University of Otago

Summary The use of both linear and generalized linear mixed‐effects models ( LMM s and GLMM s) has become popular not only in social and medical sciences, but also in biological sciences, especially in the field of ecology and evolution. Information criteria, such as Akaike Information Criterion ( AIC ), are usually presented as model comparison tools for mixed‐effects models. The presentation of ‘variance explained’ ( R 2 ) as a relevant summarizing statistic of mixed‐effects models, however, is rare, even though R 2 is routinely reported for linear models ( LM s) and also generalized linear models ( GLM s). R 2 has the extremely useful property of providing an absolute value for the goodness‐of‐fit of a model, which cannot be given by the information criteria. As a summary statistic that describes the amount of variance explained, R 2 can also be a quantity of biological interest. One reason for the under‐appreciation of R 2 for mixed‐effects models lies in the fact that R 2 can be defined in a number of ways. Furthermore, most definitions of R 2 for mixed‐effects have theoretical problems (e.g. decreased or negative R 2 values in larger models) and/or their use is hindered by practical difficulties (e.g. implementation). Here, we make a case for the importance of reporting R 2 for mixed‐effects models. We first provide the common definitions of R 2 for LM s and GLM s and discuss the key problems associated with calculating R 2 for mixed‐effects models. We then recommend a general and simple method for calculating two types of R 2 (marginal and conditional R 2 ) for both LMM s and GLMM s, which are less susceptible to common problems. This method is illustrated by examples and can be widely employed by researchers in any fields of research, regardless of software packages used for fitting mixed‐effects models. The proposed method has the potential to facilitate the presentation of R 2 for a wide range of circumstances.

Summary Haplotype networks are an intuitive method for visualising relationships between individual genotypes at the population level. Here, we present popart , an integrated software package that provides a comprehensive implementation of haplotype network methods, phylogeographic visualisation tools and standard statistical tests, together with publication‐ready figure production. popart also provides a platform for the implementation and distribution of new network‐based methods – we describe one such new method, integer neighbour‐joining . The software is open source and freely available for all major operating systems.

With advances in the effectiveness of treatment and disease management, the contribution of chronic comorbid diseases (comorbidities) found within the Charlson comorbidity index to mortality is likely to have changed since development of the index in 1984. The authors reevaluated the Charlson index and reassigned weights to each condition by identifying and following patients to observe mortality within 1 year after hospital discharge. They applied the updated index and weights to hospital discharge data from 6 countries and tested for their ability to predict in-hospital mortality. Compared with the original Charlson weights, weights generated from the Calgary, Alberta, Canada, data (2004) were 0 for 5 comorbidities, decreased for 3 comorbidities, increased for 4 comorbidities, and did not change for 5 comorbidities. The C statistics for discriminating in-hospital mortality between the new score generated from the 12 comorbidities and the Charlson score were 0.825 (new) and 0.808 (old), respectively, in Australian data (2008), 0.828 and 0.825 in Canadian data (2008), 0.878 and 0.882 in French data (2004), 0.727 and 0.723 in Japanese data (2008), 0.831 and 0.836 in New Zealand data (2008), and 0.869 and 0.876 in Swiss data (2008). The updated index of 12 comorbidities showed good-to-excellent discrimination in predicting in-hospital mortality in data from 6 countries and may be more appropriate for use with more recent administrative data.

PsychoPy is an application for the creation of experiments in behavioral science (psychology, neuroscience, linguistics, etc.) with precise spatial control and timing of stimuli. It now provides a choice of interface; users can write scripts in Python if they choose, while those who prefer to construct experiments graphically can use the new Builder interface. Here we describe the features that have been added over the last 10 years of its development. The most notable addition has been that Builder interface, allowing users to create studies with minimal or no programming, while also allowing the insertion of Python code for maximal flexibility. We also present some of the other new features, including further stimulus options, asynchronous time-stamped hardware polling, and better support for open science and reproducibility. Tens of thousands of users now launch PsychoPy every month, and more than 90 people have contributed to the code. We discuss the current state of the project, as well as plans for the future.

We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA) was found to moderate the effect of maltreatment. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems. These findings may partly explain why not all victims of maltreatment grow up to victimize others, and they provide epidemiological evidence that genotypes can moderate children's sensitivity to environmental insults.

