Development of Oxidative Lime Pretreatment and Shock Treatment to Produce Highly Digestible Lignocellulose for Biofuel and Ruminant Feed Applications

At present, the United States generates biofuels (ethanol) from corn grain. Unfortunately, low crop yields and limited growth regions result in limited availability. Furthermore, the use of staple food crops for ethanol production has generated a highly controversial food vs. fuel debate. Because of its high abundance and relatively low cost, lignocellulosic biomass is a promising alternative feedstock for biofuel production; however, structural features of lignocellulose limit accessibility of enzymes or microorganisms. These structural barriers include high lignin content, acetyl groups on hemicellulose, high cellulose crystallinity, cellulose degree of polymerization, and small pore volume. To overcome these barriers, a variety of pretreatment processes (chemical and mechanical) have been developed. Oxidative-lime pretreatment (OLP) is highly effective at reducing lignin content and removing acetyl groups from hemicellulose. Combining OLP with a mechanical treatment process greatly enhances the enzymatic digestibility of lignocellulose. Recommended OLP conditions were determined for Dacotah (120 °C, 6.89-bar O2, 240 min) and Alamo (110 °C, 6-89-bar O2, 240 min) switchgrass. Using recommended conditions, 72-h glucan digestibilities (g glucan hydrolyzed/100 g glucan in raw biomass; 15 filter paper units/g raw glucan) of 85.2 and 88.5 were achieved for Dacotah and Alamo, respectively. Adding ball milling to OLP further enhanced glucan digestibility to 91.1 (Dacotah) and 90.0 (Alamo). In previous studies, shock treatment achieved promising results, but was often inconsistent. This work refined shock treatment with a focus on using consistent procedures and performance analysis. The combination of OLP and shock treatment enhanced the 72-h glucan digestibility of several promising biomass feedstocks: bagasse (74.0), corn stover (92.0), poplar wood (94.0), sorghum (71.8), and switchgrass (89.0). Highly digestible lignocellulose can also be used as ruminant animal feed. Shock treatment plus OLP increased the total digestible nutrients (TDNN; g nutrients digested/100 g organic matter) of corn stover from 51.9 (untreated) to 72.6. Adding in pre-washed corn stover solubles to produce a combined feed (17.8 percent corn stover solubles and 82.2 percent shock OLP corn stover) increased TDNN to 74.9. Mixing in enough solubilized protein to match the crude protein content of corn grain further improved TDNN to 75.5, only 12.6 less than corn grain

Simulation of laryngotracheal reconstruction with 3D-printed models and porcine cadaveric models

ObjectivesLaryngotracheal reconstruction (LTR) is a complex operation used to treat subglottic stenosis. The use of simulator models is a valuable tool in surgical trainee education, particularly for operations such as LTR that are less common outside high-volume centers. Three-dimensional (3D) printing of the human airway may provide an effective and more accessible alternative to porcine cadaveric models. The objective of this study is to compare the educational value of a 3D-printed model and a porcine cadaveric model as LTR simulation methods.MethodsSimulated LTR procedures were completed by 12 otolaryngology residents and a faculty physician on the cadaveric model and the 3D-printed simulator model. Both models were evaluated by fellowship-trained pediatric otolaryngologists to establish construct validity. Pre-procedure surveys of participants evaluated confidence and attitude toward models and post-procedure surveys evaluated confidence, overall impressions, relevance, content validity, and face validity.ResultsParticipants reported a similar mean increase in confidence after performing LTR on the 3D-printed model (14%) and cadaveric model (11%). Participants rated both models similarly for utility as an overall training tool and in teaching surgical planning and improving operative techniques. However, participants found the 3D-printed model more useful for teaching anatomy (p = .047).Conclusion3D-printed models have practical benefits over cadaveric models; they do not decompose and can be custom made to model a disease state such as subglottic stenosis. Participants reported a similar mean increase in confidence after using either simulation. The 3D-printed model is a promising simulation candidate as it compares well to an animal model and has the advantage of being more anatomically true to pediatric patients.Level of Evidence: Level 2.Three-dimensional (3D) printing of the human airway may provide an effective and more accessible alternative to cadaveric models. This study compares the educational value of a 3D-printed model and a porcine cadaveric model as LTR simulation methods. Results showed that both models can be effective in resident education and the practical benefits of 3D-printed models are significant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175127/1/lio2884.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175127/2/lio2884_am.pd

Comprehensive value implications of surgeon volume for lung cancer surgery: Use of an analytic framework within a regional health systemCentral MessagePerspective

Objective: We used a framework to assess the value implications of thoracic surgeon operative volume within an 8-hospital health system. Methods: Surgical cases for non–small cell lung cancer were assessed from March 2015 to March 2021. High-volume (HV) surgeons performed >25 pulmonary resections annually. Metrics include length of stay, infection rates, 30-day readmission, in-hospital mortality, median 30-day charges and direct costs, and 3-year recurrence-free and overall survival. Multivariate regression-based propensity scores matched patients between groups. Metrics were graphed on radar charts to conceptualize total value. Results: All 638 lung resections were performed by 12 surgeons across 6 hospitals. Two HV surgeons performed 51% (n = 324) of operations, and 10 low-volume surgeons performed 49% (n = 314). Median follow-up was 28.8 months (14.0-42.3 months). Lobectomy was performed in 71% (n = 450) of cases. HV surgeons performed more segmentectomies (33% [n = 107] vs 3% [n = 8]; P < .001). Patients of HV surgeons had a lower length of stay (3 [2-4] vs 5 [3-7]; P < .001) and infection rates (0.6% [n = 1] vs 4% [n = 7]; P = .03). Low-volume and HV surgeons had similar 30-day readmission rates (14% [n = 23] vs 7% [n = 12]; P = .12), in-hospital mortality (0% [n = 0] vs 0.6% [n = 1]; P = .33), and oncologic outcomes; 3-year recurrence-free survival was 95% versus 91%; P = .44, and 3-year overall survival was 94% versus 90%; P = 0. Charges were reduced by 28%, and direct costs were reduced by 23% (both P < .001) in the HV cohort. Conclusions: HV surgeons provide comprehensive value across a health system. This multidomain framework can be used to help drive oncologic care decisions within a health system

Identification and Preliminary Characterization of a Potent, Safe, and Orally Efficacious Inhibitor of Acyl-CoA:Diacylglycerol Acyltransferase 1

A high-throughput screen against human DGAT-1 led to the identification of a core structure that was subsequently optimized to afford the potent, selective, and orally bioavailable compound <b>14</b>. Oral administration at doses ≥0.03 mg/kg significantly reduced postprandial triglycerides in mice following an oral lipid challenge. Further assessment in both acute and chronic safety pharmacology and toxicology studies demonstrated a clean profile up to high plasma levels, thus culminating in the nomination of <b>14</b> as clinical candidate ABT-046