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Author(s): Atwood, Todd F; Brown, Derek W; Juang, Titania; Moore, Kevin L; McConnell, Kristen A; Steers, Jennifer M; Murphy, James D; Mundt, Arno J; Pawlicki, Todd | Abstract: PurposeTo provide insight into the types of questions asked to medical physicists by patients during one-on-one physicist-patient consults at one institution.Materials and methodsMedical physicists trained in patient communication techniques met with patients to provide an overview of the treatment planning and delivery processes, discuss the patient's treatment plan, and answer any technical questions. From August 2016 to December 2019, 152 physicist-patient consults were conducted. In the initial months of the study (August 2016-December 2017), following each physicist-patient consult, all patient questions were documented by the physicists. For the remaining time period (January 2018-December 2019), any newly encountered questions were periodically added to the list. The questions were compiled into a comprehensive list and organized into categories.ResultsThere were a total of 88 unique patient questions. These questions fit into four topical categories. Fifty-four questions (61.4%) were in the "Treatment Planning and Delivery Questions" category, 15 questions (17.1%) were in the "General Radiation Questions or Concerns" category, 13 questions (14.8%) were in the "Safety and Quality Assurance Questions" category, and 6 questions (6.8%) were in the "Medical Questions" category. Overall, patients were primarily concerned about how radiation works, the treatment planning and delivery processes, and what is being done to keep them safe throughout their treatment.ConclusionPhysicist-patient consults provided an opportunity to address the technical aspects of radiation therapy with patients in greater detail. The fact that patient questions could be conveniently grouped into only four topical categories indicates that it may be straightforward for other medical physicists to prepare for effectively addressing technical questions during physicist-patient consults.

An extensive multi-country outbreak of multidrug-resistant monophasic Salmonella Typhimurium infection in 10 countries with 150 reported cases, predominantly affecting young children, has been linked to chocolate products produced by a large multinational company. Extensive withdrawals and recalls of multiple product lines have been undertaken. With Easter approaching, widespread product distribution and the vulnerability of the affected population, early and effective real-time sharing of microbiological and epidemiological information has been of critical importance in effectively managing this serious food-borne incident.

EnteroBase is an integrated software environment that supports the identification of global population structures within several bacterial genera that include pathogens. Here, we provide an overview of how EnteroBase works, what it can do, and its future prospects. EnteroBase has currently assembled more than 300,000 genomes from Illumina short reads from Salmonella, Escherichia, Yersinia, Clostridioides, Helicobacter, Vibrio, and Moraxella and genotyped those assemblies by core genome multilocus sequence typing (cgMLST). Hierarchical clustering of cgMLST sequence types allows mapping a new bacterial strain to predefined population structures at multiple levels of resolution within a few hours after uploading its short reads. Case Study 1 illustrates this process for local transmissions of Salmonella enterica serovar Agama between neighboring social groups of badgers and humans. EnteroBase also supports single nucleotide polymorphism (SNP) calls from both genomic assemblies and after extraction from metagenomic sequences, as illustrated by Case Study 2 which summarizes the microevolution of Yersinia pestis over the last 5000 years of pandemic plague. EnteroBase can also provide a global overview of the genomic diversity within an entire genus, as illustrated by Case Study 3, which presents a novel, global overview of the population structure of all of the species, subspecies, and clades within Escherichia.

BackgroundCpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis.MethodsWe searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques.ResultsThe pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21–24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries.ConclusionAlthough no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.

Background: Studies evaluating the association between peripheral blood leukocyte telomere length (LTL) and testicular germ cell tumor (TGCT) risk have produced conflicting results. Methods: Using available genotype data from the Testicular Cancer Consortium (TECAC), polygenic risk score and Mendelian randomization analyses of genetic variants previously associated with LTL were used to assess potential etiologic associations between telomere length and TGCT risk. Results: Genetically inferred telomere length was not associated with TGCT risk among 2,049 cases and 6,921 controls with individual-level genotype data (OR, 1.02; 95% confidence interval, 0.97–1.07). Mendelian randomization analyses using summary statistic data further indicated no evidence for an association between telomere length and TGCT risk among all available TECAC participants (3,558 cases and 13,971 controls). Conclusions: Our analyses in the largest molecular genetic testicular cancer study to date provide no evidence for an association between genetically inferred peripheral blood LTL and TGCT risk. Impact: The lack of evidence for an overall association indicates that peripheral blood LTL is likely not a strong biomarker for TGCT risk.

