The mental health of migrants living in limbo: A mixed-methods systematic review with meta-analysis.

The number of forcibly displaced people has more than doubled over the past decade. Many people fleeing are left in limbo without a secure pathway to citizenship or residency. This mixed-methods systematic review reports the prevalence of mental disorders in migrants living in limbo, the association between limbo and mental illness, and the experiences of these migrants in high income countries. We searched electronic databases for quantitative and qualitative studies published after January 1, 2010, on mental illness in precarious migrants living in HICs and performed a meta-analysis of prevalence rates. Fifty-eight articles met inclusion criteria. The meta-analysis yielded prevalence rates of 43.0 % for anxiety disorders (95 % CI 29.0-57.0), 49.5 % for depression (40.9-58.0) and 40.8 % for posttraumatic stress disorder (30.7-50.9). Having an insecure status was associated with higher rates of mental illness in most studies comparing migrants in limbo to those with secure status. Six themes emerged from the qualitative synthesis: the threat of deportation, uncertainty, social exclusion, stigmatization, social connection and religion. Clinicians should take an ecosocial approach to care that attends to stressors and symptoms. Furthermore, policymakers can mitigate the development of mental disorders among migrants by adopting policies that ensure rapid pathways to protected status.

Adjusting for the effect of IV contrast on automated CT body composition measures during the portal venous phase.

OBJECTIVE: Fully-automated CT-based algorithms for quantifying numerous biomarkers have been validated for unenhanced abdominal scans. There is great interest in optimizing the documentation and reporting of biophysical measures present on all CT scans for the purposes of opportunistic screening and risk profiling. The purpose of this study was to determine and adjust the effect of intravenous (IV) contrast on these automated body composition measures at routine portal venous phase post-contrast imaging. METHODS: Final study cohort consisted of 1,612 older adults (mean age, 68.0 years; 594 women) all imaged utilizing a uniform CT urothelial protocol consisting of pre-contrast, portal venous, and delayed excretory phases. Fully-automated CT-based algorithms for quantifying numerous biomarkers, including muscle and fat area and density, bone mineral density, and solid organ volume were applied to pre-contrast and portal venous phases. The effect of IV contrast upon these body composition measures was analyzed. Regression analyses, including square of the Pearson correlation coefficient (r2), were performed for each comparison. RESULTS: We found that simple, linear relationships can be derived to determine non-contrast equivalent values from the post-contrast CT biomeasures. Excellent positive linear correlation (r2 = 0.91-0.99) between pre- and post-contrast values was observed for all automated soft tissue measures, whereas moderate positive linear correlation was observed for bone attenuation (r2 = 0.58-0.76). In general, the area- and volume-based measurement require less adjustment than attenuation-based measures, as expected. CONCLUSION: Fully-automated quantitative CT-biomarker measures at portal venous phase abdominal CT can be adjusted to a non-contrast equivalent using simple, linear relationships.

Metabolic syndrome: imaging features and clinical outcomes.

Metabolic syndrome, which affects around a quarter of adults worldwide, is a group of metabolic abnormalities characterized mainly by insulin resistance and central adiposity. It is strongly correlated with cardiovascular and all-cause mortality. Early identification of the changes induced by metabolic syndrome in target organs and timely intervention (eg, weight reduction) can decrease morbidity and mortality. Imaging can monitor the main components of metabolic syndrome and identify early the development and progression of its sequelae in various organs. In this review, we discuss the imaging features across different modalities that can be used to evaluate changes due to metabolic syndrome, including fatty deposition in different organs, arterial stiffening, liver fibrosis, and cardiac dysfunction. Radiologists can play a vital role in recognizing and following these target organ injuries, which in turn can motivate lifestyle modification and therapeutic intervention.

Rayleigh step-selection functions and connections to continuous-time mechanistic movement models.

BACKGROUND: The process known as ecological diffusion emerges from a first principles view of animal movement, but ecological diffusion and other partial differential equation models can be difficult to fit to data. Step-selection functions (SSFs), on the other hand, have emerged as powerful practical tools for ecologists studying the movement and habitat selection of animals. METHODS: SSFs typically involve comparing resources between a set of used and available points at each step in a sequence of observed positions. We use change of variables to show that ecological diffusion implies certain distributions for available steps that are more flexible than others commonly used. We then demonstrate advantages of these distributions with SSF models fit to data collected for a mountain lion in Colorado, USA. RESULTS: We show that connections between ecological diffusion and SSFs imply a Rayleigh step-length distribution and uniform turning angle distribution, which can accommodate data collected at irregular time intervals. The results of fitting an SSF model with these distributions compared to a set of commonly used distributions revealed how precision and inference can vary between the two approaches. CONCLUSIONS: Our new continuous-time step-length distribution can be integrated into various forms of SSFs, making them applicable to data sets with irregular time intervals between successive animal locations.

Fully automated CT imaging biomarkers for opportunistic prediction of future hip fractures.

OBJECTIVE: Assess automated CT imaging biomarkers in patients who went on to hip fracture, compared with controls. METHODS: In this retrospective case-control study, 6926 total patients underwent initial abdominal CT over a 20-year interval at one institution. A total of 1308 patients (mean age at initial CT, 70.5 ± 12.0 years; 64.4% female) went on to hip fracture (mean time to fracture, 5.2 years); 5618 were controls (mean age 70.3 ± 12.0 years; 61.2% female; mean follow-up interval 7.6 years). Validated fully automated quantitative CT algorithms for trabecular bone attenuation (at L1), skeletal muscle attenuation (at L3), and subcutaneous adipose tissue area (SAT) (at L3) were applied to all scans. Hazard ratios (HRs) comparing highest to lowest risk quartiles and receiver operating characteristic (ROC) curve analysis including area under the curve (AUC) were derived. RESULTS: Hip fracture HRs (95% CI) were 3.18 (2.69-3.76) for low trabecular bone HU, 1.50 (1.28-1.75) for low muscle HU, and 2.18 (1.86-2.56) for low SAT. 10-year ROC AUC values for predicting hip fracture were 0.702, 0.603, and 0.603 for these CT-based biomarkers, respectively. Multivariate combinations of these biomarkers further improved predictive value; the 10-year ROC AUC combining bone/muscle/SAT was 0.733, while combining muscle/SAT was 0.686. CONCLUSION: Opportunistic use of automated CT bone, muscle, and fat measures can identify patients at higher risk for future hip fracture, regardless of the indication for CT imaging. ADVANCES IN KNOWLEDGE: CT data can be leveraged opportunistically for further patient evaluation, with early intervention as needed. These novel AI tools analyse CT data to determine a patient's future hip fracture risk.

Multicenter Evaluation of a Weakly Supervised Deep Learning Model for Lymph Node Diagnosis in Rectal Cancer at MRI.

Purpose To develop a Weakly supervISed model DevelOpment fraMework (WISDOM) model to construct a lymph node (LN) diagnosis model for patients with rectal cancer (RC) that uses preoperative MRI data coupled with postoperative patient-level pathologic information. Materials and Methods In this retrospective study, the WISDOM model was built using MRI (T2-weighted and diffusion-weighted imaging) and patient-level pathologic information (the number of postoperatively confirmed metastatic LNs and resected LNs) based on the data of patients with RC between January 2016 and November 2017. The incremental value of the model in assisting radiologists was investigated. The performances in binary and ternary N staging were evaluated using area under the receiver operating characteristic curve (AUC) and the concordance index (C index), respectively. Results A total of 1014 patients (median age, 62 years; IQR, 54-68 years; 590 male) were analyzed, including the training cohort (n = 589) and internal test cohort (n = 146) from center 1 and two external test cohorts (cohort 1: 117; cohort 2: 162) from centers 2 and 3. The WISDOM model yielded an overall AUC of 0.81 and C index of 0.765, significantly outperforming junior radiologists (AUC = 0.69, P < .001; C index = 0.689, P < .001) and performing comparably with senior radiologists (AUC = 0.79, P = .21; C index = 0.788, P = .22). Moreover, the model significantly improved the performance of junior radiologists (AUC = 0.80, P < .001; C index = 0.798, P < .001) and senior radiologists (AUC = 0.88, P < .001; C index = 0.869, P < .001). Conclusion This study demonstrates the potential of WISDOM as a useful LN diagnosis method using routine rectal MRI data. The improved radiologist performance observed with model assistance highlights the potential clinical utility of WISDOM in practice. Keywords: MR Imaging, Abdomen/GI, Rectum, Computer Applications-Detection/Diagnosis Supplemental material is available for this article. Published under a CC BY 4.0 license.

Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Comparative molecular profiling of multidrug-resistant Pseudomonas aeruginosa identifies novel mutations in regional clinical isolates from South India.

Objectives: We sought to analyse the antibiotic susceptibility profiles and molecular epidemiology of MDR clinical Pseudomonas aeruginosa isolates from South India using non-MDR isolates as a reference. Methods: We established a comprehensive clinical strain library consisting of 58 isolates collected from patients across the South Indian state of Kerala from March 2017 to July 2019. The strains were subject to antibiotic susceptibility testing, modified carbapenem inactivation method assay for carbapenemase production, PCR sequencing, comparative sequence analysis and quantitative PCR of MDR determinants associated with antibiotic efflux pump systems, fluoroquinolone resistance and carbapenem resistance. We performed in silico modelling of MDR-specific SNPs. Results: Of our collection of South Indian P. aeruginosa clinical isolates, 74.1% were MDR and 55.8% were resistant to the entire panel of antibiotics tested. All MDR isolates were resistant to levofloxacin and 93% were resistant to meropenem. We identified seven distinct, MDR-specific mutations in nalD, three of which are novel. mexA was significantly overexpressed in strains that were resistant to the entire test antibiotic panel while gyrA and gyrB were overexpressed in MDR isolates. Mutations in fluoroquinolone determinants were significantly associated with MDR phenotype and a novel GyrA Y100C substitution was observed. Carbapenem resistance in MDR isolates was associated with loss-of-function mutations in oprD and high prevalence of NDM (blaNDM-1) within our sample. Conclusions: This study provides insight into MDR mechanisms adopted by P. aeruginosa clinical isolates, which may guide the potential development of therapeutic regimens to improve clinical outcomes.

CT Colonography Reporting and Data System (C-RADS): Version 2023 Update.

The CT Colonography Reporting and Data System (C-RADS) has withstood the test of time and proven to be a robust classification scheme for CT colonography (CTC) findings. C-RADS version 2023 represents an update on the scheme used for colorectal and extracolonic findings at CTC. The update provides useful insights gained since the implementation of the original system in 2005. Increased experience has demonstrated confusion on how to classify the mass-like appearance of the colon consisting of soft tissue attenuation that occurs in segments with acute or chronic diverticulitis. Therefore, the update introduces a new subcategory, C2b, specifically for mass-like diverticular strictures, which are likely benign. Additionally, the update simplifies extracolonic classification by combining E1 and E2 categories into an updated extracolonic category of E1/E2 since, irrespective of whether a finding is considered a normal variant (category E1) or an otherwise clinically unimportant finding (category E2), no additional follow-up is required. This simplifies and streamlines the classification into one category, which results in the same management recommendation.

AI-generated CT body composition biomarkers associated with increased mortality risk in socioeconomically disadvantaged individuals.

PURPOSE: To evaluate the relationship between socioeconomic disadvantage using national area deprivation index (ADI) and CT-based body composition measures derived from fully automated artificial intelligence (AI) tools to identify body composition measures associated with increased risk for all-cause mortality and adverse cardiovascular events. METHODS: Fully automated AI body composition tools quantifying abdominal aortic calcium, abdominal fat (visceral [VAT], visceral-to-subcutaneous ratio [VSR]), and muscle attenuation (muscle HU) were applied to non-contrast CT examinations in adults undergoing screening CT colonography (CTC). Patients were partitioned into 5 socioeconomic groups based on the national ADI rank at the census block group level. Pearson correlation analysis was performed to determine the association between national ADI and body composition measures. One-way analysis of variance was used to compare means across groups. Odds ratios (ORs) were generated using high-risk, high specificity (90% specificity) body composition thresholds with the most disadvantaged groups being compared to the least disadvantaged group (ADI < 20). RESULTS: 7785 asymptomatic adults (mean age, 57 years; 4361:3424 F:M) underwent screening CTC from April 2004-December 2016. ADI rank data were available in 7644 patients. Median ADI was 31 (IQR 22-43). Aortic calcium, VAT, and VSR had positive correlation with ADI and muscle attenuation had a negative correlation with ADI (all p < .001). Compared with the least disadvantaged group, mean differences for the most disadvantaged group (ADI > 80) were: Aortic calcium (Agatston) = 567, VAT = 27 cm2, VSR = 0.1, and muscle HU = -6 HU (all p < .05). Compared with the least disadvantaged group, the most disadvantaged group had significantly higher odds of having high-risk body composition measures: Aortic calcium OR = 3.8, VAT OR = 2.5, VSR OR = 2.0, and muscle HU OR = 3.1(all p < .001). CONCLUSION: Fully automated CT body composition tools show that socioeconomic disadvantage is associated with high-risk body composition measures and can be used to identify individuals at increased risk for all-cause mortality and adverse cardiovascular events.

Natural History of Colorectal Polyps Undergoing Longitudinal in Vivo CT Colonography Surveillance.

Background The natural history of colorectal polyps is not well characterized due to clinical standards of care and other practical constraints limiting in vivo longitudinal surveillance. Established CT colonography (CTC) clinical screening protocols allow surveillance of small (6-9 mm) polyps. Purpose To assess the natural history of colorectal polyps followed with CTC in a clinical screening program, with histopathologic correlation for resected polyps. Materials and Methods In this retrospective study, CTC was used to longitudinally monitor small colorectal polyps in asymptomatic adult patients from April 1, 2004, to August 31, 2020. All patients underwent at least two CTC examinations. Polyp growth patterns across multiple time points were analyzed, with histopathologic context for resected polyps. Regression analysis was performed to evaluate predictors of advanced histopathology. Results In this study of 475 asymptomatic adult patients (mean age, 56.9 years ± 6.7 [SD]; 263 men), 639 unique polyps (mean initial diameter, 6.3 mm; volume, 50.2 mm3) were followed for a mean of 5.1 years ± 2.9. Of these 639 polyps, 398 (62.3%) underwent resection and histopathologic evaluation, and 41 (6.4%) proved to be histopathologically advanced (adenocarcinoma, high-grade dysplasia, or villous content), including two cancers and 38 tubulovillous adenomas. Advanced polyps showed mean volume growth of +178% per year (752% per year for adenocarcinomas) compared with +33% per year for nonadvanced polyps and -3% per year for unresected, unretrieved, or resolved polyps (P < .001). In addition, 90% of histologically advanced polyps achieved a volume of 100 mm3 and/or volume growth rate of 100% per year, compared with 29% of nonadvanced and 16% of unresected or resolved polyps (P < .001). Polyp volume-to-diameter ratio was also significantly greater for advanced polyps. For polyps observed at three or more time points, most advanced polyps demonstrated an initial slower growth interval, followed by a period of more rapid growth. Conclusion Small colorectal polyps ultimately proving to be histopathologically advanced neoplasms demonstrated substantially faster growth and attained greater overall size compared with nonadvanced polyps. Clinical trial registration no. NCT00204867 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Dachman in this issue.

GDF15 linked to maternal risk of nausea and vomiting during pregnancy.

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1-4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with ß-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

Automated detection of incidental abdominal aortic aneurysms on computed tomography.

PURPOSE: To detect and assess abdominal aortic aneurysms (AAAs) on CT in a large asymptomatic adult patient population using fully-automated deep learning software. MATERIALS AND METHODS: The abdominal aorta was segmented using a fully-automated deep learning model trained on 66 manually-segmented abdominal CT scans from two datasets. The axial diameters of the segmented aorta were extracted to detect the presence of AAAs-maximum axial aortic diameter greater than 3 cm were labeled as AAA positive. The trained system was then externally-validated on CT colonography scans of 9172 asymptomatic outpatients (mean age, 57 years) referred for colorectal cancer screening. Using a previously-validated automated calcified atherosclerotic plaque detector, we correlated abdominal aortic Agatston and volume scores with the presence of AAA. RESULTS: The deep learning software detected AAA on the external validation dataset with a sensitivity, specificity, and AUC of 96%, (95% CI 89%, 100%), 96% (96%, 97%), and 99% (98%, 99%) respectively. The Agatston and volume scores of reported AAA-positive cases were statistically significantly greater than those of reported AAA-negative cases (p < 0.0001). Using plaque alone as a AAA detector, at a threshold Agatston score of 2871, the sensitivity and specificity were 84% (73%, 94%) and 87% (86%, 87%), respectively. CONCLUSION: Fully-automated detection and assessment of AAA on CT is feasible and accurate. There was a strong statistical association between the presence of AAA and the quantity of abdominal aortic calcified atherosclerotic plaque.

Tristetraprolin overexpression drives hematopoietic changes in young and middle-aged mice generating dominant mitigating effects on induced inflammation in murine models.

Tristetraprolin (TTP), encoded by Zfp36 in mice, is one of the best-characterized tandem zinc-finger mRNA binding proteins involved in mRNA deadenylation and decay. TTPΔARE mice lack an AU-rich motif in the 3'-untranslated regions of TTP mRNA, leading to increased TTP mRNA stability and more TTP protein, resulting in elevated mRNA decay rates of TTP targets. We examined the effect of TTP overexpression on the hematopoietic system in both young and middle-aged mice using TTPΔARE mice and found alterations in blood cell frequencies, with loss of platelets and B220 cells and gains of eosinophils and T cells. TTPΔARE mice also have skewed primitive populations in the bone marrow, with increases in myeloid-biased hematopoietic stem cells (HSCs) but decreases in granulocyte/macrophage-biased multipotent progenitors (MPP3) in both young and middle-aged mice. Changes in the primitive cells' frequencies were associated with transcriptional alterations in the TTP overexpression cells specific to age as well as cell type. Regardless of age, there was a consistent elevation of transcripts regulated by TNFα and TGFß signaling pathways in both the stem and multipotent progenitor populations. HSCs with TTP overexpression had decreased reconstitution potential in murine transplants but generated hematopoietic environments that mitigated the inflammatory response to the collagen antibody-induced arthritis (CAIA) challenge, which models rheumatoid arthritis and other autoimmune disorders. This dampening of the inflammatory response was even present when there was only a small frequency of TTP overexpressing cells present in the middle-aged mice. We provide an analysis of the early hematopoietic compartments with elevated TTP expression in both young and middle-aged mice which inhibits the reconstitution potential of the HSCs but generates a hematopoietic system that provides dominant repression of induced inflammation.

Longitudinal follow-up of incidental renal calculi on computed tomography.

RATIONALE AND OBJECTIVES: Measuring small kidney stones on CT is a time-consuming task often neglected. Volumetric assessment provides a better measure of size than linear dimensions. Our objective is to analyze the growth rate and prognosis of incidental kidney stones in asymptomatic patients on CT. MATERIALS AND METHODS: This retrospective study included 4266 scans from 2030 asymptomatic patients who underwent two or more nonenhanced CT scans for colorectal screening between 2004 and 2016. The DL software identified and measured the volume, location, and attenuation of 883 stones. The corresponding scans were manually evaluated, and patients without follow-up were excluded. At each follow-up, the stones were categorized as new, growing, persistent, or resolved. Stone size (volume and diameter), attenuation, and location were correlated with the outcome and growth rates of the stones. RESULTS: The stone cohort comprised 407 scans from 189 (M: 124, F: 65, median age: 55.4 years) patients. The median number of stones per scan was 1 (IQR: [1, 2]). The median stone volume was 17.1 mm3 (IQR: [7.4, 43.6]) and the median peak attenuation was 308 HU (IQR: [204, 532]. The 189 initial scans contained 291stones; 91 (31.3%) resolved, 142 (48.8%) grew, and 58 (19.9) remained persistent at the first follow-up. At the second follow-up (for 27 patients with 2 follow-ups), 14/44 (31.8%) stones had resolved, 19/44 (43.2%) grew and 11/44 (25%) were persistent. The median growth rate of growing stones was 3.3 mm3/year, IQR: [1.4,7.4]. Size and attenuation had a moderate correlation (Spearman rho 0.53, P < .001 for volume, and 0.50 P < .001 for peak attenuation) with the growth rate. Growing and persistent stones had significantly greater maximum axial diameter (2.7 vs 2.3 mm, P =.047) and peak attenuation (300 vs 258 HU, P =.031) CONCLUSION: We report a 12.7% prevalence of incidental kidney stones in asymptomatic adults, of which about half grew during follow-up with a median growth rate of about 3.3 mm3/year.

