Logic-enabled textiles.

Textiles hold great promise as a soft yet durable material for building comfortable robotic wearables and assistive devices at low cost. Nevertheless, the development of smart wearables composed entirely of textiles has been hindered by the lack of a viable sheet-based logic architecture that can be implemented using conventional fabric materials and textile manufacturing processes. Here, we develop a fully textile platform for embedding pneumatic digital logic in wearable devices. Our logic-enabled textiles support combinational and sequential logic functions, onboard memory storage, user interaction, and direct interfacing with pneumatic actuators. In addition, they are designed to be lightweight, easily integrable into regular clothing, made using scalable fabrication techniques, and durable enough to withstand everyday use. We demonstrate a textile computer capable of input-driven digital logic for controlling untethered wearable robots that assist users with functional limitations. Our logic platform will facilitate the emergence of future wearables powered by embedded fluidic logic that fully leverage the innate advantages of their textile construction.

The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Consumption of aspartame and other artificial sweeteners and risk of cancer in the Spanish multicase-control study (MCC-Spain).

Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (

PI3K Targeting in Non-solid Cancer.

Despite the therapeutic progress, relapse remains a major problem in the treatment of acute lymphoblastic leukemia (ALL). Most leukemia cells that survive chemotherapy are found in the bone marrow (BM), thus resistance to chemotherapy and other treatments may be partially attributed to pro-survival signaling to leukemic cells mediated by leukemia cell-microenvironment interactions. Adhesion of leukemia cells to BM stromal cells may lead to cell adhesion-mediated drug resistance (CAM-DR) mediating intracellular signaling changes that support survival of leukemia cells. In ALL and chronic lymphocytic leukemia (CLL), adhesion-mediated activation of the PI3K/AKT signaling pathway has been shown to be critical in CAM-DR. PI3K targeting inhibitors have been approved for CLL and have been evaluated preclinically in ALL. However, PI3K inhibition has yet to be approved for clinical use in ALL. Here, we review the role of PI3K signaling for normal hematopoietic and leukemia cells and summarize preclinical inhibitors of PI3K in ALL.

Age-period-cohort analysis of lung cancer mortality inequalities in Southern Spain: missed opportunities for implementing equitable tobacco control policies.

BACKGROUND: Lung cancer mortality in European countries shows different epidemiological patterns according to sex and socioeconomic variables. Some countries show decreasing rates in both sexes, while others show a delayed profile, with increasing mortality in women, inconsistently influenced by socioeconomic status. Our aim was to evaluate the effect of age, period and birth cohort on lung cancer mortality inequalities in men and women in Andalusia, the southernmost region in Spain. METHODS: We used the Longitudinal Database of the Andalusian Population, which collects demographic and mortality data from the 2001 census cohort of more than 7.35 million Andalusians, followed up between 2002 and 2016. Mortality rates were calculated for men and women by educational level, and small-area deprivation. Poisson models were used to assess trends in socioeconomic inequalities in men and women. Finally, age-period-cohort (APC) models were used separately for each educational level and gender. RESULTS: There were 39,408 lung cancer deaths in men and 5,511 in women, yielding crude mortality rates of 78.1 and 11.4 × 105 person-years, respectively. In men higher mortality was found in less educated groups and inequalities increased during the study period: i.e. the rate ratio for primary studies compared to university studies increased from 1.30 (CI95:1.18-1.44) to 1.57 (CI95:1.43-1.73). For women, educational inequalities in favour of the less educated tended to decrease moderately. In APC analysis, a decreasing period effect in men and an increasing one in women were observed. Cohort effect differed significantly by educational level. In men, the lower the educational level, the earlier the peak effect was reached, with a 25-year difference between the least-educated and college-educated. Conversely, college-educated women reached the peak effect with a 12-year earlier cohort than the least-educated women. The decline of mortality followed the same pattern both in men and women, with the best-educated groups experiencing declining rates with earlier birth cohorts. CONCLUSIONS: Our study reveals that APC analysis by education helps to uncover changes in trends occurring in different socioeconomic and gender groups, which, combined with data on smoking prevalence, provide important clues for action. Despite its limitations, this approach to the study of lung cancer inequalities allows for the assessment of gaps in historical and current tobacco policies and the identification of population groups that need to be prioritised for public health interventions.

Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 IgG in Juba, South Sudan, 20201.

Relatively few coronavirus disease cases and deaths have been reported from sub-Saharan Africa, although the extent of its spread remains unclear. During August 10-September 11, 2020, we recruited 2,214 participants for a representative household-based cross-sectional serosurvey in Juba, South Sudan. We found 22.3% of participants had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain IgG titers above prepandemic levels. After accounting for waning antibody levels, age, and sex, we estimated that 38.3% (95% credible interval 31.8%-46.5%) of the population had been infected with SARS-CoV-2. At this rate, for each PCR-confirmed SARS-CoV-2 infection reported by the Ministry of Health, 103 (95% credible interval 86-126) infections would have been unreported, meaning SARS-CoV-2 has likely spread extensively within Juba. We also found differences in background reactivity in Juba compared with Boston, Massachusetts, USA, where the immunoassay was validated. Our findings underscore the need to validate serologic tests in sub-Saharan Africa populations.

Evaluation of Traumatic Spinal Cord Injury in a Rat Model Using 99mTc-GA-5 as a Potential In Vivo Tracer.

Spinal cord injury (SCI) refers to the damage suffered in the spinal cord by any trauma or pathology. The purpose of this work was to determine whether 99mTc-GA-5, a radiotracer targeting Glial Fibrillary Acidic Protein (GFAP), can reveal in vivo the reactivation of astrocytes in a murine model with SCI. A method for the 99mTc radiolabeling of the mouse anti-GFAP monoclonal antibody GA-5 was implemented. Radiochemical characterization was performed, and radioimmunohistochemistry assays were used to evaluate the integrity of 99mTc-GA-5. MicroSPECT/CT was used for in vivo imaging to trace SCI in the rats. No alterations in the GA-5's recognition/specificity ability were observed after the radiolabeling. The GA-5's radiolabeling procedure implemented in this work offers a practical method to allow the in vivo following of this monoclonal antibody to evaluate its biodistribution and specificity for GFAP receptors using SPECT/CT molecular imaging.

Effect of Savings on a Gas-Like Model Economy with Credit and Debt.

In kinetic exchange models, agents make transactions based on well-established microscopic rules that give rise to macroscopic variables in analogy to statistical physics. These models have been applied to study processes such as income and wealth distribution, economic inequality sources, economic growth, etc., recovering well-known concepts in the economic literature. In this work, we apply ensemble formalism to a geometric agents model to study the effect of saving propensity in a system with money, credit, and debt. We calculate the partition function to obtain the total money of the system, with which we give an interpretation of the economic temperature in terms of the different payment methods available to the agents. We observe an interplay between the fraction of money that agents can save and their maximum debt. The system's entropy increases as a function of the saved proportion, and increases even more when there is debt.

Taxonomic similarity does not predict necessary sample size for ex situ conservation: a comparison among five genera.

Effectively conserving biodiversity with limited resources requires scientifically informed and efficient strategies. Guidance is particularly needed on how many living plants are necessary to conserve a threshold level of genetic diversity in ex situ collections. We investigated this question for 11 taxa across five genera. In this first study analysing and optimizing ex situ genetic diversity across multiple genera, we found that the percentage of extant genetic diversity currently conserved varies among taxa from 40% to 95%. Most taxa are well below genetic conservation targets. Resampling datasets showed that ideal collection sizes vary widely even within a genus: one taxon typically required at least 50% more individuals than another (though Quercus was an exception). Still, across taxa, the minimum collection size to achieve genetic conservation goals is within one order of magnitude. Current collections are also suboptimal: they could remain the same size yet capture twice the genetic diversity with an improved sampling design. We term this deficiency the 'genetic conservation gap'. Lastly, we show that minimum collection sizes are influenced by collection priorities regarding the genetic diversity target. In summary, current collections are insufficient (not reaching targets) and suboptimal (not efficiently designed), and we show how improvements can be made.

Transmembrane 163 (TMEM163) protein effluxes zinc.

Recent investigations of rodent Tmem163 suggest that it binds to and transports zinc as a dimer, and that alanine mutagenesis of its two species-conserved aspartate (D123A/D127A) residues proposed to bind zinc, perturbs protein function. Direct corroboration, however, is lacking whether it is an influx or efflux transporter in cells. We hypothesized that human TMEM163 is a zinc effluxer based on its predicted protein characteristics. We used cultured human cell lines that either stably or transiently expressed TMEM163, and pre-loaded the cells with zinc to determine transport activity. We found that TMEM163-expressing cells exhibited significant reduction of intracellular zinc levels as evidenced by two zinc-specific fluorescent dyes and radionuclide zinc-65. The specificity of the fluorescence signal was confirmed upon treatment with TPEN, a high-affinity zinc chelator. Multiple sequence alignment and phylogenetic analyses showed that TMEM163 is related to distinct members of the cation diffusion facilitator (CDF) protein family. To further characterize the efflux function of TMEM163, we substituted alanine in two homologous aspartate residues (D124A/D128A) and performed site-directed mutagenesis of several conserved amino acid residues identified as non-synonymous single nucleotide polymorphism (S61R, S95C, S193P, and E286K). We found a significant reduction of zinc efflux upon cellular expression of D124A/D128A or E286K protein variant when compared with wild-type, suggesting that these particular amino acids are important for normal protein function. Taken together, our findings demonstrate that TMEM163 effluxes zinc, and it should now be designated ZNT11 as a new member of the mammalian CDF family of zinc efflux transporters.

Targeting PI3K Signaling in Acute Lymphoblastic Leukemia.

Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stroma cells triggers intracellular signals regulating cell-adhesion-mediated drug resistance (CAM-DR). Stromal cell protection of ALL cells has been shown to require active AKT. In chronic lymphocytic leukemia (CLL), adhesion-mediated activation of the PI3K/AKT pathway is reported. A novel FDA-approved PI3Kδ inhibitor, CAL-101/idelalisib, leads to downregulation of p-AKT and increased apoptosis of CLL cells. Recently, two additional PI3K inhibitors have received FDA approval. As the PI3K/AKT pathway is also implicated in adhesion-mediated survival of ALL cells, PI3K inhibitors have been evaluated preclinically in ALL. However, PI3K inhibition has yet to be approved for clinical use in ALL. Here, we review the role of PI3K in normal hematopoietic cells, and in ALL. We focus on summarizing targeting strategies of PI3K in ALL.

Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft.

Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.

Shifting Quaternary migration patterns in the Bahamian archipelago: Evidence from the Zamia pumila complex at the northern limits of the Caribbean island biodiversity hotspot.

PREMISE OF THE STUDY: The Bahamas archipelago is formed by young, tectonically stable carbonate banks that harbor direct geological evidence of global ice-volume changes. We sought to detect signatures of major changes on gene flow patterns and reconstruct the phylogeographic history of the monophyletic Zamia pumila complex across the Bahamas. METHODS: Nuclear molecular markers with both high and low mutation rates were used to capture two different time scale signatures and test several gene flow and demographic hypotheses. KEY RESULTS: Single-copy nuclear genes unveiled apparent ancestral admixture on Andros, suggesting a significant role of this island as main hub of diversity of the archipelago. We detected demographic and spatial expansion of the Zamia pumila complex on both paleo-provinces around the Piacenzian (Pliocene)/Gelasian (Pleistocene). Populations evidenced signatures of different migration models that have occurred at two different times. Populations on Long Island (Z. lucayana) may either represent a secondary colonization of the Bahamas by Zamia or a rapid and early-divergence event of at least one population on the Bahamas. CONCLUSIONS: Despite changes in migration patterns with global climate, expected heterozygosity with both marker systems remains within the range reported for cycads, but with significant levels of increased inbreeding detected by the microsatellites. This finding is likely associated with reduced gene flow between and within paleo-provinces, accompanied by genetic drift, as rising seas enforced isolation. Our study highlights the importance of the maintenance of the predominant direction of genetic exchange and the role of overseas dispersion among the islands during climate oscillations.

Characterization and in vitro evaluation of nimotuzumab conjugated with cisplatin-loaded liposomes.

In this paper, we report the conjugation of the humanized monoclonal antibody nimotuzumab with cisplatin-loaded liposomes and the in vitro evaluation of its affinity for tumor cells. The conjugation procedure was performed through derivatization of nimotuzumab with N-succinimidyl S-acetylthioacetate (SATA) followed by a covalent attachment with maleimide groups at the end of PEG-DSPE chains located at the membrane of pre-formed liposomes. Confocal microscopy was performed to evaluate the immunoliposome affinity for EGFR antigens from human epidermoid carcinoma (A-431) and normal lung (MRC-5) cell lines. Results showed that the procedures implemented in this work do not affect the capability of the nimotuzumab-immunoliposomes to recognize the tumor cells, which overexpress the EGFR antigens.

Phylogeny and historical biogeography of the cocosoid palms (Arecaceae, Arecoideae, Cocoseae) inferred from sequences of six WRKY gene family loci.

Arecaceae tribe Cocoseae is the most economically important tribe of palms, including both coconut and African oil palm. It is mostly represented in the Neotropics, with one and two genera endemic to South Africa and Madagascar, respectively. Using primers for six single copy WRKY gene family loci, we amplified DNA from 96 samples representing all genera of the palm tribe Cocoseae as well as outgroup tribes Reinhardtieae and Roystoneae. We compared parsimony (MP), maximum likelihood (ML), and Bayesian (B) analysis of the supermatrix with three species-tree estimation approaches. Subtribe Elaeidinae is sister to the Bactridinae in all analyses. Within subtribe Attaleinae, Lytocaryum, previously nested in Syagrus, is now positioned by MP and ML as sister to the former, with high support; B maintains Lytocaryum embedded within Syagrus. Both MP and ML resolve Cocos as sister to Syagrus; B positions Cocos as sister to Attalea. Bactridineae is composed of two sister clades, Bactris and Desmoncus in one, for which there is morphological support, and a second comprising Acrocomia, Astrocaryum, and Aiphanes. Two B and one ML gene tree-species estimation approaches are incongruent with the supermatrix in a few critical intergeneric clades, but resolve the same infrageneric relationships. The biogeographic history of the Cocoseae is dominated by dispersal events. The tribe originated in the late Cretaceous in South America. Evaluated together, the supermatrix and species tree analyses presented in this paper provide the most accurate picture of the evolutionary history of the tribe to date, with more congruence than incongruence among the various methodologies.

Altered lipid homeostasis is associated with cerebellar neurodegeneration in SNX14 deficiency.

Dysregulated lipid homeostasis is emerging as a potential cause of neurodegenerative disorders. However, evidence of errors in lipid homeostasis as a pathogenic mechanism of neurodegeneration remains limited. Here, we show that cerebellar neurodegeneration caused by Sorting Nexin 14 (SNX14) deficiency is associated with lipid homeostasis defects. Recent studies indicate that SNX14 is an interorganelle lipid transfer protein that regulates lipid transport, lipid droplet (LD) biogenesis, and fatty acid desaturation, suggesting that human SNX14 deficiency belongs to an expanding class of cerebellar neurodegenerative disorders caused by altered cellular lipid homeostasis. To test this hypothesis, we generated a mouse model that recapitulates human SNX14 deficiency at a genetic and phenotypic level. We demonstrate that cerebellar Purkinje cells (PCs) are selectively vulnerable to SNX14 deficiency while forebrain regions preserve their neuronal content. Ultrastructure and lipidomic studies reveal widespread lipid storage and metabolism defects in SNX14-deficient mice. However, predegenerating SNX14-deficient cerebella show a unique accumulation of acylcarnitines and depletion of triglycerides. Furthermore, defects in LD content and telolysosome enlargement in predegenerating PCs suggest lipotoxicity as a pathogenic mechanism of SNX14 deficiency. Our work shows a selective cerebellar vulnerability to altered lipid homeostasis and provides a mouse model for future therapeutic studies.

Disparities in SARS-CoV-2 Infection by Race, Ethnicity, Language, and Social Vulnerability: Evidence from a Citywide Seroprevalence Study in Massachusetts, USA.

