Time-averaged aerodynamic loads on the vane sets of the 40- by 80-foot and 80- by 120-foot wind tunnel complex

Time-averaged aerodynamic loads are estimated for each of the vane sets in the National Full-Scale Aerodynamic Complex (NFAC). The methods used to compute global and local loads are presented. Experimental inputs used to calculate these loads are based primarily on data obtained from tests conducted in the NFAC 1/10-Scale Vane-Set Test Facility and from tests conducted in the NFAC 1/50-Scale Facility. For those vane sets located directly downstream of either the 40- by 80-ft test section or the 80- by 120-ft test section, aerodynamic loads caused by the impingement of model-generated wake vortices and model-generated jet and propeller wakes are also estimated

Exome-wide association study of pancreatic cancer risk

We conducted a case-control exome-wide association study to discover germline variants in coding regions that affect risk for pancreatic cancer, combining data from 5 studies. We analyzed exome and genome sequencing data from 437 patients with pancreatic cancer (cases) and 1922 individuals not known to have cancer (controls). In the primary analysis, BRCA2 had the strongest enrichment for rare inactivating variants (17/437 cases vs 3/1922 controls) (P=3.27x10(-6); exome-wide statistical significance threshold P<2.5x10(-6)). Cases had more rare inactivating variants in DNA repair genes than controls, even after excluding 13 genes known to predispose to pancreatic cancer (adjusted odds ratio, 1.35, P=.045). At the suggestive threshold (P<.001), 6 genes were enriched for rare damaging variants (UHMK1, AP1G2, DNTA, CHST6, FGFR3, and EPHA1) and 7 genes had associations with pancreatic cancer risk, based on the sequence-kernel association test. We confirmed variants in BRCA2 as the most common high-penetrant genetic factor associated with pancreatic cancer and we also identified candidate pancreatic cancer genes. Large collaborations and novel approaches are needed to overcome the genetic heterogeneity of pancreatic cancer predisposition

Complementary paths to Chagas disease elimination: the impact of combining vector control with etiological treatment

Background. The World Health Organization's 2020 goals for Chagas disease are (1) interrupting vector-borne intradomiciliary transmission and (2) having all infected people under care in endemic countries. Insecticide spraying has proved efficacious for reaching the first goal, but active transmission remains in several regions. For the second, treatment has mostly been restricted to recently infected patients, who comprise only a small proportion of all infected individuals. Methods. We extended our previous dynamic transmission model to simulate a domestic Chagas disease transmission cycle and examined the effects of both vector control and etiological treatment on achieving the operational criterion proposed by the Pan American Health Organization for intradomiciliary, vectorial transmission interruption (ie, <2% seroprevalence in children <5 years of age). Results. Depending on endemicity, an antivectorial intervention that decreases vector density by 90% annually would achieve the transmission interruption criterion in 2-3 years (low endemicity) to >30 years (high endemicity). When this strategy is combined with annual etiological treatment in 10% of the infected human population, the seroprevalence criterion would be achieved, respectively, in 1 and 11 years. Conclusions. Combining highly effective vector control with etiological (trypanocidal) treatment in humans would substantially reduce time to transmission interruption as well as infection incidence and prevalence. However, the success of vector control may depend on prevailing vector species. It will be crucial to improve the coverage of screening programs, the performance of diagnostic tests, the proportion of people treated, and the efficacy of trypanocidal drugs. While screening and access can be incremented as part of strengthening the health systems response, improving diagnostics performance and drug efficacy will require further research

Population genomics of the Asian tiger mosquito, Aedes albopictus. Insights into the recent worldwide invasion

