Modeling Fatigue in Manual and Robot-Assisted Work for Operator 5.0.

Fatigue, and many other human performance factors, impact worker wellbeing, and thus production quality and efficiency. Adopting the Industry 5.0 perspective, we propose that integrating human performance models into wider industrial system models can improve modeling accuracy and lead to superior outcomes. Integrating our Worker Fatigue Model as part of their industrial system architect model allowed Airbus, a leading aircraft manufacturer, to more accurately predict system performance as a function of the workforce makeup, which could be a combination of human workers and robots, or a combination of highly experienced and less experienced workers. Our approach demonstrates the importance and value of including human performance models in trade studies for introducing robots on the shop floor, and can be used to include various aspects of human performance in industrial system models to address specific task requirements or different levels of automation.

IL-13-driven alterations in hepatic cholesterol handling contributes to hypercholesterolemia in a rat model of minimal change disease.

Circulating factors have been implicated in the pathogenesis of minimal change disease (MCD), and may have direct effects on cholesterol metabolism. This study investigated the pathogenesis of hypercholesterolemia in an IL-13 overexpression rat model of MCD prior to the onset of proteinuria, so as to establish the direct contribution of IL-13, especially with regard to hepatic cholesterol handling. In this model of MCD, the temporal relationship between hypercholesterolemia and proteinuria was first identified. Plasma proprotein convertase subtilisin/kexin type 9 (Pcsk9) and liver ATP-binding cassette sub-family G member 5 (Abcg5) were measured using ELISA. Liver Ldlr and liver X receptor alpha (Lxra) were quantified with Western blot. Abcg5-mediated cholesterol efflux in IL-13-stimulated rat primary hepatocytes was measured using taurocholate as cholesterol acceptor. The role of Lxra was validated using a luciferase assay in Lxre-luciferase-transfected IL-13-stimulated hepatocytes. IL-13-transfected rats developed hypercholesterolemia prior to proteinuria, with 35% of rats hypercholesterolemic but only 11% proteinuric by Day 20 (P = 0.04). These pre-proteinuric hypercholesterolemic rats showed elevations in total and LDL-cholesterol, but not hypertriglyceridemia or hepatic steatosis. The hypercholesterolemia was associated with increased hepatic Pcsk9 synthesis and enhanced circulating Pcsk9 levels, which correlated strongly with plasma total cholesterol (r = 0.73, P<0.001). The hypercholesterolemia was also contributed by decreased Abcg5 expression and activity, due to reduced Lxra expression. Lxra expression correlated with plasma total cholesterol levels (r = -0.52, P = 0.01), and overexpression of pLxra in rat hepatocytes abrogated the IL-13-mediated down-regulation of Lxre-driven gene expression. In conclusion, we have shown that IL-13 induced changes in hepatic cholesterol handling in a cytokine-induced rat model of MCD, resulting in hypercholesterolemia which can precede the onset of proteinuria.

Architecture of population-differentiated polymorphisms in the human genome.

Population variation in disease and other phenotype are partly attributed to single nucleotide polymorphisms (SNPs) in the human genome. Due to selection pressure, two individuals from the same ancestral population have more genetic similarity compared to individuals from further geographic regions. Here, we elucidated the genomic population differentiation pattern, by interrogating >22,000,000 SNPs. Majority of population-differentiated (pd) SNPs (~95%), including the potentially functional (pf) (~84%) subset reside in non-genic regions, compared to the proportion of all SNPs (58%) found in non-genic regions. This suggests that differences between populations are more likely due to differences in gene regulation rather than protein function. Actin Cytoskeleton, Axonal Guidance and Protein Kinase A signaling pathways are enriched with genes carrying at least three pdSNPs (enriched pdGenes), while Antigen Presentation, Hepatic Fibrosis and Huntington Disease Signalling pathways are over-represented by enriched pf-pdGenes. An inverse correlation between chromosome size and the proportion of pd-/pf-pdSNPs was observed. Smaller chromosomes have relatively more of such SNPs including genes carrying these SNPs. Genes associated with common diseases and enriched with these pd-/pfpdSNPs are localized to 11 different chromosomes, with immune-related disease pd/pf-pdGenes mainly residing in chromosome 6 while neurological disease pd/pf-pdGenes residing in smaller chromosomes including chromosome 21/22. The associated diseases were reported to show population differences in incidence, severity and/or etiology. In summary, this study highlights the non-sporadic nature of population differentiation footprint in the human genome, which can potentially lead to the identification of genomic regions that play roles in the manifestation of phenotypic differences, including in disease predisposition and drug response.

