Wardrop Equilibrium Can Be Boundedly Rational: A New Behavioral Theory of Route Choice

As one of the most fundamental concepts in transportation science, Wardrop equilibrium (WE) has always had a relatively weak behavioral underpinning. To strengthen this foundation, one must reckon with bounded rationality in human decision-making processes, such as the lack of accurate information, limited computing power, and sub-optimal choices. This retreat from behavioral perfectionism in the literature, however, was typically accompanied by a conceptual modification of WE. Here we show that giving up perfect rationality need not force a departure from WE. On the contrary, WE can be reached with global stability in a routing game played by boundedly rational travelers. We achieve this result by developing a day-to-day (DTD) dynamical model that mimics how travelers gradually adjust their route valuations, hence choice probabilities, based on past experiences. Our model, called cumulative logit (CULO), resembles the classical DTD models but makes a crucial change: whereas the classical models assume routes are valued based on the cost averaged over historical data, ours values the routes based on the cost accumulated. To describe route choice behaviors, the CULO model only uses two parameters, one accounting for the rate at which the future route cost is discounted in the valuation relative to the past ones and the other describing the sensitivity of route choice probabilities to valuation differences. We prove that the CULO model always converges to WE, regardless of the initial point, as long as the behavioral parameters satisfy certain mild conditions. Our theory thus upholds WE's role as a benchmark in transportation systems analysis. It also resolves the theoretical challenge posed by Harsanyi's instability problem by explaining why equally good routes at WE are selected with different probabilities

Telemobility Technical Report: Omnichannel Retail Fulfillment Strategies

69A3552047139In this research, we study the fulfillment strategies adopted by an omnichannel retailer in the post-pandemic context of a rapidly expanding e-commerce enterprise. The overarching goal is to identify what factors and circumstances influence the retailer\u2019s optimal fulfillment strategies, how the retailer should allocate resources between different fulfillment channels to maximize its profit, and how the fulfillment decisions affect traffic in road networks. To this end, we develop, analyze, and test a stylized model of omnichannel retail in three phases, of which the first two are included in this report. In the first, a base model considering a retailer that owns a large distribution center and a front-end store with limited space. The customers are assumed to be homogeneous and given three channels to choose from: in-store, online with membership (which promises express delivery), and online without membership. The retailer seeks to jointly optimize the inventory in the store, price differentiation across channels, and express delivery capacity while anticipating the uncertainty in the total demand for different channels. In the second phase, the base model is extended to accommodate customers\u2019 heterogeneous channel preferences by considering the channel-specific hassle costs as random variables that follow a joint distribution. For each model developed, we first perform theoretical analysis to generate useful insights. Numerical experiments are then conducted on a 1/3000 model of a retailer similar in scale to Amazon and Walmart, to validate the models and test their sensitivity to key parameters

Organocatalytic enantioselective Friedel-Crafts alkylation of 1-naphthol derivatives and activated phenols with ethyl trifluoropyruvate

An organocatalytic enantioselective Friedel-Crafts alkylation of a series of substituted 1‐naphthol derivatives and activated phenols with ethyl trifluoropyruvate, catalyzed by a quinine‐derived squaramide, is presented. Good yields and high to excellent enantioselectivities of the Friedel-Crafts alkylation products were obtained

Highly enantioselective copper(I)-catalyzed conjugate addition of 1,3-diynes to a,b-unsaturated trifluoromethyl ketones

