Times from Infection to Disease-Induced Death and their Influence on Final Population Sizes After Epidemic Outbreaks.

For epidemic models, it is shown that fatal infectious diseases cannot drive the host population into extinction if the incidence function is upper density-dependent. This finding holds even if a latency period is included and the time from infection to disease-induced death has an arbitrary length distribution. However, if the incidence function is also lower density-dependent, very infectious diseases can lead to a drastic decline of the host population. Further, the final population size after an epidemic outbreak can possibly be substantially affected by the infection-age distribution of the initial infectives if the life expectations of infected individuals are an unbounded function of infection age (time since infection). This is the case for lognormal distributions, which fit data from infection experiments involving tiger salamander larvae and ranavirus better than gamma distributions and Weibull distributions.

Do fatal infectious diseases eradicate host species?

In simple SI epidemic and endemic models, three classes of incidence functions are identified for their potential to be associated with host extinction: weakly upper density-dependent incidences are never associated with host extinction. Power incidences that depend on the number of susceptibles and infectives by powers strictly between 0 and 1 are associated with initial-constellation-dependent host extinction for all parameter values. Homogeneous incidences, of which frequency-dependent incidence is a very particular case, and power incidences are associated with global host extinction for certain parameter constellations and with host survival for others. Laboratory infection experiments with salamander larvae are equally well fitted by power incidences and certain upper density-dependent incidences such as the negative binomial incidence and do not rule out homogeneous incidences such as an asymmetric frequency-dependent incidence either.

A comparative case study of the accommodation of students with disabilities in online and in-person degree programs.

Fully online degree programs are an increasingly important part of the higher education ecosystem. Among the many challenges raised by the growth of fully online courses and degree programs is the question: Are institutions providing online students with disabilities accommodations that are comparable to those provided to students in traditional in-person degree programs? To explore this question, we compared students in a fully online biology degree program to students in the equivalent in-person degree program at a large research university. For each group, we assessed the frequency with which students register with the disability resource center, the range of specific accommodations provided, and course grades. Results show that students in the in-person program were nearly 30% more likely to be enrolled with the disability resource center, and that students in the online program were offered a narrower range of accommodations. However, in relative terms (i.e., compared to students without disabilities in their degree program), online students with disabilities perform better than in-person students with disabilities.

Challenges in cybersecurity: Lessons from biological defense systems.

Defending against novel, repeated, or unpredictable attacks, while avoiding attacks on the 'self', are the central problems of both mammalian immune systems and computer systems. Both systems have been studied in great detail, but with little exchange of information across the different disciplines. Here, we present a conceptual framework for structured comparisons across the fields of biological immunity and cybersecurity, by framing the context of defense, considering different (combinations of) defensive strategies, and evaluating defensive performance. Throughout this paper, we pose open questions for further exploration. We hope to spark the interdisciplinary discovery of general principles of optimal defense, which can be understood and applied in biological immunity, cybersecurity, and other defensive realms.

A landmark environmental law looks ahead.

In late December 1973, the United States enacted what some would come to call "the pitbull of environmental laws." In the 50 years since, the formidable regulatory teeth of the Endangered Species Act (ESA) have been credited with considerable successes, obliging agencies to draw upon the best available science to protect species and habitats. Yet human pressures continue to push the planet toward extinctions on a massive scale. With that prospect looming, and with scientific understanding ever changing, Science invited experts to discuss how the ESA has evolved and what its future might hold. -Brad Wible.

Evaluation of a filtration-based method for detecting Batrachochytrium dendrobatidis in natural bodies of water.

Infectious diseases are emerging as a significant threat to wildlife. The resulting increased effort to monitor wildlife diseases is driving the development of innovative pathogen monitoring techniques, including many polymerase chain reaction (PCR)-based diagnostics. Despite the utility of these PCR-based techniques, there is still much to be learned about their ability to accurately detect target pathogens in nature. We assessed the diagnostic sensitivity of a PCR-based water filtration technique to detect the directly transmitted aquatic fungal pathogen Batrachochytrium dendrobatidis (Bd) by comparing the results of 4 repeated filter sampling events from 20 ponds to those of skin swabs from ca. 60 boreal chorus frogs Pseudacris maculata from each pond. Filters failed to detect Bd in 31 to 77% of the swab-positive ponds, depending on the time of sampling. However, after 3 repeated sampling events, filtration of small volumes of water (ca. 600 ml) correctly identified 94% of the ponds that tested Bd positive with swabbing, with the highest rates of detection occurring after breeding but before larvae reached metamorphosis. Our results are a case study demonstrating the importance of timing and resampling for the detection of an aquatic microbial pathogen, Bd, from water. This will be a useful technique for monitoring Bd, but additional data are needed to test the degree to which our findings are species or population specific. Future studies need to examine the sensitivity of this technique in other habitats and species that host Bd. These studies will aid in the development of cost-effective monitoring regimes for Bd and potentially other aquatic pathogens.

Value of magnetic resonance arthrography in post-traumatic anterior shoulder instability prior to arthroscopy: a prospective evaluation of MRA versus arthroscopy.

PURPOSE: This prospective study was designed to evaluate the value of magnetic resonance arthrography (MRA) after traumatic anterior shoulder instability prior to arthroscopy. METHODS: Patients included had two or more shoulder dislocations, at least the first being traumatic. MRA images were scored for Hill Sachs lesions, superior labral anterior posterior (SLAP) lesions, rotator cuff tears, glenohumeral ligament (GHL) lesions and Bankart lesions. Consequently, a standardized shoulder arthroscopy was performed. Five surgeons were involved in the study, initially blinded to the MRA results. MRA and arthroscopic findings were compared. Interobserver agreement was calculated by using Cohen's Kappa coefficients (κ). RESULTS: Eighteen patients (13 male, 5 female) were included (mean age 26.1 years). Hill Sachs lesions demonstrated fair agreement (κ = 0.33) whereas for SLAP lesions moderate agreement was calculated (κ = 0.43). On MRA, four partial thickness rotator cuff lesions were seen, not being stated by arthroscopy. GHL lesions were described on MRA in 15 patients; only two patients turned out to have GHL lesions at arthroscopy. Two arthroscopically diagnosed Bankart lesions which needed surgical treatment were not detected by MRA (moderate agreement, κ = 0.47). CONCLUSIONS: In patients with post-traumatic anterior glenohumeral instability MRA shows many lesions that can not be confirmed by arthroscopy and therefore do not have therapeutical consequences. On the other hand some labral lesions which do need surgical treatment are not detected on MRA. At least from this study, it can be concluded that MRA has limited value prior to the arthroscopic treatment of post-traumatic shoulder instability.

The challenges and scope of theoretical biology.

Scientific theories seek to provide simple explanations for significant empirical regularities based on fundamental physical and mechanistic constraints. Biological theories have rarely reached a level of generality and predictive power comparable to physical theories. This discrepancy is explained through a combination of frozen accidents, environmental heterogeneity, and widespread non-linearities observed in adaptive processes. At the same time, model building has proven to be very successful when it comes to explaining and predicting the behavior of particular biological systems. In this respect biology resembles alternative model-rich frameworks, such as economics and engineering. In this paper we explore the prospects for general theories in biology, and suggest that these take inspiration not only from physics, but also from the information sciences. Future theoretical biology is likely to represent a hybrid of parsimonious reasoning and algorithmic or rule-based explanation. An open question is whether these new frameworks will remain transparent to human reason. In this context, we discuss the role of machine learning in the early stages of scientific discovery. We argue that evolutionary history is not only a source of uncertainty, but also provides the basis, through conserved traits, for very general explanations for biological regularities, and the prospect of unified theories of life.

Move it or lose it? The ecological ethics of relocating species under climate change.

Managed relocation (also known as assisted colonization, assisted migration) is one of the more controversial proposals to emerge in the ecological community in recent years. A conservation strategy involving the translocation of species to novel ecosystems in anticipation of range shifts forced by climate change, managed relocation (MR) has divided many ecologists and conservationists, mostly because of concerns about the potential invasion risk of the relocated species in their new environments. While this is indeed an important consideration in any evaluation of MR, moving species across the landscape in response to predicted climate shifts also raises a number of larger and important ethical and policy challenges that need to be addressed. These include evaluating the implications of a more aggressive approach to species conservation, assessing MR as a broader ecological policy and philosophy that departs from longstanding scientific and management goals focused on preserving ecological integrity, and considering MR within a more comprehensive ethical and policy response to climate change. Given the complexity and novelty of many of the issues at stake in the MR debate, a more dynamic and pragmatic approach to ethical analysis and debate is needed to help ecologists, conservationists, and environmental decision makers come to grips with MR and the emerging ethical challenges of ecological policy and management under global environmental change.

Amphibian decline and extinction: what we know and what we need to learn.

For over 350 million yr, thousands of amphibian species have lived on Earth. Since the 1980s, amphibians have been disappearing at an alarming rate, in many cases quite suddenly. What is causing these declines and extinctions? In the modern era (post 1500) there are 6 leading causes of biodiversity loss in general, and all of these acting alone or together are responsible for modern amphibian declines: commercial use; introduced/exotic species that compete with, prey on, and parasitize native frogs and salamanders; land use change; contaminants; climate change; and infectious disease. The first 3 causes are historical in the sense that they have been operating for hundreds of years, although the rate of change due to each accelerated greatly after about the mid-20th century. Contaminants, climate change, and emerging infectious diseases are modern causes suspected of being responsible for the so-called 'enigmatic decline' of amphibians in protected areas. Introduced/exotic pathogens, land use change, and infectious disease are the 3 causes with a clear role in amphibian decline as well as extinction; thus far, the other 3 causes are only implicated in decline and not extinction. The present work is a review of the 6 causes with a focus on pathogens and suggested areas where new research is needed. Batrachochytrium dendrobatidis (Bd) is a chytrid fungus that is an emerging infectious disease causing amphibian population decline and species extinction. Historically, pathogens have not been seen as a major cause of extinction, but Bd is an exception, which is why it is such an interesting, important pathogen to understand. The late 20th and early 21st century global biodiversity loss is characterized as a sixth extinction event. Amphibians are a striking example of these losses as they disappear at a rate that greatly exceeds historical levels. Consequently, modern amphibian decline and extinction is a lens through which we can view the larger story of biodiversity loss and its consequences.

Amphibian chytrid fungus and ranaviruses in the Northwest Territories, Canada.

Pathogens can cause serious declines in host species, and knowing where pathogens associated with host declines occur facilitates understanding host-pathogen ecology. Suspected drivers of global amphibian declines include infectious diseases, with 2 pathogens in particular, Batrachochytrium dendrobatidis (Bd) and ranaviruses, causing concern. We explored the host range and geographic distribution of Bd and ranaviruses in the Taiga Plains ecoregion of the Northwest Territories, Canada, in 2007 and 2008. Both pathogens were detected, greatly extending their known geographic distributions. Ranaviruses were widespread geographically, but found only in wood frogs. In contrast, Bd was found at a single site, but was detected in all 3 species of amphibians in the survey area (wood frogs, boreal chorus frogs, western toads). The presence of Bd in the Northwest Territories is not congruent with predicted distributions based on niche models, even though findings from other studies at northern latitudes are consistent with those same models. Unexpectedly, we also found evidence that swabs routinely used to collect samples for Bd screening detected fewer infections than toe clips. Our use and handling of the swabs was consistent with other studies, and the cause of the apparent lack of integrity of swabs is unknown. The ranaviruses detected in our study were confirmed to be Frog Virus 3 by sequence analysis of a diagnostic 500 bp region of the major capsid protein gene. It is unknown whether Bd or ranaviruses are recent arrivals to the Canadian north. However, the genetic analyses required to answer that question can inform larger debates about the origin of Bd in North America as well as the potential effects of climate change and industrial development on the distributions of these important amphibian pathogens.

Online biology degree program broadens access for women, first-generation to college, and low-income students, but grade disparities remain.

Online education has grown rapidly in recent years with many universities now offering fully online degree programs even in STEM disciplines. These programs have the potential to broaden access to STEM degrees for people with social identities currently underrepresented in STEM. Here, we ask to what extent is that potential realized in terms of student enrollment and grades for a fully online degree program. Our analysis of data from more than 10,000 course-enrollments compares student demographics and course grades in a fully online biology degree program to demographics and grades in an equivalent in-person biology degree program at the same university. We find that women, first-generation to college students and students eligible for federal Pell grants constitute a larger proportion of students in the online program compared to the in-person mode. However, the online mode of instruction is associated with lower course grades relative to the in-person mode. Moreover, African American/Black, Hispanic/Latinx, Native American, and Pacific Islander students as well as federal Pell grant eligible students earned lower grades than white students and non-Pell grant eligible students, respectively, but the grade disparities were similar among both in-person and online student groups. Finally, we find that grade disparities between men and women are larger online compared to in-person, but that for first-generation to college women, the online mode of instruction is associated with little to no grade gap compared to continuing generation women. Our findings indicate that although this online degree program broadens access for some student populations, inequities in the experience remain and need to be addressed in order for online education to achieve its inclusive mission.

Protection of wetlands as a strategy for reducing the spread of avian influenza from migratory waterfowl.

Highly pathogenic avian influenza (HPAI) H5N1 has led to the death or destruction of millions of domesticated and wild birds and caused hundreds of human deaths worldwide. As with other HPAIs, H5N1 outbreaks among poultry have generally been caused by contact with infected migratory waterfowl at the interface of wildlands and human-dominated landscapes. Using a case-control epidemiological approach, we analyzed the relation between habitat protection and H5N1 outbreaks in China from 2004 to 2017. We found that while proximity to unprotected waterfowl habitats and rice paddy generally increased outbreak risk, proximity to the most highly protected habitats (e.g., Ramsar-designated lakes and wetlands) had the opposite effect. Protection likely involves two mechanisms: the separation of wild waterfowl and poultry populations and the diversion of wild waterfowl from human-dominated landscapes toward protected natural habitats. Wetland protection could therefore be an effective means to control avian influenza while also contributing to avian conservation.

Comment on "Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity".

Scheele et al (Reports, 29 March 2019, p. 1459) bring needed attention to the effects of amphibian infectious disease. However, the data and methods implicating the disease chytridiomycosis in 501 amphibian species declines are deficient. Which species are affected, and how many, remains a critical unanswered question. Amphibians are imperiled; protective actions require public support and robust science.

Spatial and temporal patterns of Ambystoma tigrinum virus (ATV) prevalence in tiger salamanders Ambystoma tigrinum nebulosum.

Amphibian ranaviruses have been documented as causes of mass mortality in amphibian populations throughout the world. The temporal and spatial dynamics of ranavirus infections when epidemics are not apparent remains unclear. To address this question, we collected tissue samples from 2003 to 2006 in 4 geographically separated tiger salamander Ambystoma tigrinum nebulosum host populations on the Kaibab Plateau in northern Arizona. We tested for Ambystoma tigrinum virus (ATV), a lethal ranavirus of tiger salamanders, calculated ATV prevalence for each sampling date, and examined temporal and spatial patterns by quantifying the annual level of ATV synchrony among populations using the intraclass correlation coefficient. Salamander populations were commonly infected with ATV. We observed no morbidity or mortality in these populations even as ATV prevalence values varied from 0 to 57%. Infection prevalence across the landscape was more similar within a given year than between years. There was no statistically significant spatial pattern in prevalence across the landscape. Our findings highlight the need to explore new hypotheses regarding the population level impact of these pathogens on amphibian communities.

Safe CRISPR: Challenges and Possible Solutions.

Applications of CRISPR in human health and in gene drives are at the forefront of biological research as tools. This technology will affect humankind and our environment, so as this technology pushes forward, the design and implementation of safety measures is imperative. Novel technologies and forethought in various applications of CRISPR are essential for using this technology safely. Here, we review environmental and health-related safety concerns associated with using CRISPR and ways proposed to minimize risk.

Habitat fragmentation as a result of biotic and abiotic factors controls pathogen transmission throughout a host population.

1. The hypothesis that habitat fragmentation (biotic or abiotic) alters the transmission of disease within a population is explored using field data from a well-studied amphibian-pathogen system. 2. We used the Ambystoma tigrinum-A. tigrinum virus (ATV) model system to show how habitat fragmentation as a result of emergent vegetation and habitat management affects disease transmission dynamics in ponds across a landscape. 3. We quantified variation in ATV infection over time and across the landscape. ATV infection was significantly higher in ponds modified for livestock use (P = 0.032). Disease incidence decreased with increased amounts of emergent vegetation (P < 0.001). These factors appear to control disease transmission by altering the host contact rate and with it disease transmission. 4. A field experiment to test the effect of emergent vegetation on the distribution of larvae in ponds demonstrated a behavioural change in larvae found in sparsely vegetated ponds. Microhabitat choices resulted in larvae being concentrated at the pond edge resulting in a 'halo effect' in sparsely vegetated ponds, whereas larvae in heavily vegetated ponds were distributed more evenly throughout. Microhabitat choice affects the effective density that larvae experience. This 'halo effect' increases contact rates in the shallows of sparsely vegetated ponds and increases the transmission of a directly transmitted pathogen. 5. Despite recurrent epidemics of a lethal Ranavirus in tiger salamanders on the Kaibab Plateau, Arizona, USA, these populations persist. We discuss the implications of our results in the context of density-dependent transmission and homogeneous mixing, two increases key assumptions of epidemiological theory.

Amphibian commerce as a likely source of pathogen pollution.

The commercial trade of wildlife occurs on a global scale. In addition to removing animals from their native populations, this trade may lead to the release and subsequent introduction of nonindigenous species and the pathogens they carry. Emerging infectious diseases, such as chytridiomycosis caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), and ranaviral disease have spread with global trade in amphibians and are linked to amphibian declines and die-offs worldwide, which suggests that the commercial trade in amphibians may be a source of pathogen pollution. We screened tiger salamanders involved in the bait trade in the western United States for both ranaviruses and Bd with polymerase chain reaction and used oral reports from bait shops and ranavirus DNA sequences from infected bait salamanders to determine how these animals and their pathogens are moved geographically by commerce. In addition, we conducted 2 surveys of anglers to determine how often tiger salamanders are used as bait and how often they are released into fishing waters by anglers, and organized bait-shop surveys to determine whether tiger salamanders are released back into the wild after being housed in bait shops. Ranaviruses were detected in the tiger salamander bait trade in Arizona, Colorado, and New Mexico, and Bd was detected in Arizona bait shops. Ranaviruses were spread geographically through the bait trade. All tiger salamanders in the bait trade were collected from the wild, and in general they moved east to west and north to south, bringing with them their multiple ranavirus strains. Finally, 26-73% of anglers used tiger salamanders as fishing bait, 26-67% of anglers released tiger salamanders bought as bait into fishing waters, and 4% of bait shops released tiger salamanders back into the wild after they were housed in shops with infected animals. The tiger salamander bait trade in the western United States is a useful model for understanding the consequences of the unregulated anthropogenic movement of amphibians and their pathogens through trade.

Gene drives in our future: challenges of and opportunities for using a self-sustaining technology in pest and vector management.

Gene drives are systems of biased inheritance that enhance the likelihood a sequence of DNA passes between generations through sexual reproduction and potentially throughout a local population and ultimately all connected populations of a species. Gaps in our knowledge of gene drive systems prompted the US National Institutes of Health (NIH) and the Foundation for the NIH to ask the US National Academies of Sciences, Engineering, and Medicine (NASEM) to convene an expert panel to provide an independent, objective examination of what we know about gene drive systems. The report, "Gene drives on the horizon: Advancing science, navigating uncertainty, and aligning research with public values," outlines our understanding of the science, ethics, public engagement, governance, and risk assessment pertaining to gene drive research. Researchers have studied naturally occurring gene drive systems for more than a century. While CRISPR/Cas9 was not the first molecular tool considered to create an engineered gene drive, the advent of the CRISPR/Cas9 technology for gene editing gave a renewed impetus to developing gene drives in the laboratory for eventual release in the field. Recent experiments demonstrate that a CRISPR/Cas9-based gene drive can spread a targeted gene throughout nearly all of laboratory populations of yeast, fruit flies, or mosquitoes. Applying this basic science, there are proposals to use gene drive modified organisms to address such things as eradication of insect-borne infectious diseases and conservation of threatened and endangered species. Gene drives could potentially support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and by control of damaging, invasive species. A major recommendation of the NASEM report is that there is insufficient evidence at this time to support release of gene-drive modified organisms into the environment. Importantly, the committee also recognized that the potential benefits of gene drives for basic and applied research are significant and justify proceeding with laboratory research and controlled field trials. This review summarizes highlights of the NASEM report with its focus on using the CRISPR/Cas9 genome-editing technology to develop gene drive modified organisms.