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At least 199 records · Page 11

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

Purpose: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Results: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling “too sick.” Conclusions: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Pyrrolizidine alkaloid-derived DNA adducts are common toxicological biomarkers of pyrrolizidine alkaloid N -oxides

There are 660 pyrrolizidine alkaloids (PAs) and PA N-oxides present in the plants, with approximately half being possible carcinogens. We previously reported that a set of four PA-derived DNA adducts is formed in the liver of rats administered a series of hepatocarcinogenic PAs and a PA N-oxide. Based on our findings, we hypothesized that this set of DNA adducts is a common biological biomarker of PA-induced liver tumor formation. In this study, we determined that rat liver microsomal metabolism of five hepatocarcinogenic PAs (lasiocarpine, retrorsine, riddelliine, monocrotaline, and heliotrine) and their corresponding PA N-oxides produced the same set of DNA adducts. Among these compounds, lasiocarpine N-oxide, retrorsine N-oxide, monocrotaline N-oxide, and heliotrine N-oxide are for first time shown to be able to produce these DNA adducts. These results further support the role of these DNA adducts as potential common biomarkers of PA-induced liver tumor initiation.

59 BASIC BIOLOGICAL SCIENCES↗

Investigating the non-ideal behavior of the Amptek A111 charge sensitive preamplifier & discriminator board— 3 He proportional counter combination used in common safeguards neutron coincidence counters

Neutron coincidence counting is a well-established technique used for the nondestructive quantification of specialnuclear material during international safeguards inspections. The neutron counters are commonly designedwith an annular body, centered about an inner well or cavity into which a measurement item is placed,and the moderating annulus is populated with 3 He tubes connected to a varying number of preamplifiers.The Canberra Industries JAB-01 preamplifier/amplifier/discriminator board is employed within the company’sneutron coincidence counters, built for use by the International Atomic Energy Agency. Non-ideal behavior ofthese boards was identified during a detector characterization, using list mode data acquisition, of a CanberraIndustries JCC-71 Neutron Coincidence Collar implementing four JAB-01 boards. List mode data acquisition andanalysis reveals features that have commonly been overlooked by historic timing gate selection while using shiftregister data acquisition methods, which are routinely adopted in international safeguards. It has been shownthat double pulsing effects are not fully captured within the predelay setting; therefore, they may influencethe response of the system within the standard operating regime. We set out to identify and correct for doublepulsing in our post analysis of neutron pulse trains, while isolating this behavior to the relevant system. Tounderstand and potentially address these concerns, the responses of two different JAB-01 board systems – theJCC-71 Neutron Coincidence Collar and a modified JCC-51 Active Well Neutron Coincidence Counter – arecompared with the responses of an AnTech Inc. N2071 Neutron Coincidence Collar that also uses an amplifierbuilt on the Amptek A111 Charge Sensitive Preamplifier & Discriminator chip, and a JCC-71 that employs custompreamplifiers designed at Oak Ridge National Laboratory

42 ENGINEERING↗

Debunking common myths in coastal circulation modeling

Despite tremendous progress in algorithm development, computational efficiency and transition into operations over the past two decades, coastal modeling still lacks scientific rigor due to proliferation of many ‘gray’ areas related to various modeling choices made by modelers. Here, in this paper, we propose some guiding principles for the modeling community to improve performance, and we also debunk commonly held myths that make the coastal modeling lack rigor. Using our own experience in developing seamless cross-scale unstructured-grid based models for the past two decades, we describe in unprecedented detail the end-to-end modeling process (i.e., from digital elevation models (DEMs) to mesh generation to post analysis), and demonstrate that defensible modeling is within reach for any end user by following three guiding principles: (1) Bathymetry is a first order forcing in coastal domains and thus should be respected in all aspects of modeling; (2) Oceanographic processes are driven across multiple spatial scales and so models should enable appropriate resolution as needed; and (3) Model assessment should focus on physical processes. Through qualitative and quantitative model assessments, we demonstrate the fundamental role played by bathymetry/topography as embedded in DEMs in making the results defensible, which is unfortunately glossed over in many modeling studies. Focusing on process-based assessment simplifies the calibration process. A major conclusion of this work is that model developers and operators should maximize the scientific rigor for in silico oceanography by avoiding some common pitfalls that rely on error compensation at the expense of representation of physical system processes. We present some best practice procedures for defensive and trustworthy numerical modeling.

