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. 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. 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. 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. Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute.

GALLAGHER contributing millions of dollars to local economies through dive ecotourism (9).

The potential existence and roles of the meningeal lymphatic system in normal and pathological brain function have been a long-standing enigma. Recent evidence suggests that meningeal lymphatic vessels are present in both the mouse and human brain; in mice, they seem to play a role in clearing toxic amyloid-beta peptides, which have been connected with Alzheimer disease (AD). Here, we review the evidence linking the meningeal lymphatic system with human AD. Novel findings suggest that the recently described meningeal lymphatic vessels could be linked to, and possibly drain, the efferent paravascular glial lymphatic (glymphatic) system carrying cerebrospinal fluid, after solute and immune cell exchange with brain interstitial fluid. In so doing, the glymphatic system could contribute to the export of toxic solutes and immune cells from the brain (an exported fluid we wish to describe as glymph, similarly to lymph) to the meningeal lymphatic system; the latter, by being connected with downstream anatomic regions, carries the glymph to the conventional cervical lymphatic vessels and nodes. Thus, abnormal function in the meningeal lymphatic system could, in theory, lead to the accumulation, in the brain, of amyloid-beta, cellular debris, and inflammatory mediators, as well as immune cells, resulting in damage of the brain parenchyma and, in turn, cognitive and other neurologic dysfunctions. In addition, we provide novel insights into APOE4—the leading genetic risk factor for AD—and its relation to the meningeal lymphatic system. In this regard, we have reanalyzed previously published RNA-Seq data to show that induced pluripotent stem cells (iPSCs) carrying theAPOE4allele (either asAPOE4knock-in or stemming fromAPOE4patients) express lower levels of (a) genes associated with lymphatic markers, and (b) genes for which well-characterized missense mutations have been linked to peripheral lymphedema. Taking into account this evidence, we propose a new conceptual framework, according to which APOE4 could play a novel role in the premature shrinkage of meningeal lymphatic vessels (meningeal lymphosclerosis), leading to abnormal meningeal lymphatic functions (meningeal lymphedema), and, in turn, reduction in the clearance of amyloid-beta and other macromolecules and inflammatory mediators, as well as immune cells, from the brain, exacerbation of AD manifestations, and progression of the disease. Altogether, these findings and their potential interpretations may herald novel diagnostic tools and therapeutic approaches in patients with AD.