Articles de revues sur le sujet « Arkansas Foundation of Associated Colleges »

Relying on data from an in-depth study of 15 community colleges, this article explores online education through the lens of institutional theory. This theoretical perspective highlights the colleges’ environmental contexts and offers a critical examination of the ways that the institutional contexts have structured the colleges’ approaches to online education. At the core of this analysis is the contention that community colleges are interpreting and responding to a set of taken-for-granted ideas about online education. These ideas have taken on the status of myth and have played a powerful role in guiding and legitimating colleges’ online activity. This analysis provides a research-based foundation for understanding online activity at the community college level and for carefully addressing the challenges associated with its adoption.

Abstract Introduction: Molecular assessment using conventional karyotyping, interphase FISH and gene expression profiling (GEP) has revealed multiple subgroups of myeloma with distinct pathogenesis and clinical course. While these technologies have tremendously impacted risk assessment they have had little contribution to the identification of therapeutic targets. Next generation sequencing (NGS) technology can identify mutations in genes of key cancer pathways, which impact outcome and are targetable by new drugs. Targeted gene panels can analyze clinical samples in sufficient depth affording the opportunity to incorporate NGS into clinical decision making in a meaningful way. Using the FoundationOne Heme test (F1H), we aimed to determine the mutational spectra of cancer-associated genes in multiple myeloma (MM), their association with disease risk and their effect on clinical outcome. Methods: DNA and RNA were extracted from CD138-selected MM cells. Comprehensive genomic profiling (CGP) using F1H was performed by Foundation Medicine, Inc (Cambridge, MA). Sequencing to an average depth of 470x (range: 5-3781) was performed on a HiSeq2500 sequencer. Sequences were analyzed for base substitutions, insertions, deletions, copy number alterations, and rearrangements in frequently altered genes. Annotated germline variants (dbSNP135) were removed. Somatic alterations in COSMIC (v62) and inactivating variants in tumor suppressor genes were called as biologically significant. GEP of CD138-selected MM cells using Affymetrix U133 2.0 plus arrays was performed as described. Overall survival analysis was done using log-rank tests. Results: CGP was performed on a total of 630 patients (3.4% MGUS, 6.5% SMM, 24.9% newly diagnosed MM, 24.9% relapsed MM, 18.8% MM in remission). We found increasing mutation load in from MGUS to relapsed MM. Later stages of the disease had an increased frequency of mutations in genes coding for epigenetic modulators and proteins involved in DNA repair. Alterations of TP53 and RB1 among others weresignificantly more frequent in GEP-defined high-risk (HR) disease and after relapse. Patients of the GEP-defined MF molecular subgroup carried a significantly greater mutation load. While there was no difference in the frequency of altered RAS/MAPK pathway genes between newly diagnosed and relapsed patients, we found an increased average mutant allele frequency in relapsed patients, indicating clonal selection. Using paired GEP data we identified gene expression signatures for patients with RAS/MAPK activation and patients with loss-of-function mutations in the DNA repair pathway, suggesting a functional relevance of these mutations. Mutations in either of these pathways were associated with significantly worse overall survival (OS) (Figure 1). Presence of DNA repair gene mutations resulted in significantly worse OS within the GEP-defined low-risk subgroup. Among the 630 patients who underwent CGP, 396 had clinically relevant alterations, which were associated with either an FDA approved drug or a clinical trial. For example, 316 patients had alterations of the RAS/MAPK pathway. Recently we have shown clinical benefit of MEK directed therapy in this patient population. 39 patients had alterations in the mTOR pathway, suggesting benefit from mTOR inhibitors. 426 patients with MM had mutations in epigenetic modulators. For 37 of them therapy with demethylating agents was recommended. Many more epigenetic targeted drugs, such as EZH2 or Bromodomain inhibitors are currently in development. Conclusion: Using the F1H test we demonstrate a negative impact of somatic mutations of the MAPK and DNA repair pathways on outcome. In tandem, for 396 patients we identified genomic alterations, which suggest benefit from targeted treatment. Thus targeted therapy, guided by comprehensive genomic profiling, may be applied to the majority of MM patients, with the potential of significantly improving clinical outcomes. Comprehensive genomic profiling should therefore be considered in the routine work-up, especially for HR patients where outcomes remain poor. Figure 1. Inferior outcome of patients with mutations in the MAPK or DNA repair pathway. Panels A) and C) mutation of MAPK pathway; Panels B) and D) mutation of the DNA repair pathway. Overall survival is measured from time of disease diagnosis in panels A) and B) and is shown from sample date in panels C) and D) Figure 1. Inferior outcome of patients with mutations in the MAPK or DNA repair pathway. Panels A) and C) mutation of MAPK pathway; Panels B) and D) mutation of the DNA repair pathway. Overall survival is measured from time of disease diagnosis in panels A) and B) and is shown from sample date in panels C) and D) Disclosures Heuck: Millenium: Other: Advisory Board; Janssen: Other: Advisory Board; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment; Foundation Medicine: Honoraria. Chavan:University of Arkansas for Medical Sciences: Employment. Stein:University of Arkansas for Medical Sciences: Employment. Tytarenko:University of Arkansas for Medical Sciences: Employment. Weinhold:University of Arkansas for Medical Sciences: Employment; Janssen Cilag: Other: Advisory Board. Ali:Foundation Medicine, Inc.: Employment, Equity Ownership. Miller:Foundation Medicine, Inc.: Employment, Equity Ownership. Thanendrarajan:University of Arkansas for Medical Sciences: Employment. Schinke:University of Arkansas for Medical Sciences: Employment. Mohan:University of Arkansas for Medical Sciences: Employment. Sawyer:University of Arkansas for Medical Sciences: Employment. Peterson:University of Arkansas for Medical Sciences: Employment. Bauer:University of Arkansas for Medical Sciences: Employment. Ashby:University of Arkansas for Medical Sciences: Employment. Johann:University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Davies:Millenium: Consultancy; Onyx: Consultancy; Janssen: Consultancy; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:CancerNet: Honoraria; Weismann Institute: Honoraria; MMRF: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract Introduction: Next generation sequencing of over 800 newly diagnosed multiple myeloma (NDMM) cases has established the mutational landscape and key cancer driver pathways. The mutational basis of relapse has not been systematically studied. Two previous studies (Keats et al.; Bolli et al.) identified 4 patterns of clonal evolution. Neither study included uniformly treated patients and looked at the impact of therapy on clonal structure at relapse. Understanding the mutational patterns underlying relapse and how they relate to specific therapies is crucial in order to improve MM outcomes, especially for high-risk (HR) MM. In this study we compare the clonal structure at presentation (PRES) and at relapse (REL), after exposure to Total Therapy (TT). Materials and Methods: We studied 33 pairs of tumor samples collected at PRES and REL. 9 patients were treated on TT2, 13 on TT3, 10 on TT4 and 1 on TT5-like regimen. Eleven patients had HR disease at PRES. DNA was extracted from CD138+ selected cells from random bone marrow aspirates. Germline controls were obtained from leukapheresis products. Whole exome sequencing libraries were prepared using the Agilent qXT kit and the Agilent SureSelect Clinical Research Exome kit with additional baits covering the Ig and MYC loci. All samples were sequenced on an Illumina HiSeq2500 to a median depth of 120x. Sequencing data were aligned to the Ensembl GRCh37/hg19 human reference using BWA. Somatic variants were called using MuTect. Translocations were identified using MANTA. Copy number variations were inferred using TITAN. Gene expression profiles (GEP), generated using the Affymetrix U133plus2 microarray, were available for all tumor samples. Nonnegative matrix factorization (NMF) was used to define mutation signatures. Results: The median time to progression was 30 months with a median follow up of 9.5 years. 22 cases achieved a complete remission (CR) or near CR. There were 11 cases of HR at PRES. Of the 22 cases with low risk (LR) MM, 7 relapsed with HR disease. There were on average 478 SNVs per sample at PRES and 422 at REL. All but 2 cases had evidence of new mutations at REL. There were no consistent patterns or number of mutation associated with REL or GEP-defined risk. Patients of the MF molecular subgroup had more mutations compared to other molecular subgroups (657 vs. 379) and were enriched for mutations with an APOBEC signature. We did not detect any mutation signature consistent with chemotherapy-induced alterations, providing evidence that TT itself does not cause additional mutations. Primary recurrent IgH translocations called by MANTA were confirmed by GEP data. A number of new translocations were identified , several only at REL. In particular we demonstrate a case with a newly acquired MYC translocation at relapse, indicating that it contributed to progression. We identified 5 patterns of clonal evolution (Figure 1): A) genetically distinct relapse in 3 patients, B) linear evolution in 8 patients, C) clonal selection in 9 patients, D) branching evolution in 11 patients, and E) stable clone(s) in 2 patients. Patterns A (distinct) and B (linear) were associated with low risk and longer survival, whereas patterns D (branching) and E (stable) were associated with high risk and shorter time to relapse and overall survival (Table 1). Conclusion: This is the first study to systematically analyze the pattern of clonal evolution using NGS in patients treated with combination chemotherapy and tandem ASCT. We identified 5 patterns of evolution, which correlate with survival. We identified 3 cases with a loss of the original clone and emergence of a new clone, suggesting high effectiveness of Total Therapy for those patients. The persistence of major clones despite multi agent chemotherapy in most other cases supports a concept of a tumor-initiating cell population that persist in a protective niche, for which new therapies are needed. Table 1. Pattern of Evolution GEP70 Pres.(high risk: ≥0.66) Proliferation Index Pres. GEP70 Rel.(high risk: ≥0.66) Proliferation Index Rel Mean OS Mean TTR A: distinct (n=3) -0.690 -3.34 -0.015 2.04 8.18 5.00 B: linear (n=8) -0.171 -0.34 0.618 9.22 5.70 4.05 C: selection (n=9) 0.366 3.20 0.569 6.97 3.95 2.64 D: branching (n=11) 0.710 5.17 1.173 11.15 3.84 2.21 E: stable (n=2) 1.532 7.42 1.124 2.54 0.96 0.35 Pres.: Presentation; Rel.: Relapse; OS: Overall Survival; TTR: Time to Relapse Figure 1. Patterns of Relapse Figure 1. Patterns of Relapse Disclosures Heuck: Foundation Medicine: Honoraria; Millenium: Other: Advisory Board; Janssen: Other: Advisory Board; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment. Weinhold:Janssen Cilag: Other: Advisory Board; University of Arkansas for Medical Sciences: Employment. Peterson:University of Arkansas for Medical Sciences: Employment. Bauer:University of Arkansas for Medical Sciences: Employment. Stein:University of Arkansas for Medical Sciences: Employment. Ashby:University of Arkansas for Medical Sciences: Employment. Chavan:University of Arkansas for Medical Sciences: Employment. Stephens:University of Arkansas for Medical Sciences: Employment. Johann:University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Johnson:University of Arkansas for Medical Sciences: Employment. Zangari:University of Arkansas for Medical Sciences: Employment; Millennium: Research Funding; Onyx: Research Funding; Novartis: Research Funding. Matin:University of Arkansas for Medical Sciences: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Yaccoby:University of Arkansas for Medical Sciences: Employment. Davies:University of Arkansas for Medical Sciences: Employment; Millenium: Consultancy; Janssen: Consultancy; Onyx: Consultancy; Celgene: Consultancy. Epstein:University of Arkansas for Medical Sciences: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:Weismann Institute: Honoraria; MMRF: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; CancerNet: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract INTRODUCTION Profound osteolytic lesions are a hallmark of multiple myeloma (MM) bone disease. Bone destruction is associated with severely unbalanced bone remodeling, secondary to the secretion of osteoclast activating factors and significant osteoblast suppression. Lytic lesions of the pelvis are relatively common in MM patients and contribute to increase morbidity due to the high risk of fracture that frequently demands surgical intervention. Since we observed significant improvements in the pelvic CT of patients following total therapy 4 (TT4) we retrospectively analyzed the appearance on pelvic osteolytic lesions by CT during TT4 treatment for myeloma. METHODS The UAMS Myeloma data base was interrogated to identify patients enrolled on the TT4 trial. TT4 is a protocol designed for low risk MM patients as defined by a baseline plasma cell GEP score < than 0.66. The treatment protocol includes two induction chemotherapy cycles followed by tandem autologous bone marrow transplantation, two consolidation cycles and 3 years of maintenance. During treatment, patients were exposed to alkylating agents, IMIDS and proteasome inhibitor agents as well as bisphosphonates. Baseline pelvic osteolytic lesions with > 1 cm in minimal diameter identified by PET/CT or CT of the pelvis were compared to the most recent radiological study available for the same subject. All identified cases were reviewed by radiology faculty to confirm the baseline and follow-up reported findings. Radiological findings were correlated with disease status, molecular subgroup, PET scanning and MRI. RESULTS Sixty-three (63) patients, with a median age of 62 years, were identified for this analysis. Baseline patient characteristics are shown in Table 1. With a median follow up of 41 months, CT studies indicate that 44% (28/63) of patients with large baseline pelvic lytic lesions achieved re-accumulation of radio-dense mineralized tissue at the lytic site. Sixty-eight percent of such patients reached at least VGPR. The average size of the lytic lesions that re-mineralized was 4.0 cm (minimum 1.3 cm - maximum 10 cm). Baseline GEP-defined molecular subgroups and cytogenetic distribution was not different from the entire patient population of TT4. CONCLUSION This study clearly shows that mineral redeposition in large pelvic lytic lesions of MM patients on TT4 is achievable in a significant proportion of individuals. We observed that the amount of re-mineralization was prominent in pelvic lytic lesions with cortical bone destruction. Since flat bones, such as the pelvis, are formed via intramembranous ossification further investigation of the mechanism responsible for this effect is warranted at skeletal sites with different regenerative capacity. These data also suggest that, contrary to much dogma, MM bone lesions can regain matrix mineralization capacity. Table 1. Baseline Patient Characteristics n/N (%) Male 43/63 (69%) IgA Isotype 11/63 (17.5%) IgD Isotype 1/63 (1.6%) IgG Isotype 36/63 (57.1%) Nonsecretory 1/63 (1.6%) Light Chain Isotype 14/63 (22.2%) LDH > = 190 U/L 8/63 (12.7%) Abnormal Cytogenetics 44/63 (69.8%) GEP CD-1 subgroup 4/64 (6.3%) GEP CD-2 subgroup 17/64 (26.6%) GEP HY subgroup 24/64 (37.5%) GEP LB subgroup 8/64 (12.5%) GEP MF subgroup 1/64 (1.6%) GEP MS subgroup 2/64 (3.1%) GEP PR subgroup 5/64 (7.8%) Disclosures Mohan: University of Arkansas for Medical Sciences: Employment. Samant:University of Arkansas for Medical Sciences: Employment. Suva:University of Arkansas for Medical Sciences: Employment. Montgomery:University of Arkansas for Medical Sciences: Employment. Alapat:University of Arkansas for Medical Sciences: Employment. Morello:University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Thanendrarajan:University of Arkansas for Medical Sciences: Employment. Schinke:University of Arkansas for Medical Sciences: Employment. Heuck:Millenium: Other: Advisory Board; Celgene: Consultancy; Foundation Medicine: Honoraria; Janssen: Other: Advisory Board; University of Arkansas for Medical Sciences: Employment. Jethava:University of Arkansas for Medical Sciences: Employment. Johann:University of Arkansas for Medical Sciences: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Davies:University of Arkansas for Medical Sciences: Employment; Celgene: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Onyx: Consultancy. Morgan:CancerNet: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; MMRF: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Weismann Institute: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zangari:Novartis: Research Funding; Millennium: Research Funding; Onyx: Research Funding; University of Arkansas for Medical Sciences: Employment.

