Showing papers by "University of Iceland published in 2021"

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease.

Abstract: Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.

"I have turned into a foreman here at home." Families and work-life balance in times of Covid-19 in a gender equality paradise.

Abstract: This article explores the gendered realities of work-life balance in Iceland during the Covid-19 pandemic, in particular how these societal changes reflect and affect the gendered division of unpaid labor, such as childcare and household chores. The study draws on open ended real-time diary entries, collected for two weeks during the peak of the pandemic in Iceland. The entries represent the voices of 37 mothers in heteronormative relationships. The findings imply that, during the pandemic, the mothers took on greater mental work than before. They also described intense emotional labor, as they tried to keep everyone calm and safe. The division of tasks at home lay on their shoulders, causing them stress and frustration. The findings suggest that, even in a country that has been at the top of the Gender Gap Index for several years, an unprecedented situation like Covid-19 can reveal and exaggerate strong gender norms and expectations towards mothers. This article is protected by copyright. All rights reserved.

Modular, efficient and constant-memory single-cell RNA-seq preprocessing.

Abstract: We describe a workflow for preprocessing of single-cell RNA-sequencing data that balances efficiency and accuracy Our workflow is based on the kallisto and bustools programs, and is near optimal in speed with a constant memory requirement providing scalability for arbitrarily large datasets The workflow is modular, and we demonstrate its flexibility by showing how it can be used for RNA velocity analyses

Psychological distress among health professional students during the COVID-19 outbreak.

Abstract: Background Due to the drastic surge of COVID-19 patients, many countries are considering or already graduating health professional students early to aid professional resources. We aimed to assess outbreak-related psychological distress and symptoms of acute stress reaction (ASR) in health professional students and to characterize individuals with potential need for interventions. Methods We conducted a prospective cohort study of 1442 health professional students at Sichuan University, China. At baseline (October 2019), participants were assessed for childhood adversity, stressful life events, internet addiction, and family functioning. Using multivariable logistic regression, we examined associations of the above exposures with subsequent psychological distress and ASR in response to the outbreak. Results Three hundred and eighty-four (26.63%) participants demonstrated clinically significant psychological distress, while 160 (11.10%) met the criterion for a probable ASR. Individuals who scored high on both childhood adversity and stressful life event experiences during the past year were at increased risks of both distress (ORs 2.00–2.66) and probable ASR (ORs 2.23–3.10), respectively. Moreover, internet addiction was associated with elevated risks of distress (OR 2.05, 95% CI 1.60–2.64) and probable ASR (OR 2.15, 95% CI 1.50–3.10). By contrast, good family functioning was associated with decreased risks of distress (OR 0.43, 95% CI 0.33–0.55) and probable ASR (OR 0.48, 95% CI 0.33–0.69). All associations were independent of baseline psychological distress. Conclusions Our findings suggest that COVID-19 related psychological distress and high symptoms burden of ASR are common among health professional students. Extended family and professional support should be considered for vulnerable individuals during these unprecedented times.

A New Benchmark Based on Recent Advances in Multispectral Pansharpening: Revisiting Pansharpening With Classical and Emerging Pansharpening Methods

Abstract: Pansharpening refers to the fusion of a multispectral (MS) image and panchromatic (PAN) data aimed at generating an outcome with the same spatial resolution of the PAN data and the spectral resolution of the MS image. In the last 30 years, several approaches to deal with this issue have been proposed. However, the reproducibility of these methods is often limited, making the comparison with the state of the art hard to achieve. Thus, to fill this gap, we propose a new benchmark consisting of recent advances in MS pansharpening. In particular, optimized classical approaches [multiresolution analysis (MRA) and component substitution (CS)] are compared with methods belonging to the third generation of pansharpening, represented by variational optimization-based (VO) and machine learning (ML) techniques. The benchmark is tested on different scenarios (from urban to rural areas) acquired by different commercial sensors [i.e., IKONOS (IK), GeoEye-1 (GE-1), and WorldView-3 (WV-3)]. Both quantitative and qualitative assessments and the computational burden are analyzed in this article, and all of the implementations have been collected in a MATLAB toolbox that is made available to the community.

