Free energy computation of particles with membrane-mediated interactions via Langevin dynamics.

We apply well-established concepts of Langevin sampling to derive a new class of algorithms for the efficient computation of free energy differences of fluctuating particles embedded in a ’fast’ membrane, i.e., a membrane that instantaneously adapts to varying particle positions. A geometric poten- tial accounting for membrane-mediated particle interaction is derived in the framework of variational hybrid models for particles in membranes. Recent explicit representations of the gradient of the geometric interaction poten- tial allows to apply well-known gradient based Markov Chain Monte-Carlo (MCDC) methods such as Langevin-based sampling

A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects

GAS GENERATION MEASUREMENTS OF SCRAP PU/U MATERIALS USING A BELL JAR

ABSTRACT A bell jar is used to determine containment vessel pressurization due to gas generation from plutonium/uranium materials. Seventy eight food pack cans containing plutonium and uranium oxide bearing materials have been tested to date. Minimal change in pressure (increase or decrease) occurred in fifty one cases, depressurization occurred in seventeen cases, and pressurization occurred in ten cases. Pressurization is considered linked to the presence of certain impurities such as magnesium oxide

Phase I Study of Celecoxib with Concurrent Irinotecan, Cisplatin, and Radiation Therapy for Patients with Unresectable Locally Advanced Non-Small Cell Lung Cancer

Purpose: Preclinical findings suggest that adding targeted therapies to combination radiation-chemotherapy can enhance treatment efficacy; however, this approach may enhance normal tissue toxicity. We investigated the maximum tolerated dose, dose-limiting toxicities, and response rate when the selective cyclooxygenase-2 inhibitor celecoxib is added to concurrent irinotecan, cisplatin, and radiation therapy for patients with inoperable stage II–III non-small cell lung cancer (NSCLC). Methods and Materials: Eighteen patients were analyzed in a phase I clinical dose-escalation trial. Celecoxib was given daily beginning 5 days before radiation followed by maintenance doses for 12 weeks. Toxicity was graded with the Common Terminology Criteria for Adverse Events V3.0 and response with the World Health Organization system. Primary endpoints were maximum tolerated dose of celecoxib and treatment toxicity; secondary endpoints were response and survival rates. Results: The maximum tolerated dose of celecoxib was not reached, in part owing to discontinuation of the drug supply. At doses of 200 or 400 mg/day, no patients experienced any dose-limiting toxicity (acute grade ≥4 esophagitis or pneumonitis, neutropenic fever or thrombocytopenia requiring transfusion, or acute grade ≥3 diarrhea). Grade 3 toxicities were leukopenia (five patients), fatigue (3), pneumonitis (2), dyspnea (1), pain (1), and esophageal stricture (1). Interestingly, pulmonary fibrosis (a late toxicity) was no more severe in the higher-dose (400-mg) group and may have been less common than in the lower-dose group. The clinical response rate was 100% (8 complete, 10 partial). Two-year rates were: overall survival 65%; local-regional control 69%; distant metastasis-free survival 71%; and disease-free survival 64%. Conclusion: Although preliminary, our results suggest that adding celecoxib to concurrent chemoradiation for inoperable NSCLC is safe and can improve outcome without increasing normal tissue toxicity

Gender plays no role in student ability to perform on computer-based examinations

BACKGROUND: To see if there is a difference in performance when students switch from traditional paper-and-pencil examinations to computer-based examinations, and to determine whether there are gender differences in student performance in these two examination formats. METHODS: This study involved first year medical students at the University of Illinois at Urbana-Champaign over three Academic Years 2002–03/2003–04 and 2003–05. Comparisons of student performance by overall class and gender were made. Specific comparisons within courses that utilized both the paper-and-pencil and computer formats were analyzed. RESULTS: Overall performance scores for students among the various Academic Years revealed no differences between exams given in the traditional pen-and-paper and computer formats. Further, when we looked specifically for gender differences in performance between these two testing formats, we found none. CONCLUSION: The format for examinations in the courses analyzed does not affect student performance. We find no evidence for gender differences in performance on exams on pen-and-paper or computer-based exams

The Leiden Convention coronary coding system: translation from the surgical to the universal view

