Middle Cranial Fossa (MCF) Approach without the use of Lumbar Drain for the Management of Spontaneous Cerebral Spinal Fluid (CSF) Leaks

Objective: To determine the efficacy and morbidity of repairing spontaneous cerebrospinal fluid (CSF) leaks with the middle cranial fossa (MCF) approach without the use of a lumbar drain (LD), as perioperative use of LD remains controversial. Study Design: Retrospective review from 2003 to 2015. Setting: University of Iowa Hospitals and Clinics and Indiana University Health Center. Patients: Those with a confirmed lateral skull base spontaneous CSF leaks and/or encephaloceles. Intervention: MCF approach for repair of spontaneous CSF leak and/or encephalocele without the use of lumbar drain. Assessment of patient age, sex, body mass index (BMI), and medical comorbidities. Main Outcome Measure: Spontaneous CSF leak patient characteristics (age, sex, BMI, obstructive sleep apnea) were collected. Length of stay (LOS), hospital costs, postoperative complications, CSF leak rate, and need for LD were calculated. Results: Sixty-five operative MCF repairs were performed for spontaneous CSF leaks on 60 patients (five had bilateral CSF leaks). CSF diversion with LD was used in 15 of 60 patients, mostly before 2010. After 2010, only three of 44 patients (6.7%) had postoperative otorrhea requiring LD. The use of LD resulted in significantly longer LOS (3.6 ± 1.6 versus 8.7 ± 2.9 d) and hospital costs ($29,621). There were no postoperative complications in 77% (50 of 65) of cases. Three cases required return to the operating room for complications including frontal subdural hematoma (1), subdural CSF collection (1), and tension pneumocephalus (1). No patients experienced long-term neurologic sequelae or long-term CSF leak recurrence with an average length of follow-up of 19.5 months (range 3–137 mo). The average patient BMI was 37.5 ± 8.6 kg/m2. The average age was 57.5 ± 11.4 years and 68% were female. Obstructive sleep apnea was present in 43.3% (26 of 60) of patients. Conclusion: The morbidity of the MCF craniotomy for repair of spontaneous CSF leaks is low and the long-term efficacy of repair is high. Universal use of perioperative lumbar drain is not indicated and significantly increases length of stay and hospital costs. Obesity and obstructive sleep apnea are highly associated with spontaneous CSF leaks

Enterprise IoT Security and Scalability : How Unikernels can Improve the Status Quo

Postprin

Passive SOBP generation from a static proton pencil beam using 3D-printed range modulators for FLASH experiments

The University Proton Therapy facility in Dresden (UPTD), Germany, is equipped with an experimental room with a beamline providing a static pencil beam. High proton beam currents can be achieved at this beamline which makes it suitable for FLASH experiments. However, the established experimental setup uses only the entrance channel of the proton Bragg curve. In this work, a set of 3D-printed range modulators designed to generate spread out Bragg peaks (SOBPs) for radiobiological experiments at ultra-high dose rate at this beamline is described. A new method to optimize range modulators specifically for the case of a static pencil beam based on the central depth dose profile is introduced. Modulators for two different irradiation setups were produced and characterized experimentally by measurements of lateral and depth dose distributions using different detectors. In addition, Monte Carlo simulations were performed to assess profiles of the dose averaged linear energy transfer (LETD) in water. These newly produced range modulators will allow future proton FLASH experiments in the SOBP at UPTD with two different experimental setups

Development and evaluation of the modiolar research array – multi-centre collaborative study in human temporal bones

