Diamond-lattice photonic crystals assembled from DNA origami.

Colloidal self-assembly allows rational design of structures on the micrometer and submicrometer scale. One architecture that can generate complete three-dimensional photonic bandgaps is the diamond cubic lattice, which has remained difficult to realize at length scales comparable with the wavelength of visible or ultraviolet light. In this work, we demonstrate three-dimensional photonic crystals self-assembled from DNA origami that act as precisely programmable patchy colloids. Our DNA-based nanoscale tetrapods crystallize into a rod-connected diamond cubic lattice with a periodicity of 170 nanometers. This structure serves as a scaffold for atomic-layer deposition of high-refractive index materials such as titanium dioxide, yielding a tunable photonic bandgap in the near-ultraviolet.

Republication of "Postoperative Narcotic Prescription Practice in Orthopedic Foot and Ankle Surgery".

Background: The misuse and abuse of opioid pain medications have become a public health crisis. Because orthopedic surgeons are the third highest prescribers of opioids, understanding their postoperative pain medication prescribing practices is key to solving the opioid crisis. To this end, we conducted a study of the variability in orthopedic foot and ankle surgery postoperative opioid prescribing practice patterns. Methods: Three hundred fifty orthopedic foot and ankle surgeons were contacted; respondents completed a survey with 4 common patient scenarios and surgical procedures followed by questions regarding typical postoperative pain medication prescriptions. The scenarios ranged from minimally painful procedures to those that would be expected to be significantly more painful. Summaries were calculated as percentages and chi-square or Fisher exact tests were used to compare survey responses between groups stratified by years in practice and type of practice. Results: Sixty-four surgeons responded to the survey (92.8% male), 31% were in practice less than 5 years, 34% 6 to 15 years and 34% more than 15 years. For each scenario, there was variation in the type of pain medication prescribed (scenario 1: 17% 5 mg hydrocodone, 22% 10 mg hydrocodone, 52% oxycodone, and 3% oxycodone sustained release [SR]; scenario 2: 15% 5 mg hydrocodone, 13% 10 mg hydrocodone, 58% oxycodone, and 9% oxycodone SR; scenario 3: 11% 5 mg hydrocodone, 13% 10 mg hydrocodone, 56% oxycodone, and 14.1% oxycodone SR; scenario 4: 3% 5 mg hydrocodone, 5% 10 mg hydrocodone, 44% oxycodone, and 45% oxycodone SR) and the number of pills dispensed. Use of multimodal pain management was variable but most physicians use regional nerve blocks for each scenario (76%, 87%, 69%, 94%). Less experienced surgeons (less than 5 years in practice) supplement with tramadol more for scenario 1 (P = .034) as well as use regional nerve blocks for scenario 2 (P = .039) more than experienced surgeons (more than 15 years in practice). Conclusion: It is evident that variation exists in narcotic prescription practices for postoperative pain management by orthopedic foot and ankle surgeons. With new AAOS guidelines, it is important to try to create some standardization in opioid prescription protocols.

Growth portfolios buffer climate-linked environmental change in marine systems.

Large-scale, climate-induced synchrony in the productivity of fish populations is becoming more pronounced in the world's oceans. As synchrony increases, a population's "portfolio" of responses can be diminished, in turn reducing its resilience to strong perturbation. Here we argue that the costs and benefits of trait synchronization, such as the expression of growth rate, are context dependent. Contrary to prevailing views, synchrony among individuals could actually be beneficial for populations if growth synchrony increases during favorable conditions, and then declines under poor conditions when a broader portfolio of responses could be useful. Importantly, growth synchrony among individuals within populations has seldom been measured, despite well-documented evidence of synchrony across populations. Here, we used century-scale time series of annual otolith growth to test for changes in growth synchronization among individuals within multiple populations of a marine keystone species (Atlantic cod, Gadus morhua). On the basis of 74,662 annual growth increments recorded in 13,749 otoliths, we detected a rising conformity in long-term growth rates within five northeast Atlantic cod populations in response to both favorable growth conditions and a large-scale, multidecadal mode of climate variability similar to the East Atlantic Pattern. The within-population synchrony was distinct from the across-population synchrony commonly reported for large-scale environmental drivers. Climate-linked, among-individual growth synchrony was also identified in other Northeast Atlantic pelagic, deep-sea and bivalve species. We hypothesize that growth synchrony in good years and growth asynchrony in poorer years reflects adaptive trait optimization and bet hedging, respectively, that could confer an unexpected, but pervasive and stabilizing, impact on marine population productivity in response to large-scale environmental change.