Abstract Introduction: Recent next generation sequencing studies have defined the mutation spectrum in multiple myeloma (MM) and uncovered significant intra-clonal heterogeneity, showing that clinically relevant mutations are often only present in sub-clones. Longitudinal analyses demonstrated that tumor clones under therapeutic pressure behave in a "Darwinian" fashion, with shifting dominance of tumor clones over time. Recently, stratification of clonal substructures in distinct areas of the tumor bulk has been shown for multiple cancer types. So far, spatial genomic heterogeneity has not been systematically analyzed in MM. This stratification in space is becoming increasingly important as we begin to understand the contribution of Focal Lesions (FL) to tumor progression and emergence of drug resistance in MM. We have recently shown that high numbers of FL are associated with gene expression profiling (GEP) defined high risk (HR). A comparison of GEP data of 170 paired random bone marrow (RBM) and FL aspirates showed differences in risk signatures, supporting the concept of spatial clonal heterogeneity. In this study we have extended the analysis by performing whole exome sequencing (WES) and genotyping on paired RBM and FL in order to gain further insight into spatial clonal heterogeneity in MM and to find site-specific single nucleotide variant (SNV) spectra and copy number alterations (CNA), which contribute to disease progression and could form the basis of adaptation of the tumor to therapeutic pressure. Materials and Methods: We included 50 Total Therapy MM patients for whom paired CD138-enriched RBMA and FL samples were available. Leukapheresis products were used as controls. For WES we applied the Agilent qXT kit and a modified Agilent SureSelect Clinical Research Exome bait design additionally covering the immunoglobulin heavy chain locus and sequences located within 1Mb of the MYC locus. Paired-End sequencing to a minimum average coverage of 120x was performed on an Illumina HiSeq 2500. Sequencing data were aligned to the Ensembl GRCh37/hg19 human reference using BWA. Somatic variants were identified using MuTect. For detection of CNA we analyzed Illumina HumanOmni 2.5 bead chip data with GenomeStudio. Subclonal reconstruction was performed using PhyloWGS. Mutational signatures were investigated using SomaticSignatures. The GEP70 risk signature was calculated as described previously. Informed consent in accordance with the Declaration of Helsinki was obtained for all cases included in this study. Results: Analyzing RBM and FL WES data, we detected between 100 and 200 somatic SNVs in covered regions, with approximately 30% of them being non-synonymous, and less than 5% stop gained or splice site variants. A comparison of paired RBM and FL WES data showed different extents of spatial heterogeneity. Some pairs had very similar mutation profiles with up to 90% shared variants, whereas others demonstrated marked heterogeneity of point mutations. We did not detect differences in mutational signatures between RBM and FL using the 'SomaticSignatures' package. We found site-specific driver mutations with high variant allele frequencies, indicating replacement of other clones in these areas. For example we observed a clonal KRAS mutation exclusively in the RBM, whereas a NRAS variant was only identified in the paired FL. The same holds true for large-scale CNAs (>1 Mb). We identified a case in which the high risk CNAs gain(1q) and del(17p) were only detectable in the FL. Further examples for site-specific CNAs were a del(10q21) and a gain(4q13) detected in FLs only. As a prominent pattern, we observed outgrowth of sub-clonal RBM CNAs as clonal events in the FL. Based on mutation and CNA data we identified different forms of spatial evolution, including parallel, linear and branching patterns. Of note, a stratified analysis by GEP70-defined risk showed that a more pronounced spatial genomic heterogeneity of SNVs and CNAs was associated with HR disease. Conclusion: We show that spatial heterogeneity in clonal substructure exists in MM and that it is more pronounced in HR. The existence of site-specific HR CNAs and driver mutations highlights the importance of heterogeneity analyses for targeted treatment strategies, thereby facilitating optimal personalized MM medicine. Disclosures Weinhold: University of Arkansas for Medical Sciences: Employment; Janssen Cilag: Other: Advisory Board. Chavan:University of Arkansas for Medical Sciences: Employment. Heuck:Millenium: Other: Advisory Board; Janssen: Other: Advisory Board; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment; Foundation Medicine: Honoraria. Stephens:University of Arkansas for Medical Sciences: Employment. Tytarenko:University of Arkansas for Medical Sciences: Employment. Bauer:University of Arkansas for Medical Sciences: Employment. Peterson:University of Arkansas for Medical Sciences: Employment. Ashby:University of Arkansas for Medical Sciences: Employment. Stein:University of Arkansas for Medical Sciences: Employment. Johann:University of Arkansas for Medical Sciences: Employment. Johnson:University of Arkansas for Medical Sciences: Employment. Yaccoby:University of Arkansas for Medical Sciences: Employment. Epstein:University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Zangari:Novartis: Research Funding; Onyx: Research Funding; Millennium: Research Funding; University of Arkansas for Medical Sciences: Employment. Schinke:University of Arkansas for Medical Sciences: Employment. Thanendrarajan:University of Arkansas for Medical Sciences: Employment. Davies:Millenium: Consultancy; Onyx: Consultancy; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment; Janssen: Consultancy. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:University of Arkansas for Medical Sciences: Employment; MMRF: Honoraria; CancerNet: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Weismann Institute: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract Introduction: Focal lesions (FL) are detected by magnetic resonance imaging (MRI) and positron emission tomography (PET) and precede the development of osteolytic lesions in multiple myeloma (MM). FLs are absent in most patients with benign disease and their detection is associated with earlier disease progression suggesting that a distinct MM cell niche in the FLs is associated with conditions that promote the transition to MM. Studying the nature of this niche can significantly enhance our understanding of the biology and progression of MM. Methods: Random BM aspiration samples were taken from the posterior superior iliac crest whereas FL samples were sampled under CT guidance from newly diagnosed MM patients. Gene expression profiling (GEP) was performed on CD138-enriched plasma cells (PC, n=170) and non-enriched BM trephine biopsies (n=49) from paired RBM and FL samples from the same patients and from unrelated RBM cases with no detectable FL (n=79). 8-multicolor flow cytometry (MFC) analysis was performed on 25 paired PC samples and selected genes were validated using immunohistochemistry (IHC). Results: AComparison of GEP from paired RBM-PC and FL-PC showed discrepancies in GEP-based risk score and molecular subgroups and lower Polyclonal-PC score (reflecting the proportion of normal PC infiltration) in FL-PC samples (p=0.0001). There is 89% concordance for the GEP70 risk signature with 10 patients having low-risk PCs in RBM but high-risk PCs in the paired FL, and 8 patients showing high-risk PCs in RBM but low-risk PCs in the paired FL samples. In this setting progression-free and overall survival are mediated by the presence of a high-risk score in either sample. When molecular subgroups were identified there were more high risk-associated PR cases in FL samples (n=28) compared to only 16 PR cases in respective paired RBM-PC samples (p=0.005). Flow cytometry data from 25 paired MM cell samples showed consistently lower surface expression of CD138 in FL (p=0.0001). Cases with detectable CD81 had lower CD81 expression on FL-PC (p=0.03). Discrepancies were also observed in cell surface expression of CD38 and CD45. Pathway's analysis was based on of 523 differentially expressed genes between paired FL and RBM-PC samples (n=170; FDR<0.001) after adjusting for the level of normal PC infiltration. The top KEGG-based pathways enrichment analysis were associated with energy and drug metabolism, survival, cell-cell contact interaction and factors involved in activity of dexamethasone (e.g. NR3C1) and IMiDs (e.g. IZKF1), Figure 1A. Differential expression of ABCA1, the most upregulated gene in FL, was validated by IHC in biopsies. To test whether PCs from patients with FL have specific characteristics irrespective of their location, we compared RBM-PC GEP with RBM-PC GEP of unrelated patients with no detectable FLs. We detected increased expression of cell cycle genes in PC from patients with detectable FL. Reduced osteogenesis and interaction with mesenchymal and vascular lineages have been linked with MM cell phenotypes and dissemination in BM. Microenvironmental reactive stroma (e.g. POSTN, collagen genes) and angiogenic (e.g. EDNRA) gene signatures were significantly upregulated in non-enriched FL biopsies albeit expected high proportion of PC in this site, whereas osteoblastic markers such as BGLAP and IBSP were underexpressed in these samples in comparison to paired non-enriched RBM trephine biopsies, Figure 1B. Conclusions: PC in FL and RBM sites of the same patient are heterogeneous in their phenotype, molecular classification based on risk-score and subgroups, and pathways. GEP signatures of MM cells and the stroma in this niches stressing the biological and clinical relevance of FL as a hallmark in MM. Disclosures Yaccoby: University of Arkansas for Medical Sciences: Employment. Epstein:University of Arkansas for Medical Sciences: Employment. Johnson:University of Arkansas for Medical Sciences: Employment. Qu:Cancer Research and Biostatistics: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Jethava:University of Arkansas for Medical Sciences: Employment. Stein:University of Arkansas for Medical Sciences: Employment. Mitchell:Cancer Research and Biostatistics: Employment. Heuck:Millenium: Other: Advisory Board; University of Arkansas for Medical Sciences: Employment; Celgene: Consultancy; Janssen: Other: Advisory Board; Foundation Medicine: Honoraria. Davies:Millenium: Consultancy; Janssen: Consultancy; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment; Onyx: Consultancy. Crowley:Cancer Research and Biostatistics: Employment. Weinhold:Janssen Cilag: Other: Advisory Board; University of Arkansas for Medical Sciences: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; CancerNet: Honoraria; Weismann Institute: Honoraria; MMRF: Honoraria; University of Arkansas for Medical Sciences: Employment; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Purpose The purpose of this paper is to reflect upon experiences of measuring the influences of the Recovery Academy within Greater Manchester Mental Health (GMMH) NHS Foundation Trust amongst a student population of health professionals. This paper aims to present considerations for future quantitative research surrounding the efficacy of Recovery Colleges such as the Recovery Academy. Design/methodology/approach This paper utilised baseline data collected from health professionals as part of a quantitative evaluation of the Recovery Academy. The paper discusses challenges experienced in measuring change amongst this student population within GMMH. Findings Health professionals reported positive attitudes towards recovery at baseline presenting challenges in measuring attitudinal change associated with the Recovery Academy. The experiences of conducting research amongst health professionals within GMMH offers insights into the selection and use of self-report measures in Recovery College research; the representativeness of health professional student populations; and models of course attendance within Recovery Colleges. Originality/value The existing literature specific to Recovery College influences upon health professionals remains predominantly qualitative and anecdotal. It is important to gather empirical evidence regarding Recovery Colleges to establish their ability to re-orientate health professionals around principles of recovery. This paper therefore offers considerations for future researchers aiming to gather empirical evidence which may facilitate quantitative evaluations of Recovery Colleges such as the Recovery Academy amongst staff populations.

Abstract Introduction In multiple myeloma (MM), deletion of chromosome 17 p13 (del17p) is a poor prognostic feature. The percentage of cells carrying an abnormality has been reported to be important with thresholds of 20% being taken generally but thresholds as high as 60% being suggested more recently. We have reported previously in the Total Therapy (TT)-2 trial (NCT00083551) for newly diagnosed (ND) MM that del17p is an adverse prognostic factor (Blood 112: 4235). The TT3 trial (NCT00081939) incorporated Brtezomib into tandem Melphalan-based autotransplants with DT-PACE for induction/consolidation and Thalidomide and Dexamethasone for maintenance to treat patients with newly diagnosed MM. In more recent iterations of these trials following the introduction of novel agents in induction and during maintenance the impact of carrying del17p has not been studied. In particular we have stratified patients into low- or high-risk molecular subgroups based on the GEP-70 (TT4 protocol [NCT00734877] or TT5 protocol [NCT00869232], respectively). We have used interphase FISH (iFISH) to detect the presence of del17p in baseline bone marrow samples. Method The iFISH slides were prepared with bone marrow aspirates after removing erythrocytes. A specific TP53 probe at chromosome 17 arm p13 combined with a control probe for the ERBB3 locus (HER2, 17q12), in different colors, were hybridized to bone marrow cells. Myeloma PCs were identified by restricted Kappa or Lambda immunoglobulin light-chain staining. We investigated role of 20% cutoffs per ≥100 tumor cells for significant deletion of the TP53 probe. Kaplan-Meier analysis was used to estimate the distributions of overall survival (OS) and progression-free survival (PFS) during the follow-ups. OS was calculated from registration until the date of decease. PFS was similarly calculated, but also incorporated progressive disease as an event. Results We examined 709 baseline samples from TT3, 4, and 5 trials with the two probes at chromosome 17. Overall, 66 of 709 patients (9.3%) had deletion of TP53 locus, including 44 of the 591 (7.5%) of low-risk patients and 20 of the 118 (17.0%) high-risk patients (Table). The range of TP53-deleted cells among newly diagnosed patients is 20-99% (median=75%) overall; 35-100% (median=62%) in TT3-low-risk; 30-97% (median=80%) in TT3-high-risk; 21-99% (median=76%) in TT4; and 20-97% (median=81%) in TT5. Deletion of TP53 was associated with significant shorter OS and PFS in HR patients treated on TT3. The 3 year estimated OS of patients for TT3-HR with del17p was 33% compared with 56% for TT3-LR with del17p, and PFS of patients for TT3-HR with del17p was 25% compared with 51% for TT3-LR with del17p (Figure). The comparison of TT4 to TT5 continued showing short OS in HR patients treated on TT5. The 3 year estimated OS of patients for HRMM with del17p was 17% compared with 75% for TT5 patients without deletion (p=0.0008). But, del17p was neutral in LR patients treated on TT4 (Figure). Conclusion Since the introduction of novel agents during various stages of the disease and a focus on HRMM and LRMM defined by GEP70 we show that while TP53 deletion is an adverse prognostic factor for patients with HRMM it is no longer prognostically relevant in LRMM. Table 1. Patients with iFISH results GEP-70 riskLow ≤0.66 High >0.66 Deletion TP53 in 20-59% PCs (n/N [%]) Deletion TP53 in ≥60% PCs (n/N, [%]) Total TT3 (N=329) Low=256 9/329, [2.7%] 9/329, [2.7%] 18/329, [5.5%] High=73 3/329, [0.9%] 9/329, [2.7%] 12/329, [3.7%] TT4 (N=313) Low=313 5/313, [1.6%] 21/313, [6.7%] 26/313, [8.3%] High=0 0 0 0 TT5 (N=67) Low=22 2/67, [3.0%] 0 2/67, [3.0%] High=45 0 8/67, [11.9%] 8/67, [11.9%] Sum (N=709) Low=591 (83.4%) 14/709, [2.0%] 30/709, [4.2%] High=118 (16.6%) 3/709, [0.4%] 17/709, [2.4%] 66/709 (9.3%) Figure 1. Figure 1. Disclosures Tian: University of Arkansas for Medical Sciecnes: Employment. Epstein:University of Arkansas for Medical Sciences: Employment. Qu:Cancer Research and Biostatistics: Employment. Heuck:Millenium: Other: Advisory Board; Janssen: Other: Advisory Board; Celgene: Consultancy; Foundation Medicine: Honoraria; University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Zangari:University of Arkansas for Medical Sciences: Employment; Millennium: Research Funding; Onyx: Research Funding; Novartis: Research Funding. Hoering:Cancer Research and Biostatistics: Employment. Sawyer:University of Arkansas for Medical Sciences: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:Weismann Institute: Honoraria; CancerNet: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; MMRF: Honoraria; University of Arkansas for Medical Sciences: Employment; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract Introduction Over the last 15 years gene expression profiling (GEP) has been used to define myeloma molecular subgroups and to determine clinical prognosis. Two major molecular subgroup classifications have been used: the UAMS which determines 7 subgroups and the TC classification based on the presence of IgH translocations and expression of D group cyclins. For prognosis, although a number of different GEP signatures have been defined, the widely used GEP70 identifies 15% of patients with high risk (HR) disease who have a median PFS and OS of 1.75 and 2.83 years. An ideal classification system would identify clinically relevant subgroups with distinct etiology and biology using standardized techniques. We have examined a large group of patients characterized at multiple genetic levels to optimize the diagnostic approach of newly diagnosed patients going forward. Materials and methods Study subjects included 1349 cases enrolled in Total Therapy trials (median follow up 7.5 years). Gene expression profiling was used to determine GEP70 risk status, molecular subgroup by UAMS and TC classifications, and to devise a new and extended TC classification (TC10). Interphase FISH associated with IgH translocations and 1q+ and 17p- were used to build GEP proxies. Data from mutational analysis generated by the FoundationOne targeted sequence panel was also incorporated. Results were validated on the UK MRC MyelomaIX and Hovon65/GMMG-4 studies. Results An initial agnostic analysis of GEP data using sparse k-means clustering verified the existence of TC based groups. Six groups were identified that corresponded overwhelmingly with known TC subgroups; CCND1-t(11;14), D1-HRD, D2-HRD, MMSET, MAF/CCND2, and CCND3. Further comparisons between the molecular subgroup and TC classifier revealed that the UAMS 7 subgroups clustered strongly within one predominant TC group: CD-1 and CD-2 to t(11;14), HY to D1, LB and PR to D2, MF to t(14;16) or t(14;20), and MS to t(4;14). As the UAMS molecular subgroups are largely contained within the TC framework, we aimed to extend the TC by developing the TC10. To extend the known TC subgroups, unsupervised clustering was applied to the 3 largest subgroups [t(11;14), D1, and D2] to determine the strongest single divisor within each respective subgroup. The dominant feature within the t(11;14) cases was CD20 expression, while the D1 and D2 subgroups both split according to RRAS2. CD20 is associated with PAX5 and VPREB3 expression, and RRAS2 is associated with decreased PTP4A3 and increased TNFAIP3 and BIRC3 expression. RRAS2 activation within D1 subgroup and CD20 activation within t(11;14) cases corresponds to an increased time to response to induction therapy suggesting they constitute important biological subgroups. The TC10 combines the known etiologic subgroups of the TC with functionally relevant subdivisions to create 10 novel subgroups: t(11;14) CD20+/-, D1: RRAS2+/-, D2: RRAS2+/-, t(4;14), t(14;16), t(14;20), and t(6;14). Analysis of mutational data revealed that RRAS2 and CD20 activation within the D1, D2, and t(11;14) subgroups reduced the number of mutations in the MAPK pathway. Further mutational analysis revealed that median mutational load was highest in t(14;16) and lowest in D2: RRAS2+ subgroups. The GEP70 score identifies 15% of patients with HR disease and is specific for this purpose. In an analysis of risk assessment methods, we compared GEP detected adverse lesions [t(4;14), t(14;16), t(14;20), 17p- and 1q+] with the GEP70 and revealed that GEP70 HR identified samples have lower OS rates than cases with more than one adverse lesion (validated in external sets). GEP70 HR segregates non-uniformly across molecular subgroups as over 40% of all HR cases are found in the TC10 t(4;14), t(14;16), and t(14;20) subgroups. GEP70 HR cases also have a higher mutational load than low risk cases. Furthermore, GEP70 HR is uniquely associated with 1q+ and 17p- as cases with at least one of these adverse lesions are 4.9 times as likely to be GEP70 HR as cases with neither. Conclusion GEP profiling has a central role in simplifying and standardizing the molecular subgroup designation and risk stratifying of MM patients. The GEP70 risk score reliably identifies HR cases and outperforms FISH in risk assessment, even in validation data sets. The TC10 provides a classification system that improves upon previous methods by defining both etiological and functionally meaningful subgroups. Disclosures Stein: University of Arkansas for Medical Sciences: Employment. Davies:University of Arkansas for Medical Sciences: Employment; Celgene: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Onyx: Consultancy. Heuck:University of Arkansas for Medical Sciences: Employment; Celgene: Consultancy; Janssen: Other: Advisory Board; Millenium: Other: Advisory Board; Foundation Medicine: Honoraria. Weinhold:University of Arkansas for Medical Sciences: Employment; Janssen Cilag: Other: Advisory Board. Chavan:University of Arkansas for Medical Sciences: Employment. Thanendrarajan:University of Arkansas for Medical Sciences: Employment. Epstein:University of Arkansas for Medical Sciences: Employment. Yaccoby:University of Arkansas for Medical Sciences: Employment. Zangari:University of Arkansas for Medical Sciences: Employment; Novartis: Research Funding; Onyx: Research Funding; Millennium: Research Funding. van Rhee:University of Arkansa for Medical Sciences: Employment. Kaiser:Janssen: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; BristolMyerSquibb: Consultancy; Chugai: Consultancy. Sonneveld:Janssen-Cilag, Celgene, Onyx, Karyopharm: Honoraria, Research Funding; novartis: Honoraria. Goldschmidt:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; MMRF: Honoraria; CancerNet: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; Weismann Institute: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