Towards precision medicine: interrogating the human genome to identify drug pathways associated with potentially functional, population-differentiated polymorphisms.

Drug response variations amongst different individuals/populations are influenced by several factors including allele frequency differences of single nucleotide polymorphisms (SNPs) that functionally affect drug-response genes. Here, we aim to identify drugs that potentially exhibit population differences in response using SNP data mining and analytics. Ninety-one pairwise-comparisons of >22,000,000 SNPs from the 1000 Genomes Project, across 14 different populations, were performed to identify 'population-differentiated' SNPs (pdSNPs). Potentially-functional pdSNPs (pf-pdSNPs) were then selected, mapped into genes, and integrated with drug-gene databases to identify 'population-differentiated' drugs enriched with genes carrying pf-pdSNPs. 1191 clinically-approved drugs were found to be significantly enriched (Z > 2.58) with genes carrying SNPs that were differentiated in one or more population-pair comparisons. Thirteen drugs were found to be enriched with such differentiated genes across all 91 population-pairs. Notably, 82% of drugs, which were previously reported in the literature to exhibit population differences in response were also found by this method to contain a significant enrichment of population specific differentiated SNPs. Furthermore, drugs with genetic testing labels, or those suspected to cause adverse reactions, contained a significantly larger number (P < 0.01) of population-pairs with enriched pf-pdSNPs compared with those without these labels. This pioneering effort at harnessing big-data pharmacogenomics to identify 'population differentiated' drugs could help to facilitate data-driven decision-making for a more personalized medicine.

Comprehensive analysis of transcriptome profiles in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is the second most deadly cancer with late presentation and limited treatment options, highlighting an urgent need to better understand HCC to facilitate the identification of early-stage biomarkers and uncover therapeutic targets for the development of novel therapies for HCC. METHODS: Deep transcriptome sequencing of tumor and paired non-tumor liver tissues was performed to comprehensively evaluate the profiles of both the host and HBV transcripts in HCC patients. Differential gene expression patterns and the dys-regulated genes associated with clinical outcomes were analyzed. Somatic mutations were identified from the sequencing data and the deleterious mutations were predicted. Lastly, human-HBV chimeric transcripts were identified, and their distribution, potential function and expression association were analyzed. RESULTS: Expression profiling identified the significantly upregulated TP73 as a nodal molecule modulating expression of apoptotic genes. Approximately 2.5% of dysregulated genes significantly correlated with HCC clinical characteristics. Of the 110 identified genes, those involved in post-translational modification, cell division and/or transcriptional regulation were upregulated, while those involved in redox reactions were downregulated in tumors of patients with poor prognosis. Mutation signature analysis identified that somatic mutations in HCC tumors were mainly non-synonymous, frequently affecting genes in the micro-environment and cancer pathways. Recurrent mutations occur mainly in ribosomal genes. The most frequently mutated genes were generally associated with a poorer clinical prognosis. Lastly, transcriptome sequencing suggest that HBV replication in the tumors of HCC patients is rare. HBV-human fusion transcripts are a common observation, with favored HBV and host insertion sites being the HBx C-terminus and gene introns (in tumors) and introns/intergenic-regions (in non-tumors), respectively. HBV-fused genes in tumors were mainly involved in RNA binding while those in non-tumors tissues varied widely. These observations suggest that while HBV may integrate randomly during chronic infection, selective expression of functional chimeric transcripts may occur during tumorigenesis. CONCLUSIONS: Transcriptome sequencing of HCC patients reveals key cancer molecules and clinically relevant pathways deregulated/mutated in HCC patients and suggests that while HBV may integrate randomly during chronic infection, selective expression of functional chimeric transcripts likely occur during the process of tumorigenesis.

Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) volunteers and finally in a 3rd cohort comprising NH, CHB, cirrhotic and HCC volunteers to evaluate miRNA changes during disease progression. The associations between circulating miRNAs and liver-damage markers, clinicopathological characteristics and survival outcomes were analysed to identify prognostic markers. Twelve miRNAs are differentially expressed between HCC and NH individuals in all three cohorts. Five upregulated miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p and miR-148a-3p) in CHB, cirrhosis and HCC patients are potential biomarkers for CHB infection, while miR-34a-5p can be a biomarker for cirrhosis. Notably, four miRNAs (miR-1972, miR-193a-5p, miR-214-3p and miR-365a-3p) can distinguish HCC from other non-HCC individuals. Six miRNAs are potential prognostic markers for overall survival.

Architecture of polymorphisms in the human genome reveals functionally important and positively selected variants in immune response and drug transporter genes.

BACKGROUND: Genetic polymorphisms can contribute to phenotypic differences amongst individuals, including disease risk and drug response. Characterization of genetic polymorphisms that modulate gene expression and/or protein function may facilitate the identification of the causal variants. Here, we present the architecture of genetic polymorphisms in the human genome focusing on those predicted to be potentially functional/under natural selection and the pathways that they reside. RESULTS: In the human genome, polymorphisms that directly affect protein sequences and potentially affect function are the most constrained variants with the lowest single-nucleotide variant (SNV) density, least population differentiation and most significant enrichment of rare alleles. SNVs which potentially alter various regulatory sites, e.g. splicing regulatory elements, are also generally under negative selection. Interestingly, genes that regulate the expression of transcription/splicing factors and histones are conserved as a higher proportion of these genes is non-polymorphic, contain ultra-conserved elements (UCEs) and/or has no non-synonymous SNVs (nsSNVs)/coding INDELs. On the other hand, major histocompatibility complex (MHC) genes are the most polymorphic with SNVs potentially affecting the binding of transcription/splicing factors and microRNAs (miRNA) exhibiting recent positive selection (RPS). The drug transporter genes carry the most number of potentially deleterious nsSNVs and exhibit signatures of RPS and/or population differentiation. These observations suggest that genes that interact with the environment are highly polymorphic and targeted by RPS. CONCLUSIONS: In conclusion, selective constraints are observed in coding regions, master regulator genes, and potentially functional SNVs. In contrast, genes that modulate response to the environment are highly polymorphic and under positive selection.

Investigating the Promoter of FAT10 Gene in HCC Patients.

FAT10, which is also known as diubiquitin, has been implicated to play important roles in immune regulation and tumorigenesis. Its expression is up-regulated in the tumors of Hepatocellular Carcinoma (HCC) and other cancer patients. High levels of FAT10 in cells have been shown to result in increased mitotic non-disjunction and chromosome instability, leading to tumorigenesis. To evaluate whether the aberrant up-regulation of the FAT10 gene in the tumors of HCC patients is due to mutations or the aberrant methylation of CG dinucleotides at the FAT10 promoter, sequencing and methylation-specific sequencing of the promoter of FAT10 was performed. No mutations were found that could explain the differential expression of FAT10 between the tumor and non-tumorous tissues of HCC patients. However, six single nucleotide polymorphisms (SNPs), including one that has not been previously reported, were identified at the promoter of the FAT10 gene. Different haplotypes of these SNPs were found to significantly mediate different FAT10 promoter activities. Consistent with the experimental observation, differential FAT10 expression in the tumors of HCC patients carrying haplotype 1 was generally higher than those carrying haplotype II. Notably, the methylation status of this promoter was found to correlate with FAT10 expression levels. Hence, the aberrant overexpression of the FAT10 gene in the tumors of HCC patients is likely due to aberrant methylation, rather than mutations at the FAT10 promoter.

Validation of the VBLaST pattern cutting task: a learning curve study.