Aims: The Leiden Convention coronary coding system structures the large variety of coronary anatomical patterns; isolated and in congenital heart disease. It is widely used by surgeons but not by cardiologists as the system uses a surgeons' cranial view. Since thoracic surgeons and cardiologists work closely together, a coronary coding system practical for both disciplines is mandatory. To this purpose, the 'surgical' coronary coding system was adapted to an 'imaging' system, extending its applicability to different cardiac imaging techniques.Methods and results: The physician takes place in the non-facing sinus of the aortic valve, oriented with the back towards the pulmonary valve, looking outward from the sinus. From this position, the right-hand sinus is sinus 1, and the left-hand sinus is sinus 2. Next, a clockwise rotation is adopted starting at sinus 1 and the encountered coronary branches described. Annotation of the normal anatomical pattern is 1R-2LCx, corresponding to the 'surgical' coding system. The 'imaging' coding system was made applicable for Computed Tomography (CT), Magnetic Resonance Imaging (MRI), echocardiography, and coronary angiography, thus facilitating interdisciplinary use. To assess applicability in daily clinical practice, images from different imaging modalities were annotated by cardiologists and cardiology residents and results scored. The average score upon evaluation was 87.5%, with the highest scores for CT and MRI images (average 90%).Cardiolog

Tolerability of gefitinib in patients receiving treatment in everyday clinical practice

Gefitinib (‘Iressa’, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, has recently been approved in several countries for use in advanced or metastatic non-small-cell lung cancer (NSCLC). In contrast to chemotherapies, which are generally used at or near their maximum-tolerated dose (MTD), gefitinib is used at an optimal biological dose (250 mg day−1), which is substantially below its MTD, minimising the risk of adverse events without compromising efficacy. Tolerability data from the compassionate use of gefitinib in the ‘Iressa’ Expanded Access Programme support the favourable safety profile of the agent reported in Phase I and II trials. In both settings, the majority of adverse drug reactions were mild/moderate and consisted mainly of grade 1/2 diarrhoea and skin rash. Although skin rash has been suggested to predict response to gefitinib, available data do not support this hypothesis. Overall, these tolerability data demonstrate that gefitinib has a relatively benign side-effect profile and is a well-tolerated treatment option for patients with previously treated NCSLC, who currently have few alternatives

Observations of the lower atmosphere from the 2021 WiscoDISCO campaign

The mesoscale meteorology of lake breezes along Lake Michigan impacts local observations of high-ozone events. Previous manned aircraft and UAS observations have demonstrated non-uniform ozone concentrations within and above the marine layer over water and within shoreline environments. During the 2021 Wisconsin's Dynamic Influence of Shoreline Circulations on Ozone (WiscoDISCO-21) campaign, two UAS platforms, a fixed-wing (University of Colorado RAAVEN) and a multirotor (Purdue University DJI M210), were used simultaneously to capture lake breeze during forecasted high-ozone events at Chiwaukee Prairie State Natural Area in southeastern Wisconsin from 21&ndash;26&nbsp;May&nbsp;2021​​​​​​​. The RAAVEN platform (data DOI: https://doi.org/10.5281/zenodo.5142491, de Boer et al., 2021) measured temperature, humidity, and 3-D winds during 2&thinsp;h flights following two separate flight patterns up to three times per day at altitudes reaching 500&thinsp;m above ground level (a.g.l.). The M210 platform (data DOI: https://doi.org/10.5281/zenodo.5160346, Cleary et al., 2021a) measured vertical profiles of temperature, humidity, and ozone during 15&thinsp;min flights up to six times per day at altitudes reaching 120&thinsp;ma.g.l. near a Wisconsin DNR ground monitoring station (AIRS ID: 55-059-0019). This campaign was conducted in conjunction with the Enhanced Ozone Monitoring plan from the Wisconsin DNR that included Doppler lidar wind profiler observations at the site (data DOI: https://doi.org/10.5281/zenodo.5213039, Cleary et al., 2021b). &nbsp;</p

Age influence on effectiveness of a novel 3-phytase in barley-wheat based diets for pigs from 12 to 108 kg under commercial conditions

