Small-scale CMB Temperature and Polarization Anisotropies due to Patchy Reionization

We study contributions from inhomogeneous (patchy) reionization to arcminute scale ($1000 < \ell < 10,000$) cosmic microwave background (CMB) anisotropies. We show that inhomogeneities in the ionization fraction, rather than in the mean density, dominate both the temperature and the polarization power spectra. Depending on the ionization history and the clustering bias of the ionizing sources, we find that rms temperature fluctuations range from 2 $\mu$K to 8 $\mu$K and the corresponding values for polarization are over two orders of magnitude smaller. Reionization can significantly bias cosmological parameter estimates and degrade gravitational lensing potential reconstruction from temperature maps but not from polarization maps. We demonstrate that a simple modeling of the reionization temperature power spectrum may be sufficient to remove the parameter bias. The high-$\ell$ temperature power spectrum will contain some limited information about the sources of reionization.Comment: 11 pages, 8 figures. Minor changes to match version accepted by Ap

A Trajectory Calculus for Qualitative Spatial Reasoning Using Answer Set Programming

Spatial information is often expressed using qualitative terms such as natural language expressions instead of coordinates; reasoning over such terms has several practical applications, such as bus routes planning. Representing and reasoning on trajectories is a specific case of qualitative spatial reasoning that focuses on moving objects and their paths. In this work, we propose two versions of a trajectory calculus based on the allowed properties over trajectories, where trajectories are defined as a sequence of non-overlapping regions of a partitioned map. More specifically, if a given trajectory is allowed to start and finish at the same region, 6 base relations are defined (TC-6). If a given trajectory should have different start and finish regions but cycles are allowed within, 10 base relations are defined (TC-10). Both versions of the calculus are implemented as ASP programs; we propose several different encodings, including a generalised program capable of encoding any qualitative calculus in ASP. All proposed encodings are experimentally evaluated using a real-world dataset. Experiment results show that the best performing implementation can scale up to an input of 250 trajectories for TC-6 and 150 trajectories for TC-10 for the problem of discovering a consistent configuration, a significant improvement compared to previous ASP implementations for similar qualitative spatial and temporal calculi. This manuscript is under consideration for acceptance in TPLP.Comment: Paper presented at the 34th International Conference on Logic Programming (ICLP 2018), Oxford, UK, July 14 to July 17, 2018, 20 pages, LaTeX, 16 figure

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

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Feasibility and acceptability of a dietary intervention study to reduce salt intake and increase high-nitrate vegetable consumption among middle-aged and older Malaysian adults with elevated blood pressure: a study protocol

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420Introduction Global population ageing is one of the key factors linked to the projected rise of dementia incidence. Hence, there is a clear need to identify strategies to overcome this expected health burden and have a meaningful impact on populations’ health worldwide. Current evidence supports the role of modifiable dietary and lifestyle risk factors in reducing the risk of dementia. In South-East Asia, changes in eating and lifestyle patterns under the influence of westernised habits have resulted in significant increases in the prevalence of metabolic, cardiovascular and neurodegenerative non-communicable diseases (NCDs). Low vegetable consumption and high sodium intake have been identified as key contributors to the increased prevalence of NCDs in these countries. Therefore, nutritional and lifestyle strategies targeting these dietary risk factors are warranted. The overall objective of this randomised feasibility trial is to demonstrate the acceptability of a dietary intervention to increase the consumption of high-nitrate green leafy vegetables and reduce salt intake over 6 months among Malaysian adults with raised blood pressure. Methods and analysis Primary outcomes focus on feasibility measures of recruitment, retention, implementation and acceptability of the intervention. Secondary outcomes will include blood pressure, cognitive function, body composition and physical function (including muscle strength and gait speed). Adherence to the dietary intervention will be assessed through collection of biological samples, 24-hour recall and Food Frequency Questionnaire. A subgroup of participants will also complete postintervention focus groups to further explore the feasibility considerations of executing a larger trial, the ability of these individuals to make dietary changes and the barriers and facilitators associated with implementing these changes.http://dx.doi.org/10.1136/bmjopen-2019-03545310pubpub

Lightweight parametric optimisation method for cellular structures in additive manufactured parts

The application of cellular structures in additive manufactured parts combined with lightweight optimisation has an enormous potential, reducing weight, production time and cost. This paper presents a new method based on design of experiments, metamodels and genetic algorithms (combined with Computer Aided Design and Finite Element Method tools) to accomplish lightweight parametric optimisation of cellular structures in additive manufactured parts. Some specific strategies were implemented in the developed optimisation method to improve the performance compared with conventional methods. These strategies intensify the sampling for the surrogate model refinement in areas close to the feasible/unfeasible border, where the optimum is expected. The method was tested in different case studies and compared with a conventional optimisation tool based on the Box-Behnken design of experiments and the response surface method metamodel. The proposed method enhances the results (3–4.2% of improvement) in all the case studies, with a similar optimisation time. Compared with a previous version created during the development of the methodology, the final version achieves a similar quality of the optimum in lower optimisation time