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Encoding of Wind Direction by Central Neurons in Drosophila

Suver, Marie P; Matheson, Andrew M M; Sarkar, Sinekdha; Damiata, Matthew; Schoppik, David; Nagel, Katherine I
Wind is a major navigational cue for insects, but how wind direction is decoded by central neurons in the insect brain is unknown. Here we find that walking flies combine signals from both antennae to orient to wind during olfactory search behavior. Movements of single antennae are ambiguous with respect to wind direction, but the difference between left and right antennal displacements yields a linear code for wind direction in azimuth. Second-order mechanosensory neurons share the ambiguous responses of a single antenna and receive input primarily from the ipsilateral antenna. Finally, we identify novel "wedge projection neurons" that integrate signals across the two antennae and receive input from at least three classes of second-order neurons to produce a more linear representation of wind direction. This study establishes how a feature of the sensory environment-wind direction-is decoded by neurons that compare information across two sensors.
PMID: 30948249
ISSN: 1097-4199
CID: 3900752

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Diagnosis, pre-operative, operative and post-operative pediatric choanal atresia care

Moreddu, Eric; Rizzi, Mark; Adil, Eelam; Balakrishnan, Karthik; Chan, Kenny; Cheng, Alan; Daniel, Sam J; de Alarcon, Alessandro; Hart, Catherine; Hartnick, Christopher; Inglis, Andrew; Leboulanger, Nicolas; Pransky, Seth; Rahbar, Reza; Russell, John; Rutter, Mike; Sidell, Douglas; Smith, Richard J H; Soma, Marlene; Spratley, Jorge; Thompson, Dana; Trozzi, Marilena; Ward, Robert; Wyatt, Michelle; Yeung, Jeffrey; Zalzal, George; Zur, Karen; Nicollas, Richard
OBJECTIVE:To provide recommendations to otolaryngologists and allied physicians for the comprehensive management of young infants who present with signs or symptoms of choanal atresia. METHODS:A two-iterative delphi method questionnaire was used to establish expert recommendations by the members of the International Otolaryngology Group (IPOG), on the diagnostic, intra-operative, post-operative and revision surgery considerations. RESULTS:Twenty-eight members completed the survey, in 22 tertiary-care center departments representing 8 countries. The main consensual recommendations were: nasal endoscopy or fiberscopy and CT imaging are recommended for diagnosis; unilateral choanal atresia repair should be delayed after at least age 6 months whenever possible; transnasal endoscopic repair is the preferred technique; long term follow-up is recommended (minimum one year) using nasal nasofiberscopy or rigid endoscopy, without systematic imaging. CONCLUSION/CONCLUSIONS:Choanal atresia care consensus recommendations are aimed at improving patient-centered care in neonates, infants and children with choanal atresia.
PMID: 31103745
ISSN: 1872-8464
CID: 3901012

Autologous Reconstruction of a Face Transplant Candidate [Case Report]

Rifkin, William J; Bellamy, Justin L; Kantar, Rami S; Farber, Scott J; Diaz-Siso, J Rodrigo; Brecht, Lawrence E; Rodriguez, Eduardo D
Since 2005, facial transplantation has emerged as a viable reconstructive option for the most severe defects not amenable to conventional reconstructive techniques, with promising aesthetic and functional outcomes to date. Key facial subunits and midface structures such as the eyelids, lips, and nose are now able to be successfully replaced rather than reconstructed, enabling adequate functional outcomes in even the most extensive defects. However, even in cases of severe facial disfigurement, the decision to proceed with transplantation versus autologous reconstruction remains a source of debate, with no current consensus regarding precise indications and inclusion/exclusion criteria. This report details the case of a candidate referred for face transplantation who ultimately underwent autologous facial reconstruction. Through this representative case, our objective is to clarify the criteria that make a patient a suitable face transplant candidate, as well as to demonstrate the outcomes achievable with a conventional autologous reconstruction, using a methodically planned, multistaged approach.
PMCID:6506261
PMID: 31073366
ISSN: 1943-3875
CID: 3900912

Sequencing and curation strategies for identifying candidate glioblastoma treatments

