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Increasingly, national space agencies are expanding their goals to include Mars exploration with sample return. To better protect Earth and its biosphere from potential extraterrestrial sources of contamination, as set forth in the Outer Space Treaty of 1967, international efforts to develop planetary protection measures strive to understand the danger of cross-contamination processes in Mars sample return missions. We aim to better understand the impact of the martian surface on microbial dormancy and survivability. Radiation resistance of microbes is a key parameter in considering survivability of microbes over geologic times on the frigid, arid surface of Mars that is bombarded by solar and galactic cosmic radiation. We tested the influence of desiccation and freezing on the ionizing radiation survival of six model microorganisms: vegetative cells of two bacteria (Deinococcus radiodurans, Escherichia coli) and a strain of budding yeast (Saccharomyces cerevisiae); and vegetative cells and endospores of three Bacillus bacteria (B. subtilis, B. megaterium, B. thuringiensis). Desiccation and freezing greatly increased radiation survival of vegetative polyploid microorganisms when applied separately, and when combined, desiccation and freezing increased radiation survival even more so. Thus, the radiation survival threshold of polyploid D. radiodurans cells can be extended from the already high value of 25 kGy in liquid culture to an astonishing 140 kGy when the cells are both desiccated and frozen. However, such synergistic radioprotective effects of desiccation and freezing were not observed in monogenomic or digenomic Bacillus cells and endospores, which are generally sterilized by 12 kGy. This difference is associated with a critical requirement for survivability under radiation, that is, repair of genome damage caused by radiation. Deinococcus radiodurans and S. cerevisiae accumulate similarly high levels of the Mn antioxidants that are required for extreme radiation resistance, as do endospores, though they greatly exceed spores in radioresistance because they contain multiple identical genome copies, which in D. radiodurans are joined by persistent Holliday junctions. We estimate ionizing radiation survival limits of polyploid DNA-based life-forms to be hundreds of millions of years of background radiation while buried in the martian subsurface. Our findings imply that forward contamination of Mars will essentially be permanent, and backward contamination is a possibility if life ever existed on Mars. Abstract. Bibliografija: str. 1348-1350.

The adequacy of the surgical resection is the main controllable variable that is in the hands of the surgical team. There exists an unmet need to increase the rate of negative margins, particularly in cancers invading the craniofacial area. The study aimed 1) at developing a gross tumor model to be utilized for research, educational, and training purposes and 2) establishing the 3-dimensional relationship between the outer surface of the surgical specimen and tumor surface and test the effect of guiding ablations on cadavers with surgical navigation (SN).Seven cadaver heads were employed to create 24 craniofacial tumor models. Simulation of tumor resections was performed by 8 surgeons. Fourteen and 10 resections were performed with and without SN-guidance, respectively. Gross specimens underwent computed tomography and 3-dimensional analysis through dedicated software. Task load was assessed through a validated questionnaire. Tumor model reliability was studied based on visual analogue scale rate by surgeons and radiologists.SN reduced the rate of margin involvement, particularly by decreasing the percentage of the gross specimen outer surface involvement in areas uncovered by normal bony structures. The workload of SN-aided ablations was found to be medium-to-somewhat-high. Tumor model reliability was deemed satisfactory except for the extension to bony structures.A gross tumor model for head and neck cancers involving the craniofacial area was developed and resulted satisfactorily reliable from both a surgical and radiologic standpoint. SN reduced the rate of margin involvement, particularly by improving delineation of bone-uncovered areas.

Background Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction.Methods In this preclinical study, the performance of two bioengineered scaffolds, an hydrogel made of polyethylene glycol-chitosan (HyCh) and an hybrid core-shell combination of poly(L-lactic acid)/poly(\(\epsilon\)-caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stem cells (hMSCs) (i.e. 1000, 2000, and 3000 cells/mm3), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses.Results The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs (2000 and 3000 cells/mm3). The immunohistochemical profile showed significantly higher expression of both VEGF-A, in defects reconstructed with a PLA-PCL-HyCh, and osteopontin, in defects reconstructed with both scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group.Conclusions Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.

Surgical navigation technology combines patient imaging studies with intraoperative real-time data to improve surgical precision and patient outcomes. The navigation workflow can also include preoperative planning, which can reliably simulate the intended resection and reconstruction. The advantage of this approach in skull-base surgery is that it guides access into a complex three-dimensional area and orients tumors intraoperatively with regard to critical structures, such as the orbit, carotid artery and brain. This enhances a surgeon’s capabilities to preserve normal anatomy while resecting tumors with adequate margins. The aim of this narrative review is to outline the state of the art and the future directions of surgical navigation in the skull base, focusing on the advantages and pitfalls of this technique. We will also present our group experience in this field, within the frame of the current research trends.

BACKGROUND Balloon dilation of the eustachian tube is a new therapeutic option for eustachian tube dysfunction. One of the limiting factors of wider adoption of this technique in many parts of the world is the high cost of the devices, in spite of regulatory approval of safety. OBJECTIVE Evaluate the performance and usability of standard less-expensive endovascular balloons for eustachian tube dilation in comparison to an approved device in a preclinical study. STUDY DESIGN Comparative cadaver feasibility study. SETTING University tertiary care facility. METHODS Ten eustachian tube dilations were performed with an approved eustachian tube dilation device. Ten other procedures were carried out with an endovascular balloon of similar dimensions. Cone beam computerized tomography was performed to evaluate the extent of dilation and possible damages. The lumen and mucosal lining were inspected endoscopically post-dilation. Volume measurements were compared before and after the procedure in both groups using contrast enhancement. RESULTS All 20 eustachian tube dilations were carried out successfully. No tissue damages could be identified on cone-beam computerized tomography or via endoscopic examination. There was a statistically significant difference of eustachian tube volumes between pre- and post-dilations, with no statistically significant difference between the devices. CONCLUSION Eustachian tube dilation with a less costly endovascular balloon achieved similar results to an approved eustachian tube dilation device. No damages or any other safety concerns were identified in a cadaver study.

Acinetobacter baumannii causes multi-system diseases in both nosocomial settings and a pre-disposed general population. The bacterium is not only desiccation-resistant but also notoriously resistant to multiple antibiotics and drugs of last resort including carbapenem, colistin, and sulbactam. The World Health Organization has categorized carbapenem-resistant A. baumannii at the top of its critical pathogen list in a bid to direct urgent countermeasure development. Several early-stage vaccines have shown a range of efficacies in healthy mice, but no vaccine candidates have advanced into clinical trials. Herein, we report our findings that both an ionizing γ-radiation-inactivated and a non-ionizing ultraviolet C-inactivated whole-cell vaccine candidate protects neutropenic mice from pulmonary challenge with virulent AB5075, a particularly pathogenic isolate. In addition, we demonstrate that a humoral response is sufficient for this protection via the passive immunization of neutropenic mice.

Several technologies have been implemented in orthopedic surgery to improve surgical outcomes, usually focusing on more accurate execution of a surgical plan, but the development of the plan itself is also of great importance. The purpose of this study is to examine whether the use of preoperative computer planning platforms can improve the surgical plan? Eight surgeons created a preoperative surgical plan to resect a distal femur parosteal osteosarcoma in two settings: (1) Using a 2-D and 3-D CT scan only (current standard); and (2) using a computer-assisted planning platform. The plans were thereafter virtually executed using a novel surgical navigation system and a Sawbones model. This simulated model was derived from, and identical to, an actual patient scenario. The outcomes of interest were the number of positive margin cuts, and the volume of the resected specimen. Using the surgical plan developed with computer assistance, there were 4 positive margin cuts made by 2 surgeons. In comparison, using standard planning, there were 14 positive margin cuts made by all 8 surgeons (p = 0.02). The resection volume was larger in the computer-assisted plans (96 ± 10 mm3) than in the standard plans (88 ± 7 mm3) (p = 0.055). Computer-assisted planning significantly decreased the risk of a positive margin resection in this Sawbones tumor model used to simulate resection of a primary bone sarcoma. This proof of concept study highlights the importance of advanced surgical planning and sets the ground for developing beneficial surgical planning systems.

