Optimising the manufacturing of a ß-Ti alloy produced via direct energy deposition using small dataset machine learning.

Successful additive manufacturing involves the optimisation of numerous process parameters that significantly influence product quality and manufacturing success. One commonly used criteria based on a collection of parameters is the global energy distribution (GED). This parameter encapsulates the energy input onto the surface of a build, and is a function of the laser power, laser scanning speed and laser spot size. This study uses machine learning to develop a model for predicting manufacturing layer height and grain size based on GED constituent process parameters. For both layer height and grain size, an artificial neural network (ANN) reduced error over the data set compared with multi linear regression. Layer height predictions using ANN achieved an R2 of 0.97 and a root mean square error (RMSE) of 0.03 mm, while grain size predictions resulted in an R2 of 0.85 and an RMSE of 9.68 µm. Grain refinement was observed when reducing laser power and increasing laser scanning speed. This observation was successfully replicated in another α + ß Ti alloy. The findings and developed models show why reproducibility is difficult when solely considering GED, as each of the constituent parameters influence these individual responses to varying magnitudes.

Detection of chromosomal aneuploidy in ancient genomes.

Ancient DNA is a valuable tool for investigating genetic and evolutionary history that can also provide detailed profiles of the lives of ancient individuals. In this study, we develop a generalised computational approach to detect aneuploidies (atypical autosomal and sex chromosome karyotypes) in the ancient genetic record and distinguish such karyotypes from contamination. We confirm that aneuploidies can be detected even in low-coverage genomes ( ~ 0.0001-fold), common in ancient DNA. We apply this method to ancient skeletal remains from Britain to document the first instance of mosaic Turner syndrome (45,X0/46,XX) in the ancient genetic record in an Iron Age individual sequenced to average 9-fold coverage, the earliest known incidence of an individual with a 47,XYY karyotype from the Early Medieval period, as well as individuals with Klinefelter (47,XXY) and Down syndrome (47,XY, + 21). Overall, our approach provides an accessible and automated framework allowing for the detection of individuals with aneuploidies, which extends previous binary approaches. This tool can facilitate the interpretation of burial context and living conditions, as well as elucidate past perceptions of biological sex and people with diverse biological traits.

Wellbeing After Finalization of a Workers' Compensation Claim: A Systematic Scoping Review.

OBJECTIVE: A workers' compensation claim may have significant negative impacts on an injured worker's wellbeing. Wellbeing provides a good global measure of potential effects of a claim on an individual, and is important for contemporary economic modelling. The purpose of this study was to synthesize knowledge about the wellbeing of injured workers after the finalization of a workers' compensation claim and identify gaps in the current literature. METHODS: A systematic scoping review was conducted. RESULTS: 71 full-text articles were screened for inclusion, with 32 articles eligible for this review. None of the included articles evaluated overall wellbeing. Included articles did evaluate a variety of constructs inherent in wellbeing. Injured workers were generally disadvantaged in some manner following claim finalization. The literature recommends a focus on reducing negative impacts on injured workers after finalization of a compensation claim, with a need for regulatory bodies to review policy in this area. CONCLUSION: There appears to be potential for ongoing burden for individuals, employers, and society after finalization of a workers' compensation claim. A gap in knowledge exists regarding the specific evaluation of wellbeing of injured workers following finalization of a workers' compensation claim.

Multi-organ phenotypes in mice lacking latent TGFß binding protein 2 (LTBP2).

BACKGROUND: Latent TGFß binding protein-2 (LTBP2) is a fibrillin 1 binding component of the microfibril. LTBP2 is the only LTBP protein that does not bind any isoforms of TGFß, although it may interfere with the function of other LTBPs or interact with other signaling pathways. RESULTS: Here, we investigate mice lacking Ltbp2 (Ltbp2-/- ) and identify multiple phenotypes that impact bodyweight and fat mass, and affect bone and skin development. The alterations in skin and bone development are particularly noteworthy since the strength of these tissues is differentially affected by loss of Ltbp2. Interestingly, some tissues that express high levels of Ltbp2, such as the aorta and lung, do not have a developmental or homeostatic phenotype. CONCLUSIONS: Analysis of these mice show that LTBP2 has complex effects on development through direct effects on the extracellular matrix (ECM) or on signaling pathways that are known to regulate the ECM.

