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David Wirta1, Amanda M VanDenburgh2, Emily Weng3, Scott M Whitcup4, Sef Kurstjens5, Frederick C Beddingfield III4,61Private Practice, Newport Beach, CA, USA; 2Clinical Development, 3Biostatistics, 4Research and Development, 5Global Drug Development, Allergan, Inc, Irvine, CA, USA; 6Department of Medicine, Division of Dermatology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USABackground: Bimatoprost ophthalmic solution 0.03% was approved in the US for reducing intraoccular pressure (IOP) based on two double-masked, active-controlled clinical trials. Four additional long-term studies (≥ 12months) were conducted; however, the aggregate safety profile of the six studies has not been reported.Methods: Adverse events (AEs) were pooled from six double-masked, active-controlled, long-term clinical trials in which subjects received bimatoprost 0.03% once daily (QD) or twice daily (BID) as an eyedrop. AE terms were converted to MedDRA (V.11.0) Preferred Terms and analyzed.Results: In total, 1409 patients received more than one dose of bimatoprost 0.03% QD or BID. Most AEs were mild in severity and reported by 86.7% (QD) and 94.8% (BID) of subjects (≤ 12 months of treatment). AEs reported through month 12 (aggregate incidence of ≥ 5%) were conjunctival hyperemia, increased eyelash growth, eye pruritus, periocular skin hyperpigmentation, eye irritation, dry eye, and hypertrichosis. AE onset was generally reported within four months of treatment. The cumulative incidence of common AEs in the QD treatment group at 24–48 months was similar to that measured at 12 months of treatment.Conclusion: Bimatoprost 0.03% has a favorable safety and tolerability profile as characterized by six long-term studies. Common AEs were due to the known pharmacological activity of bimatoprost and reversible with treatment cessation.Keywords: intraocular pressure, eyelids, pharmacology, clinical trial, medical treatment

The long-term and large scale dynamics of ecosystems are in large part determined by the performances of individual plants in competition with one another for light, water and nutrients. Woody biomass, a pool of carbon (C) larger than 50% of atmospheric CO2, exists because of height-structured competition for light. However, most of the current Earth System Models that predict climate change and C cycle feedbacks lack both a mechanistic formulation for height-structured competition for light and an explicit scaling from individual plants to the globe. In this study, we incorporate height- structured competition and explicit scaling from individuals to ecosystems into the land model (LM3) currently used in the Earth System Models developed by the Geophysical Fluid Dynamics Laboratory (GFDL). The height-structured formulation is based on the Perfect Plasticity Approximation (PPA), which has been shown to accurately scale from individual-level plant competition for light, water and nutrients to the dynamics of whole communities. Because of the tractability of the PPA, the coupled LM3-PPA model is able to include a large number of phenomena across a range of spatial and temporal scales, and still retain computational tractability, as well as close linkages to mathematically tractable forms of the model. We test a range of predictions against data from temperate broadleaved forests in the northern USA. The results show the model predictions agree with diurnal and annual C fluxes, growth rates of individual trees in the canopy and understory, tree size distributions, and species-level population dynamics during succession. We also show how the competitively optimal allocation strategy - the strategy that can competitively exclude all others - shifts as a function of the atmospheric CO2 concentration. This strategy is referred as an evolutionary stable strategy (ESS) in the ecological literature and is typically not the same as a productivity- or growth-maximizing strategy. Model simulations predict that C sinks caused by CO2 fertilization in forests limited by light and water will be down-regulated if allocation tracks changes in the competitive optimum. The implementation of the model in this paper is for temperate broadleaved forest trees, but the formulation of the model is general. It can be expanded to include other growth forms and physiologies simply by altering parameter values. [ABSTRACT FROM AUTHOR]

The article presents a stud which develops the semi-analytical solution (SAS) to accelerate the spin-up of a process-oriented biogeochemical model of of a coupled carbon and nitrogen land to steady states. It states that the efficiency of the SAS method can save an estimated 95.7% and 92.4% computational time for global simulations and site-level. It adds that the method enables modeling analyses, such as ensemble analysis with regard to parameter variability.