BACKGROUND: Mastery of laparoscopic skills is essential in surgical practice and requires considerable time and effort to achieve. The Virtual Basic Laparoscopic Skill Trainer (VBLaST-PC©) is a virtual simulator that was developed as a computerized version of the pattern cutting (PC) task in the Fundamentals of Laparoscopic Surgery (FLS) system. To establish convergent validity for the VBLaST-PC©, we assessed trainees' learning curves using the cumulative summation (CUSUM) method and compared them with those on the FLS. METHODS: Twenty-four medical students were randomly assigned to an FLS training group, a VBLaST training group, or a control group. Fifteen training sessions, 30 min in duration per session per day, were conducted over 3 weeks. All subjects completed pretest, posttest, and retention test (2 weeks after posttest) on both the FLS and VBLaST© simulators. Performance data, including time, error, FLS score, learning rate, learning plateau, and CUSUM score, were analyzed. RESULTS: The learning curve for all trained subjects demonstrated increasing performance and a performance plateau. CUSUM analyses showed that five of the seven subjects reached the intermediate proficiency level but none reached the expert proficiency level after 150 practice trials. Performance was significantly improved after simulation training, but only in the assigned simulator. No significant decay of skills after 2 weeks of disuse was observed. Control subjects did not show any learning on the FLS simulator, but improved continually in the VBLaST simulator. CONCLUSIONS: Although VBLaST©- and FLS-trained subjects demonstrated similar learning rates and plateaus, the majority of subjects required more than 150 trials to achieve proficiency. Trained subjects demonstrated improved performance in only the assigned simulator, indicating specificity of training. The virtual simulator may provide better opportunities for learning, especially with limited training exposure.

OR fire virtual training simulator: design and face validity.

BACKGROUND: The Virtual Electrosurgical Skill Trainer is a tool for training surgeons the safe operation of electrosurgery tools in both open and minimally invasive surgery. This training includes a dedicated team-training module that focuses on operating room (OR) fire prevention and response. The module was developed to allow trainees, practicing surgeons, anesthesiologist, and nurses to interact with a virtual OR environment, which includes anesthesia apparatus, electrosurgical equipment, a virtual patient, and a fire extinguisher. Wearing a head-mounted display, participants must correctly identify the "fire triangle" elements and then successfully contain an OR fire. Within these virtual reality scenarios, trainees learn to react appropriately to the simulated emergency. A study targeted at establishing the face validity of the virtual OR fire simulator was undertaken at the 2015 Society of American Gastrointestinal and Endoscopic Surgeons conference. METHODS: Forty-nine subjects with varying experience participated in this Institutional Review Board-approved study. The subjects were asked to complete the OR fire training/prevention sequence in the VEST simulator. Subjects were then asked to answer a subjective preference questionnaire consisting of sixteen questions, focused on the usefulness and fidelity of the simulator. RESULTS: On a 5-point scale, 12 of 13 questions were rated at a mean of 3 or greater (92%). Five questions were rated above 4 (38%), particularly those focusing on the simulator effectiveness and its usefulness in OR fire safety training. A total of 33 of the 49 participants (67%) chose the virtual OR fire trainer over the traditional training methods such as a textbook or an animal model. CONCLUSIONS: Training for OR fire emergencies in fully immersive VR environments, such as the VEST trainer, may be the ideal training modality. The face validity of the OR fire training module of the VEST simulator was successfully established on many aspects of the simulation.

Hepatitis B Virus X Protein and Hepatocarcinogenesis.

Chronic hepatitis B virus (HBV) infection is one of the most associated factors in hepatocarcinogenesis. HBV is able to integrate into the host genome and encode the multi-functional hepatitis B virus x protein (HBx). Although the mechanism between HBx and carcinogenesis is still elusive, recent studies have shown that HBx was able to influence various signaling pathways, as well as epigenetic and genetic processes. This review will examine and summarize recent literature about HBx's role in these various processes.

Face and content validation of a Virtual Translumenal Endoscopic Surgery Trainer (VTEST™).

