High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease.

Individual reports suggest that the central nervous system (CNS) contains multiple immune cell types with diverse roles in tissue homeostasis, immune defense, and neurological diseases. It has been challenging to map leukocytes across the entire brain, and in particular in pathology, where phenotypic changes and influx of blood-derived cells prevent a clear distinction between reactive leukocyte populations. Here, we applied high-dimensional single-cell mass and fluorescence cytometry, in parallel with genetic fate mapping systems, to identify, locate, and characterize multiple distinct immune populations within the mammalian CNS. Using this approach, we revealed that microglia, several subsets of border-associated macrophages and dendritic cells coexist in the CNS at steady state and exhibit disease-specific transformations in the immune microenvironment during aging and in models of Alzheimer's disease and multiple sclerosis. Together, these data and the described framework provide a resource for the study of disease mechanisms, potential biomarkers, and therapeutic targets in CNS disease.

Clustered versus catastrophic global vertebrate declines.

Recent analyses have reported catastrophic global declines in vertebrate populations1,2. However, the distillation of many trends into a global mean index obscures the variation that can inform conservation measures and can be sensitive to analytical decisions. For example, previous analyses have estimated a mean vertebrate decline of more than 50% since 1970 (Living Planet Index2). Here we show, however, that this estimate is driven by less than 3% of vertebrate populations; if these extremely declining populations are excluded, the global trend switches to an increase. The sensitivity of global mean trends to outliers suggests that more informative indices are needed. We propose an alternative approach, which identifies clusters of extreme decline (or increase) that differ statistically from the majority of population trends. We show that, of taxonomic-geographic systems in the Living Planet Index, 16 systems contain clusters of extreme decline (comprising around 1% of populations; these extreme declines occur disproportionately in larger animals) and 7 contain extreme increases (around 0.4% of populations). The remaining 98.6% of populations across all systems showed no mean global trend. However, when analysed separately, three systems were declining strongly with high certainty (all in the Indo-Pacific region) and seven were declining strongly but with less certainty (mostly reptile and amphibian groups). Accounting for extreme clusters fundamentally alters the interpretation of global vertebrate trends and should be used to help to prioritize conservation efforts.

Role of communication in successful outpatient attendance in a New Zealand hospital: a qualitative study.

BACKGROUND: There are significant implications for both patients and providers when patients do not attend outpatient specialist appointments. Nonattendance has an impact on the efficiency of health care, provider resources and patient health outcomes. AIMS: In this qualitative study we aimed to gather insights on how Dunedin Hospital notifies patients about their appointments, the implications for the hospital and for patients and how the system could be improved. METHODS: We interviewed 13 hospital staff members and nine patients who volunteered to participate because they had missed appointments as a result of communication problems. Interviews were transcribed and analysed thematically using NVivo software. RESULTS: Dunedin Hospital relies heavily on posted letters to inform people about their appointments, with some also receiving reminder texts closer to the time of the appointment. Frustration with the current system was a common theme among both patients and staff. Almost all patients had missed an appointment because of a letter not arriving. While most patients found that the text reminders were helpful, most said they were sent too late and did not allow enough time for arrangements to be made for their appointments. Almost all patients experienced treatment delays, which caused distress. Most patients believed a self-booking system would improve the ability to attend their appointments, and most of them wanted to be notified of appointments via email. CONCLUSIONS: We recommend that a patient-oriented approach to communication should be implemented, and alternative methods of communication should be explored.

Behavioural adaptation to heat stress: shell lifting of the hermit crab Diogenes deflectomanus.

Behavioural responses to heat and desiccation stress in ectotherms are crucial for their survival in habitats where environmental temperatures are close to or even exceed their upper thermal limits. During low tide periods when pools in intertidal sediments heat up, a novel shell lifting behaviour (when hermit crabs crawl out of pools and lift up their shells) was observed in the hermit crab, Diogenes deflectomanus, on tropical sandy shores. On-shore measurements revealed that the hermit crabs left pools and lifted their shells predominantly when pool water exceeded 35.4 °C. Standing on emersed substrates above the pool water, the hermit crabs maintained their body temperatures at 26 - 29 °C, ∼ 10 °C lower than temperatures at which their physiological performances (as measured using heart rate) reached the maximum. This mismatch between preferred body temperatures and temperatures at maximal physiological performance was also observed under a laboratory controlled thermal gradient, where hermit crabs spent more time at 22 - 26 °C as compared to > 30 °C. These behaviours suggest a thermoregulatory function of the shell lifting behaviour, where the hermit crabs can avoid further increase in body temperatures when pools heat up during low tide periods. Such a behavioural decision allows the hermit crabs to be less prone to the strong temporal fluctuation in temperatures experienced during emersion periods on thermally dynamic tropical sandy shores.