Destabilisation of the Subpolar North Atlantic prior to the Little Ice Age.

The cooling transition into the Little Ice Age was the last notable shift in the climate system prior to anthropogenic global warming. It is hypothesised that sea-ice to ocean feedbacks sustained an initial cooling into the Little Ice Age by weakening the subpolar gyre circulation; a system that has been proposed to exhibit bistability. Empirical evidence for bistability within this transition has however been lacking. Using statistical indicators of resilience in three annually-resolved bivalve proxy records from the North Icelandic shelf, we show that the subpolar North Atlantic climate system destabilised during two episodes prior to the Little Ice Age. This loss of resilience indicates reduced attraction to one stable state, and a system vulnerable to an abrupt transition. The two episodes preceded wider subpolar North Atlantic change, consistent with subpolar gyre destabilisation and the approach of a tipping point, potentially heralding the transition to Little Ice Age conditions.

Rationally Designed Topological Quantum Dots in Bottom-Up Graphene Nanoribbons.

Bottom-up graphene nanoribbons (GNRs) have recently been shown to host nontrivial topological phases. Here, we report the fabrication and characterization of deterministic GNR quantum dots whose orbital character is defined by zero-mode states arising from nontrivial topological interfaces. Topological control was achieved through the synthesis and on-surface assembly of three distinct molecular precursors designed to exhibit structurally derived topological electronic states. Using a combination of low-temperature scanning tunneling microscopy and spectroscopy, we have characterized two GNR topological quantum dot arrangements synthesized under ultrahigh vacuum conditions. Our results are supported by density-functional theory and tight-binding calculations, revealing that the magnitude and sign of orbital hopping between topological zero-mode states can be tuned based on the bonding geometry of the interconnecting region. These results demonstrate the utility of topological zero modes as components for designer quantum dots and advanced electronic devices.

Relationship between Viscosity and Acyl Tail Dynamics in Lipid Bilayers.

Membrane viscosity is a fundamental property that controls molecular transport and structural rearrangements in lipid membranes. Given its importance in many cell processes, various experimental and computational methods have been developed to measure the membrane viscosity, yet the estimated values depend highly on the method and vary by orders of magnitude. Here we investigate the molecular origins of membrane viscosity by measuring the nanoscale dynamics of the lipid acyl tails using x-ray and neutron spectroscopy techniques. The results show that the membrane viscosity can be estimated from the structural relaxation times of the lipid tails.

Collective dynamics in lipid membranes containing transmembrane peptides.

Biological membranes are composed of complex mixtures of lipids and proteins that influence each other's structure and function. The biological activities of many channel-forming peptides and proteins are known to depend on the material properties of the surrounding lipid bilayer. However, less is known about how membrane-spanning channels affect the lipid bilayer properties, and in particular, their collective fluctuation dynamics. Here we use neutron spin echo spectroscopy (NSE) to measure the collective bending and thickness fluctuation dynamics in dimyristoylphosphatidylcholine (di 14 : 0 PC, DMPC) lipid membranes containing two different antimicrobial peptides, alamethicin (Ala) and gramicidin (gD). Ala and gD are both well-studied antimicrobial peptides that form oligomeric membrane-spanning channels with different structures. At low concentrations, the peptides did not have a measurable effect on the average bilayer structure, yet significantly changed the collective membrane dynamics. Despite both peptides forming transmembrane channels, they had opposite effects on the relaxation time of the collective bending fluctuations and associated effective bending modulus, where gD addition stiffened the membrane while Ala addition softened the membrane. Meanwhile, the lowest gD concentrations enhanced the collective thickness fluctuation dynamics, while the higher gD concentrations and all studied Ala concentrations dampened these dynamics. The results highlight the synergy between lipids and proteins in determining the collective membrane dynamics and that not all peptides can be universally treated as rigid bodies when considering their effects on the lipid bilayer fluctuations.

Direct localization of detergents and bacteriorhodopsin in the lipidic cubic phase by small-angle neutron scattering.

