Can mixed reality technologies teach surgical skills better than traditional methods? A prospective randomised feasibility study

Background Basic surgical skills teaching is often delivered with didactic audio-visual content, and new digital technologies may allow more engaging and effective ways of teaching to be developed. The Microsoft HoloLens 2 (HL2) is a multi-functional mixed reality headset. This prospective feasibility study sought to assess the device as a tool for enhancing technical surgical skills training. Methods A prospective randomised feasibility study was conducted. 36 novice medical students were trained to perform a basic arteriotomy and closure using a synthetic model. Participants were randomised to receive a structured surgical skills tutorial via a bespoke mixed reality HL2 tutorial (n = 18), or via a standard video-based tutorial (n = 18). Proficiency scores were assessed by blinded examiners using a validated objective scoring system and participant feedback collected. Results The HL2 group showed significantly greater improvement in overall technical proficiency compared to the video group (10.1 vs. 6.89, p = 0.0076), and a greater consistency in skill progression with a significantly narrower range of scores (SD 2.48 vs. 4.03, p = 0.026). Participant feedback showed the HL2 technology to be more interactive and engaging with minimal device related problems experienced. Conclusions This study has demonstrated that mixed reality technology may provide a higher quality educational experience, improved skill progression and greater consistency in learning when compared to traditional teaching methodologies for basic surgical skills. Further work is required to refine, translate, and evaluate the scalability and applicability of the technology across a broad range of skills-based disciplines

The use of mixed reality technology for the objective assessment of clinical skills: a validation study

Background Mixed Reality technology may provide many advantages over traditional teaching methods. Despite its potential, the technology has yet to be used for the formal assessment of clinical competency. This study sought to collect validity evidence and assess the feasibility of using the HoloLens 2 mixed reality headset for the conduct and augmentation of Objective Structured Clinical Examinations (OSCEs). Methods A prospective cohort study was conducted to compare the assessment of undergraduate medical students undertaking OSCEs via HoloLens 2 live (HLL) and recorded (HLR), and gold-standard in-person (IP) methods. An augmented mixed reality scenario was also assessed. Results 13 undergraduate participants completed a total of 65 OSCE stations. Overall inter-modality correlation was 0.81 (p=0.01), 0.98 (p=0.01) and 0.82 (p=0.01) for IP vs. HLL, HLL vs. HLR and IP vs. HLR respectively. Skill based correlations for IP vs. HLR were assessed for history taking (0.82, p=0.01), clinical examination (0.81, p=0.01), procedural (0.88, p=0.01) and clinical skills (0.92, p=0.01), and assessment of a virtual mixed reality patient (0.74, p=0.01). The HoloLens device was deemed to be usable and practical (Standard Usability Scale (SUS) score = 51.5), and the technology was thought to deliver greater flexibility and convenience, and have the potential to expand and enhance assessment opportunities. Conclusions HoloLens 2 is comparable to traditional in-person examination of undergraduate medical students for both live and recorded assessments, and therefore is a valid and robust method for objectively assessing performance. The technology is in its infancy, and users need to develop confidence in its usability and reliability as an assessment tool. However, the potential to integrate additional functionality including holographic content, automated tracking and data analysis, and to facilitate remote assessment may allow the technology to enhance, expand and standardise examinations across a range of educational contexts

Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling

Activating mutations in genes of the Ras-mitogen-activated protein kinase (MAPK) pathway occur in approximately 30% of all human cancers; however, mutation of Ras alone is rarely sufficient to induce tumour development. Scribble is a polarity regulator recently isolated from a Drosophila screen for events that cooperate with Ras mutation to promote tumour progression and cell invasion. In mammals, Scribble regulates directed cell migration and wound healing in vivo; however, no role has been identified for mammalian Scribble in oncogenic transformation. Here we show that in human epithelial cells expressing oncogenic Ras or Raf, loss of Scribble promotes invasion of cells through extracellular matrix in an organotypic culture system. Further, we show that the mechanism by which this occurs is in the regulation of MAPK signalling by Scribble. The suppression of MAPK signalling is a highly conserved function of Scribble as it also prevents Raf-mediated defects in Drosophila wing development. Our data identify Scribble as an important mediator of MAPK signalling and provide a molecular basis for the observation that Scribble expression is decreased in many invasive human cancers. © 2008 Macmillan Publishers Limited All rights reserved

