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Context Quantitative models of forest dynamics have followed a progression toward methods with increased detail, complexity, and spatial extent. Objectives We highlight milestones in the development of forest dynamics models and identify future research and application opportunities. Methods We reviewed milestones in the evolution of forest dynamics models from the 1930s to the present with emphasis on forest growth and yield models and forest landscape models We combined past trends with emerging issues to identify future needs. Results Historically, capacity to model forest dynamics at tree, stand, and landscape scales was constrained by available data for model calibration and validation; computing capacity; model applicability to real-world problems; and ability to integrate biological, social, and economic drivers of change. As computing and data resources improved, a new class of spatially explicit forest landscape models emerged. Conclusions We are at a point of great opportunity in development and application of forest dynamics models. Past limitations in computing capacity and in data suitable for model calibration or evaluation are becoming less restrictive. Forest landscape models, in particular, are ready to transition to a central role supporting forest management, planning, and policy decisions. Recommendations Transitioning forest landscape models to a central role in applied decision making will require greater attention to evaluating performance; building application support staffs; expanding the included drivers of change, and incorporating metrics for social and economic inputs and outputs.

The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug–drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.

Invasive fungal infections are associated with significant morbidity and mortality, and their management is restricted to a variety of agents from five established classes of antifungal medication. In practice, existing antifungal agents are often constrained by dose-limiting toxicities, drug interactions, and the routes of administration. An increasing prevalence of invasive fungal infections along with rising rates of resistance and the practical limitations of existing agents has created a demand for the development of new antifungals, particularly those with novel mechanisms of action. This article reviews antifungal agents currently in various stages of clinical development. New additions to existing antifungal classes will be discussed, including SUBA-itraconazole, a highly bioavailable azole, and amphotericin B cochleate, an oral amphotericin formulation, as well as rezafungin, a long-acting echinocandin capable of once-weekly administration. Additionally, novel first-in-class agents such as ibrexafungerp, an oral glucan synthase inhibitor with activity against various resistant fungal isolates, and olorofim, a pyrimidine synthesis inhibitor with a broad spectrum of activity and oral formulation, will be reviewed. Various other innovative antifungal agents and classes, including MGCD290, tetrazoles, and fosmanogepix, will also be examined.

Nitrous oxide (N2O) is the third most important long-lived GHG and an important stratospheric ozone depleting substance. Agricultural practices and the use of N-fertilizers have greatly enhanced emissions of N2O. Here, we present estimates of N2O emissions determined from three global atmospheric inversion frameworks during the period 1998–2016. We find that global N2O emissions increased substantially from 2009 and at a faster rate than estimated by the IPCC emission factor approach. The regions of East Asia and South America made the largest contributions to the global increase. From the inversion-based emissions, we estimate a global emission factor of 2.3 ± 0.6%, which is significantly larger than the IPCC Tier-1 default for combined direct and indirect emissions of 1.375%. The larger emission factor and accelerating emission increase found from the inversions suggest that N2O emission may have a nonlinear response at global and regional scales with high levels of N-input.

Substantial leaps in the understanding of quantum systems have been driven by exploring geometry, topology, dimensionality and interactions in ultracold atomic ensembles 1 – 6 . A system where atoms evolve while confined on an ellipsoidal surface represents a heretofore unexplored geometry and topology. Realizing an ultracold bubble—potentially Bose–Einstein condensed—relates to areas of interest including quantized-vortex flow constrained to a closed surface topology, collective modes and self-interference via bubble expansion 7 – 17 . Large ultracold bubbles, created by inflating smaller condensates, directly tie into Hubble-analogue expansion physics 18 – 20 . Here we report observations from the NASA Cold Atom Lab 21 facility onboard the International Space Station of bubbles of ultracold atoms created using a radiofrequency-dressing protocol. We observe bubble configurations of varying size and initial temperature, and explore bubble thermodynamics, demonstrating substantial cooling associated with inflation. We achieve partial coverings of bubble traps greater than one millimetre in size with ultracold films of inferred few-micrometre thickness, and we observe the dynamics of shell structures projected into free-evolving harmonic confinement. The observations are among the first measurements made with ultracold atoms in space, using perpetual freefall to explore quantum systems that are prohibitively difficult to create on Earth. This work heralds future studies (in orbital microgravity) of the Bose–Einstein condensed bubble, the character of its excitations and the role of topology in its evolution. Bubbles of ultracold atoms have been created, observed and characterized at the NASA Cold Atom Lab onboard the International Space Station, made possible by the microgravity environment of the laboratory.