Abstract Background Studies with the nematode model Caenorhabditis elegans have identified conserved biochemical pathways that act to modulate life span. Life span can also be influenced by the composition of the intestinal microbiome, and C. elegans life span can be dramatically influenced by its diet of Escherichia coli. Although C. elegans is typically fed the standard OP50 strain of E. coli, nematodes fed E. coli strains rendered respiratory deficient, either due to a lack coenzyme Q or the absence of ATP synthase, show significant life span extension. Here we explore the mechanisms accounting for the enhanced nematode life span in response to these diets. Results The intestinal load of E. coli was monitored by determination of worm-associated colony forming units (cfu/worm or coliform counts) as a function of age. The presence of GFP-expressing E. coli in the worm intestine was also monitored by fluorescence microscopy. Worms fed the standard OP50 E. coli strain have high cfu and GFP-labeled bacteria in their guts at the L4 larval stage, and show saturated coliform counts by day five of adulthood. In contrast, nematodes fed diets of respiratory deficient E. coli lacking coenzyme Q lived significantly longer and failed to accumulate bacteria within the lumen at early ages. Animals fed bacteria deficient in complex V showed intermediate coliform numbers and were not quite as long-lived. The results indicate that respiratory deficient Q-less E. coli are effectively degraded in the early adult worm, either at the pharynx or within the intestine, and do not accumulate in the intestinal tract until day ten of adulthood. Conclusions The findings of this study suggest that the nematodes fed the respiratory deficient E. coli diet live longer because the delay in bacterial colonization of the gut subjects the worms to less stress compared to worms fed the OP50 E. coli diet. This work suggests that bacterial respiration can act as a virulence factor, influencing the ability of bacteria to colonize and subsequently harm the animal host. Respiratory deficient bacteria may pose a useful model for probing probiotic relationships within the gut microbiome in higher organisms.

Regenerating periodontal defects in osteoporosis patients presents a significant clinical challenge. Unlike the relatively straightforward regeneration of homogeneous bone tissue, periodontal regeneration requires the intricate reconstruction of the cementum-periodontal ligament-alveolar bone interface. Strontium (Sr)-doped biomaterials have been extensively utilized in bone tissue engineering due to their remarkable pro-osteogenic attributes. However, their application in periodontal tissue regeneration has been scarcely explored. In this study, we synthesized an innovative injectable Sr-BGN/GNM scaffold by integrating Sr-doped bioactive glass nanospheres (Sr-BGNs) into the nanofiber architecture of gelatin nanofiber microspheres (GNMs). This design, mimicking the natural bone extracellular matrix (ECM), enhanced the scaffold's mechanical properties and effectively controlled the sustained release of Sr ions (Sr 2+ ), thereby promoting the proliferation, osteogenic differentiation, and ECM secretion of PDLSCs and BMSCs, as well as enhancing vascularization in endothelial cells. In vivo experiments further indicated that the Sr-BGNs/GNMs significantly promoted osteogenesis and angiogenesis. Moreover, the scaffold's tunable degradation kinetics optimized the prolonged release and pro-regenerative effects of Sr 2+ in vivo, matching the pace of periodontal regeneration and thereby facilitating the regeneration of functional periodontal tissues under osteoporotic conditions. Therefore, Sr-BGNs/GNMs emerge as a promising candidate for advancing periodontal regeneration strategies.

Natural ecosystems store large amounts of carbon globally, as organisms absorb carbon from the atmosphere to build large, long-lasting, or slow-decaying structures such as tree bark or root systems. An ecosystem's carbon sequestration potential is tightly linked to its biological diversity. Yet when considering future projections, many carbon sequestration models fail to account for the role biodiversity plays in carbon storage. Here, we assess the consequences of plant biodiversity loss for carbon storage under multiple climate and land-use change scenarios. We link a macroecological model projecting changes in vascular plant richness under different scenarios with empirical data on relationships between biodiversity and biomass. We find that biodiversity declines from climate and land use change could lead to a global loss of between 7.44-103.14 PgC (global sustainability scenario) and 10.87-145.95 PgC (fossil-fueled development scenario). This indicates a self-reinforcing feedback loop, where higher levels of climate change lead to greater biodiversity loss, which in turn leads to greater carbon emissions and ultimately more climate change. Conversely, biodiversity conservation and restoration can help achieve climate change mitigation goals., (© 2024. Isbell, Arce-Plata, Di Marco, Harfoot, Johnson, Mori, Weng, Ferrier. Parts of this work were authored by US Federal Government authors and are not under copyright protection in the US; foreign copyright protection may apply.)