54 ENVIRONMENTAL SCIENCES↗

The willow genome and divergent evolution from poplar after the common genome duplication

Willows (Salix) and poplars (Populus) are known worldwide as woody species with diverse uses. Although these two genera diverged from each other around the early Eocene, they share numerous traits, including the same chromosome number of 2n = 38 and the common ‘Salicoid’ genome duplication with a high macrosynteny. However, most willow species flower early in their lives with short, small and sometimes indistinct stems, and thus differ from poplars in their life histories and habits. In addition, multiple inter- and intrachromosomal rearrangements have been detected involving chromosomal regions present in both lineages, suggestive of the likely genomic divergence after the common genome duplication.

59 BASIC BIOLOGICAL SCIENCES↗

A reference genome for common bean and genome-wide analysis of dual domestications

Common bean (Phaseolus vulgaris L.) is the most important grain legume for human consumption and has a role in sustainable agriculture owing to its ability to fix atmospheric nitrogen. We assembled 473 Mb of the 587-Mb genome and genetically anchored 98% of this sequence in 11 chromosome-scale pseudomolecules. We compared the genome for the common bean against the soybean genome to find changes in soybean resulting from polyploidy. Using resequencing of 60 wild individuals and 100 landraces from the genetically differentiated Mesoamerican and Andean gene pools, we confirmed 2 independent domestications from genetic pools that diverged before human colonization. Less than 10% of the 74 Mb of sequence putatively involved in domestication was shared by the two domestication events. We identified a set of genes linked with increased leaf and seed size and combined these results with quantitative trait locus data from Mesoamerican cultivars. Genes affected by domestication may be useful for genomics-enabled crop improvement.

59 BASIC BIOLOGICAL SCIENCES↗

Common workflows for computing material properties using different quantum engines

The prediction of material properties based on density-functional theory has become routinely common, thanks, in part, to the steady increase in the number and robustness of available simulation packages. This plurality of codes and methods is both a boon and a burden. While providing great opportunities for cross-verification, these packages adopt different methods, algorithms, and paradigms, making it challenging to choose, master, and efficiently use them. We demonstrate how developing common interfaces for workflows that automatically compute material properties greatly simplifies interoperability and cross-verification. We introduce design rules for reusable, code-agnostic, workflow interfaces to compute well-defined material properties, which we implement for eleven quantum engines and use to compute various material properties. Each implementation encodes carefully selected simulation parameters and workflow logic, making the implementer’s expertise of the quantum engine directly available to non-experts. All workflows are made available as open-source and full reproducibility of the workflows is guaranteed through the use of the AiiDA infrastructure.

36 MATERIALS SCIENCE↗

Effects of scale of movement, detection probability, and true population density on common methods of estimating population density

Knowledge of population density is necessary for effective management and conservation of wildlife, yet rarely are estimators compared in their robustness to effects of ecological and observational processes, which can greatly influence accuracy and precision of density estimates. For this study, we simulate biological and observational processes using empirical data to assess effects of animal scale of movement, true population density, and probability of detection on common density estimators. We also apply common data collection and analytical techniques in the field and evaluate their ability to estimate density of a globally widespread species. We find that animal scale of movement had the greatest impact on accuracy of estimators, although all estimators suffered reduced performance when detection probability was low, and we provide recommendations as to when each field and analytical technique is most appropriately employed. The large influence of scale of movement on estimator accuracy emphasizes the importance of effective post-hoc calculation of area sampled or use of methods that implicitly account for spatial variation. In particular, scale of movement impacted estimators substantially, such that area covered and spacing of detectors (e.g. cameras, traps, etc.) must reflect movement characteristics of the focal species to reduce bias in estimates of movement and thus density.

