A generic scope actuation system for flexible endoscopes.

BACKGROUND: A scope actuation system assists a surgeon in steering a scope for navigating an operative field during an interventional or diagnostic procedure. Each system is tailored for a specific surgical procedure. The development of a generic scope actuation system could assist various laparoscopic and endoscopic procedures. This has the potential to reduce the deployment and maintenance costs for a hospital, making it more accessible for clinical usage. METHODS: A modular actuation system (for maneuvering rigid laparoscopes) was adapted to enable incorporation of flexible endoscopes. The design simplifies the installation and disassembly processes. User studies were conducted to assess the ability of the system to focus onto a diagnostic area, and to navigate during a simulated esophagogastroduodenoscopy procedure. During the studies, the endoscope was maneuvered with (robotic mode) and without (manual mode) the actuation system to navigate the endoscope's focus on a predefined track. RESULTS: Results show that the robotic mode performed better than the manual mode on all the measured performance parameters including (a) the total duration to traverse a track, (b) the percentage of time spent outside a track while traversing, and (c) the number of times the scope focus shifts outside the track. Additionally, robotic mode also reduced the perceived workload based on the NASA-TLX scale. CONCLUSIONS: The proposed scope actuation system enhances the maneuverability of flexible endoscopes. It also lays the groundwork for future development of modular and generic scope assistant systems that can be used in both laparoscopic and endoscopic procedures.

User interfaces for actuated scope maneuvering in surgical systems: a scoping review.

BACKGROUND: A variety of human computer interfaces are used by robotic surgical systems to control and actuate camera scopes during minimally invasive surgery. The purpose of this review is to examine the different user interfaces used in both commercial systems and research prototypes. METHODS: A comprehensive scoping review of scientific literature was conducted using PubMed and IEEE Xplore databases to identify user interfaces used in commercial products and research prototypes of robotic surgical systems and robotic scope holders. Papers related to actuated scopes with human-computer interfaces were included. Several aspects of user interfaces for scope manipulation in commercial and research systems were reviewed. RESULTS: Scope assistance was classified into robotic surgical systems (for multiple port, single port, and natural orifice) and robotic scope holders (for rigid, articulated, and flexible endoscopes). Benefits and drawbacks of control by different user interfaces such as foot, hand, voice, head, eye, and tool tracking were outlined. In the review, it was observed that hand control, with its familiarity and intuitiveness, is the most used interface in commercially available systems. Control by foot, head tracking, and tool tracking are increasingly used to address limitations, such as interruptions to surgical workflow, caused by using a hand interface. CONCLUSION: Integrating a combination of different user interfaces for scope manipulation may provide maximum benefit for the surgeons. However, smooth transition between interfaces might pose a challenge while combining controls.

Scope actuation system for articulated laparoscopes.

BACKGROUND: An articulated laparoscope comprises a rigid shaft with an articulated distal end to change the viewing direction. The articulation provides improved navigation of the operating field in confined spaces. Furthermore, incorporation of an actuation system tends to enhance the control of an articulated laparoscope. METHODS: A preliminary prototype of a scope actuation system to maneuver an off-the-shelf articulated laparoscope (EndoCAMaleon by Karl Storz, Germany) was developed. A user study was conducted to evaluate this prototype for the surgical paradigm of video-assisted thoracic surgery. In the study, the subjects maneuvered an articulated scope under two modes of operation: (a) actuated mode where an operating surgeon maneuvers the scope using the developed prototype and (b) manual mode where a surgical assistant directly maneuvers the scope. The actuated mode was further assessed for multiple configurations based on the orientation of the articulated scope at the incision. RESULTS: The data show the actuated mode scored better than the manual mode on all the measured performance parameters including (a) total duration to visualize a marked region, (a) duration for which scope focus shifts outside a predefined visualization region, and (c) number of times for which scope focus shifts outside a predefined visualization region. Among the different configurations tested using the actuated mode, no significant difference was observed. CONCLUSIONS: The proposed articulated scope actuation system facilitates better navigation of an operative field as compared to a human assistant. Secondly, irrespective of the orientation in which an articulated scope's shaft is inserted through an incision, the proposed actuation system can navigate and visualize the operative field.

