bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of neutron dose equivalent outside and inside of the treatment vault of GRID therapy
Authors: Wang Xudong , Charlton Michael A. , Esquivel Carlos , Eng Tony Y. , Li Ying , Papanikolaou Nikos 
Published: August 2013

Purpose: To evaluate the neutron and photon dose equivalent rates at the treatment vault entrance (Hn,D and HG), and to study the secondary radiation to the patient in GRID therapy. The radiation activation on the grid was studied.Methods:A Varian Clinac 23EX accelerator was working at 18 MV mode with a grid manufactured by .decimal, Inc. The Hn,D and HG were measured using an Andersson–Braun neutron REM meter, and a Geiger Müller counter. The radiation activation on the grid was measured after the irradiation with an ion chamber γ‐ray survey meter. The secondary radiation dose equivalent to patient was evaluated by etched track detectors and OSL detectors on a RANDO® phantom.Results: Within the measurement uncertainty, there is no significant difference between the Hn,D and HG with and without a grid. However, the neutron dose equivalent to the patient with the grid is, on average, 35.3% lower than that without the grid when using the same field size and the same amount of monitor unit. The photon dose equivalent to the patient with the grid is, on average, 44.9% lower. The measured average half‐life of the radiation activation in the grid is 12.0 (±0.9) min. The activation can be categorized into a fast decay component and a slow decay component with half‐lives of 3.4 (±1.6) min and 15.3 (±4.0) min, respectively. There was no detectable radioactive contamination found on the surface of the grid through a wipe test.Conclusions: This work indicates that there is no significant change of the Hn,D and HG in GRID therapy, compared with a conventional external beam therapy. However, the neutron and scattered photon dose equivalent to the patient decrease dramatically with the grid and can be clinical irrelevant. Meanwhile, the users of a grid should be aware of the possible high dose to the radiation worker from the radiation activation on the surface of the grid. A delay in handling the grid after the beam delivery is suggested.
Simultaneous optimization of dose distributions and fractionation schemes in particle radiotherapy
Authors: Unkelbach Jan , Zeng Chuan , Engelsman Martijn 
Published: August 2013

Purpose:The paper considers the fractionation problem in intensity modulated proton therapy (IMPT). Conventionally, IMPT fields are optimized independently of the fractionation scheme. In this work, we discuss the simultaneous optimization of fractionation scheme and pencil beam intensities.Methods:This is performed by allowing for distinct pencil beam intensities in each fraction, which are optimized using objective and constraint functions based on biologically equivalent dose (BED). The paper presents a model that mimics an IMPT treatment with a single incident beam direction for which the optimal fractionation scheme can be determined despite the nonconvexity of the BED‐based treatment planning problem.Results:For this model, it is shown that a small α/β ratio in the tumor gives rise to a hypofractionated treatment, whereas a large α/β ratio gives rise to hyperfractionation. It is further demonstrated that, for intermediate α/β ratios in the tumor, a nonuniform fractionation scheme emerges, in which it is optimal to deliver different dose distributions in subsequent fractions. The intuitive explanation for this phenomenon is as follows: By varying the dose distribution in the tumor between fractions, the same total BED can be achieved with a lower physical dose. If it is possible to achieve this dose variation in the tumor without varying the dose in the normal tissue (which would have an adverse effect), the reduction in physical dose may lead to a net reduction of the normal tissue BED. For proton therapy, this is indeed possible to some degree because the entrance dose is mostly independent of the range of the proton pencil beam.Conclusions:The paper provides conceptual insight into the interdependence of optimal fractionation schemes and the spatial optimization of dose distributions. It demonstrates the emergence of nonuniform fractionation schemes that arise from the standard BED model when IMPT fields and fractionation scheme are optimized simultaneously. Although the projected benefits are likely to be small, the approach may give rise to an improved therapeutic ratio for tumors treated with stereotactic techniques to high doses per fraction.
Integration of advanced 3D SPECT modeling into the open‐source STIR framework
Authors: Fuster Berta Marti , Falcon Carles , Tsoumpas Charalampos , Livieratos Lefteris , Aguiar Pablo , Cot Albert , Ros Domenec , Thielemans Kris 
Published: August 2013

Purpose:The Software for Tomographic Image Reconstruction (STIR,http://stir.sourceforge.net) package is an open source object‐oriented library implemented in C++. Although its modular design is suitable for reconstructing data from several modalities, it currently only supports Positron Emission Tomography (PET) data. In this work, the authors present results for Single Photon Emission Computed Tomography (SPECT) imaging.Methods:This was achieved by the complete integration of a 3D SPECT system matrix modeling library into STIR.Results:The authors demonstrate the flexibility of the combined software by reconstructing simulated and acquired projections from three different scanners with different iterative algorithms of STIR.Conclusions:The extension of the open source STIR project with advanced SPECT modeling will enable the research community to study the performance of several algorithms on SPECT data, and potentially implement new algorithms by expanding the existing framework.
Abstract 32: PER3 gene in association with plasma melatonin in Caucasian men.
Authors: Gu Fangyi , Chu Lisa W. , Yu Kai , Wang Zhaoming , Chanock Stephen , Hsing Ann , Caporaso Neil E. 
Published: August 2013

Abstract
Circadian rhythm disruption is classified as a possible human carcinogen, and has been associated with incidence, survival and prognosis of multiple cancers. Melatonin is the central circadian rhythm biomarker and identifying its genetic determinants will shed light on the mechanisms of the circadian rhythm-cancer relationship.
We have conducted what we believe is the first genome wide association scan (GWAS) of morning circulating melatonin levels in humans. We used data from 1250 Caucasian men from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Serum used for melatonin measurements were prospectively collected and prediagnostic of cancer; all serum were collected in the morning (7:00-11:00 am). We evaluated ∼ 2.5 million single nucleotide polymorphisms (SNP), and gave priority to 1298 SNPs in 20 candidate genes related to melatonin and circadian rhythm (20 kb upstream-10 kb downstream). Single SNP analyses were performed using linear models for log transformed melatonin concentrations, coding SNPs additively, and adjusting for age (≤59, 60-64, 65-69, ≥70 years) time of blood draw (6-7, 8, 9, 10, 11 am), study center, prostate cancer status, and eigenvectors that captured population stratification. Gene based P-values (Pgene) were computed using the minP method and 10,000 permutations. For the most significant SNPs, we also performed sensitivity analyses by restricting the analysis to men who were not subsequently diagnosed with prostate cancer. We did not detect a signal at the genome-wide significance level (10-8). However, we observed that PER3, one of the 9 core circadian rhythm regulating genes, was significantly associated with serum melatonin after Bonferroni correction for the 20 a priori candidate genes (Pgene=9×10−4). The top SNP (SNP1-7763877 G&gt;T) achieved significance after Bonferroni correction that takes into account the total number of SNPs (1298) in the 20 candidate genes selected (P=1.24×10−5). For this SNP, serum melatonin decreased by 28% (14.8-40%) per T allele.
Our study suggests that PER3 gene polymorphisms might be associated with melatonin production, the velocity of diurnal decrease, or its diurnal pattern. This results warrant replication in independent samples, in females, and in urine for metabolites of melatonin.
Citation Format: Fangyi Gu, Lisa W. Chu, Kai Yu, Zhaoming Wang, Stephen Chanock, Ann Hsing, Neil E. Caporaso. PER3 gene in association with plasma melatonin in Caucasian men. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 32.
Abstract 46: A review of the gene-environment interaction literature in cancer: What do we know?
Authors: Mechanic Leah E. , Simonds Naoko I. , Ghazarian Armen , Benedicto Camilla B. , Schully Sheri D. , Ellison Gary L. , Gillanders Elizabeth M. 
Published: August 2013

Abstract
Risk of cancer is determined by a complex interplay of genetic and environmental factors. Therefore, the study of gene-environment interactions has been an active area of research for several years. To examine the state of the science in the field of gene-environment interactions research in cancer, we performed a systematic review of the published literature. A total of 3019 articles were identified using the gene-environment or pharmacogenomic flags from the HuGE literature finder and CancerGAMAdb, curated databases of genetic association studies, from January 1, 2001 to January 31, 2010. From these articles, 243 articles were determined to be relevant based on the inclusion criteria of at least 1000 cases in the interaction studied, examining the combination of genes and environment, and investigating the interaction as related to cancer risk. Information from these articles was abstracted regarding cancer type, environmental exposure variables, genetic variables, and estimates of interaction effects. In these papers, over 3500 interactions were investigated. The majority of these interactions were examined in colon, rectal, or colorectal cancer types (40%) followed by breast cancer (30%). Most of these interactions were explored using candidate gene polymorphisms (82%) compared with polymorphisms identified from genome wide association studies (GWAS). The most common environmental exposure categories observed were “energy balance” (41%), e.g. BMI or diet, followed by “Lifestyle” (21%), e.g. smoking or alcohol intake. Further analysis regarding commonly observed interactions, analytical tests performed, number of statistically significant interactions and magnitudes of interactions is on-going. In conclusion, observations of published literature suggest that opportunity exists for more of an agnostic approach to the study of gene-environment interactions and exploring alternative environmental exposures.
Citation Format: Leah E. Mechanic, Naoko I. Simonds, Armen Ghazarian, Camilla B. Benedicto, Sheri D. Schully, Gary L. Ellison, Elizabeth M. Gillanders. A review of the gene-environment interaction literature in cancer: What do we know? [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 46.
Abstract 60: Combined effects of low-penetrance variants on breast cancer risk: Results from the Seoul Breast Cancer Study.
Authors: Sung Hyuna , Choi Ji-Yeob , Park Sue K. , Han Wonshik , Yoo Keun-Young , Ahn Sei-Hyun , Noh Dong-Young , Kang Daehee 
Published: August 2013

