Congenital microcoria deletion in mouse links Sox21 dysregulation to disease and suggests a role for TGFB2 in glaucoma and myopia.

Congenital microcoria (MCOR) is a rare hereditary developmental defect of the iris dilator muscle frequently associated with high axial myopia and high intraocular pressure (IOP) glaucoma. The condition is caused by submicroscopic rearrangements of chromosome 13q32.1. However, the mechanisms underlying the failure of iris development and the origin of associated features remain elusive. Here, we present a 3D architecture model of the 13q32.1 region, demonstrating that MCOR-related deletions consistently disrupt the boundary between two topologically associating domains (TADs). Deleting the critical MCOR-causing region in mice reveals ectopic Sox21 expression precisely aligning with Dct, each located in one of the two neighbor TADs. This observation is consistent with the TADs' boundary alteration and adoption of Dct regulatory elements by the Sox21 promoter. Additionally, we identify Tgfb2 as a target gene of SOX21 and show TGFΒ2 accumulation in the aqueous humor of an MCOR-affected subject. Accumulation of TGFB2 is recognized for its role in glaucoma and potential impact on axial myopia. Our results highlight the importance of SOX21-TGFB2 signaling in iris development and control of eye growth and IOP. Insights from MCOR studies may provide therapeutic avenues for this condition but also for glaucoma and high myopia conditions, affecting millions of people.

Eviction-driven infanticide and sexually selected adoption and infanticide in a neotropical parrot.

Infanticide and adoption have been attributed to sexual selection, where an individual later reproduces with the parent whose offspring it killed or adopted. While sexually selected infanticide is well known, evidence for sexually selected adoption is anecdotal. We report on both behaviors at 346 nests over 27 y in green-rumped parrotlets (Forpus passerinus) in Venezuela. Parrotlets are monogamous with long-term pair bonds, exhibit a strongly male-biased adult sex ratio, and nest in cavities that are in short supply, creating intense competition for nest sites and mates. Infanticide attacks occurred at 256 nests in two distinct contexts: 1) Attacks were primarily committed by nonbreeding pairs (69%) attempting to evict parents from the cavity. Infanticide attacks per nest were positively correlated with population size and evicting pairs never adopted abandoned offspring. Competition for limited nest sites was a primary cause of eviction-driven infanticide, and 2) attacks occurred less frequently at nests where one mate died (31%), was perpetrated primarily by stepparents of both sexes, and was independent of population size. Thus, within a single species and mating system, infanticide occurred in multiple contexts due to multiple drivers. Nevertheless, 48% of stepparents of both sexes adopted offspring, and another 23% of stepfathers exhibited both infanticide and long-term care. Stepfathers were often young males who subsequently nested with widows, reaching earlier ages of first breeding than competitors and demonstrating sexually selected adoption. Adoption and infanticide conferred similar fitness benefits to stepfathers and appeared to be equivalent strategies driven by limited breeding opportunities, male-biased sex ratios, and long-term monogamy.

Family secrets: Experiences and outcomes of participating in direct-to-consumer genetic relative-finder services.

In recent decades, genetic genealogy has become popular as a result of direct-to-consumer (DTC) genetic testing. Some DTC genetic testing companies offer genetic relative-finder (GRF) services that compare the DNA of consenting participants to identify genetic relatives among them and provide each participant a list of their relative matches. We surveyed a convenience sample of GRF service participants to understand the prevalence of discoveries and associated experiences. Almost half (46%) of the 23,196 respondents had participated in GRF services only for non-specific reasons that included interest in building family trees and general curiosity. However, most (82%) also learned the identity of at least one genetic relative. Separately, most respondents (61%) reported learning something new about themselves or their relatives, including potentially disruptive information such as that a person they believed to be their biological parent is in fact not or that they have a sibling they had not known about. Respondents generally reported that discovering this new information had a neutral or positive impact on their lives, and most had low regret regarding their decision to participate in GRF services. Yet some reported making life changes as a result of their discoveries. Compared to respondents making other types of discoveries, those who learned that they were donor conceived reported the highest decisional regret and represented the largest proportion reporting net-negative consequences for themselves. Our findings indicate that discoveries from GRF services may be common and that the consequences for individuals, while generally positive, can be far-reaching and complex.