Frank, Mayu O; Koyama, Takahiko; Rhrissorrakrai, Kahn; Robine, Nicolas; Utro, Filippo; Emde, Anne-Katrin; Chen, Bo-Juen; Arora, Kanika; Shah, Minita; Geiger, Heather; Felice, Vanessa; Dikoglu, Esra; Rahman, Sadia; Fang, Alice; Vacic, Vladimir; Bergmann, Ewa A; Vogel, Julia L Moore; Reeves, Catherine; Khaira, Depinder; Calabro, Anthony; Kim, Duyang; Lamendola-Essel, Michelle F; Esteves, Cecilia; Agius, Phaedra; Stolte, Christian; Boockvar, John; Demopoulos, Alexis; Placantonakis, Dimitris G; Golfinos, John G; Brennan, Cameron; Bruce, Jeffrey; Lassman, Andrew B; Canoll, Peter; Grommes, Christian; Daras, Mariza; Diamond, Eli; Omuro, Antonio; Pentsova, Elena; Orange, Dana E; Harvey, Stephen J; Posner, Jerome B; Michelini, Vanessa V; Jobanputra, Vaidehi; Zody, Michael C; Kelly, John; Parida, Laxmi; Wrzeszczynski, Kazimierz O; Royyuru, Ajay K; Darnell, Robert B
BACKGROUND:Prompted by the revolution in high-throughput sequencing and its potential impact for treating cancer patients, we initiated a clinical research study to compare the ability of different sequencing assays and analysis methods to analyze glioblastoma tumors and generate real-time potential treatment options for physicians. METHODS:A consortium of seven institutions in New York City enrolled 30 patients with glioblastoma and performed tumor whole genome sequencing (WGS) and RNA sequencing (RNA-seq; collectively WGS/RNA-seq); 20 of these patients were also analyzed with independent targeted panel sequencing. We also compared results of expert manual annotations with those from an automated annotation system, Watson Genomic Analysis (WGA), to assess the reliability and time required to identify potentially relevant pharmacologic interventions. RESULTS:WGS/RNAseq identified more potentially actionable clinical results than targeted panels in 90% of cases, with an average of 16-fold more unique potentially actionable variants identified per individual; 84 clinically actionable calls were made using WGS/RNA-seq that were not identified by panels. Expert annotation and WGA had good agreement on identifying variants [mean sensitivity = 0.71, SD = 0.18 and positive predictive value (PPV) = 0.80, SD = 0.20] and drug targets when the same variants were called (mean sensitivity = 0.74, SD = 0.34 and PPV = 0.79, SD = 0.23) across patients. Clinicians used the information to modify their treatment plan 10% of the time. CONCLUSION/CONCLUSIONS:These results present the first comprehensive comparison of technical and machine augmented analysis of targeted panel and WGS/RNA-seq to identify potential cancer treatments.
PMCID:6485090
PMID: 31023376
ISSN: 1755-8794
CID: 3900782

Machine learning to predict occult nodal metastasis in early oral squamous cell carcinoma

Bur, Andrés M; Holcomb, Andrew; Goodwin, Sara; Woodroof, Janet; Karadaghy, Omar; Shnayder, Yelizaveta; Kakarala, Kiran; Brant, Jason; Shew, Matthew
OBJECTIVES/OBJECTIVE:To develop and validate an algorithm to predict occult nodal metastasis in clinically node negative oral cavity squamous cell carcinoma (OCSCC) using machine learning. To compare algorithm performance to a model based on tumor depth of invasion (DOI). MATERIALS AND METHODS/METHODS:Patients who underwent primary tumor extirpation and elective neck dissection from 2007 to 2013 for clinical T1-2N0 OCSCC were identified from the National Cancer Database (NCDB). Multiple machine learning algorithms were developed to predict pathologic nodal metastasis using clinicopathologic data from 782 patients.The algorithm was internally validated using test data from 654 patients in NCDB and was then externally validated using data from 71 patients treated at a single academic institution. Performance was measured using area under the receiver operating characteristic (ROC) curve (AUC). Machine learning and DOI model performance were compared using Delong's test for two correlated ROC curves. RESULTS:The best classification performance was achieved with a decision forest algorithm (AUC = 0.840). When applied to the single-institution data, the predictive performance of machine learning exceeded that of the DOI model (AUC = 0.657, p = 0.007). Compared to the DOI model, machine learning reduced the number of neck dissections recommended while simultaneously improving sensitivity and specificity. CONCLUSION/CONCLUSIONS:Machine learning improves prediction of pathologic nodal metastasis in patients with clinical T1-2N0 OCSCC compared to methods based on DOI. Improved predictive algorithms are needed to ensure that patients with occult nodal disease are adequately treated while avoiding the cost and morbidity of neck dissection in patients without pathologic nodal disease.
PMID: 31010618
ISSN: 1879-0593
CID: 3858882

Laryngeal Neuromuscular Response to Short- and Long-Term Vocalization Training in Young Male Rats