A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife

Background: This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas. Methods: Patients undergoing elective surgical resection for CRC were recruited at St. Mary’s Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy. Results: Twenty-eight patients were recruited (12 males, median age 71, range 35–89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC’s 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy. Conclusion: REIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer

Dietary fibre to reduce colon cancer risk in Alaska Native people: the Alaska FIRST randomised clinical trial protocol

Introduction Diet, shown to impact colorectal cancer (CRC) risk, is a modifiable environmental factor. Fibre foods fermented by gut microbiota produce metabolites that not only provide food for the colonic epithelium but also exert regulatory effects on colonic mucosal inflammation and proliferation. We describe methods used in a double-blinded, randomised, controlled trial with Alaska Native (AN) people to determine if dietary fibre supplementation can substantially reduce CRC risk among people with the highest reported CRC incidence worldwide. Methods and analyses Eligible patients undergoing routine screening colonoscopy consent to baseline assessments and specimen/data collection (blood, urine, stool, saliva, breath and colon mucosal biopsies) at the time of colonoscopy. Following an 8-week stabilisation period to re-establish normal gut microbiota post colonoscopy, study personnel randomise participants to either a high fibre supplement (resistant starch, n=30) or placebo (digestible starch, n=30) condition, repeating stool sample collection. During the 28-day supplement trial, each participant consumes their usual diet plus their supplement under direct observation. On day 29, participants undergo a flexible sigmoidoscopy to obtain mucosal biopsy samples to measure the effect of the supplement on inflammatory and proliferative biomarkers of cancer risk, with follow-up assessments and data/specimen collection similar to baseline. Secondary outcome measures include the impact of a high fibre supplement on the oral and colonic microbiome and biofluid metabolome. Ethics and dissemination Approvals were obtained from the Alaska Area and University of Pittsburgh Institutional Review Boards and Alaska Native Tribal Health Consortium and Southcentral Foundation research review bodies. A data safety monitoring board, material transfer agreements and weekly study team meetings provide regular oversight throughout the study. Study findings will first be shared with AN tribal leaders, health administrators, providers and community members. Peer-reviewed journal articles and conference presentations will be forthcoming once approved by tribal review bodies

Antimicrobial use in European acute care hospitals: results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobial agents used to treat infections are life-saving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016-17, we performed the second point-prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2-31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials

a pilot study, 2013

Introduction After recognition of European outbreaks of Clostridium difficile infections (CDIs) associated with the emergence of PCR ribotype 027/NAP1 in 2005, CDI surveillance at country level was encouraged by the European Centre for Disease Prevention and Control (ECDC) [1]. In 2008, an ECDC-supported European CDI survey (ECDIS) identified large intercountry variations in incidence rates and distribution of prevalent PCR ribotypes, with the outbreak-related PCR ribotype 027 being detected in 5% (range: 0–26) of the characterised isolates [2]. The surveillance period was limited to one month and the representation of European hospitals was incomplete; however, this has been the only European (comprising European Union (EU)/European Economic Area (EEA) and EU candidate countries) CDI surveillance study. The authors highlighted the need for national and European surveillance to control CDI. Yet, European countries were found to have limited capacity for diagnostic testing, particularly in terms of standard use of optimal methods and absence of surveillance protocols and a fully validated, standardised and exchangeable typing system for surveillance and/or outbreak investigation. As of 2011, 14 European countries had implemented national CDI surveillance, with various methodologies [3]. National surveillance systems have since reported a decrease in CDI incidence rate and/or prevalence of PCR ribotype 027 in some European countries [4-8]. However, CDI generally remains poorly controlled in Europe [9], and PCR ribotype 027 continues to spread in eastern Europe [10-12] and globally [13]. In 2010, ECDC launched a new project, the European C. difficile Infection Surveillance Network (ECDIS-Net), to enhance surveillance of CDI and laboratory capacity to test for CDI in Europe. The goal of ECDIS- Net was to establish a standardised CDI surveillance protocol suitable for application all over Europe in order to: (i) estimate the incidence rate and total infection rate of CDI (including recurrent CDI cases) in European acute care hospitals; (ii) provide participating hospitals with a standardised tool to measure and compare their own incidence rates with those observed in other participating hospitals; (iii) assess adverse outcomes of CDI such as complications and death; and (iv) describe the epidemiology of CDI concerning antibiotic susceptibility, PCR ribotypes, presence of tcdA, tcdB and binary toxins and detect new emerging types at local, national and European level. The primary objectives of the present study were to: (i) test the pilot protocol for the surveillance of CDI in European acute care hospitals developed by ECDIS-Net (methodology, variables and indicators); (ii) assess the feasibility and workload of collecting the required hospital data, case- based epidemiological and microbiological data; and (iii) evaluate the quality of data collected, whether in the presence or absence of existing national CDI surveillance activities. A secondary aim was to assess the relationship between patient and microbiological characteristics and in-hospital outcome of CDI to confirm the added value of collecting detailed epidemiological and microbiological data on CDI at European level

Optical spectroscopy shows that the normal state of URu2_2Si2_2 is an anomalous Fermi liquid

Fermi showed that electrons, as a result of their quantum nature, form a gas of particles where the temperature and density follow the so called Fermi distribution. In a metal, as shown by Landau, that despite their strong Coulomb interaction with each other and the positive background ions, the electrons continue to act like free quantum mechanical particles but with enhanced masses. This state of matter, the Landau-Fermi liquid, is recognized experimentally by an electrical resistivity that is proportional to the square of the absolute temperature plus a term proportional to the square of the frequency of the applied field. Calculations show that, if electron-electron scattering dominates the resistivity in a Landau Fermi liquid, the ratio of the two terms, $b$ has the universal value of {\em b} = 4. We find that in the normal state of the heavy Fermion metal URu$_2$Si$_2$, instead of the Fermi liquid value of 4 the coefficient $b$ =1 $\pm$ 0.1. This unexpected result implies that the electrons in this material are experiencing a unique scattering process. This scattering is intrinsic and we suggest that, the uranium $f$ electrons do not hybridize to form a coherent Fermi liquid but instead act like a dense array of elastic impurities, interacting incoherently with the charge carriers. This behavior is not restricted to URu$_2$Si$_2$. Fermi liquid like states with $b \neq$ 4 have been observed in a number of disparate systems but the significance of this result has not been recognized.Comment: 5 pages, 6 figure

Standardised surveillance of Clostridium Difficile Infection in European acute care hospitals: A pilot study, 2013

Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a ‘minimal’ option (aggregated hospital data), a ‘light’ option (including patient data for CDI cases) and an ‘enhanced’ option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe

Cell Cycle Genes Are the Evolutionarily Conserved Targets of the E2F4 Transcription Factor

Maintaining quiescent cells in G0 phase is achieved in part through the multiprotein subunit complex known as DREAM, and in human cell lines the transcription factor E2F4 directs this complex to its cell cycle targets. We found that E2F4 binds a highly overlapping set of human genes among three diverse primary tissues and an asynchronous cell line, which suggests that tissue-specific binding partners and chromatin structure have minimal influence on E2F4 targeting. To investigate the conservation of these transcription factor binding events, we identified the mouse genes bound by E2f4 in seven primary mouse tissues and a cell line. E2f4 bound a set of mouse genes that was common among mouse tissues, but largely distinct from the genes bound in human. The evolutionarily conserved set of E2F4 bound genes is highly enriched for functionally relevant regulatory interactions important for maintaining cellular quiescence. In contrast, we found minimal mRNA expression perturbations in this core set of E2f4 bound genes in the liver, kidney, and testes of E2f4 null mice. Thus, the regulatory mechanisms maintaining quiescence are robust even to complete loss of conserved transcription factor binding events