COMBINATORIAL ADMINISTRATION OF SYNTHETIC TLR4 AGONIST INI-2002 AND NOVEL MINCLE AGONIST UM-1098 DELIVERED VIA A-SNPS RESULTS IN SYNERGISTIC IL-1β PRODUCTION IN HUMAN PRIMARY CELLS AND ENHANCES TH1 AND TH17 RESPONSES IN VIVO

Tuberculosis (TB) kills more people each year than any infectious disease worldwide with recent exception of SARS-CoV-2. Though the Bacille Calmette Guerin (BCG) vaccine confers protection against severe extrapulmonary forms of TB, there is no licensed vaccine for the prevention of pulmonary tuberculosis. The strongest correlate of protection against pulmonary tuberculosis is Th1/Th17 biased cell mediated immunity. Several candidates for TB vaccine adjuvants have shown Th1/Th17 polarizing capacity in clinical trials including Mincle agonist trehalose dibehenate (TDB) and TLR4 agonist monophosphoryl lipid A (MPL). Furthermore, combinatorial administration of MPL and TDB formulated in dimethyldioctadecylammonium (DDA) liposomes has been previously reported to produce synergistic Th1/Th17 immunity. Though this novel combination offered proof of concept for TLR4 and Mincle combination vaccines, use of shorter chain length agonists would afford increased stability and decreased toxicity while maintaining or improving efficacy. Coating of Mincle ligands to silica nanoparticles (SNPs) provides an additional opportunity to form multiple ligand-receptor interactions for increased signaling as previously characterized in Dectin-1. Herein, we characterize several molar ratios of synthetic MPL mimetic INI-2002 and novel TDB derivative UM-1098 delivered via A-SNPs, reporting synergistic IL-1β production in human peripheral blood mononuclear cells and an increased percentage of CD4+ T cells producing Th1/17 cytokines including TNF- α, IL-17, and IFN-γ following combination vaccination against recombinant TB antigen M72

Stability of commercial phytase sources under different environmental conditions

Citation: De Jong, J. A., DeRouchey, J. M., Tokach, M. D., Dritz, S. S., Goodband, R. D., Woodworth, J. C., . . . Stark, C. R. (2016). Stability of commercial phytase sources under different environmental conditions. Journal of Animal Science, 94(10), 4259-4266. doi:10.2527/jas2016-0742A 300-d study was conducted to evaluate storage stability of 4 commercially available phytase products under varied environmental conditions. Products used were: 1) Quantum Blue G (AB Vista, Plantation, FL), 2) Ronozyme Hi Phos GT (DSM Nutritional Products, Parsippany, NJ), 3) Axtra Phy TPT (Dupont, Wilmington, DE), and 4) Microtech 5000 Plus (Guangdong Vtr Bio-Tech Co., Ltd., Guangdong, China). Products were stored as pure forms, in a vitamin premix, or a vitamin trace mineral (VTM) premix. Pure products were stored at -20 degrees C, 4 degrees C, 22 degrees C, or 35 degrees C (75% humidity). Vitamin and VTM premixes were stored at 22 degrees C or 35 degrees C (75% humidity). Samples were stored in open-topped paper bags and sampled on d 30, 60, 90, 120, 210, and 300. Stability was determined as the amount of residual phytase activity (% of initial) at each sampling point. For the pure forms, all interactive and main effects of phytase product, time, and storage temperature were significant (P < 0.05). From d 30 to 300, products had similar reductions in phytase activity at the 3 highest temperatures; however, Quantum Blue G, Ronozyme HiPhos GT, and Axtra Phy TPT had reduced (P < 0.05) phytase activity as compared to Microtech 5000 at -20 degrees C. In general, as storage time increased, residual phytase activity decreased (P < 0.05) regardless of product and storage temperature. When product was stored at 4 degrees C and 22 degrees C, phytase activity was greater than that of product stored at -20 degrees C or 35 degrees C, and Microtech 5000 Plus had greater (P < 0.05) stability regardless of time and temperature as compared to the other 3 products. For vitamin and VTM premixes, a time x temperature x product interaction (P < 0.05) was observed. When stored at 22 degrees C, Axtra Phy TPT and Microtech 5000 Plus had reduced residual phytase activity (P < 0.05) when compared to the other 2 products; however, when stored at 35 degrees C Axtra Phy had even further reduced (P < 0.05) activity than the other 3 products regardless of which form the products were stored in. From d 30 to 300 Axtra Phy TPT and Microtech 5000 Plus had the lowest (P < 0.05) residual phytase activity when compared to the others regardless of storage form or temperature. Phytase products stored in VTM premix had decreased (P < 0.05) residual phytase activity when compared to pure products and vitamin premixes. In conclusion, phytase stored for longer than 90 to 120 d, at both high (35 degrees C) and low (-20 degrees C) temperatures when in pure form or as a VTM premix had reduced residual phytase activity

