Learning is enhanced by tailoring instruction to individual genetic differences.

It is widely argued that personalized instruction based on individual differences in learning styles or genetic predispositions could improve learning outcomes. However, this proposition has resisted clear demonstration in human studies, where it is difficult to control experience and quantify outcomes. Here, we take advantage of the tractable nature of vocal learning in songbirds (Lonchura striata domestica) to test the idea that matching instruction to individual genetic predispositions can enhance learning. We use both cross-fostering and computerized instruction with synthetic songs to demonstrate that matching the tutor song to individual predispositions can improve learning across genetic backgrounds. Moreover, we find that optimizing instruction in this fashion can equalize learning differences across individuals that might otherwise be construed as genetically determined. Our results demonstrate potent, synergistic interactions between experience and genetics in shaping song, and indicate the likely importance of such interactions for other complex learned behaviors

Condensins Regulate Meiotic DNA Break Distribution, thus Crossover Frequency, by Controlling Chromosome Structure

SummaryMeiotic crossover (CO) recombination facilitates evolution and accurate chromosome segregation. CO distribution is tightly regulated: homolog pairs receive at least one CO, CO spacing is nonrandom, and COs occur preferentially in short genomic intervals called hotspots. We show that CO number and distribution are controlled on a chromosome-wide basis at the level of DNA double-strand break (DSB) formation by a condensin complex composed of subunits from two known condensins: the C. elegans dosage compensation complex and mitotic condensin II. Disruption of any subunit of the CO-controlling condensin dominantly changes DSB distribution, and thereby COs, and extends meiotic chromosome axes. These phenotypes are cosuppressed by disruption of a chromosome axis element. Our data implicate higher-order chromosome structure in the regulation of CO recombination, provide a model for the rapid evolution of CO hotspots, and show that reshuffling of interchangeable molecular parts can create independent machines with similar architectures but distinct biological functions

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

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Data from: An automated approach to the quantitation of vocalizations and vocal learning in the songbird.

Studies of learning mechanisms critically depend on the ability to accurately assess learning outcomes. This assessment can be impeded by the often complex, multidimensional nature of behavior. We present a novel, automated approach to evaluating imitative learning. Conceptually, our approach estimates how much of the content present in a reference behavior is absent from the learned behavior. We validate our approach through examination of songbird vocalizations, complex learned behaviors the study of which has provided many insights into sensory-motor learning in general and vocal learning in particular. Historically, learning has been holistically assessed by human inspection or through comparison of specific song features selected by experimenters (e.g. fundamental frequency, spectral entropy). In contrast, our approach uses statistical models to broadly capture the structure of each song, and then estimates the divergence between the two models. We show that our measure of song learning (Song Divergence) is well correlated with human evaluation of song learning. We then expand the analysis beyond learning and show that Song Divergence also detects the typical song deterioration that occurs following deafening. Finally, we illustrate how this measure can be extended to quantify differences in other complex behaviors such as human speech and handwriting. This approach potentially provides a framework for assessing learning across a broad range of behaviors like song that can be described as a set of discrete and repeated motor actions

Vocalization data for assessing the utility of the measure Song Divergence.

This is a compressed archive of the vocalization data used in evaluating the utility of 'Song Divergence'

Genetic variation interacts with experience to determine interindividual differences in learned song

Learning reflects the influence of experience on genetically determined circuitry, but little is known about how experience and genetics interact to determine complex learned phenotypes. Here, we used vocal learning in songbirds to study how experience and genetics contribute to interindividual differences in learned song. Previous work has established that such differences in song within a species depend on learning, but in principle some of these differences could also depend on genetic variation. We focused on song tempo, a learned and quantifiable feature that is controlled by central neural circuitry. To identify genetic contributions to tempo we computer-tutored juvenile Bengalese finches (Lonchura striata domestica) from different genetic backgrounds with synthetic songs in which tempo was systematically varied. Computer-tutored birds exhibited unexpectedly strong heritability for song tempo and comparatively weak influence of experience. We then tested whether heritability was fixed and independent of experience by providing a second group of birds with enriched instruction via live social tutoring. Live tutoring resulted in not only a significant increase in the influence of experience on tempo but also a dramatic decrease in the influence of genetics, indicating that enriched instruction could overcome genetic biases evident under computer tutoring. Our results reveal strong heritable genetic contributions to interindividual variation in song tempo but that the degree of heritability depends profoundly on the quality of instruction. They suggest that for more complex learned phenotypes, where it can be difficult to identify and control relevant experiential variables, heritability may similarly be contingent on the specifics of experience