[EN] The conjugate diynylation of a,b-unsaturated trifluoromethyl ketones is carried out in the presence of a low catalytic load (2.5 mol%) of a copper(I)–MeOBIPHEP complex, triethylamine and a terminal 1,3-diyne. Pre-metalation of the terminal 1,3-diyne with stoichiometric or higher amounts of dialkylzinc reagent is not required. The corresponding internal diynes bearing a propargylic stereogenic center are obtained with good yields and excellent enantioselectivities.Financial support from the Ministerio de Economia y Competitividad (MINECO-Gobierno de Espana) and FEDER (EU) (CTQ2013-47494-P) and from Generalitat Valenciana (ISIC2012/001) is gratefully acknowledged. A.S.-M. thanks the MINECO for a predoctoral grant (FPI program). Access to NMR and MS facilities from the Servei Central de Suport a la Investigacio Experimental (SCSIE)-UV is also acknowledged.Sanz-Marco, A.; Blay, G.; Muñoz Roca, MDC.; Pedro, J. (2015). Highly enantioselective copper(I)-catalyzed conjugate addition of 1,3-diynes to a,b-unsaturated trifluoromethyl ketones. Chemical Communications. (51):8958-8961. https://doi.org/10.1039/C5CC01676BS8958896151Shi Shun, A. L. K., & Tykwinski, R. R. (2006). Synthesis of Naturally Occurring Polyynes. Angewandte Chemie International Edition, 45(7), 1034-1057. doi:10.1002/anie.200502071Modern Acetylene Chemistry, ed. P. J. Stang and F. Diederich, VCH, Weinheim, 1995Sindhu, K. S., & Anilkumar, G. (2014). Recent advances and applications of Glaser coupling employing greener protocols. RSC Adv., 4(53), 27867-27887. doi:10.1039/c4ra02416hJung, H.-J., Min, B.-S., Park, J.-Y., Kim, Y.-H., Lee, H.-K., & Bae, K.-H. (2002). Gymnasterkoreaynes A−F, Cytotoxic Polyacetylenes fromGymnasterkoraiensis. Journal of Natural Products, 65(6), 897-901. doi:10.1021/np0104018Mayer, S. F., Steinreiber, A., Orru, R. V. A., & Faber, K. (2002). Chemoenzymatic Asymmetric Total Syntheses of Antitumor Agents (3R,9R,10R)- and (3S,9R,10R)-Panaxytriol and (R)- and (S)-Falcarinol fromPanaxginsengUsing an Enantioconvergent Enzyme-Triggered Cascade Reaction. The Journal of Organic Chemistry, 67(26), 9115-9121. doi:10.1021/jo020073wSatoh, Y., Satoh, M., Isobe, K., Mohri, K., Yoshida, Y., & Fujimoto, Y. (2007). Studies on Panax Acetylenes: Absolute Structure of a New Panax Acetylene, and Inhibitory Effects of Related Acetylenes on the Growth of L-1210 Cells. CHEMICAL & PHARMACEUTICAL BULLETIN, 55(4), 561-564. doi:10.1248/cpb.55.561McLaughlin, N. P., Butler, E., Evans, P., Brunton, N. P., Koidis, A., & Rai, D. K. (2010). A short synthesis of (+) and (−)-falcarinol. Tetrahedron, 66(51), 9681-9687. doi:10.1016/j.tet.2010.10.049Shin, D., Yang, J.-E., Lee, S. B., & Nho, C. W. (2010). SAR studies of gymnasterkoreayne derivatives with cancer chemopreventive activities. 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Hydro-amination/-amidation of 1,3-diynes with indoles/azoles/amides under modified Ullmann conditions: stereo- and regio-selective synthesis of N-alkenynes via N–H bond activation. Tetrahedron Letters, 52(44), 5752-5757. doi:10.1016/j.tetlet.2011.08.079Cho, E. J., Kim, M., & Lee, D. (2006). Reactivity and Selectivity of 1,3-Diyn-6-enes in Electrophilic Transition Metal-Catalyzed Reactions. Organic Letters, 8(23), 5413-5416. doi:10.1021/ol062335cTrost, B. M., & Weiss, A. H. (2009). The Enantioselective Addition of Alkyne Nucleophiles to Carbonyl Groups. Advanced Synthesis & Catalysis, 351(7-8), 963-983. doi:10.1002/adsc.200800776Blay, G., Monleon, A., & Pedro, J. (2009). Recent Developments in Asymmetric Alkynylation of Imines. Current Organic Chemistry, 13(15), 1498-1539. doi:10.2174/138527209789177734Knöpfel, T. F., Zarotti, P., Ichikawa, T., & Carreira, E. M. (2005). Catalytic, Enantioselective, Conjugate Alkyne Addition. Journal of the American Chemical Society, 127(27), 9682-9683. doi:10.1021/ja052411rYazaki, R., Kumagai, N., & Shibasaki, M. (2010). Direct Catalytic Asymmetric Conjugate Addition of Terminal Alkynes to α,β-Unsaturated Thioamides. Journal of the American Chemical Society, 132(30), 