Reservoir computing using networks of memristors: effects of topology and heterogeneity.

Reservoir computing (RC) has attracted significant interest as a framework for the implementation of novel neuromorphic computing architectures. Previously attention has been focussed on software-based reservoirs, where it has been demonstrated that reservoir topology plays a role in task performance, and functional advantage has been attributed to small-world and scale-free connectivity. However in hardware systems, such as electronic memristor networks, the mechanisms responsible for the reservoir dynamics are very different and the role of reservoir topology is largely unknown. Here we compare the performance of a range of memristive reservoirs in several RC tasks that are chosen to highlight different system requirements. We focus on percolating networks of nanoparticles (PNNs) which are novel self-assembled nanoscale systems that exhibit scale-free and small-world properties. We find that the performance of regular arrays of uniform memristive elements is limited by their symmetry but that this symmetry can be broken either by a heterogeneous distribution of memristor properties or a scale-free topology. The best perfomance across all tasks is observed for a scale-free network with uniform memistor properties. These results provide insight into the role of topology in neuromorphic reservoirs as well as an overview of the computational performance of scale-free networks of memristors in a range of benchmark tasks.

Reservoir computing with 3D nanowire networks.

Networks of nanowires are currently being explored for a range of applications in brain-like (or neuromorphic) computing, and especially in reservoir computing (RC). Fabrication of real-world computing devices requires that the nanowires are deposited sequentially, leading to stacking of the wires on top of each other. However, most simulations of computational tasks using these systems treat the nanowires as 1D objects lying in a perfectly 2D plane - the effect of stacking on RC performance has not yet been established. Here we use detailed simulations to compare the performance of perfectly 2D and quasi-3D (stacked) networks of nanowires in two tasks: memory capacity and nonlinear transformation. We also show that our model of the junctions between nanowires is general enough to describe a wide range of memristive networks, and consider the impact of physically realistic electrode configurations on performance. We show that the various networks and configurations have a strikingly similar performance in RC tasks, which is surprising given their radically different topologies. Our results show that networks with an experimentally achievable number of electrodes perform close to the upper bounds achievable when using the information from every wire. However, we also show important differences, in particular that the quasi-3D networks are more resilient to changes in the input parameters, generalizing better to noisy training data. Since previous literature suggests that topology plays an important role in computing performance, these results may have important implications for future applications of nanowire networks in neuromorphic computing.

A randomized controlled trial of the impact of the Teen Council peer education program on youth development.

This paper presents results of an impact evaluation of Teen Council, a program that trains youth as peer educators. Teen Council is designed to help peer educators make healthy sexual and reproductive decisions, increase their confidence and abilities to educate their peers and inspire them to advocate for just sexual policies. The program's impact on these educators was evaluated using a randomized controlled trial. Over 5 years, interested high school students in seven states were randomly assigned to a study condition. An intent-to-treat framework using ordinary least square (OLS) regression was employed to measure program effects. Relative to control, Teen Council youth showed enhanced comfort with their own sexuality, greater comfort with and more frequent communication with parents about sexuality and more positive sexual health behaviors, including accessing reproductive health care and adopting more effective means of contraception. Teen Council youth also reported greater confidence in talking with peers about sexuality and more confidence in their civic engagement skills.

Adolescent Binge Drinking Is Associated With Accelerated Decline of Gray Matter Volume.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan-Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose-response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study.

BACKGROUND: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12. METHODS: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD). PRIMARY RESULTS: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03). CONCLUSIONS: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

Removable capping layer for air-sensitive GdN.

The strongly correlated rare earth nitrides display unusual coupled magnetic, electronic and superconducting properties, with predicted topological states. However, their air-sensitiveness has prevented in-depth investigations of their properties. In this paper, we show that a 100 nm thick epitaxial samarium layer provides adequate passivation of 100 nm thick thin films of gadolinium nitride (GdN), the prototypical rare earth nitride, enabling ex-situ magnetic and structural characterizations. Using reflection high-energy electron diffraction, atomic force microscopy and energy dispersive x-ray spectroscopy, we investigate the thermal desorption of the samarium layer under vacuum. We finally demonstrate successful removal of the samarium capping layer in a separate vacuum chamber after exposure to air using a combination of argon ion sputtering and thermal desorption at 400 °C, recovering the GdN surface.

