Sex-Specific Survival and Treatment Delay in Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: As the majority of oropharyngeal squamous cell carcinoma (OPSCC) is diagnosed in males, outcomes among females are not well-characterized. We identify sex-specific factors in OPSCC to refine female prognostication. STUDY DESIGN: Retrospective cohort. SETTING: National Cancer Database (NCDB). METHODS: OPSCC cases from the 2004 to 2019 NCDB were identified. Sociodemographic, clinical, and treatment characteristics (including timing between diagnosis and treatment administration) were compared between sexes. Multivariable Cox proportional hazard regression models were constructed to characterize survival in overall and female-only cohorts. Similar multivariable binomial logistic regression and survival models were constructed to assess odds of treatment delays and their effects on survival, respectively. RESULTS: A total of 192,973 OPSCC patients were identified; 36,695 (19%) were female. Females had more human papillomavirus (HPV) negative, lower clinical T and N stage, and higher comorbidity disease. Females experienced lower survival in HPV negative (hazard ratio, HR = 1.11, P < .001) but not HPV-positive disease. Females were more likely to have any treatment initiated over the median of 28 days (odds ratio, OR = 1.04, P = .014) or delays in adjuvant radiotherapy initiation over 6 weeks (OR = 1.11, P = .032). Treatment delay over 60 days (HR = 1.17, P = .016) and delay in adjuvant therapy initiation (HR = 1.24, P = .02) were associated with worse survival among females. CONCLUSION: In one of the largest analyses of OPSCC, females had poorer survival than males, specifically in HPV-negative disease, despite presentation with less advanced disease. Notably, delays in any treatment initiation and adjuvant radiotherapy initiation were more likely in HPV-negative women and associated with worse survival, highlighting potential systemic weaknesses contributing to poor prognosis among females.

Quantitative Neuromuscular Monitoring Permits Early Diagnosis of Abnormal Butyrylcholinestrase: Two Case Studies Demonstrating Prevention of Awareness from Premature Awakening.

Administration of succinylcholine to patients with a variant in the butyrylcholinesterase (BChE) gene increases the risk of anesthesia emergence prior to recovery from neuromuscular blockade (NMB). Application of quantitative neuromuscular monitoring (NMM) can identify residual NMB. We present two patients with abnormal BChE gene variants. In the first case, quantitative monitoring was applied too late to prevent awareness, but allowed diagnosis and prevented admission to the intensive care unit. In the second case, monitoring was applied prior to NMB, which enabled early diagnosis and prevented premature awakening from anesthesia. These cases illustrate the importance of quantitative NMM, even in short cases and with short-acting depolarizing agents such as succinylcholine. The clinical implications of this report include a more consistent use of NMM to identify and manage patients with undiagnosed abnormal BChE and to prevent premature anesthesia emergence.

Sustainability of an Operating Room to Pediatric Postanesthesia Care Unit Handoff Tool.

PURPOSE: The purpose of this quality improvement (QI) project was to reintroduce and assess the feasibility of a standardized, electronic health record (EHR) handoff tool and to evaluate the sustainability of a structured, team-based approach in a pediatric postanesthesia care unit (PACU). DESIGN: This QI project used an observational pre-post design using two separate convenience samples of handoffs and perianesthesia providers. METHODS: A standardized EHR handoff tool was reintroduced for operating room to pediatric PACU handoff communication. Handoffs between anesthesia providers, surgery team members, and PACU nurses were observed pre- and postreintroduction of the EHR handoff tool. Anesthesia providers and PACU RNs received training for giving and receiving handoffs and were provided directions on locating the EHR handoff tool. A bedside audit of items communicated for the six handoff phases (introductions, situation, background, assessment, recommendations, and questions), handoff duration, team member participation, and handoff tool utilization were performed for 149 handoffs pre- and 146 handoffs postimplementation. To evaluate sustainability, the audits were compared to postimplementation data from the 2014 pilot handoff project. FINDINGS: Following reintroduction, EHR handoff tool use increased from 4% to 19%. There was a statistically significant increase in items communicated for three of the six handoff phases when using the EHR tool (P < .05). There was no statistically significant increase in handoff duration (mean = 3.66 minutes, SD = 1.57 minutes) with the EHR handoff tool. Surgical team member presence for the team-based handoff increased from 90.7% pre to 95.9% post. Provider compliance with the team-based handoff approach, which includes a PACU RN, surgical team member, and anesthesia team member present for handoff, was sustained and increased 6 years postimplementation. Feedback from anesthesia providers and PACU RNs indicated mixed reports of satisfaction with the EHR tool, perceived handoff efficiency, and consistency in both giving and receiving handoff. Adherence to five of the six structured handoff phases, except introductions, was sustained and even improved 6 years following implementation. CONCLUSIONS: Evidence-based practice for handoff communication supports the use of a team approach and standardized EHR handoff tools. The reintroduction of a standardized EHR handoff tool improved the completeness of information transfer, yet did not lead to widespread adoption nor improved user satisfaction. There is an ongoing need to identify adoptable and sustainable perioperative handoff methods.