10275-10277. doi:10.1021/ja105141xYazaki, R., Kumagai, N., & Shibasaki, M. (2011). Enantioselective Synthesis of a GPR40 Agonist AMG 837 via Catalytic Asymmetric Conjugate Addition of Terminal Alkyne to α,β-Unsaturated Thioamide. Organic Letters, 13(5), 952-955. doi:10.1021/ol102998wSanz-Marco, A., García-Ortiz, A., Blay, G., & Pedro, J. R. (2014). Catalytic asymmetric conjugate addition of terminal alkynes to β-trifluoromethyl α,β-enones. Chem. Commun., 50(18), 2275-2278. doi:10.1039/c3cc48508kSanz-Marco, A., García-Ortiz, A., Blay, G., Fernández, I., & Pedro, J. R. (2013). Highly Enantioselective Copper(I)-Catalyzed Conjugate Addition of Terminal Alkynes to 1,1-Difluoro-1-(phenylsulfonyl)-3-en-2-ones: New Ester/Amide Surrogates in Asymmetric Catalysis. Chemistry - A European Journal, 20(3), 668-672. doi:10.1002/chem.201303920Nishimura, T., Guo, X.-X., Uchiyama, N., Katoh, T., & Hayashi, T. (2008). Steric Tuning of Silylacetylenes and Chiral Phosphine Ligands for Rhodium-Catalyzed Asymmetric Conjugate Alkynylation of Enones. Journal of the American Chemical Society, 130(5), 1576-1577. doi:10.1021/ja710540sNishimura, T., Sawano, T., & Hayashi, T. (2009). Asymmetric Synthesis of β-Alkynyl Aldehydes by Rhodium-Catalyzed Conjugate Alkynylation. Angewandte Chemie International Edition, 48(43), 8057-8059. doi:10.1002/anie.200904486Fillion, E., & Zorzitto, A. K. (2009). Enantioselective Rhodium-Catalyzed Conjugate Alkynylation of 5-Benzylidene Meldrum’s Acids with TMS-acetylene. Journal of the American Chemical Society, 131(41), 14608-14609. doi:10.1021/ja905336pBlay, G., Cardona, L., Pedro, J. R., & Sanz-Marco, A. (2012). Enantioselective Zinc-Mediated Conjugate Addition of Terminal Alkynes to Enones. Chemistry - A European Journal, 18(41), 12966-12969. doi:10.1002/chem.201201765Blay, G., Muñoz, M. C., Pedro, J. R., & Sanz-Marco, A. (2013). Enantioselective Synthesis of 4-Substituted Dihydrocoumarins through a Zinc Bis(hydroxyamide)-Catalyzed Conjugate Addition of Terminal Alkynes. Advanced Synthesis & Catalysis, 355(6), 1071-1076. doi:10.1002/adsc.201201120Cui, S., Walker, S. D., Woo, J. C. S., Borths, C. J., Mukherjee, H., Chen, M. J., & Faul, M. M. (2010). Practical Asymmetric Conjugate Alkynylation of Meldrum’s Acid-Derived Acceptors: Access to Chiral β-Alkynyl Acids. Journal of the American Chemical Society, 132(2), 436-437. doi:10.1021/ja909105sKwak, Y.-S., & Corey, E. J. (2004). Catalytic Enantioselective Conjugate Addition of Trimethylsilylacetylene to 2-Cyclohexen-1-one. Organic Letters, 6(19), 3385-3388. doi:10.1021/ol048623vLarionov, O. V., & Corey, E. J. (2010). Ni(II)-Catalyzed Enantioselective Conjugate Addition of Acetylenes to α,β-Enones. Organic Letters, 12(2), 300-302. doi:10.1021/ol902643wReber, S., Knöpfel, T. F., & Carreira, E. M. (2003). Enantioselective total synthesis of (R)-strongylodiols A and B. Tetrahedron, 59(35), 6813-6817. doi:10.1016/s0040-4020(03)00905-0Trost, B. M., Chan, V. S., & Yamamoto, D. (2010). Enantioselective ProPhenol-Catalyzed Addition of 1,3-Diynes to Aldehydes to Generate Synthetically Versatile Building Blocks and Diyne Natural Products. Journal of the American Chemical Society, 132(14), 5186-5192. doi:10.1021/ja910656bTurlington, M., Du, Y., Ostrum, S. G., Santosh, V., Wren, K., Lin, T., … Pu, L. (2011). From Highly Enantioselective Catalytic Reaction of 1,3-Diynes with Aldehydes to Facile Asymmetric Synthesis of Polycyclic Compounds. Journal of the American Chemical Society, 133(30), 11780-11794. doi:10.1021/ja204289qGraham, E. R., & Tykwinski, R. R. (2011). Chiral Propargyl Alcohols via the Enantioselective Addition of Terminal Di- and Triynes to Aldehydes. The Journal of Organic Chemistry, 76(16), 6574-6583. doi:10.1021/jo2008719Zheng, B., Li, S.-N., Mao, J.-Y., Wang, B., Bian, Q.-H., Liu, S.-Z., … Wang, M. (2012). Highly Enantioselective Addition of 1,3-Diynes to Aldehydes Catalyzed by a Zinc-Amino Alcohol Complex. Chemistry - A European Journal, 18(30), 9208-9211. doi:10.1002/chem.201200728Liu, T.-L., Ma, H., Zhang, F.-G., Zheng, Y., Nie, J., & Ma, J.