Adaptive correction of craniofacial defects in pre-metamorphic Xenopus laevis tadpoles involves thyroid hormone-independent tissue remodeling.

Although it is well established that some organisms can regenerate lost structures, the ability to remodel existing malformed structures has been less well studied. Therefore, in this study we examined the ability of pre-metamorphic Xenopus laevis tadpoles to self-correct malformed craniofacial tissues. We found that tadpoles can adaptively improve and normalize abnormal craniofacial morphology caused by numerous developmental perturbations. We then investigated the tissue-level and molecular mechanisms that mediate the self-correction of craniofacial defects in pre-metamorphic X. laevis tadpoles. Our studies revealed that this adaptive response involves morphological changes and the remodeling of cartilage tissue, prior to metamorphosis. RT-qPCR and RNA-seq analysis of gene expression suggests a thyroid hormone-independent endocrine signaling pathway as the potential mechanism responsible for triggering the adaptive and corrective remodeling response in these larvae that involves mmp1 and mmp13 upregulation. Thus, investigating how malformed craniofacial tissues are naturally corrected in X. laevis tadpoles has provided valuable insights into the maintenance and manipulation of craniofacial morphology in a vertebrate system. These insights may help in the development of novel therapies for developmental craniofacial anomalies in humans.

The International Vertebrate Pet Trade Network and Insights from US Imports of Exotic Pets.

The international trade in exotic vertebrate pets provides key social and economic benefits but also drives associated ecological, ethical, and human health impacts. However, despite its clear importance, we currently lack a full understanding of the structure of the pet trade, hampering efforts to optimize its benefits while mitigating its negative effects. In the present article, we represent and review the structure of the pet trade as a network composed of different market actors (nodes) and trade flows (links). We identify key data gaps in this network that, if filled, would enable network analyses to pinpoint targets for management. As a case study of how data-informed networks can realize this goal, we quantified spatial and temporal patterns in pets imported to the United States. Our framework and case study illustrate how network approaches can help to inform and manage the effects of the growing demand for exotic pets.

Drivers of future alien species impacts: An expert-based assessment.

Understanding the likely future impacts of biological invasions is crucial yet highly challenging given the multiple relevant environmental, socio-economic and societal contexts and drivers. In the absence of quantitative models, methods based on expert knowledge are the best option for assessing future invasion trajectories. Here, we present an expert assessment of the drivers of potential alien species impacts under contrasting scenarios and socioecological contexts through the mid-21st century. Based on responses from 36 experts in biological invasions, moderate (20%-30%) increases in invasions, compared to the current conditions, are expected to cause major impacts on biodiversity in most socioecological contexts. Three main drivers of biological invasions-transport, climate change and socio-economic change-were predicted to significantly affect future impacts of alien species on biodiversity even under a best-case scenario. Other drivers (e.g. human demography and migration in tropical and subtropical regions) were also of high importance in specific global contexts (e.g. for individual taxonomic groups or biomes). We show that some best-case scenarios can substantially reduce potential future impacts of biological invasions. However, rapid and comprehensive actions are necessary to use this potential and achieve the goals of the Post-2020 Framework of the Convention on Biological Diversity.

Comparing generalized and customized spread models for nonnative forest pests.

While generality is often desirable in ecology, customized models for individual species are thought to be more predictive by accounting for context specificity. However, fully customized models require more information for focal species. We focus on pest spread and ask: How much does predictive power differ between generalized and customized models? Further, we examine whether an intermediate "semi-generalized" model, combining elements of a general model with species-specific modifications, could yield predictive advantages. We compared predictive power of a generalized model applied to all forest pest species (the generalized dispersal kernel or GDK) to customized spread models for three invasive forest pests (beech bark disease [Cryptococcus fagisuga], gypsy moth [Lymantria dispar], and hemlock woolly adelgid [Adelges tsugae]), for which time-series data exist. We generated semi-generalized dispersal kernel models (SDK) through GDK correction factors based on additional species-specific information. We found that customized models were more predictive than the GDK by an average of 17% for the three species examined, although the GDK still had strong predictive ability (57% spatial variation explained). However, by combining the GDK with simple corrections into the SDK model, we attained a mean of 91% of the spatial variation explained, compared to 74% for the customized models. This is, to our knowledge, the first comparison of general and species-specific ecological spread models' predictive abilities. Our strong predictive results suggest that general models can be effectively synthesized with context-specific information for single species to respond quickly to invasions. We provided SDK forecasts to 2030 for all 63 United States pests in our data set.