Empirical Model of Solvophobic Interactions in Organic Solvents.

An empirical model was developed to predict organic solvophobic effects using N-phenylimide molecular balances functionalized with non-polar alkyl groups. Solution studies and X-ray crystallography confirmed intramolecular alkyl-alkyl interactions in their folded conformers. The structural modularity of the balances allowed systematic variation of alkyl group lengths. Control balances were instrumental in isolating weak organic solvophobic effects by eliminating framework solvent-solute effects. A 19 F NMR label enabled analysis across 46 deuterated and non-deuterated solvent systems. Linear correlations were observed between organic solvophobic effects and solvent cohesive energy density (ced) as well as changes in solvent-accessible surface areas (SASA). Using these empirical relationships, a model was constructed to predict organic solvophobic interaction energy per unit area for any organic solvent with known ced values. The predicted interaction energies aligned with recent organic solvophobic measurements and literature values for the hydrophobic effect on non-polar surfaces confirmed the model's accuracy and utility.

Boostability after single-visit pre-exposure prophylaxis with rabies vaccine: a randomised controlled non-inferiority trial.

BACKGROUND: After rabies pre-exposure prophylaxis (PrEP) vaccination, scarcely available rabies immunoglobulins are not required for post-exposure prophylaxis (PEP). However, PrEP is not sufficiently accessible as it is cost-intensive and time-intensive. This study investigates whether rabies PrEP schedules can be shortened to one visit, removing some of these barriers. METHODS: In a block-randomised (2:2:2:1) controlled, multicentre non-inferiority trial, healthy adult travellers (aged 18-50 years and >50 years) were randomly assigned to (A) single-visit intramuscular (1·0 mL); (B) single-visit intradermal (0·2 mL); (C) standard two-visit intramuscular (1·0 mL; day 0 and 7) PrEP; or (D) no rabies vaccination. 6 months later, participants received simulated intramuscular rabies PEP (1·0 mL; day 0 and 3). Rabies virus neutralising antibody (RVNA) concentrations were measured repeatedly. The primary outcome was the fold increase in geometric mean RVNA concentrations between day 0 and 7 after simulated PEP for all participants. The two main comparisons of this primary outcome are between the standard two-visit schedule and the one-visit intramuscular schedule, and between the standard two-visit schedule and the one-visit intradermal schedule. The non-inferiority margin was 0·67. This study is registered with EudraCT, 2017-000089-31. FINDINGS: Between May 16, 2018, and March 26, 2020, 288 healthy adult travellers were randomly assigned and 214 participants were evaluated for the primary outcome. Single-visit intramuscular rabies PrEP induced an anamnestic antibody response non-inferior compared with the two-visit intramuscular schedule; single-visit intradermal PrEP did not. The fold increases in the single-visit intramuscular and the single-visit intradermal schedule were 2·32 (95% CI [1·43-3·77]) and 1·11 (0·66-1·87) times as high as the fold increase in the standard schedule, respectively. No vaccine-related serious adverse events were observed. Adverse events related to vaccination were mostly mild. INTERPRETATION: Single intramuscular rabies vaccination can effectively prime travellers (aged 18-50 years), and potentially other populations, and could replace current standard two-visit rabies vaccination as PrEP. FUNDING: ZonMW. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.