-A. (2011). Catalytic enantioselective addition of terminal 1,3-diynes to aromatic ketones: facile access to chiral nonracemic tertiary alcohols. Chemical Communications, 47(48), 12873. doi:10.1039/c1cc15968bLiu, T.-L., Zhang, H.-X., Zheng, Y., Yao, Q., & Ma, J.-A. (2012). Catalytic enantioselective addition of terminal 1,3-diynes to N-sulfonyl aldimines: access to chiral diynylated carbinamines. Chemical Communications, 48(100), 12234. doi:10.1039/c2cc37290hZhang, F.-G., Ma, H., Zheng, Y., & Ma, J.-A. (2012). Zinc-mediated enantioselective addition of terminal 1,3-diynes to N-arylimines of trifluoropyruvates. Tetrahedron, 68(37), 7663-7669. doi:10.1016/j.tet.2012.05.086Zhang, F.-G., Ma, H., Nie, J., Zheng, Y., Gao, Q., & Ma, J.-A. (2012). Enantioselective Diynylation of Cyclic N-Acyl Ketimines: Access to Chiral Trifluoromethylated Tertiary Carbinamines. Advanced Synthesis & Catalysis, 354(8), 1422-1428. doi:10.1002/adsc.201100926Nie, J., Guo, H.-C., Cahard, D., & Ma, J.-A. (2011). Asymmetric Construction of Stereogenic Carbon Centers Featuring a Trifluoromethyl Group from Prochiral Trifluoromethylated Substrates. Chemical Reviews, 111(2), 455-529. doi:10.1021/cr100166aCahard, D., Xu, X., Couve-Bonnaire, S., & Pannecoucke, X. (2010). Fluorine & chirality: how to create a nonracemic stereogenic carbon–fluorine centre? Chem. Soc. Rev., 39(2), 558-568. doi:10.1039/b909566gKirk, K. L. (2008). Fluorination in Medicinal Chemistry: Methods, Strategies, and Recent Developments. Organic Process Research & Development, 12(2), 305-321. doi:10.1021/op700134jMa, J.-A., & Cahard, D. (2008). Update 1 of: Asymmetric Fluorination, Trifluoromethylation, and Perfluoroalkylation Reactions. Chemical Reviews, 108(9), PR1-PR43. doi:10.1021/cr800221vPurser, S., Moore, P. R., Swallow, S., & Gouverneur, V. (2008). Fluorine in medicinal chemistry. Chem. Soc. Rev., 37(2), 320-330. doi:10.1039/b610213cMorrill, L. C., Smith, S. M., Slawin, A. M. Z., & Smith, A. D. (2014). Isothiourea-Mediated Asymmetric Functionalization of 3-Alkenoic Acids. The Journal of Organic Chemistry, 79(4), 1640-1655. doi:10.1021/jo402591vYeh, P.-P., Daniels, D. S. B., Cordes, D. B., Slawin, A. M. Z., & Smith, A. D. (2014). Isothiourea-Mediated One-Pot Synthesis of Trifluoromethyl Substituted 2-Pyrones. Organic Letters, 16(3), 964-967. doi:10.1021/ol403697hMorrill, L. C., Douglas, J., Lebl, T., Slawin, A. M. Z., Fox, D. J., & Smith, A. D. (2013). Isothiourea-mediated asymmetric Michael-lactonisation of trifluoromethylenones: a synthetic and mechanistic study. Chemical Science, 4(11), 4146. doi:10.1039/c3sc51791hPei, Z., Zheng, Y., Nie, J., & Ma, J.-A. (2010). Chiral Brønsted acid-catalyzed regio- and enantioselective arylation of α,β-unsaturated trifluoromethyl ketones. Tetrahedron Letters, 51(35), 4658-4661. doi:10.1016/j.tetlet.2010.06.132Sasaki, S., Yamauchi, T., & Higashiyama, K. (2010). Dy(OTf)3/Pybox-catalyzed enantioselective Friedel–Crafts alkylation of indoles with α,β-unsaturated trifluoromethyl ketones. Tetrahedron Letters, 51(17), 2326-2328. doi:10.1016/j.tetlet.2010.02.121Li, P., Chai, Z., Zhao, S.-L., Yang, Y.-Q., Wang, H.-F., Zheng, C.-W., … Zhu, S.-Z. (2009). Highly enantio- and diastereoselective synthesis of α-trifluoromethyldihydropyrans using a novel bifunctional piperazine-thiourea catalyst. Chemical Communications, (47), 7369. doi:10.1039/b915210eZheng, C., Li, Y., Yang, Y., Wang, H., Cui, H., Zhang, J., & Zhao, G. (2009). Highly Efficient Asymmetric Epoxidation of Electron-Deficient α,β-Enones and Related Applications to Organic Synthesis. Advanced Synthesis & Catalysis, 351(10), 1685-1691. doi:10.1002/adsc.200900041Zhang, G.-W., Meng, W., Ma, H., Nie, J., Zhang, W.-Q., & Ma, J.-A. (2011). Catalytic Enantioselective Alkynylation of Trifluoromethyl Ketones: Pronounced Metal Fluoride Effects and Implications of Zinc-to-Titanium Transmetallation. Angewandte Chemie International Edition, 50(15), 3538-3542. doi:10.1002/anie.201007341Liu, Z.-J., & Liu, J.-T. (2008). 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ChemCatChem, 6(2), 580-591. doi:10.1002/cctc.20130087

