The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

A Genome-Wide Association Study of the Maize Hypersensitive Defense Response Identifies Genes That Cluster in Related Pathways

<div><p>Much remains unknown of molecular events controlling the plant hypersensitive defense response (HR), a rapid localized cell death that limits pathogen spread and is mediated by resistance (R-) genes. Genetic control of the HR is hard to quantify due to its microscopic and rapid nature. Natural modifiers of the ectopic HR phenotype induced by an aberrant auto-active R-gene (<i>Rp1-D21</i>), were mapped in a population of 3,381 recombinant inbred lines from the maize nested association mapping population. Joint linkage analysis was conducted to identify 32 additive but no epistatic quantitative trait loci (QTL) using a linkage map based on more than 7000 single nucleotide polymorphisms (SNPs). Genome-wide association (GWA) analysis of 26.5 million SNPs was conducted after adjusting for background QTL. GWA identified associated SNPs that colocalized with 44 candidate genes. Thirty-six of these genes colocalized within 23 of the 32 QTL identified by joint linkage analysis. The candidate genes included genes predicted to be in involved programmed cell death, defense response, ubiquitination, redox homeostasis, autophagy, calcium signalling, lignin biosynthesis and cell wall modification. Twelve of the candidate genes showed significant differential expression between isogenic lines differing for the presence of <i>Rp1-D21</i>. Low but significant correlations between HR-related traits and several previously-measured disease resistance traits suggested that the genetic control of these traits was substantially, though not entirely, independent. This study provides the first system-wide analysis of natural variation that modulates the HR response in plants.</p></div

Heat map showing additive allelic effects for the HTR across 24 NAM founder lines relative to the common B73 parent.

<p>Chromosome and genetic map positions (centiMorgans; cM) of QTL peaks are shown on the left vertical axis, the contribution to variance among RIL mean values across all 24 NAM populations are shown on right vertical axis and the NAM founder lines are shown on the horizontal axis. Scale below heat map indicates range of allelic effect values and corresponding color intensity. Boxes with asterisks indicate significant (<i>p</i><0.05) allelic effects.</p

Correlation coefficients between mean values of NAM RILs for lesion mimic traits and disease resistance score values obtained from previous studies (SLB, Kump et al. [34]; NLB, Poland et al. [35]; GLS, Benson [33]).

<p>LES, lesion score; HTR, height ratio; SWR, stalk width ratio; DTAR, days to anthesis ratio; SLB, southern leaf blight resistance score ; GLS, gray leaf spot resistance score; NLB, northern leaf blight resistance score; N, sample size and <i>_inv</i> indicates that the original lesion/disease rating scale was inverted so that the correlation sign was consistent between comparisons so that in every case, a positive correlation implies increased HR was correlated with increased HR or with increased disease resistance. Significance of correlation coefficients (<i>r</i>);</p><p>****<i>P</i><0.0001,</p><p>***P<i><</i>0.001,</p><p>**P<i><</i>0.01,</p><p>*P<i><</i>0.05.</p><p>ns- not significant.</p><p>Correlation coefficients between mean values of NAM RILs for lesion mimic traits and disease resistance score values obtained from previous studies (SLB, Kump et al. <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004562#pgen.1004562-Kump1" target="_blank">[34]</a>; NLB, Poland et al. <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004562#pgen.1004562-Poland1" target="_blank">[35]</a>; GLS, Benson <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004562#pgen.1004562-Benson1" target="_blank">[33]</a>).</p

Live and Let Live: Africa’s Response Options to China’s BRI

Kodzi offers a timely perspective on the ongoing debate about how China’s BRI might deliver tangible benefits to African partners. The impact of Chinese engagement on local businesses in different regions is explored both broadly, and in a specific African country context. Using the resource dependence theory and the supply chain practice view, the chapter focuses on technology- and knowledge-enhancing industry linkages to conceptualize a pragmatic response by African industry sectors to the competitive pressures associated with Chinese business engagement. By adopting a response view, this chapter proposes credible options for African countries to increase the strategic value of their contribution in BRI exchanges - rather than being casualties of power asymmetry

SNPs significantly associated with HR-related traits (LES, HTR, SWR and DTAR), and closest predicted maize genes (more details can be found in File S5).

1<p>chromosome;</p>2<p>physical map position based on B73 maize reference genome v2;</p>3<p>−log10 of average <i>p</i> value from GWA analysis based on 100 resampling method;</p>4<p>resampling model inclusion probability (RMIP);</p>5<p>positive and negative allelic effects relative to B73 imply enhancing and suppressing effect on the HR phenotype, respectively;</p>6<p>Number of HR-related trait QTL colocalizing with associated SNP hits (maximum is 4);</p>7<p>mutations of these candidate genes induce lesion phenotypes;</p>8<p>differentially expressed genes (DEG), expression level ratios of candidate genes between mutant and wild type F1 plants from the cross B73×<i>Rp1-D21</i>-H95 and Mo17: <i>Rp1-D21</i>-H95.</p>9<p>Associated SNPs/candidate genes colocalized within QTL that were detected in more than 12 of the 24 NAM populations.</p><p>Key: Lignification: LIG; Programed cell death: PCD,; Autophagy, AUT; monoubiquitination, mUBQ; Calcium signaling, Ca²⁺Sig; defense response, DFR; redox homeostasis, RxH; ubiquitination, UBQ; CWM: cell wall modification; TF, transcription factor; STR: stress response; CHP: molecular chaperone; RNAp, RNA processing.</p><p>SNPs significantly associated with HR-related traits (LES, HTR, SWR and DTAR), and closest predicted maize genes (more details can be found in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004562#pgen.1004562.s014" target="_blank">File S5</a>).</p