Importance Skull base surgery requires precise preoperative assessment and intraoperative management of the patient. Surgical navigation is routinely used for complex skull base cases; however, the image guidance is commonly based on preoperative scans alone. Objective The primary objective of this study was to assess the image quality of intraoperative cone-beam computed tomography (CBCT) within anatomical landmarks used in sinus and skull base surgery. The secondary objective was to assess the registration error of a surgical navigation system based on intraoperative CBCT. Design Present study is a retrospective case series of image quality after intraoperative cone beam CT. Setting The study was conducted at Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto. Participants A total of 46 intraoperative scans (34 patients, 21 skull base, 13 head and neck) were studied. Main Outcome and Measures Thirty anatomical landmarks (vascular, soft tissue, and bony) within the sinuses and anterior skull base were evaluated for general image quality characteristics: (1) bony detail visualization; (2) soft-tissue visualization; (3) vascular visualization; and (4) freedom from artifacts (e.g., metal). Levels of intravenous (IV) contrast enhancement were quantified in Hounsfield's units (HU). Standard paired-point registration between imaging and tracker coordinates was performed using 6 to 8 skin fiducial markers and the corresponding fiducial registration error (FRE) was measured. Results Median score for bony detail on CBCT was 5, remaining at 5 after administration of IV contrast. Median soft-tissue score was 2 for both pre- and postcontrast. Median vascular score was 1 precontrast and 3 postcontrast. Median score for artifacts on CBCT were 2 for both pre-and postcontrast, and metal objects were noted to be the most significant source of artifact. Intraoperative CBCT allowed preresection images and immediate postresection images to be available to the skull base surgeon. There was a significant improvement in mean (standard deviation [SD]) CT intensity in the left carotid artery postcontrast 334 HU (67 HU) (p Conclusion Intraoperative CBCT in complex skull base procedures provides high-resolution bony detail allowing immediate assessment of complex resections. The use of IV contrast with CBCT improves the visualization of vasculature. Image-guidance based on CBCT yields registration errors consistent with standard techniques.

Denham Harman’s oxidative damage theory identifies superoxide (O2•−) radicals as central agents of aging and radiation injury, with Mn2+-dependent superoxide dismutase (MnSOD) as the principal O2•−-scavenger. However, in the radiation-resistant nematode Caenorhabditis elegans, the mitochondrial antioxidant enzyme MnSOD is dispensable for longevity, and in the model bacterium Deinococcus radiodurans, it is dispensable for radiation resistance. Many radiation-resistant organisms accumulate small-molecule Mn2+-antioxidant complexes well-known for their catalytic ability to scavenge O2•−, along with MnSOD, as exemplified by D. radiodurans. Here, we report experiments that relate the MnSOD and Mn-antioxidant content to aging and oxidative stress resistances and which indicate that C. elegans, like D. radiodurans, may rely on Mn-antioxidant complexes as the primary defense against reactive oxygen species (ROS). Wild-type and ΔMnSOD D. radiodurans and C. elegans were monitored for gamma radiation sensitivities over their life spans while gauging Mn2+-antioxidant content by electron paramagnetic resonance (EPR) spectroscopy, a powerful new approach to determining the in vivo Mn-antioxidant content of cells as they age. As with D. radiodurans, MnSOD is dispensable for radiation survivability in C. elegans, which hyperaccumulates Mn-antioxidants exceptionally protective of proteins. Unexpectedly, ΔMnSOD mutants of both the nematodes and bacteria exhibited increased gamma radiation survival compared to the wild-type. In contrast, the loss of MnSOD renders radiation-resistant bacteria sensitive to atmospheric oxygen during desiccation. Our results support the concept that the disparate responses to oxidative stress are explained by the accumulation of Mn-antioxidant complexes which protect, complement, and can even supplant MnSOD.

Positive margins have been reported up to 80% in advanced maxillary cancers. Intraoperative navigation (IN) aims to improve margins, but provides a two-dimensional view of a registered instrument without anticipating any cutting directions, and the information is displayed in monitors outside surgical field. Augmented Reality (AR) can delineate margins while addressing the gaze-toggling drawback of IN. In a preclinical setting, we implemented preoperative-planned osteotomies needed for maxillectomies and projected this information on the surgical field using AR. We aimed to improve negative margin rates while retaining the benefits of AR.Five maxillary tumor models were built. Five fellowship-trained surgeons completed virtual unguided and AR-guided maxillectomies. Comparisons in terms of intratumoral cuts, close, adequate, and excessive distances from the tumor were performed. Differences between "ideal" cutting-plan and the AR-guided virtual osteotomies was obtained. Workload questionnaires to evaluate the technology were completed.115 virtual osteotomies were analyzed. Intra-tumoral and "close" margins were lower for the AR-assisted osteotomies (0.0% vs 1.9% p 0.0001 and 0.8% vs 7.9% p 0.0001). Proportion of "adequate" margins were higher in the AR simulations (25.3% vs 18.6%, p = 0.018). The AR osteotomies had high similarity with the pre-planned with interclass correlation index close to 1 in "adequate" margins 0.893 (95% CI: 0.804-0.949). Workload scores were better for AR-guided simulations for the domains of mental demand, performance, effort and frustration.The projector-based AR method improved margin delineation, and preoperative planning was accurately translated to the simulations. Clinical translation will aim to consolidate our preclinical findings to improve outcomes.

Computer-assisted surgery (CAS) can improve surgical precision in orthopaedic oncology. Accurate alignment of the patient's imaging coordinates with the anatomy, known as registration, is one of the most challenging aspects of CAS and can be associated with substantial error. Using intraoperative, on-the-table, cone-beam computed tomography (CBCT), we performed a pilot clinical study to validate a method for automatic intraoperative registration.Patients who were ≥18 years of age, had benign bone tumors, and underwent resection were prospectively enrolled. In addition to inserting a navigation tracking tool into the exposed bone adjacent to the surgical field, 2 custom plastic ULTEM tracking tools (UTTs) were attached to each patient's skin adjacent to the tumor using an adhesive. These were automatically localized within the 3-dimensional CBCT volume to be used as image landmarks for registration, and the corresponding tracker landmarks were captured using an infrared camera. The main outcomes were the fiducial registration error (FRE) and the target registration error (TRE). The navigation time was recorded.Thirteen patients with benign tumors in the femur (n = 10), tibia (n = 2), and humerus (n = 1) underwent navigation-assisted resections. The mean values were 0.67 ± 0.15 mm (range, 0.47 to 0.97 mm) for FRE and 0.83 ± 0.51 mm (range, 0.42 to 2.28 mm) for TRE. Registration was successful in all cases. The mean time for CBCT imaging and tracker registration was 7.5 minutes.We present a novel automatic registration method for CAS exploiting intraoperative CBCT capabilities, which provided improved accuracy and reduced operative times compared with more traditional methods.This proof-of-principle study validated a novel process for automatic registration to improve the accuracy of resecting bone tumors using a surgical navigation system.

Balloon dilation of the eustachian tube is a new therapeutic option for eustachian tube dysfunction. One of the limiting factors of wider adoption of this technique in many parts of the world is the high cost of the devices, in spite of regulatory approval of safety.Evaluate the performance and usability of standard less-expensive endovascular balloons for eustachian tube dilation in comparison to an approved device in a preclinical study.Comparative cadaver feasibility study.University tertiary care facility.Ten eustachian tube dilations were performed with an approved eustachian tube dilation device. Ten other procedures were carried out with an endovascular balloon of similar dimensions. Cone beam computerized tomography was performed to evaluate the extent of dilation and possible damages. The lumen and mucosal lining were inspected endoscopically post-dilation. Volume measurements were compared before and after the procedure in both groups using contrast enhancement.All 20 eustachian tube dilations were carried out successfully. No tissue damages could be identified on cone-beam computerized tomography or via endoscopic examination. There was a statistically significant difference of eustachian tube volumes between pre- and post-dilations, with no statistically significant difference between the devices.Eustachian tube dilation with a less costly endovascular balloon achieved similar results to an approved eustachian tube dilation device. No damages or any other safety concerns were identified in a cadaver study.