A new baseline for countrywide α-diversity and species distributions: illustration using >6,000 plant species in Panama.

Estimating α-diversity and species distributions provides baseline information to understand factors such as biodiversity loss and erosion of ecosystem services. Yet, species surveys typically cover a small portion of any country's landmass. Public, global databases could help, but contain biases. Thus, the magnitude of bias should be identified and ameliorated, the value of integration determined, and application to current policy issues illustrated. The ideal integrative approach should be powerful, flexible, efficient, and conceptually straightforward. We estimated distributions for >6,000 species, integrating species sightings (S) from the Global Biodiversity Information Facility (GBIF), systematic survey data (S2 ), and "bias-adjustment kernels" (BaK) using spatial and species trait databases (S2 BaK). We validated our approach using both locational and species holdout sets, and then applied our predictive model to Panama. Using sightings alone (the most common approach) discriminated relative probabilities of occurrences well (area under the curve [AUC] = 0.88), but underestimated actual probabilities by ~4,000%, while using survey data alone omitted over three-quarters of the >6,000 species. Comparatively, S2 BaK had no systematic underestimation, and substantially stronger discrimination (AUC = 0.96) and predictive power (deviance explained = 47%). Our model suggested high diversity (~200% countrywide mean) where urban development is projected to occur (the Panama Canal watershed) and also suggested this is not due to higher sampling intensity. However, portions of the Caribbean coast and eastern Panama (the Darién Gap) were even higher, both for total plant biodiversity (~250% countrywide mean), and CITES listed species. Finally, indigenous territories appeared half as diverse as other regions, based on survey observations. However, our model suggested this was largely due to site selection, and that richness in and out of indigenous territories was roughly equal. In brief, we provide arguably the best estimate of countrywide plant α-diversity and species distributions in the Neotropics, and make >6,000 species distributions available. We identify regions of overlap between development and high biodiversity, and improve interpretation of biodiversity patterns, including for policy-relevant CITES species, and locations with limited access (i.e., indigenous territories). We derive a powerful, flexible, efficient and simple estimation approach for biodiversity science.

Predicting the spread of all invasive forest pests in the United States.

We tested whether a general spread model could capture macroecological patterns across all damaging invasive forest pests in the United States. We showed that a common constant dispersal kernel model, simulated from the discovery date, explained 67.94% of the variation in range size across all pests, and had 68.00% locational accuracy between predicted and observed locational distributions. Further, by making dispersal a function of forest area and human population density, variation explained increased to 75.60%, with 74.30% accuracy. These results indicated that a single general dispersal kernel model was sufficient to predict the majority of variation in extent and locational distribution across pest species and that proxies of propagule pressure and habitat invasibility - well-studied predictors of establishment - should also be applied to the dispersal stage. This model provides a key element to forecast novel invaders and to extend pathway-level risk analyses to include spread.

Nonnative forest insects and pathogens in the United States: Impacts and policy options.

We review and synthesize information on invasions of nonnative forest insects and diseases in the United States, including their ecological and economic impacts, pathways of arrival, distribution within the United States, and policy options for reducing future invasions. Nonnative insects have accumulated in United States forests at a rate of ~2.5 per yr over the last 150 yr. Currently the two major pathways of introduction are importation of live plants and wood packing material such as pallets and crates. Introduced insects and diseases occur in forests and cities throughout the United States, and the problem is particularly severe in the Northeast and Upper Midwest. Nonnative forest pests are the only disturbance agent that has effectively eliminated entire tree species or genera from United States forests within decades. The resulting shift in forest structure and species composition alters ecosystem functions such as productivity, nutrient cycling, and wildlife habitat. In urban and suburban areas, loss of trees from streets, yards, and parks affects aesthetics, property values, shading, stormwater runoff, and human health. The economic damage from nonnative pests is not yet fully known, but is likely in the billions of dollars per year, with the majority of this economic burden borne by municipalities and residential property owners. Current policies for preventing introductions are having positive effects but are insufficient to reduce the influx of pests in the face of burgeoning global trade. Options are available to strengthen the defenses against pest arrival and establishment, including measures taken in the exporting country prior to shipment, measures to ensure clean shipments of plants and wood products, inspections at ports of entry, and post-entry measures such as quarantines, surveillance, and eradication programs. Improved data collection procedures for inspections, greater data accessibility, and better reporting would support better evaluation of policy effectiveness. Lack of additional action places the nation, local municipalities, and property owners at high risk of further damaging and costly invasions. Adopting stronger policies to reduce establishments of new forest insects and diseases would shift the major costs of control to the source and alleviate the economic burden now borne by homeowners and municipalities.

Isotropic band gaps and freeform waveguides observed in hyperuniform disordered photonic solids.