: Professional degree graduate students emphasize cultivating application-oriented high-level talents with a solid theoretical foundation and the ability to adapt to the industry, unlike academic degree graduate students. Providing support for national policy, Shanghai universities vigorously cultivate Master of International Business, integrating education with labor demand and cultivating MIB by integrating industry and education, thereby improving students' literacy levels and fostering the development of employment opportunities. It examines the current situation and problems associated with integrating industry and education by examining the master's degree programs in international business offered at Shanghai universities. It argues that the integration of industry and education in Shanghai universities exists in the status quo of dual tutoring, talent cultivation, schoolenterprise associations, and various ways industry and education are integrated.

With the demand of culinary arts graduates in hospitality industry, more higher learning institutions especially private colleges offer the programs. The course syllabus of culinary arts is specifically designed to provide a strong foundation for students who aspire to be chefs in the local and international fields. Students are equipped with a basic education in the culinary skills and knowledge associated with the cognitive and psychomotor domain. This study investigates the influence of the cognitive and psychomotor domain effect to private college student’s performance after internship. The internship program is gradually enhancing the students’ knowledge; confidence level and psychomotor performance which enable them to at least gain confidence when performing their practical assessment after coming back from internship. This is a positive indication in the beginning of the students’ life before expose into a real life work situation. Thus, this research can be a guidance for the private institutional lecturers to look into the effectiveness of cognitive and psychomotor domain of culinary art students’ performance in their internship programs.

Abstract Introduction Extramedullary disease (EMD) is a primary disease manifestation of MM, which while not seen frequently at presentation increases in incidence at relapse where its incidence seems to be increasing following the introduction of novel agents. Patients with EMD have a shorter overall survival as well as an increased incidence of anemia, thrombocytopenia, elevated serum lactate dehydrogenase, cytogenetic abnormalities, and high-risk features as determined by gene expression profiling. There is also an increased incidence of the high risk MAF subtypes t (14:16 or 14; 20). Understanding the biology of EMD and identifying its present could give important information about how to improve the outcome of this group. In this work we have used GEP analysis of bone marrow derived plasma cells to predict the presence of EMD so that we can identify the genomic risk factors that define the features of a plasma cell clone, which can develop the capacity to metastasize outside the BM. Materials and Methods We focused on patients treated on TT protocols, at the UAMS, Myeloma Institute between 1989 - 2010, a total of 1154 patients, of which 46 developed EMD before the start of therapy (EMD-1), and 91 developed EMD after registration to UAMS for MM treatment EMD-2. Results We show that most EMD2 cases (57.14%) develop within 3 years after initiation of therapy at the UAMS with few cases developing after this time. Predicting the risk of EMD Combining patients with EMD1 and EMD2 diagnosis within 3 years gave a total of 98 EMD cases. We used 824 samples from 1017 myeloma patients who never developed EMD and had follow up at least 3 years as a comparator group. The data were divided into training (n=619 with 66 EMD cases and 553 controls) and test sets (n=303 with 32 EMD cases and 271 controls). Using the training set, we identified 5 significant gene probes (with a q value < 0.001) and made a score to predict cases and controls. The sensitivity and specificity turned out to be 74.24% and 77.40% in the training set, and 56.25% and 76.75% in the test set, respectively. Predicting the time to EMD2 We tested whether we could predict time to EMD2 based on using baseline GEP samples. In this analysis, all EMD2 cases and controls were included. We divided the data into training (n=743 with 61 EMD2 and 682 controls) and test sets (n=365 with 30 EMD2 and 335 controls). By fitting a uniform Cox regression model to each gene in the training set, we identified 68 gene probes that are associated with time to EMD2 (with a q-value <0.1). We then created a score based on the 68 gene probes and identified an optimal cutoff based on the training set. Applying the optimal cutoff to both training and test sets, we found that the new 68-gene high/low risk model is a good predictor on the cumulative incidence of EMD2 (p value < 0.0001). Conclusion We show that EMD2 cases mostly occur within 3 years of diagnosis and a 68 gene based risk score that can predict a cumulative incidence of EMD. Of the 68 genes that are used to develop the prognostic score for EMD, 6 genes are also part of the 70-gene risk score developed by our group. GEP studies can help us identify EMD-specific gene signature that can further help develop target agents. Figure 1. Figure 1. Disclosures Waheed: University of Arkansas for Medical Sciences: Employment. Wang:Cancer Research and Biostatistics: Employment. Qu:Cancer Research and Biostatistics: Employment. Heuck:Millenium: Other: Advisory Board; Foundation Medicine: Honoraria; Janssen: Other: Advisory Board; University of Arkansas for Medical Sciences: Employment; Celgene: Consultancy. Matin:University of Arkansas for Medical Sciences: Employment. Jethava:University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Hoering:Cancer Research and Biostatistics: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Davies:University of Arkansas for Medical Sciences: Employment; Millenium: Consultancy; Onyx: Consultancy; Celgene: Consultancy; Janssen: Consultancy. Morgan:Weismann Institute: Honoraria; University of Arkansas for Medical Sciences: Employment; CancerNet: Honoraria; MMRF: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract Introduction: We have previously used global gene expression (GEP)-based clinical pharmacogenomics of dexamethasone, thalidomide, pomalidomide and bortezomib (Bor) to understand their mechanism of actions and how this impacts their clinical efficacy in multiple myeloma (MM) patients. High dose therapy with melphalan (Mel) followed by autologous stem cell transplantation is a major treatment regimen for MM and consequently assessing the pharmacogenomics of Mel is clinically relevant. Importantly not all patients benefit from Mel exposure and, therefore, it remains important to understand the molecular mechanism of its actions and how they underlie treatment resistance. Materials and methods: 252 newly diagnosed MM patients randomized to Total Therapy (TT)4 (GEP70 low-risk, N=210) and TT5 (GEP70 high-risk, n=42) clinical trials received single administration of Bor (1.0mg/m2) followed after 48 hrs latter by a single administration of Mel (10mg/m2). BM aspirates were obtained at baseline, 48 hrs post-Bor and 48 hrs Post-Mel. Purified CD138-selected MM cells underwent GEP analysis using the Affymetrix U133plus2 microarrays and the results generated were analyzed using Gene Set Enrichment Analysis (GSEA) and Ingenuity. The effect of Mel on expression of cell surface receptors in MM cell lines was validated by flow cytometry. Results: Expression of 176 probe sets was changed 48 hours after a single Bor administration at FDR < 0.01, and expression of 5117 additional probe sets was further changed after Mel. Expression of 6309 probe sets was changed when comparing post-Mel to baseline, of these 108 were also changed post-Bor and 4043 overlapped with changes observed between post-Mel and post-Bor. By utilizing GSEA and Ingenuity we identified the top pathways associated with Mel activity including activation of p53, nitrogen metabolism and metabolism of xenobiotics by p450, whereas Bor was associated with proteasome activation. Bor and Mel both downregulated pathways related to cell cycle and DNA replication and damage response. Top listed genes differentially expressed between baseline and post-Mel and/or post-Bor and post-Mel and reportedly linked to MM pathogenesis include underexpression of IRF4, ASPM, MYC and NEK2, and upregulation of TNFSF10 (TRAIL), MDM2, BAX and KLF9. Among the top upregulated genes by Mel were also set of 7 cell surface receptors (MERTK, CXCR4, OGFRL1, INSR, TGFBR2, S1PR1, IL1R2) and 5 cytokines (AREG, TNFSF8, BDNF, IGF1, TNFSF15). We initially focused our analysis on MERTK and CXCR4 which have been previously implicated in MM and whose expression was upregulated by 2.5 (FDR < 4.6x10-39) and 1.8 (FDR < 3.9x10-36) folds, respectively. Increased expression of MERTK and CXCR4 was associated with shorter progression-free survival (PFS) and over survival (OS) in our Total Therapy trials, including analysis restricted to GEP70 high-risk patients in TT3 and TT5. Moreover, GEP of paired MM cell samples obtained from focal lesion and random BM sites of the same patient (n=170) showed reduced CXCR4 expression in MM cells residing within focal lesions (FDR < 6.1x10-5), further implicating intra-patient heterogeneity of CXCR4 expression in distinct BM niches with response to Mel. To validate direct effect of Mel on these factors at the protein level, flow cytometry analysis for MERTK and CXCR4 was performed on MM cell lines (n=3) following treatment with Mel (5-10µM) or Bor (2.5-5nM) for 72 hrs. Mel but not Bor increased mean fluorescent intensity of MERTK and CXCR4 by 3.1±0.5 (p < 0.05) and 5.1±0.5 (p<0.04) folds, respectively, and the percentage of MERTK- and CXCR4-expressing MM cells by 11.9±2.5 (p < 0.04) and 4.1±0.1 (p < 0.002) folds, respectively, compared to control vehicle-treated cells. Conclusions: The upregulation of cell surface receptors and growth factors by Mel suggests that exposure to the drug promotes the retention of MM cells within the BM and their reliance on the BM microenvironment. This pharmacogenomics approach is useful as it can identify previously unrecognized biomarkers and pathways associated with Mel activity and drug resistance in MM patients. Disclosures Epstein: University of Arkansas for Medical Sciences: Employment. Qu:Cancer Research and Biostatistics: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Zangari:Millennium: Research Funding; University of Arkansas for Medical Sciences: Employment; Onyx: Research Funding; Novartis: Research Funding. Heuck:Janssen: Other: Advisory Board; Foundation Medicine: Honoraria; Millenium: Other: Advisory Board; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment. Davies:Millenium: Consultancy; University of Arkansas for Medical Sciences: Employment; Onyx: Consultancy; Celgene: Consultancy; Janssen: Consultancy. Mitchell:Cancer Research and Biostatistics: Employment. Crowley:Cancer Research and Biostatistics: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; CancerNet: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; MMRF: Honoraria; Weismann Institute: Honoraria; University of Arkansas for Medical Sciences: Employment; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

The Post 9/11 GI Bill is leading an increasing proportion of wounded warriors to enter universities. This paper describes the design and development of an adapted supported education intervention for veterans. The intervention trial was one of two projects which grew out of a participatory action research process aimed at supporting reintegration of returning veterans into the civilian community. This intervention is being tested in a foundation-funded randomized controlled trial in a large southwestern university, with participation now extended to student-veterans at colleges around the country. Some protective mechanisms which were found in theory and in prior research were also supported in early results. SEd intervention was associated with the protective mechanisms of support network density, higher mood, and resilience. Practitioners may benefit from the lessons learned in the development of this supported education intervention trial when considering implementation of this complementary intervention for veterans reintegrating into civilian life

In view of the continuing appropriation and conversion of natural land areas in North America for human uses, there is growing concern about the impacts of changing land use on terrestrial bird species. In order to promote conservation of critical remaining habitats for birds, Partners in Flight (PIF) initiated a project in 1997 in which bird conservation plans were prepared by members in each of 60 ecologically defined physiographical areas throughout the United States. Accurate, nationwide information on the location and extent of vegetative cover types, as well as lands under state and federal management, are critically important elements in the creation of effective bird conservation plans. The National Fish and Wildlife Foundation (NFWF) awarded a challenge grant to The Nature Conservancy's (TNC) Wings of the Americas Program to assist Partners in Flight in acquiring land cover data to serve as the foundation of the planning effort. Canon U.S.A., Inc. and the American Bird Conservancy also contributed support toward this goal. The Center for Advanced Spatial Technology at the University of Arkansas was contracted to produce the needed land cover maps and associated tabular products. Digital land cover databases created by the U.S. Forest Service, the U.S. Geological Survey, the Canada Centre for Remote Sensing, the University of California-Santa Barbara Department of Geography, and the U.S. Department of Transportation, Bureau of Transportation Statistics were used in this project. The final spatial products were produced during 1998–1999 and are described in this paper. This effort represents the first nationwide habitat mapping project in the United States aimed at supporting and enhancing conservation of terrestrial bird species.

The article analyzes conditions of development of psychological and pedagogical competence of teachers of special disciplines of technical colleges as a determining factor in the preparation of a highly qualified graduate. An author's scheme of scientific and methodological work of a technical college is proposed, which combines components, principles and functions of the system and conditions of its effective functioning, in which all structural components of the system (goals and objectives, content, forms and methods) are aimed at realizing the result of work and associated with the conditions, principles and functions, and the integrity and systematic use of all the components identified in the complex will contribute to the end result. It is emphasized that an important factor for becoming a beginning teacher is the moral and financial support of a pedagogical employee by the administration of an educational institution. The priority goal of improving the teachers training system is the principle of accessibility of methodological-educational services and orientation to the individual needs of each teacher, and among the ways of solving the set tasks - full-scale introduction of modern computer technologies of teaching. The key conditions for the development of psychological and pedagogical competence of teachers of special disciplines of technical colleges have been formulated, namely: the creation of a system of scientific and methodological work in the educational establishment, which allows to develop the psychological and pedagogical competence of teachers of special disciplines of technical colleges, the formation of internal and external disciplines of teaching professional activity in a technical college, providing scientific and methodological system of educational establishment with information, in particular clouds technology. It is concluded that the implementation of the above-mentioned organizational and pedagogical conditions into the scientific and methodological process of the technical college will become the foundation for the further formation and development of the psychological and pedagogical competence of teachers of special disciplines.

