Objective: The traditional use of retrospective self-report to measure exposure to community violence over long periods of time has limitations overcome by an approach described here. This article explores an innovative approach in assessing community violence exposure with time-sampling methodology, where reporting occurs within daily accounts to provide a more immediate measure of community violence exposure. Method: Data were collected over 1 week from 169 urban African American young adolescents (M age = 11.7 years, SD = .70, 62% female) using questionnaires and the Daily Sampling Method, a diary technique that captures a child’s daily accounts of community violence exposure (DCVE). Results: Analyses revealed youth experienced 841 total violent incidents, or close to 1 daily incident per youth for the week. As expected, the majority of incidents occurred between 3 p.m. and 8 p.m., and in public settings. Unexpectedly, higher rates of both victimization and witnessing occurred during weekdays compared with weekend days, and girls reported significantly more DCVE than boys. The DCVE provide a unique glimpse into the more immediate experience of life in high-risk neighborhoods. Conclusion: This study underscores the need to measure DCVE in ways that address the daily experience of youth living in high-risk environments. By identifying timing and location of exposure, we can develop interventions to keep youth safer from violence exposure.
Angiopoietin-1 (Ang1) signals via the receptor tyrosine kinase Tie2 which exists in complex with the related protein Tie1 at the endothelial cell surface. Tie1 undergoes regulated ectodomain cleavage in response to phorbol esters, vascular endothelial growth factor (VEGF) and tumour necrosis factor-α (TNFα). Recently phorbol esters and VEGF were found also to stimulate ectodomain cleavage of Tie2. Here we investigate for the first time the effects of factors activating ectodomain cleavage on both Tie1 and Tie2 within the same population of cells, and their impact on angiopoietin signalling. We find that phorbol ester and VEGF activated Tie1 cleavage within minutes followed by restoration to control levels by 24 h. However, several hours of PMA and VEGF treatment were needed to elicit a detectable decrease in cellular Tie2, with complete loss seen at 24 h of PMA treatment. TNFα stimulated Tie1 cleavage, and induced a sustained decrease in cellular Tie1 over 24 h whilst increasing cellular Tie2. These differential effects of agonists on Tie1 and Tie2 result in dynamic modulation of the cellular Tie2∶Tie1 ratio. To assess the impact of this on Ang1 signalling cells were stimulated with VEGF and TNFα for differing times and Ang1-induced Tie2 phosphorylation examined. Elevated Tie2∶Tie1, in response to acute VEGF treatment or chronic TNFα, was associated with increased Ang1-activated Tie2 in cells. These data demonstrate cellular levels of Tie1 and Tie2 are differentially regulated by pathophysiologically relevant agonists resulting in dynamic control of the cellular Tie2∶Tie1 balance and modulation of Ang1 signalling. These findings highlight the importance of regulation of signalling at the level of the receptor. Such control may be an important adaptation to allow modulation of cellular signalling responses in systems in which the activating ligand is normally present in excess or where the ligand provides a constitutive maintenance signal.
Prior studies have found that outpatients are frequently unaware of their chronic kidney disease (CKD). Little is known about CKD awareness in hospitalized patients. We conducted a retrospective study of general medicine inpatients with CKD, ascertained through International Classification of Diseases, Ninth Revision codes for non–dialysis-dependent CKD (585.0–585.9) in their first 20 admission diagnoses (n = 590). Patient awareness of their CKD, defined as correct patient self-report of “kidney problems” was 32%. Of 161 patients with advanced CKD, 48% of patients with stage 4 (estimated glomerular filtration rate [eGFR] 15–29) and 63% with stage = (eGFR <15) reported having CKD. In multivariable analysis, factors significantly associated with patient self-report of CKD included advanced CKD stage, other race (nonwhite, non-African American), and increasing Mini-Mental State Exam score (all P < 0.05). CKD awareness increased, but remained low, in patients with advanced CKD who would benefit from referral to multidisciplinary nephrology care. Hospitalization provides an opportunity to educate patients with CKD and link them to care.
ObjectiveFew studies have evaluated re-irradiation of lung cancer recurrences with stereotactic body radiotherapy (SBRT). This study evaluates outcomes with SBRT re-irradiation for recurrent lung cancer.MethodsTwo hundred and seventy-eight patients treated with SBRT for lung cancer were retrospectively reviewed. Of those, 26 patients with 29 tumors were re-irradiated with SBRT. Ninety percent of tumors received prior external beam irradiation and 10 % received prior SBRT. Previous median radiation dose was 61.2 Gy with a median 8-month interval from previous radiation. The median re-irradiation SBRT dose was 30 Gy (48 Gy10 biological effective dose (BED)). Endpoints evaluated included local control, overall survival, and progression-free survival.ResultsTwenty-five of 29 tumors were evaluable for local control, with 27 tumors (93 %) considered in-field recurrences. In-field crude local control rate was 80 % (20/25) with 1 and 2-year actuarial rates of 78.6 and 65.5 %, respectively. One and 2-year actuarial survival rates were 52.3 and 37.0 %, respectively. One and 2-year actuarial progression-free survival rates were 56.7 and 37.0 %, respectively. Fifty-five percent of patients reported acute/chronic grades 1 and 2 toxicities. No grade 3 or higher toxicities were reported.ConclusionPatients with recurrent lung cancer have limited options. SBRT re-irradiation is tolerable even after a median 61.2 Gy to the re-irradiation site. The lower BED used provided acceptable progression-free survival with low toxicity. Given the poor prognosis with current treatment options, new paradigms for re-treatment should include SBRT-re-irradiation as an adjunct to systemic therapy for in-field lung cancer recurrence.
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