Ontogenetic changes in DNA and RNA content of laboratory-reared Prochilodus lineatus larvae: use of RNA/DNA ratios as indicators of nutritional condition

The aims of the present study were to describe the ontogenetic performance of DNA and RNA content, as well as to assess the nutritional condition of Prochilodus lineatus larvae reared under different feeding treatments. The experiment consisted of two parts, the first 6-14 days after hatching (DAH) and the second 15-21 DAH. In the first part of the experiment, larvae were kept under one of two feeding treatments: fed or starved. During the second part of the experiment, larvae were kept under one of four treatments: fed, fed until 14 DAH and later starved, starved until 14 DAH and fed later or starved. It is of note that the size and weight reached of larvae that were starved during early development and later received food were higher than those of than larvae in the other feeding treatments. In addition, instantaneous growth rates were higher and nutritional condition was better in larvae that were initially starved and fed later. The availability of food following a period of starvation seems to trigger larval metabolism and cellular division. Consequently, we recommend maintaining appropriate food provision in the aquaculture of P. lineatus larvae, especially in advanced developmental stages. We verified that RNA/DNA ratio is affected by the feeding condition and that it is sensitive enough to promptly reflect changes in feeding conditions of P. lineatus larvae. Thus, the RNA/DNA ratio could be used to assess nutritional condition of both wild and cultured P. lineatus larvae.Fil: Diaz, Marina Vera. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Gómez, M. I.. Dirección de Pesca Continental; ArgentinaFil: Sánchez, S.. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias. Instituto de Ictiología del Nordeste; ArgentinaFil: Fuentes, Carlos Mariano. Dirección de Pesca Continental; Argentin

Ontogeny versus environmental forcing off the Southwest Atlantic Ocean: Nutritional condition of Fuegian sprat (Sprattus fuegensis) early stages

The Fuegian sprat, Sprattus fuegensis, plays a key trophic role in the Southwest Atlantic Ocean. Growth and survival of small pelagic fishes like sprat are strongly affected by environmental variability and can determine recruitment success. We estimated the nucleic acid composition and assessed with a standardized RNA/DNA index (sRD) the nutritional condition of 273 larvae, metamorphosing, and juvenile Fuegian sprat from two environmentally distinct habitats: the waters off Tierra del Fuego (TDF) and the Marine Protected Area Namuncurá/Burdwood Bank (MPAN/BB). A similar ontogenetic pattern, in which nucleic acid concentrations decreased and sRD increased with increasing standard length (SL) among larval stages was observed in both habitats. A higher percentage of preflexion larvae were under the sRD threshold for growth and optimal growth performance, with sRD values being significantly higher in TDF. Postflexion larvae in both habitats showed maximum sRD values, suggesting that both habitats are suitable nursery grounds. In contrast, metamorphosing and juvenile sprat (only captured in TDF) had consistently low nucleic acid concentrations and sRD values despite increasing SL. Environmental forcing (temperature, salinity, and station depth) was assessed over size-corrected larval sRD. The best model included a negative response to station depth, and the effect of processes associated with this factor are discussed. Although further analyses are needed to reveal underlying dynamics determining early development, these results comprise a baseline for future monitoring approaches on Fuegian sprat life traits and factors affecting their recruitment in this region.Fil: García Alonso, Virginia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Diaz, Marina Vera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Pajaro, Marcelo. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Capitanio, Fabiana Lia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; Argentin

Skipped spawning in the Patagonian stock of Argentine Hake (Merluccius hubbsi)

We analyzed the macroscopic and histological maturity data of Argentine hake (Merluccius hubbsi) collected off Patagonia in the spawning area of the Patagonian stock of this species between 2005 and 2014 to determine the frequency of skipped spawning. This study revealed that the only evidence of skipped spawning observed for Argentine hake was the resting stage. Analysis of 58,891 adult females of Argentine hake sampled during their reproductive peak indicates that, annually, between 6% and 22% of them had skipped spawning. These females were located mostly in the periphery of the spawning area, in deeper (>90 m) and colder waters (7–8°C). Individuals that had skipped spawning had a more intense feeding activity and a better nutritional condition (K=0.68–0.75) than females collected in the main spawning area according to the Fulton’s condition index. In contrast, postspawning females showed the poorest condition (K=0.62–0.68) because of the energy cost involved with reproduction. Females that had skipped spawning were mostly young individuals with a modal age of 3 years and a modal size of 38 cm TL. These results indicate that a significant proportion of females that had completed their first annual spawning could skip the next spawning event and stay on the periphery of the reproductive area to feed.Fil: Macchi, Gustavo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Diaz, Marina Vera. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Leonarduzzi, Ezequiel. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Militelli, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Rodrigues, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentin

The use of morphological and histological features as nutritional condition indices o Pagrus pagrus larvae

Con el objeto de determinar si las técnicas morfométricas e histológicas permiten diferenciar larvas en estado de inanición de las sometidas a tratamientos de alimentación, ejemplares de Pagrus pagrus fueron criados en laboratorio bajo condicion escontroladas. Una vez que el vitelo fue consumido (tres días luego de la eclosión) las larvas fueron sometidas a diferentes tratamientos de alimentación: completamente privadas de alimento, privadas de alimento durante tres días y luego alimentadas, y alimentadas durante todo el experimento. Algas (Nannochloropsis oculata) y rotíferos (Brachionus plicatilis) fueron proporcionados a las larvas de los tratamientos de alimentación. Diariamente se fijaron ejemplares de los tres tratamientos en formol 5% para estudios morfométricos y en Bouin para estudios histológicos. Los resultados obtenidos dan evidencias de que las metodologías presentadas son suficientemente sensibles para determinar diferencias en la condición de larvas sometidas a los tratamientos de alimentación. Por lo tanto, podrían ser empleadas para determinar la condición nutricional de las larvas de besugo recolectadas en el mar. Por otra parte, éstas metodologías podrían ser empleadas para determinar la calidad de larvas producidas en acuicultura y evaluar los efectos de modificaciones introducidas en los protocolos de crianza o en el tipo de alimento suministrado con el objeto de mejorar la supervivencia de los estadios tempranos de desarrollo.Morphometrical and histological techniques were employed to characterize Pagrus pagrus larvae nutritional condition. Larvae were reared in laboratory under controlled conditions with the main objective of testing whether these methodologies allowed finding differences between larvae from different feeding treatments. Once yolk was consumed (three days after hatching) larvae were assigned to a feeding treatment: starved during the whole experiment; delayed feeding, starved during three days; fed during the entire experiment. Algae (Nannochloropsis oculata) and rotifers (Brachionus plicatilis) were provided to larvae for feed treatments. Larvae were fixed daily; for morphometrical purposes in 5% formaldehyde solution, and in Bouin for histological sections. Results herein obtained showed that both methodologies are sensitive enough to distinguish larvae characterized by different nutritional condition states obtained from the feeding treatments. Consequently, these methodologies could be employed in wild red porgy larvae in order to asses their nutritional condition. These techniques could also be employed to check larval quality obtained with aquaculture purposes to estimate the effects of changes in rearing protocols or kind of food supply and thus, to guaranty a higher survival of early developmental stages of reared larvae.Fil: Diaz, Marina Vera. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina;Fil: Arano, María Felis. Universidad Nacional de Mar del Plata; Argentina;Fil: Pajaro, Marcelo. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina;Fil: Aristizabal Abud, Eddie Oscar. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina;Fil: Macchi, Gustavo Javier. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Evaluating the role of endogenous and exogenous features on larval hake nutritional condition

Evaluating the nutritional condition of fish larvae is imperative to establish the importance of starvation, understanding the causes of larval mortality and determining favorable zones for growth and survival within nursery areas. We assessed the nutritional condition of Merluccius hubbsi larvae employing RNA/DNA index (sRD) and its derived index of growth performance (Gpf). Larvae (N = 395) were collected during the reproductive peak in 2010 and 2011. Principal Component Analysis and Generalized Linear Models were used to study the relationship between larval condition and endogenous factors (size, weight, growth rate, trophic incidence, and carbon content per stomach) and exogenous variables (temperature, chlorophyll concentration, potential prey availability, ctenophore biomass, and hake larvae density). The year of sampling was also considered as a variable. The significant variables in the model selection were size, temperature, the density of hake larvae, and year. The larval size was positively related to the condition while larval density and temperature showed a negative relationship with the sRD index. The year was also a significant variable, with higher larval sRD values in 2010. The negative relationship between sRD and larval density suggests the existence of mechanisms of density-dependence operating upon larval condition. On the other hand, the lower temperatures occurred in stratified waters (with greater availability of food) a fact that might explain the negative relationship between sRD and temperature. The fitting of the models suggests that other explanatory variables might be considered to improve the understanding of the nutritional condition index nature.Fil: Diaz, Marina Vera. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Do Souto, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Betti, Paola. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Temperoni, Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Schiariti, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Machinandiarena, Laura. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina. Universidad de Buenos Aires; ArgentinaFil: Brown, Daniel Roberto. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Macchi, Gustavo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentin

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases

Narcissism and the strategic pursuit of short-term mating : universal links across 11 world regions of the International Sexuality Description Project-2.

Previous studies have documented links between sub-clinical narcissism and the active pursuit of short-term mating strategies (e.g., unrestricted sociosexuality, marital infidelity, mate poaching). Nearly all of these investigations have relied solely on samples from Western cultures. In the current study, responses from a cross-cultural survey of 30,470 people across 53 nations spanning 11 world regions (North America, Central/South America, Northern Europe, Western Europe, Eastern Europe, Southern Europe, Middle East, Africa, Oceania, Southeast Asia, and East Asia) were used to evaluate whether narcissism (as measured by the Narcissistic Personality Inventory; NPI) was universally associated with short-term mating. Results revealed narcissism scores (including two broad factors and seven traditional facets as measured by the NPI) were functionally equivalent across cultures, reliably associating with key sexual outcomes (e.g., more active pursuit of short-term mating, intimate partner violence, and sexual aggression) and sex-related personality traits (e.g., higher extraversion and openness to experience). Whereas some features of personality (e.g., subjective well-being) were universally associated with socially adaptive facets of Narcissism (e.g., self-sufficiency), most indicators of short-term mating (e.g., unrestricted sociosexuality and marital infidelity) were universally associated with the socially maladaptive facets of narcissism (e.g., exploitativeness). Discussion addresses limitations of these cross-culturally universal findings and presents suggestions for future research into revealing the precise psychological features of narcissism that facilitate the strategic pursuit of short-term mating

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019 : a systematic analysis from the Global Burden of Disease Study 2019

Background Ending the global tobacco epidemic is a defining challenge in global health. Timely and comprehensive estimates of the prevalence of smoking tobacco use and attributable disease burden are needed to guide tobacco control efforts nationally and globally. Methods We estimated the prevalence of smoking tobacco use and attributable disease burden for 204 countries and territories, by age and sex, from 1990 to 2019 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We modelled multiple smoking-related indicators from 3625 nationally representative surveys. We completed systematic reviews and did Bayesian meta-regressions for 36 causally linked health outcomes to estimate non-linear dose-response risk curves for current and former smokers. We used a direct estimation approach to estimate attributable burden, providing more comprehensive estimates of the health effects of smoking than previously available. Findings Globally in 2019, 1.14 billion (95% uncertainty interval 1.13-1.16) individuals were current smokers, who consumed 7.41 trillion (7.11-7.74) cigarette-equivalents of tobacco in 2019. Although prevalence of smoking had decreased significantly since 1990 among both males (27.5% [26. 5-28.5] reduction) and females (37.7% [35.4-39.9] reduction) aged 15 years and older, population growth has led to a significant increase in the total number of smokers from 0.99 billion (0.98-1.00) in 1990. Globally in 2019, smoking tobacco use accounted for 7.69 million (7.16-8.20) deaths and 200 million (185-214) disability-adjusted life-years, and was the leading risk factor for death among males (20.2% [19.3-21.1] of male deaths). 6.68 million [86.9%] of 7.69 million deaths attributable to smoking tobacco use were among current smokers. Interpretation In the absence of intervention, the annual toll of 7.69 million deaths and 200 million disability-adjusted life-years attributable to smoking will increase over the coming decades. Substantial progress in reducing the prevalence of smoking tobacco use has been observed in countries from all regions and at all stages of development, but a large implementation gap remains for tobacco control. Countries have a dear and urgent opportunity to pass strong, evidence-based policies to accelerate reductions in the prevalence of smoking and reap massive health benefits for their citizens. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs