Comparative pathogenesis of two genotype VI.2 avian paramyxovirus type-1 viruses (APMV-1) in pheasants, partridges and chickens.

Newcastle disease (ND) is caused by virulent forms of avian paramyxovirus-1 (APMV-1) and is an economically important disease of poultry world-wide. Pigeon paramyxovirus 1 (PPMV-1), a sub-group of APMV-1 is endemic in Columbiformes and can cause infections of poultry. An outbreak of ND in partridges in Scotland, UK, in 2006 (APMV-1/partridge/UK(Scotland)/7575/06) was identified as a class II, genotype VI.2.1.1.2.1, more commonly associated with PPMV-1. It has been hypothesized that game birds may be a route of transmission into commercial poultry settings due to the semi-feral rearing system, which potentially brings them into contact with both wild-birds and poultry species. Therefore, the pathogenesis and transmission of APMV-1/partridge/UK(Scotland)/7575/06 in game birds and chickens was investigated, and compared to a contemporary PPMV-1 isolate, PPMV-1/pigeon/UK/015874/15. Viral shedding and seroconversion profiles demonstrated that pheasants were susceptible to infection with APMV-1/partridge/UK(Scotland)/7575/06 with limited clinical signs observed although they were able to excrete and transmit virus. In contrast, partridges and pheasants showed limited infection with PPMV-1/pigeon/UK/015874/15, causing mild clinical disease. Chickens, however, were productively infected and were able to transmit virus in the absence of clinical signs. From the data, it can be deduced that whilst game birds may play a role in the transmission and epidemiology of genotype VI.2 APMV-1 viruses, the asymptomatic nature of circulation within these species precludes evaluation of natural infection by clinical surveillance. It therefore remains a possibility that genotype VI.2 APMV-1 infection in game birds has the potential for asymptomatic circulation and remains a potential threat to avian production systems.RESEARCH HIGHLIGHTS Demonstration of infection of game birds with Pigeon paramyxovirus-1 (PPMV-1).There are differing dynamics of infection between different game bird species.Differing dynamics of infection between different PPMV-1 isolates and genotypes in game birds and chickens.

Inductive Risk, Science, and Values: A Reply to MacGillivray.

The argument from inductive risk (AIR) is perhaps the most common argument against the value-free ideal of science. Brian MacGillivray rejects the AIR (at least as it would apply to risk assessment) and embraces the value-free ideal. We clarify the issues at stake and argue that MacGillivray's criticisms, although effective against some formulations of the AIR, fail to overcome the essential concerns that motivate the AIR. There are inevitable trade-offs in scientific enquiry that cannot be resolved with any formal methods or general rules. Choices must be made, and values will be involved. It is best to recognize this explicitly. Even so, there is more work to be done developing methods and institutional support for these choices.

Open science, the replication crisis, and environmental public health.

Concerns about a crisis of mass irreplicability across scientific fields ("the replication crisis") have stimulated a movement for open science, encouraging or even requiring researchers to publish their raw data and analysis code. Recently, a rule at the US Environmental Protection Agency (US EPA) would have imposed a strong open data requirement. The rule prompted significant public discussion about whether open science practices are appropriate for fields of environmental public health. The aims of this paper are to assess (1) whether the replication crisis extends to fields of environmental public health; and (2) in general whether open science requirements can address the replication crisis. There is little empirical evidence for or against mass irreplicability in environmental public health specifically. Without such evidence, strong claims about whether the replication crisis extends to environmental public health - or not - seem premature. By distinguishing three concepts - reproducibility, replicability, and robustness - it is clear that open data initiatives can promote reproducibility and robustness but do little to promote replicability. I conclude by reviewing some of the other benefits of open science, and offer some suggestions for funding streams to mitigate the costs of adoption of open science practices in environmental public health.

The P value plot does not provide evidence against air pollution hazards.

