SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac.

Decreased presence or activity of human SLC26A4 at the plasma membrane is a common cause of hearing loss. SLC26A4 (Pendrin) is necessary for normal reabsorption of endolymph, the fluid bathing the inner ear. We identified the µ2 subunit of adaptor protein 2 (AP-2) complex required for clathrin-mediated endocytosis as a protein-partner of SLC26A4 involved in regulating its plasma membrane abundance. We showed that, in the endolymphatic sac, where fluid reabsorption occurs, SLC26A4 is localized along the apical microvilli of mitochondria-rich cells, in contact with the endolymph, and associated with clathrin-coated pits where µ2 and AP-2 are present. Based on SLC26A4 structure, the elements involved in SLC26A4-µ2 interaction were identified and validated experimentally, allowing modeling of this interaction at the atomic level. Pharmacological inhibition of clathrin-mediated endocytosis led to an increased plasma membrane abundance of hemagglutinin-tagged SLC26A4 virally or endogenously expressed in mitochondria-rich cells. These results indicate that the SLC26A4-µ2 interaction regulates SLC26A4 abundance at the apical surface of mitochondria-rich cells.

Bnip3lb-driven mitophagy sustains expansion of the embryonic hematopoietic stem cell pool.

Embryonic hematopoietic stem and progenitor cells (HSPCs) have the unique ability to undergo rapid proliferation while maintaining multipotency, a clinically-valuable quality which currently cannot be replicated in vitro. Here, we show that embryonic HSPCs achieve this state by precise spatio-temporal regulation of reactive oxygen species (ROS) via Bnip3lb-associated developmentally-programmed mitophagy, a distinct autophagic regulatory mechanism from that of adult HSPCs. While ROS drives HSPC specification in the dorsal aorta, scRNAseq and live-imaging of Tg(ubi:mitoQC) zebrafish indicate that mitophagy initiates as HSPCs undergo endothelial-to-hematopoietic transition and colonize the caudal hematopoietic tissue (CHT). Knockdown of bnip3lb reduced mitophagy and HSPC numbers in the CHT by promoting myeloid-biased differentiation and apoptosis, which was rescued by anti-oxidant exposure. Conversely, induction of mitophagy enhanced both embryonic HSPC and lymphoid progenitor numbers. Significantly, mitophagy activation improved ex vivo functional capacity of hematopoietic progenitors derived from human-induced pluripotent stem cells (hiPSCs), enhancing serial-replating hematopoietic colony forming potential. HIGHLIGHTS: ROS promotes HSPC formation in the dorsal aorta but negatively affects maintenance thereafter.HSPCs colonizing secondary niches control ROS levels via Bnip3lb-directed mitophagy.Mitophagy protects nascent HSPCs from ROS-associated apoptosis and maintains multipotency.Induction of mitophagy enhances long-term hematopoietic potential of iPSC-derived HSPCs.

Use of cannulated screws in the treatment of unicondylar humeral condylar fractures in dogs.

OBJECTIVE: To describe unicondylar humeral fracture (UHF) repair using cannulated transcondylar screws, report postoperative fracture reduction, healing, and complication rates. STUDY DESIGN: Retrospective. ANIMALS: A total of 49 client owned dogs with UHF. METHODS: Surgical technique and approach (i.e., open, limited open, or minimally invasive) were recorded. Articular step defect (ASD) and gap (Gap) at the humeral condylar articular surface were measured on pre- and postoperative images and reported as percentages. Fracture healing was graded on follow-up radiographs. Functional outcome was based on client questionnaire over the phone. General linear models were used to assess the impact of surgical approach on %ASD, %Gap, whereas Cox regression was used to assess prognostic factors of full fracture healing. RESULTS: A total of 49 fractures repaired with a transcondylar screw with or without an antirotational pin(s) were included. Surgical approach did not have an impact on postoperative %ASD, %Gap or development of complications. The overall complication rate was 26% (11/42), with no revision surgery necessary. Of the dogs that encountered complications, 50% required pin and/or screw removal after fracture healing. For 29 dogs with a minimum of four-month owner telephone questionnaire follow-up, 90% reported no lameness and only three reported intermittent lameness. Achieving complete fracture healing was affected by increased postoperative %ASD (p = .033). CONCLUSION: The UHFs repaired by transcondylar cannulated screws had acceptable outcomes and fracture reduction with complication rates being similar regardless of the surgical approach. CLINICAL SIGNIFICANCE: Cannulated screws can be implanted with varying surgical approaches to successfully repair UHFs with comparable clinical outcome to previous reports.

