Brief report: Using global positioning system (GPS) enabled cell phones to examine adolescent travel patterns and time in proximity to alcohol outlets

As adolescents gain freedom to explore new environments unsupervised, more time in proximity to alcohol outlets may increase risks for alcohol and marijuana use. This pilot study: 1) Describes variations in adolescents' proximity to outlets by time of day and day of the week, 2) Examines variations in outlet proximity by drinking and marijuana use status, and 3) Tests feasibility of obtaining real-time data to study adolescent proximity to outlets. U.S. adolescents (N = 18) aged 16–17 (50% female) carried GPS-enabled smartphones for one week with their locations tracked. The geographic areas where adolescents spend time, activity spaces, were created by connecting GPS points sequentially and adding spatial buffers around routes. Proximity to outlets was greater during after school and evening hours. Drinkers and marijuana users were in proximity to outlets 1½ to 2 times more than non-users. Findings provide information about where adolescents spend time and times of greatest risk, informing prevention efforts

Deepening the Relational Ecology of Restorative Justice

It is our pleasure to introduce and frame this Special Issue of The International Journal of Restorative Justice. This Special Issue seeks to advance and expand thinking, research and practice of a restorative approach at the level of institutions and social systems, from families to workplaces. The articles and notes from the field included here were developed out of the 2016 International Conference in Halifax, Nova Scotia, that shared the title and focus of this issue. The conference was held to fulfil a commitment made by the parties involved in a restorative justice process at the Faculty of Dentistry, Dalhousie University, in 2015 (Llewellyn et al, 2015). As Mary McNally\u27s note from the field (this issue) explains, the process was undertaken to deal with harms related to a private Facebook group that contained sexist and other harmful comments from a group of male fourth-year students directed at their female classmates and more generally reflecting unprofessional behaviour.\u27 Many in the university, the professional and the general public assumed that the restorative justice process was focused at the level of the interpersonal relationships and harms involved in the incident. In fact, however, the process revealed and responded to the significant institutional climate and culture issues that were reflected in and structuring the interpersonal relationships involved. It also became clear through the process that examining and shifting interpersonal relationships was the key to bringing the institutional level changes required within the faculty, the university and the profession to address the issues and harms involved and to bring change for the future. This broader focus brought by a restorative approach was surprising to many outside and even some inside the field of restorative justice. It stretched the relational ecology of restorative justice from the use of tools and practices for conflict resolution and discipline to the level of institutions and systems by attending to their relational nature and impact expressed through climate and culture

ALMA 1.3 Millimeter Map of the HD 95086 System

Planets and minor bodies such as asteroids, Kuiper-belt objects and comets are integral components of a planetary system. Interactions among them leave clues about the formation process of a planetary system. The signature of such interactions is most prominent through observations of its debris disk at millimeter wavelengths where emission is dominated by the population of large grains that stay close to their parent bodies. Here we present ALMA 1.3 mm observations of HD 95086, a young early-type star that hosts a directly imaged giant planet b and a massive debris disk with both asteroid- and Kuiper-belt analogs. The location of the Kuiper-belt analog is resolved for the first time. The system can be depicted as a broad ($\Delta R/R \sim$0.84), inclined (30\arcdeg$\pm$3\arcdeg) ring with millimeter emission peaked at 200$\pm$6 au from the star. The 1.3 mm disk emission is consistent with a broad disk with sharp boundaries from 106$\pm$6 to 320$\pm$20 au with a surface density distribution described by a power law with an index of --0.5$\pm$0.2. Our deep ALMA map also reveals a bright source located near the edge of the ring, whose brightness at 1.3 mm and potential spectral energy distribution are consistent with it being a luminous star-forming galaxy at high redshift. We set constraints on the orbital properties of planet b assuming co-planarity with the observed disk.Comment: accepted for publication in A

Associations of sedentary behaviour, physical activity, blood pressure and anthropometric measures with cardiorespiratory fitness in children with cerebral palsy

Background - Children with cerebral palsy (CP) have poor cardiorespiratory fitness in comparison to their peers with typical development, which may be due to low levels of physical activity. Poor cardiorespiratory fitness may contribute to increased cardiometabolic risk. Purpose - The aim of this study was to determine the association between sedentary behaviour, physical activity and cardiorespiratory fitness in children with CP. An objective was to determine the association between cardiorespiratory fitness, anthropometric measures and blood pressure in children with CP. Methods- This study included 55 ambulatory children with CP [mean (SD) age 11.3 (0.2) yr, range 6-17 yr; Gross Motor Function Classification System (GMFCS) levels I and II]. Anthropometric measures (BMI, waist circumference and waist-height ratio) and blood pressure were taken. Cardiorespiratory fitness was measured using a 10 m shuttle run test. Children were classified as low, middle and high fitness according to level achieved on the test using reference curves. Physical activity was measured by accelerometry over 7 days. In addition to total activity, time in sedentary behaviour and light, moderate, vigorous, and sustained moderate-to-vigorous activity (≥10 min bouts) were calculated. Results - Multiple regression analyses revealed that vigorous activity (β = 0.339, p<0.01), sustained moderate-to-vigorous activity (β = 0.250, p<0.05) and total activity (β = 0.238, p<0.05) were associated with level achieved on the shuttle run test after adjustment for age, sex and GMFCS level. Children with high fitness spent more time in vigorous activity than children with middle fitness (p<0.05). Shuttle run test level was negatively associated with BMI (r2 = -0.451, p<0.01), waist circumference (r2 = -0.560, p<0.001), waist-height ratio (r2 = -0.560, p<0.001) and systolic blood pressure (r2 = -0.306, p<0.05) after adjustment for age, sex and GMFCS level. Conclusions - Participation in physical activity, particularly at a vigorous intensity, is associated with high cardiorespiratory fitness in children with CP. Low cardiorespiratory fitness is associated with increased cardiometabolic risk

Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK and Ireland and the impact on major congenital malformations

Objectives: After 20 years of data collection, pregnancy registers have informed prescribing practice. Various populations show trends for a reduction in valproate prescribing, which is associated with an increased risk of anatomical teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim was to determine if any shifts in prescribing trends have occurred in the UK and Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been any change in the overall major congenital malformation (MCM) rate over time. Methods: The UK and Ireland Epilepsy and Pregnancy Register, a prospective, observational, registration and follow-up study established in 1996, was used to determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and the MCM rate between 1996 and 2016. Linear regression analysis was used to assess changes in AED utilisation, and Poisson regression was used for the analysis of trends in the MCM rates. Results: Outcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (p<0.003) changes were found in monotherapy prescribing with increases in lamotrigine and levetiracetam and decreases in valproate and carbamazepine use. Between 1996 and 2016, the total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95% CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not statistically significant p=0.08). Conclusion: Significant changes are seen in the prescribing habits in this cohort over 20 years, but a statistically significant change in the MCM rate was not detected. This work should be replicated on a larger scale to determine if significant changes are occurring in the MCM rate, which would allow a robust economic estimate of the benefits of improvements in prescribing practice and the personal effect of such changes

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

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 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