Reducing Wait Time of Chemotherapy and Biotherapy Administration to Inpatients by Increasing the Numbers of Chemotherapy Providers

The purpose of my CNL project is to decrease the chemotherapy administration wait-time for adult oncology patients by increasing the numbers of certified providers. Unfortunately as an oncology unit, about 44% of the providers are not active chemotherapy providers. As a CNL, we must constantly evaluate our microsystems to improve our clinical practice and standards for the benefits of our patients, organization, and our clinical growth. Four barriers for not taking the online course were identified through surveys (course difficulty, low census of oncology patients, lack of knowledge or uncomfortable giving chemotherapy, and the cost of the course if failed). Chemotherapy administration records were audited from April to May 2015. It was noted that the average wait-time was over 5 hours. Fulfilling the role of an Educator, study sessions and study groups will be provided by an Oncology Certified Nurse (OCN) to the nurses to promote taking the ONS online course. Two groups were formed with one in August 2015 and the other November 2015. Total nurses enrolled are nine. Each group will meet 5 days with paid education leave and tuition reimbursement. Surveys will be distributed to the nurses at the end of the course to evaluate the effectiveness of the study sessions. Another audit will be done to compare the administration wait-times by January. Results will be analyzed and shared with unit and management in January 2016. The goals are to increase the numbers of chemotherapy providers by 25% by November 2016, and decrease chemotherapy administration wait-times by 25% by January 2016

Twin-induced plasticity of an ECAP-processed TWIP steel

The TWIP steels show high strain hardening rates with high ductility which results in high ultimate tensile strength. This makes their processing by equal channel angular pressing very difficult. Up to now, this has only been achieved at warm temperatures (above 200 °C). In this paper, a FeMnCAl TWIP steel has been processed at room temperature and the resulted microstructure and mechanical properties were investigated. For comparison, the material has also been processed at 300 °C. The TWIP steel processed at room temperature shows a large increase in yield strength (from 590 in the annealed condition to 1295 MPa) and the ultimate tensile strength (1440 MPa) as a consequence of a sharp decrease in grain size and the presence within the grains of a high density of mechanical twins and subgrains. This dense microstructure results also in a loss of strain hardening and a reduction in ductility. The material processed at 300 °C is more able to accommodate deformation and has lower reduction in grain size although there is a significant presence of mechanical twins and subgrains produced by dislocation activity. This material reaches an ultimate tensile strength of 1400 MPa with better ductility than the room temperature material.Postprint (published version

Hemagglutinin sequence conservation guided stem immunogen design from influenza A H3 subtype

Seasonal epidemics caused by influenza A (H1 and H3 subtypes) and B viruses are a major global health threat. The traditional, trivalent influenza vaccines have limited efficacy because of rapid antigenic evolution of the circulating viruses. This antigenic variability mediates viral escape from the host immune responses, necessitating annual vaccine updates. Influenza vaccines elicit a protective antibody response, primarily targeting the viral surface glycoprotein hemagglutinin (HA). However, the predominant humoral response is against the hypervariable head domain of HA, thereby restricting the breadth of protection. In contrast, the conserved, subdominant stem domain of HA is a potential ‘universal’ vaccine candidate. We designed an HA stem-fragment immunogen from the 1968 pandemic H3N2 strain (A/Hong Kong/1/68) guided by a comprehensive H3 HA sequence conservation analysis. The biophysical properties of the designed immunogen were further improved by C-terminal fusion of a trimerization motif, ‘isoleucine-zipper’ or ‘foldon’. These immunogens elicited cross-reactive, antiviral antibodies and conferred partial protection against a lethal, homologous HK68 virus challenge in vivo. Furthermore, bacterial expression of these immunogens is economical and facilitates rapid scale-up

Key Factors Influencing Consumer Intent to Recycle Denim Apparel: A Study of U.S. Millennials

Denim, recycle, sustainability, perceived valu

Liderazgo transformacional y desempeño docente en una institución educativa de Nasca, 2023

La tesis titulada “Liderazgo transformacional y desempeño docente en una institución educativa de Nasca, 2023 tuvo como finalidad determinar la relación entre las variables de liderazgo transformacional y desempeño docente. La metodología que se empleo fue de tipo de investigación básica, de diseño no experimental, de enfoque cuantitativo y nivel correlacional con corte transversal. La población de 111 padres de familia, como técnica fue la encuesta y como instrumento el cuestionario, uno para la variable Liderazgo transformacional y otro para Desempeño laboral, cuya validez se obtuvo mediante juicio de expertos y la confiabilidad por la técnica Alfa de Cronbach. Como resultados procesados mediante el software SPSS V25, se obtuvo que existe una correlación directa y significativa entre el Liderazgo transformacional y Desempeño docente (r= 0,616) y el nivel de significancia de (p=0.001) < al 5%, indicando que si existe relación directa y significativa. Se concluyó que si existe un buen liderazgo dentro de una institución educativa será eficiente el desempeño docente

Manipulations of antibody galactosylation in a fed-batch adapted perfusion process

Perfusion processes have demonstrated significantly higher volumetric productivity while maintaining consistent product quality attributes (PQAs) throughout an extended harvest period. With this, a drastic decrease of the bioreactor footprint in future commercial plants can be achieved. Therefore, there are significant efforts in biopharmaceutical industry focused on developing high productivity perfusion process for both future biologics, as well as on developing new generation processes for legacy fed-batch processes. In this presentation, we will report the adaptation of an established 14-day fed-batch process for a therapeutic monoclonal antibody to a 30-day perfusion process using alternating tangential flow (ATF) technology. In the proof-of-concept perfusion process, a 6-fold viable cell density (VCD) was reached and maintained compared to the peak VCD in the fed-batch process. The productivity increased 3.5-fold as compared to the original fed-batch process after normalization to cell culture duration. The major PQAs from this perfusion process were consistent throughout the harvest period. Most of the PQAs from the perfusion process showed no significant differences from the original fed-batch process. However, significantly higher galactosylation level was observed in the perfusion process as compared to its fed-batch version. In the presentation, we will also detail the perfusion medium and process parameter optimization, which enabled the matching of the galactosylation profile of the last version perfusion process to the established fed-batch process without compromising target VCD, productivities, and other PQA profiles

