Balancing serendipity and reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and their differentiation into neural lineages is a revolutionary experimental system for studying neurological disorders, including intellectual and developmental disabilities (IDDs). However, issues related to variability and reproducibility have hindered translating preclinical findings into drug discovery. Here, we identify areas for improvement by conducting a comprehensive review of 58 research articles that utilized iPSC-derived neural cells to investigate genetically defined IDDs. Based upon these findings, we propose recommendations for best practices that can be adopted by research scientists as well as journal editors

Avian Species Richness in Relation to Intensive Forest Management Practices in Early Seral Tree Plantations

•Background: Managers of landscapes dedicated to forest commodity production require information about how practices influence biological diversity. Individual species and communities may be threatened if management practices truncate or simplify forest age classes that are essential for reproduction and survival. For instance, the degradation and loss of complex diverse forest in young age classes have been associated with declines in forest-associated Neotropical migrant bird populations in the Pacific Northwest, USA. These declines may be exacerbated by intensive forest management practices that reduce hardwood and broadleaf shrub cover in order to promote growth of economically valuable tree species in plantations. •Methodology and Principal Findings: We used a Bayesian hierarchical model to evaluate relationships between avian species richness and vegetation variables that reflect stand management intensity (primarily via herbicide application) on 212 tree plantations in the Coast Range, Oregon, USA. Specifically, we estimated the influence of broadleaf hardwood vegetation cover, which is reduced through herbicide applications, on bird species richness and individual species occupancy. Our model accounted for imperfect detection. We used average predictive comparisons to quantify the degree of association between vegetation variables and species richness. Both conifer and hardwood cover were positively associated with total species richness, suggesting that these components of forest stand composition may be important predictors of alpha diversity. Estimates of species richness were 35–80% lower when imperfect detection was ignored (depending on covariate values), a result that has critical implications for previous efforts that have examined relationships between forest composition and species richness. •Conclusion and Significance: Our results revealed that individual and community responses were positively associated with both conifer and hardwood cover. In our system, patterns of bird community assembly appear to be associated with stand management strategies that retain or increase hardwood vegetation while simultaneously regenerating the conifer cover in commercial tree plantations

Case Study: Predictive Fairness to Reduce Misdemeanor Recidivism Through Social Service Interventions

The criminal justice system is currently ill-equipped to improve outcomes of individuals who cycle in and out of the system with a series of misdemeanor offenses. Often due to constraints of caseload and poor record linkage, prior interactions with an individual may not be considered when an individual comes back into the system, let alone in a proactive manner through the application of diversion programs. The Los Angeles City Attorney's Office recently created a new Recidivism Reduction and Drug Diversion unit (R2D2) tasked with reducing recidivism in this population. Here we describe a collaboration with this new unit as a case study for the incorporation of predictive equity into machine learning based decision making in a resource-constrained setting. The program seeks to improve outcomes by developing individually-tailored social service interventions (i.e., diversions, conditional plea agreements, stayed sentencing, or other favorable case disposition based on appropriate social service linkage rather than traditional sentencing methods) for individuals likely to experience subsequent interactions with the criminal justice system, a time and resource-intensive undertaking that necessitates an ability to focus resources on individuals most likely to be involved in a future case. Seeking to achieve both efficiency (through predictive accuracy) and equity (improving outcomes in traditionally under-served communities and working to mitigate existing disparities in criminal justice outcomes), we discuss the equity outcomes we seek to achieve, describe the corresponding choice of a metric for measuring predictive fairness in this context, and explore a set of options for balancing equity and efficiency when building and selecting machine learning models in an operational public policy setting.Comment: 12 pages, 4 figures, 1 algorithm. The definitive Version of Record will be published in the proceedings of the Conference on Fairness, Accountability, and Transparency (FAT* '20), January 27-30, 2020, Barcelona, Spai

Evaluating Multi-Level Models to Test Occupancy State Responses of Plethodontid Salamanders