Preliminary design and evaluation of a generic surgical scope adapter.

BACKGROUND: Robotic scope assistant systems are used to visualise and navigate the operative field during a laparoscopic surgery. The objective of this work is to design a surgical scope adapter that enables control of different scope types (zero-degree, angulated, and articulated), and can be connected to any six degree-of-freedom robotic manipulator for usage as a robotic scope assistant system. METHODS: A surgical scope adapter compatible with different camera heads and scope types was designed and prototyped. The technical performance of the scope adapter was evaluated and a user study was conducted to assess the human-in-the-loop control. RESULTS: All the subjects were able to navigate the simulated operative field. The scope adapter permits continuous motion to explore the operative field as well as intermittent motion to accurately focus on the targeted anatomical landmarks. CONCLUSION: The modular and generic nature of the surgical scope adapter may enable its usage across different minimally invasive surgeries.

The genome of the zebra mussel, Dreissena polymorpha: a resource for comparative genomics, invasion genetics, and biocontrol.

The zebra mussel, Dreissena polymorpha, continues to spread from its native range in Eurasia to Europe and North America, causing billions of dollars in damage and dramatically altering invaded aquatic ecosystems. Despite these impacts, there are few genomic resources for Dreissena or related bivalves. Although the D. polymorpha genome is highly repetitive, we have used a combination of long-read sequencing and Hi-C-based scaffolding to generate a high-quality chromosome-scale genome assembly. Through comparative analysis and transcriptomics experiments, we have gained insights into processes that likely control the invasive success of zebra mussels, including shell formation, synthesis of byssal threads, and thermal tolerance. We identified multiple intact steamer-like elements, a retrotransposon that has been linked to transmissible cancer in marine clams. We also found that D. polymorpha have an unusual 67 kb mitochondrial genome containing numerous tandem repeats, making it the largest observed in Eumetazoa. Together these findings create a rich resource for invasive species research and control efforts.

A Holographic Augmented Reality Interface for Visualizing of MRI Data and Planning of Neurosurgical Procedures.

The recent introduction of wireless head-mounted displays (HMD) promises to enhance 3D image visualization by immersing the user into 3D morphology. This work introduces a prototype holographic augmented reality (HAR) interface for the 3D visualization of magnetic resonance imaging (MRI) data for the purpose of planning neurosurgical procedures. The computational platform generates a HAR scene that fuses pre-operative MRI sets, segmented anatomical structures, and a tubular tool for planning an access path to the targeted pathology. The operator can manipulate the presented images and segmented structures and perform path-planning using voice and gestures. On-the-fly, the software uses defined forbidden-regions to prevent the operator from harming vital structures. In silico studies using the platform with a HoloLens HMD assessed its functionality and the computational load and memory for different tasks. A preliminary qualitative evaluation revealed that holographic visualization of high-resolution 3D MRI data offers an intuitive and interactive perspective of the complex brain vasculature and anatomical structures. This initial work suggests that immersive experiences may be an unparalleled tool for planning neurosurgical procedures.

Identification of Target Genes Mediated by Two-Component Regulators of Staphylococcus aureus Using RNA-seq Technology.

Transcriptomics enables us to elucidate comprehensive gene expression profiles in given experimental conditions. Global regulators, which include transcriptional regulators and two-component regulatory systems, have evolved in a variety of bacterial systems. They play important roles in bacterial fitness and pathogenesis by regulating target gene expression. Advanced next-generation RNA sequencing technology (RNA-seq) provides a powerful and effective tool to analyze the transcriptome of bacterial cells. In this chapter, we provide a detailed procedure for the investigation of gene expression profiles and identification of target genes, regulons, and/or pathways that are mediated by a regulator. This procedure is done using RNA-seq analysis, which involves RNA purification, mRNA enrichment, decontamination, RNA-seq data analysis, and quantitative real-time reverse transcription PCR.

Measuring sequencer size bias using REcount: a novel method for highly accurate Illumina sequencing-based quantification.