BackgroundThe resection of advanced maxillary sinus cancers can be challenging due to the anatomical proximity to surrounding critical anatomical structures. Transnasal endoscopy can effectively aid the delineation of the posterior margin of resection. Implementation with 3D-rendered surgical navigation with virtual endoscopy (3D-SNVE) may represent a step forward. This study aimed to demonstrate and quantify the benefits of this technology.Material and MethodFour maxillary tumor models with critical posterior extension were created in four artificial skulls (Sawbones®). Images were acquired with cone-beam computed tomography and the tumor and carotid were contoured. Eight head and neck surgeons were recruited for the simulations. Surgeons delineated the posterior margin of resection through a transnasal approach and avoided the carotid while establishing an adequate resection margin with respect to tumor extirpation. Three simulations were performed: 1) unguided: based on a pre-simulation study of cross-sectional imaging; 2) tumor-guided: guided by real-time tool tracking with 3D tumor and carotid rendering; 3) carotid-guided: tumor-guided with a 2-mm alert cloud surrounding the carotid. Distances of the planes from the carotid and tumor were classified as follows and the points of the plane were classified accordingly: “red”: through the carotid artery; “orange”: 2 mm from the carotid and within the tumor or 2 mm from the carotid and 5–10 mm from the tumor; and “blue”: >2 mm from the carotid and >10 mm from the tumor. The three techniques (unguided, tumor-guided, and carotid-guided) were compared.Results3D-SNVE for the transnasal delineation of the posterior margin in maxillary tumor models significantly improved the rate of margin-negative clearance around the tumor and reduced damage to the carotid artery. “Green” cuts occurred in 52.4% in the unguided setting versus 62.1% and 64.9% in the tumor- and carotid-guided settings, respectively (p < 0.0001). “Red” cuts occurred 6.7% of the time in the unguided setting versus 0.9% and 1.0% in the tumor- and carotid-guided settings, respectively (p < 0.0001).ConclusionsThis preclinical study has demonstrated that 3D-SNVE provides a substantial improvement of the posterior margin delineation in terms of safety and oncological adequacy. Translation into the clinical setting, with a meticulous assessment of the oncological outcomes, will be the proposed next step.

Networks of transcriptional and post-transcriptional regulators are critical for bacterial survival and adaptation to environmental stressors. While transcriptional regulators provide rapid activation and/or repression of a wide-network of genes, post-transcriptional regulators, such as small RNAs (sRNAs), are also important to fine-tune gene expression. However, the mechanisms of sRNAs remain poorly understood, especially in less-studied bacteria. Deinococcus radiodurans is a gram-positive bacterium resistant to extreme levels of ionizing radiation (IR). Although multiple unique regulatory systems (e.g., the Radiation and Desiccation Response (RDR)) have been identified in this organism, the role of post-transcriptional regulators has not been characterized within the IR response. In this study, we have characterized an sRNA, PprS (formerly Dsr2), as a post-transcriptional coordinator of IR recovery in D. radiodurans. PprS showed differential expression specifically under IR and knockdown of PprS resulted in reduced survival and growth under IR, suggesting its importance in regulating post-radiation recovery. We determined a number of potential RNA targets involved in several pathways including translation and DNA repair. Specifically, we confirmed that PprS binds within the coding region to stabilize the pprM (DR_0907) transcript, a RDR modulator. Overall, these results are the first to present an additional layer of sRNA-based control in DNA repair pathways associated with bacterial radioresistance.

BACKGROUND The image-guided operating room (OR) is an emerging standard for dealing with complex cases in many surgical disciplines including neurosurgery, thoracic surgery, maxillofacial trauma, and orthopedic surgery. Its use in head and neck oncological surgery is not well established. The primary aim of this study was to assess the image quality of cone-beam CT (CBCT) under real clinical conditions. The secondary aim was to assess the effect on surgical performance and decision making. METHODS Intraoperative 3D imaging was performed using a CBCT capable C-Arm mounted on a multi-axis robot (Siemens Zeego) in the image-guided OR. All patients had immediate preoperative imaging taken with further intraoperative imaging performed as required. Ten initial patients, comprising 28 intraoperative scans, were used for questionnaire-based image reviews conducted with experienced head and neck clinicians. Scans were assessed for aspects of both image quality and clinical utility, on separate 5-point Likert scales (1-5). RESULTS The median rating for bony detail was 4 out of 5. Vascular detail was increased (P < 10-8 ) from 1 to 3 with the use of IV contrast (region of interest CT# was 284 HU [SD, 47 HU]). Images were rated as 4 for freedom from artifact. Soft tissue definition was 2, with no significant improvement (P = .2) with the addition of IV iodinated contrast. Surgeons rated the greatest clinical utility (4) for the CBCT when assessing postreconstruction imaging of a complex case. CONCLUSIONS The image quality of CBCT in the image-guided OR is good for bony detail and complex oncological reconstructions in the head and neck setting but probably has limited benefit for intraoperative soft tissue delineation. Future studies must also focus on clinical outcomes to help demonstrate the value of the image-guided OR.

Clinical trials with novel fluorescence contrast agents for head and neck cancer are driving new applications for fluorescence-guided surgery. Two-dimensional fluorescence imaging systems, however, provide limited in vivo assessment capabilities to determine tumor invasion depth below the mucosal surface. Here, we investigate the use of spatial frequency domain imaging (SFDI) methods for sub-surface fluorescence in tissue-simulating oral cancer phantoms. A two-step profile-correction approach for SFDI is under development to account for the complex surface topography of the oral cavity. First, for structured-illumination estimation of the surface profile, we are evaluating gray code and phase shift profilometry methods in agar-based oral cavity phantoms to maximize resolution and minimize sensitivity to surface discontinuities. Second, for profile-correction of the diffuse reflectance, global lighting effects within the oral cavity – analogous to an integrating sphere – are modeled using a multi-bounce numerical model. Subsurface fluorescence imaging is enabled based on the variations in optical sampling depth that result from changes in spatial frequency. An analytical depth recovery approach is based on a numerical diffusion theory model for semi-infinite fluorescence slabs of variable thickness. Depth estimation is evaluated in an agar-based phantom with fluorescence inclusions of thicknesses 1-5.5 mm originating from the top surface (“iceberg model”). Future clinical studies are necessary to assess in vivo performance and intraoperative workflow.

Purpose of review Image guided navigation has had significant impact in head and neck surgery, and has been most prolific in endonasal surgeries. Although conventional image guidance involves static computed tomography (CT) images attained in the preoperative setting, the continual evolution of surgical navigation technologies is fast expanding to incorporate both real-time data and bioinformation that allows for improved precision in surgical guidance. With the rapid advances in technologies, this article allows for a timely review of the current and developing techniques in surgical navigation for head and neck surgery. Recent findings Current advances for cross-sectional-based image-guided surgery include fusion of CT with other imaging modalities (e.g., magnetic resonance imaging and positron emission tomography) as well as the uptake in intraoperative real-time 'on the table' imaging (e.g., cone-beam CT). These advances, together with the integration of virtual/augmented reality, enable potential enhancements in surgical navigation. In addition to the advances in radiological imaging, the development of optical modalities such as fluorescence and spectroscopy techniques further allows the assimilation of biological data to improve navigation particularly for head and neck surgery. Summary The steady development of radiological and optical imaging techniques shows great promise in changing the paradigm of head and neck surgery.