From the laboratory to the consumer: Innovation, supply chain, and adoption with applications to natural resources.

We analyze the transition from innovative ideas to final marketed products. This transition occurs through two synergetic supply chains for innovation and products. Basic concepts are developed, tested, upscaled, and introduced to commercial use in the innovation supply chain. Then, the products are produced and delivered to the consumer through the product supply chain. We argue that product markets trace their birth to product innovations. These markets tend to start as noncompetitive, which rewards innovators. Credit access and risk determine the reliance on contracting and product diffusion over space and time. The innovation and product supply chains are encouraged and facilitated by public policies, such as support for research and education, intellectual property rights protection, low barriers to trade, science-based regulation, and well-functioning capital markets. We argue for multidisciplinary research incorporating knowledge from economics, business, and engineering to better understand the evolution of innovative companies and supply chains. This understanding will help the development of policies to address challenges of climate change and food security among others.

Extension services can promote pasture restoration: Evidence from Brazil's low carbon agriculture plan.

Innovation and improved practices in the livestock sector represent key opportunities tomeet global climate goals. This paper provides evidence that extension services can pro-mote pasture restoration in cattle ranching in Brazil. We use a randomized controlledtrial implemented in the context of the ABC Cerrado (a large-scale program launched in2014 aimed at fostering technology adoption through a combination of training andtechnical assistance) to examine the effects of different types of extension on agriculturalpractices, input use, and productivity. Providing technical assistance to previously trainedproducers promoted pasture restoration, induced farmers to use inputs more intensively,helped them to improve their management and soil conservation practices, and substan-tially increased revenues. A cost­benefit calculation indicates that US$1 invested in theABC Cerrado program increased profits by US$1.08 to $1.45. Incorporating carbonsavings amplifies this return considerably.

Scientific selection: A century of increasing crop varietal diversity in US wheat.

A prevalent and persistent biodiversity concern is that modern cropping systems lead to an erosion in crop genetic diversity. Although certain trait uniformity provides advantages in crop management and marketing, farmers facing risks from change in climate, pests, and markets are also incentivized to adopt new varieties to address complex and spatially variable genetics, environment, and crop management interactions to optimize crop performance. In this study, we applied phylogenetically blind and phylogenetically informed diversity metrics to reveal significant increases in both the spatial and temporal diversity of the US wheat crop over the past century. Contrary to commonly held perceptions on the negative impact of modern cropping systems on crop genetic diversity, our results demonstrated a win-win outcome where the widespread uptake of scientifically selected varieties increased both crop production and crop diversity.

Encouraging voluntary government action via a solar-friendly designation program to promote solar energy in the United States.

SignificanceDue to market and system failures, policies and programs at the local level are needed to accelerate the renewable energy transition. A voluntary environmental program (VEP), such as SolSmart, can encourage local governments to adopt solar-friendly best practices. Unlike previous research, this study uses a national sample, more recent data, and a matched control group for difference-in-differences estimation to quantify the causal impact of a VEP in the public, rather than private, sector. We offer empirical evidence that SolSmart increased installed solar capacity and, with less statistical significance, the number of solar installations. The results inform the design of sustainability-focused VEPs and future research to understand the causal pathways between local governments' voluntary actions and solar market development.

Deimplementation of Ineffective and Harmful Medical Practices: A Data-Driven Commentary.

Deimplementation is the discontinuation or abandonment of medical practices that are ineffective or of unclear effectiveness, ranging from simply unhelpful to harmful. With epidemiology expanding to include more translational sciences, epidemiologists can contribute to deimplementation through defining evidence, establishing causality, and advising on study design. An estimated 10-30% of healthcare practices have minimal to no benefit to patients and should be targeted for deimplementation. The steps in deimplementation are: 1) identify low-value clinical practices, 2) facilitate the deimplementation process, 3) evaluate deimplementation outcomes, and 4) sustain deimplementation, each of which is a complex project. Deimplementation science involves researchers, healthcare and clinical stakeholders, and patient and community partners affected by the medical practice. Increasing collaboration between epidemiologists and implementation scientists is important to optimizing health care delivery.