Nordic Health Registry-Based Research: A Review of Health Care Systems and Key Registries

Abstract: The Nordic countries are Denmark, Finland, Iceland, Norway, and Sweden and comprise a total population of approximately 27 million. The countries provide unique opportunities for joint health registry-based research in large populations with long and complete follow-up, facilitated by shared features, such as the tax-funded and public health care systems, the similar population-based registries, and the personal identity number as unique identifier of all citizens. In this review, we provide an introduction to the health care systems, key registries, and how to navigate the practical and ethical aspects of setting up such studies. For each country, we provide an overview of population statistics and health care expenditures, and describe the operational and administrative organization of the health care system. The Nordic registries provide population-based, routine, and prospective data on individuals lives and health with virtually complete follow-up and exact censoring information. We briefly describe the total population registries, birth registries, patient registries, cancer registries, prescription registries, and causes of death registries with a focus on period of coverage, selected key variables, and potential limitations. Lastly, we discuss some practical and legal perspectives. The potential of joint research is not fully exploited, mainly due to legal and practical difficulties in, for example, cross-border sharing of data. Future tasks include clear and transparent legal pathways and a framework by which practical aspects are facilitated.

Genetic insights into biological mechanisms governing human ovarian ageing.

Abstract: Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease. Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Long-read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits.

Abstract: Long-read sequencing (LRS) promises to improve the characterization of structural variants (SVs). We generated LRS data from 3,622 Icelanders and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions). We discovered a set of 133,886 reliably genotyped SV alleles and imputed them into 166,281 individuals to explore their effects on diseases and other traits. We discovered an association of a rare deletion in PCSK9 with lower low-density lipoprotein (LDL) cholesterol levels, compared to the population average. We also discovered an association of a multiallelic SV in ACAN with height; we found 11 alleles that differed in the number of a 57-bp-motif repeat and observed a linear relationship between the number of repeats carried and height. These results show that SVs can be accurately characterized at the population scale using LRS data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes.

Low levels of respiratory syncytial virus activity in Europe during the 2020/21 season: what can we expect in the coming summer and autumn/winter?

Abstract: Since the introduction of non-pharmacological interventions to control COVID-19, respiratory syncytial virus (RSV) activity in Europe has been limited. Surveillance data for 17 countries showed delayed RSV epidemics in France (≥ 12 w) and Iceland (≥ 4 w) during the 2020/21 season. RSV cases (predominantly small children) in France and Iceland were older compared with previous seasons. We hypothesise that future RSV epidemic(s) could start outside the usual autumn/winter season and be larger than expected. Year-round surveillance of RSV is of critical importance.

Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group.

Abstract: This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.

Convolutional Autoencoder for Spectral–Spatial Hyperspectral Unmixing

Abstract: Blind hyperspectral unmixing is the process of expressing the measured spectrum of a pixel as a combination of a set of spectral signatures called endmembers and simultaneously determining their fractional abundances in the pixel. Most unmixing methods are strictly spectral and do not exploit the spatial structure of hyperspectral images (HSIs). In this article, we present a new spectral–spatial linear mixture model and an associated estimation method based on a convolutional neural network autoencoder unmixing (CNNAEU). The CNNAEU technique exploits the spatial and the spectral structure of HSIs both for endmember and abundance map estimation. As it works directly with patches of HSIs and does not use any pooling or upsampling layers, the spatial structure is preserved throughout and abundance maps are obtained as feature maps of a hidden convolutional layer. We compared the CNNAEU method to four conventional and three deep learning state-of-the-art unmixing methods using four real HSIs. Experimental results show that the proposed CNNAEU technique performs particularly well and consistently when it comes to endmembers’ extraction and outperforms all the comparison methods.

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.

The price of curiosity: information recovery in de Sitter space

Abstract: Recent works have revealed that quantum extremal islands can contribute to the fine-grained entropy of black hole radiation reproducing the unitary Page curve. In this paper, we use these results to assess if an observer in de Sitter space can decode information hidden behind their cosmological horizon. By computing the fine-grained entropy of the Gibbons-Hawking radiation in a region where gravity is weak we find that this is possible, but the observer’s curiosity comes at a price. At the same time the island appears, which happens much earlier than the Page time, a singularity forms which the observer will eventually hit. We arrive at this conclusion by studying de Sitter space in Jackiw-Teitelboim gravity. We emphasize the role of the observer collecting radiation, breaking the thermal equilibrium studied so far in the literature. By analytically solving for the backreacted geometry we show how an island appears in this out-of-equilibrium state.