An integrated augmented reality (AR) surgical navigation system that potentially improves intra-operative visualization of concealed anatomical structures. Integration of real-time tracking technology with a laser pico-projector allows the surgical surface to be augmented by projecting virtual images of lesions and critical structures created by multimodality imaging. We aim to quantitatively and qualitatively evaluate the performance of a prototype interactive AR surgical navigation system through a series of pre-clinical studies. Four pre-clinical animal studies using xenograft mouse models were conducted to investigate system performance. A combination of CT, PET, SPECT, and MRI images were used to augment the mouse body during image-guided procedures to assess feasibility. A phantom with machined features was employed to quantitatively estimate the system accuracy. All the image-guided procedures were successfully performed. The tracked pico-projector correctly and reliably depicted virtual images on the animal body, highlighting the location of tumour and anatomical structures. The phantom study demonstrates the system was accurate to 0.55 ± 0.33mm. This paper presents a prototype real-time tracking AR surgical navigation system that improves visualization of underlying critical structures by overlaying virtual images onto the surgical site. This proof-of-concept pre-clinical study demonstrated both the clinical applicability and high precision of the system which was noted to be accurate to

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.

The proper functioning of many proteins requires their transport to the correct cellular compartment or their secretion. Signal recognition particle (SRP) is a major protein transport pathway responsible for the co-translational movement of integral membrane proteins as well as periplasmic proteins.Deinococcus radioduransis a ubiquitous bacterium that expresses a complex phenotype of extreme oxidative stress resistance, which depends on proteins involved in DNA repair, metabolism, gene regulation, and antioxidant defense. These proteins are located extracellularly or subcellularly, but the molecular mechanism of protein localization inD. radioduransto manage oxidative stress response remains unexplored. In this study, we characterized the SRP complex inD. radioduransR1 and showed that the knockdown (KD) of the SRP RNA (Qpr6) reduced bacterial survival under hydrogen peroxide and growth under chronic ionizing radiation. Through LC-mass spectrometry (MS/MS) analysis, we detected 162 proteins in the periplasm of wild-typeD. radiodurans, of which the transport of 65 of these proteins to the periplasm was significantly reduced in the Qpr6 KD strain. Through Western blotting, we further demonstrated the localization of the catalases inD. radiodurans, DR_1998 (KatE1) and DR_A0259 (KatE2), in both the cytoplasm and periplasm, respectively, and showed that the accumulation of KatE1 and KatE2 in the periplasm was reduced in the SRP-defective strains. Collectively, this study establishes the importance of the SRP pathway in the survival and the transport of antioxidant proteins inD. radioduransunder oxidative stress.

Several technologies have been implemented in orthopedic surgery to improve surgical outcomes, usually focusing on more accurate execution of a surgical plan, but the development of the plan itself is also of great importance. The purpose of this study is to examine whether the use of preoperative computer planning platforms can improve the surgical plan?Eight surgeons created a preoperative surgical plan to resect a distal femur parosteal osteosarcoma in two settings: (1) Using a 2-D and 3-D CT scan only (current standard); and (2) using a computer-assisted planning platform. The plans were thereafter virtually executed using a novel surgical navigation system and a Sawbones model. This simulated model was derived from, and identical to, an actual patient scenario. The outcomes of interest were the number of positive margin cuts, and the volume of the resected specimen.Using the surgical plan developed with computer assistance, there were 4 positive margin cuts made by 2 surgeons. In comparison, using standard planning, there were 14 positive margin cuts made by all 8 surgeons (p = 0.02). The resection volume was larger in the computer-assisted plans (96 ± 10 mmComputer-assisted planning significantly decreased the risk of a positive margin resection in this Sawbones tumor model used to simulate resection of a primary bone sarcoma. This proof of concept study highlights the importance of advanced surgical planning and sets the ground for developing beneficial surgical planning systems.

This study evaluates a long-acting liposomal fluorescence / CT dual-modality contrast agent (CF800) in head and neck cancer to enhance intraoperative tumor demarcation with fluorescence imaging and cone-beam computed tomography (CBCT). CF800 was administered to 12 buccal cancer-bearing rabbits. Imaging was acquired at regular time points to quantify time-dependent contrast enhancement. Surgery was performed 5-7 days after, with intraoperative near-infrared fluorescence endoscopy and CBCT, followed by histological and ex-vivo fluorescence assessment. Tumor enhancement on CT was significant at 24, 96 and 120 hours. Volumetric analysis of tumor segmentation showed high correlation between CBCT and micro-CT. Fluorescence signal was apparent in both ex-vivo and in-vivo imaging. Histological correlation showed [100%] specificity for primary tumor. Sensitivity and specificity of CF800 in detecting nodal involvement require further investigation.CF800 is long acting and has dual function for CT and fluorescence contrast, making it an excellent candidate for image-guided surgery.

Background Current sentinel lymph node biopsy (SLNB) techniques, including use of radioisotopes, have disadvantages including the use of a radioactive tracer. Indocyanine green (ICG) based near-infrared (NIR) fluorescence imaging and cone beam CT (CBCT) have advantages for intraoperative use. However, limited literature exists regarding their use in head and neck cancer SLNB. Methods This was a prospective, non-randomized study using a rabbit oral cavity VX2 squamous cell carcinoma model (n = 10) which develops lymph node metastasis. Pre-operatively, images were acquired by MicroCT. During surgery, CBCT and NIR fluorescence imaging of ICG was used to map and guide the SLNB resection. Results Intraoperative use of ICG to guide fluorescence resection resulted in identification of all lymph nodes identified by pre-operative CT. CBCT was useful for near real time intraoperative imaging and 3D reconstruction. Conclusions This pre-clinical study further demonstrates the technical feasibility, limitations and advantages of intraoperative NIR-guided ICG imaging for SLN identification as a complementary method during head and neck surgery.

Background Current sentinel lymph node biopsy (SLNB) techniques, including use of radioisotopes, have disadvantages including the use of a radioactive tracer. Indocyanine green (ICG) based near-infrared (NIR) fluorescence imaging and cone beam CT (CBCT) have advantages for intraoperative use. However, limited literature exists regarding their use in head and neck cancer SLNB.Methods This was a prospective, non-randomized study using a rabbit oral cavity VX2 squamous cell carcinoma model which develops lymph node metastasis. Pre-operatively, images were acquired by MicroCT and DCE-MRI. CBCT and NIR fluorescence imaging of ICG was used to map and guide the SLNB resection.Results Intraoperative use of ICG to guide fluorescence resection resulted in identification of all lymph nodes identified by pre-operative CT. CBCT was useful for near real time intraoperative imaging and 3D reconstruction.Conclusions This pre-clinical study further demonstrates the technical feasibility, limitations and advantages of intraoperative NIR-guided ICG imaging for SLN identification as a complementary method during head and neck surgery.

A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest.

Current intraoperative methods to assess tumor invasion depth in mucosal oral cancer provide limited real-time information. The advent of targeted fluorescence contrast agents for head and neck cancer is a promising innovation, but surgical imaging systems typically provide only two-dimensional views. Here, we investigate the use of an image-guided fluorescence tomography (igFT) system to estimate the depth of tumor invasion in tissue-simulating oral cancer phantoms. Implementation of non-contact diffuse optical tomography using finite-element software (NIRFAST) is enabled with geometric data from intraoperative cone-beam CT (CBCT) imaging and surgical navigation. The tissue phantoms used gelatin for the background (5% for fat, 10% for muscle) and 2% agar for palpable, tumor-like inclusions. Standard agents were used for absorption (hemoglobin), scattering (Intralipid), fluorescence (indocyanine green), and CT contrast (iohexol). The agar inclusions were formed using 3D printed molds, and positioned at the surface of the gelatin background to mimic mucosal tumor invasion (an “iceberg” model). Simulations and phantom experiments characterize fluorescence tomography performance across a range of tumor invasion depths. To aid surgical visualization, the fluorescence volume is converted to a colored surface indicating tumor depth, and overlaid on the navigated endoscopic video. Clinical studies are necessary to assess in vivo performance and intraoperative workflow.

