Vacancy in shrinking downtowns: a comparative study of Québec, Ontario, and New England.

In North America and around the globe, there has been emerging recognition of the size and scope of urban shrinkage, yet little is understood about how decline impacts commercial centers and downtowns. In order to facilitate geographically targeted policymaking, this paper examines the physical patterns of downtown decline in three distinct regions. We seek to test the hypothesis that differences in the process of urban decline in downtown districts vary due to national or historic context. Using statistical analysis and direct observations, we found that while the scale of population decline was greatest in New England, downtowns in both Ontario and Québec have seen substantial decline and have appeared to have better weathered the change with respect to physical signs of decline.

Endrew and FAPE: Concepts and Implications for All Students With Disabilities.

The opinion of the Supreme Court of the United States in the Endrew case has implications for the education of all students with disabilities. Implications for several categories of disability are discussed: those with autism spectrum disorder and those with disabilities often considered high incidence, particularly those placed for a significant portion of their school day in general education. The aspects of the Individuals with Disabilities Education Act most relevant to the Endrew case are also compared with Article 24 of the United Nations's Convention on the Rights of Persons with Disabilities. The opinion in Endrew may affect the course of special education and the role of behavior modification in meeting the needs of all students with disabilities.

Randomized controlled trial of aerobic exercise on insulin and insulin-like growth factors in breast cancer survivors: the Yale Exercise and Survivorship study.

BACKGROUND: High insulin and insulin-like growth factor-I (IGF-I) levels may be associated with an increased breast cancer risk and/or death. Given the need to identify modifiable factors that decrease insulin, IGF-I, and breast cancer risk and death, we investigated the effects of a 6-month randomized controlled aerobic exercise intervention versus usual care on fasting insulin, IGF-I, and its binding protein (IGFBP-3) in postmenopausal breast cancer survivors. METHODS: Seventy-five postmenopausal breast cancer survivors were identified from the Yale-New Haven Hospital Tumor Registry and randomly assigned to an exercise (n = 37) or usual care (n = 38) group. The exercise group participated in 150 minutes per week of moderate-intensity aerobic exercise. The usual care group was instructed to maintain their current physical activity level. A fasting blood sample was collected on each study participant at baseline and 6 months. Blood levels of insulin and IGF were measured with ELISA. RESULTS: On average, exercisers increased aerobic exercise by 129 minutes per week compared with 45 minutes per week among usual care participants (P < 0.001). Women randomized to exercise experienced decreases in insulin, IGF-I, and IGFBP-3, whereas women randomized to usual care had increases in these hormones. Between-group differences in insulin, IGF-I, and IGFBP-3 were 20.7% (P = 0.089), 8.9% (P = 0.026), and 7.9% (P = 0.006), respectively. CONCLUSIONS: Moderate-intensity aerobic exercise, such as brisk walking, decreases IGF-I and IGFBP-3. The exercise-induced decreases in IGF may mediate the observed association between higher levels of physical activity and improved survival in women diagnosed with breast cancer.

Peptide concentrations and mRNA expression of IGF-I, IGF-II and IGFBP-3 in breast cancer and their associations with disease characteristics.

PURPOSE: To measure peptide concentrations and mRNA expression of the IGF Family in breast cancer and to examine their associations with the disease features. EXPERIMENTAL DESIGN: Fresh tumor samples were collected from 348 patients who underwent surgery for breast cancer. Tissue levels of mRNA and peptide of IGF-I, IGF-II, and IGFBP-3 were analyzed with real-time RT-PCR and ELISA, respectively. Cox proportional hazards regression model was used to examine the associations of IGF markers with patient survival. RESULTS: Age was inversely associated with IGF-I, IGF-II and IGFBP-3 at both mRNA and peptide levels. Small tumors, early TNM stages, or low grades were associated with high mRNA expression of IGFs and IGFBP-3. Hormone receptors were positively correlated with IGF-I and IGF-II expression. Survival analysis showed that patients with high expression of one of the IGF-I transcripts, IGF-IA, had lower risk of disease recurrence (HR = 0.47, 95%CI: 0.27-0.81) and death (HR = 0.35, 95%CI: 0.18-0.70) compared to those with low expression. High IGFBP-3 expression was also inversely associated with reduced risk of death (HR = 0.47, 95%CI: 0.23-0.95). Similar associations, however, were not observed when tissue levels of IGF-I peptide or IGFBP-3 protein were analyzed. High IGF-II peptide was related to increased risk of relapse (HR = 1.91, 95%CI: 1.12-3.27). CONCLUSION: Our findings of high mRNA expression of IGFs and IGFBP-3 being associated with less aggressive tumors and favorable prognosis were consistent with previous observations, but were not supported by the measurement of tissue levels of IGF-I peptide and IGFBP-3 protein, suggesting that IGF mRNA expression and tissue levels of IGF peptides are regulated by different mechanisms and assessing these molecules in tumor tissue may have different implications.

