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Patients with urothelial carcinoma tend to be older and frailer with a large number of chronic medical conditions. This is particularly pronounced in those with unresectable locally advanced and metastatic urothelial carcinoma. Prior to 2016, treatment options in advanced urothelial carcinoma were limited to chemotherapy, and as a result, a large number of patients were not receiving disease-directed management. Over the last 6 years, multiple alternative modalities including immune checkpoint inhibitors and targeted therapies have been introduced. They are being utilized clinically in older and frail patients, but there are limited studies investigating outcomes in these specific populations. Based upon current evidence, age does not impact the efficacy and tolerance of immune checkpoint inhibitors if patients are fit enough to receive therapy. In frailer patients, immune checkpoint inhibitors appear to be safe, but outcomes from largely retrospective studies demonstrate mixed data regarding their efficacy. Although there are indications from clinical trials that enfortumab vedotin, sacituzumab govitecan, and erdafitinib are also efficacious irrespective of age, there is still not enough evidence to draw definitive conclusions about their use in older and frail patients. Regardless, in all older patients with advanced urothelial carcinoma, it is critical to evaluate for frailty through geriatric screening tools and comprehensive assessments. Combining these evaluations with consideration of an individual patient's goals should be the foundation upon which therapeutic decisions are made in this population of patients.

In southeastern USA, the use of baleage has increased as an alternative technology to hay production, thereby allowing for a timelier harvest of the conserved forage. A series of studies were conducted to determine the nutritive value, fermentation parameters, and in situ disappearance of the cool-season annual forage mixtures that were ensiled with or without silage inoculant for up to 120 d. The forage mixtures were wheat (Triticum aestivum L.) + brassica hybrid (Brassica rapa L. × napus L.) (WB), wheat + crimson clover (Trifolium incarnatum L.) (WC), and annual ryegrass (Lolium multiflorum Lam.) + oat (Avena sativa L.) + crimson clover (ROC). The inoculant strategy affected the CP concentration (p < 0.05), with it increasing in WB and decreasing in ROC. Among the mixtures, the DM concentration decreased by up to 5%, and the NDF and ADF concentrations decreased by up to 10% during the ensiling period. The pH averaged 5.0, 5.0, and 5.5 for the WC, WB, and ROC mixtures, respectively. Based on our results, the baleage of the cool-season annual forage mixtures may provide a viable high-quality option to sustain animal growth and performance.

The main purpose of this study was to investigate gillnet catch composition and biodiversity caught by 130, 140, and 150 mm (STR) mesh sizes during the fishing season. This research was conducted in the fishing ground of Bushehr County located in the Persian Gulf from autumn 2018 to spring 2019. Overall, 23 families including 36 genera and 43 species were identified. Spring season with 42 species and winter season with 32 species showed the highest and lowest species biodiversity, respectively. Carangidae family with 7 genera and 8 species, Scombridae family with 3 genera and 4 species, and Dasyatidae with 3 genera and 4 species were the families with the highest species biodiversity. Scomberomorus commerson and Thunnus tonggol with 23.45% and 21.84% in autumn, 20.15% and 25.85% in winter, 21.9% and 19.78% in spring showed the most abundance percentages, respectively. The 130 mm mesh size and spring season had the highest abundance, diversity, and the number of caught species in comparison with other mesh sizes and seasons. Two-ways ANOVA results showed that the effects of mesh sizes and seasons on the calculated metrics were significant (P0.05). The highest and lowest Jaccard (J) and Sørensen (S) seasonal similarities were between autumn and spring (J: 0.805, S: 0.892) and autumn and winter (J: 0.561, S: 0.719), respectively. The results of non-metric multidimensional scaling analysis showed that 130 and 140 mm mesh sizes had overlap in terms of the fish abundance and catch composition. Cluster analysis also showed the highest similarity between S. commerson and T. tonggol, and Euthynnus affinis and Scomberoides commersonnianus.

Supplemental material, sj-pdf-1-ijm-10.1177_0255761420986234 for The creation and validation of a Jazz Theory Measure: Implications for improvisation education by Brian E Russell and Charles R Ciorba in International Journal of Music Education

Supplemental material, sj-pdf-1-ijm-10.1177_0255761420986234 for The creation and validation of a Jazz Theory Measure: Implications for improvisation education by Brian E Russell and Charles R Ciorba in International Journal of Music Education

Antibody disulfide bond reduction during monoclonal antibody (mAb) production is a phenomenon that has been attributed to the reducing enzymes from CHO cells acting on the mAb during the harvest process. However, the impact of antibody reduction on the downstream purification process has not been studied. During the production of an IgG2 mAb, antibody reduction was observed in the harvested cell culture fluid (HCCF), resulting in high fragment levels. In addition, aggregate levels increased during the low pH treatment step in the purification process. A correlation between the level of free thiol in the HCCF (as a result of antibody reduction) and aggregation during the low pH step was established, wherein higher levels of free thiol in the starting sample resulted in increased levels of aggregates during low pH treatment. The elevated levels of free thiol were not reduced over the course of purification, resulting in carry‐over of high free thiol content into the formulated drug substance. When the drug substance with high free thiols was monitored for product degradation at room temperature and 2–8°C, faster rates of aggregation were observed compared to the drug substance generated from HCCF that was purified immediately after harvest. Further, when antibody reduction mitigations (e.g., chilling, aeration, and addition of cystine) were applied, HCCF could be held for an extended period of time while providing the same product quality/stability as material that had been purified immediately after harvest. Biotechnol. Bioeng. 2017;114: 1264–1274. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals Inc.

