Multi-attribute Raman spectroscopy (MARS) for monitoring product quality attributes in formulated monoclonal antibody therapeutics.

Rapid release of biopharmaceutical products enables a more efficient drug manufacturing process. Multi-attribute methods that target several product quality attributes (PQAs) at one time are an essential pillar of the rapid-release strategy. The novel, high-throughput, and nondestructive multi-attribute Raman spectroscopy (MARS) method combines Raman spectroscopy, design of experiments, and multivariate data analysis (MVDA). MARS allows the measurement of multiple PQAs for formulated protein therapeutics without sample preparation from a single spectroscopic scan. Variable importance in projection analysis is used to associate the chemical and spectral basis of targeted PQAs, which assists in model interpretation and selection. This study shows the feasibility of MARS for the measurement of both protein purity-related and formulation-related PQAs; measurements of protein concentration, osmolality, and some formulation additives were achieved by a generic multiproduct model for various protein products containing the same formulation components. MARS demonstrates the potential to be a powerful methodology to improve the efficiency of biopharmaceutical development and manufacturing, as it features fast turnaround time, good robustness, less human intervention, and potential for automation.

Advanced Practitioner-Led Shared Visits: A Novel Approach to Cancer Survivorship.

Background: The continued increase in the number of cancer survivors is encouraging and credited to better prevention, screening, and treatment. Cancer care authorities call for survivorship follow-up focusing on surveillance, health behaviors, and lingering effects of treatment. Despite the recommendations, cancer centers struggle to provide cost-effective, time efficient, comprehensive programming to address this call. Objectives: The primary objectives of this quality improvement project were to (1) develop and pilot a shared survivorship visit for breast cancer survivors and (2) evaluate the feasibility and acceptability of the program. Methods: The participants in this 4-week pilot project included five female breast cancer survivors, ages 18 and older, diagnosed with stage I, II, or III breast cancer within the past year. Each survivor completed a one-time, 2-hour shared survivorship visit. Results: The shared, interdisciplinary survivorship visit was directed by an advanced practice nurse. A team of nursing and ancillary experts presented information on their specialized area. Upon completion of the visit, the survivor received an individualized survivorship care plan. There were 21 eligible breast cancer survivors and 5 participants. The pilot was successfully implemented, acknowledged the feasibility, and identified the adaptability to other cancer survivors. An evaluation concluded that the APRN-led, shared survivorship visit model was accepted by the patients and the survivorship team. The shared survivorship visits will be implemented into the cancer care program to address the needs of breast cancer survivors. Furthermore, there will be an expansion of the shared survivorship visits to meet the needs of those with other types of cancers.

Rapid Identification of Disulfide Bonds and Cysteine-Related Variants in an IgG1 Knob-into-Hole Bispecific Antibody Enhanced by Machine Learning.

Bispecific antibodies are regarded as the next generation of therapeutic modalities as they can simultaneously bind multiple targets, increasing the efficacy of treatments for several diseases and opening up previously unattainable treatment designs. Linking two half antibodies to form the knob-into-hole bispecific antibody requires an additional in vitro assembly step, starting with reduction of the antibodies and then reoxidization. Analysis of the disulfide bonds (DSBs) is vital to ensuring the correct assembly, stability, and higher-order structures of these important biomolecules because incorrect disulfide bond formation and/or presence of cysteine-related post-translational modifications can cause a loss of biological activity or even elicit an immune response from the host. Despite advancements in analytical methods, characterization of cysteine forms remains technically challenging and time-consuming. Herein, we report the development of an improved nonreduced peptide map method coupled with machine learning to enable rapid identification of disulfide bonds and cysteine-related variants in an IgG1 knob-into-hole bispecific antibody. The enhanced method offers a fast, consistent, and accurate workflow in mapping-out expected disulfide bonds in both half antibodies and bispecific antibodies and identifying cysteine-related modifications. Comparisons between two versions of the bispecific antibody molecule and analysis of stressed samples were also accomplished, indicating this method can be utilized to identify alterations originating from bioprocess changes and to determine the impact of assembly and postassembly stress conditions to product quality.

Articulation rate: effects of age, fluency, and syntactic structure

(Reportamos los hallazgos básicos sobre los efectos del índice de articulación, derivados de la investigación experimental sobre la planificación de oraciones de los niños. Los experimentos fueron diseñados para evaluar los procesos de producción con atención a las variables sintácticas, a la vez que se controlaban las variables léxicas y fonológicas. Las mediciones del índice de articulación reflejaron que: (1) los índices difirieron entre niños (de 3 a 8,11) y adultos, donde los índices de los adultos fueron considerablemente más rápidos que los de los niños; (2) los efectos de la expresión de fluidez y falta de fluidez del sujeto sobre las subseries de fluidez difirieron para adultos y niños; y (3) el patrón del índice de articulación para las oraciones de relativo y las oraciones coordinadas difirió tanto de un tipo de oraciones a otro como dentro del grupo de edad (AU)

We report basic findings on articulation rate effects derived from experimental research on children's sentence planning. The experiments were designed to evaluate production processes with attention to syntactic variables while controlling for lexical and phonological variables. Articulatory rate measures showed (1) rates differed for children (3–8.11) and adults, with adult rates significantly faster than child rates; (2) the effects of fluent and dysfluent host utterances on fluent substrings differed for adults and children; (3) rate patterns for relative clause and conjoined clause utterances differed, both from each other and across age group (AU)

Children's sentence planning: syntactic correlates of fluency variations.

This paper argues for broader consideration of children's language production systems and, in that context, describes research on children's planning of syntactic structures. The research presented here measures non-fluency patterns in elicited utterances of varied syntactic type. We describe and interpret several regularities in these patterns for two groups of children ('young': three-five-year-olds; and 'older': six-eight-year-olds) and an adult comparison group. The evidence indicates a strong correspondence of adult and child responses to structural complexity, both in terms of global fluency measures and in terms of more detailed indicators of planning load. In addition, we report some specific contrasts in the patterning for children and adults that suggest disparities in processing resources and/or in local planning strategies.

Moving Beyond Conventional Wisdom: Advancements in Cross-Cultural Theories of Leadership, Conflict, and Teams.

In this article, we discuss the importance of a cross-cultural approach to organizational behavior. To do so, we illustrate how cross-cultural research in the past two decades has enabled us to reconceptualize constructs, revise models, and extend boundary conditions in traditional organizational behavior theories. We focus on three domains-teams, leadership, and conflict-and review cross-cultural empirical evidence that has extended several theories in each of these domains. We support the claim that even well-established organizational behavior theories vary in the extent to which they may be applied unilaterally across cultures, thus identifying the critical need to advance these theories via a cross-cultural research agenda.