Klotho expression in epithelial ovarian cancer and its association with insulin-like growth factors and disease progression.

Klotho is an anti-aging hormone and is able to suppress the action of IGFs. High IGF activities are associated with cancer risk and tumor progression. Klotho's role in cancer is unknown. To evaluate Klotho expression in ovarian cancer and its association with IGFs and ovarian cancer progression, a clinical follow-up study of 189 ovarian cancer patients was conducted. Patients were recruited from a teaching hospital at University of Turin in Italy. All patients were diagnosed with epithelial ovarian cancer and underwent surgery for the disease. Fresh tumor tissue was collected from each patient during surgery. Patient clinical and pathological information was collected, including patient age at surgery, disease stage, tumor grade, tumor histology, residual tumor size, debulking result, post-operative chemotherapeutic agent, treatment response, follow-up time and survival outcome. Expressions of total and secreted Klotho as well as IGFs in tumor tissue were analyzed using quantitative real-time PCR. Survival analysis was performed to evaluate the association of Klotho expression with the risk of disease progression and death using Cox proportional hazards regression model. High expression of secreted Klotho was associated with increased risk of disease progression and death. These associations were independent of patient clinical and pathological characteristics. Expression of secreted Klotho was positively correlated with the expression of IGF-I and IGFBP-3 but not with IGF-II. In conclusion, Klotho expression is associated with epithelial ovarian cancer progression, and the protein may serve as an independent marker for ovarian cancer prognosis. Klotho's role in cancer warrants further elucidation.

Expression of MDR1 in epithelial ovarian cancer and its association with disease progression.

The purposes of this study were to analyze MDR1 expression in ovarian tumors prior to chemotherapy, to correlate the expression with p16, IGFs, ERalpha, and BRCA1, and to examine the association of MDR1 expression with ovarian cancer prognosis. A primary ovarian cancer cohort of 206 patients after surgery was followed up. MDR1, IGFs, ERalpha, p16, and BRCA1 expressions were analyzed in ovarian tumor samples using quantitative real-time PCR. MDR1 was detected in 177 of 206 specimens. MDR1 expression was positively correlated with IGFBP3, ERalpha, p16, and BRCA1, but not correlated with IGF-II, age, and other clinicopathological parameters. MDR1 expression significantly elevated the risk for disease progression (p = 0.02), and this association remained statistically significant after controlling for patient age and clinicopathological parameters or other correlated genes. No association was found between MDR1 expression and overall survival. MDR1 expression may be an independent marker for ovarian cancer progression and combination of different agents targeting different molecules may improve the outcome of ovarian cancer treatment and prevent drug resistance.

The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer.