Avalanches and criticality in self-organized nanoscale networks.

Current efforts to achieve neuromorphic computation are focused on highly organized architectures, such as integrated circuits and regular arrays of memristors, which lack the complex interconnectivity of the brain and so are unable to exhibit brain-like dynamics. New architectures are required, both to emulate the complexity of the brain and to achieve critical dynamics and consequent maximal computational performance. We show here that electrical signals from self-organized networks of nanoparticles exhibit brain-like spatiotemporal correlations and criticality when fabricated at a percolating phase transition. Specifically, the sizes and durations of avalanches of switching events are power law distributed, and the power law exponents satisfy rigorous criteria for criticality. These signals are therefore qualitatively and quantitatively similar to those measured in the cortex. Our self-organized networks provide a low-cost platform for computational approaches that rely on spatiotemporal correlations, such as reservoir computing, and are an important step toward creating neuromorphic device architectures.

Beyond HbA1c : using continuous glucose monitoring metrics to enhance interpretation of treatment effect and improve clinical decision-making.

Assessment of glycaemic outcomes in the management of Type 1 and Type 2 diabetes has been revolutionized in the past decade with the increasing availability of accurate, user-friendly continuous glucose monitoring (CGM). This advancement has brought a need for new techniques to appropriately analyse and understand the voluminous and complex CGM data for application in research-related goals and clinical guidance for individuals. Traditionally, HbA1c was established using the Diabetes Control and Complications Trial (DCCT) and other trials as the ultimate measure of glycaemic control in terms of efficacy and, by default, risk of microvascular complications of diabetes. However, it is acknowledged that HbA1c alone is inadequate at describing an individual's daily glycaemic variation and risks for hypo- and hyperglycaemia, and it does not provide the guidance needed to decrease those risks. CGM data provide means by which to characterize an individual's daily glycaemic excursions on a different time scale measured in minutes rather than months. As a consequence, clinical reports, such as the ambulatory glucose profile, increasingly include summary statistics related to averages (mean glucose, time in range) as well as markers related to glycaemic variability (coefficient of variation, standard deviation). However, there is a need to translate those metrics into specific risks that can be addressed in an actionable plan by individuals with diabetes and providers. This review presents several clinical scenarios of glycaemic outcomes from CGM data that can be analysed to describe glycaemic variability and its attendant risks of hyperglycaemia and hypoglycaemia, moving towards relevant interpretation of the complex CGM data streams.

Synaptic dynamics in complex self-assembled nanoparticle networks.

We report a detailed study of neuromorphic switching behaviour in inherently complex percolating networks of self-assembled metal nanoparticles. We show that variation of the strength and duration of the electric field applied to this network of synapse-like atomic switches allows us to control the switching dynamics. Switching is observed for voltages above a well-defined threshold, with higher voltages leading to increased switching rates. We demonstrate two behavioral archetypes and show how the switching dynamics change as a function of duration and amplitude of the voltage stimulus. We show that the state of each synapse can influence the activity of the other synapses, leading to complex switching dynamics. We further demonstrate the influence of the morphology of the network on the measured device properties, and the constraints imposed by the overall network conductance. The correlated switching dynamics, device stability over long periods, and the simplicity of the device fabrication provide an attractive pathway to practical implementation of on-chip neuromorphic computing.

MRI in idiopathic, stable, slipped capital femoral epiphysis: evaluation of contralateral pre-slip.