Policy-makers are considering large-scale programs aimed at self-control to improve citizens' health and wealth and reduce crime. Experimental and economic studies suggest such programs could reap benefits. Yet, is self-control important for the health, wealth, and public safety of the population? Following a cohort of 1,000 children from birth to the age of 32 y, we show that childhood self-control predicts physical health, substance dependence, personal finances, and criminal offending outcomes, following a gradient of self-control. Effects of children's self-control could be disentangled from their intelligence and social class as well as from mistakes they made as adolescents. In another cohort of 500 sibling-pairs, the sibling with lower self-control had poorer outcomes, despite shared family background. Interventions addressing self-control might reduce a panoply of societal costs, save taxpayers money, and promote prosperity.

Elaboration of Bayesian phylogenetic inference methods has continued at pace in recent years with major new advances in nearly all aspects of the joint modelling of evolutionary data. It is increasingly appreciated that some evolutionary questions can only be adequately answered by combining evidence from multiple independent sources of data, including genome sequences, sampling dates, phenotypic data, radiocarbon dates, fossil occurrences, and biogeographic range information among others. Including all relevant data into a single joint model is very challenging both conceptually and computationally. Advanced computational software packages that allow robust development of compatible (sub-)models which can be composed into a full model hierarchy have played a key role in these developments. Developing such software frameworks is increasingly a major scientific activity in its own right, and comes with specific challenges, from practical software design, development and engineering challenges to statistical and conceptual modelling challenges. BEAST 2 is one such computational software platform, and was first announced over 4 years ago. Here we describe a series of major new developments in the BEAST 2 core platform and model hierarchy that have occurred since the first release of the software, culminating in the recent 2.5 release.

BACKGROUND: Recent studies have provided a detailed census of genes that are mutated in acute myeloid leukemia (AML). Our next challenge is to understand how this genetic diversity defines the pathophysiology of AML and informs clinical practice. METHODS: We enrolled a total of 1540 patients in three prospective trials of intensive therapy. Combining driver mutations in 111 cancer genes with cytogenetic and clinical data, we defined AML genomic subgroups and their relevance to clinical outcomes. RESULTS: We identified 5234 driver mutations across 76 genes or genomic regions, with 2 or more drivers identified in 86% of the patients. Patterns of co-mutation compartmentalized the cohort into 11 classes, each with distinct diagnostic features and clinical outcomes. In addition to currently defined AML subgroups, three heterogeneous genomic categories emerged: AML with mutations in genes encoding chromatin, RNA-splicing regulators, or both (in 18% of patients); AML with TP53 mutations, chromosomal aneuploidies, or both (in 13%); and, provisionally, AML with IDH2(R172) mutations (in 1%). Patients with chromatin-spliceosome and TP53-aneuploidy AML had poor outcomes, with the various class-defining mutations contributing independently and additively to the outcome. In addition to class-defining lesions, other co-occurring driver mutations also had a substantial effect on overall survival. The prognostic effects of individual mutations were often significantly altered by the presence or absence of other driver mutations. Such gene-gene interactions were especially pronounced for NPM1-mutated AML, in which patterns of co-mutation identified groups with a favorable or adverse prognosis. These predictions require validation in prospective clinical trials. CONCLUSIONS: The driver landscape in AML reveals distinct molecular subgroups that reflect discrete paths in the evolution of AML, informing disease classification and prognostic stratification. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT00146120.).

BACKGROUND: In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs. PURPOSE: The objective of this statement is to update the 2002 ATS/ERS classification of IIPs. METHODS: An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011. RESULTS: Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment. CONCLUSIONS: This update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.