Interaction between the TBC1D24 TLDc domain and the KIBRA C2 domain is disrupted by two epilepsy-associated TBC1D24 missense variants.

Mutations of human TBC1D24 are associated with deafness, epilepsy, or DOORS syndrome (deafness, onychodystrophy, osteodystrophy, cognitive disability, and seizures). The causal relationships between TBC1D24 variants and the different clinical phenotypes are not understood. Our hypothesis is that phenotypic heterogeneity of missense mutations of TBC1D24 results, in part, from perturbed binding of different protein partners. To discover novel protein partners of TBC1D24, we conducted yeast two-hybrid (Y2H) screen using mouse full-length TBC1D24 as bait. Kidney and brain protein (KIBRA), a scaffold protein encoded by Wwc1, was identified as a partner of TBC1D24. KIBRA functions in the Hippo signaling pathway and is important for human cognition and memory. The TBC1D24 TLDc domain binds to KIBRA full-length and to its C2 domain, confirmed by Y2H assays. No interaction was detected with Y2H assays between the KIBRA C2 domain and TLDc domains of NCOA7, MEAK7, and OXR1. Moreover, the C2 domains of other WWC family proteins do not interact with the TLDc domain of TBC1D24, demonstrating specificity. The mRNAs encoding TBC1D24 and KIBRA proteins in mouse are coexpressed at least in a subset of hippocampal cells indicating availability to interact in vivo. As two epilepsy-associated recessive variants (Gly511Arg and Ala515Val) in the TLDc domain of human TBC1D24 disrupt the interaction with the human KIBRA C2 domain, this study reveals a pathogenic mechanism of TBC1D24-associated epilepsy, linking the TBC1D24 and KIBRA pathways. The interaction of TBC1D24-KIBRA is physiologically meaningful and necessary to reduce the risk of epilepsy.

Annelids from the Cambrian (Wuliuan Stage, Miaolingian) Spence Shale Lagerstätte of northern Utah, USA.

The Spence Shale Member of the Langston Formation in northern Utah and southern Idaho preserves generally non-biomineralized fossil assemblages referred to as the Spence Shale Lagerstätte. The biota of this Lagerstätte is dominated by panarthropods, both biomineralized and soft-bodied examples, but also preserves diverse infaunal organisms, including species of scalidophorans, echinoderms, lobopodians, stalked filter feeders, and various problematic taxa. To date, however, only a single annelid fossil, originally assigned to Canadia sp., has been described from the Spence Shale. This lone specimen and another recently collected specimen were analyzed in this study using scanning electron microscopy and energy dispersive X-ray spectrometry. The previous occurrence is reassigned to Burgessochaeta cf. B. setigera Walcott, 1911. The new fossil, however, is identified as a novel polychaete taxon, Shaihuludia shurikeni gen. et sp. nov., characterized by the presence of fused, bladed chaetae and a wide body. The occurrence of Burgessochaeta is the first outside the Burgess Shale and its vicinity, whereas Shaihuludia shurikeni gen. et sp. nov. adds to the diversity of annelids in the middle Cambrian and highlights the diversity of the Spence Shale Lagerstätte.

Dual-AAV vector-mediated expression of MYO7A improves vestibular function in a mouse model of Usher syndrome 1B.