A number of papers by Young and collaborators have criticized epidemiological studies and meta-analyses of air pollution hazards using a graphical method that the authors call a P value plot, claiming to find zero effects, heterogeneity, and P hacking. However, the P value plot method has not been validated in a peer-reviewed publication. The aim of this study was to investigate the statistical and evidentiary properties of this method. Methods: A simulation was developed to create studies and meta-analyses with known real effects δ , integrating two quantifiable conceptions of evidence from the philosophy of science literature. The simulation and analysis is publicly available and automatically reproduced. Results: In this simulation, the plot did not provide evidence for heterogeneity or P hacking with respect to any condition. Under the right conditions, the plot can provide evidence of zero effects; but these conditions are not satisfied in any actual use by Young and collaborators. Conclusion: The P value plot does not provide evidence to support the skeptical claims about air pollution hazards made by Young and collaborators.

Census Demographics and Chlorpyrifos Use in California's Central Valley, 2011-15: A Distributional Environmental Justice Analysis.

Chlorpyrifos, an acetylcholinesterase inhibitor (ACI), is one of the most widely used insecticides in the world, and is generally recognized to be a moderate human neurotoxin. This paper reports a distributional environmental justice (dEJ) analysis of chlorpyrifos use in California's Central Valley, examining the way distributions of environmental risks are associated with race, ethnicity, class, gender, and other systems of structural oppression. Spatial data on chlorpyrifos use were retrieved from California's Department of Pesticide Registration public pesticide use records for 2011-2015. These data were combined with demographic data for the Central Valley from the American Community Survey (ACS). Spatial regression models were used to estimate effects of demographic covariates on local chlorpyrifos use. A novel bootstrap method was used to account for measurement error in the ACS estimates. This study finds consistent evidence that Hispanic population proportion is associated with increased local chlorpyrifos use. A 10-point increase in Hispanic proportion is associated with an estimated 1.05-1.4-fold increase in local chlorpyrifos use across Census tract models. By contrast, effects of agricultural employment and poverty on local chlorpyrifos use are ambiguous and inconsistent between Census tracts and Census-designated places.

The effect of BCG vaccination on macrophage phenotype in a mouse model of intranasal Mycobacterium bovis challenge.

In order to develop improved vaccinations against tuberculosis, it is essential to understand the effect of vaccination on the immune response, and to overcome the mechanisms by which mycobacteria regulate this immune response. In this study, we examine the effect of intradermal vaccination with Mycobacterium bovis bacille Calmette-Guèrin on macrophage phenotype following intranasal challenge with virulent Mycobacterium bovis. Preserved lung tissues used in the present study were obtained from a previous vaccination trial in BALB/c mice. Vaccinated mice showed less extensive pulmonary lesions along with a significant decrease in bacterial lung burden when compared to control mice. Immunohistochemical markers of classically activated macrophages (iNOS) and alternatively activated macrophages (Arg1, FIZZ1) were applied to lung sections. Vaccination led to a statistically significant decrease in the number of Arg1+ macrophages. The presence of macrophages that expressed Arginase 1 in pulmonary lesions was much smaller than the presence of macrophages expressing iNOS. The low presence of Arg1+ macrophages induced by vaccination may be caused by Th1 polarization and may reduce alternative activation of macrophages, with an overall more effective intracellular killing of bacteria.

West Nile Virus spread and differential chemokine response in the central nervous system of mice: Role in pathogenic mechanisms of encephalitis.

