Pre-operative radiotherapy is associated with superior local relapse-free survival in advanced synovial sarcoma

PURPOSE: Optimization of local therapies in synovial sarcoma (SS) considered unresectable at diagnosis is needed. We evaluated the effects of neoadjuvant versus adjuvant radiation versus surgery only on long-term outcomes. METHODS: Patients with macroscopic SS tumors before chemotherapy (IRS-group-III) in the trials CWS-81, CWS-86, CWS-91, CWS-96, CWS-2002-P and SoTiSaR-registry were analyzed. Local therapies were scheduled after 3 neoadjuvant chemotherapy cycles. RESULTS: Median age of 145 patients was 14.5 years. 106 survivors had median follow-up of 7.0 years. Tumor site was 96 extremities, 19 head-neck, 16 shoulder/hip, 14 trunk. Tumors were  10 cm in 34 patients. In a secondary resection during chemotherapy, R0-status was accomplished in 82, R1 in 30, R2 in 21 (12 missing). Radiotherapy was administered to 115 (R0 61, R1 29, R2 20, missing 5), thereof 57 before and 52 after tumor resection. 23 were treated with surgery only. For all patients, 5 year event-free (EFS) and overall survival (OS) was 68.9% ± 7.6 (95%CI) and 79.1% ± 6.9. To establish independent significance, tumor site, size, surgical results and sequencing of local therapies were analyzed in a Cox regression analysis. Variables associated with EFS and OS are site, size and sequencing of local therapies. Variables associated with local recurrence are site, surgical results and sequencing of local therapies. The only variable associated with suffering metastatic recurrence is tumor size. CONCLUSION: Differences in sequencing of local therapy procedures are independently associated with outcomes. Best local control is achieved when tumors are irradiated pre-operatively and undergo R0 or R1 resection thereafter

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Rational expectations, learning and stock market efficiency

SIGLEAvailable from British Library Document Supply Centre- DSC:D61388 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

How learning in financial markets generates excess volatility and predictability in stock prices

SIGLEGBUnited Kingdo

International asset allocation with time-varying investment opportunities

Also available via the InternetSIGLEAvailable from British Library Document Supply Centre-DSC:3597.9512(no 3464) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The statistical and economic significance of the predictability of excess returns on common stocks

SIGLEAvailable from British Library Document Supply Centre- DSC:3509.88(CU-DAE-WP--9022) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Forecast evaluation with shared data sets

Also available via the InternetAvailable from British Library Document Supply Centre-DSC:3597.9512(no 3060) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Associations between Exposure to Persistent Organic Pollutants in Childhood and Overweight up to 12 Years Later in a Low Exposed Danish Population

Background: Persistent organic pollutants (POPs) have metabolic disrupting abilities and are suggested to contribute to the obesity epidemic. We investigated whether serum concentrations of POPs at 8-10 years of age were associated with subsequent development of overweight at age 14-16 and 20-22 years. Methods: The study was based on data from the European Youth Heart Study, Danish component (1997). Concentrations of several polychlorinated biphenyls (PCBs) and the organochlorine pesticides p,p-dichlorodiphenyldichloroethylene (DDE) and hexachlorobenzene (HCB) were measured in serum from children aged 8-10 years (n = 509). Information on BMI z-scores, waist circumference and % body fat were collected at clinical examinations at ages 8-10, 14-16 and 20-22 years. Multiple linear regression analyses were performed taking potential confounders into account. Results: Overall, POP serum concentrations were low: median ΣPCB 0.18 µg/g lipid, DDE 0.04 µg/g lipid and HCB 0.03 µg/g lipid. POPs were generally not associated with weight gain at 14-16 and 20-22 years of age, except for an inverse association among the highest exposed girls at 20-22 years of age, which might possibly be explained by multiple testing or residual confounding. Conclusion: This study suggests that, in a low exposed population, childhood serum concentrations of PCB, DDE, and HCB are not associated with subsequent weight gain