detention contexts, and their effects on the lives of detained migrants and all people exposed to them. Making use of existing literature, Kelly’s four principles (interdependence, cycling of resources, adaptation, succession) are analyzed at multiple ecological levels (personal, interpersonal, organizational, communal), highlighting implications for future research in this field. A focus on justice, as a key-dimension of analysis, is also discussed. Wellbeing is acknowledged as a multilevel, dynamic, and value-dependent phenomenon. Summary: In presenting this alternative framework, the potential for studying migration-related detention through an ecological lens is highlighted, pointing the way for future fields of study. We argue that ecological multilevel analyses, conceptualized in terms of interdependent systems and with a focus on justice, can enhance the comprehension of the dynamics at play in migration-related detention centers, providing an effective tool to address the multi-level challenges of doing research within them. Furthermore, they can contribute to the development of policies and practices concerned with health, equality, and human rights of all people exposed to migration-related detention. Consistent with these assumptions, empirical studies adopting such a framework are strongly encouraged. These studies should use mixed and multi-method culturally situated designs, based on the development of collaborative and empowering relationships with participants. Ethnographic approaches are recommended.Fundação para a Ciência e Tecnologia (FCT

High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS

Objective: To evaluate the safety, efficacy, and durability of multiple sclerosis (MS) disease stabilization after high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT). Methods: High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is a phase II clinical trial of HDIT/HCT for patients with relapsing-remitting (RR) MS who experienced relapses with disability progression (Expanded Disability Status Scale [EDSS] 3.0–5.5) while on MS disease-modifying therapy. The primary endpoint was event-free survival (EFS), defined as survival without death or disease activity from any one of: disability progression, relapse, or new lesions on MRI. Participants were evaluated through 5 years posttransplant. Toxicities were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (AE). Results: Twenty-five participants were evaluated for transplant and 24 participants underwent HDIT/HCT. Median follow-up was 62 months (range 12–72). EFS was 69.2% (90% confidence interval [CI] 50.2–82.1). Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3% (90% CI 74.7%–97.2%), 86.9% (90% CI 69.5%–94.7%), and 86.3% (90% CI 68.1%–94.5%), respectively. AE due to HDIT/HCT were consistent with expected toxicities and there were no significant late neurologic adverse effects noted. Improvements were noted in neurologic disability with a median change in EDSS of −0.5 (interquartile range −1.5 to 0.0; p = 0.001) among participants who survived and completed the study. Conclusion: HDIT/HCT without maintenance therapy was effective for inducing long-term sustained remissions of active RRMS at 5 years