Grassland and other herbaceous communities cover significant portions of Earth's terrestrial surface and provide many critical services, such as carbon sequestration, wildlife habitat, and food production. Forecasts of global change impacts on these services will require predictive tools, such as process-based dynamic vegetation models. Yet, model representation of herbaceous communities and ecosystems lags substantially behind that of tree communities and forests. The limited representation of herbaceous communities within models arises from two important knowledge gaps: first, our empirical understanding of the principles governing herbaceous vegetation dynamics is either incomplete or does not provide mechanistic information necessary to drive herbaceous community processes with models; second, current model structure and parameterization of grass and other herbaceous plant functional types limits the ability of models to predict outcomes of competition and growth for herbaceous vegetation. In this review, we provide direction for addressing these gaps by: (1) presenting a brief history of how vegetation dynamics have been developed and incorporated into earth system models, (2) reporting on a model simulation activity to evaluate current model capability to represent herbaceous vegetation dynamics and ecosystem function, and (3) detailing several ecological properties and phenomena that should be a focus for both empiricists and modelers to improve representation of herbaceous vegetation in models. Together, empiricists and modelers can improve representation of herbaceous ecosystem processes within models. In so doing, we will greatly enhance our ability to forecast future states of the earth system, which is of high importance given the rapid rate of environmental change on our planet., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Global biodiversity and ecosystem service models typically operate independently. Ecosystem service projections may therefore be overly optimistic because they do not always account for the role of biodiversity in maintaining ecological functions. We review models used in recent global model intercomparison projects and develop a novel model integration framework to more fully account for the role of biodiversity in ecosystem function, a key gap for linking biodiversity changes to ecosystem services. We propose two integration pathways. The first uses empirical data on biodiversity-ecosystem function relationships to bridge biodiversity and ecosystem function models and could currently be implemented globally for systems and taxa with sufficient data. We also propose a trait-based approach involving greater incorporation of biodiversity into ecosystem function models. Pursuing both approaches will provide greater insight into biodiversity and ecosystem services projections. Integrating biodiversity, ecosystem function, and ecosystem service modeling will enhance policy development to meet global sustainability goals., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Institute of Biological Sciences. Elements of the work have been written by employees of the US Government.)

Background: People of culturally and linguistically diverse (CALD) background face significant barriers in accessing effective health services in multicultural countries such as the United States, Canada, Europe and Australia. To address these barriers, government and nongovernment organisations globally have taken the approach of creating ethno-specific services, which cater to the specific needs of CALD clients. These services are often complementary to mainstream services, which cater to the general population including CALD communities., Methods: This systematic review uses the Evidence Gap Map (EGM) approach to map the available evidence on the effectiveness of ethno-specific and mainstream services in the Australian context. We reviewed Scopus, Web of Science and PubMed databases for articles published from 1996 to 2021 that assessed the impact of health services for Australian CALD communities. Two independent reviewers extracted and coded all the documents, and discussed discrepancies until reaching a 100% agreement. The main inclusion criteria were: 1) time (published after 1996); 2) geography (data collected in Australia); 3) document type (presents results of empirical research in a peer-reviewed outlet); 4) scope (assesses the effectiveness of a health service on CALD communities). We identified 97 articles relevant for review., Results: Ninety-six percent of ethno-specific services (i.e. specifically targeting CALD groups) were effective in achieving their aims across various outcomes. Eighteen percent of mainstream services (i.e. targeting the general population) were effective for CALD communities. When disaggregating our sample by outcomes (i.e. access, satisfaction with the service, health and literacy), we found that 50 % of studies looking at mainstream services' impact on CALD communities found that they were effective in achieving health outcomes. The use of sub-optimal methodologies that increase the risk of biased findings is widespread in the research field that we mapped., Conclusions: Our findings provide partial support to the claims of advocacy stakeholders that mainstream services have limitations in the provision of effective health services for CALD communities. Although focusing on the Australian case study, this review highlights an under-researched policy area, proposes a viable methodology to conduct further research on this topic, and points to the need to disaggregate the data by outcome (i.e. access, satisfaction with the service, health and literacy) when assessing the comparative effectiveness of ethno-specific and mainstream services for multicultural communities., (© 2022. The Author(s).)