PURPOSE: Early diagnosis and treatment of slipped capital femoral epiphysis (SCFE) is important to prevent slip progression and avoid complications. We sought to determine if MRI findings in patients with unilateral SCFE could indicate 'pre-slip' or predict future SCFE in the contralateral hip. METHODS: A prospective study evaluated patients with unilateral SCFE over a two-year period. MRI of the asymptomatic hip was performed within the perioperative period. Patients were followed with radiographs until a contralateral slip occurred or until physeal closure. Demographics, clinical stability, severity, posterior slope angle (PSA), modified Oxford Bone Score (mOBS) and patency of the triradiate cartilage were recorded and statistical analysis performed. RESULTS: In all, 33 of 54 patients with unilateral SCFE were enrolled into the study. In all, 29 (87.8%) had complete follow-up. Five of the enrolled patients (15.2%) developed a sequential slip requiring in situ pinning. Six of 33 (18.2%) patients had positive MRI findings: four of which proceeded to sequential SCFE and two which did not. One sequential slip had a negative MRI. PSA predicted 1/11 sequential slips (sensitivity 9.09%, specificity 81.4%, positive predictive value (PPV) 11.1%, negative predictive value (NPV) 77.8%) and mOBS predicted 5/11 sequential slips (sensitivity 45.5%, specificity 93%, PPV 62.5%, NPV 87%). An open triradiate cartilage was present in 8/11 patients with sequential slips (sensitivity 72.7%, specificity 81.4%, PPV 50%, NPV 92.1%). CONCLUSION: MRI findings consistent with 'pre-slip' were present in 66.7% of patients who developed a sequential SCFE. Further study on the utility/sensitivity of MRI in predicting sequential SCFE is warranted. LEVEL OF EVIDENCE: II, diagnostic.

Preliminary investigation of orally administered benazepril in horses with left-sided valvular regurgitation.

BACKGROUND: Despite the paucity of data available, orally administered angiotensin-converting enzyme (ACE) inhibitors are empirically used in horses with valvular regurgitation. OBJECTIVE: Evaluate the echocardiographic and hormonal changes in response to oral benazepril in horses with left-sided valvular regurgitation. STUDY DESIGN: Prospective, randomised double-blind, placebo-controlled trial. METHODS: Horses with mitral valve (MR) and/or aortic valve regurgitation (AR) received oral benazepril (n = 6) at a dosage of 1 mg/kg q 12 h or a placebo (n = 5) for 28 days. Echocardiography was performed before drug administration and after 28 days of treatment. Plasma renin activity, serum ACE activity, angiotensin II concentration, aldosterone concentration and biochemical variables were measured before drug administration and after 7 and 28 days of treatment. RESULTS: Relative to baseline, horses treated with benazepril had statistically significant reduction in left ventricular internal diameter in systole (mean difference between groups = -0.97 cm; 95% CI = -1.5 to -0.43 cm), aortic sinus diameter (-0.31 cm; -0.54 to -0.07 cm), and percentage of the aortic annulus diameter occupied by the base of the AR jet (-17.05%; -31.17 to -2.93%) compared with horses receiving a placebo. In addition, horses treated with benazepril had a significantly greater increase in cardiac output (11.95 L/min; 1.17-22.73 L/min) and fractional shortening (7.59%; 3.3-11.88%) compared with horses receiving a placebo. Despite profound serum ACE inhibition, renin activity and concentrations of angiotensin II and aldosterone were not significantly different between treatment groups or among time points. MAIN LIMITATIONS: Very small sample size and short treatment period. CONCLUSIONS: Treatment with oral benazepril resulted in statistically significant echocardiographic changes that might indicate reduced cardiac afterload in horses with left-sided valvular regurgitation. Additional studies with a larger sample size will be necessary to determine if administration of benazepril is beneficial in horses with valvular regurgitation. The Summary is available in Spanish - see Supporting Information.

Topological phases in double layers of bismuthene and antimonene.

Two-dimensional topological insulators show great promise for spintronic applications. Much attention has been placed on single atomic or molecular layers, such as bismuthene. The selections of such materials are, however, limited. To broaden the base of candidate materials with desirable properties for applications, we report herein an exploration of the physics of double layers of bismuthene and antimonene. The electronic structure of a film depends on the number of layers, and it can be modified by epitaxial strain, by changing the effective spin-orbit coupling strength, and by the manner in which the layers are geometrically stacked. First-principles calculations for the double layers reveal a number of phases, including topological insulators, topological semimetals, Dirac semimetals, trivial semimetals, and trivial insulators. Their phase boundaries and the stability of the phases are investigated. The results illustrate a rich pattern of phases that can be realized by tuning lattice strain and effective spin-orbit coupling.

Gauging circadian variation in ketamine metabolism by real-time breath analysis.