The northeastern United States is a predominately-forested region that, like most of the eastern U.S., has undergone a 400-year history of intense logging, land clearance for agriculture, and natural reforestation. This setting affords the opportunity to address a major ecological question: How similar are today's forests to those existing prior to European colonization? Working throughout a nine-state region spanning Maine to Pennsylvania, we assembled a comprehensive database of archival land-survey records describing the forests at the time of European colonization. We compared these records to modern forest inventory data and described: (1) the magnitude and attributes of forest compositional change, (2) the geography of change, and (3) the relationships between change and environmental factors and historical land use. We found that with few exceptions, notably the American chestnut, the same taxa that made up the pre-colonial forest still comprise the forest today, despite ample opportunities for species invasion and loss. Nonetheless, there have been dramatic shifts in the relative abundance of forest taxa. The magnitude of change is spatially clustered at local scales (<125 km) but exhibits little evidence of regional-scale gradients. Compositional change is most strongly associated with the historical extent of agricultural clearing. Throughout the region, there has been a broad ecological shift away from late successional taxa, such as beech and hemlock, in favor of early- and mid-successional taxa, such as red maple and poplar. Additionally, the modern forest composition is more homogeneous and less coupled to local climatic controls.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Resource selection is a key component in understanding the ecological processes underlying population dynamics, particularly for species such as northern bobwhite ( Colinus virginianus ), which are declining across their range in North America. There is a growing body of literature quantifying breeding season resource selection in bobwhite; however, winter information is particularly sparse despite it being a season of substantial mortality. Information regarding winter resource selection is necessary to quantify the extent to which resource requirements are driving population change. We modeled bobwhite fall and winter resource selection as a function of vegetation structure, composition, and management from traditionally (intensively) managed sites and remnant (extensively managed) grassland sites in southwest Missouri using multinomial logit discrete choice models in a Bayesian framework. We captured 158 bobwhite from 67 unique coveys and attached transmitters to 119 individuals. We created 671 choice sets comprised of 1 used location and 3 available locations. Bobwhite selected for locations which were closer to trees during the winter; the relative probability of selection decreased from 0.45 (85% Credible Interval [CRI]: 0.17–0.74) to 0.00 (85% CRI: 0.00–0.002) as distance to trees ranged from 0–313 m. The relative probability of selection increased from near 0 (85% CRI: 0.00–0.01) to 0.33 (85% CRI: 0.09–0.56) and from near 0 (85% CRI: 0.00–0.00) to 0.51 (85% CRI: 0.36–0.71) as visual obstruction increased from 0 to 100% during fall and winter, respectively. Bobwhite also selected locations with more woody stems; the relative probability of selection increased from near 0.00 (85% CRI: 0.00–0.002) to 0.30 (85% CRI: 0.17–0.46) and near 0.00 (85% CRI: 0.00–0.001) to 0.35 (85% CRI: 0.22–0.55) as stem count ranged from 0 to 1000 stems in fall and winter, respectively. The relative probability of selection also decreased from 0.35 (85% CRI: 0.20–0.54) to nearly 0 (85% CRI: 0.00–0.001) as percent grass varied from 0 to 100% in fall. We suggest that dense shrub cover in close proximity to native grasslands is an important component of fall and winter cover given bobwhite selection of shrub cover and previously reported survival benefits in fall and winter.

Case reports have identified invasive fungal diseases in persons who use cannabis, and fungal contamination of cannabis has been described. In a large health insurance claims database, persons who used cannabis were 3.5 (95% CI 2.6-4.8) times more likely than persons who did not use cannabis to have a fungal infection in 2016.