The Clinical Impact of Electronic Patient-Reported Outcome Measures in the Remote Monitoring of Inflammatory Arthritis: A Systematic Review and Meta-analysis.

OBJECTIVE: The inflammatory arthritides (IAs) make up a significant proportion of conditions followed up in rheumatology clinics. These patients require regular monitoring, but this is increasingly difficult with rising patient numbers and demand on clinics. Our objective is to evaluate the clinical impact of electronic patient-reported outcome measures (ePROMs) as a digital remote-monitoring intervention on disease activity, treatment decisions, and health care resource use in patients with IA. METHODS: Five databases (MEDLINE, Embase, PubMed, Cochrane Library, and Web of Science) were searched, with randomized controlled trials and (nonrandomized) controlled clinical trials included, and meta-analysis and forest plots conducted for each outcome. Risk of bias was assessed using the Risk of Bias-2 tool and Risk of Bias in Nonrandomized Studies of Interventions. RESULTS: Eight studies were included with a total of 4,473 patients, with seven studies assessing patients with rheumatoid arthritis. Compared with control, the disease activity in the ePROM group was lower (standardized mean difference [SMD] -0.15; 95% confidence interval [CI] -0.27 to -0.03) and rates of remission/low disease activity were higher (odds ratio1.65; 95% CI 1.02-2.68), but five of eight studies provided additional combined interventions (e.g., disease education). Fewer face to face visits were needed in the remote ePROM group (SMD -0.93; 95% CI -2.14-0.28). CONCLUSION: Most studies were at high risk of bias with significant heterogeneity in design, but our results suggest there is an advantage in using ePROM monitoring in patients with IAs, with the potential for reduction in health care resource use without detrimental impact in disease outcomes.

Identifying the potential causal role of insomnia symptoms on 11,409 health-related outcomes: a phenome-wide Mendelian randomisation analysis in UK Biobank.

BACKGROUND: Insomnia symptoms are widespread in the population and might have effects on many chronic conditions and their risk factors but previous research has focused on select hypothesised associations/effects rather than taking a systematic hypothesis-free approach across many health outcomes. METHODS: We performed a Mendelian randomisation (MR) phenome-wide association study (PheWAS) in 336,975 unrelated white-British UK Biobank participants. Self-reported insomnia symptoms were instrumented by a genetic risk score (GRS) created from 129 single-nucleotide polymorphisms (SNPs). A total of 11,409 outcomes from UK Biobank were extracted and processed by an automated pipeline (PHESANT) for the MR-PheWAS. Potential causal effects (those passing a Bonferroni-corrected significance threshold) were followed up with two-sample MR in MR-Base, where possible. RESULTS: Four hundred thirty-seven potential causal effects of insomnia symptoms were observed for a diverse range of outcomes, including anxiety, depression, pain, body composition, respiratory, musculoskeletal and cardiovascular traits. We were able to undertake two-sample MR for 71 of these 437 and found evidence of causal effects (with directionally concordant effect estimates across main and sensitivity analyses) for 30 of these. These included novel findings (by which we mean not extensively explored in conventional observational studies and not previously explored using MR based on a systematic search) of an adverse effect on risk of spondylosis (OR [95%CI] = 1.55 [1.33, 1.81]) and bronchitis (OR [95%CI] = 1.12 [1.03, 1.22]), among others. CONCLUSIONS: Insomnia symptoms potentially cause a wide range of adverse health-related outcomes and behaviours. This has implications for developing interventions to prevent and treat a number of diseases in order to reduce multimorbidity and associated polypharmacy.

Reporting and methodological quality of studies that use Mendelian randomisation in UK Biobank: a meta-epidemiological study.

OBJECTIVES: To identify whether Mendelian randomisation (MR) studies are appropriately conducted and reported in enough detail for other researchers to accurately replicate and interpret them. DESIGN: Cross-sectional meta-epidemiological study. DATA SOURCES: Web of Science, EMBASE, PubMed and PsycINFO were searched on 15 July 2022 for literature. ELIGIBILITY CRITERIA: Full research articles that conducted an MR analysis exclusively using individual-level UK Biobank data to obtain a causal estimate of the exposure-outcome relationship (for no more than ten exposures or outcomes). METHODS AND ANALYSIS: Data were extracted using a 25-item checklist relating to reporting and methodological quality (based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines and the guidelines for performing MR investigations). Article characteristics, such as 2021 Journal Impact Factor, publication year, journal word limit/recommendation, whether the MR analysis was the primary analysis, open access status and whether reporting guidelines were followed, were also extracted. Descriptive statistics were calculated for each item, and whether article characteristics predicted overall article completeness was investigated with linear regression. RESULTS: 116 articles were included in this review. The proportion of articles which reported complete information/adequate methodology ranged from 3% to 100% across the different items. Palindromic variants, variant replication, missing data, associations of the instrumental variable with the exposure or outcome and bias introduced by two-sample methods used on a single sample were often not completely addressed (<11%). There was no clear evidence that article characteristics predicted overall completeness except for primary analysis status. CONCLUSIONS: The results identify areas in which the reporting and conducting of MR studies needs to be improved and also suggest researchers do not make use of supplementary materials to sufficiently report secondary analyses. Future research should focus on the quality of code and analyses, attempt direct replications and investigate the impact of the STROBE-MR specifically. STUDY REGISTRATION: https://osf.io/nwrdj.

Tools for assessing quality and risk of bias in Mendelian randomization studies: a systematic review.

BACKGROUND: The use of Mendelian randomization (MR) in epidemiology has increased considerably in recent years, with a subsequent increase in systematic reviews of MR studies. We conducted a systematic review of tools designed for assessing risk of bias and/or quality of evidence in MR studies and a review of systematic reviews of MR studies. METHODS: We systematically searched MEDLINE, Embase, the Web of Science, preprints servers and Google Scholar for articles containing tools for assessing, conducting and/or reporting MR studies. We also searched for systematic reviews and protocols of systematic reviews of MR studies. From eligible articles we collected data on tool characteristics and content, as well as details of narrative description of bias assessment. RESULTS: Our searches retrieved 2464 records to screen, from which 14 tools, 35 systematic reviews and 38 protocols were included in our review. Seven tools were designed for assessing risk of bias/quality of evidence in MR studies and evaluation of their content revealed that all seven tools addressed the three core assumptions of instrumental variable analysis, violation of which can potentially introduce bias in MR analysis estimates. CONCLUSION: We present an overview of tools and methods to assess risk of bias/quality of evidence in MR analysis. Issues commonly addressed relate to the three standard assumptions of instrumental variables analyses, the choice of genetic instrument(s) and features of the population(s) from which the data are collected (particularly in two-sample MR), in addition to more traditional non-MR-specific epidemiological biases. The identified tools should be tested and validated for general use before recommendations can be made on their widespread use. Our findings should raise awareness about the importance of bias related to MR analysis and provide information that is useful for assessment of MR studies in the context of systematic reviews.

Therapeutic Metabolic Reprograming Using microRNAs: From Cancer to HIV Infection.

MicroRNAs (miRNAs) are crucial regulators of cellular processes, including metabolism. Attempts to use miRNAs as therapeutic agents are being explored in several areas, including the control of cancer progression. Recent evidence suggests fine tuning miRNA activity to reprogram tumor cell metabolism has enormous potential as an alternative treatment option. Indeed, cancer growth is known to be linked to profound metabolic changes. Likewise, the emerging field of immunometabolism is leading to a refined understanding of how immune cell proliferation and function is governed by glucose homeostasis. Different immune cell types are now known to have unique metabolic signatures that switch in response to a changing environment. T-cell subsets exhibit distinct metabolic profiles which underlie their alternative differentiation and phenotypic functions. Recent evidence shows that the susceptibility of CD4+ T-cells to HIV infection is intimately linked to their metabolic activity, with many of the metabolic features of HIV-1-infected cells resembling those found in tumor cells. In this review, we discuss the use of miRNA modulation to achieve metabolic reprogramming for cancer therapy and explore the idea that the same approach may serve as an effective mechanism to restrict HIV replication and eliminate infected cells.

Predicting intraurban airborne PM1.0-trace elements in a port city: Land use regression by ordinary least squares and a machine learning algorithm.

Airborne particulate matter (PM) has been associated with cardiovascular and respiratory morbidity and mortality, and there is some evidence that spatially varying metals found in PM may contribute to adverse health effects. We developed spatially refined models for PM trace elements using ordinary least squares land use regression (OLS-LUR) and machine leaning random forest land-use regression (RF-LUR). Two-week integrated measurements of PM1.0 (median aerodiameter < 1.0 µm) were collected at 50 sampling sites during fall (2010), winter (2011), and summer (2011) in the Halifax Regional Municipality, Nova Scotia, Canada. PM1.0 filters were analyzed for metals and trace elements using inductively coupled plasma-mass spectrometry. OLS- and RF-LUR models were developed for approximately 30 PM1.0 trace elements in each season. Model predictors included industrial, commercial, and institutional/ government/ military land use, roadways, shipping, other transportation sources, and wind rose information. RF generated more accurate models than OLS for most trace elements based on 5-fold cross validation. On average, summer models had the highest cross validation R2 (OLS-LUR = 0.40, RF-LUR = 0.46), while fall had the lowest (OLS-LUR = 0.27, RF-LUR = 0.31). Many OLS-LUR models displayed overprediction in the final exposure surface. In contrast, RF-LUR models did not exhibit overpredictions. Taking overpredictions and cross validation performances into account, OLS-LUR performed better than RF-LUR in roughly 20% of the seasonal trace element models. RF-LUR models provided more interpretable predictors in most cases. Seasonal predictors varied, likely due to differences in seasonal distribution of trace elements related to source activity, and meteorology.

Air quality in Canadian port cities after regulation of low-sulphur marine fuel in the North American Emissions Control Area.

Large marine vessels have historically used high-sulphur (S) residual fuel oil (RFO), with substantial airborne releases of sulphur dioxide (SO2) and fine particulate matter (PM2.5) enriched in vanadium (V), nickel (Ni) and other air pollutants. To address marine shipping air pollution, Canada and the United States have jointly implemented a North American Emissions Control Area (NA ECA) within which ships are regulated to use lower-sulphur marine fuel or equivalent SO2 scrubbers (i.e., 3.5% maximum fuel S reduced to 1% S in 2012 and 0.1% S in 2015). To investigate the effects of these regulations on local air quality, we examined changes in air pollutant (SO2, PM2.5, NO2, O3), and related PM2.5 components (V, Ni, sulphate) concentrations over 2010-2016 at the Canadian port cities of Halifax, Vancouver, Victoria, Montreal, and Quebec City. SO2 concentrations showed large statistically significant decreases at all sites (-28% to -83% mean hourly change), with the largest improvements in the coastal cities when the 0.1% fuel S regulation took effect. Statistically significant PM2.5 but smaller fractional reductions were also observed (-7% to -37% mean hourly change), reflecting the importance of non-marine PM sources. RFO marker species V and Ni in PM2.5 dramatically declined following regulation implementation, consistent with decreased RFO use likely indicating the switch to low-S distillate fuel oil rather than exhaust scrubbers for initial compliance. Significant changes in other pollutants with non-marine sources (NO2, O3) were not contemporaneous with the regulatory timeline. The large SO2 improvements in the port cities have reduced 1-h concentrations to <30 ppb, comparable to Canadian urban locations with few local SO2 sources and likely reducing health risks to susceptible populations such as asthmatics and the elderly. Our findings indicate that the implementation of the NA ECA improved air quality at Canadian port cities immediately following the requirement for lower-S fuel. These air quality improvements suggest that large-scale international benefits can result from implementation of the 2020 global low-S marine fuel regulations.

Molecular cloning and characterisation of chicken IL-18 binding protein.

The human IL-1 receptor family is comprised of 11 membrane bound or soluble receptors and the IL-18 binding protein (IL-18BP). These receptors are dispersed across seven genomic loci, with the majority at a single locus. Direct orthologues were identified in the chicken at conserved genomic loci; however, the IL-18BP remained absent from the first four builds of the chicken genome sequence. Subsequent assemblies identified the gene at a locus syntenic with mammals; however, these predicted sequences differed between genome builds and contained multiple errors. A partial IL-18BP-like sequence in the NCBI EST database was used to clone the full-length cDNA. A splice variant, which lacks the exon that encodes part of the signal peptide, was also cloned. Human IL-18BP is differentially spliced to produce a number of variants, which are all secreted. By contrast, the spliced chicken isoform was predicted to be intracellular, and we identified similar variants with the same exon missing in a limited number of divergent vertebrate species. Mammalian and viral IL-18BPs inhibit IL-18 activity by directly binding to this cytokine. Full-length and intracellular chicken IL-18BPs were equally effective at inhibiting IL-18-mediated IFN-γ release from an avian B-cell line. Analysis of the predicted chIL-18BP protein sequence revealed two crucial residues, which account for 50% of the binding affinity between human IL-18 and IL-18BP, are conserved in the chicken and a fowlpox-encoded homologue, fpv214. This suggests specific fowlpox viruses used in humans as a vaccine vector have the potential to dampen anti-viral host immune responses.

Skill Development Versus Performativity Among Beginners in Aerial Practice: An Embodied and Meaningful Learning Experience.

The purpose of this quasi-experimental, phenomenological study was to use embodied cognition in understanding learning experiences in skill development and performativity (e.g., storytelling and emotional expression) among 17 beginners in aerial practice (Mage = 20.59 ± 1.37 years old). Eight people were in the treatment-group class (skill development and performativity) and nine individuals participated in the control-group class (only skill development). Four themes emerged from the analysis: linking other exercises to aerial (e.g., cheerleading, dancing, and gymnastics) and uniqueness of aerial (e.g., artistic aspect while in the air); success in meeting aerial goals (at the posttest, performativity was valued more in the treatment group than the control group); exercise changes due to aerial, such as enhanced upper-body strengthening activities and stretches; and lessons learned, including importance of conditioning and small class size, switching Teaching Assistants (TAs), and silk awareness. Practitioners in community-based movement education programs like dancing and physical theater should recognize the need for embodied knowledge by emphasizing not only skill development but also performativity for enhanced learning experiences within supportive class settings. Although adding performative qualities to skill learning is more challenging than skill development alone, it can lead to enhanced performance, joy, and meaning of movement.

Large global variations in measured airborne metal concentrations driven by anthropogenic sources.

Globally consistent measurements of airborne metal concentrations in fine particulate matter (PM2.5) are important for understanding potential health impacts, prioritizing air pollution mitigation strategies, and enabling global chemical transport model development. PM2.5 filter samples (N ~ 800 from 19 locations) collected from a globally distributed surface particulate matter sampling network (SPARTAN) between January 2013 and April 2019 were analyzed for particulate mass and trace metals content. Metal concentrations exhibited pronounced spatial variation, primarily driven by anthropogenic activities. PM2.5 levels of lead, arsenic, chromium, and zinc were significantly enriched at some locations by factors of 100-3000 compared to crustal concentrations. Levels of metals in PM2.5 and PM10 exceeded health guidelines at multiple sites. For example, Dhaka and Kanpur sites exceeded the US National Ambient Air 3-month Quality Standard for lead (150 ng m-3). Kanpur, Hanoi, Beijing and Dhaka sites had annual mean arsenic concentrations that approached or exceeded the World Health Organization's risk level for arsenic (6.6 ng m-3). The high concentrations of several potentially harmful metals in densely populated cites worldwide motivates expanded measurements and analyses.

Author Correction: Additive manufacturing of ultrafine-grained high-strength titanium alloys.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Impact of Chemical Bonding on Mass Absorption Coefficients of Soft X-rays.

Accurate elemental quantification of materials by X-ray detection techniques in electron microscopes or microprobes can only be carried out if the appropriate mass absorption coefficients (MACs) are known. With continuous advancements in experimental techniques, databases of MACs must be expanded in order to account for new detection limits. Soft X-ray emission spectroscopy (SXES) is a characterization technique that can detect emitted X-rays whose energies are in the range of 10 eV to 2 keV by using a varied-line-spaced grating. Transitions producing soft X-rays can be detected and accurate MACs are required for use in quantification. This work uses Monte Carlo modeling coupled with multivoltage SXES measurements in an electron probe micro-analyzer (EPMA) to compute MACs for the L2,3-M and Li Kα transitions in a variety of aluminum alloys. Electron depth distribution curves obtained by the software MC X-ray are used in a parametrized fitting equation. The MACs are calculated using a least-squares regression analysis. It is shown that X-ray distribution cross-sections at such low energies need to take into account additional contributions, such as Coster­Kronig transitions, Auger yields, and wave function effects in order to be accurate.

Two Lineages of KLRA with Contrasting Transcription Patterns Have Been Conserved at a Single Locus during Ruminant Speciation.

Cattle possess the most diverse repertoire of NK cell receptor genes among all mammals studied to date. Killer cell receptor genes encoded within the NK complex and killer cell Ig-like receptor genes encoded within the leukocyte receptor complex have both been expanded and diversified. Our previous studies identified two divergent and polymorphic KLRA alleles within the NK complex in the Holstein-Friesian breed of dairy cattle. By examining a much larger cohort and other ruminant species, we demonstrate the emergence and fixation of two KLRA allele lineages (KLRA*01 and -*02) at a single locus during ruminant speciation. Subsequent recombination events between these allele lineages have increased the frequency of KLRA*02 extracellular domains. KLRA*01 and KLRA*02 transcription levels contrasted in response to cytokine stimulation, whereas homozygous animals consistently transcribed higher levels of KLRA, regardless of the allele lineage. KLRA*02 mRNA levels were also generally higher than KLRA*01 Collectively, these data point toward alternative functional roles governed by KLRA genotype and allele lineage. On a background of high genetic diversity of NK cell receptor genes, this KLRA allele fixation points to fundamental and potentially differential function roles.

Additive manufacturing of ultrafine-grained high-strength titanium alloys.

Additive manufacturing, often known as three-dimensional (3D) printing, is a process in which a part is built layer-by-layer and is a promising approach for creating components close to their final (net) shape. This process is challenging the dominance of conventional manufacturing processes for products with high complexity and low material waste1. Titanium alloys made by additive manufacturing have been used in applications in various industries. However, the intrinsic high cooling rates and high thermal gradient of the fusion-based metal additive manufacturing process often leads to a very fine microstructure and a tendency towards almost exclusively columnar grains, particularly in titanium-based alloys1. (Columnar grains in additively manufactured titanium components can result in anisotropic mechanical properties and are therefore undesirable2.) Attempts to optimize the processing parameters of additive manufacturing have shown that it is difficult to alter the conditions to promote equiaxed growth of titanium grains3. In contrast with other common engineering alloys such as aluminium, there is no commercial grain refiner for titanium that is able to effectively refine the microstructure. To address this challenge, here we report on the development of titanium-copper alloys that have a high constitutional supercooling capacity as a result of partitioning of the alloying element during solidification, which can override the negative effect of a high thermal gradient in the laser-melted region during additive manufacturing. Without any special process control or additional treatment, our as-printed titanium-copper alloy specimens have a fully equiaxed fine-grained microstructure. They also display promising mechanical properties, such as high yield strength and uniform elongation, compared to conventional alloys under similar processing conditions, owing to the formation of an ultrafine eutectoid microstructure that appears as a result of exploiting the high cooling rates and multiple thermal cycles of the manufacturing process. We anticipate that this approach will be applicable to other eutectoid-forming alloy systems, and that it will have applications in the aerospace and biomedical industries.