The time-of-day of drug application is an important factor in maximizing efficacy and minimizing toxicity. Real-time in vivo mass spectrometric breath analysis of mice was deployed to investigate time-of-day variation in ketamine metabolism. Different production rates of ketamine metabolites, including the recently described anti-depressant hydroxynorketamine, were found in opposite circadian phases. Thus, breath analysis has potential as a rapid and 3Rs (Replacement, Reduction and Refinement) conforming screening method to estimate the time-dependence of drug metabolism.

Attenuation of the blood pressure response to exogenous angiotensin I after oral administration of benazepril to healthy adult horses.

BACKGROUND: Benazepril has been shown to inhibit circulating angiotensin-converting enzyme (ACE) activity in horses but the optimal dosage is unknown. OBJECTIVES: To determine the lowest tested dose of benazepril that results in ≥75% attenuation in the response of arterial blood pressure (BP) to exogenous angiotensin I (ANG-I) administration. STUDY DESIGN: Prospective experimental study. METHODS: A total of 5 healthy horses were instrumented for the direct measurement of BP. Each horse received 4 intragastric doses of benazepril (0.5, 1, 2 and 4 mg/kg bwt) with a washout period of 7 days between doses. Prior to and 2, 12 and 24 h after benazepril administration, each horse received intravenous (i.v.) boluses of ANG-I at 20, 60 and 200 ng/kg. Attenuation of the systolic arterial pressure (SBP) response to ANG-I and serum ACE activity were quantified and expressed as percentage of inhibition. RESULTS: There was a significant effect of benazepril dose (P = 0.004) and time (P = 0.004) on the percentage of inhibition of the systolic pressor response to ANG-I. Regardless of benazepril dose, the percentage of inhibition was significantly greater 2 h after administration of benazepril compared with 12 and 24 h. At an ANG-I dose of 20 ng/kg, the percentage of inhibition after administration of benazepril at 1 mg/kg bwt (46.6 ± 18.9%) was significantly greater than that achieved after 0.5 mg/kg bwt (19 ± 14%) but not significantly different from that achieved at higher doses of benazepril. Benazepril doses ≥1 mg/kg bwt resulted in serum ACE inhibition of at least 90%. MAIN LIMITATIONS: Small sample size and resulting low statistical power. CONCLUSIONS: Attenuation of the rise in SBP in response to ANG-I after administration of benazepril is modest in horses despite adequate serum ACE inhibition. A dose of 1 mg/kg bwt would be recommended for future investigations of benazepril for the management of cardiovascular diseases in horses.

Cardiovascular Toxicities of Small Molecule Tyrosine Kinase Inhibitors: An Opportunity for Systems-Based Approaches.

Once universally considered a rapidly fatal condition, cancer has increasingly become a chronic medical condition and comorbidities and adverse effects of cancer therapies have become increasingly significant. One of the leading advancements that has gained traction for the treatment of a variety of malignancies is the class of small molecule tyrosine kinase inhibitors (TKIs). Although, in many aspects revolutionary, TKIs have their own profile of side effects, including cardiovascular side effects, the most common being hypertension (HTN), congestive heart failure, corrected QT (QTc) prolongation, and instances of premature coronary heart disease. Herein, we describe the mechanisms of small TKI-induced cardiovascular toxicity and related intracellular signaling. In particular, systems-based approaches to the understanding of small TKI-induced cardiovascular toxicity are addressed. The pathophysiology of synergic cardiovascular toxicity from TKIs, anthracyclines, and monoclonal antibodies (e.g., trastuzumab, bevacizumab) is illustrated. Finally, recommendations are made for implementing systems medicine in clinical practice, for individualized cardiovascular wellness after cancer therapy.

Assessment and validation of a defined fluid restriction protocol in the use of subcutaneous desmopressin for children with inherited bleeding disorders.