Rapid CRISPR-Cas13a genetic identification enables new opportunities for listed Chinook salmon management.

Accurate taxonomic identification is foundational for effective species monitoring and management. When visual identifications are infeasible or inaccurate, genetic approaches provide a reliable alternative. However, these approaches are sometimes less viable (e.g., need for near real-time results, remote locations, funding concerns, molecular inexperience). In these situations, CRISPR-based genetic tools can fill an unoccupied niche between real-time, inexpensive, but error-prone visual identification and more expensive or time-consuming, but accurate genetic identification for taxonomic units that are difficult or impossible to visually identify. Herein, we use genomic data to develop CRISPR-based SHERLOCK assays capable of rapidly (<1 h), accurately (94%-98% concordance between phenotypic and genotypic assignments), and sensitively (detects 1-10 DNA copies/reaction) distinguishing ESA-listed Chinook salmon runs (winter- and spring-run) from each other and from unlisted runs (fall- and late fall-run) in California's Central Valley. The assays can be field deployable with minimally invasive mucus swabbing negating the need for DNA extraction (decreasing costs and labour), minimal and inexpensive equipment needs, and minimal training to conduct following assay development. This study provides a powerful genetic approach for a species of conservation concern that benefits from near real-time management decision-making but also serves as a precedent for transforming how conservation scientists and managers view genetic identification going forward. Once developed, CRISPR-based tools can provide accurate, sensitive, and rapid results, potentially without the prohibitive need for expensive specialty equipment or extensive molecular training. Further adoption of this technology will have widespread value for the monitoring and protection of our natural resources.

Incorporating Evidence-Based Ultrasound-Guided Vascular Access (USGVA) Standards Into the Nurse Anesthetist Armamentarium: A Quality Improvement Project.

PURPOSE: This quality improvement (QI) project developed and implemented a hybrid training program, that included online modules and hands-on training for experienced certified registered nurse anesthetists (CRNAs) to increase confidence, knowledge, and competency with ultrasound-guided vascular access (USGVA). DESIGN: This QI project used a pre-post design. Seventeen volunteer CRNAs participated in USGVA training and education, and a 90-day follow-up assessment was performed. METHODS: The Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) guidelines were used as a framework to assess confidence, knowledge, and hands-on competency of 17 CRNAs who regularly place vascular access devices using USGVA in patients with difficult vascular access at a single facility. These assessments were measured at: (1) baseline, (2) immediately after attending a hybrid training educational program, and (3) 90 days after implementation into clinical practice. Additionally, the number of vascular access attempts required for successful placement of peripheral intravenous (PIV) catheters, arterial catheters, and central venous catheters (CVC) with ultrasound assistance over a 90-day period was reviewed. FINDINGS: Certified registered nurse anesthetists' median confidence score increased significantly from pre- to posteducation (P = .009). The confidence reported from post- to 90 days posteducation improved, however it did not reach statistical significance (P = .812). The knowledge scores from pre- to posteducation indicated significant improvement (P <. 001), as well as from pre- to 90 days posteducation (P = .03). However, knowledge scores from post- to 90 days posteducation revealed a statistically significant decline (P = .004). The overall median score for hands-on USGVA competency declined from post- to 90 days posteducation (P = .109). The number of successful USGVA placements increased from 50% to 80% within a 90-day period. CONCLUSIONS: The implementation of a USGVA hybrid training and education program improved overall provider confidence, knowledge, and competency. While confidence remained high in the 90-day follow-up, knowledge retention declined. Despite a decline in knowledge retention over time, results showed a significant improvement when compared to baseline scores. Although a decline in hands-on USGVA competency was seen at 90 days posteducation, it was not statistically significant. The percentage of overall successful USGVA placements in clinical practice increased following implementation.

