The state of adolescent sexual and reproductive health

In the 25 years since the 1994 International Conference on Population and Development, significant progress has been made in adolescent sexual and reproductive health and rights (ASRHR). Trend analysis of key ASRHR indicators at global, national, and subnational levels indicates that adolescent girls today are more likely to marry later, delay their first sexual experience, and delay their first childbirth, compared with 25 years ago; they are also more likely to use contraceptives. Despite overall progress, however, unequal progress in many ASRHR outcomes is evident both within and between countries, and in some locations, the state of adolescents' lives has worsened. Population growth in countries with some of the worst shortfalls in ASRHR mean that declining rates, of child marriage, for example, coexist with higher absolute numbers of girls affected, compared with 25 years ago. Emerging trends that warrant closer attention include increasing rates of ovarian and breast cancer among adolescent girls and sharp increases in the proportion of adolescents who are overweight or obese, which has long-term health implications. (C) 2019 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine

The political, research, programmatic, and social responses to adolescent sexual and reproductive health and rights in the 25 years since the International Conference on Population and Development

Among the ground-breaking achievements of the International Conference on Population and Development (ICPD) was its call to place adolescent sexual and reproductive health (ASRH) on global health and development agendas. This article reviews progressmade in low- and middle-income countries in the 25 years since the ICPD in six areas central to ASRH-adolescent pregnancy, HIV, child marriage, violence against women and girls, female genital mutilation, and menstrual hygiene and health. It also examines the ICPD's contribution to the progress made. The article presents epidemiologic levels and trends; political, research, programmatic and social responses; and factors that helped or hindered progress. To do so, it draws on research evidence and programmatic experience and the expertise and experiences of a wide number of individuals, including youth leaders, in numerous countries and organizations. Overall, looking across the six health topics over a 25-year trajectory, there has been great progress at the global and regional levels in putting adolescent health, and especially adolescent sexual and reproductive health and rights, higher on the agenda, raising investment in this area, building the epidemiologic and evidence-base, and setting norms to guide investment and action. At the national level, too, there has been progress in formulating laws and policies, developing strategies and programs and executing them, and engaging communities and societies in moving the agenda forward. Still, progress has been uneven across issues and geography. Furthermore, it has raced ahead sometimes and has stalled at others. The ICPD's Plan of Action contributed to the progress made in ASRH not just because of its bold call in 1994 but also because it provided a springboard for advocacy, investment, action, and research that remains important to this day. (C) 2019 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD

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

Forward, Together: A Collaborative Path to Comprehensive Adolescent Sexual and Reproductive Health and Rights in Our Time

The 1994 International Conference on Population and Development established a basis for the advancement of adolescent sexual and reproductive health and rights (ASRHR) that endures today. Twenty-five years later, our vision for the future warrants reflection based on a clear understanding of the opportunities and challenges before us. Inclusion of adolescents on global, regional, and national agendas; increased investment in ASRHR policies and programs; renewed commitments to universal health coverage; increased school enrollment; and advances in technology are all critical opportunities we can and must leverage to catalyze progress for adolescents. At the same time, a range of significant challenges remain, have newly emerged, or can be seen on the horizon, including persistent denial of adolescent sexuality; entrenched gender inequality; resistance to meaningfully engaging adolescents and young people in political and programmatic processes; weak systems, integration, and multisectoral coordination; changes in population dynamics; humanitarian and climate crises; and changes in family and community structures. To achieve as much progress toward our vision for ASRHR as possible, the global ASRHR community must take strategic and specific steps in the next 10 years within five areas for action: (1) mobilize and make full use of political and social support for ASRHR policies and programs; (2) increase and make effective use of external and domestic funding for ASRHR; (3) develop, communicate, apply, and monitor enabling and protective laws and policies for ASRHR; (4) use and improve available ASRHR data and evidence to strengthen advocacy, policies, and programs; and (5) manage the implementation of ASRHR strategies at scale with quality and equity. (C) 2019 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine

Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neuro-developmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD

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 science. © The Author(s) 2019. Published by Oxford University Press