Over the last ten years, Chikungunya virus (CHIKV), an Old World alphavirus has caused numerous outbreaks in Asian and European countries and the Americas, making it an emerging pathogen of great global health importance. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, on the other hand, has been developed as a bioweapon in the past due to its ease of preparation, aerosol dispersion and high lethality in aerosolized form. Currently, there are no FDA approved vaccines against these viruses. In this study, we used a novel approach to develop inactivated vaccines for VEEV and CHIKV by applying gamma-radiation together with a synthetic Mn-decapeptide-phosphate complex (MnDpPi), based on manganous-peptide-orthophosphate antioxidants accumulated in the extremely radiation-resistant bacterium Deinococcus radiodurans. Classical gamma-irradiated vaccine development approaches are limited by immunogenicity-loss due to oxidative damage to the surface proteins at the high doses of radiation required for complete virus-inactivation. However, addition of MnDpPi during irradiation process selectively protects proteins, but not the nucleic acids, from the radiation-induced oxidative damage, as required for safe and efficacious vaccine development. Previously, this approach was used to develop a bacterial vaccine. In the present study, we show that this approach can successfully be applied to protecting mice against viral infections. Irradiation of VEEV and CHIKV in the presence of MnDpPi resulted in substantial epitope preservation even at supra-lethal doses of gamma-rays (50,000Gy). Irradiated viruses were found to be completely inactivated and safe in vivo (neonatal mice). Upon immunization, VEEV inactivated in the presence of MnDpPi resulted in drastically improved protective efficacy. Thus, the MnDpPi-based gamma-inactivation approach described here can readily be applied to developing vaccines against any pathogen of interest in a fast and cost-effective manner.

Background Knowledge of the cochlear implant array’s precise position is important because of the correlation between electrode position and speech understanding. Several groups have provided recent image processing evidence to determine scalar translocation, angular insertion depth, and cochlear duct length (CDL); all of which are being used for patient-specific programming. Cone beam computed tomography (CBCT) is increasingly used in otology due to its superior resolution and low radiation dose. Our objectives are as followed: Validate CBCT by measuring cochlear metrics, including basal turn diameter (A-value) and lateral wall cochlear duct length at different angular intervals and comparing it against microcomputed CT (uCT).Explore the relationship between measured lateral wall cochlear duct length at different angular intervals and insertion depth among 3 different length electrodes using CBCT. Methods The study was performed using fixed human cadaveric temporal bones in a tertiary academic centre. Ten temporal bones were subjected to the standard facial recess approach for cochlear implantation and imaged by CBCT followed by uCT. Measurements were performed on a three-dimensional reconstructed model of the cochlea. Sequential insertion of 3 electrodes (Med-El Flex24, 28 and Soft) was then performed in 5 bones and reimaged by CBCT. Statistical analysis was performed using Pearson’s correlation. Results There was good agreement between CBCT and uCT for cochlear metrics, validating the precision of CBCT against the current gold standard uCT in imaging. The A-value recorded by both modalities showed a high degree of linear correlation and did not differ by more than 0.23 mm in absolute values. For the measurement of lateral wall CDL at various points along the cochlea, there was a good correlation between both modalities at 360 deg and 720 deg (r = 0.85, p Conclusions CBCT reliably performs cochlear metrics and measures electrode insertion depth. The low radiation dose, fast acquisition time, diminished metallic artifacts and portability of CBCT make it a valid option for imaging in cochlear implant surgery.

A hybrid system for intraoperative cone-beam CT (CBCT) imaging and continuous-wave fluorescence tomography (FT) has been developed using an image-guidance framework. Intraoperative CBCT images with sub-millimeter spatial resolution are acquired with a flat-panel C-Arm. Tetrahedral meshes are generated from CBCT for finite element method implementation of diffuse optical tomography (NIRFAST). Structural data from CBCT is incorporated directly into the optical reconstruction process using Laplacian-type regularization ('soft spatial priors'). Experiments were performed using an in-house optical system designed for indocyanine green (ICG) fluorescence. A dynamic non-contact geometry was achieved using a stereoscopic optical tracker for real-time localization of a laser diode and CCD camera. Source and detector positions were projected onto the boundary elements of the tissue mesh using algorithms for ray-triangle intersection and camera lens calibration. Simulation studies showed the capabilities of a soft-prior approach, even in the presence of segmentation uncertainties. Experiments with ICG targets embedded in liquid phantoms determined the improvements in the quantification of the fluorophore yield, with errors of 85% and

Exposure to chronic ionizing radiation (CIR) from nuclear power plant accidents, acts of terrorism, and space exploration poses serious threats to humans. Fungi are a group of highly radiation-resistant eukaryotes, and an understanding of fungal CIR resistance mechanisms holds the prospect of protecting humans. We compared the abilities of 95 wild-type yeast and dimorphic fungal isolates, representing diverse Ascomycota and Basidiomycota, to resist exposure to five environmentally-relevant stressors: CIR (long-duration growth under 36 Gy/h) and acute (10 kGy/h) ionizing radiation (IR), heavy metals (chromium, mercury), elevated temperature (up to 50 °C), and low pH (2.3). To quantify associations between resistances to CIR and these other stressors, we used correlation analysis, logistic regression with multi-model inference, and customized machine learning. The results suggest that resistance to acute IR in fungi is not strongly correlated with the ability of a given fungal isolate to grow under CIR. Instead, the strongest predictors of CIR resistance in fungi were resistance to chromium (III) and to elevated temperature. These results suggest fundamental differences between the mechanisms of resistance to chronic and acute radiation. Convergent evolution towards radioresistance among genetically distinct groups of organisms is considered here.

A non-contact approach for diffuse optical tomography (DOT) has been developed for on-demand image updates using surgical navigation technology. A stereoscopic optical tracker provides real-time localization of reflective spheres mounted to a laser diode and near-infrared camera. Standard camera calibration is combined with tracking data to determine the intrinsic camera parameters (focal length, principal point and non-linear lens distortion) and the tracker-to-camera transform. Tracker-to-laser calibration is performed using images of laser beam intersection with a tracked calibration surface. Source and detector positions for a finite-element DOT implementation are projected onto the boundary elements of the tissue mesh by finding ray-triangle intersections. A multi-stage model converts camera counts to surface flux by accounting for lens aperture settings, fluorescence filter transmittance, photodetector quantum efficiency, photon energy, exposure time, readout offset and camera gain. The image-guidance framework was applied to an in-house optical tomography system configured for indocyanine green (ICG) fluorescence. Mean target registration errors for camera and laser calibration were less than 1 mm. Surface flux measurements of total reflectance and fluorescence in Intralipid-based fluorescence phantoms (0-2 μg ml-1) had mean errors of 3.1% and 4.4%, respectively, relative to diffusion theory predictions. Spatially-resolved reflectance measurements in a calibrated optical phantom agreed with theory for radial distances up to 25 mm from the laser source. Inverse fluorescence reconstructions of a sub-surface fluorescence target confirmed the localization accuracy (average target centroid error of 0.44 mm). This translational research system is under investigation for clinical applications in head and neck surgery, including oral cavity tumor resection, lymph node mapping and free-flap perforator assessment.