Student transitions from secondary to tertiary education have attracted global attention as universities and colleges of higher education seek to improve student retention. Over the course of one academic year, I documented the transitional experiences of first-year male Emirati students at a college of higher education in a rural location of the United Arab Emirates (UAE). In this paper I describe four categories of cultural border crossing experiences – smooth, managed, difficult, and impossible – with easier and smoother crossing experiences associated with close congruency (related to the students’ self-perceived attitude and scholastic preparedness as broadly reflected in their competence in their second language, English) between the predominantly Arabic life-world associated with Emirati families and government schooling and the dominant Western/English language culture in institutes of higher education. Additionally, I describe and evaluate students’ cultural border crossing experiences with some Foundation program faculty, finding that those teachers who developed a classroom culture based on Kleinfeld’s (1975) notion of ‘warm demandingness’ and caring rapport-building appeared to have the most positive impact upon the students. Implications from this research have the potential to positively impact both the student and faculty classroom experience in the Gulf tertiary classroom, in addition to improving overall student retention rates.

In the face of escalating global concerns about the occurrence of animal disease outbreaks, effective and sustainable methods for the management of animal mortalities have become a critical component of public health and biosecurity strategies. This abstract presents a comprehensive overview of recent advancements in the field of animal mortality management, with a specific focus on innovative technologies, practices, and policies designed to mitigate the environmental, economic, and health impacts associated with mass mortalities during disease outbreaks. (1) Emerging technologies for mortality disposal: this section highlights current technologies such as composting, shallow burial with carbon, rendering, and incineration that offer more efficient and environmentally responsible alternatives to traditional disposal methods like deep burial and open burning. These technologies demonstrate promise in minimizing the spread of pathogens and reducing the environmental impact of traditional methods. (ii) biosecurity measures in mortality handling: addressing biosecurity risks associated with the transportation and disposal of animal carcasses is paramount in preventing secondary outbreaks. The abstract examines the opportunities posed by centralized carcass disposal and the protocols required to ensure that proper measures are in place to protect human and animal health. (iii) Regulatory frameworks and policy innovations: a critical aspect of effective mortality management involves the development and implementation of robust regulatory frameworks and guidance documents. This section explores recent policy developments at local, national, and international levels, with a focus on adaptive strategies that promote rapid response and coordination during outbreaks. (iv) Community engagement and stakeholder collaboration: successful mortality management necessitates transparent communication, community engagement, and collaboration among various stakeholders, including government agencies, veterinary professionals, farmers, and the public. This section explores innovative approaches to fostering partnerships and enhancing public awareness and understanding of mortality management practices. By synthesizing recent research and developments in animal mortality management, this abstract provides a comprehensive resource for policymakers, veterinarians, researchers, and practitioners involved in public health and biosecurity efforts. These advancements offer a promising foundation for more effective, environmentally conscious, and sustainable approaches to managing animal mortalities during disease outbreaks.

The year 2010 brought an unprecedented public health response to the novel H1N1 influenza pandemic. Included in that response were colleges and universities across the globe. At universities not associated with medical centers, medical directors of student health looked to nursing faculty or nurse practitioner directors of student health for leadership. From the day novel H1N1 was formally declared a public health emergency, Arkansas State University utilized a nurse faculty member with expertise in homeland security as its Incident Commander. A portion of the nurse's time was dedicated to managing the incident. The nurse was positioned to provide guidance and lead the response with an understanding of university structures as well as business and academic continuity. From the beginning, the nurse utilized the Incident Command System to manage the response. Portions of the University's Incident Command structure were activated and Incident Command meetings were held no less than every two weeks. A tabletop exercise was developed specifically for a university setting and to give University officials practice at pandemic management. The nurse's clinical focus and pre-established relationships with disaster response and public health officials allowed critical access to important resources that the University would have otherwise gone without. She guided the University through redefining their pandemic plan, including assisting residence life in establishing alternative housing for sick students. An on-line reporting system was developed that was utilized by faculty, students, staff, and other concerned constituents. A public awareness campaign on the campus was instituted and 1,000 posters were posted around campus encouraging sick students to stay home and/or seek medical care. The World Health Organization, (US) Centers for Disease Control and Prevention, and Department of Education guidelines were monitored and implemented. Two mass-immunization clinics were held on the campus with > 7,000 immunizations provided.

Objective: To find the frequency and risk factors associated with musculoskeletal pain (MSP) among the medical students of Rawalpindi. Study Design: Analytical cross-sectional study Place and Duration of Study: Army Medical College students, Rawalpindi Pakistan, were enrolled from Mar 2022 to Jul 2022. Methodology: An online, self-administered, altered version of the standardized Nordic Questionnaire was distributed among the students of Army Medical College, Foundation Medical University and Rawalpindi Medical University. Data were analyzed using IBM SPSS-25. Frequencies and means were calculated. Chi-square test and student’s t test were done to find any significant associations with p-value <0.05 taken as statistically significant. Results: The study population consisted of 371 medical students of which 127(34.2%) were males and 244(65.8%) were females. Musculoskeletal pain prevalence reported in the last week was significantly higher in students of clinical years (p=0.008), those with history of trauma (p=0.005), family history of musculoskeletal pain (p<0.001) and those with a higher screen time (p=0.007). Similarly, musculoskeletal pain prevalence reported in the last year was significantly higher in students of clinical years (p=0.003), those with a history of trauma (p=0.004), family history of musculoskeletal pain (p=0.011) and those with higher screen time (p=0.017). Coffee consumption, hours of study and body mass index had no significant association with musculoskeletal pain prevalence. Conclusion: Musculoskeletal pain prevalence proved to be significantly high among the medical students of Rawalpindi.Awareness needs to be spread about this highly prevalent problem with medical colleges taking steps to reduce the contributing factors.

Background: Medical knowledge is advancing at a rapid pace in a world, where technological evolution is at an all-time high. However, the health-care system falls well short of acceptable standards when it comes to meeting patient demands. Our medical environment, on the other hand, requires conscious revamping to increase healthcare quality. Traditional training approaches are significantly lacking in this era of value-based medicine, which prioritizes quality measurement and provider proficiency. Competency-based medical education (CBME), with its emphasis on individual, programmatic and institutional outcomes, has the ability to realign medical education with this social expectation. However, CBME implementation, on the other hand, is fraught with many challenges. Aim and Objectives: The aim and objective of this article is to study the challenges in implementation of “foundation course (FC)” ofnewly launch CBME in Indian settings. Materials and Methods: The study was conducted in a tertiary care center in the specialty of advanced course in Research Methodology. This was an observational study with records of 180 participants in 2019–2020 year. The average age of group was 13–50 years. Results: One hundred and forty students and 40 teachers from various Medical Colleges had participated in the study. Around 70% participants had rated positive for the implementation of FC, while around 17% rated below average for the implementation of FC. Classes on Communication and Language (52.2%) and Computer and IT (45%) could not be taken was pointed out by the students. 35% of the students and 22.5% of the teachers pointed out that existing infrastructure is not sufficient for implementation of CBME. About 12.5% students express the concern that less study material is available on new CBME and topics included in the FC. Around 40% of the students and 17.5% of the teachers had express their concerned about time management during FC. Conclusion: The education community has begun to address the difficulties associated with implementing of CBME. Models and guidance are available to inform implementation strategies across the educational continuum, with a focus on the more efficient use of resources and technology, as well as the use of milestones and entrustable professional activities-based frameworks.

Background/Context The traditional literature on the history of higher education in the United States focuses on linear explanations of the inexorable growth of the size, mission, and importance of colleges and universities. That approach ignores or minimizes a recurrent strain of discontent with the higher education sector, especially from policy elites. Purpose/Objective/Research Question/Focus of Study This article examines the century-old origins of a continuing reform impulse in higher education. It identifies the reforms in question as “systemic,” both because they extended beyond the workings of individual colleges and universities and because they had at their heart the dream of systemization, linking and coordinating policy at groupings of institutions at the state, regional, or national level. The narrative focuses on the establishment, operations, and ideology of two early philanthropic foundations designed to spur systemic reform in the higher education sector: the Carnegie Foundation for the Advancement of Teaching and the General Education Board. Research Design This article relies on historical analysis informed by organizational theory. Data Collection and Analysis The data for this article come from new archival research, mostly conducted at the Rockefeller Archive Center (Sleepy Hollow, NY), Library of Congress Manuscript Division (Washington, DC), and Columbia University Rare Book and Manuscript Library (New York, NY). Conclusions/Recommendations This article identifies an ideologically consistent, interlocked cohort of reformers whom the author calls “the academic engineers.” These individuals, associated with elite universities and philanthropic foundations, articulated a vision of higher education reform based on increasing the efficiency and utility of institutions and linking them together in a hierarchical system. The author identifies four key features of this vision and describes the academic engineers’ efforts to enact them. The reformers had some successes but failed to realize their overarching goals; in the article's conclusion, the author examines the historical context and organizational theory as partial explanations for this shortfall.

The COVID-19 pandemic disrupted scientific research, teaching, and learning in higher education and forced many institutions to explore new modalities in response to the abrupt shift to remote learning. Accordingly, many colleges and universities struggled to provide the training, technology, and best practices to support faculty and students, especially those at historically disadvantaged and underrepresented institutions. In this study we investigate different remote learning modalities to improve and enhance research education training for faculty and students. We specifically focus on Responsible and Ethical Conduct of Research (RECR) and research mentoring content to help address the newly established requirements of the National Science Foundation for investigators. To address this need we conducted a workshop to determine the effectiveness of three common research education modalities: Live Lecture, Podcast, and Reading. The Live Lecture sessions provided the most evidence of learning based on the comparison between pre- and post-test results, whereas the Podcast format was well received but produced a slight (and non-significant) decline in scores between the pre- and post-tests. The Reading format showed no significant improvement in learning. The results of our workshop illuminate the effectiveness and obstacles associated with various remote learning modalities, enabling us to pinpoint areas that require additional refinement and effort, including the addition of interactive media in Reading materials.

The article is dedicated to the sociological interpretation of such a phenomenon as human capital transfer in educational communities. The first part reveals the content of the concept of «transfer of students’ human capital», while justifying its application in the study of the educational failure/success of schoolchildren and students. The second part presents a theoretical model of the considered phenomenon through such structural elements as goals, subjects, processes and mechanisms. The third part is devoted to the contradictions in the transfer of human capital within educational communities in Russia. The contradictions between goals and interests of the subjects of education are regarded as the key ones. The final part expands on how significant the concept under consideration is to sociology of education. The results of an interdisciplinary study conducted in 2019–2021 in Sverdlovsk region’s educational facilities (schools, colleges, universities) serve as the empirical foundation for the article. It is shown that transfer of students’ human capital is a kind of capital movement, with its features determined by the social nature of educational activities and interaction. The process under study is associated with such a phenomenon as academic success/failure of students, given that while it unfolds the human capital of schoolchildren and students can either be developed or depleted. The transfer of human capital involves three groups of education subjects — actors, agents and participants who perform certain social roles and possess varying opportunities for regulating this process. The empirical data is interpreted based on the proposed theoretical model, with the results indicating the contradictions of the goals, vectors and results of the transfer of human capital among Russian students.

Abstract Background: Whole body medical imaging is an integral component of Multiple Myeloma (MM) evaluation as it reveals bone disease and/or focal lesions. While established imaging techniques, such as PET-CT, are powerful in delineating focal pathologies, they suffer from low specificity when it comes to assessment of diffuse bone marrow (BM) signals. Especially in patients treated with G-CSF, discrimination between malignant and non-malignant BM signals is barely possible. Diffusion-weighted MRI with background suppression (DWIBS) is a novel functional MRI technique which measures water diffusion in vivo. Basically, diffusion of water is more restricted in tissues with high cellularity, making DWIBS a promising tool to investigate malignant diffuse signals. Initially, we searched for an internal reference to classify the level of BM infiltration. We selected the spleen, since it is the abdominal organ with the highest restriction on DWIBS. Unexpectedly, we observed significant heterogeneity in the spleen signal itself including a subgroup of MM patients with total loss of the signal on DWIBS. Perplexingly, these patients suffered from high tumor burden and poor outcome. Here, we report on our strategy to elucidate this phenomenon and to evaluate its clinical value. Methods: We investigated 295 transplant-eligible newly diagnosed MM patients and 72 cases with monoclonal gammopathy of undetermined significance (MGUS). This study was approved by the institutional review board (#205415). DWIBS was performed on a 1.5 Tesla Philips Achieva scanner. The spleen signal was assessed on DWI and ADC maps by two experienced investigators in consensus read. The Kaplan-Meier method was used for survival analyses. Molecular characterization included fluorescence in situ hybridization, and gene expression profiling of CD138-enriched plasma cells (PCs). Differential gene expression was performed using a threshold of 2-fold expression difference. Wilcoxon or Fisher's exact tests were used to compare the median of a continuous variable or the distribution of discrete variables across groups, respectively. Correlation coefficients were determined using Spearman's rank correlation. Results: Absence of the spleen signal on DWIBS was a frequent phenomenon in MM, seen in 71/295 (24%) patients. In all of these patients asplenia was excluded using alternative imaging techniques. Lack of a signal was highly positively associated with tumor-load parameters, such as the degree of BMPC infiltration (P=1x10-10) or International Staging System (ISS) 3 (P=0.0001). In contrast, it was not associated with age, gender, or the tumor progression markers gain(1q) and del(17p). Patients with absence of spleen signal experienced unfavorable outcome (hazard ratio of 1.8 for PFS and OS). In order to further investigate the biological underpinnings of this phenomenon we performed a differential gene expression analysis of purified CD138 MM cells. No differentially expressed genes were found between patients with and without spleen signal, suggesting that the absence of the spleen signal mainly reflected increased tumor burden rather than specific tumor features. As a proof of concept, we addressed the spleen signal in individuals with MGUS, and longitudinally in MM patients who presented with absence of the spleen signal at diagnoses. Indeed, in all 78 individuals with MGUS the signal was preserved, and the majority of MM patients showed re-appearance of the spleen on DWIBS during treatment as the tumor burden declined. Interestingly, re-appearance of the spleen was helpful to distinguish between malignant and non-malignant hyperintensities in the BM, making the spleen signal a promising parameter for MM follow-up investigations. Conclusions: Due to the low frequency of abnormalities affecting the spleen, this organ is often overlooked during abdominal examinations using cross-sectional imaging techniques. Here we show that the spleen signal on DWIBS provides clinically useful information on tumor burden in MM. Moreover, it opens the avenue to distinguish between malignant and reactive BM hypercellularity on imaging in patients receiving treatment. Our observation strongly supports the hypothesis, that the spleen signal is suppressed by a high BMPC involvement. Yet, the reasons for this phenomenon are still elusive. Figure. Figure. Disclosures Roy Choudhury: University of Arkansas for Medical Sciences: Employment, Research Funding. Epstein:University of Arkansas for Medical Sciences: Employment. Barlogie:Dana Farber Cancer Institute: Other: travel stipend; International Workshop on Waldenström's Macroglobulinemia: Other: travel stipend; ComtecMed- World Congress on Controversies in Hematology: Other: travel stipend; European School of Haematology- International Conference on Multiple Myeloma: Other: travel stipend; Celgene: Consultancy, Research Funding; Millenium: Consultancy, Research Funding; Myeloma Health, LLC: Patents & Royalties: : Co-inventor of patents and patent applications related to use of GEP in cancer medicine licensed to Myeloma Health, LLC; Multiple Myeloma Research Foundation: Other: travel stipend. Davies:Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Morgan:Janssen: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding.