Usher syndrome is the most common cause of deafness-blindness in the world. Usher syndrome type 1B (USH1B) is associated with mutations in MYO7A. Patients with USH1B experience deafness, blindness, and vestibular dysfunction. In this study, we applied adeno-associated virus (AAV)-mediated gene therapy to the shaker-1 (Myo7a4626SB/4626SB) mouse, a model of USH1B. The shaker-1 mouse has a nonsense mutation in Myo7a, is profoundly deaf throughout life, and has significant vestibular dysfunction. Because of the ∼6.7-kb size of the MYO7A cDNA, a dual-AAV approach was used for gene delivery, which involves splitting human MYO7A cDNA into 5' and 3' halves and cloning them into two separate AAV8(Y733F) vectors. When MYO7A cDNA was delivered to shaker-1 inner ears using the dual-AAV approach, cochlear hair cell survival was improved. However, stereocilium organization and auditory function were not improved. In contrast, in the vestibular system, dual-AAV-mediated MYO7A delivery significantly rescued hair cell stereocilium morphology and improved vestibular function, as reflected in a reduction of circling behavior and improved vestibular sensory-evoked potential (VsEP) thresholds. Our data indicate that dual-AAV-mediated MYO7A expression improves vestibular function in shaker-1 mice and supports further development of this approach for the treatment of disabling dizziness from vestibular dysfunction in USH1B patients.

Intravenous antibiotics in preterm infants have a negative effect upon microbiome development throughout preterm life.

BACKGROUND: Intestinal dysbiosis is implicated in the origins of necrotising enterocolitis and late-onset sepsis in preterm babies. However, the effect of modulators of bacterial growth (e.g. antibiotics) upon the developing microbiome is not well-characterised. In this prospectively-recruited, retrospectively-classified, case-control study, high-throughput 16S rRNA gene sequencing was combined with contemporaneous clinical data collection, to assess the within-subject relationship between antibiotic administration and microbiome development, in comparison to preterm infants with minimal antibiotic exposure. RESULTS: During courses of antibiotics, diversity progression fell in comparison to that seen outside periods of antibiotic use (-0.71units/week vs. + 0.63units/week, p < 0.01); Enterobacteriaceae relative abundance progression conversely rose (+ 10.6%/week vs. -8.9%/week, p < 0.01). After antibiotic cessation, diversity progression remained suppressed (+ 0.2units/week, p = 0.02). CONCLUSIONS: Antibiotic use has an acute and longer-lasting impact on the developing preterm intestinal microbiome. This has clinical implications with regard to the contribution of antibiotic use to evolving dysbiosis, and affects the interpretation of existing microbiome studies where this effect modulator is rarely accounted for.

Relational reasoning network for anatomical landmarking.

Purpose: We perform anatomical landmarking for craniomaxillofacial (CMF) bones without explicitly segmenting them. Toward this, we propose a simple, yet efficient, deep network architecture, called relational reasoning network (RRN), to accurately learn the local and the global relations among the landmarks in CMF bones; specifically, mandible, maxilla, and nasal bones. Approach: The proposed RRN works in an end-to-end manner, utilizing learned relations of the landmarks based on dense-block units. For a given few landmarks as input, RRN treats the landmarking process similar to a data imputation problem where predicted landmarks are considered missing. Results: We applied RRN to cone-beam computed tomography scans obtained from 250 patients. With a fourfold cross-validation technique, we obtained an average root mean squared error of < 2 mm per landmark. Our proposed RRN has revealed unique relationships among the landmarks that help us in inferring informativeness of the landmark points. The proposed system identifies the missing landmark locations accurately even when severe pathology or deformations are present in the bones. Conclusions: Accurately identifying anatomical landmarks is a crucial step in deformation analysis and surgical planning for CMF surgeries. Achieving this goal without the need for explicit bone segmentation addresses a major limitation of segmentation-based approaches, where segmentation failure (as often is the case in bones with severe pathology or deformation) could easily lead to incorrect landmarking. To the best of our knowledge, this is the first-of-its-kind algorithm finding anatomical relations of the objects using deep learning.

