The OneFlorida Data Trust: a centralized,translational research data infrastructure of statewide scope

The OneFlorida Data Trust is a centralized research patient data repository created and managed by the OneFlorida Clinical Research Consortium (“OneFlorida”). It comprises structured electronic health record (EHR), administrative claims, tumor registry, death, and other data on 17.2 million individuals who received healthcare in Florida between January 2012 and the present. Ten healthcare systems in Miami, Orlando, Tampa, Jacksonville, Tallahassee, Gainesville, and rural areas of Florida contribute EHR data, covering the major metropolitan regions in Florida. Deduplication of patients is accomplished via privacy-preserving entity resolution (precision 0.97–0.99, recall 0.75), thereby linking patients’ EHR, claims, and death data. Another unique feature is the establishment of mother-baby relationships via Florida vital statistics data. Research usage has been significant, including major studies launched in the National Patient-Centered Clinical Research Network (“PCORnet”), where OneFlorida is 1 of 9 clinical research networks. The Data Trust’s robust, centralized, statewide data are a valuable and relatively unique research resource.     

Homologous Recombination Deficiency: Concepts,Definitions, and Assays

BackgroundHomologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting.MethodsFriends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status.ResultsThis publication provides findings from the group’s discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community.ConclusionOverall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors.     

Patterns of change in cortical morphometry following traumatic brain injury in adults

Progressive cortical volumetric loss following moderate–severe traumatic brain injury (TBI) has been observed; however, regionally specific changes in the structural determinants of cortical volume, namely, cortical thickness (CT) and cortical surface area (CSA), are unknown and may inform the patterns and neural substrates of neurodegeneration and plasticity following injury. We aimed to (a) assess differences in CT and CSA between TBI participants and controls in the early chronic stage post‐injury, (b) describe longitudinal changes in cortical morphometry following TBI, and (c) examine how regional changes in CT and CSA are associated. We acquired magnetic resonance images for 67 participants with TBI at up to 4 time‐points spanning 5 months to 7 years post‐injury, and 18 controls at 2 time‐points. In the early chronic stage, TBI participants displayed thinner cortices than controls, predominantly in frontal regions, but no CSA differences. Throughout the chronic period, TBI participants showed widespread CT reductions in posterior cingulate/precuneus regions and moderate CT increase in frontal regions. Additionally, CSA showed a significant decrease in the orbitofrontal cortex and circumscribed increase in posterior regions. No changes were identified in controls. Relationships between regional cortical changes in the same morphological measure revealed coordinated patterns within participants, whereas correlations between regions with CT and CSA change yielded bi‐directional relationships. This suggests that these measures may be differentially affected by neurodegenerative mechanisms such as transneuronal degeneration following TBI and that degeneration may be localized to the depths of cortical sulci. These findings emphasize the importance of dissecting morphometric contributions to cortical volume change.     

Biodiversity and infrastructure interact to drive tourism to and within Costa Rica

Nature-based tourism has potential to sustain biodiversity and economic development, yet the degree to which biodiversity drives tourism patterns, especially relative to infrastructure, is poorly understood. Here, we examine relationships between different types of biodiversity and different types of tourism in Costa Rica to address three questions. First, what is the contribution of species richness in explaining patterns of tourism in protected areas and country-wide in Costa Rica? Second, how similar are the patterns for birdwatching tourism compared to those of overall tourism? Third, where in the country is biodiversity contributing more than other factors to birdwatching tourism and to overall tourism? We integrated environmental data and species occurrence records to build species distribution models for 66 species of amphibians, reptiles, and mammals, and for 699 bird species. We used built infrastructure variables (hotel density and distance to roads), protected area size, distance to protected areas, and distance to water as covariates to evaluate the relative importance of biodiversity in predicting birdwatching tourism (via eBird checklists) and overall tourism (via Flickr photographs) within Costa Rica. We found that while the role of infrastructure is larger than any other variable, it alone is not sufficient to explain birdwatching and tourism patterns. Including biodiversity adds predictive power and alters spatial patterns of predicted tourism. Our results suggest that investments in infrastructure must be paired with successful biodiversity conservation for tourism to generate the economic revenue that countries like Costa Rica derive from it, now and into the future.