Lipidic cubic phase (LCP) crystallization methods have been essential in obtaining crystals of certain membrane proteins, particularly G-protein-coupled receptors. LCP crystallization is generally optimized across a large number of potential variables, one of which may be the choice of the solubilizing detergent. A better fundamental understanding of the behavior of detergents in the LCP may guide and simplify the detergent selection process. This work investigates the distribution of protein and detergent in LCP using the membrane protein bacteriorhodopsin (bR), with the LCP prepared from highly deuterated monoolein to allow contrast-matched small-angle neutron scattering. Contrast-matching allows the scattering from the LCP bilayer itself to be suppressed, so that the distribution and behavior of the protein and detergent can be directly studied. The results showed that, for several common detergents, the detergent micelle dissociates and incorporates into the LCP bilayer essentially as free detergent monomers. In addition, the detergent octyl glucoside dissociates from bR, and neither the protein nor detergent forms clusters in the LCP. The lack of detergent assemblies in the LCP implies that, upon incorporation, micelle sizes and protein/detergent interactions become less important than they would be in solution crystallization. Crystallization screening confirmed this idea, with crystals obtained from bR in the presence of most detergents tested. Thus, in LCP crystallization, detergents can be selected primarily on the basis of protein stabilization in solution, with crystallization suitability a lesser consideration.

Enhanced dynamics in the anomalous melting regime of DMPG lipid membranes.

Like many soft materials, lipids undergo a melting transition associated with a significant increase in their dynamics. At temperatures below the main melting transition (Tm ), all molecular and collective dynamics are suppressed, while above Tm the alkyl tail motions, lipid diffusivity, and collective membrane undulations are at least an order of magnitude faster. Here we study the collective dynamics of dimyristoylphosphatidylglycerol (DMPG, di 14:0 PG) using neutron spin echo spectroscopy throughout its anomalous phase transition that occurs over a 12 °C-20° C wide temperature window. Our results reveal that the membranes are softer and more dynamic during the phase transition than at higher temperatures corresponding to the fluid phase and provide direct experimental evidence for the predicted increase in membrane fluctuations during lipid melting. These results provide new insights into the nanoscale lipid membrane dynamics during the melting transition and demonstrate how these dynamics are coupled to changes in the membrane structure.

Nonclinical safety assessment of epigenetic modulatory drugs: Current status and industry perspective.

Pharmaceutic products designed to perturb the function of epigenetic modulators have been approved by regulatory authorities for treatment of advanced cancer. While the predominant effort in epigenetic drug development continues to be in oncology, non-oncology indications are also garnering interest. A survey of pharmaceutical companies was conducted to assess the interest and concerns for developing small molecule direct epigenetic effectors (EEs) as medicines. Survey themes addressed (1) general levels of interest and activity with EEs as therapeutic agents, (2) potential safety concerns, and (3) possible future efforts to develop targeted strategies for nonclinical safety assessment of EEs. Thirteen companies contributed data to the survey. Overall, the survey data indicate the consensus opinion that existing ICH guidelines are effective and appropriate for nonclinical safety assessment activities with EEs. Attention in the framework of study design should, on a case by case basis, be considered for delayed or latent toxicities, carcinogenicity, reproductive toxicity, and the theoretical potential for transgenerational effects. While current guidelines have been appropriate for the nonclinical safety assessments of epigenetic targets, broader experience with a wide range of epigenetic targets will provide information to assess the potential need for new or revised risk assessment strategies for EE drugs.

Scaling relationships for the elastic moduli and viscosity of mixed lipid membranes.

The elastic and viscous properties of biological membranes play a vital role in controlling cell functions that require local reorganization of the membrane components as well as dramatic shape changes such as endocytosis, vesicular trafficking, and cell division. These properties are widely acknowledged to depend on the unique composition of lipids within the membrane, yet the effects of lipid mixing on the membrane biophysical properties remain poorly understood. Here, we present a comprehensive characterization of the structural, elastic, and viscous properties of fluid membranes composed of binary mixtures of lipids with different tail lengths. We show that the mixed lipid membrane properties are not simply additive quantities of the single-component analogs. Instead, the mixed membranes are more dynamic than either of their constituents, quantified as a decrease in their bending modulus, area compressibility modulus, and viscosity. While the enhanced dynamics are seemingly unexpected, we show that the measured moduli and viscosity for both the mixed and single-component bilayers all scale with the area per lipid and collapse onto respective master curves. This scaling links the increase in dynamics to mixing-induced changes in the lipid packing and membrane structure. More importantly, the results show that the membrane properties can be manipulated through lipid composition the same way bimodal blends of surfactants, liquid crystals, and polymers are used to engineer the mechanical properties of soft materials, with broad implications for understanding how lipid diversity relates to biomembrane function.