[EN] The main objective of this study was to evaluate the influence of pig's age on the effectiveness of a new microbial 3-phytase, produced by Komagataella phaffii, under commercial conditions in barley-wheat based diets. Two experiments were conducted in weaned, growing and finishing pigs; firstly, to determine phytase efficacy on dry matter, organic matter, energy, protein and mineral (phosphorus, P and calcium, Ca) digestibility (n = 48; Experiment 1), and secondly, to evaluate the effect of phytase on growth performance and bone mineralization (n = 312; Experiment 2). In each experiment, three barley-wheat based diets were formulated following the recommendations for each animal age, of which two versions were manufactured, including 0 and 1000 phytase units (FTU)/kg of feed of the new 3-phytase to be tested. Results showed the new phytase had the potential to increase the digestibility of Ca and P (on av. + 0.05 and +0.06, respectively; P < 0.01), especially P digestibility in growing pigs (+0.10; P < 0.001), consequently decreasing P and Ca excretion. Digestible energy (DE) of the diet increased with the addition of phytase in weaned pigs (+0.69 MJ/kg of dry matter (DM); P < 0.001). Dietary inclusion of new 3-phytase enhanced average daily gain from 46 to 94 days of age (+0.07 kg/d; P < 0.05) and decreased feed conversion ratio from 46 to 154 days of age (on av. -0.13; P < 0.05), although no significant effect was observed from 154 to 185 days of age. Addition of the new 3-phytase also promoted bone mineralization, increasing the weight of the bones (+3.99 and +3.64 g of tibia at 95 days and metacarpus at 100 days of age, respectively; P < 0.05) and the ash, Ca and P content in these bones (e.g. + 0.46 and +0.33 g of P in tibia at 95 days and metacarpus at 100 days of age, respectively; P < 0.001). In conclusion, pig age affected the efficacy of a new 3-phytase on P and Ca digestibility both in weaned and growing diets and DE content of the weaned diets, which also resulted in improvements in growth, feed conversion and bone development until 154 days of age. These effects seem to be reduced during the finishing period, although the advantages of the new 3-phytase on bone mineralization were maintained until 185 days of age.We thank the technical staff at the experimental farms of the Research and Technology Animal Centre (CITA-IVIA), the Institute of Animal Science and Technology (Universitat Politècnica de Valencia) and Javier Gómez (Crianzas Campovivo) for expert technical assistance and experimental support.Cambra López, M.; Cerisuelo, A.; Ferrer, P.; Ródenas Martínez, L.; Aligué, R.; Moset, V.; Pascual Amorós, JJ. (2020). Age influence on effectiveness of a novel 3-phytase in barley-wheat based diets for pigs from 12 to 108 kg under commercial conditions. Animal Feed Science and Technology. 267:1-13. https://doi.org/10.1016/j.anifeedsci.2020.114549S113267Adeola, O., & Cowieson, A. J. (2011). BOARD-INVITED REVIEW: Opportunities and challenges in using exogenous enzymes to improve nonruminant animal production. Journal of Animal Science, 89(10), 3189-3218. doi:10.2527/jas.2010-3715Almeida, F. N., Sulabo, R. C., & Stein, H. H. (2013). Effects of a novel bacterial phytase expressed in Aspergillus Oryzae on digestibility of calcium and phosphorus in diets fed to weanling or growing pigs. Journal of Animal Science and Biotechnology, 4(1). doi:10.1186/2049-1891-4-8Arredondo, M. A., Casas, G. A., & Stein, H. H. (2019). Increasing levels of microbial phytase increases the digestibility of energy and minerals in diets fed to pigs. Animal Feed Science and Technology, 248, 27-36. doi:10.1016/j.anifeedsci.2019.01.001Atakora, J. K. A., Moehn, S., Sands, J. S., & Ball, R. O. (2011). Effects of dietary crude protein and phytase–xylanase supplementation of wheat grain based diets on energy metabolism and enteric methane in growing finishing pigs. Animal Feed Science and Technology, 