West Nile virus (WNV) is a zoonotic mosquito-borne flavivirus able to cause severe neurological disease in humans, horses and various avian species. The more severe pathological changes of neurotropic WNV infection are caused by virus neuroinvasion and/or the immunological response in the central nervous system (CNS). The extent in which inflammatory cell trafficking orchestrated by chemokines is involved in the pathogenesis of CNS lesions has not been entirely elucidated. To understand the sequence of pro-inflammatory chemokine induction during WNV encephalitis, a murine intranasal inoculation model was used. The relationship between lesional patterns in the mice CNS, the viral antigen distribution and the expression of pro-inflammatory chemokine (CCL2, CCL5 and CXCL10) were evaluated. Viral antigen was first observed in olfactory tract and pyriform cortex neurons, suggesting a retrograde neuronal infection from the olfactory nerve. A spatio-temporal association between WNV antigen and perivascular cuffs development was observed. Chemokine immunostaining was widely distributed in the brain from early stages. CCL2 immunolabelling was localised in neurons, astrocytes, microglia and endothelial cells as well as mononuclear leucocytes within perivascular cuffs. In contrast, CCL5 and CXCL10 immunostaining were mainly observed in astroglia and neurons, respectively. A strong correlation was demonstrated between the presence of perivascular cuffs and CCL2 and CCL5 expression in most brain areas, while CXCL10 was only associated with inflammatory lesions in few specific regions. Importantly, a strong correlation between WNV and CCL5 distribution was observed. However, no correlation was observed between CXCL10 and viral antigen. Neurons were confirmed as the main target cells of WNV, as well as one of the sources of CCL2, CCL5 and CXCL10. This study shows the sequence and comparative distribution pattern between histological lesions, WNV antigen and chemokine expression over the infection process. Furthermore, it identifies potential targets for immune intervention to suppress damaging chemokine responses.

Legitimizing Values in Regulatory Science.

BACKGROUND: Over the last several decades, scientists and social groups have frequently raised concerns about politicization or political interference in regulatory science. Public actors (environmentalists and industry advocates, politically aligned public figures, scientists and political commentators, in the United States as well as in other countries) across major political-regulatory controversies have expressed concerns about the inappropriate politicization of science. Although we share concerns about the politicization of science, they are frequently framed in terms of an ideal of value-free science, according to which political and economic values have no legitimate role to play in science. For several decades, work in philosophy of science has identified serious conceptual and practical problems with the value-free ideal. OBJECTIVES: Our objectives are to discuss the literature regarding the conceptual and practical problems with the value-free ideal and offer a constructive alternative to the value-free ideal. DISCUSSION: We first discuss the prevalence of the value-free ideal in regulatory science, then argue that this ideal is self-undermining and has been exploited to delay protective regulation. To offer a constructive alternative, we analyze the relationship between the goals of regulatory science and the standards of good scientific activity. This analysis raises questions about the relationship between methodological and practical standards for good science, tensions among various important social goods, and tensions among various social interests. We argue that the aims of regulatory science help to legitimize value-laden choices regarding research methods and study designs. Finally, we discuss how public deliberation, adaptive management, and community-based participatory research can be used to improve the legitimacy of scientists as representatives of the general public on issues of environmental knowledge. CONCLUSIONS: Reflecting on the aims of regulatory science-such as protecting human health and the environment, informing democratic deliberation, and promoting the capacities of environmental justice and Indigenous communities-can clarify when values have legitimate roles in regulatory science. https://doi.org/10.1289/EHP3317.

Network analysis to evaluate the impact of research funding on research community consolidation.

In 2004, the Alfred P. Sloan Foundation launched a new program focused on incubating a new field, "Microbiology of the Built Environment" (MoBE). By the end of 2017, the program had supported the publication of hundreds of scholarly works, but it was unclear to what extent it had stimulated the development of a new research community. We identified 307 works funded by the MoBE program, as well as a comparison set of 698 authors who published in the same journals during the same period of time but were not part of the Sloan Foundation-funded collaboration. Our analysis of collaboration networks for both groups of authors suggests that the Sloan Foundation's program resulted in a more consolidated community of researchers, specifically in terms of number of components, diameter, density, and transitivity of the coauthor networks. In addition to highlighting the success of this particular program, our method could be applied to other fields to examine the impact of funding programs and other large-scale initiatives on the formation of research communities.

Bibliometrics for Social Validation.