59 BASIC BIOLOGICAL SCIENCES↗

Population co-divergence in common cuttlefish (Sepia officinalis) and its dicyemid parasite in the Mediterranean Sea

Population structure and biogeography of marine organisms are formed by different drivers than in terrestrial organisms. Yet, very little information is available even for common marine organisms and even less for their associated parasites. Here we report the first analysis of population structure of both a cephalopod host ( Sepia officinalis ) and its dicyemid parasite, based on a homologous molecular marker (cytochrome oxidase I). We show that the population of common cuttlefish in the Mediterranean area is fragmented into subpopulations, with some areas featuring restricted level of gene flow. Amongst the studied areas, Sardinia was genetically the most diverse and Cyprus the most isolated. At a larger scale, across the Mediterranean, the population structure of the parasite shows co-diversification pattern with its host, but a slower rate of diversification. Differences between the two counterparts are more obvious at a finer scale, where parasite populations show increased level of fragmentation and lower local diversities. This discrepancy can be caused by local extinctions and replacements taking place more frequently in the dicyemid populations, due to their parasitic lifestyle.

59 BASIC BIOLOGICAL SCIENCES↗

Increased abundance of a common scavenger affects allocation of carrion but not efficiency of carcass removal in the Fukushima Exclusion Zone

Abstract The 2011 nuclear accident in Fukushima, Japan caused the evacuation of > 100,000 people and prompted studies on environmental impacts of radiological contamination. However, few researchers have explored how the human evacuation has affected ecosystem processes. Despite contamination, one common scavenger (wild boar, Sus scrofa ) is 2–3× more abundant inside the Fukushima Exclusion Zone (FEZ). Shifts in abundance of some scavenger species can have cascading effects on ecosystems, so our objective was to investigate impacts of the evacuation and the resulting increase in wild boar on vertebrate scavenger communities. We deployed cameras at 300 carcasses in the FEZ and a nearby inhabited area, and quantified carcass fate, scavenger species, and detection/persistence times. We also tested effects of carcass size and habitat on scavenger community composition and efficiency by balancing trials across two carcass sizes and habitats in each zone. Overall scavenger richness and carcass removal rates (73%) were similar in the FEZ and inhabited area, but species-specific carcass removal rates and occurrence differed between zones. Wild boar removed substantially more carcasses inside the FEZ, with implications for nutrient and contaminant distribution. Our results suggest carcass size affects scavenging dynamics more than human activity or habitat, and abundance changes of common scavengers can influence carrion resource allocation.

59 BASIC BIOLOGICAL SCIENCES↗

PHYSLITE - A new reduced common data format for ATLAS

The High Luminosity LHC (HL-LHC) era brings unprecedented computing challenges that call for novel approaches to reduce the amount of real and Monte Carlo-simulated data that is stored, while continuing to support the rich physics program of the ATLAS experiment. With the beginning of LHC Run 3, ATLAS introduced a new common data format, PHYS, that replaces most of the analysis-specific formats that were used in Run 2, and therefore reduces the disk storage significantly. ATLAS also launched the prototype of another common format, PHYSLITE, that is about a third of the size of PHYS. PHYSLITE will be the main format for ATLAS at the HL-LHC and aims to serve 80% of all physics analyses. To simplify analysis workloads and further reduce disk usage it is designed to largely replace user-defined analysis n-tuples and consequently contains pre-calibrated objects. Various forms of validations are in place to ensure correct functionality for users. Developments continue towards HL-LHC to improve the PHYSLITE format further.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Quantum Chemistry Common Driver and Databases (QCDB) and Quantum Chemistry Engine (QCEngine): Automation and interoperability among computational chemistry programs