Lenell, Charles; Newkirk, Bethany; Johnson, Aaron M
Purpose Although vocal training is often purported to restore and rebalance laryngeal muscle function, little is known about the direct effects of vocal training on the laryngeal muscles themselves. Consequently, parameters of vocal exercise dose, such as training duration and intensity, have not been well defined. The goal of this study was to use a behavioral animal model to determine the effects of short- and long-term ultrasonic vocalization (USV) training on USV acoustics, thyroarytenoid (TA) muscle neuromuscular junctions (NMJs), and TA muscle fiber size in adult rats. Method Twenty-four young adult male Long-Evans rats were divided into 3 groups (untrained control, 4-week training, and 8-week training). Baseline and posttraining USVs were recorded and acoustically analyzed for fundamental frequency, frequency bandwidth, amplitude, and duration. Presynaptic and postsynaptic NMJ morphological features and muscle fiber size were measured in the TA. Results USV training had no effect on USV acoustics. Eight weeks of USV training, however, resulted in a lower NMJ motor endplate dispersion ratio, consistent with previous findings. USV training did not affect fiber size within the TA muscle. Conclusions This study demonstrated that 8 weeks of USV training can induce peripheral neural adaptations in the NMJ of the TA muscle in young rats. The observed adaptations suggest that vocal training is consistent with endurance-type exercise, but the adaptations occur on a longer time scale than similar adaptations in the limb muscles.
PMCID:6436889
PMID: 30950702
ISSN: 1558-9102
CID: 3858182

Validating a Quick Spectral Modulation Detection Task

Landsberger, David M; Dwyer, Robert T; Stupak, Natalia; Gifford, René H
OBJECTIVES/OBJECTIVE:The Quick Spectral Modulation Detection (QSMD) test provides a quick and clinically implementable spectral resolution estimate for cochlear implant (CI) users. However, the original QSMD software (QSMD(MySound)) has technical and usability limitations that prevent widespread distribution and implementation. In this article, we introduce a new software package EasyQSMD, which is freely available software with the goal of both simplifying and standardizing spectral resolution measurements. DESIGN/METHODS:QSMD was measured for 20 CI users using both software packages. RESULTS:No differences between the two software packages were detected, and based on the 95% confidence interval of the difference between tests, the difference between the tests is expected to be <2% points. The average test duration was under 4 minutes. CONCLUSIONS:EasyQSMD is considered functionally equivalent to QSMD(MySound) providing a clinically feasible and quick estimate of spectral resolution for CI users.
PMID: 31033635
ISSN: 1538-4667
CID: 3854362

Clinical experience with mechanically coupled anastomoses in skull base reconstruction [Meeting Abstract]

Benjamin, C; Delacure, M
Background: The reconstruction of major skull base, scalp and calvarial defects with microvascular free flaps has revolutionized the predictable and safe conduct of multidisciplinary oncologic surgery of this region. While extended resections can be more confidently completed, this has not necessarily been accompanied by increased local control or cure. This is due to limitations of radiation tolerance of surrounding tissues, necessary acceptance of involved microscopically close or involved margins, tolerable morbidity, and the lack of specific medical oncologic agents for benign and malignant CNS tumors. Use of coupler devices in routine head and neck defects evolved into use in skull base, calvarial, and intracranial settings where flap loss can be catastrophic.
Method(s): Mechanical microvascular anastomosis became increasingly widely used in head and neck reconstruction in the late 1980s and 1990s as a method to speed the process, and perhaps patency over hand-sewn anastomoses. These have been incorporated primarily in venous interposition graft and end-to-end, and end-to side venous configurations facilitated by vessel pliability and the ability to evert vessel walls over coupler pins. The coupler itself is constructed of 2 polyethylene rings and staggered ferromagnetic pins which match holes on the opposing ring through a friction fit, thus joining the vessels. Because of its construction, and the increased use and preference of MRI for perioperative evaluation early concern for heating and/or rotation, torquing or disruption of new anastomoses, it was studied in a relevant model and found in clinical experience, to be irrelevant.[1]
Conclusion(s): The use of the superficial temporal vessels for recipients is often preferred to save pedicle length, minimize the need for interposition vein grafts (doubling the number of anastomoses and thrombotic opportunity/risk), and often influenced by prior treatment (bicoronal flaps) in which ligation and scar may limit suitability. Additionally, the vein is often thin-walled and technically unusable. The incision for access to these vessels is usually placed immediately in the junctional creases of the ear and cheek, and thus several millimeters removed from the actual course of the vessels. In a broad and significant experience spanning 25 years including 40 skull base microvascular reconstructions, 15 of which used temporal recipient vessels, there have been 2 cases (one calvarial, one intracranial) where the coupler rings have eroded through the temporal skin, and self-ejected, without flap loss, and implying the acquisition of adequate venous supply to support flap survival. Given this observation, unique to this region, hand-sewn anastomoses are specifically recommended when using these vessels so as to minimize potentially catastrophic flap loss. Our experience in microvascular skull base reconstruction in this context is reviewed in support of this recommendation
EMBASE:627318551
ISSN: 2193-6331
CID: 3831702

