Clinical variants paired with phenotype: A rich resource for brain gene curation.

PURPOSE: Clinically ascertained variants are under-utilized in neurodevelopmental disorder research. We established the Brain Gene Registry (BGR) to coregister clinically identified variants in putative brain genes with participant phenotypes. Here, we report 179 genetic variants in the first 179 BGR registrants and analyze the proportion that were novel to ClinVar at the time of entry and those that were absent in other disease databases. METHODS: From 10 academically affiliated institutions, 179 individuals with 179 variants were enrolled into the BGR. Variants were cross-referenced for previous presence in ClinVar and for presence in 6 other genetic databases. RESULTS: Of 179 variants in 76 genes, 76 (42.5%) were novel to ClinVar, and 62 (34.6%) were absent from all databases analyzed. Of the 103 variants present in ClinVar, 37 (35.9%) were uncertain (ClinVar aggregate classification of variant of uncertain significance or conflicting classifications). For 5 variants, the aggregate ClinVar classification was inconsistent with the interpretation from the BGR site-provided classification. CONCLUSION: A significant proportion of clinical variants that are novel or uncertain are not shared, limiting the evidence base for new gene-disease relationships. Registration of paired clinical genetic test results with phenotype has the potential to advance knowledge of the relationships between genes and neurodevelopmental disorders.

Taking high conservation value from forests to freshwaters.

The high conservation value (HCV) concept, originally developed by the Forest Stewardship Council, has been widely incorporated outside the forestry sector into companies' supply chain assessments and responsible purchasing policies, financial institutions' investment policies, and numerous voluntary commodity standards. Many, if not most, of these newer applications relate to production practices that are likely to affect freshwater systems directly or indirectly, yet there is little guidance as to whether or how HCV can be applied to water bodies. We focus this paper on commodity standards and begin by exploring how prominent standards currently address both HCVs and freshwaters. We then highlight freshwater features of high conservation importance and examine how well those features are captured by the existing HCV framework. We propose a new set of freshwater 'elements' for each of the six values and suggest an approach for identifying HCV Areas that takes out-of-fence line impacts into account, thereby spatially extending the scope of existing methods to define HCVs. We argue that virtually any non-marine HCV assessment, regardless of the production sector, should be expanded to include freshwater values, and we suggest how to put those recommendations into practice.

Magnetically driven formation of 3D freestanding soft bioscaffolds.

3D soft bioscaffolds have great promise in tissue engineering, biohybrid robotics, and organ-on-a-chip engineering applications. Though emerging three-dimensional (3D) printing techniques offer versatility for assembling soft biomaterials, challenges persist in overcoming the deformation or collapse of delicate 3D structures during fabrication, especially for overhanging or thin features. This study introduces a magnet-assisted fabrication strategy that uses a magnetic field to trigger shape morphing and provide remote temporary support, enabling the straightforward creation of soft bioscaffolds with overhangs and thin-walled structures in 3D. We demonstrate the versatility and effectiveness of our strategy through the fabrication of bioscaffolds that replicate the complex 3D topology of branching vascular systems. Furthermore, we engineered hydrogel-based bioscaffolds to support biohybrid soft actuators capable of walking motion triggered by cardiomyocytes. This approach opens new possibilities for shaping hydrogel materials into complex 3D morphologies, which will further empower a broad range of biomedical applications.

Surface electromyography using dry polymeric electrodes.