Abstract
Background: Although several low-penetrance loci associated with breast cancer risk were identified and confirmed, knowledge of the effect of multiple risk alleles is limited especially in Asian women. Therefore we evaluated the association between the polygenic risk scores and breast cancer risk in Korean women using the most recent list of breast cancer susceptibility loci.
Methods: We analyzed 51 single-nucleotide polymorphisms (SNPs) located in 34 loci in 1,774 cases and age-frequency matched 1,774 control subjects participating in Seoul Breast Case-Control Study. The fourteen independent SNPs associated with breast cancer risk were selected based on the results of single SNP analysis. The genetic risk score (GRS) were calculated using simple count method and weighted method. Tests of association were conducted using the logistic regression for quintiles of each GRS with or without adjustment. The c-statistic was estimated to evaluate the contribution of GRS to risk prediction model including non-genetic factors (age, family history of breast cancer, education, BMI, menopausal status, age at menarche, age at first full-term pregnancy, and number of children).
Results: Fourteen SNPs (rs13393577, rs4973768, rs7716600, rs1092913, rs889312, rs9485372, rs2046210, rs1562430, rs704010, rs10736303, rs7107217, rs10771399, rs3803662, and rs4784227), each of which reflected a genetically independent locus, were found to be associated with breast cancer risk. A highly significant trend was observed between the GRS and the risk of breast cancer. The adjusted odds ratios for women in the highest quintile of count GRS or weighted GRS vs. those in the lowest were 2.64 (95% confidence interval (95% CI), 2.09- 3.35; Ptrend=9.3E-19) and 2.76 (95% CI, 2.18- 3.50; Ptrend=5.9E-21), respectively. The c-statistic for model including the GRS in additional to the conventional risk factors was 0.6389 (95% CI, 0.620-0.658) vs. 0.6041 (95% CI, 0.585-0.623) with the conventional risk factors only.
Conclusions: Supporting the polygenic inheritance model of breast cancer, our study showed that GRS based on low-penetrance SNPs adds very modest improvement to risk prediction models.
Citation Format: Hyuna Sung, Ji-Yeob Choi, Sue K. Park, Wonshik Han, Keun-Young Yoo, Sei-Hyun Ahn, Dong-Young Noh, Daehee Kang. Combined effects of low-penetrance variants on breast cancer risk: Results from the Seoul Breast Cancer Study. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 60.
Abstract IA07: The phenome and pleiotropy: Dissecting the architecture of complex traits.
Authors: Ritchie Marylyn D. , Sarah Pendergrass A. 
Published: August 2013

Abstract
The efforts of the human genome project are beginning to provide important findings for human health. Technological advances in the laboratory, particularly in characterizing human genomic variation, have created new approaches for studying the human genome. However, current statistical and computational strategies are taking only partial advantage of this wealth of information. In the quest for disease susceptibility genes for common, complex disease, we are faced with many challenges. Selecting genetic, clinical, and environmental factors important for the trait of interest is increasingly more difficult as high throughput data generation technologies are developed. We know that genes do not act in isolation, thus numerous other factors are likely important in complex disease phenotypes. Ultimately, we want to know what factors are important to provide superior prevention, diagnosis, and treatment of human disease. Unfortunately, interpretation of statistical models in a meaningful way for biomedical research has been lacking due to the inherent difficulty in making such connections.
One of the emerging areas for exploring the architecture of complex traits includes phenome-wide association studies, or PheWAS. It is conceivable that be exploiting the interrelationships between traits, we can uncover novel mechanistic insights and identify evidence for pleiotropy. A number of strategies are being explored to capitalize on the network of phenotypes to then test for association with genotypes. In this presentation, a number of PheWAS examples will be provided as well as next steps in the quest for understanding the architecture of complex traits.
Citation Format: Marylyn D. Ritchie, Pendergrass A. Sarah. The phenome and pleiotropy: Dissecting the architecture of complex traits. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA07.
Abstract IA08: Characterizing the exposome.
Authors: Smith Martyn T. 
Published: August 2013