Movement education is the most important element in developing human capital. Education is associated with formal forms through institutions such as study classes, schools, colleges and universities. The existence of educational institutions in developing societies is very important to make society have a high level of civilization. Not to mention the education that has an Islamic nuance that is fully supported by the institution of the sultanate and encouraged by the scholars who are willing to put energy and effort so that the dream of the educational institution stands firmly. Sambas is recognized as the portico of Mecca after Acheh because of the role of its educational institutions that produced outstanding scholars in Sambas and even spread throughout the archipelago and Mecca. The objective of this study is to highlight Islamic education figures such as Sultan Muhammad Shafiuddin II bin Sultan Abubakar Tajuddin II (1866 - 1924), Sheikh Ahmad Khathib bin Abdul Ghaffar bin Abdullah bin Muhammad as-Sambasi (1803-1875) and Maharaja Imam Muhammad Basiuni Imran (1885 -1976). While the second objective is to highlight Islamic educational institutes such as Madrasah Al-Sulthaniyah which is the foundation of superior education in Sambas. The methodology of this study is to use a historical methodology that uses the Kuntowijoyo model, which is through 4 stage processes, namely heuristics, criticism, analysis and historical writing (historiography). The results of this study found that Sultan Muhammad Shafiuddin II bin Sultan Abubakar Tajuddin II (1866 - 1924), Sheikh Ahmad Khathib bin Abdul Ghaffar bin Abdullah bin Muhammad as-Sambasi (1803-1875) and Maharaja Imam Muhammad Basiuni Imran (1885-1976) were figures major in Islamic education in Sambas and Madrasah Al-Sulthaniyah became the basis for the development of Islamic education institutions in Sambas.

Highly Pathogenic Avian Influenza (HPAI), particularly caused by the influenza virus A genus, is a paramount concern for global poultry health. The strains associated with HPAI are known to precipitate mortality rates exceeding 90\%. Beyond the immediate and catastrophic impact on poultry, the emergence of HPAI strains disrupts international poultry trade, leading countries to impose trade bans and shake consumer confidence. By September 19th, 2023, Brazil had reported 106 confirmed outbreaks of HPAI. Most of these incidents were linked to wild birds, totaling 103 cases, while backyard chickens accounted for the remaining three. Notably, most of these outbreaks are situated in coastal regions. However, an exception that demanded attention was the HPAI detection in backyard chickens in Bonito, Mato Grosso do Sul. State-wise analysis reveals differential prevalence patterns. São Paulo and Rio Grande do Sul have documented cases far from their primary poultry hubs. In juxtaposition, Espírito Santo's proximity to the outbreak areas heightens its risk profile. The southern broiler-producing regions, which account for a significant 64\% of Brazil's total production and a whopping 79\% of exports, currently face diminished immediate threats due to their inland geographies. Nevertheless, the episode in Bonito-MS underscores the escalating risks even in regions previously considered low-threat and amplifies the call for perpetual vigilance. Brazil's approach to HPAI defense is structured and well-planned, not a result of hasty improvisation or last-minute measures. It's a result of a long-standing commitment and rigorous planning. The country's legal framework for HPAI prevention has evolved since the 1994 introduction of the National Poultry Health Plan. Successive years saw further tightening of regulations, climaxing with the 2013 National Contingency Plan for Avian Influenza, which underwent revision in 2023. Brazil’s strategy to ward off HPAI is deeply rooted in stringent biosecurity measures. Farms are mandated to erect physical barriers, strictly regulate vehicular and human movement, and uphold rigorous cleaning and disinfection standards. Farm personnel are also trained in and adhere to meticulous personal hygiene protocols. Simultaneously, comprehensive waste management practices are firmly in place. Additionally, the Brazilian government plays a proactive role. Border surveillance, active monitoring of avian populations, and the deployment of passive surveillance within commercial flocks manifest the government's unwavering dedication to the poultry sector. One of Brazil's trump cards against diseases like HPAI is its vertically integrated poultry production model. This modus operandi permits companies and cooperatives to oversee every production stage. Such centralized oversight minimizes financial risks, guarantees consistent quality, and facilitates the swift roll-out of biosecurity directives. Traceability, a cornerstone for rapid disease containment, is inherently assured in this system. The private sector in Brazil not only meets governmental biosecurity standards but frequently surpasses them. It's common to see the integration of extended quarantine durations, intensified disinfection routines, and stringent farm access controls. The commitment to a tiered biosecurity mechanism across diverse poultry production stages is a testament to the industry's intent to ensure a holistic health foundation. Brazil's comprehensive and adaptive approach to HPAI is commendable. The country's strategic alignment between governmental regulations and private sector commitment, especially in the face of recent outbreaks, underscores Brazil's unwavering focus on safeguarding its poultry industry. While the road ahead demands continuous vigilance, Brazil's current strategies and learnings provide valuable insights for global stakeholders.

Introduction Treating High Risk myeloma (HRMM) is an important clinical challenge and understanding the basis of its pathogenesis could offer new therapeutic options. At present very few clues exist as to what is crucially deregulated between HR and LR and micro RNA (miR) are prominent candidates. Since the first miRNA was discovered over 20 years ago, the important role of these small noncoding RNA molecules in multiple myeloma pathogenesis has been recognized. In addition to their function in regulating gene expression within their cell of origin, miR molecules encased in exosomes are also secreted into the circulation. In this setting exosomes can deliver their content to other cells throughout the body, and have been suggested to be a key factor mediating the interaction of the MM cells and their microenvironment. We have tested the hypothesis that miR content of exosomes in bone marrow serum of patients with myeloma have an impact on biological behavior and as such can distinguish between patients with GEP 70-defined high- and low-risk disease. Methods Exosomes were isolated from bone marrow serum using Invitrogen kits according to manufacturer's instructions. Aliquots from the resulting samples were analyzed using electron microscopy to confirm the presence of exosomes. The exosome preparations were spiked with the Caenorhabditis elegance miR mimetic Ce_miRNA39_1 as a control, and miR was subsequently isolated using miRNeasy Kit (Qiagen). The miR were converted to cDNA with polyA tailing, pre-amplified 10 cycles. Aliquots of the preamplified cDNA were loaded into the samples wells and primer pairs of 68 miR, reported to be differentially expressed in myeloma or other cancers, were loaded into the reagent wells of Fluidigm's 96x96 Dynamic Array IFCs (integrated fluidic circuit) and the arrays processed on a Fluidigm BioMark. Results were analyzed using the company's Real-Time PCR analysis software. The level of the 68 miRs were analyzed in preamplified exosomal miR cDNA from 13 healthy donors, and 76 untreated NDMM patients (54 low-risk, 22 high-risk as categorized by GEP 70 gene model). Results Electron microscopy analysis confirmed the presence of exosomes, sized between 50 and 150nm in all of the sample preparations. With a cutoff ratio of 1.5, 3 miRs were differentially expressed between HRMM and LRMM: miR-192, and 215 were present at a higher level in exosomes from LRMM (1.6, and 1.8 fold, respectively) than in HRMM, while miR 720 and 1308 were higher in HR MM (2.9 and 3.3 fold, respectively). Of the 4 differentially expressed miRs, 2 ( 192, and 1308) were 2-82 fold higher in MM bone marrow serum exosomes than in exosomes from the healthy donors, one (720) had equal levels, and one (miR-215) was not detected in healthy donor samples. Among the 68 miRs analyzed, 4 were differentially expressed between HR- and LRMM. miRNA 192 and 215 both target the MDM2/TP53 axis, and are lower in bone marrow serum exosomes from HRMM in comparison LRMM. In contrast, miR-720 and 1308 are higher in HRMM. In this context miR-720 inhibits tumor invasion in breast cancer and modulates proliferation in esophageal cancer; miR-1308 is a fragment of t-RNA, targets the apoptotic pathway, and has anti-apoptotic function. It has been reported that miR-137 is deregulated in solid tumors, and that overexpression can induce apoptosis in MM cell lines. It is interesting that it was present in bone marrow serum exosomes from only 2 low-risk myeloma patients and not in exosomes isolated from purified myeloma plasma cells from 12 high-risk patients. Conclusion These results indicate that exosomal microRNA are associated with the risk status of myeloma patients at presentation, either as a reflection of risk or as effectors. Their presence in protecting vesicles in the circulation indicates that miR have the capacity to modulate the properties of the microenvironment and myeloma cells in remote loci. To better elucidate the role of exosomal miR in the interaction of myeloma cells with the microenvironment it is important to determine the source of the exosomes. Figure 1. Figure 1. Disclosures Chen: University of Arkansas for Medical Sciences: Employment. Morgan:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Weismann Institute: Honoraria; MMRF: Honoraria; CancerNet: Honoraria; University of Arkansas for Medical Sciences: Employment; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Barlogie:Multiple Myeloma Research Foundation: Other: Travel Stipend; Dana Farber Cancer Institute: Other: Travel Stipend; International Workshop on Waldenström's Macroglobulinemia: Other: Travel Stipend; ComtecMed- World Congress on Controversies in Hematology: Other: Travel Stipend; European School of Haematology- International Conference on Multiple Myeloma: Other: Travel Stipend; Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Myeloma Health, LLC: Patents & Royalties: Co-inventor of patents and patent applications related to use of GEP in cancer medicine licensed to Myeloma Health, LLC. Epstein:University of Arkansas for Medical Sciences: Employment.

Abstract INTRODUCTION : Leukemia is the seventh leading cause of cancer death in the United States (US) in 2021. The Mortality Incidence Rate Ratio, also known as Mortality-to-Incidence Ratio (MIR), is calculated by dividing the mortality rate by the incidence rate for selected cancers and population. The MIR provides a population-based indicator of cancer survival which has previously been used to assess healthcare disparities among different countries. Here weevaluated the potential association between leukemia MIR and state-based health disparities in the US. METHODS: Leukemia (AML, CML, ALL, CLL and other leukemias) MIRs for 2008-2017 were obtained from United States Cancer Statistics (USCS) database provided by the Centers for Disease Control and Prevention (CDC). America's Health Rankings (AHR), a partnership of the United Health Foundation and the American Public Health Association, evaluates the nation's health on a state-by-state basis by using weighted measures in 5 different categories (25% for Behaviors, 22.5% for Community & Environment, 12.5% for Policy, 15% for Clinical Care, and 25% for Outcomes). AHR then determines state health rankings and reflects state health disparities based on these specific factors. Here we analyzed the potential association between leukemia MIRs and state health rankings by linear regression. RESULTS: From 2008 to 2017, a total of 489,037 people were diagnosed with leukemia and 231,069 people died from leukemia in the US. The 10-year average of age-adjusted incidence rate and mortality rate were 14.2 and 6.7 per 100,000 population respectively. The average MIR between all states was calculated to be 0.470. As seen in Table 1, the lowest MIR (best survival) was found in Florida (0.374), New York (0.391), and New Jersey (0.412) with AHR 34, 19 and 11 respectively. The highest MIR (worst survival) was found in Mississippi (0.579), Wyoming (0.570), and Ohio (0.569) with AHR 50, 24 and 37 respectively. According to AHR, over the last decade, the states with the highest health rankings were reported in Vermont (No. 1), Hawaii (No. 2), and Massachusetts (No. 3) with MIR 0.508, 0.439 and 0.502 respectively. The states with the lowest health rankings were reported in Arkansas (No. 48), Louisiana (No. 49), and Mississippi (No. 50) with MIR 0.559, 0.503 and 0.579 respectively. In our analysis, states with better health rankings were significantly associated with lower MIRs (R 2=0.232, P&lt;0.001), as seen in Figure 1. CONCLUSIONS: There is a remarkable geographic difference in leukemia MIRs in the US between 2008-2017. Leukemia MIR was significantly associated with state health rankings reported by the AHR. Although the quality of clinical care for leukemia patients remains to be an important predictor of mortality, our findings suggest that other aggregate determinants of health, including social, economic, and community and physical environment may also play a vital role in influencing leukemia survival. More in-depth analysis of these data focusing on specific leukemia subtypes as well as other factors (race, gender, age) may be helpful in identifying and addressing other non-medical issues negativity impacting on leukemia outcomes in different geographical regions in the United States. Figure 1 Figure 1. Disclosures Wang: Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau; Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Takeda: Consultancy, Honoraria, Other: Advisory board; Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Advisory Board; Mana Therapeutics: Consultancy, Honoraria; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; DAVA Oncology: Consultancy, Speakers Bureau; Rafael Pharmaceuticals: Other: Data safety monitoring committee; Gilead: Consultancy, Honoraria, Other: Advisory board; Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board; PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board; Genentech: Consultancy; MacroGenics: Consultancy.

Abstract Introduction Gene expression and comprehensive genomic profiling (CGP) underscore the importance of multiple myeloma (MM) being driven by diverse genomic abnormalities and are increasingly being integrated into personalized treatment algorithms to optimize clinical outcomes, in particular that of high risk disease. Furthermore, CGP allow for ultra-deep sequencing of various clinically relevant and targetable genomic alterations using a single assay, with an advantage of detection of low frequency variants. Methods Samples from 578 patients (monoclonal gammopathy of undetermined significance, MGUS, (n=19); smoldering multiple myeloma, SMM, (n=42); or multiple myeloma, MM, (n=517; 87 newly diagnosed (NDMM), 107after treatment (TRMM), and 323 at relapse (RLMM)) were analyzed using the FoundationOne® Heme (F1H) assay. 50 ng of DNA and RNA from CD138+ selected cells were analyzed for genomic alterations including base substitutions, indels, copy number alterations, and rearrangements. Sequencing was performed to a median depth of 468x in 405 genes, as well as selected introns of 31 genes involved in rearrangements. Additionally, matched Gene Expression Profiling (GEP) was performed using Affymetrix U133 Plus 2 array, and GEP70-defined risk status and molecular subgroups were calculated. Results Results of the F1H assay revealed the most common alterations in MM to be: KRAS (28.8%), NRAS (23.2%), TP53 (17.4%), BRAF (6.8%), CDKN2C (6.0%), RB1 (5.8%), TRAF3 (5.8%), DNMT3A (3.9%), TET2 (3.7%) and ATM (2.5%), including mutations, homozygous loss and rearrangements. When these frequencies were split across GEP70 risk groups, TP53, CDKN2C/FAF1, RB1, and the t(4;14) were significantly different (p<0.05). As the disease progressed from MGUS to relapse, the number of mutations showed an increasing trend. Likewise, there were significant differences in the number of mutations between CCND1/CCND3 (CD-1) and low bone disease, CD-1 and hyperdiploid, and hyperdiploid and proliferation groups. In order to identify independent prognostic genomic alterations, we performed a multivariate Cox regression analysis on all the gene alterations that were present in at least 5% of the patient cohort, resulting in identification of four significant alterations: the t(4;14), mutation/loss of TP53, CDKN2C/FAF1 or RB1. Alterations in CDKN2C and RB1 were associated with the PR group. When the MM samples were split according to type (NDMM, TRMM, RLMM) the effect on survival of each of these alteration was more pronounced at relapse, but still present at diagnosis for CDKN2C and t(4;14). Bi-allelic events in CDKN2C, TP53 and RB1 were examined, by both homozygous deletion and monosomy with accompanying mutation, showing the rate of inactivation increased from 9.2% in NDMM to 17.9% at relapse, indicating that bi-allelic inactivation of these genes are correlated with relapse. CDKN2C and TP53 are known prognostic markers but the prognostic significance of RB1 has been debated. Previous data have shown that the association of t(4;14) with del(13q) results in insignificance of del(13q) as a prognostic marker in multivariate analyses. Here, we confirmed that the prognostic effect of RB1 is not due to association with t(4;14), and show that patients with either the t(4;14) or alteration of RB1 have a poor prognosis, which is worse when both lesions are present. Conclusions Using the F1H assay, we establish the mutational spectrum in MM, identifying lesions associated with high risk. This is the first study in MM to identify and confirm the poor prognostic effect of RB1 driven by bi-allelic inactivation, which is more prevalent at relapse. Furthermore, we determined the gene alterations that are independent prognostic markers in relapsed MM, thereby identifying novel therapeutic targets. Disclosures He: Foundation Medicine, Inc: Employment, Equity Ownership. Bailey:Foundation Medicine, Inc: Employment, Equity Ownership. Ashby:University of Arkansas for Medical Sciences: Employment. Zhong:foundation medicine: Employment. Nahas:Foundation medicine: Employment. Ali:Foundation Medicine: Employment, Equity Ownership. Vergillo:Foundation Medicine, Inc: Employment. Ross:Foundation Medicine, Inc: Employment. Miller:Foundation Medicine: Employment, Equity Ownership. Stephens:Foundation Medicine: Employment, Equity Ownership. Barlogie:Signal Genetics: Patents & Royalties. Mughal:Foundation Medicine: Employment, Equity Ownership. Davies:Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Morgan:Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Bristol Meyers: Consultancy, Honoraria; Janssen: Research Funding; Univ of AR for Medical Sciences: Employment.

