Environmental sources of infection can play a primary role in shaping epidemiological dynamics; however, the relative impact of environmental transmission on host‐pathogen systems is rarely ...estimated. We developed and fit a spatially explicit model of African swine fever virus (ASFV) in wild boar to estimate what proportion of carcass‐based transmission is contributing to the low‐level persistence of ASFV in Eastern European wild boar. Our model was developed based on ecological insight and data from field studies of ASFV and wild boar in Eastern Poland. We predicted that carcass‐based transmission would play a substantial role in persistence, especially in low‐density host populations where contact rates are low. By fitting the model to outbreak data using approximate Bayesian computation, we inferred that between 53% and 66% of transmission events were carcass‐based that is, transmitted through contact of a live host with a contaminated carcass. Model fitting and sensitivity analyses showed that the frequency of carcass‐based transmission increased with decreasing host density, suggesting that management policies should emphasize the removal of carcasses and consider how reductions in host densities may drive carcass‐based transmission. Sensitivity analyses also demonstrated that carcass‐based transmission is necessary for the autonomous persistence of ASFV under realistic parameters. Autonomous persistence through direct transmission alone required high host densities; otherwise re‐introduction of virus periodically was required for persistence when direct transmission probabilities were moderately high. We quantify the relative role of different persistence mechanisms for a low‐prevalence disease using readily collected ecological data and viral surveillance data. Understanding how the frequency of different transmission mechanisms vary across host densities can help identify optimal management strategies across changing ecological conditions.
African swine fever (ASF) is a highly virulent disease of swine with devastating socio‐economic consequences with persistence mechanisms that remain unknown in Eastern Europe. In this manuscript, we developed and fit a spatially explicit mechanistic epidemiological model to spatio‐temporal disease surveillance data using approximate Bayesian computation (ABC) to estimate the relative role of carcass‐based transmission in ASF virus persistence and spatial spread. We inferred that 53%‐66% of ASF virus transmission events occurred through the contact of susceptible hosts with dead carcasses and we found that the relative importance of transmission mechanisms depended critically on host density.
Elucidating correlations between wild pig (Sus scrofa) behavior and landscape attributes can aid in the advancement of management strategies for controlling populations. Using GPS data from 49 wild ...pigs in the southeastern U.S., we used hidden Markov models to define movement path characteristics and assign behaviors (e.g., resting, foraging, travelling). We then explored the connection between these behaviors and resource selection for both sexes between two distinct seasons based on forage availability (i.e., low forage, high forage). Females demonstrated a crepuscular activity pattern in the high-forage season and a variable pattern in the low-forage season, while males exhibited nocturnal activity patterns across both seasons. Wild pigs selected for bottomland hardwoods and dense canopy cover in all behavioral states in both seasons. Males selected for diversity in vegetation types while foraging in the low-forage season compared to the high-forage season and demonstrated an increased use of linear anthropogenic features across seasons while traveling. Wild pigs can establish populations and home ranges in an array of landscapes, but our results demonstrate male and female pigs exhibit clear differences in movement behavior and there are key resources associated with common behaviors that can be targeted to improve the efficiency of management programs.
Abstract
Background
Replenishing the physician-scientist workforce constitutes a central mission of medical education, but the loss of qualified trainees to non-academic positions remains an ongoing ...threat. Among the barriers facing physician-scientists today is the game-like model of U.S. medical residency matching through the National Research Matching Program (NRPM), which applies several assumptions regarding the comparability of applicant qualifications, cohort size, and the institutional breadth of applicants’ training needs.
Methods
The current report therefore summarizes the survey-based views and experiences of physician-scientist trainees obtained following the 2021–2022 application cycle for research-oriented residency programs, or physician-scientist training programs (PSTPs). From among this small cohort of applicants, we obtained survey-based feedback of 27 PSTP applicants across 17 U.S. medical universities, among whom 85% (23/27) matched into a PSTP.
Results
Among these PSTP applicants, 25/27 (93%) recognized “scientific community” as the most important feature of a postgraduate training program, with applicants identifying as female placing a higher value on the program’s infrastructure of personal and/or family support. Most (18/27) respondents found “waiting for interviews” as the most stressful phase of their application cycle, and roughly half of all respondents encountered at least one NRMP policy violation through post-interview communication. Specifically, 93% (25/27) respondents were contacted by at least one PSTP following interviews, and 1/3 of them admitted to feeling pressured into sharing their ranking preferences.