Abstract
The exposome is defined as the totality of environmental exposures from conception onwards. It offers a conceptual leap towards understanding the environmental causes of human disease through comprehensive studies of the internal chemical environment using repeated blood and other biological samples taken during critical life stages (Rappaport, S.M. and M.T. Smith, Science, 2010. 330:460-1). It augments the chemical-by-chemical approach to finding causes of disease as it includes both endogenous and exogenous exposures. From a toxicological viewpoint it is the chemicals present in biological fluids, such as the plasma, that the body's cell and tissues encounter that then cause aberrant health conditions. Hence, it is the internal exposome that represents the total target dose of chemical agents in the body, no matter what their source or how they are derived. This includes chemicals arising from inflammation, oxidative stress and other endogenous sources. Several ‘omic’ technologies can be applied to characterize the exposome of specific diseases and may promote discovery of the key exposures responsible for chronic diseases. Characterizing the human exposome represents a challenge similar to the human genome project, which began when DNA sequencing was in its infancy and has generated by some accounts $140 for every $1 invested. Given the magnitude of the exposome challenge international participation is of paramount importance. Thus, we have formed the Exposome Alliance (http://www.exposomealliance.org) to promote investment in a human exposome project. The European Union recently took the first steps in this regard by funding a European Exposome initiative that will support several international projects.
Citation Format: Martyn T. Smith. Characterizing the exposome. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA08.
Abstract IA11A: Tumor heterogeneity: Making the most of diversity.
Authors: Couch Fergus J. 
Published: August 2013

Abstract
Initial genome wide association studies (GWAS) of common cancers focused on combining all available cases in order to maximize the statistical power of the studies. While many genome wide significant associations (p &lt; 5 × 10−8) were observed, this approach overlooked the possibility that certain genetic risk factors might have greater effects in specific populations. With this in mind more recent studies have focused on associations between common genetic variants and disease in populations other than those of northern European ancestry. In addition, GWAS of predisposed individuals, such as carriers of BRCA1 and BRCA2 mutations, have been conducted based on the hypothesis that unique modifiers of breast and ovarian cancer risk might influence disease in these populations. More recently, associations with histological subtypes of tumors have been observed for a number of different cancer types. In the setting of breast cancer, specific associations with estrogen receptor status of tumors and even triple negative tumors (estrogen receptor, progesterone receptor, and HER2 negative) have been reported. Ongoing studies further suggest that specific associations with histochemical markers and tumor grade may also exist in the general population. Here we will discuss recent associations between genetic variants and subpopulations of disease using breast cancer as a model, and consider the importance of these findings for an improved understanding of the etiology of breast cancer and enhanced cancer risk assessment.
Citation Format: Fergus J. Couch. Tumor heterogeneity: Making the most of diversity. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA11A.
The Dissociation between Early and Late Selection in Older Adults
Authors: Alperin Brittany R. , Haring Anna E. , Zhuravleva Tatyana Y. , Holcomb Phillip J. , Rentz Dorene M. , Daffner Kirk R. 
Published: August 2013

Abstract
Older adults exhibit a reduced ability to ignore task-irrelevant stimuli; however, it remains to be determined where along the information processing stream the most salient age-associated changes occur. In the current study, ERPs provided an opportunity to determine whether age-related differences in processing task-irrelevant stimuli were uniform across information processing stages or disproportionately affected either early or late selection. ERPs were measured in young and old adults during a color-selective attention task in which participants responded to target letters in a specified color (attend condition) while ignoring letters in a different color (ignore condition). Old participants were matched to two groups of young participants on the basis of neuropsychological test performance: one using age-appropriate norms and the other using test scores not adjusted for age. There were no age-associated differences in the magnitude of early selection (attend–ignore), as indexed by the size of the anterior selection positivity and posterior selection negativity. During late selection, as indexed by P3b amplitude, both groups of young participants generated neural responses to target letters under the attend versus ignore conditions that were highly differentiated. In striking contrast, old participants generated a P3b to target letters with no reliable differences between conditions. Individuals who were slow to initiate early selection appeared to be less successful at executing late selection. Despite relative preservation of the operations of early selection, processing delays may lead older participants to allocate excessive resources to task-irrelevant stimuli during late selection.