Translation of in vitro cannabinoid 1 receptor agonist activity to in vivo pharmacodynamic endpoints.

INTRODUCTION: Building an understanding of in vivo efficacy based on the evaluation of in vitro affinity or potency is critical in expediting early decision making in drug discovery and can significantly reduce the need for animal studies. The aim of the present study was to understand the translation of in vitro to in vivo endpoints for the cannabinoid receptor 1 (CB1). METHODS: Using a selection of CB1 agonists we describe an evaluation of in vitro to in vivo translation comparing in vitro receptor affinity or functional potency, using both cAMP and ß-arrestin endpoints, to various in vivo CB1 agonist-associated endpoints. RESULTS: We demonstrate that in vitro CB1 agonism significantly correlates with the CB1-induced cue in the drug discrimination model in vivo, but not with other purported CB1 agonist-mediated in vivo endpoints, including hypothermia and sedation. Thus, these data challenge common perceptions regarding CB1 agonist-induced tetrad effects in rodents. DISCUSSION: This work exemplifies how in vitro profiling of receptor affinity or potency can predict in vivo pharmacodynamic effects, using the CB1 as an example system. The translatability of in vitro activity to in vivo efficacy allows for the ability to rapidly contextualize off-target CB1 in vitro findings, allowing clear and rapid definition of the risk posed by such activity without the need for extensive animal studies. This has significant implications in terms of early decision making in drug discovery and reducing the use of animals in research, while also outlining a template for expanding the approach for additional targets.

Bottom-up Assembly of Nanoporous Graphene with Emergent Electronic States.

The incorporation of nanoscale pores into a sheet of graphene allows it to switch from an impermeable semimetal to a semiconducting nanosieve. Nanoporous graphenes are desirable for applications ranging from high-performance semiconductor device channels to atomically thin molecular sieve membranes, and their performance is highly dependent on the periodicity and reproducibility of pores at the atomic level. Achieving precise nanopore topologies in graphene using top-down lithographic approaches has proven to be challenging due to poor structural control at the atomic level. Alternatively, atomically precise nanometer-sized pores can be fabricated via lateral fusion of bottom-up synthesized graphene nanoribbons. This technique, however, typically requires an additional high temperature cross-coupling step following the nanoribbon formation that inherently yields poor lateral conjugation, resulting in 2D materials that are weakly connected both mechanically and electronically. Here, we demonstrate a novel bottom-up approach for forming fully conjugated nanoporous graphene through a single, mild annealing step following the initial polymer formation. We find emergent interface-localized electronic states within the bulk band gap of the graphene nanoribbon that hybridize to yield a dispersive two-dimensional low-energy band of states. We show that this low-energy band can be rationalized in terms of edge states of the constituent single-strand nanoribbons. The localization of these 2D states around pores makes this material particularly attractive for applications requiring electronically sensitive molecular sieves.

Catalyzing sustainable fisheries management through behavior change interventions.

Small-scale fisheries are an important livelihood and primary protein source for coastal communities in many of the poorest regions in the world, yet many are overfished and thus require effective and scalable management solutions. Positive ecological and socioeconomic responses to management typically lag behind immediate costs borne by fishers from fishing pressure reductions necessary for fisheries recovery. These short-term costs challenge the long-term success of these interventions. However, social marketing may increase perceptions of management benefits before ecological and socioeconomic benefits are fully realized, driving new social norms and ultimately long-term sustainable behavior change. By conducting underwater visual surveys to quantify ecological conditions and by conducting household surveys with community members to quantify their perceptions of management support and socioeconomic conditions, we assessed the impact of a standardized small-scale fisheries management intervention that was implemented across 41 sites in Brazil, Indonesia, and the Philippines. The intervention combines TURF reserves (community-based territorial use rights for fishing coupled with no-take marine reserves) with locally tailored social-marketing behavior change campaigns. Leveraging data across 22 indicators and 4 survey types, along with data from 3 control sites, we found that ecological and socioeconomic impacts varied and that communities supported the intervention and were already changing their fishing practices. These results suggest that communities were developing new social norms and fishing more sustainably before long-term ecological and socioeconomic benefits of fisheries management materialized.