Improving Nursing Knowledge and Patient Education About Aprepitant's Effects on Hormonal Contraception: A Performance Improvement Project.

PURPOSE: The purpose of this project was to improve the consistency of verbal and written discharge instructions for women of childbearing age (13-55 years) taking hormonal contraceptives who receive aprepitant perioperatively, to address the need to use a secondary form of birth control for 28 days, as well as to increase the knowledge and confidence of Registered Nurses when providing discharge instructions. DESIGN: This quality improvement project used a pre-/postdesign to evaluate two separate groups of patients and registered nurses. METHODS: The patient sample consisted of 30 total women of childbearing age who received aprepitant during the perioperative period (15 pre and 15 post). The PACU nurse sample included 15 ambulatory surgery center nurses and 58 main hospital nurses for a combined sample of 73 PACU nurses. The PACU nurses were provided with educational in-service regarding information about aprepitant and its drug interactions. PACU nurses were additionally instructed to provide patient discharge instructions using both a written and verbal format. Patients were called postoperatively before and after both the written after visit summary (AVS) changes and the PACU nurse in-services, PACU nurses were evaluated on their knowledge, confidence, and frequency of discharge teaching before and after their educational in-service. The PACU nurses were surveyed 90 days after the intervention to assess their long-term knowledge retention. FINDINGS: There was a significant increase in nurse knowledge about aprepitant from preimplementation to postimplementation (61.39% vs 81.95%, P < .001). Nursing knowledge showed a nonsignificant decline at 90-days postimplementation (81.95% vs 73.68%, P = .096) although remained significantly higher than preimplementation scores (73.68% vs 61.39%, P = .003). There was an overall 33.3% increase in the percentage of patients who were able to recall receiving aprepitant and the need to use a secondary form of birth control when comparing the preintervention group to the postintervention group (26.7% vs 60%, P = .123). CONCLUSIONS: The findings suggest that providing a standardized presentation about aprepitant may improve the PACU nurses' ability to verbalize key information about aprepitant, including the need for patients to use a secondary form of birth control. This increase in nursing knowledge and confidence, along with improved written discharge instructions, may have led to improved patient comprehension of aprepitant discharge education. Additionally, there was an increase in the percentage of patients who were able to recall the need to use a secondary form birth control for 28 days, to reduce the likelihood of an unintentional pregnancy.

Anesthetic Implications in Alternating Hemiplegia of Childhood: A Case Report.

The following case report describes a 13-year-old child with alternating hemiplegia of childhood (AHC) who underwent magnetic resonance imaging MRI with general anesthesia and experienced a hemiplegic spell, seizure, apnea, and sudden cardiac arrest with successful resuscitation. AHC is a rare neurodevelopmental disorder characterized by repeated episodes of weakness or paralysis affecting one or both sides of the body and multiple other neurologic problems. The challenges associated with this disorder include management of developmental delay, dystonia, hemiplegia, cerebrovascular dysfunction, apnea, and autonomic dysfunction. The current literature is extremely limited in describing the effects of general anesthesia for a patient with AHC. While the neurologic manifestations of AHC are well described, autonomic dysfunction and the potential for sudden cardiac arrest have not been widely reported. To our knowledge, this is the first case report to emphasize anesthetic considerations in a pediatric patient with AHC, specifically the unrecognized potential for cardiac arrhythmia and sudden cardiac arrest.

Characterization of sedation and anesthesia complications in patients with alternating hemiplegia of childhood.