We present CELER ( C orpus of E ye Movements in L 1 and L2 E nglish R eading), a broad coverage eye-tracking corpus for English. CELER comprises over 320,000 words, and eye-tracking data from 365 participants. Sixty-nine participants are L1 (first language) speakers, and 296 are L2 (second language) speakers from a wide range of English proficiency levels and five different native language backgrounds. As such, CELER has an order of magnitude more L2 participants than any currently available eye movements dataset with L2 readers. Each participant in CELER reads 156 newswire sentences from the Wall Street Journal ( WSJ ), in a new experimental design where half of the sentences are shared across participants and half are unique to each participant. We provide analyses that compare L1 and L2 participants with respect to standard reading time measures, as well as the effects of frequency, surprisal, and word length on reading times. These analyses validate the corpus and demonstrate some of its strengths. We envision CELER to enable new types of research on language processing and acquisition, and to facilitate interactions between psycholinguistics and natural language processing (NLP)., Competing Interests: Competing Interests: The authors declare no conflict of interest., (© 2022 Massachusetts Institute of Technology.)

Background: The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported., Objective: To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia., Design: Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505)., Setting: 46 U.S. and Canadian hospitals., Participants: Patients aged 50 years or older undergoing hip fracture surgery., Intervention: Spinal or general anesthesia., Measurements: Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care., Results: A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups., Limitation: Missing outcome data and multiple outcomes assessed., Conclusion: Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia., Primary Funding Source: Patient-Centered Outcomes Research Institute .

This paper describes the GISS-E2.1 contribution to the Coupled Model Intercomparison Project, Phase 6 (CMIP6). This model version differs from the predecessor model (GISS-E2) chiefly due to parameterization improvements to the atmospheric and ocean model components, while keeping atmospheric resolution the same. Model skill when compared to modern era climatologies is significantly higher than in previous versions. Additionally, updates in forcings have a material impact on the results. In particular, there have been specific improvements in representations of modes of variability (such as the Madden-Julian Oscillation and other modes in the Pacific) and significant improvements in the simulation of the climate of the Southern Oceans, including sea ice. The effective climate sensitivity to 2 × CO 2 is slightly higher than previously at 2.7-3.1°C (depending on version) and is a result of lower CO 2 radiative forcing and stronger positive feedbacks., (©2020. The Authors.)

Recent studies show coordinated relationships between plant leaf traits and their capacity to predict ecosystem functions. However, how leaf traits will change within species and whether interspecific trait relationships will shift under future environmental changes both remain unclear. Here, we examine the bivariate correlations between leaf economic traits of 515 species in 210 experiments which mimic climate warming, drought, elevated CO 2 , and nitrogen deposition. We find divergent directions of changes in trait-pairs between species, and the directions mostly do not follow the interspecific trait relationships. However, the slopes in the logarithmic transformed interspecific trait relationships hold stable under environmental changes, while only their elevations vary. The elevation changes of trait relationship are mainly driven by asymmetrically interspecific responses contrary to the direction of the leaf economic spectrum. These findings suggest robust interspecific trait relationships under global changes, and call for linking within-species responses to interspecific coordination of plant traits.