Catalización del Manejo de Pesquerías Sustentables por medio de Intervenciones de Cambio de Comportamiento Resumen Las pesquerías a pequeña escala son un sustento importante y la principal fuente de proteína para las comunidades costeras en muchas de las regiones más pobres del mundo, sin embargo, muchas sufren de sobrepesca y por lo tanto requieren soluciones de manejo efectivas y escalables. Las respuestas ecológicas y socioeconómicas positivas al manejo generalmente se retrasan con respecto a los costos inmediatos asumidos por los pescadores a partir de las reducciones de la presión ocasionada por la pesca necesarias para la recuperación de la pesquería. Estos costos a corto plazo son un reto para el éxito a largo plazo de las intervenciones. Sin embargo, la mercadotecnia social puede incrementar las percepciones de los beneficios del manejo antes de que se conozcan por completo los beneficios ecológicos y socioeconómicos, lo que genera nuevas normas sociales y finalmente un cambio en el comportamiento a largo plazo. Realizamos censos submarinos visuales para cuantificar las condiciones ecológicas y censos domésticos a los miembros de la comunidad para cuantificar sus percepciones del apoyo al manejo y de las condiciones socioeconómicas. Con esto, evaluamos el impacto de la intervención de manejo para pesquerías estandarizadas a pequeña escala que fue implementada en 41 sitios de Brasil, Indonesia y las Filipinas. La intervención combina las reservas TURF (derechos de uso de pesca territorial basados en la comunidad acoplados con reservas marinas con restricción de pesca) con campañas de mercadotecnia social para el cambio de comportamiento ajustadas al contexto local. Con la movilización de datos a lo largo de 22 indicadores y cuatro tipos de censos, junto con los datos de tres sitios de control, encontramos que los impactos ecológicos y socioeconómicos variaron y que las comunidades apoyaban la intervención y ya se encontraban cambiando sus prácticas de pesca. Estos resultados sugieren que las comunidades ya estaban desarrollando nuevas normas sociales y pescando de manera más sustentable antes de que los beneficios ecológicos y socioeconómicos a largo plazo del manejo de las pesquerías se materializaran.

In situ neutron scattering of antibody adsorption during protein A chromatography.

A deeper understanding of the nanoscale and mesoscale structure of chromatographic adsorbents and the distribution of proteins within the media, is critical to a mechanistic understanding of separation processes using these materials. Characterisation of the media's architecture at this scale and protein adsorption within, is challenging using conventional techniques. In this study, we propose a novel resin characterisation technique that enables in-situ measurement of the structure of the adsorbed protein layer within the resin, under typical chromatographic conditions. A quartz flow-through cell was designed and fabricated for use with Small Angle Neutron Scattering (SANS), in order to measure the nanoscale to mesoscale structures of a silica based protein A chromatography resin during the monoclonal antibody sorption process. We were able to examine the pore-to-pore (˜133 nm) and pore size (˜63 nm) correlations of the resin and the in-plane adsorbed antibody molecules (˜ 4.2 nm) correlation at different protein loadings and washing buffers, in real time using a contrast matching approach. When 0.03 M sodium phosphate with 1 M urea and 10 % isopropanol buffer, pH 8, was introduced into the system as a wash buffer, it disrupted the system's order by causing partial unfolding of the adsorbed antibody, as evidenced by a loss of the in-plane protein correlation. This method offers new ways to investigate the nanoscale structure and ligand immobilisation within chromatography resins; and perhaps most importantly understand the in-situ behaviour of adsorbed proteins within the media under different mobile phase conditions within a sample environment replicating that of a chromatography column.

Anomalous inter-membrane cholesterol transport in fluid phase phosphoserine vesicles driven by headgroup ordered to disordered entropic transition.

POPS is highly enriched in the inner leaflet of the plasma membrane. Here we present measurements of inter-membrane cholesterol transport rates in POPS vesicles. We find that the cholesterol transport kinetics are not only an order of magnitude slower than in POPC lipids at near physiological temperatures, they exhibit a surprising discontinuous Arrhenius behavior around 48 °C. Moreover, thermodynamic analysis suggests that for biologically relevant temperatures, below the discontinuity, the exchange of cholesterol is entropically dominated while it is enthalpically driven, as is the case in POPC vesicles, above that discontinuity. Using the polar fluorescent probe Laurdan we found that POPS fluid membranes retain a large degree of order in the headgroup region for temperatures below the discontinuity but undergo an order-to-disorder transition in the region coinciding with the discontinuity in the transport of cholesterol in POPS membranes providing an explanation not only for the discontinuity but for the entropic dominance at physiological temperatures.