BACKGROUND: Alternating hemiplegia of childhood (AHC) pathophysiology suggests predisposition to sedation and anesthesia complications. GOALS: Hypotheses: 1) AHC patients experience high rates of sedation-anesthesia complications. 2) ATP1A3 mutation genotype positivity, age, and AHC severity correlate with more severe complications. 3) Prior short QTc correlates with cardiac rhythm complications. METHODS: Analysis of 34 consecutive AHC patients who underwent sedation or anesthesia. Classification of complications: mild (not requiring intervention), moderate (intervention), severe (intervention, risk for permanent injury or potential life-threatening emergency). STATISTICS: Fisher Exact test, Spearman correlations. RESULTS: These patients underwent 129 procedures (3.79 ± 2.75 procedures/patient). Twelve (35%) experienced complications during at least one procedure. Fourteen/129 procedures (11%) manifested one or more complications (2.3% mild, 7% moderate, 1.6% severe). Of the total 20 observed complications, six (33.3%) were severe: apneas (2), seizures (2), bradycardia (1), ventricular fibrillation that responded to resuscitation (1). Moderate complications: non-life-threatening bradycardias, apneas, AHC spells or seizures. Complications occurred during sedation or anesthesia and during procedures or recovery periods. Patients with disease-associated ATP1A3 variants were more likely to have moderate or severe complications. There was no correlation between complications and age or AHC severity. Presence of prior short QTc correlated with cardiac rhythm complications. After this series was analyzed, another patient had severe recurrent laryngeal dystonia requiring tracheostomy following anesthesia with intubation. CONCLUSIONS: During sedation or anesthesia, AHC patients, particularly those with ATP1A3 variants and prior short QTc, are at risk for complications consistent with AHC pathophysiology. Increased awareness is warranted during planning, performance, and recovery from such procedures.

Remote telesurgery in humans: a systematic review.

BACKGROUND: Since the conception of robotic surgery, remote telesurgery has been a dream upon which incredible technological advances haven been built. Despite the considerable enthusiasm for, there have been few published studies of remote telesurgery on humans. METHODS: We performed a systematic review of the English literature (PubMed, EMbase, Inspec & Compendex and Web of Science) to report studies of remote telesurgery in humans. Keywords included telesurgery, remote surgery, long-distance surgery, and telerobotics. Subjects had to be human (live patients or cadavers). The operating surgeon had to be remote from the patient, separated by more than one kilometer. The article had to explicitly report the use of a long-distance telerobotic technique. Articles that focused on telepresence or tele-mentoring were excluded. RESULTS: The study included eight articles published from 2001 to 2020. One manuscript (1 subject) described remote surgery on a cadaver model, and the other seven were on live humans (72 subjects). Procedure types included percutaneous, endovascular, laparoscopic, and transoral. Communication methods varied, with the first report using a telephone line and the most recent studies using a 5G network. Six of the studies reported signal latency as a single value and it ranged from 28 ms to 280 ms. CONCLUSIONS: Few studies have described remote telesurgery in humans, and there is considerable variability in robotic and communication methods. Future efforts should work to improve reporting of signal latency and follow careful research methodology.

Transoral Excision of a Large Accessory Parotid Gland Tumor.

Accessory parotid gland (APG) tumors account for 1% to 7% of all parotid gland neoplasms but are more likely to be malignant than main parotid gland tumors. Management of APG neoplasms entails surgical excision. Four primary approaches to resection have been described in the literature with varying facial nerve outcomes. We report a case of a 4-cm APG pleomorphic adenoma utilizing a transoral approach for excision without postoperative facial nerve injury. A transoral approach is known to mitigate patients' cosmetic concerns; however, prior reports utilized endoscopic assistance on patients with smaller tumors. We conclude that large APG tumors can be excised through a transoral approach without undue risk to the distal facial nerves, though this transoral approach ultimately may not be appropriate for malignant neoplasms or difficult dissections.

ATP1A3-Encoded Sodium-Potassium ATPase Subunit Alpha 3 D801N Variant Is Associated With Shortened QT Interval and Predisposition to Ventricular Fibrillation Preceded by Bradycardia.

