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This paper reports a multiple case study of a training center collaboration with three offshore companies and a coastline authority. Through a qualitative inquiry, we utilized the actor-network theory to analyze the common understanding of simulator use in these organizations. The paper argues that the simulator itself is an actor that can integrate shared interests with other actors to establish an actor-network. Such an actor-network expands simulator use beyond purely training purposes. It advocates that the simulator is a medium between maritime academia and industry and aligns it with the same actor-network to facilitate the process of "meaning construction." Such a meaning construction process offers simulator-based training with a valuable definition of the learning outcomes. It helps clarifying who will gain the benefits from simulator use in the future, as well as when and on what basis. The paper also reflects on the benefits and limitations of utilizing a multiple case study in the maritime domain.

This article discusses the detection of the cfr gene in Citrobacter braakii and the characterization of two cfr-carrying plasmids from a chicken farm in Jiangxi, China. The cfr gene is a multidrug resistance gene that has spread globally in Gram-positive and Gram-negative bacteria. The study identified three cfr-positive strains, including one C. braakii and two E. coli strains, and found that the cfr gene was located on different plasmids in these strains. The article highlights the widespread distribution and rapid dissemination of cfr in animal-derived bacteria and emphasizes the need for monitoring and control of cfr plasmids. [Extracted from the article]

(1) Many patients with inflammatory bowel disease (IBD) in endoscopic remission have persistent histologic activity, which is associated with worse outcomes. There are limited data on the association between adalimumab drug concentrations and histologic outcomes using validated histologic indices. We aimed to assess the relationship between adalimumab concentrations and the Robarts Histopathology Index (RHI). (2) Patients from a tertiary IBD center from 2013 to 2020 with serum adalimumab (ADA) trough concentrations measured during maintenance therapy (≥14 weeks) and a colonoscopy or flexible sigmoidoscopy with biopsies performed within 90 days of drug level were included. Blinded histologic scoring using the RHI was performed. Primary analysis assessed the relationship between adalimumab drug concentrations and histologic remission using receiver operating characteristic curve analysis. (3) In 36 patients (26 Crohn's Disease, 9 ulcerative colitis, 1 indeterminate), median adalimumab concentrations were higher (17.3 ug/mL, 12.2–24.0) in patients with histologic remission compared to those without (10.3 ug/mL, 6.8–13.9, p = 0.008). The optimal ADA concentration identified using the Youden threshold was ≥16.3 ug/mL (sensitivity 70%, specificity 90%). Patients with ADA ≥ 16.3 ug/mL had higher histologic remission rates (78%) compared to lower ADA concentrations (14%, p= 0.002), as well as higher mucosal healing rates (86%) compared to lower levels (12%, p = 0.001). Symptoms correlated weakly and non-significantly with both histologic (RHI) scores (r = 0.25, p = 0.2) and adalimumab concentrations (r = 0.05, p = 0.8). (4) The current study demonstrated that higher serum adalimumab concentrations (≥16.3 ug/mL) are needed for histologic remission and mucosal healing assessed using the RHI. [ABSTRACT FROM AUTHOR]

Objectives: To characterize a novel tigecycline resistance gene, tet(X6), and a novel SXT-related integrative and conjugative element (ICE), ICEPgs6Chn1, found in a tigecycline-resistant Proteus genomospecies 6 strain, T60.Methods: Strain T60 was identified by the VITEK 2 system, biochemical reactions and an SNP-based approach. The genetic profile of strain T60 was determined by WGS analysis. ICEPgs6Chn1 was analysed by PCR, conjugation experiments and bioinformatics tools. tet(X6) was characterized by cloning and protein structure prediction.Results: Strain T60 was resistant to ampicillin, tetracycline, tigecycline, florfenicol, colistin and kanamycin, but susceptible to cefotaxime; it also exhibited high MICs of eravacycline (32 mg/L) and omadacycline (>64 mg/L). Only one chromosome was identified and tet(X6) was located in chromosomal ICEPgs6Chn1, a member of the SXT/R391 ICE family, of 114 368 bp and encoding the antimicrobial resistance genes floR, strB, strA, aph(3')-Ia, aac(3)-IV, aph(4)-Ia, tet(X6) and sul2. The circular intermediate of ICEPgs6Chn1 was detected by PCR and sequencing, but conjugation experiments showed that it was not self-transmissible. Cloning of the novel gene tet(X6) and protein structure prediction revealed that Tet(X6) confers tigecycline resistance.Conclusions: To our knowledge, this is the first report of a novel SXT/R391 ICE in a Proteus genomospecies 6 strain. Importantly, a novel high-level tigecycline resistance gene, tet(X6), emerged for the first time in the SXT/R391 element of Proteus genomospecies 6, revealing that ICEs may serve as an important platform for the accumulation of antibiotic resistance genes. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the complete sequences of four plasmids in MCR-1-producing clinical Escherichia coli strain D72, and to depict the formation mechanism and characteristics of the cointegrate plasmid derived from the pD72-mcr1 and pD72-F33 plasmids.Methods: The genetic profiles of plasmids in strain D72 and its transconjugant were determined by conjugation, S1-PFGE, Southern hybridization, WGS analysis and PCR. Plasmid sequences were analysed with bioinformatic tools. The traits of the fusion plasmid were characterized by cointegration, stability and conjugation assays.Results: Strain D72, belonging to ST1114, contained four plasmids, including mcr-1-carrying pD72-mcr1, blaCTX-M-55-carrying pD72-F33, blaTEM-238-bearing pD72-IncP and pD72-IncX1 carrying aph(3')-Ia, qnrS2 and floR. A single plasmid, pD72C, in the transconjugant was found to be larger than any plasmid in the original strain D72. Sequence analysis showed that pD72C was the fusion product of pD72-mcr1 and pD72-F33, and the recombinant event involved an intermolecular replicative mechanism. Plasmid fusion occurred at a frequency of 1.75 × 10-4 cointegrates per transconjugant. The fusion plasmid presented a high stability and conjugation frequency of 8.00 × 10-3.Conclusions: To our knowledge, this is the first report of the IS26-mediated fusion of an IncN1-F33:A-:B- plasmid and an mcr-1-carrying phage-like plasmid, providing evidence for the important role of IS26 in the recombination of plasmids. The biological advantages of the fusion plasmid indicated that the fusion event presumably plays a potential role in the dissemination of mcr-1. [ABSTRACT FROM AUTHOR]