8.2 ka event North Sea hydrography determined by bivalve shell stable isotope geochemistry.

The abrupt 8.2 ka cold event has been widely described from Greenland and North Atlantic records. However, its expression in shelf seas is poorly documented, and the temporal resolution of most marine records is inadequate to precisely determine the chronology of major events. A robust hydrographical reconstruction can provide an insight on climatic reaction times to perturbations to the Atlantic Meridional Overturning Circulation. Here we present an annually-resolved temperature and water column stratification reconstruction based on stable isotope geochemistry of Arctica islandica shells from the Fladen Ground (northern North Sea) temporally coherent with Greenland ice core records. Our age model is based on a growth increment chronology obtained from four radiometrically-dated shells covering the 8290-8100 cal BP interval. Our results indicate that a sudden sea level rise (SSLR) event-driven column stratification occurred between ages 8320-8220 cal BP. Thirty years later, cold conditions inhibited water column stratification but an eventual incursion of sub-Arctic waters into the North Sea re-established density-driven stratification. The water temperatures reached their minimum of ~3.7 °C 55 years after the SSLR. Intermittently-mixed conditions were later established when the sub-Arctic waters receded.

The revolution of crossdating in marine palaeoecology and palaeoclimatology.

Over the past century, the dendrochronology technique of crossdating has been widely used to generate a global network of tree-ring chronologies that serves as a leading indicator of environmental variability and change. Only recently, however, has this same approach been applied to growth increments in calcified structures of bivalves, fish and corals in the world's oceans. As in trees, these crossdated marine chronologies are well replicated, annually resolved and absolutely dated, providing uninterrupted multi-decadal to millennial histories of ocean palaeoclimatic and palaeoecological processes. Moreover, they span an extensive geographical range, multiple trophic levels, habitats and functional types, and can be readily integrated with observational physical or biological records. Increment width is the most commonly measured parameter and reflects growth or productivity, though isotopic and elemental composition capture complementary aspects of environmental variability. As such, crossdated marine chronologies constitute powerful observational templates to establish climate-biology relationships, test hypotheses of ecosystem functioning, conduct multi-proxy reconstructions, provide constraints for numerical climate models, and evaluate the precise timing and nature of ocean-atmosphere interactions. These 'present-past-future' perspectives provide new insights into the mechanisms and feedbacks between the atmosphere and marine systems while providing indicators relevant to ecosystem-based approaches of fisheries management.

Scaling of lipid membrane rigidity with domain area fraction.

Biological membranes are highly heterogeneous in composition which in turn leads to local variations in the physical properties. Here we quantify how heterogeneity in stiffness determines the effective bending modulus, κeff, of model phase-separated membranes with coexisting soft fluid and rigid gel domains. We find that the temperature- and composition- dependent trends in membrane rigidity collapse onto a single curve, such that κeff directly scales with the area fraction of the rigid gel domains. Using no adjustable parameters, the measurements are found to agree with theoretical predictions for inhomogenous membranes and indicate that κeff is sensitive to the lateral distribution of the rigid phase within the membrane. This key finding confirms that the properties of heterogeneous membranes can be quantitatively predicted if the area fraction and properties of the individual phases are known.

Transforming phosphorus use on the island of Ireland: A model for a sustainable system.

Phosphorus is an essential part of the world food web and a non-substitutable nutrient in all biological systems. Losses of phosphorus occur along the food-supply chain and cause environmental degradation and eutrophication. A key global challenge is to meet rising worldwide food demand while protecting water and environmental quality, and seeking to manage uncertainty around potential future phosphorus price or supply shocks. This paper presents a stakeholder-generated conceptual model of potential transformative change for implementing phosphorus sustainability on the island of Ireland via an 'All-Island Phosphorus Sustainability' workshop. Key transition pathways identified by stakeholders included: incentivising phosphorus recovery, developing collaborative networks to facilitate change, developing markets and value chains for recovered products; implementing data-informed practices on-farm to prevent losses and increase efficiencies, and harmonisation of technologies with end-user needs. A comparable model was previously produced for the North American region. We describe consensus and differences around key priorities between the two regions' conceptual models, and assess how the model produced for the island of Ireland can effect system-wide change and policy moving forward. Many of the transitional pathways and future aspirations presented in both models resonate globally and are highly pertinent to other jurisdictions.