Background: Poor dietary choices are a risk factor for non-communicable diseases. Young adults have low levels of engagement towards their health and may not see the importance in the adoption of healthy eating behaviours at this stage in their lives. Here we utilise social marketing principles, digital ethnography and online conversations to gain insights into young adults' attitudes and sentiments towards healthy eating., Methods: Young Australian adults who use social media at least twice a day were recruited by a commercial field house. Using a mixture of methods, combining online polls, forums and conversations, participants (n = 195, 18-24 years old) engaged in facilitated discussions over an extended 4 week period about health and eating-related topics. Data were analysed using thematic analysis constant comparison approach. A post-hoc conceptual framework related to religion was theorised and used as a metaphor to describe the results., Results: Findings demonstrate that different segments of young adults with varying attitudes and interest towards healthy eating exist. We developed a conceptual framework based on consumer segmentation which adopted religious metaphors as a typology of 'consumers'. Some young adults practice and believe in the message of healthy eating (saints), whilst some oppose these messages and are not motivated to make any change (sinners), another segment are both aware of and interested in the issues but do not put healthy eating behaviours as a current priority (person in the pew)., Conclusions: Consumer segmentation and social marketing techniques assist health professionals to understand their target audience and tailor specific messages to different segments. Segmentation provides insights on which groups may be most easily influenced to adopt the desired behaviours. The typology presented may be a useful tool for health professionals and social marketers to design strategies to engage young adults in healthy eating, particularly those in the pew who are contemplating a change but lacking the motivation. The utilisation of marketing segmentation in health promotion has the potential to enhance health messaging by tailoring messages to specific segments based on their needs, beliefs and intentions and therefore drive the efficient use of resources towards those most likely to change.

Stem xylem-specific hydraulic conductivity (K S ) represents the potential for plant water transport normalized by xylem cross section, length, and driving force. Variation in K S has implications for plant transpiration and photosynthesis, growth and survival, and also the geographic distribution of species. Clarifying the global-scale patterns of K S and its major drivers is needed to achieve a better understanding of how plants adapt to different environmental conditions, particularly under climate change scenarios. Here, we compiled a xylem hydraulics dataset with 1,186 species-at-site combinations (975 woody species representing 146 families, from 199 sites worldwide), and investigated how K S varied with climatic variables, plant functional types, and biomes. Growing-season temperature and growing-season precipitation drove global variation in K S independently. Both the mean and the variation in K S were highest in the warm and wet tropical regions, and lower in cold and dry regions, such as tundra and desert biomes. Our results suggest that future warming and redistribution of seasonal precipitation may have a significant impact on species functional diversity, and is likely to be particularly important in regions becoming warmer or drier, such as high latitudes. This highlights an important role for K S in predicting shifts in community composition in the face of climate change., (© 2019 John Wiley & Sons Ltd.)

Background: Rosacea is a chronic dermatologic condition with limited treatment options. Methods: Data were pooled from two identically designed phase 3 trials. Patients with moderate to severe persistent erythema of rosacea were randomized to receive oxymetazoline cream 1.0% or vehicle once daily for 29 days and were followed for 28 days posttreatment. The primary efficacy outcome was the proportion of patients with ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) at 3, 6, 9, and 12 hours postdose, day 29. Results: The pooled population included 885 patients (78.8% female); 85.8% and 91.2% had moderate erythema based on CEA and SSA, respectively. The primary outcome was achieved by significantly more patients in the oxymetazoline than vehicle group (P<0.001). Individual CEA and SSA scores and reduction in facial erythema (digital image analysis) favored oxymetazoline over vehicle (P<0.001). The incidence of treatment-emergent adverse events was low (oxymetazoline, 16.4%; vehicle, 11.8%). No clinically relevant erythema worsening (based on CEA and SSA) was observed during the 28-day posttreatment follow-up period (oxymetazoline, 1.7%; vehicle, 0.6%). Conclusion: Oxymetazoline effectively reduced moderate to severe persistent facial erythema of rosacea and was well tolerated. J Drugs Dermatol. 2018;17(11):1201-1208.

