The numerical model developed previously for coastal structures is slightly modified and applied to predict the wave transformation in the surf and swash zones on gentle slopes as well as the wave reflection and swash oscillation on relatively steep beaches. The numerical model is one‐dimensional in the cross‐shore direction and is based on the finite amplitude, shallow water equations, including the effect of bottom friction, which are solved in the time domain for the incident wave train specified as input at the seaward boundary of the computation located outside the breakpoint. The slight modification is related to the effect of the time‐averaged current on the seaward boundary condition and improves the agreement between the computed and measured mean water levels on gentle slopes. The modified numerical model is compared with available small‐scale test data for monochromatic waves spilling on gentle slopes as well as for monochromatic waves plunging and surging on a relatively steep slope. Additional comparisons are made with small‐scale tests conducted using transient monochromatic and grouped waves on a 1:8 smooth slope with and without an idealized nearshore bar at the toe of the 1:8 slope. As a whole, the numerical model is shown to be capable of predicting both time‐varying and time‐averaged hydrodynamic quantities in the surf and swash zones on gentle as well as steep slopes.

Since the first approval of a biosimilar medicinal product in 2006, scientific understanding of the features and development of biosimilar medicines has accumulated. This review scrutinizes public information on development programs and the contribution of the clinical studies for biosimilar approval in the European Union (EU) and/or the United States (US) until November 2019. The retrospective evaluation of the programs that eventually obtained marketing authorization and/or licensure revealed that in 95% (36 out of 38) of all programs, the comparative clinical efficacy studies confirmed similarity. In the remaining 5% (2 out of 38), despite meeting efficacy outcomes, the biosimilar candidates exhibited clinical differences in immunogenicity that required changes to the manufacturing process and additional clinical studies to enable biosimilar approval. Both instances of clinical differences in immunogenicity occurred prior to 2010, and the recurrence of these cases is unlikely today due to state-of-the-art assays and improved control of process-related impurities. Biosimilar candidates that were neither approved in the EU nor in the US were not approved due to reasons other than clinical confirmation of efficacy. This review of the development history of biosimilars allows the proposal of a more efficient and expedited biosimilar development without the routine need for comparative clinical efficacy and/or pharmacodynamic studies and without any compromise in quality, safety, or efficacy. This proposal is scientifically valid, consistent with regulation of all biologics, and maintains robust regulatory standards in the assessment of biosimilar candidates. Note: The findings and conclusion of this paper are limited to biosimilar products developed against the regulatory standards in the EU and the US.

The reactions of 2-(N-ary1formimidoyl)pyridines with a number of active methylene compounds have been investigated. Reduction of the products gave octahydroindolizine derivatives, some of which were also prepared by other routes. The interaction of 2-(N-phenylforrnimidoyl) pyridine and diethyl succinate gave an octahydropyrrolo [3,4-c] pyrrole.

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Three of the four possible racemic forms of ethyl octahydro-3-methylindolizine-2-carboxylate have been isolated, and their stereochemistry has been elucidated.

ABSTRACT:The objective of this monitoring at Bamegat Inlet was to determine the response of the inlet system to a new south jetty completed in 1991 that essentially parallels the existing north jetty. Bamegat Inlet is accessed by a large number of commercial, sport fishing, and recreational vessels each year. An unstable navigation channel and numerous accidents and deaths at Bamegat Inlet led to the constmction of the new south jetty. The response of the new south jetty and inlet system was determined by data collection and monitoring and compared with design predictions, lliis new knowledge will contribute to improved jetty and inlet system design guidance, enhance construction of rabble-mound jetties, and develop better maintenance techniques for tidal inlets. The monitoring plan evaluated four fundamental hypotheses of the project design objectives: (a) the new south jetty and new channel alignment will not adversely affect tidal hydraulic response or high tide level in the inlet by system (i.e., no flooding problem), and prototype hydraulic response will be as predicted by a previous physical model evaluation; (b) the new south jetty realignment will improve navigation safety by stabilizing the navigation channel and depth between the jetties and over the outer bar (ebb tidal shoal), and will eliminate dredging in these regions; (c) flie new south jetty will be stracturally stable; and (d) the jetty system realignment will not adversely affect upcoast or downcoast beaches. DISCLAIMER:The contents of this report are not to be used for advertising, publication, or promotional purposes. Citation of trade names does not constitute an oflScial endorsement or approval of the use of such commercial products. All product names and trademarks cited are the property of their respective owners. The findings of this report are not to be constraed as an official Department of the Army position unless so designated by other authorized documents. DESTROY Tins REPORT WHEN IT IS NO LONGER NEEDED. DO NOT RETURN TO THE ORIGINATOR.

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