BACKGROUND: Approximately 30% of people over 65 years of age living in the community fall each year. This is an update of a Cochrane review first published in 2009. OBJECTIVES: To assess the effects of interventions designed to reduce the incidence of falls in older people living in the community. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (February 2012), CENTRAL (The Cochrane Library 2012, Issue 3), MEDLINE (1946 to March 2012), EMBASE (1947 to March 2012), CINAHL (1982 to February 2012), and online trial registers. SELECTION CRITERIA: Randomised trials of interventions to reduce falls in community-dwelling older people. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias and extracted data. We used a rate ratio (RaR) and 95% confidence interval (CI) to compare the rate of falls (e.g. falls per person year) between intervention and control groups. For risk of falling, we used a risk ratio (RR) and 95% CI based on the number of people falling (fallers) in each group. We pooled data where appropriate. MAIN RESULTS: We included 159 trials with 79,193 participants. Most trials compared a fall prevention intervention with no intervention or an intervention not expected to reduce falls. The most common interventions tested were exercise as a single intervention (59 trials) and multifactorial programmes (40 trials). Sixty-two per cent (99/159) of trials were at low risk of bias for sequence generation, 60% for attrition bias for falls (66/110), 73% for attrition bias for fallers (96/131), and only 38% (60/159) for allocation concealment.Multiple-component group exercise significantly reduced rate of falls (RaR 0.71, 95% CI 0.63 to 0.82; 16 trials; 3622 participants) and risk of falling (RR 0.85, 95% CI 0.76 to 0.96; 22 trials; 5333 participants), as did multiple-component home-based exercise (RaR 0.68, 95% CI 0.58 to 0.80; seven trials; 951 participants and RR 0.78, 95% CI 0.64 to 0.94; six trials; 714 participants). For Tai Chi, the reduction in rate of falls bordered on statistical significance (RaR 0.72, 95% CI 0.52 to 1.00; five trials; 1563 participants) but Tai Chi did significantly reduce risk of falling (RR 0.71, 95% CI 0.57 to 0.87; six trials; 1625 participants).Multifactorial interventions, which include individual risk assessment, reduced rate of falls (RaR 0.76, 95% CI 0.67 to 0.86; 19 trials; 9503 participants), but not risk of falling (RR 0.93, 95% CI 0.86 to 1.02; 34 trials; 13,617 participants).Overall, vitamin D did not reduce rate of falls (RaR 1.00, 95% CI 0.90 to 1.11; seven trials; 9324 participants) or risk of falling (RR 0.96, 95% CI 0.89 to 1.03; 13 trials; 26,747 participants), but may do so in people with lower vitamin D levels before treatment.Home safety assessment and modification interventions were effective in reducing rate of falls (RR 0.81, 95% CI 0.68 to 0.97; six trials; 4208 participants) and risk of falling (RR 0.88, 95% CI 0.80 to 0.96; seven trials; 4051 participants). These interventions were more effective in people at higher risk of falling, including those with severe visual impairment. Home safety interventions appear to be more effective when delivered by an occupational therapist.An intervention to treat vision problems (616 participants) resulted in a significant increase in the rate of falls (RaR 1.57, 95% CI 1.19 to 2.06) and risk of falling (RR 1.54, 95% CI 1.24 to 1.91). When regular wearers of multifocal glasses (597 participants) were given single lens glasses, all falls and outside falls were significantly reduced in the subgroup that regularly took part in outside activities. Conversely, there was a significant increase in outside falls in intervention group participants who took part in little outside activity.Pacemakers reduced rate of falls in people with carotid sinus hypersensitivity (RaR 0.73, 95% CI 0.57 to 0.93; three trials; 349 participants) but not risk of falling. First eye cataract surgery in women reduced rate of falls (RaR 0.66, 95% CI 0.45 to 0.95; one trial; 306 participants), but second eye cataract surgery did not.Gradual withdrawal of psychotropic medication reduced rate of falls (RaR 0.34, 95% CI 0.16 to 0.73; one trial; 93 participants), but not risk of falling. A prescribing modification programme for primary care physicians significantly reduced risk of falling (RR 0.61, 95% CI 0.41 to 0.91; one trial; 659 participants).An anti-slip shoe device reduced rate of falls in icy conditions (RaR 0.42, 95% CI 0.22 to 0.78; one trial; 109 participants). One trial (305 participants) comparing multifaceted podiatry including foot and ankle exercises with standard podiatry in people with disabling foot pain significantly reduced the rate of falls (RaR 0.64, 95% CI 0.45 to 0.91) but not the risk of falling.There is no evidence of effect for cognitive behavioural interventions on rate of falls (RaR 1.00, 95% CI 0.37 to 2.72; one trial; 120 participants) or risk of falling (RR 1.11, 95% CI 0.80 to 1.54; two trials; 350 participants).Trials testing interventions to increase knowledge/educate about fall prevention alone did not significantly reduce the rate of falls (RaR 0.33, 95% CI 0.09 to 1.20; one trial; 45 participants) or risk of falling (RR 0.88, 95% CI 0.75 to 1.03; four trials; 2555 participants).No conclusions can be drawn from the 47 trials reporting fall-related fractures.Thirteen trials provided a comprehensive economic evaluation. Three of these indicated cost savings for their interventions during the trial period: home-based exercise in over 80-year-olds, home safety assessment and modification in those with a previous fall, and one multifactorial programme targeting eight specific risk factors. AUTHORS' CONCLUSIONS: Group and home-based exercise programmes, and home safety interventions reduce rate of falls and risk of falling.Multifactorial assessment and intervention programmes reduce rate of falls but not risk of falling; Tai Chi reduces risk of falling.Overall, vitamin D supplementation does not appear to reduce falls but may be effective in people who have lower vitamin D levels before treatment.