Background: Limited treatments are available for persistent erythema of rosacea., Objective: To examine the long-term safety and efficacy of oxymetazoline cream 1.0% in patients with rosacea with moderate-to-severe persistent erythema., Methods: Patients applied oxymetazoline once daily for 52 weeks. Safety assessments included treatment-emergent adverse events (TEAEs), skin blanching, inflammatory lesion counts, telangiectasia, disease severity, and rebound effect. Efficacy was assessed by the Clinician Erythema Assessment and Subject Self-Assessment composite score at 3 and 6 hours after the dose on day 1 and at weeks 4, 26, and 52., Results: Among 440 patients, 8.2% reported treatment-related TEAEs; the most common were application-site dermatitis, paresthesia, pain, and pruritus. The rate of discontinuation due to adverse events (mostly application-site TEAEs) was 3.2%. No clinically meaningful changes were observed in skin blanching, inflammatory lesions, or telangiectasia. At week 52, 36.7%, and 43.4% of patients achieved a 2-grade or greater composite improvement from baseline in both Clinician Erythema Assessment and Subject Self-Assessment 3 and 6 hours after a dose, respectively. Less than 1% of patients experienced a rebound effect following treatment cessation., Limitations: A vehicle-control group was not included., Conclusion: This long-term study demonstrated sustained safety, tolerability, and efficacy of oxymetazoline for moderate-to-severe persistent erythema of rosacea., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Rosacea is a chronic dermatologic condition with limited treatment options, particularly for persistent erythema. This pivotal phase 3 study evaluated oxymetazoline, an a1A-adrenoceptor agonist, for the treatment of moderate to severe persistent erythema of rosacea. Eligible patients were randomly assigned 1:1 to receive oxymetazoline cream 1.0% or vehicle applied topically to the face once daily for 29 days. The primary efficacy outcome was ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for rosacea facial redness (SSA) (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Digital image analysis of rosacea facial erythema was evaluated as a secondary efficacy outcome measure. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal tolerability. Patients were followed for 28 days posttreatment to assess worsening of erythema (1-grade increase in severity from baseline on composite CEA/SSA in patients with moderate erythema at baseline; rebound effect). The study included 445 patients (mean age: 50.3 years; 78.7% female); most had moderate erythema at baseline (84.0% on CEA; 91.5% on SSA). The proportion of patients achieving the primary efficacy outcome was significantly greater with oxymetazoline versus vehicle (P=0.001). Similar results favoring oxymetazoline over vehicle were observed for the individual CEA and SSA scores (P less than 0.001 and P=0.011, respectively). Median reduction in rosacea facial erythema on day 29 as assessed by digital image analysis also favored oxymetazoline over vehicle (P less than 0.001). Safety results were similar between oxymetazoline and vehicle; discontinuations due to TEAEs were low (2.7% vs 0.5%). Following cessation of treatment, 2 (1.2%) patients in the oxymetazoline group and no patient in the vehicle group had rebound effect compared with their day 1 baseline score. Topical oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in the treatment of moderate to severe persistent facial erythema of rosacea.

J Drugs Dermatol. 2018;17(3):290-298.

Numerous current efforts seek to improve the representation of ecosystem ecology and vegetation demographic processes within Earth System Models (ESMs). These developments are widely viewed as an important step in developing greater realism in predictions of future ecosystem states and fluxes. Increased realism, however, leads to increased model complexity, with new features raising a suite of ecological questions that require empirical constraints. Here, we review the developments that permit the representation of plant demographics in ESMs, and identify issues raised by these developments that highlight important gaps in ecological understanding. These issues inevitably translate into uncertainty in model projections but also allow models to be applied to new processes and questions concerning the dynamics of real-world ecosystems. We argue that stronger and more innovative connections to data, across the range of scales considered, are required to address these gaps in understanding. The development of first-generation land surface models as a unifying framework for ecophysiological understanding stimulated much research into plant physiological traits and gas exchange. Constraining predictions at ecologically relevant spatial and temporal scales will require a similar investment of effort and intensified inter-disciplinary communication., (© 2017 John Wiley & Sons Ltd.)