PURPOSE: The insulin-like growth factor (IGF) system plays important roles in cancer; blocking IGF signaling has been shown to have therapeutic effects on tumor growth. Many studies have focused on the effect of IGF-I, but few have addressed IGF-II. To assess the role of IGF-II in cancer, we analyzed IGF-II expression in ovarian cancer and examined its association with disease characteristics and prognosis. EXPERIMENTAL DESIGN: Included in the study were 215 patients with primary epithelial ovarian cancer. Fresh tumor specimens were collected during surgery, and the patients were followed for a median of 31 months. Total RNA was extracted from the tumor and analyzed for IGF-II, IGF binding protein 3 (IGFBP-3), and estrogen receptor-alpha expressions using quantitative reverse transcription PCR. Survival analysis was done to examine the associations of IGF-II with disease progression. RESULTS: IGF-II expression was found to be higher in tumors with poor prognosis; this included tumors with advanced stage, poor differentiation, serous histology, and large residual lesions. Patients with high IGF-II had elevated risk for disease progression and death, although the significance became less evident when the analysis was adjusted for clinical and pathologic variables. IGFBP-3 expression was higher in less aggressive tumors, but was not associated with disease progression. The expression of estrogen receptor-alpha had no effect on survival. CONCLUSION: This study found evidence that IGF-II expression is associated with disease progression, suggesting that IGF-II and IGF signaling are potential targets for ovarian cancer treatment. The study also indicates that IGF-II and IGFBP-3 have limited value in prognosis because of their strong associations with disease stage and tumor grade.

The relationship between family medical history and childhood vitiligo.

BACKGROUND: The association between a family history of vitiligo and other autoimmune/endocrine diseases and increased incidence of childhood vitiligo has been described; however, the influence of family history on the clinical characteristics of childhood vitiligo has rarely been investigated. OBJECTIVE: We sought to examine the relationship between family history and the incidence, extent, and course of childhood vitiligo. METHODS: A retrospective chart review and telephone interviews were performed for 137 pediatric patients with vitiligo and 140 control patients (patients with acne, warts, or molluscum contagiosum matched in age, sex, and ethnicity to the study group). Information about the age, sex, ethnicity, age of onset and diagnosis, site of onset, distribution, treatment, course of disease, and family history was obtained. RESULTS: Patients with vitiligo and an extended family history of vitiligo were more likely to have an earlier age of onset of disease than those with a negative family history (odds ratio = 3.70, P = .024). There was no association between family history and site of onset, distribution, or course of disease. LIMITATIONS: A relatively small sample size, recall bias, disease misclassification, and confounding factors are potential limitations of this study. CONCLUSION: Earlier onset of pediatric vitiligo is linked to a family history of vitiligo. Awareness of this association can allow for closer monitoring, earlier detection, and earlier initiation of treatment.

ALCOHOL, TOBACCO AND OTHER DRUGS NURSING WITHIN A CORRECTIONAL SETTING.

In Australia 67% of prisoners report previous illicit drug use (AIHW, 2015) with 39% reporting high risk of alcohol-related harm. The links between effective ATOD health programs and outcomes are clearly linked to reduced recidivism (Ombudsman report, 2015) and better biopsychosocial determinates. Correctional nurses' work in challenging environments but their adaptability and passion are key to the provision of community equivalent care.

IGF-I in epithelial ovarian cancer and its role in disease progression.

Insulin-like growth factor-I (IGF-I) is known to be involved in the development and progression of several types of solid tumors including ovarian cancer. IGF-I levels in local tissue is subject to both endocrine and paracrine/autocrine regulation. To investigate which regulation is more importantly involved in IGF-I action in ovarian cancer regarding tumor progression, we analyzed IGF-I mRNA expression (assuming only from paracrine/autocrine regulation) and peptide concentration (subject to both endocrine and paracrine/autocrine regulation) as well as a genetic polymorphism (CA dinucleotide repeats) in 215 epithelial ovarian cancer patients. Genomic DNA, total RNA and cytosol proteins were extracted from fresh tumor samples. Two alternatively spliced IGF-I transcripts (IGF-IA and IGF-IB) were analyzed using real-time PCR. Cytosol levels of free and total IGF-I were measured with enzyme-linked immunosorbent assay. DNA sizing analysis was performed to determine the CA polymorphism. The study showed that the CA polymorphism had a weak influence on IGF-I expression, but no effect on tumor progression. High levels of free, not total, IGF-I peptide were associated with elevated risk of disease progression (HR = 2.06; 95%CI: 1.22-3.50), and the association was independent of clinicopathologic features of the disease. One of the IGF-I transcripts (IGF-IA) had a similar but less significant impact on disease progression. Women with high IGF-I mRNA and peptide were at greater risk for disease progression compared to those with low in both (HR = 2.13; 95%CI: 1.13-3.95). These findings support the notion that IGF-I is involved in ovarian cancer progression and free IGF-I plays a more important role in the disease. The study also suggests that both endocrine and paracrine/autocrine are involved in the regulation of IGF-I activity in ovarian cancer.

