19 research outputs found

    Revisiting fetal dose during radiation therapy: evaluating treatment techniques and a custom shield [JACMP, 17(5), 2016]

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139980/1/acm212191_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139980/2/acm212191.pd

    Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.

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    OBJECTIVES: To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. METHODS: Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. RESULTS: A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10-9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. CONCLUSION: We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Sex Trafficking of Young Women and Girls from Nepal to India: Searching for a Solution, Addressing Issues of Police Complicity

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    The United States State Department estimates that between 600,000 to 800,000 people a year are trafficked across international borders. The United Nations estimates between 700,000 to two million young women alone are trafficked annually, the majority of whom are trafficked for sexual exploitation. In Nepal and India, despite domestic and international law, the police and border officials do little to address the problem. Multiple human rights violations coincide with this issue; including issues of bodily integrity, development of self (individuation), torture, rights to education, and issues of family rights. Adequately addressing this intractable problem necessitates a multi-pronged approach including addressing the socio-economic issues, political corruption, cultural views of women, and police complicity. The solution to end the trafficking of young women and girls involves a multi-faceted approach which includes changing the attitudes of the police and citizens of India and Nepal towards women, improving the socio-economic conditions of the Nepali families who send their daughters to India, educating the peoples of each county on the risks and long-lasting effects of sex trafficking on young girls, and strengthening the existing laws both domestic and international. Victims, families, police, government, officials, and citizens need to work together to formulate a creative solution to this ongoing problem. Because of the complex cultural issues, the solution must be generated from the people of these countries, not by outside authorities. Within this multi- pronged solution police education, sensitivity training, and cultural awareness will be an important lynch pin

    Multi-institutional evaluation of end-to-end protocol for IMRT/VMAT treatment chains utilizing conventional linacs

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    We conducted a multi-institutional assessment of a recently developed end-to-end monthly quality assurance (QA) protocol for external beam radiation therapy treatment chains. This protocol validates the entire treatment chain against a baseline to detect the presence of complex errors not easily found in standard component-based QA methods. Participating physicists from 3 institutions ran the end-to-end protocol on treatment chains that include Imaging and Radiation Oncology Core (IROC)-credentialed linacs. Results were analyzed in the form of American Association of Physicists in Medicine (AAPM) Task Group (TG)-119 so that they may be referenced by future test participants. Optically stimulated luminescent dosimeter (OSLD), EBT3 radiochromic film, and A1SL ion chamber readings were accumulated across 10 test runs. Confidence limits were calculated to determine where 95% of measurements should fall. From calculated confidence limits, 95% of measurements should be within 5% error for OSLDs, 4% error for ionization chambers, and 4% error for (96% relative gamma pass rate) radiochromic film at 3% agreement/3 mm distance to agreement. Data were separated by institution, model of linac, and treatment protocol (intensity-modulated radiation therapy [IMRT] vs volumetric modulated arc therapy [VMAT]). A total of 97% of OSLDs, 98% of ion chambers, and 93% of films were within the confidence limits; measurements were found outside these limits by a maximum of 4%, \u3c 1%, and \u3c 1%, respectively. Data were consistent despite institutional differences in OSLD reading equipment and radiochromic film calibration techniques. Results from this test may be used by clinics for data comparison. Areas of improvement were identified in the end-to-end protocol that can be implemented in an updated version. The consistency of our data demonstrates the reproducibility and ease-of-use of such tests and suggests a potential role for their use in broad end-to-end QA initiatives

    Randomized phase II trial of urethral sparing intensity modulated radiation therapy in low-risk prostate cancer: implications for focal therapy

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    Abstract Background Low-risk prostate cancer (PCa) patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Acute urinary symptoms are common during external beam radiotherapy (EBRT), while chronic symptoms have been linked to urethral dose. Since most low-risk PCa occurs in the peripheral zone (PZ), we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT) could improve urinary health-related quality of life (HRQOL) while maintaining high rates of PCa control. Methods Patients with National Comprehensive Cancer Network (NCCN) defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were randomized to US-IMRT or standard (S-) IMRT. Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3–5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT. For US-IMRT, mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy, respectively. HRQOL was assessed using the Expanded Prostate Cancer Index (EPIC) Quality of Life questionnaire. The primary endpoint was change in urinary HRQOL at 3 months. Results From June 2004 to November 2006, 16 patients were randomized, after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint. Mean change in EPIC urinary HRQOL at 3 months was −0.5 ± 11.2 in the US-IMRT arm and +3.9 ± 15.3 in the S-IMRT arm (p = 0.52). Median PSA nadir was higher in the US-IMRT arm (1.46 vs. 0.78, p = 0.05). At 4.7 years median follow-up, three US-IMRT and no S-IMRT patients experienced PSA failure (p = 0.06; HR 8.8, 95% CI 0.9–86). Two out of 3 patients with PSA failure had biopsy-proven local failure, both located contralateral to the original site of disease. Conclusions Compared with S-IMRT, US-IMRT failed to improve urinary HRQOL and resulted in higher PSA nadir and inferior biochemical control. The high rate of PSA failure and contralateral local failures in US-IMRT patients, despite careful selection of MRI-screened low-risk patients, serve as a cautionary tale for focal PCa treatments.</p

    “The big wide world of school”: Supporting children on the autism spectrum to successfully transition to primary school: Perspectives from parents and early intervention professionals

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    Background: The transition to primary school is often a complex and uncertain time for autistic children and their families. Understanding how best to develop school readiness and support transition to primary school for autistic children is essential. School readiness and transition planning are influenced by a range of personal and contextual factors, and it is important to understand the perspectives of the various stakeholders involved in the transition process. Methods: A qualitative exploration employing focus groups and interviews was undertaken with early intervention (EI) staff (n = 45) and parents (n = 18) across Australia to understand their perspectives on school readiness and the transition to primary school. Results: Thematic analysis identified four emerging themes facilitating transition including: 1) building the child; 2) building the parents; 3) building the receiving school; and, 4) connecting the system. Conclusion: Findings highlight the need to consider school readiness and transition planning from a holistic perspective, ensuring clear, collaborative and ongoing communication between parents, teachers and EI staff, using a strength-based approach, and individualizing transition planning

    Clinician Proposed Predictors of Spoken Language Outcomes for Minimally Verbal Children with Autism Spectrum Disorder

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    Our aim was to explore insights from clinical practice that may inform efforts to understand and account for factors that predict spoken language outcomes for children with Autism Spectrum Disorder who use minimal verbal language. We used a qualitative design involving three focus groups with 14 speech pathologists to explore their views and experiences. Using the Framework Method of analysis, we identified 9 themes accounting for 183 different participant references to potential factors. Participants highlighted the relevance of clusters of fine-grained social, communication, and learning behaviours, including novel insights into prelinguistic vocal behaviours. The participants suggested the potential value of dynamic assessment in predicting spoken language outcomes. The findings can inform efforts to developing clinically relevant methods for predicting children's communication outcomes.David Trembath, Rebecca Sutherland, Teena Caithness, Cheryl Dissanayake, Valsamma Eapen, Kathryn Fordyce, Grace Frost, Teresa Iacono, Nicole Mahler, Anne Masi, Jessica Paynter, Katherine Pye, Sheena Reilly, Veronica Rose, Stephanie Sievers, Abirami Thirumanickam, Marleen Westerveld, Madonna Tucke
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