OBJECTIVE: To compare the accuracy of existing classification criteria for the diagnosis of psoriatic arthritis (PsA) and to construct new criteria from observed data. METHODS: Data were collected prospectively from consecutive clinic attendees with PsA and other inflammatory arthropathies. Subjects were classified by each of 7 criteria. Sensitivity and specificity were compared using conditional logistic regression analysis. Latent class analysis was used to calculate criteria accuracy in order to confirm the validity of clinical diagnosis as the gold standard definition of "case"-ness. Classification and Regression Trees methodology and logistic regression were used to identify items for new criteria, which were then constructed using a receiver operating characteristic curve. RESULTS: Data were collected on 588 cases and 536 controls with rheumatoid arthritis (n = 384), ankylosing spondylitis (n = 72), undifferentiated arthritis (n = 38), connective tissue disorders (n = 14), and other diseases (n = 28). The specificity of each set of criteria was high. The sensitivity of the Vasey and Espinoza method (0.97) was similar to that of the method of McGonagle et al (0.98) and greater than that of the methods of Bennett (0.44), Moll and Wright (0.91), the European Spondylarthropathy Study Group (0.74), and Gladman et al (0.91). The CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria consisted of established inflammatory articular disease with at least 3 points from the following features: current psoriasis (assigned a score of 2; all other features were assigned a score of 1), a history of psoriasis (unless current psoriasis was present), a family history of psoriasis (unless current psoriasis was present or there was a history of psoriasis), dactylitis, juxtaarticular new bone formation, rheumatoid factor negativity, and nail dystrophy. These criteria were more specific (0.987 versus 0.960) but less sensitive (0.914 versus 0.972) than those of Vasey and Espinoza. CONCLUSION: The CASPAR criteria are simple and highly specific but less sensitive than the Vasey and Espinoza criteria.

While exploration and exploitation represent two fundamentally different approaches to organizational learning, recent literature has increasingly indicated the need for firms to achieve a balance between the two. This balanced view is embedded in the concept of ambidextrous organizations. However, there is little direct evidence of the positive effect of ambidexterity on firm performance. This paper seeks to test the ambidexterity hypothesis by examining how exploration and exploitation can jointly influence firm performance in the context of firms' approach to technological innovation. Based on a sample of 206 manufacturing firms, we find evidence consistent with the ambidexterity hypothesis by showing that (1) the interaction between explorative and exploitative innovation strategies is positively related to sales growth rate, and (2) the relative imbalance between explorative and exploitative innovation strategies is negatively related to sales growth rate.

Transformative artificially intelligent tools, such as ChatGPT, designed to generate sophisticated text indistinguishable from that produced by a human, are applicable across a wide range of contexts. The technology presents opportunities as well as, often ethical and legal, challenges, and has the potential for both positive and negative impacts for organisations, society, and individuals. Offering multi-disciplinary insight into some of these, this article brings together 43 contributions from experts in fields such as computer science, marketing, information systems, education, policy, hospitality and tourism, management, publishing, and nursing. The contributors acknowledge ChatGPT’s capabilities to enhance productivity and suggest that it is likely to offer significant gains in the banking, hospitality and tourism, and information technology industries, and enhance business activities, such as management and marketing. Nevertheless, they also consider its limitations, disruptions to practices, threats to privacy and security, and consequences of biases, misuse, and misinformation. However, opinion is split on whether ChatGPT’s use should be restricted or legislated. Drawing on these contributions, the article identifies questions requiring further research across three thematic areas: knowledge, transparency, and ethics; digital transformation of organisations and societies; and teaching, learning, and scholarly research. The avenues for further research include: identifying skills, resources, and capabilities needed to handle generative AI; examining biases of generative AI attributable to training datasets and processes; exploring business and societal contexts best suited for generative AI implementation; determining optimal combinations of human and generative AI for various tasks; identifying ways to assess accuracy of text produced by generative AI; and uncovering the ethical and legal issues in using generative AI across different contexts.

Parasite communities are arranged into hierarchical levels of organization, covering various spatial and temporal scales. These range from all parasites within an individual host to all parasites exploiting a host species across its geographic range. This arrangement provides an opportunity for the study of patterns and structuring processes operating at different scales. Across the parasite faunas of various host species, several species-area relationships have been published, emphasizing the key role of factors such as host size or host geographical range in determining parasite species richness. When corrections are made for unequal sampling effort or phylogenetic influences, however, the strength of these relationships is greatly reduced, casting a doubt over their validity. Component parasite communities, or the parasites found in a host population, are subsets of the parasite fauna of the host species. They often form saturated communities, such that their richness is not always a reflection of that of the entire parasite fauna. The species richness of component communities is instead influenced by the local availability of parasite species and their probability of colonization. At the lowest level, infracommunities in individual hosts are subsets of the species occurring in the component community. Generally, their structure does not differ from that expected from a random assembly of available species, although comparisons with precise null models are still few. Overall studies of parasite communities suggest that the action of processes determining species richness of parasite assemblages becomes less detectable as focus shifts from parasite faunas to infracommunities.