Background Pathogenic variation in the ATP1A3-encoded sodium-potassium ATPase, ATP1A3, is responsible for alternating hemiplegia of childhood (AHC). Although these patients experience a high rate of sudden unexpected death in epilepsy, the pathophysiologic basis for this risk remains unknown. The objective was to determine the role of ATP1A3 genetic variants on cardiac outcomes as determined by QT and corrected QT (QTc) measurements. Methods and Results We analyzed 12-lead ECG recordings from 62 patients (male subjects=31, female subjects=31) referred for AHC evaluation. Patients were grouped according to AHC presentation (typical versus atypical), ATP1A3 variant status (positive versus negative), and ATP1A3 variant (D801N versus other variants). Manual remeasurements of QT intervals and QTc calculations were performed by 2 pediatric electrophysiologists. QTc measurements were significantly shorter in patients with positive ATP1A3 variant status (P<0.001) than in patients with genotype-negative status, and significantly shorter in patients with the ATP1A3-D801N variant than patients with other variants (P<0.001). The mean QTc for ATP1A3-D801N was 344.9 milliseconds, which varied little with age, and remained <370 milliseconds throughout adulthood. ATP1A3 genotype status was significantly associated with shortened QTc by multivariant regression analysis. Two patients with the ATP1A3-D801N variant experienced ventricular fibrillation, resulting in death in 1 patient. Rare variants in ATP1A3 were identified in a large cohort of genotype-negative patients referred for arrhythmia and sudden unexplained death. Conclusions Patients with AHC who carry the ATP1A3-D801N variant have significantly shorter QTc intervals and an increased likelihood of experiencing bradycardia associated with life-threatening arrhythmias. ATP1A3 variants may represent an independent cause of sudden unexplained death. Patients with AHC should be evaluated to identify risk of sudden death.

The bowfin genome illuminates the developmental evolution of ray-finned fishes.

The bowfin (Amia calva) is a ray-finned fish that possesses a unique suite of ancestral and derived phenotypes, which are key to understanding vertebrate evolution. The phylogenetic position of bowfin as a representative of neopterygian fishes, its archetypical body plan and its unduplicated and slowly evolving genome make bowfin a central species for the genomic exploration of ray-finned fishes. Here we present a chromosome-level genome assembly for bowfin that enables gene-order analyses, settling long-debated neopterygian phylogenetic relationships. We examine chromatin accessibility and gene expression through bowfin development to investigate the evolution of immune, scale, respiratory and fin skeletal systems and identify hundreds of gene-regulatory loci conserved across vertebrates. These resources connect developmental evolution among bony fishes, further highlighting the bowfin's importance for illuminating vertebrate biology and diversity in the genomic era.

Sugammadex Effects on Hormonal Contraception Effectiveness: Implementation of Uniform Postoperative Teaching.

PURPOSE: The purpose of this quality improvement project was to improve consistency of discharge teaching in women who used progesterone-containing hormonal contraceptive medications and received sugammadex during general anesthesia, as there is a risk of unintended pregnancy for 1 week after administration of sugammadex. DESIGN: This project used a predesign and postdesign using two separate sample groups of patients and postanesthesia care unit (PACU) nurses. METHODS: The sample consisted of 31 total women of childbearing age and 59 PACU nurses. Simplification of sugammadex discharge instructions was achieved by incorporating evidence-based recommendations for electronic discharge instructions and nursing education. PACU nurses were educated and surveyed before and after regarding frequency of discharge teaching, clarity, and comprehension of the after-visit summary and knowledge of sugammadex. Patients were called via telephone postoperatively to assess recall of sugammadex discharge teaching. FINDINGS: Postoperative patient phone calls identified a small increase in patient recall of discharge instructions from 5 of 14 patients (35.7%) before implementation to 7 of 17 after implementation (41.2%). PACU nurse surveys indicated an increase in self-reported frequency of sugammadex discharge teaching (34.8% vs 64.2%, P = .024) and that new discharge instructions contained more clear, comprehensive information as compared with previous instructions (29.4% vs 75.5%, P = .001). CONCLUSIONS: This quality improvement project successfully implemented more consistent and comprehensive discharge instructions for women who receive sugammadex intraoperatively. Limitations of the project included a small sample size and short implementation intervals. As a result of switching to uniform discharge instructions, more patients received important discharge teaching from PACU nurses, and the percentage of patients who recalled this information increased.