Abstract Introduction Segmenting multiple myeloma (MM) into subgroups with distinct pathogenesis and clinical behavior is important in order to move forward with advancements in therapy and implement a targeted therapy approach. Current technologies have elucidated five major translocation groups, which have a varying effect on prognosis: t(4;14), t(6;14), t(11;14), t(14;16) and t(14;20) along with recurrent copy number changes including deletion of CDKN2C (1p32.3) and TP53 (17p13.1) as well as gain or amplification of 1q21. However, minor translocation and mutational groups are poorly described because sample numbers are limited in small datasets. The availability of multiple sets of high quality mutation data associated with clinical outcomes has provided a unique opportunity in MM whereby clustering mutational data with chromosomal aberrations in the context of gene expression we can develop a molecular classification system to segment the disease into therapeutically meaningful subgroups. The Multiple Myeloma Genome Project (MGP) is a global collaborative initiative that aims to develop a molecular segmentation strategy for MM to develop clinically relevant tests that could improve diagnosis, prognosis, and treatment of patients with MM. Materials and methods We have established a set of 2161 patients for which whole exome sequencing (WES; n=1436), Whole Genome Sequencing (WGS; n=708), targeted panel sequencing (n=993) and expression data from RNA-Seq and Gene Expression arrays (n=1497) were available. These data were derived from the Myeloma XI trial (UK), Intergroupe Francophone du Myeloma/Dana-Faber Cancer Institute (MA), The Myeloma Institute (AR) and the Multiple Myeloma Research Foundation (IA1 - IA8). We assembled all data on a secure site and analyzed it using a streamlined and consistent pipeline using state of the art tools. First, BAM were converted to FASTQ using Picard tools v2.1.1 to extract read sequences and base quality scores. Next, all reads were realigned to the human genome assembly hg19 using BWA-mem. Duplicate marking and sorting was performed using Picard tools v2.1.1. For QAQC we use FASTQC and Picard tools. We identified somatic single nucleotide variants and indels with Mutect2 using default parameters. Translocations and large chromosomal aberrations were identified using MANTA and breakdancer and inferred copy number abnormalities and homozygous deletions using Sequenza v2.1.2 and ControlFreeC. Results We have begun to integrate these diverse large genomic datasets with various correlates. Samples were stratified by RNA-seq expression values and WES/WGS to identify the main cytogenetic groups with high concordance. In addition to the main translocation groups, translocations into MAFA, t(8;14), were detected in 1.2% of samples by both RNA-seq and WES/WGS. RNA-seq also detected fusion transcripts, including the known Ig-WHSC1 transcript in t(4;14). However, a proportion of identified in-frame fusion genes involved kinase domains consistent with activation of the Ras/MAPK pathway, which may be clinical targets for therapy. The main recurrent mutations included KRAS and NRAS, and negative regulators of the NF-κB pathway. In addition we identified recurrent copy number abnormalities and examined the interaction of these with mutations. This highlighted the interaction of the recurrent changes at 1p, 13q, and 17p with mutation of genes located within these regions, specifically indicating bi-allelic inactivation of CDKN2C, RB1 and TP53. Using WGS and RNA-Seq data we identified recurrent translocations and fusion genes that can be used to instruct therapy. Based on these data and the presence of homogeneous inactivation of key tumor expressed genes we will present clinically relevant clusters of MM that can form the basis of future risk and molecular targeted trials. Interaction of mutation with expression patterns has identified distinct expression signatures associated with mutational groups. Conclusions We have established the largest repository of molecular profiling data in MM along with associated clinical outcome data. Integrated analyses of these are enabling generation of clinically meaningful disease segments associated with differing risk. The MGP intends to build a global network by expanding collaboration with leading MM centers around the world and incorporating additional datasets through current and new collaborations. Disclosures Mavrommatis: Discitis DX: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Employment, Equity Ownership. Ashby:University of Arkansas for Medical Sciences: Employment. Ortiz:Celgene: Employment. Towfic:Celgene: Employment, Equity Ownership; Immuneering Corp: Equity Ownership. Amatangelo:Celgene: Employment, Equity Ownership. Yu:Celgene: Employment, Equity Ownership. Avet-Loiseau:celgene: Consultancy; janssen: Consultancy; sanofi: Consultancy; amgen: Consultancy. Jackson:Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Thakurta:Celgene: Employment, Equity Ownership. Munshi:Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Merck: Consultancy; Pfizer: Consultancy; Oncopep: Patents & Royalties. Morgan:Univ of AR for Medical Sciences: Employment; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Bristol Meyers: Consultancy, Honoraria.

Abstract Introduction Recently a number of clinical trials have reported on a comparison between autologous stem cell transplantation (ASCT) for multiple myeloma (MM) versus conventional dose therapies. These studies have shown that even in the era of "novel agents", early ASCT is associated with significant improvements in progression free survival (PFS). Further a recent population based study has suggested that having received ASCT is one of the most important prognostic factors governing long-term outcomes for patients with MM. These observations prompted us to examine the long-term outcomes achievable in a series of ASCT patients where novel agents were incorporated into patient management and how these outcomes have changed over time. Methods To investigate long-term survival, we followed patients with newly diagnosed MM who received an ASCT at the University of Arkansas for Medical Sciences (UAMS) Myeloma Institute, from 1989 to 2018. Patients with smoldering myeloma, and those who did not receive an ASCT were excluded from the study. In addition to ASCT, patients who were enrolled on a clinical trial received experimental chemotherapeutic regimens determined by the clinical trials protocol being implemented at the time. All other patients received standard therapies appropriate at the time of diagnosis. Based on the year of their first ASCT, patients were separated into time periods that roughly corresponded to the dates of different protocols when novel agents were being tested at UAMS (1997 or earlier [reference group], 1998-2003, 2004-2008, 2009-2013, and 2014 or later). Kaplan-Meier curves with log-rank tests, and Cox proportional hazards models adjusting for age, sex and race/ethnicity were used to evaluate survival during the different time periods. Because the demographics of the UAMS patients have changed over time (with older and non-White patients becoming more common in more recent years), we also explored approaches to correct for temporal changes in both MM patients at UAMS and within the general US population, including a Fine-Gray competing risk analysis, and a relative survival analysis using SEER life tables to account for population differences in mortality by age, year, sex, and race/ethnicity. Results A total of 4,326 MM patients met the eligibility criteria for this study, with 2,465 patients enrolled on a clinical trial. The median follow-up time was 10.4 years, with median overall survival of 6.9 years. In the adjusted Cox proportional hazards model, patients who had their first ASCT in 2014 or later had significantly improved survival compared to those who had their first ASCT in 1997 or earlier (HR, 0.32; 95% CI, 0.25-0.41). Among patients who had a valid cause of death (n=2961), Fine-Gray competing risk analyses confirmed this finding (HR, 0.10; 95%CI, 0.05-0.19). After using SEER life tables to correct for differences in normal mortality, we find less relative excess risk (RER) for MM death with each successive time period compared to the "1997 or earlier" reference group: 1998-2003 (RER, 0.67; 95%CI, 0.57-0.78), 2004-2008 (RER, 0.56; 95% CI, 0.48-0.66), 2009-2013 (RER, 0.56; 95% CI, 0.47-0.66), 2014 or later (RER, 0.31; 95% CI, 0.22-0.42). These results suggest that as chemotherapeutics and patient management strategies have changed over time, the MM survival has steadily and consistently improved at UAMS. Conclusions Our results suggest that after correcting for population differences in mortality by age, sex, year, and race/ethnicity, MM survival in UAMS patients has improved over time. These trends could be due to a number of factors, including improvements in MM therapies, risk stratification models, management of older patients, and increased understanding of MM biology and meaningful prognostic factors. Additional analyses to examine these traits, and Cure-Rate survival models to determine the likelihood of achieving long-term disease-free survivorship, are currently ongoing. Disclosures Davies: MMRF: Honoraria; ASH: Honoraria; Abbvie: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; TRM Oncology: Honoraria. Barlogie:European School of Haematology- International Conference on Multiple Myeloma: Other: travel stipend; ComtecMed- World Congress on Controversies in Hematology: Other: travel stipend; Myeloma Health, LLC: Patents & Royalties: : Co-inventor of patents and patent applications related to use of GEP in cancer medicine licensed to Myeloma Health, LLC; Multiple Myeloma Research Foundation: Other: travel stipend; Dana Farber Cancer Institute: Other: travel stipend; Millenium: Consultancy, Research Funding; International Workshop on Waldenström's Macroglobulinemia: Other: travel stipend; Celgene: Consultancy, Research Funding. Morgan:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Research Funding.

Statement of the problem. The paper is devoted to the analysis of the pedagogical system of piano technique evolution which developed in the works of an outstanding Polish composer, pianist, teacher and conductor M. Moszkowski. Under consideration are pedagogical principles of the musician, his extensive editing work. Under analysis is the instructive pedagogical repertoire of Moszkowski: “School of double notes” op. 64, “A Book of Scales”, which outlines the fingering principles of the musician, etudes op. 72, 78, 91, 92, a collection of compositions “The Master and His Pupil” op. 96 and “Technical sketches” op. 97. The arsenal of techniques used in these works is rich and diverse, which emphasizes the artistic advantages of these compositions. The value of M. Moszkowski’s pedagogical system in the evolution of piano technique and development of a young pianist is defined, since the pedagogical works of the composer can still serve as a good help for middle and high school students of music schools and colleges. The purpose of the article is to reveal the value of M. Moszkowski’s pedagogical system in the evolution of piano technique and development of a young pianist. Methods. The methodological basis of the study is the unity of scientific approaches, among which the most important is a functional one, associated with the analysis of the genre as a typical structure. Results. The study of M. M. Moszkowski’s piano etudes became a significant contribution to the development of West-European art of the second half of the 19th and early 20th centuries. The analysis of etudes allowed highlighting a free choice of figurative and stylistic priorities, tendency towards small size, focus on a certain type of technique, expressiveness of technically virtuoso tasks, use of simple forms, artistic diversity, prevelance of light mood and moving pace. These piano exercises are clearly presented as an integral part of Moszkowski’s pedagogical method, as well as the specifics of the author’s performance style. Moszkowski’s etudes are a kind of bridge between virtuosity skills and bright images, they help not only improve the technique but also develop student’s musicality. Undoubtedly, this approach provides a solid foundation in all areas of piano performance. Moszkowski’s etudes are less difficult to study, they have technical value that can be quickly acquired, but at the same time they are sustainable and program. Sometimes Moszkowski treats the etude genre very freely: as a substitute for another genre (Two miniatures op 67) as part of the dilogy cycle (Caprice-etude and Improvisation op. 70) and others. These works are little used in modern performing practice. At the same time, they represent a very interesting material that clearly reflects the distinctiveness of musical language of late romantic pianists, to which Moszkowski belonged. Conclusions. Special attention should be paid to the composter’s great contribution to the enrichment of the instructive piano repertoire. Unfortunately, pedagogically orientated works are not so often performed in today’s educational practice. Only 15 virtuoso etudes from op. 72. are widely used. It would be very useful for young musicians to get acquainted with numerous etudes of the composer, since they are of unquestionable interest from the viewpoint of the development of both technical skills and figurative thinking of students. This publication is intended to attract the attention of teachers and performers to wider mastering of piano etudes by M. Moszkowski, which would greatly enrich modern piano repertoire. Unfortunately, many piano compositions of the composer, which were created with a pedagogical purpose, are not used widely enough in educational practice today. Many of them are aimed at the development of elementary piano skills necessary for the development of a young performer: five-finger position, scale sequences, and chords. They are very important, that is why they are described in easy etudes, systematizing the basic forms of virtuosity. Such compositions of Moszkowski take the performer from the basics to the tasks of the highest virtuoso difficulty. His pedagogical system allows us to gradually and systematically improve pianism. The piece must be learnt in a certain sequence: mastering the musical text; playing in the tempo specified by the composer; analysis of the content of the work. Indeed, the performer should be able to divide the work into certain stages, especially if it concerns etudes – to strive for the maximum clear statement of the technical task, excluding anything that could hinder its accomplishment.