Promoter-specific transcription of insulin-like growth factor-II in epithelial ovarian cancer.

OBJECTIVES: The IGF-II gene has four promoters (P1-P4); each initiates promoter-specific transcription. Studies have shown that IGF-II promoters normally active during fetal growth, but silent in postnatal life, are reactivated in cancer. In a previous study, we found IGF-II transcription evaluated at a common translated region was associated with ovarian cancer progression. This study was conducted to further determine which IGF-II promoters were responsible for the association. METHODS: Promoter-specific transcription at each IGF-II promoter was analyzed in 201 ovarian tumor samples using quantitative RT-PCR. Cox regression analysis was performed to determine the association of IGF-II promoter-specific expression with patient survival. RESULTS: P3 and P4 transcripts were detected more frequently and at significantly higher levels than the transcripts of P1 and P2. P3 and P4 transcripts were strongly correlated with the common IGF-II translated region and were significantly higher in patients with late stage disease, large residual tumor, suboptimal debulking or serous histology compared to those with early stage, small residual tumor, optimal debulking or non-serous histology. Survival analysis showed that patients with high P3 or P4 expression had a 2-fold increase in risk for death compared to those with low P3 or P4. These associations remained significant after adjustment for patient age at surgery, disease stage, tumor grade and histology. P1 and P2 transcripts, however, were not associated with disease characteristics or survival. CONCLUSIONS: These findings suggest that IGF-II transcription from P3 and P4 promoters is important in ovarian cancer and evaluation of IGF-II promoter-specific transcription may have clinical implications in ovarian cancer prognosis and treatment.

Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential.

BACKGROUND: Methylation-mediated suppression of detoxification, DNA repair, and tumor suppressor genes has been implicated in cancer development and progression. Studies also have indicated that concordant methylation of multiple genes (methylator phenotypes), rather than a single gene, may predict cancer prognosis. The current study was designed to determine whether a methylator phenotype exists in ovarian cancer, whether methylation frequencies differ between malignant ovarian tumors and ovarian tumors with low malignant potential (LMP or borderline), and whether methylation of multiple genes affects patient survival. METHODS: The current study included 234 consecutively diagnosed patients with either LMP (n = 19 patients) or malignant (n = 215 patients) ovarian tumors. DNA samples were extracted from fresh frozen tissues and were analyzed for methylation in the promoter region of 6 genes (p16, breast cancer 1 [BRCA1], insulin-like growth factor-binding protein 3 [IGFBP-3], glutathione S-transferase pi 1 [GSTP1], estrogen receptor-alpha [ER-alpha], and human MutL homologue 1 [hMLH1]) by using methylation-specific polymerase chain reaction analysis. RESULTS: The frequencies of methylation in malignant tumors and LMP tumors were 0% and 0% for GSTP1, respectively; 9% and 0% for hMLH1, respectively; 21% and 5% for BRCA1, respectively; 42% and 21% for p16, respectively; 44% and 26% for IGFBP-3, respectively; and 57% and 42% for ER-alpha, respectively. A methylator phenotype was not detected, but a calculated methylation index (MI) that was based on the total number of genes methylated in each tumor was associated with ovarian cancer risk and progression. A higher MI was associated with malignant tumors (odds ratio, 10.11; 95% confidence interval [95% CI], 1.19-85.75) and disease progression (hazards ratio, 6.53; 95% CI, 1.39-30.65). CONCLUSIONS: Although a methylator phenotype was not identified, the current results suggested that methylation of multiple genes may play an important role in ovarian cancer development and progression and may have clinical implications in prognosis.