Preclinical experience with a novel single-port platform for transoral surgery.

BACKGROUND: We investigated a novel minimally invasive surgical platform for use in the oropharynx, hypopharynx, and larynx for single-port transoral surgery used in concert with standard transoral laryngeal and pharyngeal instrumentation. METHODS: The preclinical investigational device by Fortimedix Surgical B.V. (Netherlands) features two channels for manually controlled flexible articulating surgical instruments. A third central channel accepts both rigid and flexible endoscopes. The system is coupled to a standard laryngoscope for transoral access. In three cadaver models, we evaluated the surgical capabilities using wristed grasping instruments, microlaryngeal scissors, monopolar cautery, and a laser fiber sheath. Procedures were performed within the oropharynx, supraglottis, glottis, subglottis, and hypopharynx. RESULTS: Within the oropharynx, we found adequate strength, range of motion, and dexterity to perform lateral oropharyngectomy and tongue base resection. Within the larynx, visualization was achieved with a variety of instruments including a flexible, 0° and 30° rigid endoscope. The glottis, supraglottis, pyriform sinuses, post-cricoid space, and esophageal inlet were readily accessible. Visualization and manipulation of grasping, laser, and monopolar cautery instruments were also possible within the subglottis. Instrument reach and accuracy facilitated completion of a delicate micro-flap on the true vocal fold. Other procedures included vocal fold resection, cricopharyngeal myotomy, and resection of subglottic mucosa. CONCLUSIONS: From this initial proof of concept experience with this novel platform, we found a wide range of procedures within the oropharynx, larynx, and hypopharynx to be feasible. Further work is needed to evaluate its applicability to the clinical setting. The ability of this platform to be used with conventional instrumentation may provide an opportunity for complex transoral surgery to be performed in a facile manner at greatly reduced cost.

Does the bowfin gas bladder represent an intermediate stage during the lung-to-gas bladder evolutionary transition?

Whether phenotypic evolution occurs gradually through time has prompted the search for intermediate forms between the ancestral and derived states of morphological features, especially when there appears to be a discontinuous origin. The gas bladder, a derived character of the Actinopteri, is a modification of lungs, which characterize the common ancestor of bony vertebrates. While gas bladders and lungs are similar in many ways, the key morphological difference between these organs is the direction of budding from the foregut during development; essentially, the gas bladder buds dorsally and the lungs bud ventrally from the foregut. Did the shift from ventral lungs to dorsal gas bladder transition through a lateral-budding stage? To answer this question, the precise location of budding during gas bladder development in bowfin, representing the sister lineage to teleosts, has been debated. In the early 20th-century, it was suggested that the bowfin gas bladder buds laterally from the right wall of the foregut. We used nano-CT scanning to visualize the early development of the bowfin gas bladder to verify the historical studies of gas bladder developmental morphology and determine whether the direction of gas bladder budding in bowfin could be intermediate between ventrally budding lungs and dorsally budding gas bladders. We found that the bowfin gas bladder buds dorsally from the anterior foregut; however, during early development, the posterior gas bladder twists right. As development progresses, the posterior, right-hand twist becomes shallower, and the gas bladder itself shifts toward a mid-dorsal position. The budding site is definitively dorsal, despite the temporary lateral twist of the posterior gas bladder.

Sensors for detecting per- and polyfluoroalkyl substances (PFAS): A critical review of development challenges, current sensors, and commercialization obstacles.

Per- and polyfluoroalkyl substances (PFAS) are a class of compounds that have become environmental contaminants of emerging concern. They are highly persistent, toxic, bioaccumulative, and ubiquitous which makes them important to detect to ensure environmental and human health. Multiple instrument-based methods exist for sensitive and selective detection of PFAS in a variety of matrices, but these methods suffer from expensive costs and the need for a laboratory and highly trained personnel. There is a big need for fast, inexpensive, robust, and portable methods to detect PFAS in the field. This would allow environmental laboratories and other agencies to perform more frequent testing to comply with regulations. In addition, the general public would benefit from a fast method to evaluate the drinking water in their homes for PFAS contamination. A PFAS sensor would provide almost real-time data on PFAS concentrations that can also provide actionable information for water quality managers and consumers around the planet. In this review, we discuss the sensors that have been developed up to this point for PFAS detection by their molecular detection mechanism as well as the goals that should be considered during sensor development. Future research needs and commercialization challenges are also highlighted.