Background Cancer epidemiology studies require sufficient power to assess spatial relationships between exposures and cancer incidence accurately. However, methods for power calculations of spatial statistics are complicated and underdeveloped, and therefore underutilized by investigators. The spatial relative risk function, a cluster detection technique that detects spatial clusters of point-level data for two groups (e.g., cancer cases and controls, two exposure groups), is a commonly used spatial statistic but does not have a readily available power calculation for study design. Results We developed sparrpowR as an open-source R package to estimate the statistical power of the spatial relative risk function. sparrpowR generates simulated data applying user-defined parameters (e.g., sample size, locations) to detect spatial clusters with high statistical power. We present applications of sparrpowR that perform a power calculation for a study designed to detect a spatial cluster of incident cancer in relation to a point source of numerous environmental emissions. The conducted power calculations demonstrate the functionality and utility of sparrpowR to calculate the local power for spatial cluster detection. Conclusions sparrpowR improves the current capacity of investigators to calculate the statistical power of spatial clusters, which assists in designing more efficient studies. This newly developed R package addresses a critically underdeveloped gap in cancer epidemiology by estimating statistical power for a common spatial cluster detection technique.

Summary A concern when conducting genome-wide association studies (GWAS) is the potential for population stratification, i.e. ancestry-based genetic differences between cases and controls, that if not properly accounted for, could lead to biased association results. We developed PCAmatchR as an open source R package for performing optimal case–control matching using principal component analysis (PCA) to aid in selecting controls that are well matched by ancestry to cases. PCAmatchR takes user supplied PCA outputs and selects matching controls for cases by utilizing a weighted Mahalanobis distance metric which weights each principal component by the percentage of genetic variation explained. Results from the 1000 Genomes Project data demonstrate both the functionality and performance of PCAmatchR for selecting matching controls for case populations as well as reducing inflation of association test statistics. PCAmatchR improves genomic similarity between matched cases and controls, which minimizes the effects of population stratification in GWAS analyses. Availability and implementation PCAmatchR is freely available for download on GitHub (https://github.com/machiela-lab/PCAmatchR) or through CRAN (https://CRAN.R-project.org/package=PCAmatchR). Supplementary information Supplementary data are available at Bioinformatics online.

BACKGROUND: CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors. METHODS: We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model. RESULTS: We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatum bacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion. CONCLUSION: The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment.

Context Advances in sports injury-surveillance methods have made it possible to accommodate non–time-loss (NTL) injury reporting; however, the analysis of surveillance data now requires careful consideration of the nuances of NTL injury records. Background Injury-surveillance mechanisms that record NTL injuries are more likely to contain multiple injury records per athlete. These must be handled appropriately in statistical analyses to make methodologically sound inferences. Methods We simulated datasets of NTL injuries using varying degrees of observation clustering and compared the inferences made using traditional techniques with those made after accounting for clustering in computations of injury proportion ratios. Results Inappropriate handling of even moderate clustering resulted in flawed inferences in 10% to 12% of our simulations. We observed greater bias in our estimates as the degree of clustering increased. Conclusions We urge investigators to carefully consider observation clustering and adapt analytical methods to accommodate the evolving sophistication of surveillance.

// Claire L. Meaney 1 , Adriana Zingone 1 , Derek Brown 1 , Yunkai Yu 2 , Liang Cao 2 and Brid M. Ryan 1 1 Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA 2 Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA Correspondence to: Brid M. Ryan, email: Brid.Ryan@nih.gov Keywords: lung cancer, biomarkers, survival, inflammation, IL-6 Received: June 30, 2016 Accepted: February 20, 2017 Published: April 03, 2017 ABSTRACT Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Low-dose CT (LDCT) imaging is now recommended to screen high-risk lung cancer individuals in the USA. LDCT has resulted in increased detection of stage I lung cancer for which the current standard of care is surgery alone. However, approximately 30% of these patients develop recurrence and therefore are in need of further treatment upon diagnosis. This study aims to explore blood-based inflammatory biomarkers to identify patients at high-risk of mortality for which additional treatment modalities can be offered at time of diagnosis. Patients and Methods: Recent work on a small panel of circulating cytokines identified elevated levels of IL-6, a pro-inflammatory cytokine, as an indicator of poor survival for lung cancer patients. To reflect the broader role of inflammation in lung cancer, we examined a large panel of 33 inflammatory proteins in the sera of 129 lung cancer patients selected from the National Cancer Institute-Maryland case-control study. To reduce heterogeneity, we specifically focused our study on stage I lung adenocarcinoma patients. Results: We replicated the previous observations that IL-6 is associated with prognosis of lung cancer and extended its utility to prognosis in this highly-selected population of stage I lung adenocarcinoma patients. In addition, we developed a multi-marker, combined prognostic classifier that includes the pro-inflammatory Th-17 cell effector cytokine, IL-17. Patients with high levels of IL-6 and IL-17A had a significantly adverse survival compared with patients with low levels ( P for trend

Little is known about prejudicial attitudes patients have toward physicians. Past research shows that physicians commonly face discrimination 1–3, and although Asian physicians constitute the largest ethnic minority population of practicing physicians,4, there is no research that examines their experiences with discrimination explicitly. Asian professionals are subject to both positive and negative stereotypes, such that they are categorized as high-achieving (e.g., intelligent, successful), yet also perpetually foreign and never accepted into the American milieu.5 This research examined how patient biases can influence evaluations of physicians as a function of physician race, gender, and severity of a medical error.

Importance Treatment options for patients with young-onset colon cancer remain to be defined and their effects on prognosis are unclear. Objective To investigate receipt of adjuvant chemotherapy by age category (18-49, 50-64, and 65-75 years) and assess whether age differences in chemotherapy matched survival gains among patients diagnosed as having colon cancer in an equal-access health care system. Design, Setting, and Participants This cohort study was based on linked and consolidated data from the US Department of Defense’s Central Cancer Registry and Military Heath System medical claims databases. There were 3143 patients aged 18 to 75 years with histologically confirmed primary colon adenocarcinoma diagnosed between 1998 and 2007. This study was conducted from December 2015 to August 2016. Exposures Patients who underwent surgery and postoperative systemic chemotherapy. Main Outcomes and Measures The primary outcome measure of the study was overall survival of patients who only received surgery and those who received both surgery and postoperative systemic chemotherapy. Results Of the 3143 patients, 1841 were men (58.6%). Young (18-49 years) and middle-aged (50-64 years) patients were 2 to 8 times more likely to receive postoperative systemic chemotherapy compared with older patients (65-75 years) across all tumor stages. Middle-aged patients with stage I (odds ratio, 5.04; 95% CI, 2.30-11.05) and stage II (odds ratio, 2.42; 95% CI, 1.58-3.72) disease were more likely to receive postoperative chemotherapy compared with older patients. Both groups were more likely to receive multiagent chemotherapy than were older patients (patients aged 18-49 years: odds ratio, 2.48; 95% CI, 1.42-4.32 and patients aged 50-64 years: odds ratio, 2.66; 95% CI, 1.70-4.18). Among patients who received surgery and postoperative systemic chemotherapy, no significant differences were observed in survival among age groups (the 95% CIs of hazard ratios included 1 for young and middle-aged patients compared with older patients for all tumor stages). Conclusions and Relevance In an equal-access health care system, we found potential overuse of chemotherapy among young and middle-aged adults with colon cancer. The addition of postoperative systemic chemotherapy did not result in matched survival improvement.

Purpose: Both humans and software are notoriously challenging to account for in traditional hazard analysis models. The purpose of this work is to investigate and demonstrate the application of a new, extended accident causality model, called systems theoretic accident model and processes (STAMP), to radiation oncology. Specifically, a hazard analysis technique based on STAMP, system-theoretic process analysis (STPA), is used to perform a hazard analysis. Methods: The STPA procedure starts with the definition of high-level accidents for radiation oncology at the medical center and the hazards leading to those accidents. From there, the hierarchical safety control structure of the radiation oncology clinic is modeled, i.e., the controls that are used to prevent accidents and provide effective treatment. Using STPA, unsafe control actions (behaviors) are identified that can lead to the hazards as well as causal scenarios that can lead to the identified unsafe control. This information can be used to eliminate or mitigate potential hazards. The STPA procedure is demonstrated on a new online adaptive cranial radiosurgery procedure that omits the CT simulation step and uses CBCT for localization, planning, and surface imaging system during treatment. Results: The STPA procedure generated a comprehensive set of causal scenarios that are traced back to system hazards and accidents. Ten control loops were created for the new SRS procedure, which covered the areas of hospital and department management, treatment design and delivery, and vendor service. Eighty three unsafe control actions were identified as well as 472 causal scenarios that could lead to those unsafe control actions. Conclusions: STPA provides a method for understanding the role of management decisions and hospital operations on system safety and generating process design requirements to prevent hazards and accidents. The interaction of people, hardware, and software is highlighted. The method of STPA produces results that can be used to improve safety and prevent accidents and warrants further investigation., Varian Medical Systems