Recently, disordered photonic media and random textured surfaces have attracted increasing attention as strong light diffusers with broadband and wide-angle properties. We report the experimental realization of an isotropic complete photonic band gap (PBG) in a 2D disordered dielectric structure. This structure is designed by a constrained optimization method, which combines advantages of both isotropy due to disorder and controlled scattering properties due to low-density fluctuations (hyperuniformity) and uniform local topology. Our experiments use a modular design composed of Al2O3 walls and cylinders arranged in a hyperuniform disordered network. We observe a complete PBG in the microwave region, in good agreement with theoretical simulations, and show that the intrinsic isotropy of this unique class of PBG materials enables remarkable design freedom, including the realization of waveguides with arbitrary bending angles impossible in photonic crystals. This experimental verification of a complete PBG and realization of functional defects in this unique class of materials demonstrate their potential as building blocks for precise manipulation of photons in planar optical microcircuits and has implications for disordered acoustic and electronic band gap materials.

Comparison of mechanical properties of three machinable ceramics with an experimental fluorophlogopite glass ceramic.

STATEMENT OF PROBLEM: Fluorophlogopite glass ceramic (FGC) is a biocompatible, etchable, and millable ceramic with fluoride releasing property. However, its mechanical properties and reliability compared with other machinable ceramics remain undetermined. PURPOSE: The purpose of this in vitro study was to compare the mechanical properties of 3 commercially available millable ceramic materials, IPS e.max CAD, Vitablocs Mark II, and Vita Enamic, with an experimental FGC. MATERIAL AND METHODS: Each type of ceramic block was sectioned into beams (n=15) of standard dimensions of 2×2×15 mm. Before mechanical testing, specimens of the IPS e.max CAD group were further fired for final crystallization. Flexural strength was determined by the 3-point bend test with a universal loading machine at a cross head speed of 1 mm/min. Hardness was determined with a hardness tester with 5 Vickers hardness indentations (n=5) using a 1.96 N load and a dwell time of 15 seconds. Selected surfaces were examined by scanning electron microscopy and energy-dispersive x-ray spectroscopy. Data were analyzed by the 1-way ANOVA test and Weibull analysis (α=.05). Weibull parameters, including the Weibull modulus (m) as well as the characteristic strength at 63.2% (η) and 10.0% (B10), were obtained. RESULTS: A significant difference in flexural strength (P<.001) was found among groups, with IPS e.max CAD (341.88 ±40.25 MPa)>Vita Enamic (145.95 ±12.65 MPa)>Vitablocs Mark II (106.67 ±18.50 MPa), and FGC (117.61 ±7.62 MPa). The Weibull modulus ranged from 6.93 to 18.34, with FGC showing the highest Weibull modulus among the 4 materials. The Weibull plot revealed that IPS e.max CAD>Vita Enamic>FGC>Vitablocs Mark II for the characteristic strength at both 63.2% (η) and 10.0% (B10). Significant difference in Vickers hardness among groups (P<.001) was found with IPS e.max CAD (731.63 ±30.64 H(V))>Vitablocs Mark II (594.74 ±25.22 H(V))>Vita Enamic (372.29 ±51.23 H(V))>FGC (153.74 ±23.62 H(V)). CONCLUSIONS: The flexural strength and Vickers hardness of IPS e.max CAD were significantly higher than those of the 3 materials tested. The FGC's flexural strength was comparable with Vitablocs Mark II. The FGC's Weibull modulus was the highest, while its Vickers hardness was the lowest among the materials tested.

The interacting effects of diversity and propagule pressure on early colonization and population size.

We are now beginning to understand the role of intraspecific diversity on fundamental ecological phenomena. There exists a paucity of knowledge, however, regarding how intraspecific, or genetic diversity, may covary with other important factors such as propagule pressure. A combination of theoretical modelling and experimentation was used to explore the way propagule pressure and genetic richness may interact. We compare colonization rates of the Australian bivalve Saccostrea glomerata (Gould 1885). We cross propagule size and genetic richness in a factorial design in order to examine the generalities of our theoretical model. Modelling showed that diversity and propagule pressure should generally interact synergistically when positive feedbacks occur (e.g. aggregation). The strength of genotype effects depended on propagule size, or the numerical abundance of arriving individuals. When propagule size was very small (<4 individuals), however, greater genetic richness unexpectedly reduced colonization. The probability of S. glomerata colonization was 76% in genetically rich, larger propagules, almost 39 percentage points higher than in genetically poor propagules of similar size. This pattern was not observed in less dense, smaller propagules. We predict that density-dependent interactions between larvae in the water column may explain this pattern.