OBJECTIVE: Overweight/obesity is characterized by decreased growth hormone (GH) secretion whereas circulating IGF-I levels are less severely reduced. Yet, the activity of the circulating IGF-system appears to be normal in overweight/obese subjects, as estimated by the ability of serum to activate the IGF-I receptor in vitro (bioactive IGF or IGF-1R activation). We hypothesized that preservation of IGF-1R activation in overweight/obese women is regulated by an insulin-mediated suppression of IGF-binding protein-1 (IGFBP-1) and IGFBP-2, and by suppression of IGFBP-3, mediated by low GH. We additionally hypothesized that increases in IGF-1R activation would drive changes in body composition with low-dose GH administration. DESIGN: Cross-sectional analysis and 6-month randomized, placebo-controlled study of GH administration in 50 overweight/obese women without diabetes mellitus. IGF-1R activation (kinase receptor activation assay) and body composition (DXA) were measured. RESULTS: Prior to treatment, IGFBP-3 (r=−0.33, p=0.02), but neither IGFBP-1 nor IGFBP-2 associated inversely with IGF-1R activation. In multivariate analysis, lower IGFBP-3 correlated with lower peak stimulated GH (r=0.45, p=0.05) and higher insulin sensitivity (r=−0.74, p=0.003). GH administration resulted in an increase in mean serum IGF-I concentrations (144±56 to 269±66μg/L, p

The nodes in a wireless ad hoc network must act as routers in a self-configuring network without infrastructure. An application running on nodes in the ad hoc network may require that intermediate nodes act as routers, receiving and forwarding data packets to other nodes to overcome limitations of noise, router congestion and limited transmission power. In existing routing protocols, the ``self-configuring'' aspect of network construction has generally been limited to route selection using a shortest-path routing metric as a predictor of routing efficiency. This limited, network-layer predictor fails to consider the effects of existing traffic on router loads and fails to consider the effects of noise experienced at the MAC layer. Not all network topologies are suited to efficient routing using a shortest-path metric. The location of the nodes and physical characteristics of the network environment can create topologies where shortest-path routing overloads some routers and underutilizes others. Similarly, noise sources can undermine the quality of wireless links depending on the relative distance between the noise sources and the receiving nodes. This dissertation presents a cross-layer predictor that combines the effects of noise and router congestion into a single time-based routing metric based on statistical estimation from recent experience. Also presented is a new cross-layer, adaptive routing protocol, called Warp-5, that not only uses the new routing metric to make better initial routing decisions in a noisy or congested network, but can also adjust previously existing routes as new routes or new noise sources are added to the network. Simulation results for Warp-5 are presented and compared to the existing shortest-path routing protocol AODV. The results show the cross-layer approach of Warp-5 to be superior to shortest-path routing protocols for managing router congestion and noise in wireless ad hoc networks.

Bibliography: p. 317-323, Some pages are in colour., In this dissertation, I develop a number of new ideas for the statistical determination of reservoir parameters using seismic attributes, combining the classical techniques of multivariate statistics and the more recent methods of neural network analysis. I apply these techniques to both full seismic volumes and maps derived from intervals averaged through these volumes, using the Blackfoot dataset from central Alberta. In this dissertation I show that multilinear regression often provides too simple a solution to the parameter estimation problem, but that the traditional feedforward neural network often provides a solution that is overly complex. My proposed solution is to use radial basis function neural networks for the prediction of reservoir parameters, since this approach combines the power of the multilinear regression technique with the nonlinearity of neural networks. This conclusion is illustrated using both a model dataset that involves an A VO classification problem and the Blackfoot dataset that was mentioned earlier. In this dissertation, several new ideas are presented. First, I derive an improved regression formula for the prediction of S-wave sonic logs from combinations of other logs. Second, I apply a new approach to data clustering, called Mahalanobis clustering, to the interpretation of A VO crossplots and to the extraction of optimal clusters for the radial basis function neural network with centres. Finally, I develop a new approach that combines geostatistics with multiattribute transforms. This technique uses multivariate statistics and neural networks to improve the secondary dataset used in the collocated cokriging technique.

Through a continuing search for anticancer compounds as part of an International Cooperative Biodiversity Grant program, the extracts of two plants were selected for study on the basis of their cytotoxic activity. These extracts were further fractionated to yield four compounds. The structures of these compounds were elucidated with mass spectrometry and 1-D and 2-D NMR spectroscopy. The ethyl acetate extract of the twigs of Garcinia macrophylla from Suriname was weakly cytotoxic in the A2780 human ovarian cancer cell bioassay. The known benzophenone guttiferone A and a new guttiferone analog, named guttiferone G, were isolated from the extract and found to be responsible for the bioactivity. A known triterpene, friedelin, was also isolated from the extract and found to be inactive. The structure of guttiferone A was determined by comparison of its NMR data to those found in the literature. The structure of guttiferone G was determined by comparison to guttiferone A and through careful examination of both 1D and 2D NMR data. An extract of Bridelia tulasneana from Madagascar yielded one compound. It was identified as the known lignan deoxypodophyllotoxin and was responsible for the bioactivity. It was identified by a comparison of its spectral data to those found in the literature and those of an authentic sample. Master of Science

The report is intended to be used as an aid to military mission planners in determining allowable proximity to a nuclear fireball from the standpoints of permanent retinal injury and the temporary effects of flashblindness. Pertinent physical and physiological phenomena are discussed in moderate detail; the nucleus of the work being a family of curves which indicate acceptable separation distances for the prevention of retinal burns and flashblindness. Detailed instructions for approximating acceptable separation distances using a slide rule are included as an appendix.