Impact of lockdown and school closure on children's health and well-being during the first wave of COVID-19: A narrative review

Abstract: Background In the context of containment measures against the COVID-19 pandemic, the aims were to examine the impact of lockdown and school closures on childs' and adolescents' health and well-being and social inequalities in health. Methods Literature review by searching five databases until November 2020. We included quantitative peer-reviewed studies reporting health and well-being outcomes in children (0-18 years) related to closure measures' impact due to COVID-19. A pair of authors assessed the risk of bias of included studies. A descriptive and narrative synthesis was carried out. Findings Twenty-two studies, including high-income, middle-income and low-income countries, fulfilled our search criteria and were judged not to have an increased risk of bias. Studies from Australia, Spain and China showed an increase in depressive symptoms and decrease in life satisfaction. A decrease in physical activity and increase in unhealthy food consumption were shown in studies from two countries. There was a decrease in the number of visits to the emergency department in four countries, an increase in child mortality in Cameroon and a decrease by over 50% of immunisations administered in Pakistan. A significant drop of 39% in child protection medical examination referrals during 2020 compared with the previous years was found in the UK, a decrease in allegations of child abuse and neglect by almost one-third due to school closures in Florida, and an increase in the number of children with physical child abuse trauma was found in one centre in the USA. Interpretation From available reports, pandemic school closure and lockdown have adverse effects on child health and well-being in the short and probably long term. We urge governments to take the negative public health consequences into account before adopting restrictive measures in childhood.

Nudged Elastic Band Method for Molecular Reactions Using Energy-Weighted Springs Combined with Eigenvector Following.

Abstract: The climbing image nudged elastic band method (CI-NEB) is used to identify reaction coordinates and to find saddle points representing transition states of reactions. It can make efficient use of parallel computing as the calculations of the discretization points, the so-called images, can be carried out simultaneously. In typical implementations, the images are distributed evenly along the path by connecting adjacent images with equally stiff springs. However, for systems with a high degree of flexibility, this can lead to poor resolution near the saddle point. By making the spring constants increase with energy, the resolution near the saddle point is improved. To assess the performance of this energy-weighted CI-NEB method, calculations are carried out for a benchmark set of 121 molecular reactions. The performance of the method is analyzed with respect to the input parameters. Energy-weighted springs are found to greatly improve performance and result in successful location of the saddle points in less than a thousand energy and force evaluations on average (about a hundred per image) using the same set of parameter values for all of the reactions. Even better performance is obtained by stopping the calculation before full convergence and complete the saddle point search using an eigenvector following method starting from the location of the climbing image. This combination of methods, referred to as NEB-TS, turns out to be robust and highly efficient as it reduces the average number of energy and force evaluations down to a third, to 305. An efficient and flexible implementation of these methods has been made available in the ORCA software.

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Abstract: Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.

Iterative Training Sample Expansion to Increase and Balance the Accuracy of Land Classification From VHR Imagery

Abstract: Imbalanced training sets are known to produce suboptimal maps for supervised classification. Therefore, one challenge in mapping land cover is acquiring training data that will allow classification with high overall accuracy (OA) in which each class is also mapped onto similar user’s accuracy. To solve this problem, we integrated local adaptive region and box-and-whisker plot (BP) techniques into an iterative algorithm to expand the size of the training sample for selected classes in this article. The major steps of the proposed algorithm are as follows. First, a very small initial training sample (ITS) for each class set is labeled manually. Second, potential new training samples are found within an adaptive region by conducting local spectral variation analysis. Lastly, three new training samples are acquired to capture information regarding intraclass variation; these samples lie in the lower, median, and upper quartiles of BP. After adding these new training samples to the ITS, classification is retrained and the process is continued iteratively until termination. The proposed approach was applied to three very high-resolution (VHR) remote-sensing images and compared with a set of cognate methods. The comparison demonstrated that the proposed approach produced the best result in terms of OA and exhibited superiority in balancing user’s accuracy. For example, the proposed approach was typically 2%-10% more accurate than the compared methods in terms of OA and it generally yielded the most balanced classification.

Subduction-Driven Volatile Recycling: A Global Mass Balance

Abstract: Volatile elements (water, carbon, nitrogen, sulfur, halogens, and noble gases) played an essential role in the secular evolution of the solid Earth and emergence of life. Here we provide an overvie...

Sustainable energy development: History of the concept and emerging themes

Abstract: This research was financially supported by Rannis – The Icelandic Centre for Research [grant number: 163464–051], the National Power Company of Iceland, the Icelandic Road and Coastal Administration, the Eimskip University Fund, and the Icelandic national federation of Graduate Women International.