Qualitative Interviews to Assess the Content Validity and Usability of the Electronic Raynaud Diary in Patients with Systemic Sclerosis.

OBJECTIVE: To better understand the symptoms and impacts of Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc) and to evaluate the content validity and usability of a new electronic patient-reported outcome (PRO) measure for RP: the Raynaud Diary. METHODS: The Raynaud Diary was developed as a daily eDiary for assessing the number and duration of symptomatic Raynaud attacks; worst pain, numbness, tingling, and discomfort in the fingers; and overall disease severity, captured using the Raynaud's Condition Score. The Raynaud Diary was debriefed in two waves of qualitative interviews with adults with self-reported RP secondary to SSc. All interviews included open-ended questions about participants' experiences of RP. RESULTS: Participants (N = 39) had a mean age of 55.1 years, and 87% were female. Frequently reported RP symptoms were color change (reported by all participants), numbness (90%), tingling (82%), pain (77%), and discomfort (72%). Common attack triggers included temperature-related factors and stress. Participants reported being unable to be outside or do outdoor activities and had problems gripping objects. All participants demonstrated understanding of the Raynaud Diary instructions. Most participants indicated that they would be able to use the Raynaud Diary to record the worst severity of individual RP symptoms in the previous 24 hours. CONCLUSION: Patients with RP secondary to SSc bear a heavy symptom burden. The Raynaud Diary is a content valid PRO measure that captures the most frequent symptoms of RP in patients with SSc.

Outcome and Cost Comparisons Between Surgical and Transcatheter Aortic Valve Replacements.

OBJECTIVE: Surgical aortic valve replacement (SAVR) has been the standard of care for severe aortic stenosis. In 2019, annual transcatheter aortic valve replacement (TAVR) implantations surpassed SAVR. We compared in-hospital costs and outcomes between these two procedures. METHODS: A single-center retrospective review was performed of patients who underwent isolated SAVR or TAVR from October 2013 to December 2019. Baseline patient characteristics, operating room (OR) time, intensive care unit (ICU) length of stay (LOS), total LOS, cumulative cost, and complication rates were collected. Propensity matching was performed to identify differences in costs and outcomes between comparable groups. RESULTS: There were 515 patients who met inclusion criteria. TAVR was performed in 402 patients, while SAVR was performed in 113. Propensity matching resulted in 82 matched pairs. The SAVR cohort more frequently spent >1 day in the ICU, had longer total hospital LOS, longer OR time, and higher hospitalization cost. However, TAVR was associated with higher mean OR cost and higher valve cost. The cumulative index admission costs were not significantly different between groups. TAVR patients had less postoperative atrial fibrillation but more frequent pacemaker placement. One-year mortality was similar between SAVR (2.4%) and TAVR (3.8%), but 3-year (5.8% vs 19.2%) and 5-year (5.8% vs 37.2%) mortality favored SAVR. CONCLUSIONS: In propensity-matched groups, TAVR was associated with shorter ICU and hospital LOS and OR times but increased permanent pacemaker rates. In addition, while 1-year survival was similar between groups, SAVR had significantly improved 3-year and 5-year survival.

Monitored Anesthesia Care Versus General Anesthesia for Transcatheter Aortic Valve Replacement.