Polymer functionalized nanocomposites for metals removal from water and wastewater: An overview

Pollution by metal and metalloid ions is one of the most widespread environmental concerns. They are non-biodegradable, and, generally, present high water solubility facilitating their environmental mobilisation interacting with abiotic and biotic components such as adsorption onto natural colloids or even accumulation by living organisms, thus, threatening human health and ecosystems. Therefore, there is a high demand for effective removal treatments of heavy metals, making the application of adsorption materials such as polymer-functionalized nanocomposites (PFNCs), increasingly attractive. PFNCs retain the inherent remarkable surface properties of nanoparticles, while the polymeric support materials provide high stability and processability. These nanoparticle-matrix materials are of great interest for metals and metalloids removal thanks to the functional groups of the polymeric matrixes that provide specific bindings to target pollutants. This review discusses PFNCs synthesis, characterization and performance in adsorption processes as well as the potential environmental risks and perspectives. (C) 2016 Elsevier Ltd. All rights reserved

3D bioactive composite scaffolds for bone tissue engineering

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed

Mapping child growth failure across low- and middle-income countries

Child growth failure (CGF), manifested as stunting, wasting, and underweight, is associated with high 5 mortality and increased risks of cognitive, physical, and metabolic impairments. Children in low- and middle-income countries (LMICs) face the highest levels of CGF globally. Here we illustrate national and subnational variation of under-5 CGF indicators across LMICs, providing 2000–2017 annual estimates mapped at a high spatial resolution and aggregated to policy-relevant administrative units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the World Health 10 Organization’s ambitious Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and rates of progress exist across regions, countries, and within countries; our maps identify areas where high prevalence persists even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where subnational disparities exist and the highest-need populations reside, these geospatial estimates can support policy-makers in planning locally 15 tailored interventions and efficient directing of resources to accelerate progress in reducing CGF and its health implications

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

Background: Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades. Methods: Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings: In 2019, 369 061 deaths (of which 214 337 [58%] were transport related) and 31·1 million DALYs (of which 16·2 million [52%] were transport related) among adolescents aged 10–24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34·4% (from 17·5 to 11·5 per 100 000) for transport injuries, and by 47·7% (from 15·9 to 8·3 per 100 000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80·5% to 42 774 for transport injuries and by 39·4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010–19, the rate per 100 000 of transport injury DALYs was reduced by 16·7%, from 838 in 2010 to 699 in 2019. This was a substantially slower pace of reduction compared with the 48·5% reduction between 1990 and 2010, from 1626 per 100 000 in 1990 to 838 per 100 000 in 2010. Between 2010 and 2019, the rate of unintentional injury DALYs per 100 000 also remained largely unchanged in high-SDI countries (555 in 2010 vs 554 in 2019; 0·2% reduction). The number and rate of adolescent deaths and DALYs owing to environmental heat and cold exposure increased for the high-SDI quintile during 2010–19. Interpretation: As other causes of mortality are addressed, inadequate progress in reducing transport and unintentional injury mortality as a proportion of adolescent deaths becomes apparent. The relative shift in the burden of injury from high-SDI countries to low and low–middle-SDI countries necessitates focused action, including global donor, government, and industry investment in injury prevention. The persisting burden of DALYs related to transport and unintentional injuries indicates a need to prioritise innovative measures for the primary prevention of adolescent injury. Funding: Bill & Melinda Gates Foundation

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts