NOViSE: a virtual natural orifice transluminal endoscopic surgery simulator

Purpose: Natural Orifice Transluminal Endoscopic Surgery (NOTES) is a novel technique in minimally invasive surgery whereby a flexible endoscope is inserted via a natural orifice to gain access to the abdominal cavity, leaving no external scars. This innovative use of flexible endoscopy creates many new challenges and is associated with a steep learning curve for clinicians. Methods: We developed NOViSE - the first force-feedback enabled virtual reality simulator for NOTES training supporting a flexible endoscope. The haptic device is custom built and the behaviour of the virtual flexible endoscope is based on an established theoretical framework – the Cosserat Theory of Elastic Rods. Results: We present the application of NOViSE to the simulation of a hybrid trans-gastric cholecystectomy procedure. Preliminary results of face, content and construct validation have previously shown that NOViSE delivers the required level of realism for training of endoscopic manipulation skills specific to NOTES Conclusions: VR simulation of NOTES procedures can contribute to surgical training and improve the educational experience without putting patients at risk, raising ethical issues or requiring expensive animal or cadaver facilities. In the context of an experimental technique, NOViSE could potentially facilitate NOTES development and contribute to its wider use by keeping practitioners up to date with this novel surgical technique. NOViSE is a first prototype and the initial results indicate that it provides promising foundations for further development

Visual gaze patterns reveal surgeons' ability to identify risk of bile duct injury during laparoscopic cholecystectomy

BACKGROUND: Bile duct injury is a serious surgical complication of laparoscopic cholecystectomy. The aim of this study was to identify distinct visual gaze patterns associated with the prompt detection of bile duct injury risk during laparoscopic cholecystectomy. METHODS: Twenty-nine participants viewed a laparoscopic cholecystectomy that led to a serious bile duct injury ('BDI video') and an uneventful procedure ('control video') and reported when an error was perceived that could result in bile duct injury. Outcome parameters include fixation sequences on anatomical structures and eye tracking metrics. Surgeons were stratified into two groups based on performance and compared. RESULTS: The 'early detector' group displayed reduced common bile duct dwell time in the first half of the BDI video, as well as increased cystic duct dwell time and Calot's triangle glances count during Calot's triangle dissection in the control video. Machine learning based classification of fixation sequences demonstrated clear separability between early and late detector groups. CONCLUSION: There are discernible differences in gaze patterns associated with early recognition of impending bile duct injury. The results could be transitioned into real time and used as an intraoperative early warning system and in an educational setting to improve surgical safety and performance

Metagenomic analysis of double-stranded DNA viruses in healthy adults

BackgroundThe Human Microbiome Project (HMP) was undertaken with the goal of defining microbial communities in and on the bodies of healthy individuals using high-throughput, metagenomic sequencing analysis. The viruses present in these microbial communities, the `human virome¿, are an important aspect of the human microbiome that is particularly understudied in the absence of overt disease. We analyzed eukaryotic double-stranded DNA (dsDNA) viruses, together with dsDNA replicative intermediates of single-stranded DNA viruses, in metagenomic sequence data generated by the HMP. 706 samples from 102 subjects were studied, with each subject sampled at up to five major body habitats: nose, skin, mouth, vagina, and stool. Fifty-one individuals had samples taken at two or three time points 30 to 359 days apart from at least one of the body habitats.ResultsWe detected an average of 5.5 viral genera in each individual. At least 1 virus was detected in 92% of the individuals sampled. These viruses included herpesviruses, papillomaviruses, polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and circoviruses. Each individual had a distinct viral profile, demonstrating the high interpersonal diversity of the virome. Some components of the virome were stable over time.ConclusionsThis study is the first to use high-throughput DNA sequencing to describe the diversity of eukaryotic dsDNA viruses in a large cohort of normal individuals who were sampled at multiple body sites. Our results show that the human virome is a complex component of the microbial flora. Some viruses establish long-term infections that may be associated with increased risk or possibly with protection from disease. A better understanding of the composition and dynamics of the virome may hold important keys to human health. BMC Biol 2014 Sep 10; 12(1):71

Sequence Analysis of the Human Virome in Febrile and Afebrile Children

Unexplained fever (UF) is a common problem in children under 3 years old. Although virus infection is suspected to be the cause of most of these fevers, a comprehensive analysis of viruses in samples from children with fever and healthy controls is important for establishing a relationship between viruses and UF. We used unbiased, deep sequencing to analyze 176 nasopharyngeal swabs (NP) and plasma samples from children with UF and afebrile controls, generating an average of 4.6 million sequences per sample. An analysis pipeline was developed to detect viral sequences, which resulted in the identification of sequences from 25 viral genera. These genera included expected pathogens, such as adenoviruses, enteroviruses, and roseoloviruses, plus viruses with unknown pathogenicity. Viruses that were unexpected in NP and plasma samples, such as the astrovirus MLB-2, were also detected. Sequencing allowed identification of virus subtype for some viruses, including roseoloviruses. Highly sensitive PCR assays detected low levels of viruses that were not detected in approximately 5 million sequences, but greater sequencing depth improved sensitivity. On average NP and plasma samples from febrile children contained 1.5- to 5-fold more viral sequences, respectively, than samples from afebrile children. Samples from febrile children contained a broader range of viral genera and contained multiple viral genera more frequently than samples from children without fever. Differences between febrile and afebrile groups were most striking in the plasma samples, where detection of viral sequence may be associated with a disseminated infection. These data indicate that virus infection is associated with UF. Further studies are important in order to establish the range of viral pathogens associated with fever and to understand of the role of viral infection in fever. Ultimately these studies may improve the medical treatment of children with UF by helping avoid antibiotic therapy for children with viral infections

SpBase: the sea urchin genome database and web site

SpBase is a system of databases focused on the genomic information from sea urchins and related echinoderms. It is exposed to the public through a web site served with open source software (http://spbase.org/). The enterprise was undertaken to provide an easily used collection of information to directly support experimental work on these useful research models in cell and developmental biology. The information served from the databases emerges from the draft genomic sequence of the purple sea urchin, Strongylocentrotus purpuratus and includes sequence data and genomic resource descriptions for other members of the echinoderm clade which in total span 540 million years of evolutionary time. This version of the system contains two assemblies of the purple sea urchin genome, associated expressed sequences, gene annotations and accessory resources. Search mechanisms for the sequences and the gene annotations are provided. Because the system is maintained along with the Sea Urchin Genome resource, a database of sequenced clones is also provided

A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from Pancreatic Cancer Patients Treated with Endoscopic Ultrasound Guided Radiofrequency Ablation.

BACKGROUND: Most patients with pancreatic ductal adenocarcinoma (PDAC) are metastatic at presentation with dismal prognosis warranting improved systemic therapy options. Longitudinal sampling for the assessment of treatment response poses a challenge for validating novel therapies. In this case study, we evaluate the feasibility of collecting endoscopic ultrasound (EUS)-guided longitudinal fine-needle aspiration biopsies (FNABs) from two PDAC patients and conduct gene expression studies associated with tumour microenvironment changes associated with radiofrequency ablation (RFA). METHODS: EUS-guided serial/longitudinal FNABs of tumour were collected before and after treatment from two stage III inoperable gemcitabine-treated PDAC patients treated with targeted RFA three times. Biopsies were analysed using a custom NanoString panel (144 genes) consisting of cancer and cancer-associated fibroblast (CAFs) subtypes and immune changes. CAF culture was established from one FNAB and characterised by immunofluorescence and immunoblotting. RESULTS: Two-course RFA led to the upregulation of the CD1E gene (involved in antigen presentation) in both patients 1 and 2 (4.5 and 3.9-fold changes) compared to baseline. Patient 1 showed increased T cell genes (CD4-8.7-fold change, CD8-35.7-fold change), cytolytic function (6.4-fold change) and inflammatory response (8-fold change). A greater than 2-fold upregulation of immune checkpoint genes was observed post-second RFA in both patients. Further, two-course RFA led to increased PDGFRα (4.5-fold change) and CAF subtypes B and C genes in patient 1 and subtypes A, B and D genes in patient 2. Patient 2-derived CAFs post-first RFA showed expression of PDGFRα, POSTN and MYH11 proteins. Finally, RFA led to the downregulation of classical PDAC subtype-specific genes in both patients. CONCLUSIONS: This case study suggests longitudinal EUS-FNAB as a potential resource to study tumour and microenvironmental changes associated with RFA treatment. A large sample size is required in the future to assess the efficacy and safety of the treatment and perform comprehensive statistical analysis of EUS-RFA-based molecular changes in PDAC