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is an emerging surgical paradigm, where peritoneal access is achieved through one of the natural orifices of the body. It is being reported as a safe and feasible surgical technique with significantly reduced external scarring. Virtual Translumenal Endoscopic Surgical Trainer (VTEST™) is the first virtual reality simulator for the NOTES. The VTEST™ simulator was developed to train surgeons in the hybrid transvaginal NOTES cholecystectomy procedure. The initial version of the VTEST™ simulator underwent face validation at the 2013 Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) summit. Several areas of improvement were identified as a result, and the corresponding modifications were implemented in the simulator. This manuscript outlines the results of the subsequent evaluation study, performed in order to assess the face and content validity of the latest VTEST™ simulator. METHODS: Twelve subjects participated in an institutional review board-approved study that took place at the 2014 NOSCAR summit. Six of the 12 subjects, who are experts with NOTES experience, were used for face and content validation. The subjects performed the hybrid transvaginal NOTES cholecystectomy procedure on VTEST™ that included identifying the Calot's triangle, clipping and cutting the cystic duct/artery, and detaching the gallbladder. The subjects then answered five-point Likert scale feedback questionnaires for face and content validity. RESULTS: Overall, subjects rated 12/15 questions as 3.0 or greater (60 %), for face validity questions regarding the realism of the anatomical features, interface, and the tasks. Subjects also highly rated the usefulness of the simulator in learning the fundamental NOTES technical skills (3.50 ± 0.84). Content validity results indicate a high level of usefulness of the VTEST™ for training prior to operating room experience (4.17 ± 0.75).

Use of stochastic resonance methods for improving laparoscopic surgery performance.

BACKGROUND: Vibrotactile feedback (VIB) has been utilized in previous research as sensory augmentation to improve performance during minimally invasive surgical tasks. Stochastic resonance (SR), introduced into the human control system as white noise at a subthreshold level, has shown promise to improve the sensitivity of tactile receptors resulting in performance enhancement for sensorimotor tasks. The purpose of this study was to determine whether SR could improve performance (accuracy, speed) in a simulated laparoscopic palpation task. METHODS: Sixteen subjects performed a palpation task using a laparoscopic tool to detect the presence of tumors (compacted felt) embedded in simulated tissue samples (silicone gel) inside a laparoscopic trainer box. Subjects were randomly assigned to one of the four different conditions: (1) SR, (2) VIB, (3) VIB + SR, and (4) Control. The VIB and SR signals were administered via two separate haptic actuators attached to the subjects' dominant upper arms and forearms, respectively. All subjects were presented with 36 tissue samples with no sensory augmentation (Control) to establish baseline, followed by another 36 samples under one of the randomly assigned vibration conditions (SR, VIB, VIB + SR, or Control). RESULTS: Results show a significantly larger improvement in tumor detection accuracy in the SR group compared to the VIB and Control groups. There was no difference in the time to task completion, indicating that there was no speed-accuracy trade-off. CONCLUSIONS: The results have implications for the design of instruments and methods for increasing detection accuracy such as in palpation tasks. This technology could help surgeons better identify tumors located in healthy surrounding tissue.

Achieving Interface and Environment Fidelity in the Virtual Basic Laparoscopic Surgical Trainer.