This paper introduces a bibliometric, citation network-based method for assessing the social validation of novel research, and applies this method to the development of high-throughput toxicology research at the US Environmental Protection Agency. Social validation refers to the acceptance of novel research methods by a relevant scientific community; it is formally independent of the technical validation of methods, and is frequently studied in history, philosophy, and social studies of science using qualitative methods. The quantitative methods introduced here find that high-throughput toxicology methods are spread throughout a large and well-connected research community, which suggests high social validation. Further assessment of social validation involving mixed qualitative and quantitative methods are discussed in the conclusion.

The Virtues of Scientific Practice: MacIntyre, Virtue Ethics, and the Historiography of Science.

"Practice" has become a ubiquitous term in the history of science, and yet historians have not always reflected on its philosophical import and in particular on its potential connections with ethics. This essay draws on the work of the virtue ethicist Alasdair MacIntyre to develop a theory of "communal practices" and explore how such an approach can inform the history of science, including allegations about the corruption of science by wealth or power, consideration of scientific ethics or "moral economies," the role of values in science, the ethical distinctiveness (or not) of scientific vocations, and the relationship between history of science and the practice of science itself.

Epistemological depth in a GM crops controversy.

This paper examines the scientific controversy over the yields of genetically modified [GM] crops as a case study in epistemologically deep disagreements. Appeals to "the evidence" are inadequate to resolve such disagreements; not because the interlocutors have radically different metaphysical views (as in cases of incommensurability), but instead because they assume rival epistemological frameworks and so have incompatible views about what kinds of research methods and claims count as evidence. Specifically, I show that, in the yield debate, proponents and opponents of GM crops cite two different sets of claims as evidence, which correspond to two rival epistemological frameworks, classical experimental epistemology and Nancy Cartwright's evidence for use. I go on to argue that, even if both sides of the debate accepted Cartwright's view, they might still disagree over what counts as evidence, because evidence for use ties standards of evidence to what is sometimes called the "context of application."

Lyssavirus infection: 'low dose, multiple exposure' in the mouse model.

The European bat lyssaviruses (EBLV-1 and EBLV-2) are zoonotic pathogens present within bat populations across Europe. The maintenance and transmission of lyssaviruses within bat colonies is poorly understood. Cases of repeated isolation of lyssaviruses from bat roosts have raised questions regarding the maintenance and intraspecies transmissibility of these viruses within colonies. Furthermore, the significance of seropositive bats in colonies remains unclear. Due to the protected nature of European bat species, and hence restrictions to working with the natural host for lyssaviruses, this study analysed the outcome following repeat inoculation of low doses of lyssaviruses in a murine model. A standardized dose of virus, EBLV-1, EBLV-2 or a 'street strain' of rabies (RABV), was administered via a peripheral route to attempt to mimic what is hypothesized as natural infection. Each mouse (n=10/virus/group/dilution) received four inoculations, two doses in each footpad over a period of four months, alternating footpad with each inoculation. Mice were tail bled between inoculations to evaluate antibody responses to infection. Mice succumbed to infection after each inoculation with 26.6% of mice developing clinical disease following the initial exposure across all dilutions (RABV, 32.5% (n=13/40); EBLV-1, 35% (n=13/40); EBLV-2, 12.5% (n=5/40)). Interestingly, the lowest dose caused clinical disease in some mice upon first exposure ((RABV, 20% (n=2/10) after first inoculation; RABV, 12.5% (n=1/8) after second inoculation; EBLV-2, 10% (n=1/10) after primary inoculation). Furthermore, five mice developed clinical disease following the second exposure to live virus (RABV, n=1; EBLV-1, n=1; EBLV-2, n=3) although histopathological examination indicated that the primary inoculation was the most probably cause of death due to levels of inflammation and virus antigen distribution observed. All the remaining mice (RABV, n=26; EBLV-1, n=26; EBLV-2, n=29) survived the tertiary and quaternary inoculations although the serological response did not necessarily reflect the repeated exposure. We conclude that despite repeated exposure, neither clinical disease nor serological response can be predicted and that further studies are required to understand the mechanisms behind survival following multiple exposures to lyssaviruses.