Introduction: Emicizumab-a subcutaneously administered, bispecific, humanized, monoclonal antibody-promotes effective hemostasis in people with hemophilia A (PwHA). The primary efficacy and safety of emicizumab were reported previously, but long-term data are limited. Here, data from a wide age-range of PwHA with/without factor (F)VIII inhibitors enrolled in the Phase III HAVEN 1 (NCT02622321), HAVEN 2 (NCT02795767), HAVEN 3 (NCT02847637), and HAVEN 4 (NCT03020160) studies are pooled to establish the durable efficacy and safety of emicizumab. Methods: The studies enrolled pediatric and adult PwHA with/without FVIII inhibitors. Participants received emicizumab prophylaxis 1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks. All participants assigned to receive emicizumab (including those assigned to control arms who later switched) are included in this analysis. Participants and/or caregivers recorded outcomes of bleeding events via the Bleed and Medication Questionnaire (BMQ). Data from HAVEN 1-4 were pooled for an aggregate analysis of emicizumab efficacy and safety. Efficacy endpoints include calculated mean annualized bleed rates (ABRs; discrete, consecutive 24-week treatment intervals), model-based ABRs (calculated via negative binomial regression for full study period), percentage of participants with zero and 1-3 treated bleeds, and annualized cumulative dose of coagulation factor (ACD). Safety endpoints include incidence of adverse events (AEs) and AEs of special interest. Results: Overall, 400 PwHA in HAVEN 1, 2, 3 and 4 (n=113, 88, 151, and 48, respectively) are included in the efficacy analysis for a total of 970.3 patient years (cutoff: 15 May 2020). The safety population comprises 399 PwHA who received ≥1 dose of emicizumab (1 PwHA was randomized to receive emicizumab but did not start treatment). The median age at baseline was 28.5 (range 1-77) years. The majority of participants were White (66.8%) or Asian (18.8%); 52.3% had FVIII inhibitors. In the 24 weeks prior to study entry, 60.9% of participants had target joints. The median duration of efficacy period was 120.4 (interquartile range 89.0-164.4) weeks; 85.0% of participants had an efficacy period of ≥74 weeks; 11 participants (2.8%) discontinued study treatment. Across all 4 studies, 90.9-94.8% of the observation period was covered by completed BMQs. Across all studies, the model-based treated bleed ABR was 1.4 (95% confidence interval 1.1-1.7); treated bleed ABRs remained low throughout, and were seen to decrease with successive 24-week treatment intervals (Table 1). During Weeks 121-144 (n=170), 82.4% of participants had zero treated bleeds, and 15.3% of participants had 1-3 treated bleeds. During the same period, 91.8% and 90.0% had zero treated spontaneous/joint bleeds respectively (Figure 1). The proportion of participants with target joints reduced from 60.9% prior to study entry to 4.6% at Weeks 1-24, then &lt;1.5% in all subsequent treatment intervals. ACD of FVIII (Table 2), activated prothrombin complex concentrate (aPCC) and activated recombinant FVII (rFVIIa, Table 3) generally decreased across each 24-week treatment interval. Emicizumab was well tolerated (Table 4), and no participants discontinued due to AEs beyond the five previously described (Oldenburg et al. N Engl J Med 2017; Young et al. Blood 2019; Mahlangu et al. N Engl J Med 2018; Pipe et al. Lancet Haem 2019). At data cut, 1 fatality, 3 thrombotic microangiopathies (TMAs), and 4 thromboembolic events (TEs) have been reported; all but 1 occurred in HAVEN 1. All TMAs and 2 of 4 TEs were associated with concomitant aPCC use. The percentage of participants with ≥1 drug-related AE in Weeks 1-24, 25-48 and 49-72 were 28.8%, 6.8%, and 3.0% respectively; over the same intervals, injection site reactions were observed in 23.3%, 4.8%, and 2.5% of participants. Conclusions: With nearly 3 years of follow-up, emicizumab maintained low bleed rates in PwHA of all ages, with/without FVIII inhibitors. ABRs continued to decrease and the proportion of participants with zero treated bleeds increased with each consecutive 24-week period; the trend was the same for the proportion of participants with zero joint bleeds and almost all target joints resolved. The ACDs of FVIII, aPCC, and rFVIIa decreased with successive treatment intervals. Emicizumab remains well tolerated over long-term follow-up, and no new safety concerns have been identified to date. Disclosures Callaghan: Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Speakers Bureau; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Research Funding; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Hema Biologics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alnylum: Current equity holder in publicly-traded company; Spark: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Roche/Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Speakers Bureau; NovoNordisk: Other, Speakers Bureau; Sancillio: Other. Négrier:CSL Behring, Octapharma, Shire/Takeda, Sobi: Research Funding; CSL, F. Hoffmann-La Roche Ltd, Sobi: Other: Travel support; Bayer, Biomarin, CSL Behring, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Shire/Takeda, Sobi, Spark: Consultancy. Paz-Priel:Genentech, Inc: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Other: All authors received editorial support for this abstract, provided by Scott Battle, PhD, of Health Interactions and funded by F. Hoffmann-La Roche.. Chang:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Chebon:F. Hoffmann-La Roche Ltd: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Lehle:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in private company. Mahlangu:CSL Behring, Catalyst Biosciences, Freeline Therapeutics, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi, Spark and Takeda: Consultancy; South Africa Medical Research Council, Wits Health Consortium, Colleges of Medicine of South Africa: Membership on an entity's Board of Directors or advisory committees; CSL Behring, Catalyst Biosciences, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi, Spark and Takeda: Speakers Bureau; BioMarin, CSL Behring, Freeline Therapeutics, Novo Nordisk, Novartis, Pfizer, Sanofi, F. Hoffmann-La Roche Ltd, uniQure: Research Funding. Young:Bayer, CSL Behring, Freeline, UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding; BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria. Kruse-Jarres:Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Consultancy; CSL Behring, Genentech, Inc., Spark: Research Funding; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Honoraria; F. Hoffmann-La Roche Ltd: Speakers Bureau. Mancuso:Bayer, CSL Behring, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd, Octapharma, Kedrion, Grifols, Sobi, PedNet Foundation: Consultancy; Bayer, CSL Behring, Novo Nordisk, F. Hoffmann-La Roche Ltd, Octapharma, Grifols, Sobi: Speakers Bureau; Bayer, CSL Behring, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd, Octapharma, Kedrion, Grifols, Catalyst, Kedrion, Sobi: Membership on an entity's Board of Directors or advisory committees; Center for Thrombosis and Hemorrhagic Diseases, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy: Current Employment. Niggli:F Hoffmann-La Roche Ltd: Current Employment. Kuebler:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Selak Bienz:F. Hoffmann-La Roche Ltd: Current Employment. Shima:Chugai Pharmaceutical Co., F. Hoffmann-La Roche Ltd, BioMarin, Bayer, Sanofi: Membership on an entity's Board of Directors or advisory committees; Chugai Pharmaceutical Co. , Sanofi, Bayer, Sysmex: Speakers Bureau; Patents related to anti-FIXa/FX bispecific antibodies: Patents & Royalties; Chugai Pharmaceutical Co.: Honoraria; Chugai Pharmaceutical Co. , F. Hoffmann-La Roche Ltd, Sanofi, CSL Behring, KM Biologics, Novo Nordisk, Shire/Takeda: Research Funding; Chugai Pharmaceutical Co.: Consultancy. Jimenez-Yuste:F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer, Grifols, Octapharma, CSL Behring, Bayer: Honoraria; F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer: Consultancy; Grifols, Novo Nordisk, Takeda, Sobi, Pfizer: Research Funding. Schmitt:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Asikanius:Fimea: Current Employment; F Hoffman-La Roche Ltd: Ended employment in the past 24 months; F Hoffmann-La Roche Ltd: Divested equity in a private or publicly-traded company in the past 24 months. Levy:F Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Ended employment in the past 24 months; Spark Therapeutics: Current Employment; Baxalta US: Patents & Royalties: Royalties from ADAMTS13 patent . Pipe:Medical and Scientific Advisory Council to the National Hemophilia Foundation; Medical Advisory Board to World Federation of Hemophilia: Membership on an entity's Board of Directors or advisory committees; Apcintex, Bayer, BioMarin, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., Sangamo Therapeutics, Sanofi, Takeda, Spark Therapeutics, uniQure: Consultancy; Siemens: Research Funding. Oldenburg:Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche, Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Speakers Bureau; Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche. Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Other; Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche, Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Membership on an entity's Board of Directors or advisory committees; University Clinic Bonn: Current Employment; Bayer, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer and Takeda: Research Funding; Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche, Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Honoraria.

This review discusses how teacher knowledge of assistive technology significantly impacts student success with assistive technology and that many teachers enter the field feeling unprepared to implement these technologies with students. This article explores the University of Arkansas at Pine Bluff’s process in setting up an assistive technology laboratory for students to explore. Historically Black Colleges and Universities (HBCU) are currently working harder since the COVID-19 pandemic to address challenges within their communities with accessing updated technology. As well as engaging students and the communities through increasing knowledge about digital and assistive technology by utilizing hands-on techniques. Such experiential learning opportunities are vital to the success of rehabilitation counseling professionals and educators. This paper explores how the lab is set up and the engagement activities to provide a foundation for those looking to develop a comparable lab. Key words: Student success, access, experiential, engagement, educators

This paper looks at Values Education and its implications on Guidance and Counseling, as well as its recommendation for use in the Colleges of Education in Ghana. It considers the classification, methods, theoretical framework, advantages, and disadvantages of values education. The Psychoanalytic and behavioural theories were used to explain the link and effects of people’s past experiences and those of the present experiences. It further examines the values counsellors and counsellees are expected to develop and exhibit, and its implications on Guidance and Counseling services. Published books, articles, and personal observation during teaching and counseling services provided the main sources of information. The study brings to the fore the fact that values education serves as a preparatory ground for effective Guidance and Counseling Services to take place in educational institutions. It is therefore recommended that educators be exposed to values education and be encouraged to teach values that are associated with their courses. This is vital to lay a good foundation for counsellors and counsellees for effective counseling services to go on in the Colleges of Education in Ghana.

The COVID-19 pandemic emptied universities, colleges, and schools across the United States in March 2020, forcing instructors into an unavoidable culture in which a networked commercial technology mediated teaching and learning. In the tradition of critical pedagogy, this article argues that students and instructors alike engaged through the artificial lenses and screens of Zoom. The “pinhole intimacy” of the Zoomscape is assessed using conscientization, the concept offered by the Brazilian educator Paulo Freire, to describe most pedagogy as an oppressive apparatus that can be overcome with direct engagement between students and instructors. In such an opticentric context, the Zoomosphere’s intimacy is used to explore how the emancipation proposed by conscientization might be applied to the culture of pedagogy in a college with a diverse student population, including pedagogical interventions to address the challenges associated with teaching Division I athletes. The context of a large communication department at Boston College provides the empirical foundation for the exploration of coronavirus pedagogy.

This study examined the impact of a National Science Foundation-funded support program for academically promising STEM students from low-income backgrounds. The program operates as a collaborative consortium, bringing together three public community colleges and one private university, to support the retention and graduation of program scholars. Using propensity score matching, we compared 169 program scholars to 169 matched non-scholars with similar demographic, academic, and financial characteristics ( Mage = 24.82 years; 41% female; 60% students of color). Participation in the program was associated with favorable academic outcomes, with large to moderate effect sizes. Specifically, program scholars had significantly higher cumulative and STEM-specific grade point averages than their non-scholar counterparts. They also completed significantly more STEM courses and were less likely to withdraw from college than non-scholars. These findings underscore the potential of comprehensive and equity-oriented approaches to STEM education in facilitating academic success for STEM students, particularly those from low-income backgrounds.

One advantage of online learning settings relative to conventional classrooms is their anytime, anywhere accessibility. While online education programs provide students with flexible learning opportunities free from the restrictions of geographic location, a consistently growing number of students who prefer to learn exclusively online still choose nearby colleges. The choice to attend a local college by exclusively online learners is an interesting phenomenon, because most of these students rarely visit campus at any point in the process of obtaining their degrees. This study aims to explain this localized distance student enrollment pattern using Integrated Postsecondary Education Data System data and Homeland Infrastructure Foundation-Level Data from the fall of 2016. This research uses a multiple regression technique to explain the relationship between institutional factors and localized distance student enrollment patterns in the US. This study utilizes the C2Q (cost, convenience, and quality) model to explain the local orientation of e-learners. The findings show that convenience and quality of education are significantly associated with each local institution’s share of exclusively online learners in the same state.

BackgroundCD161, encoded by killer cell lectin-like receptor B1 gene, is a newly reported candidate inhibitor of tumour-infiltrating T cells. Antibody-mediated CD161 blockade enhances T cell-mediated killing of cancer cells in vitro and in vivo in several tumour types. We evaluated the role of CD161 using The Cancer Genome Atlas (TCGA) Pan-Cancer Data.MethodsCD161 expression was analysed using RNAseq data from TCGA and the Genotype-Tissue Expression (GTEx) database. HPA, GeneCards, and String database were used to explore the protein information of CD161. The prognostic value of CD161 was analysed using clinical survival data from the TCGA. Enrichment analysis of CD161 was conducted using the R package “clusterProfiler”. We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases and performed a correlation analysis between immune cell infiltration levels and CD161 expression. We further assessed the association between CD161 and immune checkpoints, immune activating genes, immunosuppressive genes, chemokines, and chemokine receptors.FindingsCD161 was differentially expressed and predicted better survival status in most tumour types in TCGA. In addition, CD161 expression was significantly associated with immunoregulatory interactions between lymphoid and non-lymphoid cells. CD161 expression was closely correlated with T cell infiltration, immune checkpoints, immune activating genes, immunosuppressive genes, chemokines, and chemokine receptors.InterpretationOur results suggest that CD161 is a potential cancer biomarker. CD161 might synergize with other immune checkpoints to regulate the immune microenvironment, which could be applied in the development of new-targeted drugs for immunotherapy.FundingThis work was supported by the National Nature Science Foundation of China (grant numbers 81773008, 81672756, 81872399, 81972897), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2015), the Natural Science Foundation of Guangdong Province (grant number 2017A030311023), the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program: 2017BT01S131 and the Guangzhou Technology Project (grant number 201804010044), National Key R&amp;D Program of China (Grant Nos. 2020YFC2006400), Key-Area Research and Development Program of Guangdong Province (2019B020227004).

Digital technologies are rapidly changing the process of education. Online courses have become a common tool of gaining knowledge outside the university. Multimedia education, penetrating traditional educational institutions (schools, colleges, and universities), changes the structure of education and brings new elements to the communications during the educational process. This article considers one level of change in the model of education. On the one hand, there are advantages associated with the democratization of education. At the time of their foundation, universities were the creators of new elites – scientific and educational meanwhile, in the twenty-first century, the process of democratization and the accessibility of university education has been linked to the digitalization. On the other hand, territorial and other restrictions have been lifted. And this is a very controversial process that poses many challenges for students, one of the most noticeable of which is the lack of real contact with the teacher and the transformation of the educational process into an ”educational conveyor belt.” At the same time, personal contact with the teacher is becoming more expensive. The authors have collected studies that examine the dynamics of this emerging stratification of education. Based on the work of the pioneers in the study of digital education, the authors develop their ideas, focusing on the formation of the modern models of education, defined as affordable electronic and elite traditional. Keywords: online courses, online education, MOOC

The importance of microbiota in the health and diseases of farm animals has been well-documented for diverse animal species. However, studies on microbiotas in turkey and turkey farms are relatively limited as compared to other farm animal species. In this study, we performed a comprehensive survey of the litter microbiotas in 5 commercial turkey farms in the Northwest Arkansas (H, M, V, K, and R farms) including one farm with positive incidence of cellulitis (R farm). Altogether 246 boot swabs were used for 16S rRNA gene profiling of bacterial communities. At phylum level, 11 major bacterial phyla (≥0.01%) were recovered. At genus level, 13 major bacterial genera were found whose relative abundance were ≥2%. The microbial composition at both phylum and genus levels as well as their diversities varied across different farms, which were further affected by different flocks within the same farms and the ages of turkeys. Generally, the Firmicutes were higher in the flocks of younger birds, while the Actinobacteria and Bacteroidetes were higher in the flocks of the older birds. The Proteobacteria were highly enriched (47.97%) in K farm housing 56-day-old turkeys (K-56), but Bacteroidetes were found the highest in the flock C of M farm housing 63-day-old turkeys (M-C-63; 22.38%), followed by K-84 group (17.26%). Four core bacterial genera (Staphylococcus, Brevibacterium, Brachybacterium, and Lactobacillus) were identified in all samples except for those from R farm. In contrast, 24 core bacterial genera were found based in all cellulitis-associated samples (R farm), including Corynebacterium, an unknown genus of family Bacillaceae, Clostridium sensu stricto 1 (&gt;97% similarity with C. septicum), and Ignatzschineria among others, suggesting their possible roles in etiopathogenesis of cellulitis in turkeys. Overall results of this study may provide valuable foundation for future studies focusing on the role of microbiota in the health and diseases of turkeys.

Abstract Background Efforts to achieve improved student outcomes in STEM are critically reliant on the success of reform efforts associated with teaching and learning. Reform efforts include the transformation of course-based practices, community values, and the institutional policies and structures associated with teaching and learning in higher education. Enacting change is a complex process that can be guided by change theories that describe how and why a desired change takes place. We analyzed the utility of a theory-based change model applied in a higher education setting. Our results provide guidance for change efforts at other institutions. Results Use of the CACAO model to guide the transformation of STEM instruction at a large public university resulted in changes to faculty teaching practices and department culture consistent with the vision defined for the project. Such changes varied across STEM departments in accordance with the emergent nature of project activities at the department level. Our application of the CACAO model demonstrates the importance of (1) creating a vision statement (statement of desired change or end-state); (2) attending to different levels of the organization (e.g., individuals, departments, and colleges); (3) working with change agents who are situated to be effective at different organizational levels; and (4) employing strategies to meet the needs and interests of faculty at different stages of adoption with respect to the desired change. Conclusion Our work, which demonstrates the utility of the CACAO model for change and captures its key elements in a matrix, provides a potential foundation for others considering how to frame and study change efforts. It reinforces the value of using change theories to inform change efforts and creates a structure that others can build on and modify, either by applying our CACAO matrix in their own setting or by using the matrix to identify elements that connect to other change theories. We contribute to the growing body of literature which seeks to understand how change theories can be useful and generalizable beyond a single project.

Abstract Objectives Obese women may be at risk for poor iron status in pregnancy due to pro-inflammatory driven overexpression of hepcidin that leads to decreased iron bioavailability. Our objective was to determine the impact of pre-pregnancy (PP) obesity on maternal iron utilization in the third trimester of a singleton pregnancy. Methods Using the stable isotope 57Fe prepared as an oral ferrous sulfate solution, we measured iron absorption based on red blood cell incorporation in 50 adult (mean age: 27.6 ± 6.8 years) pregnant women [n = 29 PP non-obese (body mass index (BMI) 18.5–29.9 kg/m2) and n = 21 PP obese (BMI ≥ 30.0 kg/m2] at the 32nd-34th gestational week (mean 32.7 ± 0.7 weeks). We also assessed maternal iron status, hepcidin, inflammation, erythropoietin, dietary iron intake and gestational weight gain. Results Iron deficiency defined as hemoglobin < 11.0 g/dL was highly prevalent (PP obese 67% vs. PP non-obese 48%, P = 0.19). 57Fe utilization (PP non-obese 11.2% (interquartile range (IQR), 8.3) vs. PP obese 7.7% (IQR 8.9), P = 0.23), hepcidin, hemoglobin, and soluble transferrin receptor was similar between the PP BMI groups. PP obesity was associated with significantly higher ferritin, high sensitivity C-reactive protein, and total body iron. In the women who were non-obese PP, 57Fe utilization was not linearly associated with any of the iron-related or inflammatory indices tested. However, 57Fe utilization was significantly inversely associated with serum ferritin (r = −0.42) and serum hepcidin (r = −0.48) in women with PP obesity. In post-hoc analysis, compared to non-obese women, iron utilization was 23% lower in women with class 2 and 3 PP obesity and 3% lower in women with class 1 PP obesity, respectively. Conclusions Iron utilization from an oral ferrous sulfate solution in the third trimester of pregnancy was similar in women with and without PP obesity. Given the growing prevalence of class 2 and 3 obesity among reproductive age women, and the importance of iron for optimal maternal and fetal health, our post-hoc analysis suggests that future efforts should examine iron utilization in women with severe PP obesity. Funding Sources Robert Wood Johnson Foundation, Nurse Faculty Scholars Program #72,117 and University of Illinois at Chicago Colleges of Nursing and Medicine.

