A Novel Interdisciplinary Course in Gerontechnology for Disseminating Computational Thinking

While specialized knowledge and skills are the hallmark of modern society, the size and complexity of contemporary problems often require cooperative effort to analyze and solve. Therefore, experiences with skills, methodologies, and tools for effective interdisciplinary collaboration and structured problem solving are vital for preparing students for future academic and professional success. Meanwhile, computational systems have permeated much of modern professional and personal life, making computational thinking an essential skill for members of modern society. However, formal training in these techniques is primarily limited to students within computer science, mathematics, management of information systems, and engineering. At Iowa State University, we have designed and offered an experimental course to develop undergraduate students’ abilities for interdisciplinary teamwork and to disseminate computational thinking skills to a broader range of students. This novel course was jointly designed and instructed by faculty from the Computer Science Department, Gerontology Program, and Graphic Design Program to incorporate diverse faculty expertise and pedagogical approaches. Students were required to interview real users to identify real-life problems, gather requirements, and assess candidate solutions, which necessitated communication both within the group and with technologically-disinclined users. In-class presentations and wiki-based project websites provided regular practice at disseminating domain expertise to larger interdisciplinary audiences. Workshops, group-based mentoring, peer learning, and guided discovery allowed non-CS majors to learn much more about computer programs and tools, and grading criteria held students individually accountable within their disciplines but also emphasized group collaboration

Overall and cause-specific mortality rates among men and women with high exposure to indoor air pollution from the use of smoky and smokeless coal: a cohort study in Xuanwei, China

OBJECTIVES: Never-smoking women in Xuanwei (XW), China, have some of the highest lung cancer rates in the country. This has been attributed to the combustion of smoky coal used for indoor cooking and heating. The aim of this study was to evaluate the spectrum of cause-specific mortality in this unique population, including among those who use smokeless coal, considered 'cleaner' coal in XW, as this has not been well-characterised. DESIGN: Cohort study. SETTING: XW, a rural region of China where residents routinely burn coal for indoor cooking and heating. PARTICIPANTS: Age-adjusted, cause-specific mortality rates between 1976 and 2011 were calculated and compared among lifetime smoky and smokeless coal users in a cohort of 42 420 men and women from XW. Mortality rates for XW women were compared with those for a cohort of predominately never-smoking women in Shanghai. RESULTS: Mortality in smoky coal users was driven by cancer (41%), with lung cancer accounting for 88% of cancer deaths. In contrast, cardiovascular disease (CVD) accounted for 32% of deaths among smokeless coal users, with 7% of deaths from cancer. Total cancer mortality was four times higher among smoky coal users relative to smokeless coal users, particularly for lung cancer (standardised rate ratio (SRR)=17.6). Smokeless coal users had higher mortality rates of CVD (SRR=2.9) and pneumonia (SRR=2.5) compared with smoky coal users. These patterns were similar in men and women, even though XW women rarely smoked cigarettes. Women in XW, regardless of coal type used, had over a threefold higher rate of overall mortality, and most cause-specific outcomes were elevated compared with women in Shanghai. CONCLUSIONS: Cause-specific mortality burden differs in XW based on the lifetime use of different coal types. These observations provide evidence that eliminating all coal use for indoor cooking and heating is an important next step in improving public health particularly in developing countries

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Household air pollution and epigenetic aging in Xuanwei, China

BACKGROUND: Household air pollution (HAP) from indoor combustion of solid fuel is a global health burden linked to lung cancer. In Xuanwei, China, lung cancer rate for nonsmoking women is among the highest in the world and largely attributed to high levels of polycyclic aromatic hydrocarbons (PAHs) that are produced from combustion of smoky (bituminous) coal used for cooking and heating. Epigenetic age acceleration (EAA), a DNA methylation-based biomarker of aging, has been shown to be highly correlated with biological processes underlying the susceptibility of age-related diseases. We aim to assess the association between HAP exposure and EAA. METHODS: We analyzed data from 106 never-smoking women from Xuanwei, China. Information on fuel type was collected using a questionnaire, and validated exposure models were used to predict levels of 43 HAP constituents. Exposure clusters were identified using hierarchical clustering. EAA was derived for five epigenetic clocks defined as the residuals resulting from regressing each clock on chronological age. We used generalized estimating equations to test associations between exposure clusters derived from predicted levels of HAP exposure, ambient 5-methylchrysene (5-MC), a PAH previously found to be associated with risk of lung cancer, and EAA, while accounting for repeated-measurements and confounders. RESULTS: We observed an increase in GrimAge EAA for clusters with 31 and 33 PAHs reflecting current (β = 0.77 y per standard deviation (SD) increase, 95 % CI:0.36,1.19) and childhood (β = 0.92 y per SD, 95 % CI:0.40,1.45) exposure, respectively. 5-MC (ng/m 3-year) was found to be associated with GrimAge EAA for current (β = 0.15 y, 95 % CI:0.05,0.25) and childhood (β = 0.30 y, 95 % CI:0.13,0.47) exposure. CONCLUSIONS: Our findings suggest that exposure to PAHs from indoor smoky coal combustion, particularly 5-MC, is associated with GrimAge EAA, a biomarker of mortality

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H