Correction 23 Dec 2015: The PLOS ONE Staff (2015) Correction: Evaluating Multi-Level Models to Test Occupancy State Responses of Plethodontid Salamanders. PLOS ONE 10(12): e0145899. https://doi.org/10.1371/journal.pone.0145899Plethodontid salamanders are diverse and widely distributed taxa and play critical roles in ecosystem processes. Due to salamander use of structurally complex habitats, and because only a portion of a population is available for sampling, evaluation of sampling designs and estimators is critical to provide strong inference about Plethodontid ecology and responses to conservation and management activities. We conducted a simulation study to evaluate the effectiveness of multi-scale and hierarchical single-scale occupancy models in the context of a Before-After Control-Impact (BACI) experimental design with multiple levels of sampling. Also, we fit the hierarchical single-scale model to empirical data collected for Oregon slender and Ensatina salamanders across two years on 66 forest stands in the Cascade Range, Oregon, USA. All models were fit within a Bayesian framework. Estimator precision in both models improved with increasing numbers of primary and secondary sampling units, underscoring the potential gains accrued when adding secondary sampling units. Both models showed evidence of estimator bias at low detection probabilities and low sample sizes; this problem was particularly acute for the multi-scale model. Our results suggested that sufficient sample sizes at both the primary and secondary sampling levels could ameliorate this issue. Empirical data indicated Oregon slender salamander occupancy was associated strongly with the amount of coarse woody debris (posterior mean = 0.74; SD = 0.24); Ensatina occupancy was not associated with amount of coarse woody debris (posterior mean = -0.01; SD = 0.29). Our simulation results indicate that either model is suitable for use in an experimental study of Plethodontid salamanders provided that sample sizes are sufficiently large. However, hierarchical single-scale and multi-scale models describe different processes and estimate different parameters. As a result, we recommend careful consideration of study questions and objectives prior to sampling data and fitting models

Spillway-Induced Salmon Head Injury Triggers the Generation of Brain αII-Spectrin Breakdown Product Biomarkers Similar to Mammalian Traumatic Brain Injury

Recent advances in biomedical research have resulted in the development of specific biomarkers for diagnostic testing of disease condition or physiological risk. Of specific interest are αII-spectrin breakdown products (SBDPs), which are produced by proteolytic events in traumatic brain injury and have been used as biomarkers to predict the severity of injury in humans and other mammalian brain injury models. This study describes and demonstrates the successful use of antibody-based mammalian SBDP biomarkers to detect head injury in migrating juvenile Chinook salmon (Oncorhynchus tshawytscha) that have been injured during passage through high-energy hydraulic environments present in spillways under different operational configurations. Mortality and injury assessment techniques currently measure only near-term direct mortality and easily observable acute injury. Injury-based biomarkers may serve as a quantitative indicator of subacute physical injury and recovery, and aid hydropower operators in evaluation of safest passage configuration and operation actions for migrating juvenile salmonids. We describe a novel application of SBDP biomarkers for head injury for migrating salmon. To our knowledge, this is the first documented cross-over use of a human molecular biomarker in a wildlife and operational risk management scenario

Sustainable development goal 2: improved targets and indicators for agriculture and food security

The pursuit of global food security and agricultural sustainability, the dual aim of the second Sustainable Development Goal (SDG-2), requires urgent and concerted action from developing and developed countries. This, in turn, depends on clear and universally applicable targets and indicators which are partially lacking. The novel and complex nature of the SDGs poses further challenges to their implementation on the ground, especially in the face of interlinkages across SDG objectives and scales. Here we review the existing SDG-2 indicators, propose improvements to facilitate their operationalization and illustrate their practical implementation in Nigeria, Brazil and the Netherlands. This exercise provides insights into the concrete actions needed to achieve SDG-2 across contrasting development contexts and highlights the challenges of addressing the links between targets and indicators within and beyond SDG-2. Ultimately, it underscores the need for integrated policies and reveals opportunities to leverage the fulfillment of SDG-2 worldwide