Background The UK 100,000 Genomes Project is in the process of investigating the role of genome sequencing of patients with undiagnosed rare disease following usual care, and the alignment of research with healthcare implementation in the UK’s national health service. (Other parts of this Project focus on patients with cancer and infection.) Methods We enrolled participants, collected clinical features with human phenotype ontology terms, undertook genome sequencing and applied automated variant prioritization based on virtual gene panels (PanelApp) and phenotypes (Exomiser), alongside identification of novel pathogenic variants through research analysis. We report results on a pilot study of 4660 participants from 2183 families with 161 disorders covering a broad spectrum of rare disease. Results Diagnostic yields varied by family structure and were highest in trios and larger pedigrees. Likely monogenic disorders had much higher diagnostic yields (35%) with intellectual disability, hearing and vision disorders, achieving yields between 40 and 55%. Those with more complex etiologies had an overall 25% yield. Combining research and automated approaches was critical to 14% of diagnoses in which we found etiologic non-coding, structural and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohort-wide burden testing across 57,000 genomes enabled discovery of 3 new disease genes and 19 novel associations. Of the genetic diagnoses that we made, 24% had immediate ramifications for the clinical decision-making for the patient or their relatives. Conclusion Our pilot study of genome sequencing in a national health care system demonstrates diagnostic uplift across a range of rare diseases. (Funded by National Institute for Health Research and others)

Do experiences with nature – from wilderness backpacking to plants in a preschool, to a wetland lesson on frogs—promote learning? Until recently, claims outstripped evidence on this question. But the field has matured, not only substantiating previously unwarranted claims but deepening our understanding of the cause-and-effect relationship between nature and learning. Hundreds of studies now bear on this question, and converging evidence strongly suggests that experiences of nature boost academic learning, personal development, and environmental stewardship. This brief integrative review summarizes recent advances and the current state of our understanding. The research on personal development and environmental stewardship is compelling although not quantitative. Report after report – from independent observers as well as participants themselves – indicate shifts in perseverance, problem solving, critical thinking, leadership, teamwork, and resilience. Similarly, over fifty studies point to nature playing a key role in the development of pro-environmental behavior, particularly by fostering an emotional connection to nature. In academic contexts, nature-based instruction outperforms traditional instruction. The evidence here is particularly strong, including experimental evidence; evidence across a wide range of samples and instructional approaches; outcomes such as standardized test scores and graduation rates; and evidence for specific explanatory mechanisms and active ingredients. Nature may promote learning by improving learners’ attention, levels of stress, self-discipline, interest and enjoyment in learning, and physical activity and fitness. Nature also appears to provide a calmer, quieter, safer context for learning; a warmer, more cooperative context for learning; and a combination of “loose parts” and autonomy that fosters developmentally beneficial forms of play. It is time to take nature seriously as a resource for learning – particularly for students not effectively reached by traditional instruction.

A growing number of studies demonstrate significant associations between nature experiences and positive mental health outcomes (e.g., improved mood, decreased stress). However, implementation of this research by practitioners in fields such as urban design or public health has been limited. One reason for this is that it remains unclear what elements of nature and types of participant experience are consistently associated with mental health benefits. As a result, decision-makers who aim to enhance mental health in cities have little guidance about which elements of nature and types of experiences in natural areas may lead to positive mental health outcomes. We reviewed 30 studies with 41 distinct exposures in nature that elicited positive mental health benefits and characterized the elements of nature found at these sites, as well as aspects of participants’ experience. Elements of natural areas considered include: forest, managed grass, and water as dominant land cover types, specific water features (e.g., small ponds, fountains) and built features (e.g., trails, paths). The majority of the studies we reviewed assessed the experiences of individuals (vs. in groups) participating in walks during warmer seasons. Most studies did not describe the “nature of the nature” associated with positive mental health outcomes. We contacted authors and used Google Earth imagery to reconstruct the specific natural elements, landscape typology, and site adjacencies present in past studies. We recommend specific ways researchers could better and more transparently document important elements of nature and participant experience in study design and reporting that will enhance the planning and design relevance of their work.