Quality improvement in endoscopic endonasal surgery [Meeting Abstract]

Benjamin, C G; Pacione, D; Bevilacqua, J; Kurland, D; Lewis, A; Golfinos, J G; Sen, C; Lebowitz, R; Liberman, S; Placantonakis, D; Jafar, J
Background: Surgical resection of pituitary adenomas is associated with a 10 to 30% rate of temporary diabetes insipidus with ~50% resolving within 1 week and 80% resolving at 3 months.[1] Adrenal insufficiency occurs in ~ 5 % of patients and can result in an Addisonian crisis if left undiagnosed postoperatively.[1] [2] Many studies have been performed looking at readmission rates after pituitary surgery. A review of over 1,200 cases demonstrated a readmission rate of 8.5% with the most common cause being hyponatremia (29.5%).[3] To reduce the rate of readmission for hyponatremia, some groups have demonstrated the effective use of outpatient fluid restriction criteria during the first week post-op.[4] These guidelines are intended for the management of standard postoperative hormonal fluctuations which do not necessitate endocrine consultation during hospitalization.
Objective(s): Retrospectively evaluate patients undergoing endoscopic endonasal resection of pituitary adenomas to identify areas for quality improvement through the development of more standardized postoperative guidelines.
Method(s): A retrospective review of 75 patients who underwent endoscopic endonasal resection of pituitary adenomas at a single academic center from 2013 to 2018. We evaluated the average length of stay, number of laboratory studies performed, need for hormone supplementation long term and short term, rate of gross-total resection, rate of cerebrospinal fluid leak, rate of infection, and 30-day readmission rate ([Table 1]). From this, we have developed a change in guidelines aimed at reducing length of stay, redundant laboratory studies, and reduced rate of readmission.
Conclusion(s): Although our current outcomes for resection of pituitary adenoma are on par with published data, we have identified areas of possible quality improvement which have since been implemented
EMBASE:627318116
ISSN: 2193-6331
CID: 3831712

Use of delayed staged combined transcranial and endoscopic endonasal resection of anterior skull base meningioma to reduce risk of cerebrospinal fluid leak [Meeting Abstract]

Pacione, D; Lieberman, S
Background: Large anterior skull base meningiomas with significant extension through the floor of the anterior fossa into the ethmoid and sphenoid sinuses pose a surgical dilemma. Radical resection of these tumors as well as the skull base and sinus component can be curative. This can be achieved through either a transcranial approach or a combined transcranial/endonasal approach depending on the involvement of the sinuses. However, in doing so, patients are at significant risk for postoperative cerebrospinal fluid leak as well as infection. Given these risks and the benign nature of these tumors, especially WHO grade I meningiomas, many surgeons will choose not to resect the portion going through the skull base. The residual tumor can then be observed or radiated if there are signs of growth.
Objective(s): We propose the use of a staged combined approach to maximize resection and minimize risk of CSF leak or infection. Case Presentation: We present the case of a 55-year-old male, BMI of 37, who presented with 3 weeks of left eye blurry vision, 2 years of anosmia, and personality changes. The patient was found to have a 7.3x5.9x4.6 cm anterior skull base meningioma with significant surrounding parenchymal edema in the bilateral frontal lobes as well as extension through the floor of the anterior skull base and into the ethmoid and sphenoid sinuses ([Fig. 1a], b). He was taken for a bifrontal craniotomy and resection of the intracranial component with planned amputation of the tumor at the skull base which was covered with a pericranial flap. He recovered well with return of his vision to normal. Pathology demonstrated a WHO grade II atypical meningioma. Follow-up imaging demonstrated persistent residual tumor within the ethmoid and sphenoid sinus ([Fig. 2]). We discussed an endoscopic endonasal resection of the residual tumor and anterior skull base in a delayed fashion once the pericranial graft healed versus radiation. The patient preferred to proceed with resection. He underwent an endoscopic endonasal resection of the residual tumor within the sinus and remaining anterior skull base. At the time of surgery the tumor was easily separated from the pericranial graft which was well healed. No CSF was observed but a nasoseptal flap was placed for protection. He was discharged on POD2. Postoperative imaging demonstrated gross total resection of the residual tumor ([Fig. 3]).
Conclusion(s): The use of a delayed combined transcranial and endoscopic endonasal approach for anterior skull base meningiomas with significant intracranial and sinus tumor component potentially maximizes surgical resection while reducing the risk of CSF leak and infection. (Figure Presented)
EMBASE:627318098
ISSN: 2193-6331
CID: 3831722