166-167, 422-429. doi:10.1016/j.anifeedsci.2011.04.030Blaabjerg, K., Nørgaard, J. V., & Poulsen, H. D. (2012). Effect of microbial phytase on phosphorus digestibility in non-heat-treated and heat-treated wheat–barley pig diets1. Journal of Animal Science, 90(suppl_4), 206-208. doi:10.2527/jas.53920Brady, S., Callan, J., Cowan, D., McGrane, M., & O’Doherty, J. (2002). Effect of phytase inclusion and calcium/phosphorus ratio on the performance and nutrient retention of grower-finisher pigs fed barley/wheat/soya bean meal-based diets. Journal of the Science of Food and Agriculture, 82(15), 1780-1790. doi:10.1002/jsfa.1262Braña, D. V., Ellis, M., Castañeda, E. O., Sands, J. S., & Baker, D. H. (2006). Effect of a novel phytase on growth performance, bone ash, and mineral digestibility in nursery and grower-finisher pigs. Journal of Animal Science, 84(7), 1839-1849. doi:10.2527/jas.2005-565Dersjant‐Li, Y., Awati, A., Schulze, H., & Partridge, G. (2014). Phytase in non‐ruminant animal nutrition: a critical review on phytase activities in the gastrointestinal tract and influencing factors. Journal of the Science of Food and Agriculture, 95(5), 878-896. doi:10.1002/jsfa.6998Eeckhout, W., & De Paepe, M. (1994). Total phosphorus, phytate-phosphorus and phytase activity in plant feedstuffs. Animal Feed Science and Technology, 47(1-2), 19-29. doi:10.1016/0377-8401(94)90156-2EMIOLA, A., AKINREMI, O., SLOMINSKI, B., & NYACHOTI, C. M. (2009). Nutrient utilization and manure P excretion in growing pigs fed corn-barley-soybean based diets supplemented with microbial phytase. Animal Science Journal, 80(1), 19-26. doi:10.1111/j.1740-0929.2008.00590.xGonzález-Vega, J. C., Walk, C. L., & Stein, H. H. (2015). Effects of microbial phytase on apparent and standardized total tract digestibility of calcium in calcium supplements fed to growing pigs1. Journal of Animal Science, 93(5), 2255-2264. doi:10.2527/jas.2014-8215Harper, A. F., Kornegay, E. T., & Schell, T. C. (1997). Phytase supplementation of low-phosphorus growing-finishing pig diets improves performance, phosphorus digestibility, and bone mineralization and reduces phosphorus excretion. Journal of Animal Science, 75(12), 3174. doi:10.2527/1997.75123174xHaug, W., & Lantzsch, H.-J. (1983). Sensitive method for the rapid determination of phytate in cereals and cereal products. Journal of the Science of Food and Agriculture, 34(12), 1423-1426. doi:10.1002/jsfa.2740341217Heaney, R. P., Abrams, S., Dawson-Hughes, B., Looker, A., Looker, A., Marcus, R., … Weaver, C. (2001). Peak Bone Mass. Osteoporosis International, 11(12), 985-1009. doi:10.1007/s001980070020Jørgensen, B. (1995). Effect of different energy and protein levels on leg weakness and osteochondrosis in pigs. Livestock Production Science, 41(2), 171-181. doi:10.1016/0301-6226(94)00048-cKemme, P. A., Jongbloed, A. W., Mroz, Z., & Beynen, A. C. (1997). The efficacy of Aspergillus niger phytase in rendering phytate phosphorus available for absorption in pigs is influenced by pig physiological status. Journal of Animal Science, 75(8), 2129. doi:10.2527/1997.7582129xKiela, P. R., & Ghishan, F. K. (2016). Physiology of Intestinal Absorption and Secretion. Best Practice & Research Clinical Gastroenterology, 30(2), 145-159. doi:10.1016/j.bpg.2016.02.007Kim, J. C., Simmins, P. H., Mullan, B. P., & Pluske, J. R. (2005). The effect of wheat phosphorus content and supplemental enzymes on digestibility and growth performance of weaner pigs. Animal Feed Science and Technology, 118(1-2), 139-152. doi:10.1016/j.anifeedsci.2004.08.016Koch, M. E., & Mahan, D. C. (1985). Biological Characteristics for Assessing Low Phosphorus Intake in Growing Swine. Journal of Animal Science, 60(3), 699-708. doi:10.2527/jas1985.603699xKonietzny, U., & Greiner, R. (2002). Molecular and catalytic properties of phytate-degrading enzymes (phytases). International Journal of Food Science and Technology, 37(7), 