Effects of grinding corn through a 2-, 3-, or 4-high roller mill on milling characteristics, and finishing pig growth performance and carcass characteristics

Citation: Gebhardt, J. T., Tokach, M. D., Woodworth, J. C., DeRouchey, J. M., Goodband, R. D., Coble, K. F., . . . Dritz, S. S. (2016). Effects of grinding corn through a 2-, 3-, or 4-high roller mill on milling characteristics, and finishing pig growth performance and carcass characteristics. Journal of Animal Science, 94, 59-59. doi:10.2527/msasas2016-126Finishing pigs (n = 922, initial BW = 40.1 kg) were used in a 97-d experiment to determine the effects of grinding corn through various roller mill configurations on milling characteristics and growth performance and carcass characteristics of finishing pigs in a commercial setting. Pens were randomly allotted to 1 of 4 experimental treatments by initial BW with 11 pens/treatment and 21 pigs/pen. All diets were fed in 5 phases with the same corn-soybean meal-based diets containing 20% dried distiller’s grains with solubles. Experimental treatments included corn ground to 685 µm using 2 sets of rolls (2-high), corn ground to 577 µm using 3 sets of rolls (3-high), corn ground to 360 µm using 4 sets of rolls in a fine grind configuration (4-high fine), and corn ground to 466 µm using 4 sets of rolls in a coarse grind configuration (4-high coarse). The same roller mill was used for all configurations with the appropriate lower rolls completely open when using 2 or 3 sets of rolls. Grinding rate (tonnes/hour) was greatest (P < 0.05) for the 2-high and 4-high coarse configurations followed by the 3-high configuration and lowest for the 4-high fine configuration. Electricity cost was lowest (P < 0.05) per tonne of ground corn for the 2-high configuration and was greatest for the 4-high fine configuration. Pigs fed diets containing corn ground with the 2-high configuration had the greatest (P < 0.05) ADFI and ADG with pigs fed diets with corn ground using the 4-high fine configuration having the poorest ADFI and ADG (2.81, 2.73, 2.65, 2.73 kg for ADFI and 0.987, 0.967, 0.940, 0.971 kg for ADG for 2-high, 3-high, 4-high fine, 4-high coarse, respectively). There were no differences in G:F, caloric efficiency, or carcass characteristics among pigs fed diets ground with the different roller mill configurations. Feed cost/kg gain was lowest (P < 0.05) for the 4-high coarse configuration and revenue/pig was greatest (P < 0.05) for the 2-high and 4-high coarse configurations. Income over feed cost (IOFC) was lowest (P < 0.05) for pigs fed diets with corn ground using the 4-high fine configuration; however, there were no differences in IOFC among the other milling configurations. In our study, roller mill configuration had a significant impact on grinding electricity cost, grinding rate, as well as ADFI and ADG; however, roller mill configuration had no impact on G:F

Effects of wheat source and particle size in meal and pelleted diets on finishing pig growth performance, carcass characteristics, and nutrient digestibility

Citation: De Jong, J. A., Derouchey, J. M., Tokach, M. D., Dritz, S. S., Goodband, R. D., Paulk, C. B., . . . Stark, C. R. (2016). Effects of wheat source and particle size in meal and pelleted diets on finishing pig growth performance, carcass characteristics, and nutrient digestibility. Journal of Animal Science, 94(8), 3303-3311. doi:10.2527/jas2016-0370Two experiments were conducted to test the effects of wheat source and particle size in meal and pelleted diets on finishing pig performance, carcass characteristics, and diet digestibility. In Exp. 1, pigs (PIC 327 × 1050; n = 288; initially 43.8 kg BW) were balanced by initial BW and randomly allotted to 1 of 3 treatments with 8 pigs per pen (4 barrows and 4 gilts) and 12 pens per treatment. The 3 dietary treatments were hard red winter wheat ground with a hammer mill to 728, 579, or 326 ?m, respectively. From d 0 to 40, decreasing wheat particle size decreased (linear, P < 0.033) ADFI but improved (quadratic, P < 0.014) G:F. From d 40 to 83, decreasing wheat particle size increased (quadratic, P < 0.018) ADG and improved (linear, P < 0.002) G:F. Overall from d 0 to 83, reducing wheat particle size improved (linear, P < 0.002) G:F. In Exp. 2, pigs (PIC 327 × 1050; n = 576; initially 43.4 ± 0.02 kg BW) were used to determine the effects of wheat source and particle size of pelleted diets on finishing pig growth performance and carcass characteristics. Pigs were randomly allotted to pens, and pens of pigs were balanced by initial BW and randomly allotted to 1 of 6 dietary treatments with 12 replications per treatment and 8 pigs/pen. The experimental diets used the same wheat–soybean meal formulation, with the 6 treatments using hard red winter or soft white winter wheat that were processed to 245, 465, and 693 ?m and 258, 402, and 710 ?m, respectively. All diets were pelleted. Overall, feeding hard red winter wheat increased (P < 0.05) ADG and ADFI when compared with soft white winter wheat. There was a tendency (P < 0.10) for a quadratic particle size × wheat source interaction for ADG, ADFI, and both DM and GE digestibility, as they were decreased for pigs fed 465-?m hard red winter wheat and were greatest for pigs fed 402-?m soft white winter wheat. There were no main or interactive effects of particle size or wheat source on carcass characteristics. In summary, fine grinding hard red winter wheat fed in meal form improved G:F and nutrient digestibility, whereas reducing particle size of wheat from approximately 700 to 250 ?m in pelleted diets did not influence growth or carcass traits. Finally, feeding hard red winter wheat improved ADG and ADFI compared with feeding soft white winter wheat. © 2016 American Society of Animal Science. All rights reserved