Virtual reality trainers are educational tools with great potential for laparoscopic surgery. They can provide basic skills training in a controlled environment and free of risks for patients. They can also offer objective performance assessment without the need for proctors. However, designing effective user interfaces that allow the acquisition of the appropriate technical skills on these systems remains a challenge. This paper aims to examine a process for achieving interface and environment fidelity during the development of the Virtual Basic Laparoscopic Surgical Trainer (VBLaST). Two iterations of the design process were conducted and evaluated. For that purpose, a total of 42 subjects participated in two experimental studies in which two versions of the VBLaST were compared to the accepted standard in the surgical community for training and assessing basic laparoscopic skills in North America, the FLS box-trainer. Participants performed 10 trials of the peg transfer task on each trainer. The assessment of task performance was based on the validated FLS scoring method. Moreover, a subjective evaluation questionnaire was used to assess the fidelity aspects of the VBLaST relative to the FLS trainer. Finally, a focus group session with expert surgeons was conducted as a comparative situated evaluation after the first design iteration. This session aimed to assess the fidelity aspects of the early VBLaST prototype as compared to the FLS trainer. The results indicate that user performance on the earlier version of the VBLaST resulting from the first design iteration was significantly lower than the performance on the standard FLS box-trainer. The comparative situated evaluation with domain experts permitted us to identify some issues related to the visual, haptic and interface fidelity on this early prototype. Results of the second experiment indicate that the performance on the second generation VBLaST was significantly improved as compared to the first generation and not significantly different from that of the standard FLS box-trainer. Furthermore, the subjects rated the fidelity features of the modified VBLaST version higher than the early version. These findings demonstrate the value of the comparative situated evaluation sessions entailing hands on reflection by domain experts to achieve the environment and interface fidelity and training objectives when designing a virtual reality laparoscopic trainer. This suggests that this method could be used successfully in the future to enhance the value of VR systems as an alternative to physical trainers for laparoscopic surgery skills. Some recommendations on how to use this method to achieve the environment and interface fidelity of a VR laparoscopic surgical trainer are identified.

A systematic review of the effect of distraction on surgeon performance: directions for operating room policy and surgical training.

BACKGROUND: Distractions during surgical procedures have been linked to medical error and team inefficiency. This systematic review identifies the most common and most significant forms of distraction in order to devise guidelines for mitigating the effects of distractions in the OR. METHODS: In January 2015, a PubMed and Google Scholar search yielded 963 articles, of which 17 (2 %) either directly observed the occurrence of distractions in operating rooms or conducted a laboratory experiment to determine the effect of distraction on surgical performance. RESULTS: Observational studies indicated that movement and case-irrelevant conversation were the most frequently occurring distractions, but equipment and procedural distractions were the most severe. Laboratory studies indicated that (1) auditory and mental distractions can significantly impact surgical performance, but visual distractions do not incur the same level of effects; (2) task difficulty has an interaction effect with distractions; and (3) inexperienced subjects reduce their speed when faced with distractions, while experienced subjects did not. CONCLUSION: This systematic review suggests that operating room protocols should ensure that distractions from intermittent auditory and mental distractions are significantly reduced. In addition, surgical residents would benefit from training for intermittent auditory and mental distractions in order to develop automaticity and high skill performance during distractions, particularly during more difficult surgical tasks. It is unclear as to whether training should be done in the presence of distractions or distractions should only be used for post-training testing of levels of automaticity.

Face and construct validation of a next generation virtual reality (Gen2-VR) surgical simulator.

INTRODUCTION: Surgical performance is affected by distractors and interruptions to surgical workflow that exist in the operating room. However, traditional surgical simulators are used to train surgeons in a skills laboratory that does not recreate these conditions. To overcome this limitation, we have developed a novel, immersive virtual reality (Gen2-VR) system to train surgeons in these environments. This study was to establish face and construct validity of our system. METHODS AND PROCEDURES: The study was a within-subjects design, with subjects repeating a virtual peg transfer task under three different conditions: Case I: traditional VR; Case II: Gen2-VR with no distractions and Case III: Gen2-VR with distractions and interruptions. In Case III, to simulate the effects of distractions and interruptions, music was played intermittently, the camera lens was fogged for 10 s and tools malfunctioned for 15 s at random points in time during the simulation. At the completion of the study subjects filled in a 5-point Likert scale feedback questionnaire. A total of sixteen subjects participated in this study. RESULTS: Friedman test showed significant difference in scores between the three conditions (p < 0.0001). Post hoc analysis using Wilcoxon signed-rank tests with Bonferroni correction further showed that all the three conditions were significantly different from each other (Case I, Case II, p < 0.0001), (Case I, Case III, p < 0.0001) and (Case II, Case III, p = 0.009). Subjects rated that fog (mean 4.18) and tool malfunction (median 4.56) significantly hindered their performance. CONCLUSION: The results showed that Gen2-VR simulator has both face and construct validity and that it can accurately and realistically present distractions and interruptions in a simulated OR, in spite of limitations of the current HMD hardware technology.