OBJECTIVES: Uncovering and addressing disparities in infectious disease outbreaks require a rapid, methodical understanding of local epidemiology. We conducted a seroprevalence study of SARS-CoV-2 infection in Holyoke, Massachusetts, a majority Hispanic city with high levels of socio-economic disadvantage to estimate seroprevalence and identify disparities in SARS-CoV-2 infection. METHODS: We invited 2000 randomly sampled households between 11/5/2020 and 12/31/2020 to complete questionnaires and provide dried blood spots for SARS-CoV-2 antibody testing. We calculated seroprevalence based on the presence of IgG antibodies using a weighted Bayesian procedure that incorporated uncertainty in antibody test sensitivity and specificity and accounted for household clustering. RESULTS: Two hundred eighty households including 472 individuals were enrolled. Three hundred twenty-eight individuals underwent antibody testing. Citywide seroprevalence of SARS-CoV-2 IgG was 13.1% (95% CI 6.9-22.3) compared to 9.8% of the population infected based on publicly reported cases. Seroprevalence was 16.1% (95% CI 6.2-31.8) among Hispanic individuals compared to 9.4% (95% CI 4.6-16.4) among non-Hispanic white individuals. Seroprevalence was higher among Spanish-speaking households (21.9%; 95% CI 8.3-43.9) compared to English-speaking households (10.2%; 95% CI 5.2-18.0) and among individuals in high social vulnerability index (SVI) areas based on the CDC SVI (14.4%; 95% CI 7.1-25.5) compared to low SVI areas (8.2%; 95% CI 3.1-16.9). CONCLUSIONS: The SARS-CoV-2 IgG seroprevalence in a city with high levels of social vulnerability was 13.1% during the pre-vaccination period of the COVID-19 pandemic. Hispanic individuals and individuals in communities characterized by high SVI were at the highest risk of infection. Public health interventions should be designed to ensure that individuals in high social vulnerability communities have access to the tools to combat COVID-19.

Association between chlorine-treated drinking water, the gut microbiome, and enteric pathogen burden in young children in Haiti: an observational study.

OBJECTIVE: The effects of sanitation and hygiene interventions on the gut microbiome and enteric pathogen burden are not well understood. We measured the association between free chlorine residue (FCR) levels in drinking water, microbiome composition, and stool enteric pathogens in infants and young children in Haiti. METHODS: FCR levels were measured in household drinking water and enteric pathogen burden was evaluated using multiplex RT-PCR of stool among 131 children from one month to five years of age living in Mirebalais, Haiti. Microbiome profiling was performed using metagenomic sequencing. RESULTS: Most individuals lived in households with undetectable FCR measured in the drinking water (112/131, 86%). Detection of enteric pathogen DNA in stool was common and did not correlate with household water FCR. The infant microbiome in households with detectable FCR demonstrated reduced richness (fewer total number of species, P=0.04 Kruskall-Wallis test) and less diversity by Inverse Simpson measures (P=0.05) than households with undetectable FCR. Infants in households with a detectable FCR were more likely to have abundant Bifidobacterium. Using in vitro susceptibility testing, we found that some Bifidobacterium species were resistant to chlorine. CONCLUSIONS: FCR in household drinking water did not correlate with enteric pathogen burden in our study.

Gut microbiome perturbation, antibiotic resistance, and Escherichia coli strain dynamics associated with international travel: a metagenomic analysis.

