Investigating the language of time: Evaluating the use and comprehension of before and after

Before-initial sentences are thought to be more difficult to comprehend than after-initial sentences because they structurally mismatch the temporal order of real-world events (Münte et al., 1998). Although event knowledge is known to affect how people understand before/after-initial sentences, little is known about the role of language knowledge in comprehending these sentences. A corpus analysis of before/after-initial sentences revealed that before typically is paired with a pronoun (Before he…) whereas after is paired with verb-ing (After leaving…). Participants\u27 eyes were tracked while they read Before/After-pronoun/verbing sentences. Reading times did not match the corpus statistics. The beginning of verbing-sentences was read faster than pronoun-sentences regardless of whether they began with before or after. Reading times were similar for before- and after-initial sentences. The results suggest that when people read natural sounding sentences, they do not have difficulty with sentences in which the order of events mismatches real world temporal order

Targeted advertisement of chlamydia screening on social media: A mixed-methods analysis

Objective Chlamydia is one of the most common sexually transmitted infections in teenagers and young adults. This study used a mixed-methods analysis to investigate targeted promotion of chlamydia home-testing on social media. Methods Our first study, in which face-to-face interviews with young women were conducted, sought to explore their attitudes and preferences towards social media-based health promotion. Our second study used Facebook and Google analytics to examine visits to a chlamydia testing page (where chlamydia testing kits could be ordered online), both before and after a targeted Facebook-based health promotion campaign was conducted. Results The interviews revealed Facebook to be the preferred choice of social media, with participants perceiving it to be a powerful and far-reaching platform for social interaction. Participants also highlighted several aspects of promotional content to be important at increasing engagement with the target population, including appropriate use of colour, level of interactivity, use of humour and anonymity. The website analysis showed a 277% increase in the direct entrance on the chlamydia testing kit page and a 41% increase in chlamydia test kit orders, in comparison with the baseline period prior to the intervention. Conclusions The findings support social media as an engaging medium for the online promotion of chlamydia self-testing and implicate Facebook advertising as a useful tool in addition to community-based chlamydia screening services. Future research needs to identify whether targeted social media-based health promotion could lead to higher chlamydia diagnosis rate in comparison to traditional communication channels

Review of Fluorescence Guided Surgery Systems: Identification of Key Performance Capabilities Beyond Indocyanine Green Imaging

There is growing interest in using fluorescence imaging instruments to guide surgery, and the leading options for open-field imaging are reviewed here. While the clinical fluorescence-guided surgery (FGS) field has been focused predominantly on indocyanine green (ICG) imaging, there is accelerated development of more specific molecular tracers. These agents should help advance new indications for which FGS presents a paradigm shift in how molecular information is provided for resection decisions. There has been a steady growth in commercially marketed FGS systems, each with their own differentiated performance characteristics and specifications. A set of desirable criteria is presented to guide the evaluation of instruments, including: (i) real-time overlay of white-light and fluorescence images, (ii) operation within ambient room lighting, (iii) nanomolar-level sensitivity, (iv) quantitative capabilities, (v) simultaneous multiple fluorophore imaging, and (vi) ergonomic utility for open surgery. In this review, United States Food and Drug Administration 510(k) cleared commercial systems and some leading premarket FGS research systems were evaluated to illustrate the continual increase in this performance feature base. Generally, the systems designed for ICG-only imaging have sufficient sensitivity to ICG, but a fraction of the other desired features listed above, with both lower sensitivity and dynamic range. In comparison, the emerging research systems targeted for use with molecular agents have unique capabilities that will be essential for successful clinical imaging studies with low-concentration agents or where superior rejection of ambient light is needed. There is no perfect imaging system, but the feature differences among them are important differentiators in their utility, as outlined in the data and tables here

DPOAEs in Children With Sickle Cell Disease

The purpose of this study was to investigate distortion product otoacoustic emissions (DPOAEs) in young normal-hearing children with sickle cell disease (SCD). It was hypothesized that the prevalence of DPOAEs and response amplitudes would be lower than those in children with normal hemoglobin due to suspected compromised cochlear function as a result of vaso-occlusive events characteristic of SCD. Twenty African-American children with SCD and 15 African-American children with normal hemoglobin participated. Distortion product OAEs were evoked by thirteen primary tone pairs with f2 frequencies ranging from 1000 to 4500 Hz. The primary tones were presented at and L1 and L2 levels of 70 and 60 dB SPL (high) and 50 and 40 dB SPL (low), respectively. The findings of this study were completely unexpected and contrary to our original hypotheses. The likelihood of detecting a DPOAE response was not related to the clinical status of the children. Distortion product OAE amplitudes were significantly larger for children with SCD (p = .01). Educational Objectives: After completing this article the reader will (1) have a basic knowledge of the audiometric complications of sickle cell disease and (2) appreciate the differences in DPOAEs between young normal-hearing children with sickle cell DPOAEs in Children With Sickle Cell Disease 3 disease and young normal-hearing children with normal hemoglobin

Epigenome-wide association study of asthma- and wheeze characterizes loci within HK1

Background:To identify novel epigenetic markers of adolescent asthma and replicate findings in an independent cohort, then explore whether such markers are detectable at birth, predictive of early-life wheeze, and associated with gene expression in cord blood.Methods:We performed epigenome-wide screening with recursive random forest feature selection and internal validation in the IOW birth cohort. We then tested whether we could replicate these findings in the independent cohort ALSPAC and followed-up our top finding with children of the IOW cohort.Results:We identified 10 CpG sites associated with adolescent asthma at a 5% false discovery rate (IOW, n = 370), five of which exhibited evidence of associations in the replication study (ALSPAC, n = 720). One site, cg16658191, within HK1 displayed particularly strong associations after cellular heterogeneity adjustments in both cohorts (ORIOW = 0.17, 95% CI 0.04–0.57) (ORALSPAC = 0.57, 95% CI 0.38–0.87). Additionally, higher expression of HK1 (OR = 3.81, 95% CI 1.41–11.77) in cord blood was predictive of wheezing in infancy (n = 82).Conclusion:We identified novel associations between asthma and wheeze with methylation at cg16658191 and the expression of HK1, which may serve as markers of, predictors of, and potentially etiologic factors involved in asthma and early life wheeze

Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course

Rationale: We aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course. Methods: We meta-analysed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio and forced expiratory flow at 75% of FVC at ages 7-13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes. Results: We identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and nine with COPD in adulthood. Genes annotated to the top 10 identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways. Interpretation: Our findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course

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