Conclusion
We highlight many previously unrecognized priorities among applicants to PSTPs, which include fostering community among its trainees and reinforcing structured mentoring. We uncover an inconsistency among PSTPs regarding the post-interview process, which represents an opportunity to better support applicants seeking to gauge programs according to their clinical, scientific, and academic interests as physician-scientists, while still adhering to NRMP policies.
Global biodiversity in river and riparian ecosystems is generated and maintained by geographic variation in stream processes and fluvial disturbance regimes, which largely reflect regional ...differences in climate and geology. Extensive construction of dams by humans has greatly dampened the seasonal and interannual streamflow variability of rivers, thereby altering natural dynamics in ecologically important flows on continental to global scales. The cumulative effects of modification to regional-scale environmental templates caused by dams is largely unexplored but of critical conservation importance. Here, we use 186 long-term streamflow records on intermediate-sized rivers across the continental United States to show that dams have homogenized the flow regimes on third- through seventh-order rivers in 16 historically distinctive hydrologic regions over the course of the 20th century. This regional homogenization occurs chiefly through modification of the magnitude and timing of ecologically critical high and low flows. For 317 undammed reference rivers, no evidence for homogenization was found, despite documented changes in regional precipitation over this period. With an estimated average density of one dam every 48 km of third- through seventh-order river channel in the United States, dams arguably have a continental scale effect of homogenizing regionally distinct environmental templates, thereby creating conditions that favor the spread of cosmopolitan, nonindigenous species at the expense of locally adapted native biota. Quantitative analyses such as ours provide the basis for conservation and management actions aimed at restoring and maintaining native biodiversity and ecosystem function and resilience for regionally distinct ecosystems at continental to global scales.
Tissue mechanical properties are significantly altered with the development of cancer. Magnetic resonance elastography (MRE) is a noninvasive technique capable of quantifying tissue mechanical ...properties in vivo. This review describes the basic principles of MRE and introduces some of the many promising MRE methods that have been developed for the detection and characterization of cancer, evaluation of response to therapy, and investigation of the underlying mechanical mechanisms associated with malignancy.
Management and policy decisions are continually made to mitigate disease introductions in animal populations despite often limited surveillance data or knowledge of disease transmission processes. ...Science-based management is broadly recognized as leading to more effective decisions yet application of models to actively guide disease surveillance and mitigate risks remains limited. Disease-dynamic models are an efficient method of providing information for management decisions because of their ability to integrate and evaluate multiple, complex processes simultaneously while accounting for uncertainty common in animal diseases. Here we review disease introduction pathways and transmission processes crucial for informing disease management and models at the interface of domestic animals and wildlife. We describe how disease transmission models can improve disease management and present a conceptual framework for integrating disease models into the decision process using adaptive management principles. We apply our framework to a case study of African swine fever virus in wild and domestic swine to demonstrate how disease-dynamic models can improve mitigation of introduction risk. We also identify opportunities to improve the application of disease models to support decision-making to manage disease at the interface of domestic and wild animals. First, scientists must focus on objective-driven models providing practical predictions that are useful to those managing disease. In order for practical model predictions to be incorporated into disease management a recognition that modeling is a means to improve management and outcomes is important. This will be most successful when done in a cross-disciplinary environment that includes scientists and decisionmakers representing wildlife and domestic animal health. Lastly, including economic principles of value-of-information and cost-benefit analysis in disease-dynamic models can facilitate more efficient management decisions and improve communication of model forecasts. Integration of disease-dynamic models into management and decision-making processes is expected to improve surveillance systems, risk mitigations, outbreak preparedness, and outbreak response activities.
Congenital hydrocephalus (CH) is a common neurological disorder affecting many newborns. Imbalanced neurogenesis is a major cause of CH. Multiple CH-associated mutations are within the RNA-binding ...domain of Trim71, a conserved, stem cell-specific RNA-binding protein. How these mutations alter stem cell fate is unclear. Here, we show that the CH-associated mutations R595H and R783H in Trim71 accelerate differentiation and enhance neural lineage commitment in mouse embryonic stem cells (mESCs), and reduce binding to mRNAs targeted by wild-type Trim71, consistent with previous reports. Unexpectedly, however, each mutant binds an ectopic and distinct repertoire of target mRNAs. R595H-Trim71, but not R783H-Trim71 nor wild-type Trim71, binds the mRNA encoding β-catenin and represses its translation. Increasing β-catenin by overexpression or treatment with a Wnt agonist specifically restores differentiation of R595H-Trim71 mESCs. These results suggest that Trim71 mutations give rise to unique gain-of-function pathological mechanisms in CH. Further, our studies suggest that disruption of the Wnt/β-catenin signaling pathway can be used to stratify disease etiology and develop precision medicine approaches for CH.