Quasi-experimental methods for pharmacoepidemiology: difference-in-differences and synthetic control methods with case studies for vaccine evaluation.

Difference-in-differences and synthetic control methods have become common study designs for evaluating the effects of changes in policies, including health policies. They also have potential for providing real-world effectiveness and safety evidence in pharmacoepidemiology. To effectively add to the toolkit of the field, however, designs-including both their benefits and drawbacks-must be well understood. Quasi-experimental designs provide an opportunity to estimate the average treatment effect on the treated without requiring the measurement of all possible confounding factors, and to assess population-level effects. This requires, however, other key assumptions, including the parallel trends or stable weighting assumptions, a lack of other concurrent events that could alter time trends, and an absence of contamination between exposed and unexposed units. The targeted estimands are also highly specific to the settings of the study, and combining across units or time periods can be challenging. Case studies are presented for 3 vaccine evaluation studies, showcasing some of these challenges and opportunities in a specific field of pharmacoepidemiology. These methods provide feasible and valuable sources of evidence in various pharmacoepidemiologic settings and can be improved through research to identify and weigh the advantages and disadvantages in those settings. This article is part of a Special Collection on Pharmacoepidemiology.

Permanently infertile couples and family building-a cross-sectional survey in Denmark.

STUDY QUESTION: Which decision-making factors influence family building among permanently infertile couples? SUMMARY ANSWER: Ethical, legal, and financial considerations outweigh genetic relatedness in decision-making, favouring domestic gestational surrogacy, if this were possible, over international options. WHAT IS KNOWN ALREADY: Permanent infertility affects 4-5% of people in the fertile age. Their family-building options include adoption, surrogacy, uterus transplantation, foster care, and intentional multiple parenthood. However, in most countries, including Denmark, legal barriers constrain these methods due to surrogacy restrictions, suspended international adoptions, and the experimental status of uterus transplantation. Despite existing research on surrogacy, adoption, and specific causes of permanent infertility, a significant gap remains in our understanding of how couples with permanent infertility make family-building decisions within these limited frameworks. STUDY DESIGN, SIZE, DURATION: This cross-sectional study with 150 permanently infertile Danish participants was conducted from June to November 2023 using an online questionnaire. Multiple strategies, such as online forums, fertility clinics, hospital departments, and snowballing, were used to recruit a diverse sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included couples aged 26-50 years facing permanent infertility due to the following primary causes: women without a uterus (15%), women with a non-functional uterus (47%) or women for whom pregnancy would be life-threatening (9%), male couples (16%), transgender partner couples (2%), and other causes (11%). The survey collected data on demographics, reproductive history, family-building choices, and communication strategies. Closed questions were analysed using descriptive statistics. MAIN RESULTS AND THE ROLE OF CHANCE: Among 150 respondents, 41% had used transnational surrogacy, 27% adoption, 14% chose to remain childless, and 19% were undecided. Critical factors on family-building decisions were ethical, legal, and financial concerns which ranked higher than genetic relatedness. Despite the complexity of family building, most participants were open about their child's origin and received social support. If all family-building methods were legal and available in Denmark, domestic gestational surrogacy would be the preferred method, with uterus transplantation and remaining childless being least popular. LIMITATIONS, REASONS FOR CAUTION: The sample size is relatively small, despite the use of a variety of recruitment strategies. Nevertheless, this has ensured a diverse cohort representing the different reasons for infertility and family-building choices. It is important to note that the strategies may have favoured individuals achieving parenthood. WIDER IMPLICATIONS OF THE FINDINGS: The finding of our study reveals a notable gap between available family-building options in Denmark and the preferences of couples facing permanent infertility. These insights could be instrumental for organizations reviewing and developing family-building frameworks. Furthermore, for healthcare professionals guiding couples experiencing infertility issues in their attempts to build a family, an understanding of these preferences is essential to facilitate informed decisions about their future family plans. STUDY FUNDING/COMPETING INTEREST(S): The project was financed by the Independent Research Fund Denmark. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.