In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.

The reliability and validity of traditional taxonomies are limited by arbitrary boundaries between psychopathology and normality, often unclear boundaries between disorders, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. These taxonomies went beyond evidence available on the structure of psychopathology and were shaped by a variety of other considerations, which may explain the aforementioned shortcomings. The Hierarchical Taxonomy Of Psychopathology (HiTOP) model has emerged as a research effort to address these problems. It constructs psychopathological syndromes and their components/subtypes based on the observed covariation of symptoms, grouping related symptoms together and thus reducing heterogeneity. It also combines co-occurring syndromes into spectra, thereby mapping out comorbidity. Moreover, it characterizes these phenomena dimensionally, which addresses boundary problems and diagnostic instability. Here, we review the development of the HiTOP and the relevant evidence. The new classification already covers most forms of psychopathology. Dimensional measures have been developed to assess many of the identified components, syndromes, and spectra. Several domains of this model are ready for clinical and research applications. The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies. It also provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response. This can greatly improve the utility of the diagnosis of mental disorders. The new classification remains a work in progress. However, it is developing rapidly and is poised to advance mental health research and care significantly as the relevant science matures. (PsycINFO Database Record

The environmental conditions of Earth, including the climate, are determined by physical, chemical, biological, and human interactions that transform and transport materials and energy. This is the "Earth system": a highly complex entity characterized by multiple nonlinear responses and thresholds, with linkages between disparate components. One important part of this system is the iron cycle, in which iron-containing soil dust is transported from land through the atmosphere to the oceans, affecting ocean biogeochemistry and hence having feedback effects on climate and dust production. Here we review the key components of this cycle, identifying critical uncertainties and priorities for future research.

Abstract High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species 1–4 . To address this issue, the international Genome 10K (G10K) consortium 5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.

The emergence of artificial intelligence (AI) and its progressively wider impact on many sectors requires an assessment of its effect on the achievement of the Sustainable Development Goals. Using a consensus-based expert elicitation process, we find that AI can enable the accomplishment of 134 targets across all the goals, but it may also inhibit 59 targets. However, current research foci overlook important aspects. The fast development of AI needs to be supported by the necessary regulatory insight and oversight for AI-based technologies to enable sustainable development. Failure to do so could result in gaps in transparency, safety, and ethical standards.

CONTEXT: In 2002, an estimated 877,000 lives were lost worldwide through suicide. Some developed nations have implemented national suicide prevention plans. Although these plans generally propose multiple interventions, their effectiveness is rarely evaluated. OBJECTIVES: To examine evidence for the effectiveness of specific suicide-preventive interventions and to make recommendations for future prevention programs and research. DATA SOURCES AND STUDY SELECTION: Relevant publications were identified via electronic searches of MEDLINE, the Cochrane Library, and PsychINFO databases using multiple search terms related to suicide prevention. Studies, published between 1966 and June 2005, included those that evaluated preventative interventions in major domains; education and awareness for the general public and for professionals; screening tools for at-risk individuals; treatment of psychiatric disorders; restricting access to lethal means; and responsible media reporting of suicide. DATA EXTRACTION: Data were extracted on primary outcomes of interest: suicidal behavior (completion, attempt, ideation), intermediary or secondary outcomes (treatment seeking, identification of at-risk individuals, antidepressant prescription/use rates, referrals), or both. Experts from 15 countries reviewed all studies. Included articles were those that reported on completed and attempted suicide and suicidal ideation; or, where applicable, intermediate outcomes, including help-seeking behavior, identification of at-risk individuals, entry into treatment, and antidepressant prescription rates. We included 3 major types of studies for which the research question was clearly defined: systematic reviews and meta-analyses (n = 10); quantitative studies, either randomized controlled trials (n = 18) or cohort studies (n = 24); and ecological, or population- based studies (n = 41). Heterogeneity of study populations and methodology did not permit formal meta-analysis; thus, a narrative synthesis is presented. DATA SYNTHESIS: Education of physicians and restricting access to lethal means were found to prevent suicide. Other methods including public education, screening programs, and media education need more testing. CONCLUSIONS: Physician education in depression recognition and treatment and restricting access to lethal methods reduce suicide rates. Other interventions need more evidence of efficacy. Ascertaining which components of suicide prevention programs are effective in reducing rates of suicide and suicide attempt is essential in order to optimize use of limited resources.