Compensatory motion scaling for time-delayed robotic surgery.

BACKGROUND: Round trip signal latency, or time delay, is an unavoidable constraint that currently stands as a major barrier to safe and efficient remote telesurgery. While there have been significant technological advancements aimed at reducing the time delay, studies evaluating methods of mitigating the negative effects of time delay are needed. Herein, we explored instrument motion scaling as a method to improve performance in time-delayed robotic surgery. METHODS: This was a robotic surgery user study using the da Vinci Research Kit system. A ring transfer task was performed under normal circumstances (no added time delay), and with 250 ms, 500 ms, and 750 ms delay. Robotic instrument motion scaling was modulated across a range of values (- 0.15, - 0.1, 0, + 0.1, + 0.15), with negative values indicating less instrument displacement for a given amount of operator movement. The primary outcomes were task completion time and total errors. Three-dimensional instrument movement was compared against different motion scales using dynamic time warping to demonstrate the effects of scaling. RESULTS: Performance declined with increasing time delay. Statistically significant increases in task time and number of errors were seen at 500 ms and 750 ms delay (p < 0.05). Total errors were positively correlated with task time on linear regression (R = 0.79, p < 0.001). Under 750 ms delay, negative instrument motion scaling improved error rates. Negative motion scaling trended toward improving task times toward those seen in non-delayed scenarios. Improvements in instrument path motion were seen with the implementation of negative motion scaling. CONCLUSIONS: Under time-delayed conditions, negative robotic instrument motion scaling yielded fewer surgical errors with slight improvement in task time. Motion scaling is a promising method of improving the safety and efficiency of time-delayed robotic surgery and warrants further investigation.

Dorsoventral inversion of the air-filled organ (lungs, gas bladder) in vertebrates: RNAsequencing of laser capture microdissected embryonic tissue.

How modification of gene expression generates novel traits is key to understanding the evolutionary process. We investigated the genetic basis for the origin of the piscine gas bladder from lungs of ancestral bony vertebrates. Distinguishing these homologous organs is the direction of budding from the foregut during development; lungs bud ventrally and the gas bladder buds dorsally.

Changes in Nkx2.1, Sox2, Bmp4, and Bmp16 expression underlying the lung-to-gas bladder evolutionary transition in ray-finned fishes.

The key to understanding the evolutionary origin and modification of phenotypic traits is revealing the responsible underlying developmental genetic mechanisms. An important organismal trait of ray-finned fishes is the gas bladder, an air-filled organ that, in most fishes, functions for buoyancy control, and is homologous to the lungs of lobe-finned fishes. The critical morphological difference between lungs and gas bladders, which otherwise share many characteristics, is the general direction of budding during development. Lungs bud ventrally and the gas bladder buds dorsally from the anterior foregut. We investigated the genetic underpinnings of this ventral-to-dorsal shift in budding direction by studying the expression patterns of known lung genes (Nkx2.1, Sox2, and Bmp4) during the development of lungs or gas bladder in three fishes: bichir, bowfin, and zebrafish. Nkx2.1 and Sox2 show reciprocal dorsoventral expression patterns during tetrapod lung development and are important regulators of lung budding; their expression during bichir lung development is conserved. Surprisingly, we find during gas bladder development, Nkx2.1 and Sox2 expression are inconsistent with the hypothesis that they regulate the direction of gas bladder budding. Bmp4 is expressed ventrally during lung development in bichir, akin to the pattern during mouse lung development. During gas bladder development, Bmp4 is not expressed. However, Bmp16, a paralogue of Bmp4, is expressed dorsally in the developing gas bladder of bowfin. Bmp16 is present in the known genomes of Actinopteri (ray-finned fishes excluding bichir) but absent from mammalian genomes. We hypothesize that Bmp16 was recruited to regulate gas bladder development in the Actinopteri in place of Bmp4.