Few infectious diseases are entirely human-specific: Most human pathogens also circulate in animals or else originated in nonhuman hosts. Influenza, plague, and trypanosomiasis are classic examples ...of zoonotic infections that transmit from animals to humans. The multihost ecology of zoonoses leads to complex dynamics, and analytical tools, such as mathematical modeling, are vital to the development of effective control policies and research agendas. Much attention has focused on modeling pathogens with simpler life cycles and immediate global urgency, such as influenza and severe acute respiratory syndrome. Meanwhile, vector-transmitted, chronic, and protozoan infections have been neglected, as have crucial processes such as cross-species transmission. Progress in understanding and combating zoonoses requires a new generation of models that addresses a broader set of pathogen life histories and integrates across host species and scientific disciplines.
Effective management of widespread invasive species such as wild pigs (Sus scrofa) is limited by resources available to devote to the effort. Better insight of the effectiveness of different ...management strategies on population dynamics is important for guiding decisions of resource allocation over space and time. Using a dynamic population model, we quantified effects of culling intensities and time between culling events on population dynamics of wild pigs in the USA using empirical culling patterns and data-based demographic parameters. In simulated populations closed to immigration, substantial population declines (50-100%) occurred within 4 years when 20-60% of the population was culled annually, but when immigration from surrounding areas occurred, there was a maximum of 50% reduction, even with the maximum culling intensity of 60%. Incorporating hypothetical levels of fertility control with realistic culling intensities was most effective in reducing populations when they were closed to immigration and when intrinsic population growth rate was too high (> = 1.78) to be controlled by culling alone. However, substantial benefits from fertility control used in conjunction with culling may only occur over a narrow range of net population growth rates (i.e., where net is the result of intrinsic growth rates and culling) that varies depending on intrinsic population growth rate. The management implications are that the decision to use fertility control in conjunction with culling should rely on concurrent consideration of achievable culling intensity, underlying demographic parameters, and costs of culling and fertility control. The addition of fertility control reduced abundance substantially more than culling alone, however the effects of fertility control were weaker than in populations without immigration. Because these populations were not being reduced substantially by culling alone, fertility control could be an especially helpful enhancement to culling for reducing abundance to target levels in areas where immigration can't be prevented.
Vitamin B12 supplements typically contain doses that far exceed the recommended daily amount, and high exposures are generally considered safe. Competitive and syntrophic interactions for B12 exist ...between microbes in the gut. Yet, to what extent excessive levels contribute to the activities of the gut microbiota remains unclear. The objective of this study was to evaluate the effect of B12 on microbial ecology using a B12 supplemented mouse model with Citrobacter rodentium, a mouse-specific pathogen. Mice were fed a standard chow diet and received either water or water supplemented with B12 (cyanocobalamin: ~120 μg/day), which equates to approximately 25 mg in humans. Infection severity was determined by body weight, pathogen load, and histopathologic scoring. Host biomarkers of inflammation were assessed in the colon before and after the pathogen challenge.
Cyanocobalamin supplementation enhanced pathogen colonization at day 1 (P < 0.05) and day 3 (P < 0.01) postinfection. The impact of B12 on gut microbial communities, although minor, was distinct and attributed to the changes in the Lachnospiraceae populations and reduced alpha diversity. Cyanocobalamin treatment disrupted the activity of the low-abundance community members of the gut microbiota. It enhanced the amount of interleukin-12 p40 subunit protein (IL12/23p40; P < 0.001) and interleukin-17a (IL-17A; P < 0.05) in the colon of naïve mice. This immune phenotype was microbe dependent, and the response varied based on the baseline microbiota. The cecal metatranscriptome revealed that excessive cyanocobalamin decreased the expression of glucose utilizing genes by C. rodentium, a metabolic attribute previously associated with pathogen virulence.
Oral vitamin B12 supplementation promoted C. rodentium colonization in mice by altering the activities of the Lachnospiraceae populations in the gut. A lower abundance of select Lachnospiraceae species correlated to higher p40 subunit levels, while the detection of Parasutterella exacerbated inflammatory markers in the colon of naïve mice. The B12-induced change in gut ecology enhanced the ability of C. rodentium colonization by impacting key microbe-host interactions that help with pathogen exclusion. This research provides insight into how B12 impacts the gut microbiota and highlights potential consequences of disrupting microbial B12 competition/sharing through over-supplementation. Video Abstract.
PDF