This paper focuses on the process of translating insights from a Computer Supported Cooperative Work (CSCW)-based study, conducted on a vessel at sea, into a model that can assist systems developers working with simulators, which are used by vessel operators for training purposes on land. That is, the empirical study at sea brought about rich insights into cooperation, which is important for systems developers to know about and consider in their designs. In the paper, we establish a model that primarily consists of a 'computational artifact'. The model is designed to support researchers working with systems developers. Drawing on marine examples, we focus on the translation process and investigate how the model serves to visualize work activities; how it addresses relations between technical and computational artifacts, as well as between functions in technical systems and functionalities in cooperative systems. In turn, we link design back to fieldwork studies. [ABSTRACT FROM AUTHOR]

Modern operating systems are increasingly complex and require a large number of individual subsystems and procedures; operators also must cooperate to make them function. In this paper the authors consider usability from a broad perspective based on this understanding, recognizing the challenges a team of operators, complex subsystems, and other technical aspects pose as they work together. It seeks to expand usability by adding insights from Computer- Supported Cooperative Work (CSCW)-based fieldwork in offshore operations. To contribute to the current usability literature, we investigated and analyzed through a network-based approach how operators, ship bridge hardware and software, and other physical environments work together. We propose a process for evaluating the usability of complex systems: field observation and interviews to determine how work is organized and executed by human and nonhuman actors and to identify whether additional artifacts are being used to supplement the nonhuman components. The use of those artifacts often identifies usability issues in complex systems. [ABSTRACT FROM AUTHOR]

Background: The mammillary bodies (MB) share direct connections with key components of memory circuitry including the hippocampus. Additionally, MB atrophy is present in a number of clinical conditions including late stages of Alzheimer’s disease (AD); however, whether MB atrophy occurs in early stages of AD remains unclear. Voxel‐Based Morphometry (VBM) was conducted to determine whether structural changes to MB are an early feature of AD and to quantify the association between MB atrophy and performance on neurocognitive assessments. Method: This cross‐sectional study included subjects (n=470) from the Alzheimer’s Disease Neuroimaging Initiative aged ≥ 50 years with volumetric T1‐weighted MR scans at 3 Tesla and cerebrospinal fluid (CSF) AD biomarkers. Normal cognition (cognitively normal, CN, and preclinical AD) was defined as Clinical Dementia Rating (CDR) of 0. Based on previously established criteria, CN subjects (n=112) were negative for CSF AD pathology, while preclinical AD (n=39), early mild cognitive impairment (EMCI, n=108), late mild cognitive impairment (LMCI, n=100), and AD (n=111) subjects were positive for CSF AD pathology. Average grey matter (GM) densities in the MB, hippocampus, and cerebellar vermis were assessed by VBM (SPM12 with MarsBaR toolbox). Result: GM densities in MB and hippocampi decreased with worsening clinical severity with significant differences beginning in the EMCI stage for both regions. Compared to CN subjects, the relative decrease in GM densities was greater in MB than in the hippocampi in EMCI, LMCI, and AD subjects. Cerebellar vermian GM densities were similar across all groups. Adjusting for age and sex, MB GM densities were associated with CSF levels of amyloid‐β42 (β=0.189, p<0.001) but not with tau or phosphorylated‐tau181 (p>0.05). Hippocampal GM densities were associated with all CSF AD biomarkers (p<0.05). Adjusting for age, sex, and education, MB and hippocampal GM densities were associated with Mini‐Mental State Examination (MB: β=0.270, p<0.001, hippocampi β=0.512, p<0.001) and CDR Sum of Boxes (MB: β=‐0.337, p<0.001, hippocampi: β=‐0.561, p<0.001). Conclusion: Evidence for MB atrophy was found in early stages of AD and increased with clinical severity, correlating with CSF amyloid‐β42 and neurocognitive measures. These findings support MB atrophy as an early manifestation of AD. [ABSTRACT FROM AUTHOR]