OBJECTIVE: Monitored anesthesia care (MAC) has been increasingly used in lieu of general anesthesia (GA) for transcatheter aortic valve replacement (TAVR). We sought to compare outcomes and in-hospital costs between MAC and GA for TAVR at a Veterans Affairs Medical Center. METHODS: A single-center retrospective review was performed of 349 patients who underwent transfemoral TAVR (MAC, n = 244 vs GA, n = 105) from January 2014 to December 2019. Baseline patient characteristics, operating room (OR) time, intensive care unit (ICU) length of stay (LOS), and cost, total LOS, hospital cost, total cost, and complication rates were collected. Propensity matching was performed and resulted in 83 matched pairs. RESULTS: In the unmatched TAVR cohort, MAC TAVR was associated with reduced OR time (146 vs 198 min, P < 0.001), ICU LOS (1.4 vs 1.8 days, P < 0.001), total hospital LOS (3.4 vs 5.4 days, P < 0.001), and lower index total cost ($81,300 vs $85,400, P = 0.010). After propensity matching, MAC TAVR patients had reduced OR time (146 vs 196 min, P < 0.05), ICU LOS (1.2 vs 1.7 days, P = 0.006), total LOS (3.5 vs 5.1 days, P = 0.001), and 180-day mortality (2.4% vs 12%, P < 0.03). There was no difference in total hospitalization cost or total cost. CONCLUSIONS: In propensity-matched groups, TAVR utilizing MAC is associated with improved OR time efficiency, decreased LOS, and a reduction in 180-day mortality but no significant difference in cost.

AAV8BP2 and AAV8 transduce the mammalian cochlear lateral wall and endolymphatic sac with high efficiency.

Inner ear gene therapy using adeno-associated viruses (AAVs) has been successfully applied to several mouse models of hereditary hearing loss to improve their auditory function. While most inner ear gene therapy studies have focused on the mechanosensory hair cells and supporting cells in the organ of Corti, the cochlear lateral wall and the endolymphatic sac have not garnered much attention. The cochlear lateral wall and the endolymphatic sac play critical roles in inner ear ionic and fluid homeostasis. Mutations in genes expressed in the cochlear lateral wall and the endolymphatic sac are present in a large percentage of patients with hereditary hearing loss. In this study, we examine the transduction patterns and efficiencies of conventional (AAV2 and AAV8) and synthetic (AAV2.7m8, AAV8BP2, and Anc80L65) AAVs in the mouse inner ear. We found that AAV8BP2 and AAV8 are capable of transducing the marginal cells and intermediate cells in the stria vascularis. These two AAVs can also transduce the epithelial cells of the endolymphatic sac. Our data suggest that AAV8BP2 and AAV8 are highly useful viral vectors for gene therapy studies targeting the cochlear lateral wall and the endolymphatic sac.

Assessment of a Decision Support System for Adults with Type 1 Diabetes on Multiple Daily Insulin Injections.

Introduction: DailyDose is a decision support system designed to provide real-time dosing advice and weekly insulin dose adjustments for adults living with type 1 diabetes using multiple daily insulin injections. Materials and Methods: Twenty-five adults were enrolled in this single-arm study. All participants used Dexcom G6 for continuous glucose monitoring, InPen for short-acting insulin doses, and Clipsulin to track long-acting insulin doses. Participants used DailyDose on an iPhone for 8 weeks. The primary endpoint was % time in range (TIR) comparing the 2-week baseline to the final 2-week period of DailyDose use. Results: There were no significant differences between TIR or other glycemic metrics between the baseline period compared to final 2-week period of DailyDose use. TIR significantly improved by 6.3% when more than half of recommendations were accepted and followed compared with 50% or fewer recommendations (95% CI 2.5%-10.1%, P = 0.001). Conclusions: Use of DailyDose did not improve glycemic outcomes compared to the baseline period. In a post hoc analysis, accepting and following recommendations from DailyDose was associated with improved TIR. Clinical Trial Registration Number: NCT04428645.

Tunable alginate hydrogels as injectable drug delivery vehicles for optic neuropathy.