Intraoperative visualization of molecular processes delineated by fluorescence contrast agents offers the potential for increased surgical precision and better patient outcomes. To exploit fully the clinical potential for targeted fluorescence guidance, there is a growing need to develop high-resolution, quantitative imaging systems suitable for surgical use. Diffuse optical fluorescence tomography (DOFT) systems in pre-clinical and diagnostic imaging applications have demonstrated improvements in fluorescence quantification with the addition of a priori data from structural imaging modalities (e.g., MR, CT). Here, we investigate the use of a cone-beam CT (CBCT) surgical guidance system to generate spatial priors for intraoperative DOFT. Imaging and localization data is incorporated directly into a finite element method DOFT implementation (NIRFAST) at multiple stages. First, CBCT data from an intraoperative flat-panel C-arm is used to generate tetrahedral meshes. Second, optical tracking of laser and camera devices enables an adaptable non-contact DOFT approach to accommodate various anatomical sites and acquisition geometries. Finally, anatomical segmentations from CBCT are included in the optical reconstruction process using Laplacian-type regularization (“soft spatial priors”). Calibration results showed that light rays between the tissue surface and navigated optical devices were mapped with sub-millimeter accuracy. Liquid phantom experiments determined the improvements in quantification of fluorescence yield, with errors of 85% and

Background Left circumflex culprit is often missed by the standard 12‐lead ECG. Extended lead systems (body surface potential map [BSPM]) should improve the diagnosis of culprit left circumflex stenosis with myocardial infarction. Methods and Results Retrospective analysis of a hospital research registry (August 2000–August 2010) comprising consecutive patients with (1) ischemic‐type chest pain at rest; (2) 12‐lead ECG and 80‐lead BSPM at first medical contact; and (3) cardiac troponin‐T 12 hours after symptom onset and/or creatine kinase MB fraction, were undertaken. Enrolled in the cohort were patients with culprit left circumflex stenosis (thrombolysis in myocardial infarction flow grade 0/1) at angiography. Acute myocardial infarction AMI was defined as cardiac troponin‐T ≥0.1 μg/L and/or creatine kinase MB fraction >2 upper limits of normal. Enrolled were 482 patients: 168 had exclusion criteria. Of the remaining 314 (age 64±11 years; 62% male), 254 (81%) had AMI: of these, 231 had BSPM STE—sensitivity 0.91, specificity 0.72, positive predictive value 0.93, negative predictive value 0.65, and c‐statistic 0.803 for AMI (P, See Editorial by Kontos

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.

Epicardial potentials (EPs) derived from the body surface potential map (BSPM) improve acute myocardial infarction (AMI) diagnosis. In this study, we compared EPs derived from the 80-lead BSPM using a standard thoracic volume conductor model (TVCM) with those derived using a patient-specific torso model (PSTM) based on body mass index (BMI).Consecutive patients presenting to both the emergency department and pre-hospital coronary care unit between August 2009 and August 2011 with acute ischaemic-type chest pain at rest were enrolled. At first medical contact, 12-lead electrocardiograms and BSPMs were recorded. The BMI for each patient was calculated. Cardiac troponin T (cTnT) was sampled 12 hours after symptom onset. Patients were excluded from analysis if they had any ECG confounders to interpretation of the ST-segment. A cardiologist assessed the 12-lead ECG for ST-segment elevation myocardial infarction by Minnesota criteria and the BSPM. BSPM ST-elevation (STE) was ⩾0.2 mV in anterior, ⩾0.1 mV in lateral, inferior, right ventricular or high right anterior and ⩾0.05 mV in posterior territories. To derive EPs, the BSPM data were interpolated to yield values at 352 nodes of a Dalhousie torso. Using an inverse solution based on the boundary element method, EPs at 98 cardiac nodes positioned within a standard TVCM were derived. The TVCM was then scaled to produce a PSTM using a model developed from computed tomography in 48 patients of varying BMIs, and EPs were recalculated. EPs0.3 mV defined STE. A cardiologist blinded to both the 12-lead ECG and BSPM interpreted the EP map. AMI was defined as cTnT ⩾0.1 µg/L.Enrolled were 400 patients (age 62 ± 13 years; 57% male); 80 patients had exclusion criteria. Of the remaining 320 patients, the BMI was an average of 27.8 ± 5.6 kg/mAmong patients presenting with ischaemic-type chest pain at rest, EPs derived from BSPM using a novel PSTM significantly improve sensitivity for AMI diagnosis.

Objectives/Hypothesis Providing image guidance in a 3-dimensional (3D) format, visually more in keeping with the operative field, could potentially reduce workload and lead to faster and more accurate navigation. We wished to assess a 3D virtual-view surgical navigation prototype in comparison to a traditional 2D system. Methods Thirty-seven otolaryngology surgeons and trainees completed a randomized crossover navigation exercise on a cadaver model. Each subject identified three sinonasal landmarks with 3D virtual (3DV) image guidance and three landmarks with conventional cross-sectional computed tomography (CT) image guidance. Subjects were randomized with regard to which side and display type was tested initially. Accuracy, task completion time, and task workload were recorded. Results Display type did not influence accuracy (P > 0.2) or efficiency (P > 0.3) for any of the six landmarks investigated. Pooled landmark data revealed a trend of improved accuracy in the 3DV group by 0.44 millimeters (95% confidence interval [0.00–0.88]). High-volume surgeons were significantly faster (P 0.28). Conclusion Real-time 3D image guidance did not influence accuracy, efficiency, or task workload when compared to conventional triplanar image guidance. The subtle pooled accuracy advantage for the 3DV view is unlikely to be of clinical significance. Experience level was strongly correlated to task completion time and workload but did not influence accuracy. Level of Evidence N/A. Laryngoscope, 126:1510–1515, 2016

Objectives Surgical navigation systems based on preoperative imaging are now increasingly used for guidance of head and neck resection and reconstruction. The primary aim of this study was to quantify osteotomy cutting accuracy using an image-guidance system for intraoperative cone-beam computed tomography (CBCT) imaging and surgical saw navigation. To enable clinical translation of this CBCT-guided navigation system, a secondary aim of the study was to design and fabricate a patient reference tracker suitable for clinical use on a mobile mandible. Methods First, a preclinical cadaveric study was performed to quantify navigation accuracy with the use of clinically suitable patient reference trackers. Second, a proof-of-principle patient study was conducted to evaluate this technique under clinical conditions. Results In both preclinical (5 cadavers) and clinical (5 patients) experiments, the mean cutting accuracy was less than 2 mm. In all preclinical specimens, bilateral mandibulectomies and bilateral maxillectomies were performed, for a total of 20 cut planes for analysis. The mean (standard deviation [SD]) values for distance, pitch, and roll were 1.4 mm (1.1 mm), 4.2° (3.5°), and 2.9° (2.5°) mm, respectively. Five mandibulectomies were performed on five patients, for a total of 10 cut planes for analysis. The mean (SD) values for distance, pitch, and roll were 1.7 mm (0.8 mm), 5.4° (1.5°), and 6.7° (4.6°) mm, respectively. Conclusions The overall performance in comparison to alternative approaches warrants further consideration. In terms of accuracy, the results presented here are comparable to recent systematic reviews assessing CAD-CAM cutting guides that cite accuracies of ~2 to 2.5 mm. Level of evidence 2 Laryngoscope, 130:1122-1127, 2020.

Objectives To demonstrate and quantify, in a preclinical setting, the benefit of three-dimensional (3D) navigation guidance for margin delineation during ablative open surgery for advanced sinonasal cancer. Materials and methods Seven tumor models were created. 3D images were acquired with cone beam computed tomography, and 3D tumor segmentations were contoured. Eight surgeons with variable experience were recruited for the simulation of osteotomies. Three simulations were performed: 1) Unguided, 2) Guided using real-time tool tracking with 3D tumor segmentation (tumor-guided), and 3) Guided by 3D visualization of both the tumor and 1-cm margin segmentations (margin-guided). Analysis of cutting planes was performed and distance from the tumor surface was classified as follows: “intratumoral” when 0 mm or negative, “close” when greater than 0 mm and less than or equal to 5 mm, “adequate” when greater than 5 mm and less than or equal to 15 mm, and “excessive” over 15 mm. The three techniques (unguided, tumor-guided, margin-guided) were statistically compared. Results The use of 3D navigation for margin delineation significantly improved control of margins: unguided cuts had 18.1% intratumoral cuts compared to 0% intratumoral cuts with 3D navigation (p Conclusion This preclinical study has demonstrated the significant benefit of navigation-guided osteotomies for sinonasal tumors. Translation into the clinical setting – with rigorous assessment of oncological outcomes – would be the proposed next step.