Global changes in gene expression accompany the development of cancer. Thus, inherited variants in miRNA-binding sites are likely candidates for conferring inherited susceptibility. Using an in silico approach, we compiled a comprehensive list of SNPs predicted to modulate miRNA binding in genes from several key lung cancer pathways. We then investigated whether these SNPs were associated with lung cancer risk in two independent populations. In general, SNPs in miRNA-binding sites are rare. However, some allelic variation was observed. We found that rs1126579 in CXCR2 was associated with a reduced risk of lung cancer in both European American [ORTT vs. CC 0.56 (0.37–0.88); P = 0.008] and Japanese [ORTT vs. CC 0.62 (0.38–1.00); P = 0.049] populations. Furthermore, we found that the SNP disrupted a novel binding site for miR-516a-3p, led to a moderate increase in CXCR2 mRNA and protein expression, and increased MAPK signaling. Moreover, analysis of rs1126579 with serum levels of IL8, its endogenous ligand, supported an interaction whereby rs1126579-T and high serum IL8 conferred synergistic protection from lung cancer. Our findings demonstrate a function for a 3′UTR SNP in modulating CXCR2 expression, signaling, and susceptibility to lung cancer. Cancer Res; 75(3); 566–75. ©2014 AACR.

Author(s): Griffiths, Richard; Wegmann, Alex; Hanson, Chad; Keitt, Brad; Howald, Gregg; Brown, Derek; Tershy, Bernie; Pitt, William; Moran, Matthew; Rex, Kristen; White, Susan; Flint, Beth; Torr, Nick | Abstract: Rodent eradications undertaken on tropical islands have had a lower success rate than those attempted in temperate regions. A recent project undertaken to eradicate Rattus tanezumi and R. exulans from the 3 islands comprising Wake Atoll is illustrative. R. tanezumi was successfully removed from all 3 islands. R. exulans was permanently eradicated on Peale Island (95 ha) and temporarily on Wilkes Island (76 ha). R. exulans eradication on Wake Island (525 ha) was unsuccessful and the species has since repopulated Wake Island and recolonized Wilkes Island. We completed a detailed review of the project in an attempt to isolate potential causes of eradication failure. Based on the evidence available, we were not able to positively identify a single factor to explain why R. exulans survived on Wake Island. However, monitoring after the operation points to a sequence of events that comprised delayed mortality amongst a subset of breeding females and the emergence of young rats after bait was no longer readily available. Such an event was likely influenced by an abundance of natural food resources throughout the treatment area, a high density of rats, interspecific competition for toxic bait, and rapid disappearance of bait because of consumption by non-target consumers (land crabs). These factors are common to many tropical islands. We provide recommendations for addressing these factors in a future attempt to remove rats from Wake Atoll.

The diet of black rhinoceros (Diceros bicornis minor) was studied using backtracking and faecal analysis in South Africa. Both methods yielded different results, with a large bias for dominant species. Results of backtracking showed that the rhinos browsed on 80 plant species. Grasses comprised 4.5% of the diet in the faecal analysis, but were not recorded during the backtracking. The backtracking method, along with a measure of forage availability, was used to identify two groups of plant species, those species taken in a higher proportion than available in the field and those taken in a lower proportion. Chemical analyses showed that these two species groups were similar in in vitro digestibility, macro-elements and fibre constituents. Mean bite size and species contribution to the diet were not correlated with any of the forage quality parameters, indicating that rhinos were not maximising nutrient intake or minimising fibre intake of these consumed plant species.

Purpose It is challenging for the radiation oncology practitioner to manage and implement the plethora of recently generated recommendations on quality and safety improvement. The online Safety Profile Assessment (SPA) tool uses an easy-to-use question-and-answer format to assess safety/quality within a clinic, provide a way to benchmark against peers, and facilitate improvement. This report describes the design and development of the SPA and experience from the first year of use. Methods Performance indicators for the SPA were derived from 4 foundations: the Agency for Healthcare Research and Quality, a review of 7 recent authoritative documents specific to radiation oncology, a recent American Association of Physicists in Medicine report on incident learning, and the American College of Radiology–American Society for Radiation Oncology accreditation system as of 2011. After pilot testing, the free-access tool was launched through the American Association of Physicists in Medicine website (http://spa.aapm.org) in July 2013. Questionnaire data were collected to assess the experience of users. Results The SPA tool consists of 92 indicators designed to probe safety and quality. A clinic's performance is benchmarked against all other responses in the database, and aided by a downloadable log, quality/safety improvement strategies can be developed and tracked over time. At the time this paper was written, 279 individuals had registered, and 107 had completed the SPA. On average, the SPA required 1.3 hours to complete. The majority of respondents to the questionnaire (56%) completed the SPA with a multidisciplinary group of 4 people on average. Respondents noted that the SPA was easy or very easy to use (70%) and that they would definitely or very probably complete it again (63%). Conclusions SPA provides a straightforward means of gauging a clinic's performance in key safety-critical areas and has been evaluated favorably by the first cohort of users. The tool has been qualified by the American Board of Radiology (ABR) as meeting the criteria for Practice Quality Improvement requirements of the ABR Maintenance of Certification Program.