The tourism sector is well-poised to generate win–win approaches to biodiversity conservation and sustainable development given its nonextractive nature and its dependence on scenic beauty (1). However, for sustainable tourism to succeed as a strategy for biodiversity conservation, the role that biodiversity plays in driving tourism patterns needs to be better understood. On one hand, wildlife and nature motivate a significant portion of global tourism (2), and protected areas with higher species richness tend to attract more tourists and yield higher economic benefits (3). On the other hand, tourism hotspots also tend to occur in places where more human-built infrastructure (e.g., hotels, roads, and airports) enables access (4, 5). Studies have reached mixed conclusions on the relative importance of biodiversity and accessibility for tourism, and little is known about how they work in concert (6–11). Given the potential negative impacts of infrastructure on biodiversity conservation, their relative contributions to tourism deserves explicit study, particularly in developing countries where both biodiversity conservation and sustainable development are urgently needed (7, 12).Drivers of tourism patterns across landscapes have been explored through questionnaire surveys and structured interviews that ask tourists about their affinity for landscape features (13–15) and through spatial models that predict recreation using photographs (e.g., geographically weighted regression, MaxEnt) (16, 17). Recently, geo-tagged photographs and species lists shared on social media platforms have become popular tools for tourism-focused research (18–22). These studies, however, typically focus narrowly on the role of single taxa (22, 23) and landscape attributes without accounting for species diversity (14, 20), or they focus only on the role of infrastructure as a driver of tourism (5). Recent advances in satellite Earth observations make it possible to capture more of the ecosystem heterogeneity that can drive variability in species distributions, compared to more conventional modeling based on land cover (24–26). An integrated approach is needed, linking species richness of multiple taxa along with infrastructure variables, both modeled and mapped through high resolution Earth observations. Such an approach could be scaled up to larger regions and applied globally, helping to identify where biodiversity is playing a significant role in driving tourism, such that governments and the tourism sector can prioritize investments in biodiversity conservation.Here, we ask three questions in the iconic case of Costa Rica. First, what is the contribution of species richness (of vertebrate taxa) in explaining patterns of tourism in protected areas and also country-wide? Second, how similar are the patterns for birdwatching tourism compared to those of overall tourism? Third, where in the country is biodiversity contributing more than other factors to birdwatching tourism and to overall tourism? We predict that vertebrate species richness is more important for driving tourism in protected areas than in the rest of the country, because nature-seeking tourists often go to protected areas to find wildlife (3). We also expect that birdwatching tourism is predicted by richness of threatened and endemic bird species rather than total species richness, given birdwatchers’ preferences for rare birds (27). We predict a saturating relationship between species richness and tourism, because beyond a large number of species additional species are unlikely to contribute more to tourism (28). Finally, we predict that national-level tourism is better explained by infrastructure (such as roads and hotels) and distance to water than by biodiversity, because tourists going to Costa Rica often seek activities such as surfing and relaxing in beach resorts (29, 30). We predict nonlinear effects of proximity to roads and water, because a place is deemed inaccessible if it is further away from roads, and a beach tourist destination is also either close to water or not a destination at all. Access diminishes rapidly over a few miles (31).To answer our research questions, we analyze patterns of tourism at two different spatial scales. First, we analyze tourism patterns in protected areas only. Many protected areas provide reliable data on visitation rates and biodiversity tends to be higher inside than outside protected areas (29). However, given that they are often visited by tourists who are already interested in biodiversity, protected areas are not representative of all tourism patterns (30). Second, we evaluate the relative importance of biodiversity to all tourism across Costa Rica (excluding offshore islands). Investigating tourism across the whole nation may give a better understanding of how biodiversity contributes to tourism writ large and not only for tourists with a predisposition for finding wildlife. At both the protected area and national scales, we use a modified MaxEnt model that integrates species distribution models for 66 terrestrial vertebrate species (including amphibians, reptiles, and mammals) and 699 bird species, based on remotely sensed climate and habitat variables, with spatial patterns of infrastructure (hotel density and distance to roads) and distance to water. We measure tourism in two ways for both scales: using eBird checklists as a proxy for birdwatching (32), and using Flickr photographs as a proxy for all international and domestic tourism (19).Costa Rica is an ideal country to explore these questions because tourism represents 7% of the national gross domestic product and employs 3% of the working population directly and a further 9% indirectly (33). Approximately 70% of all international visitors to Costa Rica state that the wildlife, dramatic scenery, and opportunities for adventure sports are the main motivation for visiting the country (33, 34). However, the importance of biodiversity as a factor that influences tourism to, or domestically within, the country has not been evaluated (apart from very local studies) (35, 36). The Central Bank of Costa Rica is currently piloting a nature-based tourism account under the United Nations System of Environmental Economic Accounts (UN SEEA). The state of the art with this methodology is to attribute value to different ecosystems, which may vary widely in their biodiversity. Understanding the relationships between biodiversity and tourism in Costa Rica is a key step toward maintaining the vibrant ecotourism industry and can serve as an example for other biodiverse nations that often look to Costa Rica as a leader in sustainable development (37).     

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration’s RWE Data Working Group

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8–11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration’s Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.     

The Importance of Prisons in Achieving Hepatitis C Elimination: Insights from the Australian Experience

Following the availability of highly effective direct-acting antivirals (DAAs) to treat hepatitis C infection, the uptake of treatment by people living with hepatitis C rose dramatically in high- and middle-income countries but has since declined. To achieve the World Health Organization’s (WHO) 2030 target to eliminate hepatitis C as a public health threat among people who inject drugs, an increase in testing and treatment is required, together with improved coverage of harm reduction interventions. The population that remains to be treated in high- and middle-income countries with high hepatitis C prevalence are among the most socially disadvantaged, including people who inject drugs and are involved in the criminal justice system, a group with disproportionate hepatitis C prevalence, compared with people in the wider community. Imprisonment provides an unrivalled opportunity for screening and treating large numbers of people for hepatitis C, who may not access mainstream health services in the community. Despite some implementation challenges, evidence of the efficacy, acceptability, and cost-effectiveness of in-prison hepatitis treatment programs is increasing worldwide, and evaluations of these programs have demonstrated the capacity for treating people in high numbers. In this Perspective we argue that the scale-up of hepatitis C prevention, testing, and treatment programs in prisons, along with the investigation of new and adapted approaches, is critical to achieving WHO elimination goals in many regions; the Australian experience is highlighted as a case example. We conclude by discussing opportunities to improve access to prevention, testing, and treatment for people in prison and other justice-involved populations, including harnessing the changed practices brought about by the COVID-19 pandemic.