Quantification of DNA sequence tags from engineered constructs such as plasmids, transposons, or other transgenes underlies many functional genomics measurements. Typically, such measurements rely on PCR followed by next-generation sequencing. However, PCR amplification can introduce significant quantitative error. We describe REcount, a novel PCR-free direct counting method. Comparing measurements of defined plasmid pools to droplet digital PCR data demonstrates that REcount is highly accurate and reproducible. We use REcount to provide new insights into clustering biases due to molecule length across different Illumina sequencers and illustrate the impacts on interpretation of next-generation sequencing data and the economics of data generation.

Fabrication of multipoint side-firing optical fiber by laser micro-ablation.

A multipoint, side-firing design enables an optical fiber to output light at multiple desired locations along the fiber body. This provides advantages over traditional end-to-end fibers, especially in applications requiring fiber bundles such as brain stimulation or remote sensing. This Letter demonstrates that continuous wave (CW) laser micro-ablation can controllably create conical-shaped cavities, or side windows, for outputting light. The dimensions of these cavities determine the amount of firing light and their firing angle. Experimental data show that a single side window on a 730 µm fiber can deliver more than 8% of the input light. This can be increased to more than 19% on a 65 µm fiber with side windows created using femtosecond laser ablation and chemical etching. Fine control of light distribution along an optical fiber is critical for various biomedical applications such as light-activated drug-release and optogenetics studies.

Simultaneous steering and imaging of magnetic particles using MRI toward delivery of therapeutics.

Magnetic resonance navigation (MRN) offers the potential for real-time steering of drug particles and cells to targets throughout the body. In this technique, the magnetic gradients of an MRI scanner perform image-based steering of magnetically-labelled therapeutics through the vasculature and into tumours. A major challenge of current techniques for MRN is that they alternate between pulse sequences for particle imaging and propulsion. Since no propulsion occurs while imaging the particles, this results in a significant reduction in imaging frequency and propulsive force. We report a new approach in which an imaging sequence is designed to simultaneously image and propel particles. This sequence provides a tradeoff between maximum propulsive force and imaging frequency. In our reported example, the sequence can image at 27 Hz while still generating 95% of the force produced by a purely propulsive pulse sequence. We implemented our pulse sequence on a standard clinical scanner using millimetre-scale particles and demonstrated high-speed (74 mm/s) navigation of a multi-branched vascular network phantom. Our study suggests that the magnetic gradient magnitudes previously demonstrated to be sufficient for pure propulsion of micron-scale therapeutics in magnetic resonance targeting (MRT) could also be sufficient for real-time steering of these particles.

Systematic improvement of amplicon marker gene methods for increased accuracy in microbiome studies.

Amplicon-based marker gene surveys form the basis of most microbiome and other microbial community studies. Such PCR-based methods have multiple steps, each of which is susceptible to error and bias. Variance in results has also arisen through the use of multiple methods of next-generation sequencing (NGS) amplicon library preparation. Here we formally characterized errors and biases by comparing different methods of amplicon-based NGS library preparation. Using mock community standards, we analyzed the amplification process to reveal insights into sources of experimental error and bias in amplicon-based microbial community and microbiome experiments. We present a method that improves on the current best practices and enables the detection of taxonomic groups that often go undetected with existing methods.

Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in altered liver transcriptomic response.

Hemorrhagic shock is a leading cause of trauma-related mortality in both civilian and military settings. Resuscitation often results in reperfusion injury and survivors are susceptible to developing multiple organ failure (MOF). The impact of fed state on the overall response to shock and resuscitation has been explored in some murine models but few clinically relevant large animal models. We have previously used metabolomics to establish that the fed state results in a different metabolic response in the porcine liver following hemorrhagic shock and resuscitation. In this study, we used our clinically relevant model of hemorrhagic shock and polytrauma and the Illumina HiSeq platform to determine if the liver transcriptomic response is also altered with respect to fed state. Functional analysis of the response to shock and resuscitation confirmed several typical responses including carbohydrate metabolism, cytokine inflammation, decreased cholesterol synthesis, and apoptosis. Our findings also suggest that the fasting state, relative to a carbohydrate prefed state, displays decreased carbohydrate metabolism, increased cytoskeleton reorganization and decreased inflammation in response to hemorrhagic shock and reperfusion. Evidence suggests that this is a consequence of a shrunken, catabolic state of the liver cells which provides an anti-inflammatory condition that partially mitigates hepatocellar damage.