INTRODUCTION: Despite the availability of subcutaneous desmopressin (1-deamino-8-d-arginine vasopressin, SC-DDAVP) as a haemostatic agent for children with mild bleeding disorders, few publications specifically address the safety or efficacy of this mode of administration. AIM: Our aim was to assess whether a defined fluid restriction protocol was effective in preventing hyponatremia in children receiving perioperative SC-DDAVP, and to document adequate biological and clinical response in this setting. METHODS: We retrospectively analysed a cohort of children with mild bleeding disorders prescribed SC-DDAVP over a 5-year period following institution of a 'two-thirds maintenance' fluid restriction protocol. RESULTS: Sixty-nine patients received SC-DDAVP following this protocol, including 15 with mild haemophilia A, 49 with von Willebrand disease (VWD) and five with platelet storage pool disorder. In patients who underwent formal preoperative assessment a complete or partial response was observed in 28/29 with type 1 VWD and 14/15 with mild haemophilia A. Perioperative SC-DDAVP provided excellent haemostasis in all patients, with no requirement for factor concentrate or blood products. Mild asymptomatic hyponatremia was detected in seven children who received multiple doses of DDAVP (lowest sodium 129 mmol L(-1) ); however, adherence to the prescribed fluid restriction protocol was questionable in six of these cases. Symptomatic hyponatremia was not observed. CONCLUSION: Subcutaneous desmopressin was well-tolerated, with no serious side-effects observed, and good biological responses in preoperative trials. A two-thirds maintenance fluid regimen was effective at preventing symptomatic hyponatremia in our cohort, and is now the standard protocol for fluid restriction post-DDAVP administration in our centre.

Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10(-8)) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Chronic Kidney Disease in Aged Cats: Clinical Features, Morphology, and Proposed Pathogeneses.

Chronic kidney disease (CKD) is the most common metabolic disease of domesticated cats, with most affected cats being geriatric (>12 years of age). The prevalence of CKD in cats exceeds that observed in dogs, and the frequency of the diagnosis of CKD in cats has increased in recent decades. Typical histologic features include interstitial inflammation, tubular atrophy, and fibrosis with secondary glomerulosclerosis. In contrast to people and dogs, primary glomerulopathies with marked proteinuria are remarkably rare findings in cats. Although a variety of primary renal diseases have been implicated, the disease is idiopathic in most cats. Tubulointerstitial changes, including fibrosis, are present in the early stages of feline CKD and become more severe in advanced disease. A variety of factors-including aging, ischemia, comorbid conditions, phosphorus overload, and routine vaccinations-have been implicated as factors that could contribute to the initiation of this disease in affected cats. Factors that are related to progression of established CKD, which occurs in some but not all cats, include dietary phosphorus intake, magnitude of proteinuria, and anemia. Renal fibrosis, a common histologic feature of aged feline kidneys, interferes with the normal relationship between peritubular capillaries and renal tubules. Experimentally, renal ischemia results in morphologic changes similar to those observed in spontaneous CKD. Renal hypoxia, perhaps episodic, may play a role in the initiation and progression of this disease.

Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease.

Challenges in hemophilia care in Australia and New Zealand.

BACKGROUND: Health and life expectancy for people with hemophilia have improved significantly in recent years, but we face new challenges, especially in the context of resource-constrained health services. AIM: This paper aims to highlight such challenges and propose practical solutions. METHODS: Nine hemophilia specialists from Australia and New Zealand reached consensus on areas of greatest need for improvement in hemophilia care in these countries, based on clinical experience and published data, and agreed on how to address these. RESULTS: Demography, optimizing treatment and assessing treatment success were identified as broad areas of challenge which included: comorbidities in ageing patients; transitioning from pediatric to adult care; equity of care for remote populations; weight-based dosing in obese patients; tailoring prophylaxis; accurate diagnosis of acute joint pain; managing chronic arthropathy; providing psychosocial support; consistency in definitions and assessment; and quantifiable outcome measures. Practice points included increased cross-specialty coordination and including psychologists and rheumatologists as part of comprehensive care teams; close collaboration between pediatric and adult centers to facilitate transition of care; systems such as telehealth that ensure continuity of care for remote populations; using pharmacokinetic data to tailor therapy; rapid and accurate diagnosis of acute joint pain; using data from bleeding registries to assess treatment effects and help with service planning; and ensuring consistency through benchmarking and standardization of HTCs. SUMMARY: Achieving treatment equity, optimal outcomes and cost savings may be possible through investing in national governance structures, expanding the comprehensive model of care and implementing innovative solutions tailored to local needs.