The effect of stress on learning in surgical skill acquisition.

BACKGROUND: An excessive level of stress and anxiety in medical education can have a negative impact on learning. In particular, the interaction between attending surgeons and trainees in the operating room could induce stress on trainees that is counterproductive, especially if the teaching style or feedback is unduly harsh or critical. AIM: To characterize the effects of stress resulting from attending-trainee interaction during surgical skill acquisition. METHODS: Forty medical students learned to perform the FLS pattern-cutting task for the first time in one of four scenarios. In the control condition, no mentor was present. In the three experimental conditions, participants were observed, encouraged, or criticized by an expert surgeon. RESULTS: Task performance, as well as physiological and subjective indicators of stress, were measured. Taking both speed and accuracy into account, participants who were criticized performed the worst on the task, and those who were encouraged performed best. Physiological and subjective measures indicated that the criticized participants experienced the highest level of stress and anxiety. CONCLUSION: Even though providing constructive criticism to trainees is inevitable during the course of teaching, an exceedingly critical and negative mentoring style by attending physicians could be detrimental to trainees' acquisition of surgical skills.

Haptic Communication in Collaborative Virtual Environments.

OBJECTIVE: To understand the interaction between haptic and verbal communication, we quantified the relative effect of verbal, haptic, and haptic-plus-verbal feedback in a collaborative virtual pointing task. BACKGROUND: Collaborative virtual environments (CVEs) provide a medium for interaction among remote participants. Better understanding of the role of haptic feedback as a supplement to verbalization can improve the design of CVEs. METHODS: Thirty-six participants were randomly paired into 18 dyads to complete a 2-D pointing task in a CVE. In a mixed experimental design, participants completed the task in three communication conditions: haptic only (H), verbal only (V), and haptic plus verbal (HV). The order of the conditions presented to the participants was counterbalanced. RESULTS: The time to task completion, path length, overshoot, and root mean square error were analyzed. Overall, performance in the V and HV conditions was significantly better than in the H condition. H was the least efficient communication channel but elicited response with the shortest reaction time. When verbalization was not available, the use of the haptic device was more likely to be exaggerated to ensure information transmission. When verbalization was used, participants converged on the use of a Cartesian coordinate system for communicating spatial information. CONCLUSION: Haptic communication can be used to complete a collaborative virtual task but is less efficient than verbal communication. A training period may help to improve the efficiency of haptic communication. APPLICATION: These results can be used to design remote collaboration tasks incorporating haptic components and for improving the design of CVEs that support haptic communication.

Silibinin down-regulates FAT10 and modulate TNF-α/IFN-γ-induced chromosomal instability and apoptosis sensitivity.

Pleiotropic pro-inflammatory cytokines, TNF-α and IFN-γ (TI), play important yet diverse roles in cell survival, proliferation, and death. Recent evidence highlights FAT10 as a downstream molecule in the pathway of inflammation-induced tumorigenesis through mediating the effect of cytokines in causing numerical CIN and protecting cells from cytokines-induced cell death. cDNA microarray analysis of cells treated with TI revealed 493 deregulated genes with FAT10 being the most up-regulated (85.7-fold) gene and NF-κB being the key nodal hub of TI-response genes. Silibinin is reported to be a powerful antioxidant and has anti-C effects against various carcinomas by affecting various signaling molecules/pathways including MAPK, NF-κB and STATs. As NF-κB signaling pathway is a major mediator of the tumor-promoting activities of TI, we thus examine the effects of silibinin on TI-induced FAT10 expression and CIN. Our data showed that silibinin inhibited expression of FAT10, TI-induced chromosome instability (CIN) as well as sensitizes cells to TI-induced apoptosis. Significantly, silibinin suppressed intra-tumorally injected TNF-α-induced tumor growth. This represents the first report associating silibinin with FAT10 and demonstrating that silibinin can modulate TI-induced CIN, apoptosis sensitivity and suppressing TNF-α-induced tumor growth.