BACKGROUND: Culture-based studies have shown that acquisition of extended-spectrum ß-lactamase-producing Enterobacterales is common during international travel; however, little is known about the role of the gut microbiome before and during travel, nor about acquisition of other antimicrobial-resistant organisms. We aimed to identify (1) whether the gut microbiome provided colonisation resistance against antimicrobial-resistant organism acquisition, (2) the effect of travel and travel behaviours on the gut microbiome, and (3) the scale and global heterogeneity of antimicrobial-resistant organism acquisition. METHODS: In this metagenomic analysis, participants were recruited at three US travel clinics (Boston, MA; New York, NY; and Salt Lake City, UT) before international travel. Participants had to travel internationally between Dec 8, 2017, and April 30, 2019, and have DNA extractions for stool samples both before and after travel for inclusion. Participants were excluded if they had at least one low coverage sample (<1 million read pairs). Stool samples were collected at home before and after travel, sent to a clinical microbiology laboratory to be screened for three target antimicrobial-resistant organisms (extended-spectrum ß-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales), and underwent DNA extraction and shotgun metagenomic sequencing. We profiled metagenomes for taxonomic composition, antibiotic-resistant gene content, and characterised the Escherichia coli population at the strain level. We analysed pre-travel samples to identify the gut microbiome risk factors associated with acquisition of the three targeted antimicrobial resistant organisms. Pre-travel and post-travel samples were compared to identify microbiome and resistome perturbation and E coli strain acquisition associated with travel. FINDINGS: A total of 368 individuals travelled between the required dates, and 296 had DNA extractions available for both before and after travel. 29 travellers were excluded as they had at least one low coverage sample, leaving a final group of 267 participants. We observed a perturbation of the gut microbiota, characterised by a significant depletion of microbial diversity and enrichment of the Enterobacteriaceae family. Metagenomic strain tracking confirmed that 67% of travellers acquired new strains of E coli during travel that were phylogenetically distinct from their pre-travel strains. We observed widespread enrichment of antibiotic-resistant genes in the gut, with a median 15% (95% CI 10-20, p<1 × 10-10) increase in burden (reads per kilobase per million reads). This increase included antibiotic-resistant genes previously classified as threats to public health, which were 56% (95% CI 36-91, p=2 × 10-11) higher in abundance after travel than before. Fluoroquinolone antibiotic-resistant genes were aquired by 97 (54%) of 181 travellers with no detected pre-travel carriage. Although we found that visiting friends or relatives, travel to south Asia, and eating uncooked vegetables were risk factors for acquisition of the three targeted antimicrobial resistant organisms, we did not observe an association between the pre-travel microbiome structure and travel-related antimicrobial-resistant organism acquisition. INTERPRETATION: This work highlights a scale of E coli and antimicrobial-resistant organism acquisition by US travellers not apparent from previous culture-based studies, and suggests that strategies to control antimicrobial-resistant organisms addressing international traveller behaviour, rather than modulating the gut microbiome, could be worthwhile. FUNDING: US Centers for Disease Control and Prevention and National Institute of Allergy and Infectious Diseases.

Primary staging in patients with intermediate- and high-risk prostate cancer: Multiparametric MRI and 68Ga-PSMA-PET/MRI - What is the value of quantitative data from multiparametric MRI alone or in conjunction with clinical information?

PURPOSE: Comparing mpMRI and 68Ga-PSMA-PET/MRI in primary staging of PCa and investigating the value of quantitative mpMRI-measurements for prediction of extracapsular extension and N-metastases. METHODS: Patients with PCa undergoing 68Ga-PSMA-PET/MRI and mpMRI during January 2016 to February 2019 were retrospectively included. Two readers each on 68Ga-PSMA-PET/MRI or mpMRI rated extraprostatic extension (≥T3) and regional lymph-node-metastasis (N1) on a Likert-scale. A fifth reader measured tumor volume, maximum diameter, and capsular contact length on mpMRI. Probability of lymph-node-metastasis was additionally calculated using the 2018 Briganti model. Interobserver-agreement was assessed by squared Cohen's kappa, and diagnostic accuracy was determined using radical prostatectomy (n = 35/49) as reference standard. RESULTS: 49 patients (median age 66 years [IQR: 61-72 years]) were evaluated. Interobserver-agreement for mpMRI and 68Ga-PSMA-PET/MRI was: ≥T3: κ = 0.58/0.47; N1: κ = 0.55/0.92. Diagnostic accuracy for mpMRI vs 68Ga-PSMA-PET/MRI readers for ≥ T3 was AUC: 0.72, 0.62 vs 0.71, 0.72 (p > 0.38) and for N1 was AUC: 0.39, 0.55 vs 0.72, 0.78 (p < 0.01). Quantitative parameters delivered diagnostic accuracies of: AUC: 0.70-0.72 for ≥ T3. The 2018 Briganti model achieved an AUC of 0.89 for N1. CONCLUSIONS: Interreader-agreement regarding ≥ T3 was similar for mpMRI and 68Ga-PSMA-PET/MRI while for N1 it was higher for 68Ga-PSMA-PET/MRI. Diagnostic accuracy was comparable for ≥ T3 while for N1 it was higher in 68Ga-PSMA-PET/MRI and the 2018 Briganti model. Combining clinical data and quantitative data from mpMRI in the 2018 Briganti model yielded the highest AUC for prediction of lymph node metastasis and may aid in selecting patients who will benefit from 68Ga-PSMA-PET/MRI for primary staging.