OBJECTIVE: Multi-centre collaborative study to develop and refine the design of a prototype thin perimodiolar cochlear implant electrode array and to assess feasibility for use in human subjects. STUDY DESIGN: Multi-centre temporal bone insertion studies. MATERIALS AND METHODS: The modiolar research array (MRA) is a thin pre-curved electrode that is held straight for initial insertion with an external sheath rather than an internal stylet. Between November 2006 and February 2009, six iterations of electrode design were studied in 21 separate insertion studies in which 140 electrode insertions were performed in 85 human temporal bones by 12 surgeons. These studies aimed at addressing four fundamental questions related to the electrode concept, being: (1) Could a sheath result in additional intra-cochlear trauma? (2) Could a sheath accommodate variations in cochlea size and anatomies? (3) Could a sheath be inserted via the round window? and (4) Could a sheath be safely removed once the electrode had been inserted? These questions were investigated within these studies using a number of evaluation techniques, including X-ray and microfluoroscopy, acrylic fixation and temporal bone histologic sectioning, temporal bone microdissection of cochlear structures with electrode visualization, rotational tomography, and insertion force analysis. RESULTS: Frequent examples of electrode rotation and tip fold-over were demonstrated with the initial designs. This was typically caused by excessive curvature of the electrode tip, and also difficulty in handling of the electrode and sheath. The degree of tip curvature was progressively relaxed in subsequent versions with a corresponding reduction in the frequency of tip fold-over. Modifications to the sheath facilitated electrode insertion and sheath removal. Insertion studies with the final MRA design demonstrated minimal trauma, excellent perimodiolar placement, and very small electrode dimensions within scala tympani. Force measurements in temporal bones demonstrated negligible force on cochlear structures with angular insertion depths of between 390 and 450°. CONCLUSION: The MRA is a novel, very thin perimodiolar prototype electrode array that has been developed using a systematic collaborative approach. The different evaluation techniques employed by the investigators contributed to the early identification of issues and generation of solutions. Regarding the four fundamental questions related to the electrode concept, the studies demonstrated that (1) the sheath did not result in additional intra-cochlear trauma; (2) the sheath could accommodate variations in cochlea size and anatomies; (3) the sheath was more successfully inserted via a cochleostomy than via the round window; and (4) the sheath could be safely removed once the electrode had been inserted

Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs

Abstract Background This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. Methods We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive. For each scenario, we evaluated genetic gain, genetic variance ( \u3c3 A 2 ) , rate of change in inbreeding ( \u394 F ), number of distinct quantitative trait nucleotides (QTN) edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles. Results Gene drives enhanced the benefits of genome editing in seven ways: (1) they amplified the increase in genetic gain brought about by genome editing; (2) they amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them; (3) they enabled more rapid targeting of QTN with lesser effect for genome editing; (4) they distributed fixed editing resources across a larger number of distinct QTN across generations; (5) they focussed editing on a smaller number of QTN within a given generation; (6) they reduced the level of inbreeding when editing a subset of the sires; and (7) they increased the efficiency of converting genetic variation into genetic gain. Conclusions Genome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency caused by editing, which results in even higher genetic gain over a shorter period of time with no impact on inbreeding

Cas9-triggered chain ablation of cas9 as a gene drive brake

With the advent of clustered, regularly interspaced, short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) technology, researchers can construct gene drives that can bias the inheritance of edited alleles to alter entire populations. As demonstrated with the mutagenic chain reaction in Drosophila4, the CRISPR-Cas9 system can propagate genomic modification together with the genome-editing machinery itself. Although gene drives might have the potential to control insect-borne diseases and agricultural pests, substantial concerns have been raised over unanticipated ecological consequences as a result of drive use. Here we report the development of a potential Cas9-based gene drive 'brake' that remains inert in a wild-type genome but is activated by Cas9 to both cleave the genomic cas9 sequence and to convert an incoming cas9 allele into a brake. This means that the propagation of the brake is favored in a cas9-carrying population

Modulating signaling networks by CRISPR/Cas9-mediated transposable element insertion

In a recent past, transposable elements (TEs) were referred to as selfish genetic components only capable of copying themselves with the aim of increasing the odds of being inherited. Nonetheless, TEs have been initially proposed as positive control elements acting in synergy with the host. Nowadays, it is well known that TE movement into host genome comprises an important evolutionary mechanism capable of increasing the adaptive fitness. As insights into TE functioning are increasing day to day, the manipulation of transposition has raised an interesting possibility of setting the host functions, although the lack of appropriate genome engineering tools has unpaved it. Fortunately, the emergence of genome editing technologies based on programmable nucleases, and especially the arrival of a multipurpose RNA-guided Cas9 endonuclease system, has made it possible to reconsider this challenge. For such purpose, a particular type of transposons referred to as miniature inverted-repeat transposable elements (MITEs) has shown a series of interesting characteristics for designing functional drivers. Here, recent insights into MITE elements and versatile RNA-guided CRISPR/Cas9 genome engineering system are given to understand how to deploy the potential of TEs for control of the host transcriptional activity.Fil: Vaschetto, Luis Maria Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Diversidad Animal I; Argentin