Transcriptomic analysis of Staphylococcus aureus using microarray and advanced next-generation RNA-seq technologies.

The transcriptome has shown tremendous potential for the comprehensive investigation of gene expression profiles and transcriptional levels in comparative biology, the identification of regulatory mechanism of transcriptional regulators, and the evaluation of target gene for developing new chemotherapeutic agents, vaccine, and diagnostic methods. The traditional microarray and advanced next-generation RNA sequencing technologies (RNA-seq) provide powerful and effective tools for the determination of the transcriptome of bacterial cells. In this chapter, we provide a detailed protocol for scientists who want to investigate gene expression profiles by performing microarray and/or RNA-seq analysis, including different RNA purification methods, mRNA enrichment, decontamination, cDNA synthesis, fragmentation, biotin labeling for hybridization using Affymetrix Staphylococcus aureus chips, quantitative real-time reverse transcription PCR, and RNA-seq data analysis.

Financing your strategic plan: finding the right tool for the right job.

Financing options available through the private sector and government agencies can fund facility renovations or new construction. To upgrade IT, hospital leaders have three major financing options: purchase, use cloud-based services for a fee, or lease. Hospital leaders may finance physician integration like other capital projects, but there are risks to diverting dollars from buildings.

A pilot study of preoperative gefitinib for early-stage lung cancer to assess intratumor drug concentration and pathways mediating primary resistance.

BACKGROUND: Targeted agents such as tyrosine kinase inhibitors have been extensively studied in preclinical systems and in advanced-stage patients. Little is known about levels of kinase inhibitors found in tumors as opposed to plasma. Similarly, effects of inhibitors on tumor signaling pathways in patient-based materials are unclear. To explore these questions, we conducted a trial of a brief course of preoperative gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, in early-stage non-small cell lung cancer. METHODS: Patient with early-stage non-small cell lung cancer received 4 weeks of gefitinib 250 mg daily before surgical resection. Pre- and posttreatment computerized tomography scans and positron emission tomography scans were used to assess clinical response. Gefitinib and surgical toxicity were evaluated. Tumor tissue was evaluated for gefitinib levels and was compared with plasma gefitinib levels. Activated signaling molecules including EGFR, STAT3, ERK, and AKT were examined in surgically resected tumor tissue. RESULTS: Twenty-three patients participated in the study, and all had surgical resection of tumors. No toxicities unrelated to known effects of gefitinib or surgery were encountered. Twenty-two patients had stable disease, and one had progression in tumor size. There was no correlation with positron emission tomography response and computerized tomography response. Tumor levels of gefitinib were approximately 40-fold higher than plasma levels, indicating potential tumor concentration of gefitinib. Tyrosine phosphorylated STAT3 was abundant in the surgically resected tumor tissue, indicating potential role in primary resistance in vivo. CONCLUSIONS: This study confirms previous preclinical observations that tumor tissues concentrate gefitinib. Persistent STAT3 may be leading to primary resistance to EGFR inhibitors in vivo.

Prostatic involution after intraprostatic injection of cobra toxin.