Effects of grinding corn through a 2-, 3-, or 4-high roller mill on pig performance and feed preference of nursery pigs

Citation: Gebhardt, J. T., De Jong, J. A., Tokach, M. D., Woodworth, J. C., DeRouchey, J. M., Goodband, R. D., . . . Dritz, S. S. (2016). Effects of grinding corn through a 2-, 3-, or 4-high roller mill on pig performance and feed preference of nursery pigs. Journal of Animal Science, 94, 101-102. doi:10.2527/msasas2016-215A total of 410 pigs were used in 2 experiments to determine the effects of grinding corn through various roller mill configurations on feed preference and performance of nursery pigs. In Exp. 1, 320 pigs (DNA 400 × 200; initial BW = 10.7 kg) were randomly allotted to 1 of 4 dietary treatments with 16 pens/treatment and 5 pigs/pen for a 21-d growth trial. The 4 dietary treatments used the same corn-soybean meal-based formulation that were mixed from the same batch of ingredients. Corn was ground through the same 4-high roller mill, but using different roller configurations including feed with corn fraction ground to 650 µm using 2 sets of rolls (2-high), feed with corn fraction ground to 495 µm using 3 sets of rolls (3-high), feed with corn fraction ground to 340 µm using 4 sets of rolls in a fine grind configuration (4-high fine), and feed with the corn fraction ground to 490 µm using 4 sets of rolls in a coarse grind configuration (4-high coarse). In Exp. 2, 90 pigs (PIC 327 × 200; initial BW = 12.2 kg) were randomly allotted to 1 of 3 diet comparisons to determine feed preference. The 3 diets compared were the 2-high, 4-high fine, and 4-high coarse configurations. Each pen contained 2 feeders, each containing 1 of the 3 treatment diets. Feeders were rotated once daily within each pen for the 7-d study, with 5 pigs per pen, and 6 pens per comparison. In Exp. 1, there were no differences in ADG, ADFI or G:F between roller mill configurations. Similarly, no differences were observed for caloric efficiency or economics among roller mill configurations. In Exp. 2, when given a choice, pigs consumed 67% (P < 0.05) of the diet containing corn ground through the 2-high roller mill when compared to the diet containing 4-high fine corn. There was no difference in feed consumption comparing diets with 2-high roller mill corn or corn from the 4-high roller mill in a coarse configuration. When comparing corn from the two 4-high configurations, pigs consumed 63% (P < 0.05) of the diet manufactured in the coarse configuration and 37% when manufactured in the fine grind configuration. When given a choice, pigs preferred diets manufactured using a mill configuration producing coarser ground corn (490 to 650 µm) to fine ground corn (340 µm); however, roller mill configuration did not affect performance

Stability of commercial phytase products under increasing thermal conditioning temperatures