Background: The plasmid-encoded multidrug efflux pump oqxAB confers bacterial resistance primarily to olaquindox, quinolones, and chloramphenicol. The aims of this study were to investigate the prevalence of oqxAB among Escherichia coli isolates from dogs, cats, and humans in Henan, China and the susceptibilities of E. coli isolates to common antibiotics. Methods: From 2012 to 2014, a total of 600 samples which included 400 rectal samples and 200 clinical human specimens were tested for the presence of E. coli. All isolates were screened for oqxAB genes by PCR and sequencing. The MICs of 11 antimicrobial agents were determined by the broth microdilution method. A total of 30 representative oqxAB-positive isolates were subjected to ERIC-PCR and MLST. Additionally, conjugation experiments and southern hybridizations were performed. Results: Of 270 isolates, 58.5% (62/106) of the isolates from dogs, 56.25% (36/64) of the isolates from cats, and 42.0% (42/100) of the isolates from humans were positive for the oqxAB. Olaquindox resistance was found for 85.7%-100% of oqxAB-positive isolates. Of oqxAB-positive isolates from dogs, cats, and humans, ciprofloxacin resistance was inspected for 85.8%, 59.1%, and 93.8%, respectively. Several oqxAB-positive isolates were demonstrated by ERIC-PCR and MLST, and have high similarity. Phylogenetic analysis showed that oqxAB-positive isolates could be divided into 7 major clusters. OqxAB-positive conjugants were obtained, southern hybridization verified that the oqxAB gene complex was primarily located on plasmids. Conclusion: In conclusion, oqxAB-positive isolates were widespread in animals and humans in Henan, China. Carriage of oqxAB on plasmids of E. coli isolates may facilitate the emergence of multidrug resistant and its transmission via horizontal transfer, and might pose a potential threat to public health. [ABSTRACT FROM AUTHOR]

This study was designed to depict prevalence and antimicrobial resistance characteristics of Proteus mirabilis ( P. mirabilis ) strains in 4 chicken farms and to probe the transfer mechanism of resistance genes. A total of 187 P. mirabilis isolates were isolated from 4 chicken farms. The susceptibility testing of these isolates to 14 antimicrobials showed that the multidrug resistance (MDR) rate was as high as 100%. The β-lactamase resistance genes bla OXA-1 , bla CTX-M-1G , bla CTX-M-9G and colistin resistance gene mcr-1 were highly carried in the P. mirabilis isolates. An MDR strain W47 was selected for whole genome sequencing (WGS) and conjugation experiment. The results showed that W47 carried 23 resistance genes and 64 virulence genes, and an SXT/R391 integrated conjugative elements (ICEs) named ICE Pmi Chn5 carrying 17 genes was identified in chromosome. ICE Pmi Chn5 was able to be excised from the chromosome of W47 forming a circular intermediate, but repeated conjugation experiments were unsuccessful. Among 187 P. mirabilis isolates, 144 (77.01%, 144/187) isolates carried ICE Pmi Chn5-like ICEs, suggesting that ICEs may be the major vector for the transmission of resistance genes among MDR chicken P. mirabilis strains in this study. The findings were conducive to insight into the resistance mechanism of chicken P. mirabilis strains and provide a theoretical basis for the use of antibiotics for the treatment of MDR P. mirabilis infections in veterinary clinic. [ABSTRACT FROM AUTHOR]

It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr -1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella. • In our study, the combination of tetrandrine and colistin drastically enhanced colistin bactericidal activity compared with monotreatment. • In-depth mechanistic analysis showed that tetrandrine potentiated colistin activity through enhancing the membrane-damaging ability of colistin. • Tetrandrine dramatically undermines the function of PMF and result in decreased intracellular ATP levels. In addition, the activity of efflux pump was significantly inhibited by the addition of tetrandrine in both single or combination treatments. • Tetrandrine not only affects the expression of mcr -1 but also as an effective MCR-1 inhibitor. • The discovery of tetrandrine as a potential adjuvant for colistin therapy in combination therapy for severe infections caused by MCR-1 positive Salmonella. [ABSTRACT FROM AUTHOR]