We report that community efforts in the computational molecular sciences (CMS) are evolving toward modular, open, and interoperable interfaces that work with existing community codes to provide more functionality and composability than could be achieved with a single program. The Quantum Chemistry Common Driver and Databases (QCDB) project provides such capability through an application programming interface (API) that facilitates interoperability across multiple quantum chemistry software packages. In tandem with the Molecular Sciences Software Institute and their Quantum Chemistry Archive ecosystem, the unique functionalities of several CMS programs are integrated, including CFOUR, GAMESS, NWChem, OpenMM, Psi4, Qcore, TeraChem, and Turbomole, to provide common computational functions, i.e., energy, gradient, and Hessian computations as well as molecular properties such as atomic charges and vibrational frequency analysis. Both standard users and power users benefit from adopting these APIs as they lower the language barrier of input styles and enable a standard layout of variables and data. These designs allow end-to-end interoperable programming of complex computations and provide best practices options by default.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Detection of common fragments in a series of images by superimposed volume Fourier holograms

The paper adresses the problem of detecting common fragments in a sequence of images recorded in volume recording medium by the method of superimposed Fourier holograms in the joint-transform scheme. As applied to the description of images as realisations of a homogeneous random field, the dependence of the detection efficiency on the number of superimposed holograms is analysed by estimating the image information capacity and the common and distinct fragments of images in the recorded sequences. Theoretical conclusions are confirmed by the results of numerical experiments. (holographic memory)

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Prediction of inherited genomic susceptibility to 20 common cancer types by a supervised machine-learning method

Prevention and early intervention are the most effective ways of avoiding or minimizing psychological, physical, and financial suffering from cancer. However, such proactive action requires the ability to predict the individual’s susceptibility to cancer with a measure of probability. Of the triad of cancer-causing factors (inherited genomic susceptibility, environmental factors, and lifestyle factors), the inherited genomic component may be derivable from the recent public availability of a large body of whole-genome variation data. However, genome-wide association studies have so far showed limited success in predicting the inherited susceptibility to common cancers. We present here a multiple classification approach for predicting individuals’ inherited genomic susceptibility to acquire the most likely phenotype among a panel of 20 major common cancer types plus 1 “healthy” type by application of a supervised machine-learning method under competing conditions among the cohorts of the 21 types. This approach suggests that, depending on the phenotypes of 5,919 individuals of “white” ethnic population in this study, (i) the portion of the cohort of a cancer type who acquired the observed type due to mostly inherited genomic susceptibility factors ranges from about 33 to 88% (or its corollary: the portion due to mostly environmental and lifestyle factors ranges from 12 to 67%), and (ii) on an individual level, the method also predicts individuals’ inherited genomic susceptibility to acquire the other types ranked with associated probabilities. These probabilities may provide practical information for individuals, heath professionals, and health policymakers related to prevention and/or early intervention of cancer.

59 BASIC BIOLOGICAL SCIENCES↗

A lincRNA connected to cell mortality and epigenetically-silenced in most common human cancers

Immortality is an essential characteristic of human carcinoma cells. We recently developed an efficient, reproducible method that immortalizes human mammary epithelial cells (HMEC) in the absence of gross genomic changes by targeting 2 critical senescence barriers. Consistent transcriptomic changes associated with immortality were identified using microarray analysis of isogenic normal finite pre-stasis, abnormal finite post-stasis, and immortal HMECs from 4 individuals. A total of 277 genes consistently changed in cells that transitioned from post-stasis to immortal. Gene ontology analysis of affected genes revealed biological processes significantly altered in the immortalization process. These immortalization-associated changes showed striking similarity to the gene expression changes seen in The Cancer Genome Atlas (TCGA) clinical breast cancer data. The most dramatic change in gene expression seen during the immortalization step was the downregulation of an unnamed, incompletely annotated transcript that we called MORT, for mortality, since its expression was closely associated with the mortal, finite lifespan phenotype. We show here that MORT (ZNF667-AS1) is expressed in all normal finite lifespan human cells examined to date and is lost in immortalized HMEC. MORT gene silencing at the mortal/immortal boundary was due to DNA hypermethylation of its CpG island promoter. This epigenetic silencing is also seen in human breast cancer cell lines and in a majority of human breast tumor tissues. The functional importance of DNA hypermethylation in MORT gene silencing is supported by the ability of 5-aza-2'- deoxycytidine to reactivate MORT expression. Analysis of TCGA data revealed deregulation of MORT expression due to DNA hypermethylation in 15 out of the 17 most common human cancers. In conclusion, the epigenetic silencing of MORT in a large majority of the common human cancers suggests a potential fundamental role in cellular immortalization during human carcinogenesis.