791-812. doi:10.1046/j.1365-2621.2002.00617.xLittell, R. C., Henry, P. R., & Ammerman, C. B. (1998). Statistical analysis of repeated measures data using SAS procedures. Journal of Animal Science, 76(4), 1216. doi:10.2527/1998.7641216xMahan, D. C. (1982). Dietary Calcium and Phosphorus Levels for Weanling Swine. Journal of Animal Science, 54(3), 559-564. doi:10.2527/jas1982.543559xMavromichalis, I., Hancock, J. D., Kim, I. H., Senne, B. W., Kropf, D. H., Kennedy, G. A., … Behnke, K. C. (1999). Effects of omitting vitamin and trace mineral premixes and(or) reducing inorganic phosphorus additions on growth performance, carcass characteristics, and muscle quality in finishing pigs. Journal of Animal Science, 77(10), 2700. doi:10.2527/1999.77102700xMoehn, S., Atakora, J. K. A., Sands, J., & Ball, R. O. (2007). Effect of phytase-xylanase supplementation to wheat-based diets on energy metabolism in growing–finishing pigs fed ad libitum. Livestock Science, 109(1-3), 271-274. doi:10.1016/j.livsci.2007.01.118Oryschak, M. A., Simmins, P. H., & Zijlstra, R. T. (2002). Effect of dietary particle size and carbohydrase and/or phytase supplementation on nitrogen and phosphorus excretion of grower pigs. Canadian Journal of Animal Science, 82(4), 533-540. doi:10.4141/a02-016Peter, C. ., Parr, T. ., Parr, E. ., Webel, D. ., & Baker, D. . (2001). The effects of phytase on growth performance, carcass characteristics, and bone mineralization of late-finishing pigs fed maize–soyabean meal diets containing no supplemental phosphorus, zinc, copper and manganese. Animal Feed Science and Technology, 94(3-4), 199-205. doi:10.1016/s0377-8401(01)00300-5Rodehutscord, M., Faust, M., & Lorenz, H. (1996). Digestibility of phosphorus contained in soybean meal, barley, and different varieties of wheat, without and with supplemental phytase fed to pigs and additivity of digestibility in a wheatsoybean-meal diet. Journal of Animal Physiology and Animal Nutrition, 75(1-5), 40-48. doi:10.1111/j.1439-0396.1996.tb00466.xSelle, P. H., & Ravindran, V. (2008). Phytate-degrading enzymes in pig nutrition. Livestock Science, 113(2-3), 99-122. doi:10.1016/j.livsci.2007.05.014Selle, P. H., Cadogan, D. J., & Bryden, W. L. (2003). Effects of phytase supplementation of phosphorus-adequate, lysine-deficient, wheat-based diets on growth performance of weaner pigs. Australian Journal of Agricultural Research, 54(3), 323. doi:10.1071/ar02121She, Y., Su, Y., Liu, L., Huang, C., Li, J., Li, P., … Piao, X. (2015). Effects of microbial phytase on coefficient of standardized total tract digestibility of phosphorus in growing pigs fed corn and corn co-products, wheat and wheat co-products and oilseed meals. Animal Feed Science and Technology, 208, 132-144. doi:10.1016/j.anifeedsci.2015.07.011Van Soest, P. J., Robertson, J. B., & Lewis, B. A. (1991). Methods for Dietary Fiber, Neutral Detergent Fiber, and Nonstarch Polysaccharides in Relation to Animal Nutrition. Journal of Dairy Science, 74(10), 3583-3597. doi:10.3168/jds.s0022-0302(91)78551-2Varley, P. F., Callan, J. J., & O’Doherty, J. V. (2011). Effect of dietary phosphorus and calcium level and phytase addition on performance, bone parameters, apparent nutrient digestibility, mineral and nitrogen utilization of weaner pigs and the subsequent effect on finisher pig bone parameters. Animal Feed Science and Technology, 165(3-4), 201-209. doi:10.1016/j.anifeedsci.2011.02.017Varley, P. F., Flynn, B., Callan, J. J., & O’Doherty, J. V. (2011). Effect of phytase level in a low phosphorus diet on performance and bone development in weaner pigs and the subsequent effect on finisher pig bone development. Livestock Science, 138(1-3), 152-158. doi:10.1016/j.livsci.2010.12.014Vipperman, P. E., Peo, E. R., & Cunningham, P. J. (1974). Effect of Dietary Calcium and Phosphorus Level upon Calcium, Phosphorus and Nitrogen Balance in Swine. Journal of Animal Science, 38(4), 758-765. doi:10.2527/jas1974.384758