PO-0698: Clinical outcomes of 4D CBCT-guided stereotactic body radiotherapy for inoperable hepatocellular carcinomas

Poster: Clinical track: Gastrointestinal tumours (upper and lower GI)published_or_final_version3rd ESTRO Forum, Barcelona, Spain, 24-28 April 2015. In Radiotherapy & Oncology, 2015, v. 115, p. S342-S34

Integration of molecular biology tools for identifying promoters and genes abundantly expressed in flowers of Oncidium Gower Ramsey

<p>Abstract</p> <p>Background</p> <p>Orchids comprise one of the largest families of flowering plants and generate commercially important flowers. However, model plants, such as <it>Arabidopsis thaliana </it>do not contain all plant genes, and agronomic and horticulturally important genera and species must be individually studied.</p> <p>Results</p> <p>Several molecular biology tools were used to isolate flower-specific gene promoters from <it>Oncidium </it>'Gower Ramsey' (<it>Onc</it>. GR). A cDNA library of reproductive tissues was used to construct a microarray in order to compare gene expression in flowers and leaves. Five genes were highly expressed in flower tissues, and the subcellular locations of the corresponding proteins were identified using lip transient transformation with fluorescent protein-fusion constructs. BAC clones of the 5 genes, together with 7 previously published flower- and reproductive growth-specific genes in <it>Onc</it>. GR, were identified for cloning of their promoter regions. Interestingly, 3 of the 5 novel flower-abundant genes were putative trypsin inhibitor (<it>TI</it>) genes (<it>OnTI1</it>, <it>OnTI2 </it>and <it>OnTI3</it>), which were tandemly duplicated in the same BAC clone. Their promoters were identified using transient GUS reporter gene transformation and stable <it>A. thaliana </it>transformation analyses.</p> <p>Conclusions</p> <p>By combining cDNA microarray, BAC library, and bombardment assay techniques, we successfully identified flower-directed orchid genes and promoters.</p

1/Nc1/N_c Expansion for Excited Baryons

We derive consistency conditions which constrain the possible form of the strong couplings of the excited baryons to the pions. The consistency conditions follow from requiring the pion-excited baryon scattering amplitudes to satisfy the large-N_c Witten counting rules and are analogous to consistency conditions used by Dashen, Jenkins and Manohar and others for s-wave baryons. The consistency conditions are explicitly solved, giving the most general allowed form of the strong vertices for excited baryons in the large-N_c limit. We show that the solutions to the large-N_c consistency conditions coincide with the predictions of the nonrelativistic quark model for these states, extending the results previously obtained for the s-wave baryons. The 1/N_c corrections to these predictions are studied in the quark model with arbitrary number of colors N_c.Comment: 56 pages, REVTeX; one new Appendix added containing a discussion of the results in the language of quark operator

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Cranial Magnetic Resonance Imaging Findings in Children With Nonsyndromic Mitochondrial Diseases

Cranial magnetic resonance imaging findings suggestive of specific mitochondrial syndromes are reported. However, cranial magnetic resonance imaging features in children with nonsyndromic mitochondrial diseases are rarely described. From January 1992-September 2009, data from 33 patients with nonsyndromic mitochondrial diseases were collected. We investigated cranial magnetic resonance imaging features in children with nonsyndromic mitochondrial diseases, and identified potential diagnostic characteristics. Eleven of 33 patients (33.3%) demonstrated normal findings, and 22 (66.7%) demonstrated abnormal findings. The most common abnormal finding was cerebral atrophy, with or without other lesion sites (15133; 45.5%). The second most common was bilateral basal ganglia involvement (6/33; 18.2%). Follow-up imaging was performed in 20 patients. Ten of these 20 (50.0%) demonstrated evolutionary changes, in which progressive global brain atrophy was evident. Three patients with normal results and one patient with cerebral atrophy on initial imaging demonstrated prominent signal changes over the basal ganglia, brainstem, gray. matter, white matter, and bilateral cerebellar hemispheres on follow-up imaging. Imaging in children With nonsyndromic mitochondrial diseases may produce variable findings. Normal results and cerebral atrophy on the initial cranial magnetic resonance. imaging are commonly evident in this patient group. (C) 2011 Elsevier Inc. All rights reserved