Aedes albopictus, the “Asian tiger mosquito,” is an aggressive biting mosquito native to Asia that has colonized all continents except Antarctica during the last ~30–40 years. The species is of great public health concern as it can transmit at least 26 arboviruses, including dengue, chikungunya, and Zika viruses. In this study, using double- digest Restriction site-Associated DNA (ddRAD) sequencing, we developed a panel of ~58,000 single nucleotide polymorphisms (SNPs) based on 20 worldwide Ae. albopic-tus populations representing both the invasive and the native range. We used this genomic- based approach to study the genetic structure and the differentiation of Ae. albopictus populations and to understand origin(s) and dynamics of the recent inva-sions. Our analyses indicated the existence of two major genetically differentiated population clusters, each one including both native and invasive populations. The de-tection of additional genetic structure within each major cluster supports that these SNPs can detect differentiation at a global and local scale, while the similar levels of genomic diversity between native and invasive range populations support the scenario of multiple invasions or colonization by a large number of propagules. Finally, our re-sults revealed the possible source(s) of the recent invasion in Americas, Europe, and Africa, a finding with important implications for vector- control strategies

Incorporating multiple sets of eQTL weights into gene-by-environment interaction analysis identifies novel susceptibility loci for pancreatic cancer.

It is of great scientific interest to identify interactions between genetic variants and environmental exposures that may modify the risk of complex diseases. However, larger sample sizes are usually required to detect gene-by-environment interaction (G × E) than required to detect genetic main association effects. To boost the statistical power and improve the understanding of the underlying molecular mechanisms, we incorporate functional genomics information, specifically, expression quantitative trait loci (eQTLs), into a data-adaptive G × E test, called aGEw. This test adaptively chooses the best eQTL weights from multiple tissues and provides an extra layer of weighting at the genetic variant level. Extensive simulations show that the aGEw test can control the Type 1 error rate, and the power is resilient to the inclusion of neutral variants and noninformative external weights. We applied the proposed aGEw test to the Pancreatic Cancer Case-Control Consortium (discovery cohort of 3,585 cases and 3,482 controls) and the PanScan II genome-wide association study data (replication cohort of 2,021 cases and 2,105 controls) with smoking as the exposure of interest. Two novel putative smoking-related pancreatic cancer susceptibility genes, TRIP10 and KDM3A, were identified. The aGEw test is implemented in an R package aGE.We thank the two anonymous reviewers for their constructive comments. This research was supported by the National Institutes of Health (NIH) grant R01CA169122; P.W. was supported by NIH grants R01HL116720 and R21HL126032. S.H.O. was supported by NIH grant P30CA008748. R.E.N. and the Queensland Pancreatic Cancer Study were funded by the Australian National Health and Medical Research Council. The authors thank Ms. Jessica Swann and the National Institute of Statistical Sciences writing workshop for editorial assistance and suggestions. The authors acknowledge the Texas Advanced Computing Center at The University of Texas at Austin for providing computing resources. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated. The authors declare that there is no conflict of interest

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

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

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

The second physical therapy summit on global health: developing an action plan to promote health in daily practice and reduce the burden of non-communicable diseases

Based on indicators that emerged from The First Physical Therapy Summit on Global Health (2007), the Second Summit (2011) identified themes to inform a global physical therapy action plan to integrate health promotion into practice across the World Confederation for Physical Therapy (WCPT) regions. Working questions were: (1) how well is health promotion implemented within physical therapy practice; and (2) how might this be improved across five target audiences (i.e. physical therapist practitioners, educators, researchers, professional body representatives, and government liaisons/consultants). In structured facilitated sessions, Summit representatives (n=32) discussed: (1) within WCPT regions, what is working and the challenges; and (2) across WCPT regions, what are potential directions using World CaféTM methodology. Commonalities outweighed differences with respect to strategies to advance health-focused physical therapy as a clinical competency across regions and within target audiences. Participants agreed that health-focused practice is a professional priority, and a strategic action plan was needed to develop it as a clinical competency. The action plan and recommendations largely paralleled the principles and objectives of the World Health Organization's non-communicable diseases action plan. A third Summit planned for 2015 will provide a mechanism for follow-up to evaluate progress in integrating health-focused physical therapy within the profession.info:eu-repo/semantics/acceptedVersio