60 APPLIED LIFE SCIENCES↗

Precursors prior to type IIn supernova explosions are common: Precursor rates, properties, and correlations

There is a growing number of Type IIn supernovae (SNe) which present an outburst prior to their presumably final explosion. These precursors may affect the SN display, and are likely related to poorly charted phenomena in the final stages of stellar evolution. By coadding Palomar Transient Factory (PTF) images taken prior to the explosion, here we present a search for precursors in a sample of 16 Type IIn SNe. We find five SNe IIn that likely have at least one possible precursor event (PTF 10bjb, SN 2010mc, PTF 10weh, SN 2011ht, and PTF 12cxj), three of which are reported here for the first time. For each SN we calculate the control time. We find that precursor events among SNe IIn are common: at the one-sided 99% confidence level, >50% of SNe IIn have at least one pre-explosion outburst that is brighter than 3 × 10{sup 7} L{sub ☉} taking place up to 1/3 yr prior to the SN explosion. The average rate of such precursor events during the year prior to the SN explosion is likely ≳ 1 yr{sup –1}, and fainter precursors are possibly even more common. Ignoring the two weakest precursors in our sample, the precursors rate we find is still on the order of one per year. We also find possible correlations between the integrated luminosity of the precursor and the SN total radiated energy, peak luminosity, and rise time. These correlations are expected if the precursors are mass-ejection events, and the early-time light curve of these SNe is powered by interaction of the SN shock and ejecta with optically thick circumstellar material.

79 ASTRONOMY AND ASTROPHYSICS↗

Using the GlideinWMS System as a Common Resource Provisioning Layer in CMS

CMS will require access to more than 125k processor cores for the beginning of Run 2 in 2015 to carry out its ambitious physics program with more and higher complexity events. During Run1 these resources were predominantly provided by a mix of grid sites and local batch resources. During the long shut down cloud infrastructures, diverse opportunistic resources and HPC supercomputing centers were made available to CMS, which further complicated the operations of the submission infrastructure. In this presentation we will discuss the CMS effort to adopt and deploy the glideinWMS system as a common resource provisioning layer to grid, cloud, local batch, and opportunistic resources and sites. We will address the challenges associated with integrating the various types of resources, the efficiency gains and simplifications associated with using a common resource provisioning layer, and discuss the solutions found. We will finish with an outlook of future plans for how CMS is moving forward on resource provisioning for more heterogenous architectures and services.

Balcas, J.↗

Towards more transparent and reproducible omics studies through a common metadata checklist and data publications

Biological processes are fundamentally driven by complex interactions between biomolecules. Integrated high-throughput omics studies enable multifaceted views of cells, organisms, or their communities. With the advent of new post-genomics technologies omics studies are becoming increasingly prevalent yet the full impact of these studies can only be realized through data harmonization, sharing, meta-analysis, and integrated research,. These three essential steps require consistent generation, capture, and distribution of the metadata. To ensure transparency, facilitate data harmonization, and maximize reproducibility and usability of life sciences studies, we propose a simple common omics metadata checklist. The proposed checklist is built on the rich ontologies and standards already in use by the life sciences community. The checklist will serve as a common denominator to guide experimental design, capture important parameters, and be used as a standard format for stand-alone data publications. This omics metadata checklist and data publications will create efficient linkages between omics data and knowledge-based life sciences innovation and importantly, allow for appropriate attribution to data generators and infrastructure science builders in the post-genomics era. We ask that the life sciences community test the proposed omics metadata checklist and data publications and provide feedback for their use and improvement.

Kolker, Eugene↗