Citation: De Jong, J. A., DeRouchey, J. M., Tokach, M. D., Goodband, R. D., Woodworth, J. C., Jones, C. K., . . . Bergstrom, J. R. (2016). Stability of commercial phytase products under increasing thermal conditioning temperatures. Journal of Animal Science, 94, 101-101. doi:10.2527/msasas2016-214The objective was to determine the stability of 4 commercial phytase products exposed to increasing thermal conditioning temperatures. The 4 commercial products used were: Quantum Blue 5G (AB Vista, Marlborough, United Kingdom); Ronozyme Hi Phos GT (DSM Nutritional Products, Parsippany, NJ); Axtra Phy TPT (Dupont, Wilmington, DE), and Microtech 5000 Plus (Guangdong VTR Bio-Tech Co., Ltd., Guangdong, China). The phytase products were mixed as part of a corn-soybean meal-based swine diet at a concentration recommended by the manufacturer to provide a 0.12% aP release. Diets were exposed to each of 4 thermal conditioning temperatures (65, 75, 85, and 95°C) for approximately 40 s and the entire process was repeated on 4 consecutive days to create 4 replicates. Samples were taken while feed exited the conditioner and before entering the pellet die. Phytase activity was determined from complete feed samples before conditioning to establish a baseline diet phytase activity level for each product. Phytase stability was measured as the residual phytase activity (% of initial) at each conditioning temperature. There were no product × temperature interactions for conditioning temperature, throughput, or residual phytase activity. As expected, as the target temperature was increased, conditioning temperature increased (linear, P < 0.001) and conditioner throughput decreased (linear, P < 0.001). As target temperature increased, phytase activity decreased (linear, P < 0.001) for each product. There was a significant phytase product main effect which was primarily caused by Microtech 5000 Plus having decreased (P < 0.05) phytase activity when compared to all other products at all conditioning temperatures. In summary, increasing conditioning temperatures decreased phytase stability regardless of product. In addition, Microtech 5000 Plus had decreased residual phytase activity (% of initial) when compared to all other products

Stability of commercial phytase products stored under different environmental conditions

Citation: De Jong, J. A., DeRouchey, J. M., Tokach, M. D., Goodband, R. D., Woodworth, J. C., Jones, C. K., . . . Bergstrom, J. R. (2016). Stability of commercial phytase products stored under different environmental conditions. Journal of Animal Science, 94, 114-114. doi:10.2527/msasas2016-241A 300-d study evaluated the stability of 4 phytase products stored under varied environmental conditions. The 4 products were: 1) Quantum Blue 5G (AB Vista, Marlborough, United Kingdom); 2) Ronozyme HiPhos GT 2700 (DSM Nutritional Products, Parsippany, NJ); 3) Axtra Phy TPT (Dupont, Wilmington, DE); and 4) Microtech 5000 Plus (Guangdong VTR Bio-Tech Co., Ltd., Guangdong, China). Products were stored as pure forms at ?20, 4, 22, or 35°C (75% humidity), or in a vitamin or vitamin trace mineral (VTM) premix at 22 and 35°C (75% humidity). Samples were stored in paper bags and sampled on d 30, 60, 90, 120, 210, and 300. Stability was determined as amount of residual phytase activity (% of initial). For pure forms, all interactive and main effects of product, time, and temperature were significant (P < 0.05). From d 30 to 300, products had similar reductions in phytase activity at the 3 highest temperatures; however, Quantum Blue 5G, Ronozyme HiPhos GT 2700, and Axtra Phy TPT had reduced (P < 0.05) phytase activity compared to Microtech 5000 Plus at ?20°C. As storage time increased, residual phytase activity was reduced (P < 0.05) regardless of product and storage temperature. Also, when product was stored at 4 and 22°C, phytase activity was improved compared to ?20 and 35°C. For vitamin and VTM premixes, a time×temperature × product interaction (P < 0.05) was observed as a result of, Axtra Phy TPT and Microtech 5000 Plus having reduced residual phytase activity (P < 0.05) compared to the other 2 products when stored at 22°C, while activity of Axtra Phy TPT was reduced (P < 0.05) even further than the other 3 products when stored at 35°C regardless of form. From d 30 to 300, Axtra Phy TPT and Microtech 5000 Plus had the lowest (P < 0.05) residual phytase activity compared to the other 2 products. The VTM had decreased (P < 0.05) residual phytase activity compared to the pure product and vitamin premixes. In conclusion, phytase stored for longer than 90–120 d at 35°C or ?20°C in pure form, or when stored as a VTM premix had reduced residual phytase activity

A survey tool for measuring evidence-based decision making capacity in public health agencies