Many disease pathologies, particularly in the eye, are induced by oxidative stress. In particular, injury to the optic nerve (ON), or optic neuropathy, is one of the most common causes of vision loss. Traumatic optic neuropathy (TON) occurs when the ON is damaged following blunt or penetrating trauma to either the head or eye. Currently, there is no effective treatment for TON, only management options, namely the systematic delivery of corticosteroids and surgical decompression of the optic nerve. Unfortunately, neither option alleviates the generation of reactive oxygen species (ROS) which are responsible for downstream damage to the ON. Additionally, the systemic delivery of corticosteroids can cause fatal off-target effects in cases with brain involvement. In this study, we developed a tunable injectable hydrogel delivery system for local methylene blue (MB) delivery using an internal method of crosslinking. MB was chosen due to its ROS scavenging ability and neuroprotective properties. Our MB-loaded polymeric scaffold demonstrated prolonged release of MB as well as in situ gel formation. Additionally, following rheological characterization, these alginate hydrogels demonstrated minimal cytotoxicity to human retinal pigment epithelial cells in vitro and exhibited injection feasibility through small-gauge needles. Our chosen MB concentrations displayed a high degree of ROS scavenging following release from the alginate hydrogels, suggesting this approach may be successful in reducing ROS levels following ON injury, or could be applied to other ocular injuries.

CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development.

Intercellular communication orchestrates a multitude of physiologic and pathologic conditions. Algorithms to infer cell-cell communication and predict downstream signalling and regulatory networks are needed to illuminate mechanisms of stem cell differentiation and tissue development. Here, to fill this gap, we developed and applied CellComm to investigate how the aorta-gonad-mesonephros microenvironment dictates haematopoietic stem and progenitor cell emergence. We identified key microenvironmental signals and transcriptional networks that regulate haematopoietic development, including Stat3, Nr0b2, Ybx1 and App, and confirmed their roles using zebrafish, mouse and human models. Notably, CellComm revealed extensive crosstalk among signalling pathways and convergence on common transcriptional regulators, indicating a resilient developmental programme that ensures dynamic adaptation to changes in the embryonic environment. Our work provides an algorithm and data resource for the scientific community.

External validation of Solomon-Greenwell nomogram for female bladder outlet obstruction.

AIM: There is no unified diagnostic standard for female bladder outlet obstruction (BOO) to date. The Solomon-Greenwell (S-G) nomogram was developed to indicate the probability of female BOO by performing a pressure-flow study, and the equation of the BOO Index in females (BOOIf) is PdetQmax - 2.2 × Qmax. We aimed to validate the diagnostic value of the S-G nomogram in female BOO. MATERIALS AND METHODS: We retrospectively reviewed a videourodynamic study (VUDS) cohort in our institution. Between 2015 and 2020, 192 female patients underwent VUDS for lower urinary tract dysfunction (LUTD). We excluded patients with neurogenic LUTD (n = 30) and patients with no detrusor contraction and/or no void during VUDS (n = 51). The diagnosis of female BOO was based on the Nitti criteria (radiological evidence of urethral narrowing in the presence of a sustained detrusor pressure). BOOIf was calculated for each enrolled patient. The cutoff values of BOOIf were set at <0, >5, and >18 as the original S-G nomogram proposed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each threshold to diagnose female BOO were calculated. RESULTS: Out of the 111 enrolled patients, 43 (38.7%) were diagnosed as having female BOO by VUDS. The most common etiology of female BOO was dysfunctional voiding (19/43, 44.2%), followed by primary bladder neck obstruction (PBNO, 15/43, 34.9%). When the cutoff value was <0 (low probability of obstruction), the sensitivity, specificity, PPV, and NPV were 90%, 91%, 92%, and 87%, respectively; when >5 (likely obstructed), the values were 79%, 96%, 92%, and 88%, respectively; and when >18 (obstruction almost certain), the values were 47%, 100%, 100%, and 75%, respectively. Fourteen of 15 PBNO patients would be classified as non-BOO if the cutoff value was >18. Six PBNO patients would not be diagnosed as female BOO if the threshold was >5. CONCLUSION: A BOOIf <0 showed good diagnostic value for excluding female BOO. A BOOIf >18 had perfect specificity and PPV for diagnosing female BOO. However, the sensitivity of the S-G nomogram for detecting female BOO was unsatisfactory, especially for patients with PBNO. VUDS remains the examination of choice for patients with suspected female BOO.