Acid activation mechanism of the influenza A M2 proton channel

The homotetrameric influenza A M2 channel (AM2) is an acid-activated proton channel responsible for the acidification of the influenza virus interior, an important step in the viral lifecycle. Four histidine residues (His37) in the center of the channel act as a pH sensor and proton selectivity filter. Despite intense study, the pH-dependent activation mechanism of the AM2 channel has to date not been completely understood at a molecular level. Herein we have used multiscale computer simulations to characterize (with explicit proton transport free energy profiles and their associated calculated conductances) the activation mechanism of AM2. All proton transfer steps involved in proton diffusion through the channel, including the protonation/deprotonation of His37, are explicitly considered using classical, quantum, and reactive molecular dynamics methods. The asymmetry of the proton transport free energy profile under high-pH conditions qualitatively explains the rectification behavior of AM2 (i.e., why the inward proton flux is allowed when the pH is low in viral exterior and high in viral interior, but outward proton flux is prohibited when the pH gradient is reversed). Also, in agreement with electrophysiological results, our simulations indicate that the C-terminal amphipathic helix does not significantly change the proton conduction mechanism in the AM2 transmembrane domain; the four transmembrane helices flanking the channel lumen alone seem to determine the proton conduction mechanism.United States. National Institutes of Health (R01-GM088204

Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells

<p>Abstract</p> <p>Background</p> <p>The Tec-family kinase Itk plays an important role during T-cell activation and function, and controls also conventional versus innate-like T-cell development. We have characterized the transcriptome of Itk-deficient CD3⁺T-cells, including CD4⁺and CD8⁺subsets, using Affymetrix microarrays.</p> <p>Results</p> <p>The largest difference between Itk^-/-and Wt CD3⁺T-cells was found in unstimulated cells, e.g. for killer cell lectin-like receptors. Compared to anti-CD3-stimulation, anti-CD3/CD28 significantly decreased the number of transcripts suggesting that the CD28 co-stimulatory pathway is mainly independent of Itk. The signatures of CD4⁺and CD8⁺T-cell subsets identified a greater differential expression than in total CD3⁺cells. Cyclosporin A (CsA)-treatment had a stronger effect on transcriptional regulation than Itk-deficiency, suggesting that only a fraction of TCR-mediated calcineurin/NFAT-activation is dependent on Itk. Bioinformatic analysis of NFAT-sites of the group of transcripts similarly regulated by Itk-deficiency and CsA-treatment, followed by chromatin-immunoprecipitation, revealed NFATc1-binding to the <it>Bub1</it>, <it>IL7R, Ctla2a</it>, <it>Ctla2b</it>, and <it>Schlafen1 </it>genes. Finally, to identify transcripts that are regulated by Tec-family kinases in general, we compared the expression profile of Itk-deficient T-cells with that of Btk-deficient B-cells and a common set of transcripts was found.</p> <p>Conclusion</p> <p>Taken together, our study provides a general overview about the global transcriptional changes in the absence of Itk.</p

RibSeg v2: A Large-scale Benchmark for Rib Labeling and Anatomical Centerline Extraction

Automatic rib labeling and anatomical centerline extraction are common prerequisites for various clinical applications. Prior studies either use in-house datasets that are inaccessible to communities, or focus on rib segmentation that neglects the clinical significance of rib labeling. To address these issues, we extend our prior dataset (RibSeg) on the binary rib segmentation task to a comprehensive benchmark, named RibSeg v2, with 660 CT scans (15,466 individual ribs in total) and annotations manually inspected by experts for rib labeling and anatomical centerline extraction. Based on the RibSeg v2, we develop a pipeline including deep learning-based methods for rib labeling, and a skeletonization-based method for centerline extraction. To improve computational efficiency, we propose a sparse point cloud representation of CT scans and compare it with standard dense voxel grids. Moreover, we design and analyze evaluation metrics to address the key challenges of each task. Our dataset, code, and model are available online to facilitate open research at https://github.com/M3DV/RibSegComment: 10 pages, 6 figures, journa

A preexisting rare PIK3CA e545k subpopulation confers clinical resistance to MEK plus CDK4/6 inhibition in NRAS melanoma and is dependent on S6K1 signaling

Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA E545K mutation as conferring drug resistance. We demonstrate that PIK3CA E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and persisted in all successive samples even after immune checkpoint therapy and distant metastasis. Functional studies identified activated S6K1 as both a key marker and specific therapeutic vulnerability downstream of PIK3CA E545K -induced resistance. These results demonstrate that difficult-to-detect preexisting resistance mutations may exist more often than previously appreciated and also posit S6K1 as a common downstream therapeutic nexus for the MAPK, CDK4/6, and PI3K pathways. SIGNIFICANCE: We report the first characterization of clinical acquired resistance to MEKi + CDK4i, identifying a rare preexisting PIK3CA E545K subpopulation that expands upon therapy and exhibits drug resistance. We suggest that single-region pretreatment biopsy is insufficient to detect rare, spatially segregated drug-resistant subclones. Inhibition of S6K1 is able to resensitize PIK3CA E545K -expressing NRAS-mutant melanoma cells to MEKi + CDK4i. © 2018 AAC