BACKGROUND: While increasing attention is placed on using evidence-based decision making (EBDM) to improve public health, there is little research assessing the current EBDM capacity of the public health workforce. Public health agencies serve a wide range of populations with varying levels of resources. Our survey tool allows an individual agency to collect data that reflects its unique workforce. METHODS: Health department leaders and academic researchers collaboratively developed and conducted cross-sectional surveys in Kansas and Mississippi (USA) to assess EBDM capacity. Surveys were delivered to state- and local-level practitioners and community partners working in chronic disease control and prevention. The core component of the surveys was adopted from a previously tested instrument and measured gaps (importance versus availability) in competencies for EBDM in chronic disease. Other survey questions addressed expectations and incentives for using EBDM, self-efficacy in three EBDM skills, and estimates of EBDM within the agency. RESULTS: In both states, participants identified communication with policymakers, use of economic evaluation, and translation of research to practice as top competency gaps. Self-efficacy in developing evidence-based chronic disease control programs was lower than in finding or using data. Public health practitioners estimated that approximately two-thirds of programs in their agency were evidence-based. Mississippi participants indicated that health department leaders' expectations for the use of EBDM was approximately twice that of co-workers' expectations and that the use of EBDM could be increased with training and leadership prioritization. CONCLUSIONS: The assessment of EBDM capacity in Kansas and Mississippi built upon previous nationwide findings to identify top gaps in core competencies for EBDM in chronic disease and to estimate a percentage of programs in U.S. health departments that are evidence-based. The survey can serve as a valuable tool for other health departments and non-governmental organizations to assess EBDM capacity within their own workforce and to assist in the identification of approaches that will enhance the uptake of EBDM processes in public health programming and policymaking. Localized survey findings can provide direction for focusing workforce training programs and can indicate the types of incentives and policies that could affect the culture of EBDM in the workplace

Examiners\u27 decision‐making processes in observation-based clinical examinations

Background: Objective structured clinical examinations (OSCEs) are commonly used to assess the clinical skills of health professional students. Examiner judgement is one acknowledged source of variation in candidate marks. This paper reports an exploration of examiner decision making to better characterise the cognitive processes and workload associated with making judgements of clinical performance in exit‐level OSCEs. Methods: Fifty‐five examiners for exit‐level OSCEs at five Australian medical schools completed a NASA Task Load Index (TLX) measure of cognitive load and participated in focus group interviews immediately after the OSCE session. Discussions focused on how decisions were made for borderline and clear pass candidates. Interviews were transcribed, coded and thematically analysed. NASA TLX results were quantitatively analysed. Results: Examiners self‐reported higher cognitive workload levels when assessing a borderline candidate in comparison with a clear pass candidate. Further analysis revealed five major themes considered by examiners when marking candidate performance in an OSCE: (a) use of marking criteria as a source of reassurance; (b) difficulty adhering to the marking sheet under certain conditions; (c) demeanour of candidates; (d) patient safety, and (e) calibration using a mental construct of the \u27mythical [prototypical] intern\u27. Examiners demonstrated particularly higher mental demand when assessing borderline compared to clear pass candidates. Conclusions: Examiners demonstrate that judging candidate performance is a complex, cognitively difficult task, particularly when performance is of borderline or lower standard. At programme exit level, examiners intuitively want to rate candidates against a construct of a prototypical graduate when marking criteria appear not to describe both what and how a passing candidate should demonstrate when completing clinical tasks. This construct should be shared, agreed upon and aligned with marking criteria to best guide examiner training and calibration. Achieving this integration may improve the accuracy and consistency of examiner judgements and reduce cognitive workload

Organic farming provides reliable environmental benefits but increases variability in crop yields: a global meta-analysis

To promote food security and sustainability, ecologically intensive farming systems should reliably produce adequate yields of high-quality food, enhance the environment, be profitable, and promote social wellbeing. Yet, while many studies address the mean effects of ecologically intensive farming systems on sustainability metrics, few have considered variability. This represents a knowledge gap because producers depend on reliable provisioning of yields, profits, and environmental services to enhance the sustainability of their production systems over time. Further, stable crop yields are necessary to ensure reliable access to nutritious foods. Here we address this by conducting a global meta-analysis to assess the average magnitude and variability of seven sustainability metrics in organic compared to conventional systems. Specifically, we explored the effects of these systems on (i) biotic abundance, (ii) biotic richness, (iii) soil organic carbon, (iv) soil carbon stocks, (v) crop yield, (vi) total production costs, and (vii) profitability. Organic farms promoted biotic abundance, biotic richness, soil carbon, and profitability, but conventional farms produced higher yields. Compared to conventional farms, organic farms had lower variability in abundance and richness but greater yield variability. Organic farms thus provided a “win-win” (high means and low variability) for environmental sustainability, while conventional farms provided a “win-win” for production by promoting high crop yields with low variability. Despite lower yields, and greater yield variability, organic systems had similar costs to conventional systems and were more profitable due to organic premiums. Our results suggest certification guidelines for organic farms successfully promote reliable environmental benefits, but greater reliance on ecological processes may reduce predictability of crop production