Temporal Aspects of Word Initial Single Consonants and Consonants in Clusters in Spanish.

We examined gestural coordination in C1C2 (C1 stop, C2 lateral or tap) word initial clusters using articulatory (electromagnetic articulometry) and acoustic data from six speakers of Standard Peninsular Spanish. We report on patterns of voice onset time (VOT), gestural plateau duration of C1, C2, and their overlap. For VOT, as expected, place of articulation is a major factor, with velars exhibiting longer VOTs than labials. Regarding C1 plateau duration, voice and place effects were found such that voiced consonants are significantly shorter than voiceless consonants, and velars show longer duration than labials. For C2 plateau duration, lateral duration was found to vary as a function of onset complexity (C vs. CC). As for overlap, unlike in French, where articulatory data for clusters have also been examined, clusters where both C1 and C2 are voiced show more overlap than where voicing differs. Further, overlap was affected by the C2 such that clusters where C2 is a tap show less overlap than clusters where C2 is a lateral. We discuss these results in the context of work aiming to uncover phonetic (e.g., articulatory or perceptual) and phonological forces (e.g., syllabic organization) on timing.

Evidence for Genetic Correlations and Bidirectional, Causal Effects Between Smoking and Sleep Behaviors.

INTRODUCTION: Cigarette smokers are at increased risk of poor sleep behaviors. However, it is largely unknown whether these associations are due to shared (genetic) risk factors and/or causal effects (which may be bidirectional). METHODS: We obtained summary-level data of genome-wide association studies of smoking (smoking initiation [n = 74 035], cigarettes per day [n = 38 181], and smoking cessation [n = 41 278]) and sleep behaviors (sleep duration and chronotype, or "morningness" [n = 128 266] and insomnia [n = 113 006]). Using linkage disequilibrium (LD) score regression, we calculated genetic correlations between smoking and sleep behaviors. To investigate causal effects, we employed Mendelian randomization (MR), both with summary-level data and individual-level data (n = 333 581 UK Biobank participants). For MR with summary-level data, individual genetic variants were combined with inverse variance-weighted meta-analysis, weighted median regression, MR-Robust Adjusted Profile Score, and MR Egger methods. RESULTS: We found negative genetic correlations between smoking initiation and sleep duration (rg = -.14, 95% CI = -0.26 to -0.01) and smoking cessation and chronotype (rg = -.18, 95% CI = -0.31 to -0.06), and positive genetic correlations between smoking initiation and insomnia (rg = .27, 95% CI = 0.06 to 0.49) and cigarettes per day and insomnia (rg = .15, 95% CI = 0.01 to 0.28). MR provided strong evidence that smoking more cigarettes causally decreases the odds of being a morning person, (RAPS) and weak evidence that insomnia causally increases smoking heaviness and decreases smoking cessation odds. CONCLUSIONS: Smoking and sleep behaviors show moderate genetic correlation. Heavier smoking seems to causally affect circadian rhythm and there is some indication that insomnia increases smoking heaviness and hampers cessation. Our findings point to sleep as a potentially interesting smoking treatment target. IMPLICATIONS: Using LD score regression, we found evidence that smoking and different sleep behaviors (sleep duration, chronotype (morningness), and insomnia) are moderately genetically correlated-genetic variants associated with less or poorer sleep also increased the odds of smoking (more heavily). MR analyses suggested that heavier smoking causally affects circadian rhythm (decreasing the odds of being a morning person) and there was some indication that insomnia increases smoking heaviness and hampers smoking cessation. Our findings indicate a complex, bidirectional relationship between smoking and sleep behaviors and point to sleep as a potentially interesting smoking treatment target.