Energy supply

The 2019 Exponential Roadmap focuses on moving from incremental to exponential climate action in the next decade. It presents 36 economically- viable solutions to cut global greenhouse gas emissions 50% by 2030 and the strategies to scale this transformation.The roadmap is consistent with the Paris Agreement’s goal to keep global average temperature “well below 2\ub0C” and aiming for 1.5\ub0C above pre- industrial levels.The 2019 roadmap is the second in the series. Each new roadmap updates solutions that have proven potential to scale and charts progress towards exponential scaling. The roadmap, based on the carbon law (see box) is a collaboration between academia, business and civil society.The roadmap is complemented with a high-ambition narrative, Meeting the 1.5\ub0C Ambition, that presents the case why holding global average temperature increase to just 1.5\ub0C above pre-industrial levels is important. Since the first roadmap, the Intergovernmental Panel on Climate Change (IPCC) published its special report on 1.5\ub0C. The report concluded that the economic and humanitarian risks of a 2\ub0C world are significantly higher than 1.5\ub0C.The remaining emissions budget for 1.5\ub0C is small, and will be exceeded within ten to fifteen years at current emission rates. The window of feasibility is closing rapidly.The global economic benefit of a low-carbon future is estimated at US$26 trillion by 2030 compared with staying on the current high-carbon pathway.The scale of transformation – halving emissions by 2030 – is unprecedented but the speed is not. Some cities and companies can transform significantly faster.Developed nations with significant historic emissions have a responsibility to reduce emissions faster.Greenhouse gas emissions, and the solutions to reduce them, are grouped by six sectors: energy, industry, transport, buildings, food consumption, nature-based solutions (sources and sinks).Meeting the 1.5\ub0C goal means implementing solutions in parallel across all sectors.The solutions must scale exponentially. The roadmap identifies four levers required to scale the transformation as well as necessary actions for each: policy, climate leadership and movements, finance and exponential technology.Implementation must be fair and just or risk deep resistance

Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants:an evaluation of the Danish strain 1331 SSI in a randomized clinical trial

AbstractObjectiveTo evaluate adverse reactions of the Bacillus Calmette–Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial.DesignA randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG or no intervention. Follow-up until 13 months of age.SettingPediatric and maternity wards at three Danish university hospitals.ParticipantsAll women planning to give birth at the three study sites (n=16,521) during the recruitment period were invited to participate in the study. Four thousand one hundred and eighty four families consented to participate and 4262 children, gestational age 32 weeks and above, were randomized: 2129 to BCG vaccine and 2133 to no vaccine. None of the participants withdrew because of adverse reactions.Main outcome and measureTrial-registered adverse reactions after BCG vaccination at birth. Follow-up at 3 and 13 months by telephone interviews and clinical examinations.ResultsAmong the 2118 BCG-vaccinated children we registered no cases of severe unexpected adverse reaction related to BCG vaccination and no cases of disseminated BCG disease. Two cases of regional lymphadenitis were hospitalized and thus classified as serious adverse reactions related to BCG. The most severe adverse reactions were 10 cases of suppurative lymphadenitis. This was nearly a fivefold increase compared to what was expected based on the summary of product characteristics of the vaccine. All cases were treated conservatively and recovered. Six of 10 (60%) families of children experiencing suppurative lymphadenitis compared to 117/2071 (6%) of those with no lymphadenitis indicated that the vaccine had more adverse effects than expected (p-value <0.001).Conclusions and relevanceBCG vaccination was associated with only mild morbidity and no mortality. A higher incidence of suppurative lymphadenitis than expected was observed. All children were treated conservatively without sequelae or complications.Trial registrationTrial registration number NCT01694108 at www.clinicaltrials.go

BCG vaccination at birth and early childhood hospitalisation:a randomised clinical multicentre trial

BACKGROUND: The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. METHODS: Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses. RESULTS: 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics. CONCLUSIONS: BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15 months of age in this Danish study population. TRIAL REGISTRATION NUMBER: NCT01694108, results

Biomass burning in eastern Europe during spring 2006 caused high deposition of ammonium in northern Fennoscandia

High air concentrations of ammonium were detected at low and high altitude sites in Sweden, Finland and Norway during the spring 2006, coinciding with polluted air from biomass burning in eastern Europe passing over central and northern Fennoscandia. Unusually high values for throughfall deposition of ammonium were detected at one low altitude site and several high altitude sites in north Sweden. The occurrence of the high ammonium in throughfall differed between the summer months 2006, most likely related to the timing of precipitation events. The ammonia dry deposition may have contributed to unusual visible injuries on the tree vegetation in northern Fennoscandia that occurred during 2006, in combination with high ozone concentrations. It is concluded that long-range transport of ammonium from large-scale biomass burning may contribute substantially to the nitrogen load at northern latitudes. (C) 2013 Elsevier Ltd. All rights reserved

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