Highly concentrated radionuclide waste produced during the Cold War era is stored at US Department of Energy (DOE) production sites. This radioactive waste was often highly acidic and mixed with heavy metals, and has been leaking into the environment since the 1950s. Because of the danger and expense of cleanup of such radioactive sites by physicochemical processes, in situ bioremediation methods are being developed for cleanup of contaminated ground and groundwater. To date, the most developed microbial treatment proposed for high-level radioactive sites employs the radiation-resistant bacterium Deinococcus radiodurans. However, the use of Deinococcus spp. and other bacteria is limited by their sensitivity to low pH. We report the characterization of twenty-seven diverse environmental yeasts for their resistance to ionizing radiation (chronic and acute), heavy metals, pH minima, temperature maxima and optima, and their ability to form biofilms. Remarkably, many yeasts are extremely resistant to ionizing radiation and heavy metals. They also excrete carboxylic acids and are exceptionally tolerant to low pH. A special focus is placed on Rhodotorula taiwanensis MD1149, which was the most resistant to acid and gamma radiation. MD1149 is capable of growing under 66 Gy/h at pH 2.3 and in the presence of high concentrations of mercury and chromium compounds, and forming biofilms under high-level chronic radiation and low pH. We present the whole genome sequence and annotation of R. taiwanensis strain MD1149, with a comparison to other Rhodotorula species. This survey elevates yeasts to the frontier of biology’s most radiation-resistant representatives, presenting a strong rationale for a role of fungi in bioremediation of acidic radioactive waste sites.

Background: This Sawbones and cadaver study was performed to assess the accuracy and reproducibility of pelvic bone cuts made with use of a novel navigation system with a navigated osteotome and oscillating saw. Methods: Using a novel navigation system and a three-dimensional planning tool, we navigated pelvic bone cuts that were representative of typical cuts made in pelvic tumor resections. The system includes a prototype mobile C-arm for intraoperative cone-beam computed tomography, real-time optical tracking (Polaris), and three-dimensional visualization software. Three-dimensional virtual radiographs were utilized in addition to triplanar (axial, sagittal, and coronal) navigation. In part one of the study, we navigated twenty-four sacral bone cuts in Sawbones models and validated our results in sixteen similar cuts in cadavers. In part two, we developed three Sawbones models of pelvic tumors based on actual patient scenarios and compared three navigated resections with three non-navigated resections for each tumor model. Part three assessed the accuracy of the system with multiple users. Results: There were ninety navigated cuts in Sawbones that were compared with fifty-four non-navigated cuts. In the navigated Sawbones cuts, the mean entry and exit cuts were 1.4 ± 1 mm and 1.9 ± 1.2 mm from the planned cuts, respectively. In comparison, the entry and exit cuts in Sawbones that were not navigated were 2.8 ± 4.9 mm and 3.5 ± 4.6 mm away from the planned osteotomy site. The navigated cuts were significantly more accurate (p ≤ 0.01). In the cadaver study, navigated entry and exit cuts were 1.5 ± 0.9 mm and 2.1 ± 1.5 mm from the planned cuts. The variation among three different users was 1 mm on both the entry and exit cuts. Conclusions: Navigation to guide pelvic bone cuts is accurate and feasible. Three-dimensional radiographs should be used for improved accuracy. Navigated cuts were significantly more accurate than non-navigated cuts were. A margin of 5 mm between the target tumor volume and the planned cut plane would result in a negative margin resection in more than 95% of the cuts. Clinical Relevance: The accuracy of pelvic bone tumor resections and pelvic osteotomies can be improved with navigation to within 5 mm of the planned cut.

Despite concerted functional genomic efforts to understand the complex phenotype of ionizing radiation (IR) resistance, a genome sequence cannot predict whether a cell is IR-resistant or not. Instead, we report that absorption-display electron paramagnetic resonance (EPR) spectroscopy of nonirradiated cells is highly diagnostic of IR survival and repair efficiency of DNA double-strand breaks (DSBs) caused by exposure to gamma radiation across archaea, bacteria, and eukaryotes, including fungi and human cells. IR-resistant cells, which are efficient at DSB repair, contain a high cellular content of manganous ions (Mn2+) in high-symmetry (H) antioxidant complexes with small metabolites (e.g., orthophosphate, peptides), which exhibit narrow EPR signals (small zero-field splitting). In contrast, Mn2+ ions in IR-sensitive cells, which are inefficient at DSB repair, exist largely as low-symmetry (L) complexes with substantially broadened spectra seen with enzymes and strongly chelating ligands. The fraction of cellular Mn2+ present as H-complexes (H-Mn2+), as measured by EPR of live, nonirradiated Mn-replete cells, is now the strongest known gauge of biological IR resistance between and within organisms representing all three domains of life: Antioxidant H-Mn2+ complexes, not antioxidant enzymes (e.g., Mn superoxide dismutase), govern IR survival. As the pool of intracellular metabolites needed to form H-Mn2+ complexes depends on the nutritional status of the cell, we conclude that IR resistance is predominantly a metabolic phenomenon. In a cross-kingdom analysis, the vast differences in taxonomic classification, genome size, and radioresistance between cell types studied here support that IR resistance is not controlled by the repertoire of DNA repair and antioxidant enzymes.

Understanding chronic ionizing radiation (CIR) effects is of utmost importance to protecting human health and the environment. Diverse bacteria and fungi inhabiting extremely radioactive waste and disaster sites (e.g. Hanford, Chernobyl, Fukushima) represent new targets of CIR research. We show that many microorganisms can grow under intense gamma-CIR dose rates of 13-126 Gy/h, with fungi identified as a particularly CIR-resistant group of eukaryotes: among 145 phylogenetically diverse strains tested, 78 grew under 36 Gy/h. Importantly, we demonstrate that CIR resistance can depend on cell concentration and that certain resistant microbial cells protect their neighbors (not only conspecifics, but even radiosensitive species from a different phylum), from high-level CIR. We apply a mechanistically-motivated mathematical model of CIR effects, based on accumulation/removal kinetics of reactive oxygen species (ROS) and antioxidants, in bacteria (3 Escherichia coli strains and Deinococcus radiodurans) and in fungi (Candida parapsilosis, Kazachstania exigua, Pichia kudriavzevii, Rhodotorula lysinophila, Saccharomyces cerevisiae, and Trichosporon mucoides). We also show that correlations between responses to CIR and acute ionizing radiation (AIR) among studied microorganisms are weak. For example, in D. radiodurans, the best molecular correlate for CIR resistance is the antioxidant enzyme catalase, which is dispensable for AIR resistance; and numerous CIR-resistant fungi are not AIR-resistant. Our experimental findings and quantitative modeling thus demonstrate the importance of investigating CIR responses directly, rather than extrapolating from AIR. Protection of radiosensitive cell-types by radioresistant ones under high-level CIR is a potentially important new tool for bioremediation of radioactive sites and development of CIR-resistant microbiota as radioprotectors.

The genetic platforms of Deinococcus species remain the only systems in which massive ionizing radiation (IR)-induced genome damage can be investigated in vivo at exposures commensurate with cellular survival. We report the whole genome sequence of the extremely IR-resistant rod-shaped bacterium Deinococcus ficus KS 0460 and its phenotypic characterization. Deinococcus ficus KS 0460 has been studied since 1987, first under the name Deinobacter grandis, then Deinococcus grandis. The D. ficus KS 0460 genome consists of a 4.019 Mbp sequence (69.7% GC content and 3894 predicted genes) divided into six genome partitions, five of which are confirmed to be circular. Circularity was determined manually by mate pair linkage. Approximately 76% of the predicted proteins contained identifiable Pfam domains and 72% were assigned to COGs. Of all D. ficus KS 0460 proteins, 79% and 70% had homologues in Deinococcus radiodurans ATCC BAA-816 and Deinococcus geothermalis DSM 11300, respectively. The most striking differences between D. ficus KS 0460 and D. radiodurans BAA-816 identified by the comparison of the KEGG pathways were as follows: (i) D. ficus lacks nine enzymes of purine degradation present in D. radiodurans, and (ii) D. ficus contains eight enzymes involved in nitrogen metabolism, including nitrate and nitrite reductases, that D. radiodurans lacks. Moreover, genes previously considered to be important to IR resistance are missing in D. ficus KS 0460, namely, for the Mn-transporter nramp, and proteins DdrF, DdrJ and DdrK, all of which are also missing in Deinococcus deserti. Otherwise, D. ficus KS 0460 exemplifies the Deinococcus lineage. Electronic supplementary material The online version of this article (doi:10.1186/s40793-017-0258-y) contains supplementary material, which is available to authorized users.