Conventional wet Ag/AgCl electrodes are widely used in electrocardiography, electromyography (EMG), and electroencephalography (EEG) and are considered the gold standard for biopotential measurements. However, these electrodes require substantial skin preparation, are single use, and cannot be used for continuous monitoring (>24 h). For these reasons, dry electrodes are preferable during surface electromyography (sEMG) due to their convenience, durability, and longevity. Dry conductive elastomers (CEs) combine conductivity, flexibility, and stretchability. In this study, CEs combining poly(3,4-ehtylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) in polyurethane are explored as dry, skin contacting EMG electrodes. This study compares these CE electrodes to commercial wet Ag/AgCl electrodes in five subjects, classifying four movements: open hand, fist, wrist extension, and wrist flexion. Classification accuracy is tested using a backpropagation artificial neural network. The control Ag/AgCl electrodes have a 98.7% classification accuracy, while the dry conductive elastomer electrodes have a classification accuracy of 99.5%. As a conclusion, PEDOT based dry CEs were shown to successfully function as on-skin electrodes for EMG recording, matching the performance of Ag/AgCl electrodes, while addressing the need for minimal skin prep, no gel, and wearable technology.

Ecosystem service information to benefit sustainability standards for commodity supply chains.

The growing base of information about ecosystem services generated by ecologists, economists, and other scientists could improve the implementation, monitoring, and evaluation of commodity-sourcing standards being adopted by corporations to mitigate risk in their supply chains and achieve sustainability goals. This review examines various ways that information about ecosystem services could facilitate compliance with and auditing of commodity-sourcing standards. We also identify gaps in the current state of knowledge on the ecological effectiveness of sustainability standards and demonstrate how ecosystem-service information could complement existing monitoring efforts to build credible evidence. This paper is a call to the ecosystem-service scientists to engage in this decision context and tailor the information they are generating to the needs of the standards community, which we argue would offer greater efficiency of standards implementation for producers and enhanced effectiveness for standard scheme owners and corporations, and should thus lead to more sustainable outcomes for people and nature.

Challenges in evaluating all-cause hospital readmission measures for use as national consensus standards.

CONTEXT: The National Quality Forum (NQF) aims to improve the quality of health care for all Americans through fulfillment of its three-part mission. The NQF uses its formal Consensus Development Process to evaluate and endorse consensus standards, including performance measures, best practices, frameworks, and reporting guidelines. OBJECTIVE: To understand the opportunities and challenges in endorsing measures addressing all-cause readmissions to hospitals for use as national voluntary consensus standards for accountability and quality-improvement purposes. DESIGN: Report of standards development process. MAIN OUTCOME MEASURES: The Consensus Development Process was used to evaluate 3 candidate standards using the NQF Measure Evaluation Criteria. A 21-member steering committee rated each standard according to the criteria and made initial endorsement recommendations for all measures. RESULTS: Through the evaluation of measures for endorsement, several overarching issues in measuring all-cause readmissions were identified, including statistical modeling and the usability of the measures for quality improvement and accountability. Additionally, it was decided that, for the first time, quality monitoring and accountability of readmissions will take place at the health-plan level. Measuring at various levels of accountability reinforces the idea that multiple stakeholders have a responsibility and a role to reduce readmissions. CONCLUSIONS: These NQF-endorsed measures are a major step in promoting better understanding of readmissions and a reduction in hospital readmission rates, when appropriate. These measures can help reduce the substantial financial and emotional stress that readmissions place on the health care system, and patients will be able to communicate hospital-level performance on this important quality indicator.

Volunteer environmental monitoring and the role of the universities: the case of Citizens' Environment Watch.

Universities can provide a stable home for launching collaborative community research projects. Citizens' Environment Watch (CEW), an environmental monitoring initiative based at the University of Toronto, has made significant contributions to environmental education and stewardship in Ontario, Canada. Following dramatic cuts in provincial monitoring programs, citizens and youth have used chemical parameters and biological indicators to gauge water and air quality, and to identify areas requiring remediation and pollution prevention efforts. The relationship of Citizens' Environment Watch to government agencies, funders and other grassroots environmental groups has evolved over the past 5 years as CEW attempts to remain effective without taking on the investigative and enforcement roles to support the regulatory enforcement that has been largely abandoned by government. We explore the challenges inherent in developing and maintaining a volunteer organization that carries out rigorous and useful scientific work and we outline the ability of a university to help overcome these critical challenges. Finally, we present lessons learned for the benefit of other citizen and youth monitoring projects.