PURPOSE: We evaluated the comparative effects of intraprostatic injection of cobra cardiotoxin D and botulinum toxin type A on prostate structure in the rat model. MATERIALS AND METHODS: A total of 18 Sprague-Dawley® rats weighing 500 to 600 gm received a single 0.1 ml injection of saline (6), botulinum toxin type A (6) or the cardiotoxin D (6) component of cobra (Naja naja atra) toxin in the right and left ventral lobes of the prostate. At 14 days the rats were sacrificed. The prostate glands were harvested, weighed and processed for immunohistochemical and morphological studies. RESULTS: Prostate glands injected with cardiotoxin D showed significantly decreased weight compared to that of prostates injected with botulinum toxin type A and the saline control. Prostatic atrophy in the glandular component with flattening of the epithelial lining was seen histologically in rats that received botulinum toxin and cardiotoxin D. Each group injected with cardiotoxin D and botulinum toxin showed a significant increase in the number of apoptotic cells compared with controls while only the botulinum toxin group showed a significant increase in the number of proliferating cells. Only rats injected with botulinum toxin had body weight loss. CONCLUSIONS: Our study shows that intraprostatic injection of cobra cardiotoxin D induces prostatic atrophy and leads to a decrease in prostatic weight greater than that of intraprostatic injection of botulinum toxin type A. No systemic effects, such as decreased body weight, were noted after cardiotoxin D injection. Further studies are warranted but the statistically significant decrease in the number of proliferating cells implies a prolonged effect of cardiotoxin D.

Conservative management of a grade V injury to an ectopic pelvic kidney following blunt trauma to the lower abdomen: a case report.

INTRODUCTION: Ectopic pelvic kidneys represent an anatomic variant that remains clinically asymptomatic in most patients. While there is some literature to suggest that ectopic kidneys may be more predisposed to blunt trauma injuries, there are few examples to guide the management of these injuries. To our knowledge, we present the first case of a grade V renal injury to an ectopic pelvic kidney managed successfully with conservative measures. CASE PRESENTATION: We present a case of grade V renal injury to an ectopic pelvic kidney in a 21 year-old African-American male. The clinical and radiographic findings are presented, along with the patient's conservative hospital course. CONCLUSION: We suggest that management of grade V renal injuries to ectopic pelvic kidneys can be treated similarly to that of kidneys in normal anatomic position. Conservative measures may be considered in properly selected patients.

Effect of alpha1-adrenoceptor antagonist exposure on prostate cancer incidence: an observational cohort study.

PURPOSE: The quinazoline based alpha1-adrenoceptor antagonists doxazosin and terazosin suppress prostate tumor growth via the induction of apoptosis and decrease in tissue vascularity. To assess the effect of alpha1-blocker exposure on the incidence of prostate cancer we performed an exploratory, observational cohort study. MATERIALS AND METHODS: The medical records of all male patients enrolled at Lexington Veterans Affairs Medical Center were searched to identify men treated with quinazoline based alpha1-adrenoreceptor antagonists between January 1, 1998 and December 31, 2002 for hypertension and/or benign prostatic enlargement. Medical records were subsequently linked to the Markey Cancer Center Kentucky Cancer Registry, a statewide population based central cancer registry that is part of the National Cancer Institute Surveillance, Epidemiology and End Results Program, to identify all incident prostate cancer cases diagnosed. All newly diagnosed prostate cancer cases unexposed to alpha1-adrenoreceptor antagonists in the total male Veterans Affairs population during this period were also identified from the Kentucky Cancer Registry database. Measures of disease incidence, relative risk and attributable risk were calculated to compare the risk of prostate cancer in alpha1-blocker exposed vs unexposed men. Kaplan-Meier curves and Cox regression models were used to compare overall survival between alpha1-blocker exposed and unexposed prostate cancer cases. RESULTS: Our analysis revealed a cumulative incidence of 1.65% in alpha1-blocker exposed men compared to 2.41% in the unexposed group. These data yielded an unadjusted RR of 0.683 (95% CI 0.532, 0.876) and a risk difference of -0.0076, indicating that 7.6 fewer prostate cancer cases developed per 1,000 exposed men. Thus, exposure to quinazoline alpha1-blockers may have prevented 32 prostate cancer cases among the 4,070 treated men during the study period. Therefore, men exposed to quinazoline alpha1-adrenoceptor antagonists were at 1.46 times lower RR and 31.7% lower attributable risk for prostate cancer than unexposed men. There was no association between alpha1-adrenoceptor antagonist exposure and overall survival. CONCLUSIONS: These data suggest that exposure to quinazoline based alpha1-adrenoceptor antagonists significantly decreases the incidence of prostate cancer. This evidence suggests that the apoptotic and anti-angiogenic effects of these drugs may prevent the development of prostate cancer.