Synchronous communication in PLM environments using annotated CAD models

The connection of resources, data, and knowledge through communication technology plays a vital role in current collaborative design methodologies and Product Lifecycle Management (PLM) systems, as these elements act as channels for information and meaning. Despite significant advances in the area of PLM, most communication tools are used as separate services that are disconnected from existing development environments. Consequently, during a communication session, the specific elements being discussed are usually not linked to the context of the discussion, which may result in important information getting lost or becoming difficult to access. In this paper, we present a method to add synchronous communication functionality to a PLM system based on annotated information embedded in the CAD model. This approach provides users a communication channel that is built directly into the CAD interface and is valuable when individuals need to be contacted regarding the annotated aspects of a CAD model. We present the architecture of a new system and its integration with existing PLM systems, and describe the implementation details of an annotation-based video conferencing module for a commercial CAD application.This work was supported by the Spanish Ministry of Economy and Competitiveness and the FEDER Funds, through the ANNOTA project (Ref. TIN2013-46036-C3-1-R).Camba, JD.; Contero, M.; Salvador Herranz, GM.; Plumed, R. (2016). Synchronous communication in PLM environments using annotated CAD models. Journal of Systems Science and Systems Engineering. 25(2):142-158. https://doi.org/10.1007/s11518-016-5305-5S142158252Abrahamson, S., Wallace, D., Senin, N. & Sferro, P. (2000). Integrated design in a service marketplace. Computer-Aided Design, 32(2):97–107.Ahmed, S. (2005). Encouraging reuse of design knowledge: a method to index knowledge. Design Studies, 26:565–592.Alavi, M. & Tiwana, A (2002). Knowledge integration in virtual teams: the potential role of KMS. Journal of the American Society for Information Science and Technology, 53:1029–1037.Ameri, F. & Dutta, D. (2005). Product lifecycle management: closing the knowledge loops. Computer-Aided Design and Applications, 2(5):577–590.Anderson, A.H., Smallwood, L., MacDonald, R., Mullin, J., Fleming, A. & O'Malley, C. (2000). Video data and video links in mediated communication: what do users value? International Journal of Human-Computer Studies, 52(1):165–187.Arias, E., Eden, H., Fischer, G., Gorman, A. & Scharff, E. (2000). Transcending the individual human mind–creating shared understanding through collaborative design. ACM Transactions on Computer-Human Interaction (TOCHI) 7(1): 84–113.Barley, W.C., Leonardi, P.M., & Bailey, D.E. (2012). Engineering objects for collaboration: strategies of ambiguity and clarity at knowledge boundaries. Human Communication Research, 38:280–308.Boujut, J.F. & Dugdale, J. (2006). Design of a 3D annotation tool for supporting evaluation activities in engineering design. Cooperative Systems Design, COOP 6:1–8.Camba, J., Contero, M., Johnson, M. & Company, P. (2014). Extended 3D annotations as a new mechanism to explicitly communicate geometric design intent and increase CAD model reusability. Computer-Aided Design, 57:61–73.Camba, J., Contero, M. & Salvador-Herranz, G. (2014). Speak with the annotator: promoting interaction in a knowledge-based CAD environment built on the extended annotation concept. Proceedings of the 2014 IEEE 18th International Conference on Computer Supported Cooperative Work in Design (CSCWD), 196–201.Chudoba, K.M., Wynn, E., Lu, M. & Watson-Manheim, M.B. (2005). How virtual are we? Measuring virtuality and understanding its impact in a global organization. Information Systems Journal, 15(4):279–306.Danesi, F., Gardan, N. & Gardan, Y. (2006). Collaborative Design: from Concept to Application. Geometric Modeling and Imaging—New Trends, 90–96.Durstewitz, M., Kiefner, B., Kueke, R., Putkonen, H., Repo, P. & Tuikka, T. (2002). Virtual collaboration environment for aircraft design. Proceedings of the IEEE 6th International Conference on Information Visualisation, 502–507.Fisher, D., Brush, A.J., Gleave, E. & Smith, M.A. (2006). Revisiting Whittaker and Sidner’s email overload ten years later. Proceedings of the 2006 20th Anniversary Conference on Computer Supported Cooperative Work. ACM, BanffFonseca, M.J., Henriques, E., Silva, N., Cardoso, T. & Jorge, J.A. (2006). A collaborative CAD conference tool to support mobile engineering. Rapid Product Development (RPD’06), Marinha Grande, Portugal.Frechette, S.P. (2011). Model based enterprise for manufacturing. Proceedings of the 44th CIRP International Conference on Manufacturing Systems.Fu, W.X., Bian, J. & Xu, Y.M. (2013). A video conferencing system for collaborative engineering design. Applied Mechanics and Materials, 344:246–252.Fuh, J.Y.H. & Li, W.D. (2005). Advances in collaborative CAD: the-state-of-the art. Computer-Aided Design, 37:571–581.Fussell, S.R., Kraut, R.E. & Siegel, J. (2000). Coordination of communication: effects of shared visual context on collaborative work. Proceedings of the 2000 ACM Conference on Computer Supported Cooperative Work, 21–30.Gajewska, H., Kistler, J., Manasse, M.S. & Redell, D. (1994). Argo: a system for distributed collaboration. Proceedings of the ACM Second International Conference on Multimedia, San Francisco, CA, USA. 433–440.Gantz, J., Reinsel, D., Chute, C., Schlichting, W., Mcarthur, J., Minton, S., Xheneti, I., Toncheva, A. & Manfrediz, A. (2007). The expanding digital universe: a forecast of worldwide information growth through 2010. IDC, Massachusetts.Gowan, Jr. J.A. & Downs, J.M. (1994). Video conferencing human-machine interface: a field study. Information and Management, 