Making Blood from the Vessel: Extrinsic and Environmental Cues Guiding the Endothelial-to-Hematopoietic Transition.

It is increasingly recognized that specialized subsets of endothelial cells carry out unique functions in specific organs and regions of the vascular tree. Perhaps the most striking example of this specialization is the ability to contribute to the generation of the blood system, in which a distinct population of "hemogenic" endothelial cells in the embryo transforms irreversibly into hematopoietic stem and progenitor cells that produce circulating erythroid, myeloid and lymphoid cells for the lifetime of an animal. This review will focus on recent advances made in the zebrafish model organism uncovering the extrinsic and environmental factors that facilitate hemogenic commitment and the process of endothelial-to-hematopoietic transition that produces blood stem cells. We highlight in particular biomechanical influences of hemodynamic forces and the extracellular matrix, metabolic and sterile inflammatory cues present during this developmental stage, and outline new avenues opened by transcriptomic-based approaches to decipher cell-cell communication mechanisms as examples of key signals in the embryonic niche that regulate hematopoiesis.

Development of a Fission Neutron Spectrum from a D-T Neutron Generator by Spectrum Subtraction Technique.

ABSTRACT: Californium-252 (252Cf) is considered essential by the National Institute of Standards and Technology for the calibration of neutron instrumentation and dosimetry. Californium-252 has a relatively short half-life of 2.645 y; consequently, it must be replaced frequently to produce an adequate neutron flux for calibration. The user community is currently looking for a replacement for 252Cf. The patented technology described herein has a high probability of being that replacement. A preferred method to replace 252Cf would use an affordable and easily maintained neutron source that generates neutrons in an energy spectrum as close to that of 252Cf as possible. Deuterium-tritium (D-T) neutron generators are both affordable and easily maintained, which makes them highly attractive for replacing 252Cf. The patented technology discussed in this paper simulates the 252Cf fission spectrum through a D-T neutron generator by using spectral subtraction. The primary spectrum is built using principally (n,xn) and (n,n') reactions in a variety of materials. In conjunction with the primary spectrum, an engineered background spectrum is generated using a second set of materials. This engineered background spectrum corrects for differences between the primary and desired spectra. This subtraction technique generates a spectrum very similar to 252Cf while maintaining a reasonable flux. Further, by choosing different scattering materials, any fission spectrum can be matched, including the thermal and epithermal components. This flexibility expands the potential use of this technology beyond simulating 252Cf to any desired neutron spectrum below 14 MeV.

Validation of a 3D-printed human temporal bone model for otology surgical skill training.

HYPOTHESIS: Three-dimensional (3D) printed temporal bones are comparable to cadaveric temporal bones as a training tool for otologic surgery. BACKGROUND: Cadaveric temporal bone dissection is an integral part of otology surgical training. Unfortunately, availability of cadaveric temporal bones is becoming much more limited and concern regarding chemical and biological risks persist. In this study, we examine the validity of 3D-printed temporal bone model as an alternative training tool for otologic surgery. METHODS: Seventeen otolaryngology trainees participated in the study. They were asked to complete a series of otologic procedures using 3D-printed temporal bones. A semi-structured questionnaire was used to evaluate their dissection experience on the 3D-printed temporal bones. RESULTS: Participants found that the 3D-printed temporal bones were anatomically realistic compared to cadaveric temporal bones. They found that the 3D-printed temporal bones were useful as a surgical training tool in general and also for specific otologic procedures. Overall, participants were enthusiastic about incorporation of 3D-printed temporal bones in temporal bone dissection training courses and would recommend them to other trainees. CONCLUSION: 3D-printed temporal bone model is a viable alternative to human cadaveric temporal bones as a teaching tool for otologic surgery.