Differences between germline genomes of monozygotic twins

Abstract: Despite the important role that monozygotic twins have played in genetics research, little is known about their genomic differences. Here we show that monozygotic twins differ on average by 5.2 early developmental mutations and that approximately 15% of monozygotic twins have a substantial number of these early developmental mutations specific to one of them. Using the parents and offspring of twins, we identified pre-twinning mutations. We observed instances where a twin was formed from a single cell lineage in the pre-twinning cell mass and instances where a twin was formed from several cell lineages. CpG>TpG mutations increased in frequency with embryonic development, coinciding with an increase in DNA methylation. Our results indicate that allocations of cells during development shapes genomic differences between monozygotic twins.

Developing a Sustainable and Circular Bio-Based Economy in EU: By Partnering Across Sectors, Upscaling and Using New Knowledge Faster, and For the Benefit of Climate, Environment & Biodiversity, and People & Business.

Abstract: This paper gives an overview of development of the EU-bioeconomy, 2014-2020. The Vision of the new Circular Bio-based Economy, CBE is presented: Unlocking the full potential of all types of sustainably sourced biomass, crop residues, industrial side-streams, and wastes by transforming it into value-added products. The resulting product portfolio consists of a wide spectrum of value-added products, addressing societal and consumer needs. Food and feed, bio-based chemicals, materials, health-promoting products; and bio-based fuels. The pillars of CBE are described, including biotechnology, microbial production, enzyme technology, green chemistry, integrated physical/chemical processing, policies, conducive framework conditions and public private partnerships. Drivers of CBE are analyzed: Biomass supply, biorefineries, value chain clusters, rural development, farmers, foresters and mariners; urgent need for climate change mitigation and adaptation, and stopping biodiversity loss. Improved framework conditions can be drivers but also obstacles if not updated to the era of circularity. Key figures, across the entire BBI-JU project portfolio (2014-2020) are provided, including expansion into biomass feedstocks, terrestrial and aquatic, and an impressive broadening of bio-based product portfolio, including higher-value, health-promoting products for man, animal, plants and soil. Parallel to this, diversification of industrial segments and types of funding instruments developed, reflecting industrial needs and academic research involvement. Impact assessment is highlighted. A number of specific recommendations are given; e.g., including international win/win CBE-collaborations, as e.g., expanding African EU collaboration into CBE. In contrast to fossil resources biological resources are found worldwide. In its outset, circular bio-based economy, can be implemented all over, in a just manner, not the least stimulating rural development.

STOPPFall(Screening Tool of Older Persons Prescriptions in older adults with high fall risk): a Delphi study by the EuGMS Task and Finish Group on Fall-Risk-Increasing Drugs

Abstract: BACKGROUND: Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. METHODS: STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. RESULTS: The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. CONCLUSION: STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies.

Change Detection From Very-High-Spatial-Resolution Optical Remote Sensing Images: Methods, applications, and future directions

Abstract: Change detection is a vibrant area of research in remote sensing. Thanks to increases in the spatial resolution of remote sensing images, subtle changes at a finer geometrical scale can now be effectively detected. However, change detection from very-high-spatial-resolution (VHR) (≤5 m) remote sensing images is challenging due to limited spectral information, spectral variability, geometric distortion, and information loss. To address these challenges, many change detection algorithms have been developed. However, a comprehensive review of change detection in VHR images is lacking in the existing literature. This review aims to fill the gap and mainly includes three aspects: methods, applications, and future directions.

Governing AI safety through independent audits

Abstract: Highly automated systems are becoming omnipresent. They range in function from self-driving vehicles to advanced medical diagnostics and afford many benefits. However, there are assurance challenges that have become increasingly visible in high-profile crashes and incidents. Governance of such systems is critical to garner widespread public trust. Governance principles have been previously proposed offering aspirational guidance to automated system developers; however, their implementation is often impractical given the excessive costs and processes required to enact and then enforce the principles. This Perspective, authored by an international and multidisciplinary team across government organizations, industry and academia, proposes a mechanism to drive widespread assurance of highly automated systems: independent audit. As proposed, independent audit of AI systems would embody three ‘AAA’ governance principles of prospective risk Assessments, operation Audit trails and system Adherence to jurisdictional requirements. Independent audit of AI systems serves as a pragmatic approach to an otherwise burdensome and unenforceable assurance challenge. As highly automated systems become pervasive in society, enforceable governance principles are needed to ensure safe deployment. This Perspective proposes a pragmatic approach where independent audit of AI systems is central. The framework would embody three AAA governance principles: prospective risk Assessments, operation Audit trails and system Adherence to jurisdictional requirements.