27(6):341–356.Gupta, A., Mattarelli, E., Seshasai, S. & Broschak, J. (2009). Use of collaborative technologies and knowledge sharing in co-located and distributed teams: towards the 24-h knowledge factory. The Journal of Strategic Information Systems, 18:147–161.Hickson, I. (2009). The Web Socket Protocol IETF, Standards Track.Hong, J., Toye, G. & Leifer, L.J. (1996). Engineering design notebook for sharing and reuse. Computers in Industry, 29:27–35.Isaacs, E.A. & Tang, J.C. (1994). What video can and cannot do for collaboration: a case study. Multimedia Systems, 2(2):63–73.Karsenty, L. (1999). Cooperative work and shared visual context: an empirical study of comprehension problems in side-by-side and remote help dialogues. Human Computer Interaction, 14(3): 283–315.Lahti, H., Seitamaa-Hakkarainen, P. & Hakkarainen, K. (2004). Collaboration patterns in computer supported collaborative designing. Design Studies, 25:351–371.Leenders, R.T.A., Van Engelen, J.M. & Kratzer, J. (2003). Virtuality, communication, and new product team creativity: a social network perspective. Journal of Engineering and Technology Management, 20(1):69–92.Levitt, R.E., Jin, Y. & Dym, C.L. (1991). Knowledge-based support for management of concurrent, multidisciplinary design. Artificial Intelligence for Engineering, Design, Analysis and Manufacturing, 5(2):77–95.Li, C., McMahon, C. & Newnes, L. (2009). Annotation in product lifecycle management: a review of approaches. Proceedings of the ASME International Design Engineering Technical Conferences and Computers and Information in Engineering Conference, DETC2009. Vol. 2. New York: ASME, 797–806.Li, W.D., Lu, W.F., Fuh, J.Y. & Wong, Y.S. (2005). Collaborative computer-aided design-research and development status. Computer-Aided Design, 37(9):931–940.Londono, F., Cleetus, K.J., Nichols, D.M., Iyer, S., Karandikar, H.M., Reddy, S.M., Potnis, S.M., Massey, B., Reddy, A. & Ganti, V. (1992). Coordinating a virtual team. CERC-TR-RN-92-005, Concurrent Engineering Research Centre, West Virginia University, West Virginia.Lubell, J., Chen, K., Horst, J., Frechette, S., & Huang, P. (2012). Model based enterprise/technical data package summit report. NIST Technical Note, 1753.May, A. & Carter, C. (2001). A case study of virtual team working in the European automotive industry. International Journal of Industrial Ergonomics, 27(3):171–186.Olson, J.S., Olson, G.M. & Meader, D.K. (1995). What mix of video and audio is useful for small groups doing remote real-time design work? Proceedings of the SIGCHI Conference on Human Factors in Computing Systems. ACM Press, Addison-Wesley Publishing Co.Ping-Hung, H., Mishra, C.S. & Gobeli, D.H. (2003). The return on R&D versus capital expenditures in pharmaceutical and chemical industries. IEEE Transactions on Engineering Management, 50:141–150.Sharma, A. (2005). Collaborative product innovation: integrating elements of CPI via PLM framework. Computer-Aided Design, 37(13):1425–1434.Shum, S.J.B., Selvin, A.M., Sierhuis, M., Conklin, J., Haley, C.B. & Nuseibeh, B. (2006). Hypermedia support for argumentation-based rationale: 15 Years on from Gibis and Qoc. Rationale Management in Software Engineering, 111–132.Siltanen, P. & Valli, S. (2013). Web-based 3D Mediated Communication in Manufacturing Industry. Concurrent Engineering Approaches for Sustainable Product Development in a Multidisciplinary Environment, 1181–1192. Springer London.Stark, J. (2011). Product Lifecycle Management. 1–16. Springer London.Tavcar, J., Potocnik, U. & Duhovnik, J. (2013). PLM used as a backbone for concurrent engineering in supply chain. Concurrent Engineering Approaches for Sustainable Product Development in a Multi-Disciplinary Environment, 681–692.Tay, F.E.H. & Ming, C. (2001). A shared multi-media design environment for concurrent engineering over the internet. Concurrent Engineering, 9(1):55–63.Tay, F.E.H. & Roy, A. (2003). CyberCAD: a collaborative approach in 3D-CAD technology in a multimedia-supported environment. Computers in Industry, 52(2):127–145.Toussaint, J. & Cheng, K. (2002). Design agility and manufacturing responsiveness on the web. Integrated Manufacturing Systems, 13(5):328–339.Tsoi, K.N. & Rahman, S.M. (1996). Media-on-demand multimedia electronic mail: a tool for collaboration on the web. Proceedings of the 5th IEEE International Symposium on High Performance Distributed Computing.Upton, D.M. & Mcafee, A. (1999). The Real Virtual Factory. Harvard Business School Press, 69–89.Vila, C., Estruch, A., Siller, H.R., Abellán, J.V. & Romero, F. (2007). Workflow methodology for collaborative design and manufacturing. Cooperative Design, Visualization, and Engineering 42–49, Springer Berlin Heidelberg.Wasiak, J., Hicks, B., Newnes, L., Dong, A., & Burrow, L. (2010). Understanding engineering email: the development of a taxonomy for identifying and classifying engineering work. Research in Engineering Design, 21(1):43–64.Wasko, M.M. & Faraj, S. (2005). Why should I share? Examining social capital and knowledge contribution in electronic networks of practice. MIS Quarterly: Management Information Systems, 29:35–57.Yang, Q.Z., Zhang, Y., Miao, C.Y. & Shen, Z.Q. (2008). Semantic annotation of digital engineering resources for multidisciplinary design collaboration. ASME 2008 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference, 617–624. American Society of Mechanical Engineers.You, C.F. & Chao, S.N. (2006). Multilayer architecture in collaborative environment. Concurrent Engineering Research and Applications, 14(4):273–281.Yuan, Y.C., Fulk, J., Monge, P.R. & Contractor, N. (2010). Expertise directory development, shared task interdependence, and strength of communication network ties as multilevel predictors of expertise exchange in transactive memory work groups. Communication Research, 37: 20–47

Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

The melanocortin 1 receptor is a G-protein-coupled receptor, described to be expressed on melanomas and melanocytes. Subsequent RT–PCR studies demonstrated the presence of melanocortin 1 receptor mRNA in other tissues such as pituitary gland and testis. Previously, we have demonstrated that three HLA-A2 binding nonamer peptides derived from melanocortin 1 receptor can elicit peptide-specific CTL which can recognize target cells transfected with the melanocortin 1 receptor gene and MHC class I matched melanoma lines. The potential of targeting melanocortin 1 receptor in therapy and diagnosis will depend on a preferential expression of this receptor in the majority of primary and metastatic melanomas vs normal tissues. We tested a panel of melanomas, carcinomas and other cell lines for the presence of melanocortin 1 receptor, using two monoclonal antibodies. The receptor was detected in 83% of the tested melanoma cell lines but not in other carcinoma lines. Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes. Flow cytometry studies showed that melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of that found in melanomas. Peripheral blood-derived dendritic cells, also express melanocortin 1 receptor in vitro. This extensive analysis of melanocortin 1 receptor tissue distribution may be of relevance not only for melanoma immunology, but also for research on the pathogenicity of inflammatory conditions in the skin and neurologic tissues. It remains to be seen if the over-expression of melanocortin 1 receptor in melanomas is sufficiently high to allow a ‘therapeutic window’ to be exploited in cancer immunotherapy