Previous preclinical studies of localized intraoperative virtual endoscopy-image-guided surgery (LIVE-IGS) for skull base surgery suggest a potential clinical benefit.The first aim was to evaluate the registration accuracy of virtual endoscopy based on high-resolution magnetic resonance imaging under clinical conditions. The second aim was to implement and assess real-time proximity alerts for critical structures during skull base drilling.Patients consecutively referred for sinus and skull base surgery were enrolled in this prospective case series.Five patients were used to check registration accuracy and feasibility with the subsequent 11 patients being treated under LIVE-IGS conditions with presentation to the operating surgeon (phase 2).Sixteen skull base patients were endoscopically operated on by using image-based navigation while LIVE-IGS was tested in a clinical setting.Workload was quantitatively assessed using the validated National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire.Real-time localization of the surgical drill was accurate to ~1 to 2 mm in all cases. The use of 3-mm proximity alert zones around the carotid arteries and optic nerve found regular clinical use, as the median minimum distance between the tracked drill and these structures was 1 mm (0.2-3.1 mm) and 0.6 mm (0.2-2.5 mm), respectively. No statistical differences were found in the NASA-TLX indicators for this experienced surgical cohort.Real-time proximity alerts with virtual endoscopic guidance was sufficiently accurate under clinical conditions. Further clinical evaluation is required to evaluate the potential surgical benefits, particularly for less experienced surgeons or for teaching purposes.

Introduction It is well known that accurate interpretation of the 12-lead electrocardiogram (ECG) requires a high degree of skill. There is also a moderate degree of variability among those who interpret the ECG. While this is the case, there are no best practice guidelines for the actual ECG interpretation process. Hence, this study adopts computerized eye tracking technology to investigate whether eye-gaze can be used to gain a deeper insight into how expert annotators interpret the ECG. Annotators were recruited in San Jose, California at the 2013 International Society of Computerised Electrocardiology (ISCE). Methods Each annotator was recruited to interpret a number of 12-lead ECGs (N = 12) while their eye gaze was recorded using a Tobii X60 eye tracker. The device is based on corneal reflection and is non-intrusive. With a sampling rate of 60 Hz, eye gaze coordinates were acquired every 16.7 ms. Fixations were determined using a predefined computerized classification algorithm, which was then used to generate heat maps of where the annotators looked. The ECGs used in this study form four groups (3 = ST elevation myocardial infarction [STEMI], 3 = hypertrophy, 3 = arrhythmias and 3 = exhibiting unique artefacts). There was also an equal distribution of difficulty levels (3 = easy to interpret, 3 = average and 3 = difficult). ECGs were displayed using the 4x3 + 1 display format and computerized annotations were concealed. Results Precisely 252 expert ECG interpretations (21 annotators × 12 ECGs) were recorded. Average duration for ECG interpretation was 58 s (SD = 23). Fleiss' generalized kappa coefficient (Pa = 0.56) indicated a moderate inter-rater reliability among the annotators. There was a 79% inter-rater agreement for STEMI cases, 71% agreement for arrhythmia cases, 65% for the lead misplacement and dextrocardia cases and only 37% agreement for the hypertrophy cases. In analyzing the total fixation duration, it was found that on average annotators study lead V1 the most (4.29 s), followed by leads V2 (3.83 s), the rhythm strip (3.47 s), II (2.74 s), V3 (2.63 s), I (2.53 s), aVL (2.45 s), V5 (2.27 s), aVF (1.74 s), aVR (1.63 s), V6 (1.39 s), III (1.32 s) and V4 (1.19 s). It was also found that on average the annotator spends an equal amount of time studying leads in the frontal plane (15.89 s) when compared to leads in the transverse plane (15.70 s). It was found that on average the annotators fixated on lead I first followed by leads V2, aVL, V1, II, aVR, V3, rhythm strip, III, aVF, V5, V4 and V6. We found a strong correlation (r = 0.67) between time to first fixation on a lead and the total fixation duration on each lead. This indicates that leads studied first are studied the longest. There was a weak negative correlation between duration and accuracy (r = − 0.2) and a strong correlation between age and accuracy (r = 0.67). Conclusions Eye tracking facilitated a deeper insight into how expert annotators interpret the 12-lead ECG. As a result, the authors recommend ECG annotators to adopt an initial first impression/pattern recognition approach followed by a conventional systematic protocol to ECG interpretation. This recommendation is based on observing misdiagnoses given due to first impression only. In summary, this research presents eye gaze results from expert ECG annotators and provides scope for future work that involves exploiting computerized eye tracking technology to further the science of ECG interpretation.

Background Augmented reality (AR) surgical navigation systems, designed to increase accuracy and efficiency, have been shown to negatively impact on attention. We wished to assess the effect “head-up” AR displays have on attention, efficiency, and accuracy, while performing a surgical task, compared with the same information being presented on a submonitor (SM). Methods Fifty experienced otolaryngology surgeons (n = 42) and senior otolaryngology trainees (n = 8) performed an endoscopic surgical navigation exercise on a predissected cadaveric model. Computed tomography-generated anatomic contours were fused with the endoscopic image to provide an AR view. Subjects were randomized to perform the task with a standard endoscopic monitor with the AR navigation displayed on an SM or with AR as a single display. Accuracy, task completion time, and the recognition of unexpected findings (a foreign body and a critical complication) were recorded. Results Recognition of the foreign body was significantly better in the SM group (15/25 [60%]) compared with the AR alone group (8/25 [32%]; p = 0.02). There was no significant difference in task completion time (p = 0.83) or accuracy (p = 0.78) between the two groups. Conclusion Providing identical surgical navigation on a SM, rather than on a single head-up display, reduced the level of inattentional blindness as measured by detection of unexpected findings. These gains were achieved without any measurable impact on efficiency or accuracy. AR displays may distract the user and we caution injudicious adoption of this technology for medical procedures.

We describe a case of transcatheter aortic valve replacement (TAVR) using carotid artery access and regional anesthesia in a patient with rheumatic heart disease, previous mitral valve replacement, and multiple co-morbidities. It highlights the role of the multidisciplinary Heart Team and multimodality imaging in reaching and implementing an appropriate management plan in this complex patient group.

Conventional computed tomography (CT) imaging is the standard imaging technique for temporal bone diseases, whereas cone-beam CT (CBCT) imaging is a very fast imaging tool with a significant less radiation dose compared with conventional CT. We hypothesize that a system for intraoperative cone-beam CT provides comparable image quality to diagnostic CT for identifying temporal bone anatomical landmarks in cadaveric specimens.Cross-sectional study.University tertiary care facility.Twenty cadaveric temporal bones were affixed into a head phantom and scanned with both a prototype cone-beam CT C-arm and multislice helical CT. Imaging performance was evaluated by 3 otologic surgeons and 1 head and neck radiologist. Participants were presented images in a randomized order and completed landmark identification questionnaires covering 21 structures.CBCT and multislice CT have comparable performance in identifying temporal structures. Three otologic surgeons indicated that CBCT provided statistically equivalent performance for 19 of 21 landmarks, with CBCT superior to CT for the chorda tympani and inferior for the crura of the stapes. Subgroup analysis showed that CBCT performed superiorly for temporal bone structures compared with CT. The radiologist rated CBCT and CT as statistically equivalent for 18 of 21 landmarks, with CT superior to CBCT for the crura of stapes, chorda tympani, and sigmoid sinus.CBCT provides comparable image quality to conventional CT for temporal bone anatomical sites in cadaveric specimens. Clinical applications of low-dose CBCT imaging in surgical planning, intraoperative guidance, and postoperative assessment are promising but require further investigation.