Abstract It has long been acknowledged that personal competencies are required for success in medical school, residency training, and medical practice. Over the last decade, medical schools have begun to introduce standardized assessments of personal competencies, but many still rely on interviews to assess these competencies, which occur after about half of the applicant pool has already been screened out. In this article, the authors discuss the development, evaluation, and launch of the Association of American Medical Colleges (AAMC) situational judgment test (SJT) for use in medical school admissions. The AAMC SJT is designed to assess an examinee’s understanding of effective and ineffective behaviors related to the core competencies for entering medical students, including service orientation, social skills, cultural competence, teamwork, ethical responsibility to self and others, reliability and dependability, resilience and adaptability, and capacity for improvement. The authors evaluate the evidence for the need for SJTs in medical school admissions by exploring common derailers in medical school, gaps in the admissions process regarding information about personal competencies, and the challenge of conducting holistic review in a high-volume context. They summarize existing research from the employment, international medical education, and residency selection contexts suggesting that SJT scores are positively associated with subsequent performance and may add value to the admissions process. The authors discuss 5 goals that were the foundation for developing the AAMC SJT: (1) assess the preprofessional competencies needed for success in medical school using a proven method, (2) enable holistic review in a high-volume admissions context, (3) create and share a program of research to support the appropriate use of SJT scores, (4) signal the need for preparation in professionalism to learners, and (5) balance the need for a new assessment with minimizing the burden and risk for applicants.

Abstract Background Professional satisfaction of health professional students can impact on their medical professional achievement. Understanding the professional satisfaction of health professional students and identifying its relative factors is beneficial to strengthen the professionalism education of health professional students, and provide solid foundation for future medical achievements. Methods A self-made questionnaire was used to survey undergraduate students of six medical universities in Hebei province. The survey included three aspects: students’ basic situation, professional selection and cognition, and basic situation of colleges. The Kruskal–Wallis H test was used to compare the professional satisfaction of students with different characteristics. All covariates were used in the ordinal logistics regression analysis to identify the independent factors associated with professional satisfaction. Results A total of 1238 (97.7%) students responded to the questionnaire in the survey, and 66.0% were women. Students with public health majors had decreased satisfaction compared with those with clinical-related majors. Professional satisfaction decreased among women compared with men. The non-first-choice students had lower professional satisfaction compared with the first-choice students. Students who chose their volunteer with the help of others had lower professional satisfaction compared with students who independently chose their volunteer. Students who did not understand the employment status had lower professional satisfaction compared with students who understood the employment status. Students with fewer employment prospects had lower professional satisfaction compared with students with bright employment prospects. Students generally dissatisfied with the canteen had lower professional satisfaction compared with students satisfied with the canteen. Students who were very satisfied or satisfied with teaching levels were more likely to have professional satisfaction. Conclusions The professional satisfaction of health professional undergraduates in Hebei province is high. Employment-related aspects and university environment influence professional satisfaction including canteens, understanding of employment status, teachers’ teaching level, etc., which are the main factors affecting professional satisfaction, but the factors such as student employment prospects and majors cannot be changed in the current environment.

Abstract Background Head injury (HI) in older adults due to low-energy falls result in a substantial number of emergency department (ED) attendances. However, mortality associated with minor HI is very low. Reducing conveyance to hospital is important for older adults and is a priority for the National Health Service (NHS). Therefore, paramedics are required to make accurate decisions regarding conveyance to the ED. This study used routine data and semi-structured interviews to explore the factors that influence paramedic decision-making when considering whether to convey an adult aged 65 years and over with a minor HI to the ED. Methods Semi-structured telephone interviews were completed with ten UK paramedics from a single EMS (ambulance) provider organisation. Interviews explored the factors influencing the paramedics’ conveyance decision-making in adults aged 65 years and over with a minor HI. Data were initially analysed inductively to develop a thematic framework. A retrospective analysis of ambulance service data was also completed to determine the scope and scale of the issue in Southwest England. An in-depth audit of 100 conveyed patient records was used to determine the proportion of patients conveyed to the ED who met National Institute for Health and Care Excellence (NICE) and Joint Royal Colleges Ambulance Liaison Committee (JRCALC) guidelines. Results In 2019 South Western Ambulance Service NHS Foundation Trust (SWASFT) attended 15,650 emergency calls to patients aged 65 and over with minor HI, with 70.5% conveyed to ED. 81% of conveyed patients met NICE and JRCALC guideline criteria for conveyance, with the remainder conveyed due to wound care or other medical concerns. The framework developed from the interviews comprised four themes: resources; patient factors; consequences; paramedic factors. Important factors included: the patient’s social situation; guidelines; clinical support availability; the history and presentation of the patient; risk. Conclusion This study examined paramedic conveyance decisions for older people with minor HI. It identified multiple influencing factors, highlighting the complex nature of these decisions, and may serve as a basis for developing an intervention to safely decrease ED conveyance in this patient group.

ObjectiveTo provide tools to generate national and local syndromic surveillance electronic messaging specifications and to test implementations in which the set of requirements have been implemented in order to confirm or refute the conformance to those requirements, thereby promoting healthcare information technology (HIT) interoperability in the public health sector.IntroductionThe ability to harness data science for use in improving population health and public health surveillance begins with the application of interoperability standards to electronic messaging for data exchange between HIT used by public health authorities (PHAs) and the providers who submit patient data to them. When electronic transmissions between these entities are not based on interoperability standards, the patient data that are exchanged may be incomplete, inaccurate, invalid, and/or untimely. As a result, local PHAs and the Centers for Disease Control and Prevention (CDC) may be unable to fulfill their goals of monitoring public health trends and improving population health.MethodsAs part of the effort to meet the need for the application of interoperability standards to electronic messaging for data exchange between HIT modules that submit and collect syndromic surveillance data for public health, the National Institute of Standards and Technology (NIST), in collaboration with the CDC and the International Society for Disease Surveillance (ISDS), developed and maintains a set of validation tools. These tools are focused on standardized syndromic surveillance messaging and are used for HIT certification testing by the Office of the National Coordinator (ONC) and for on-boarding by various public health jurisdictions in the US. In addition, ISDS informatics personnel are using the NIST Implementation Guide Authoring and Management Tool (IGAMT) for creating the first HL7-ballotted version of a guide for syndromic messaging, the HL7 2.5.1 Implementation Guide for Syndromic Surveillance Release 1. This guide is a messaging specification that defines how disparate healthcare applications are to codify and transmit administrative and clinical data for public health surveillance and response. IGAMT is part of an integrated platform that also includes the NIST Test Case Authoring and Management Tool (TCAMT), a Testing Infrastructure and Framework, and the NIST General Validation Tool (GVT). This Web-based platform enables domain experts, such as the ISDS informatics experts, to control the automatic process for generating computable standards and associated testing tools.ResultsDeveloped through collaboration between NIST, the CDC, and ISDS, the 2015 Edition Syndromic Surveillance Test Suite has been used in the ONC HIT Certification Program for validating over one hundred HIT modules against the syndromic messaging guide developed by the CDC and the Public Health Information Network, the PHIN Guide for Syndromic Surveillance Messaging Release 2.0 and the associated Erratum. During the collaborative process, NIST contributed expertise based on many years of co-authoring and using HIT interoperability specifications, and the CDC and ISDS contributed expertise pertaining to the syndromic surveillance domain. Outcomes of this process included increased awareness by all involved parties regarding the challenges of writing computable standards and the challenges associated with testing HIT under constrained circumstances, such as with the ONC HIT Certification Program. The recognition of the need for well-defined standards, as well as testing using real-world scenarios and clinical data, led to the development of IGAMT and TCAMT for automating the production of these artifacts; and with these tools came the ability to automate generation of testing resources, such as syndromic surveillance validation tools that are customized to national-level specifications as well as to state/local-level specifications for use in on-boarding procedures. As of early 2017, states with jurisdictions requiring providers to validate the ability of their HIT modules to generate syndromic messages using the NIST national-level Syndromic Surveillance Test Suite in their on-boarding process included Arkansas, Florida, Indiana, Kansas, Maryland, South Carolina, and Washington. Now that a national-level HL7-balloted syndromic surveillance implementation guide has been generated using IGAMT, representatives of several additional PHAs have expressed interest in using the components of the NIST Integrated Platform for generating local-level specifications and testing tools. State and local jurisdictions often require certain data to be submitted in addition to the data required by the national-level specification. Local-level testing tools used during the on-boarding process would enable jurisdictions to validate syndromic messages created by submitters in order to confirm or refute the conformance to the local-level requirements.ConclusionsImproving population health and public health surveillance by utilizing the power of data science requires the ubiquitous deployment of standards-based data exchange, that is, interoperability, between the numerous disparate HIT modules in use by providers and PHAs today. NIST has created a development platform that enables the domain experts at the CDC and ISDS to use automated tools to generate national- and local-level syndromic surveillance electronic messaging specifications and the associated testing tools that confirm or refute conformance to the requirements in these specifications. These tools promote interoperability as the foundation for harnessing data science for the benefit of the public and the public health entities that serve them.

Photo by niu niu on Unsplash ABSTRACT Shackling prisoners has been implemented as standard procedure when transporting prisoners in labor and during childbirth. This procedure ensures the protection of both the public and healthcare workers. However, the act of shackling pregnant prisoners violates the principles of ethics that physicians are supposed to uphold. This paper will explore how shackling pregnant prisoners violates the principle of justice and beneficence, making the practice unethical. INTRODUCTION Some states allow shackling of incarcerated pregnant women during transport and while in the hospital for labor and delivery. Currently, only 22 states have legislation prohibiting the shackling of pregnant women.[1] Although many states have anti-shackling laws prohibiting restraints, these laws also contain an “extraordinary circumstances” loophole.[2] Under this exception, officers shackle prisoners if they pose a flight risk, have any history of violence, and are a threat to themselves or others.[3] Determining as to whether a prisoner is shackled is left solely to the correctional officer.[4] Yet even state restrictions on shackling are often disregarded. In shackling pregnant prisoners during childbirth, officers and institutions are interfering with the ability of incarcerated women to have safe childbirth experiences and fair treatment. Moreover, physicians cannot exercise various ethical duties as the law constrains them. In this article, I will discuss the physical and mental harms that result from the use of restraints under the backdrop of slavery and discrimination against women of color particularly. I argue that stereotypes feed into the phenomenon of shackling pregnant women, especially pregnant women of color. I further assert that shackling makes it difficult for medical professionals to be beneficent and promote justice. BACKGROUND Female incarceration rates in the United States have been fast growing since the 1980s.[5] With a 498 percent increase in the female incarceration population between 1981 and 2021, the rates of pregnancy and childbirth by incarcerated people have also climbed.[6],[7] In 2021, over 1.2 million women were incarcerated in the United States.[8] An estimated 55,000 pregnant women are admitted to jails each year.[9],[10] Many remain incarcerated throughout pregnancy and are transported to a hospital for labor and delivery. Although the exact number of restrained pregnant inmates is unclear, a study found that 83 percent of hospital prenatal nurses reported that their incarcerated patients were shackled.[11] I. Harms Caused by Shackling Shackling has caused many instances of physical and psychological harm. In the period before childbirth, shackled pregnant women are at high risk for falling.[12] The restraints shift pregnant women’s center of gravity, and wrist restraints prevent them from breaking a fall, increasing the risk of falling on their stomach and harming the fetus.[13] Another aspect inhibited by using restraints is testing and treating pregnancy complications. Delays in identifying and treating conditions such as hypertension, pre-eclampsia, appendicitis, kidney infection, preterm labor, and especially vaginal bleeding can threaten the lives of the mother and the fetus.[14] During labor and delivery, shackling prevents methods of alleviating severe labor pains and giving birth.[15] Usually, physicians recommend that women in labor walk or assume various positions to relieve labor pains and accelerate labor.[16] However, shackling prevents both solutions.[17] Shackling these women limits their mobility during labor, which may compromise the health of both the mother and the fetus.[18] Tracy Edwards, a former prisoner who filed a lawsuit for unlawful use of restraints during her pregnancy, was in labor for twelve hours. She was unable to move or adjust her position to lessen the pain and discomfort of labor.[19] The shackles also left the skin on her ankles red and bruised. Continued use of restraints also increases the risk of potentially life-threatening health issues associated with childbirth, such as blood clots.[20] It is imperative that pregnant women get treated rapidly, especially with the unpredictability of labor. Epidural administration can also become difficult, and in some cases, be denied due to the shackled woman’s inability to assume the proper position.[21] Time-sensitive medical care, including C-sections, could be delayed if permission from an officer is required, risking major health complications for both the fetus and the mother.[22] After childbirth, shackling impedes the recovery process. Shackling can result in post-delivery complications such as deep vein thrombosis.[23] Walking prevents such complications but is not an option for mothers shackled to their hospital beds.[24] Restraints also prevent bonding with the baby post-delivery and the safe handling of the baby while breast feeding.[25] The use of restraints can also result in psychological harm. Many prisoners feel as though care workers treat them like “animals,” with some women having multiple restraints at once— including ankles, wrists, and even waist restraints.[26] Benidalys Rivera describes the feeling of embarrassment as she was walking while handcuffed, with nurses and patients looking on, “Being in shackles, that make you be in stress…I about to have this baby, and I’m going to go back to jail. So it’s too much.”[27] Depression among pregnant prisoners is highly prevalent. The stress of imprisonment and the anticipation of being separated from their child is often overwhelming for these mothers.[28] The inhumane action has the potential to add more stress, anxiety, and sadness to the already emotionally demanding process of giving birth. Shackling pregnant prisoners displays indifference to the medical needs of the prisoner.[29] II. Safety as a Pretense While public safety is an argument for using shackles, several factors make escape or violence extremely unlikely and even impossible.[30] For example, administering epidural anesthesia causes numbness and eliminates flight risk.[31] Although cited as the main reason for using shackles, public safety is likely just an excuse and not the main motivator for shackling prisoners. I argue that underlying the shackling exemplifies the idea that these women should not have become pregnant. The shackling reflects a distinct discrimination: the lawmakers allowing it perhaps thought that people guilty of crimes would make bad mothers. Public safety is just a pretense. The language used to justify the use of restraint of Shawanna Nelson, the plaintiff in Nelson v. Correctional Medical Services, discussed below, included the word “aggressive.”[32] In her case, there was no evidence that she posed any danger or was objectively aggressive. Officer Turnesky, who supervised Nelson, testified that she never felt threatened by Nelson.[33] The lack of documented attempts of escape and violence from pregnant prisoners suggests that shackling for flight risk is a false pretense and perhaps merely based on stereotypes.[34] In 2011, an Amnesty International report noted that “Around the USA, it is common for restraints to be used on sick and pregnant incarcerated women when they are transported to and kept in hospital, regardless of whether they have a history of violence (which only a minority have) and regardless of whether they have ever absconded or attempted to escape (which few women have).”[35] In a 2020 survey of correctional officers in select midwestern prisons, 76 percent disagreed or strongly disagreed with restraining pregnant women during labor and delivery.[36] If a correctional officer shackles a pregnant prisoner, it is not because they pose a risk but because of a perception that they do. This mindset is attributed to select law enforcement, who have authority to use restraints.[37] In 2022, the Tennessee legislature passed a bill prohibiting the use of restraints on pregnant inmates. However, legislators amended the bill due to the Tennessee Sherriff Association’s belief that even pregnant inmates could pose a “threat.”[38] Subjecting all prisoners to the same “precautions” because a small percentage of individuals may pose such risks could reflect stereotyping or the assumption that all incarcerated people pose danger and flight risk. To quell the (unjustified) public safety concern, there are other options that do not cause physical or mental harm to pregnant women. For example, San Francisco General Hospital does not use shackles but has deputy sheriffs outside the pregnant women’s doors.[39] III. Historical Context and Race A. Slavery and Post-Civil War The treatment of female prisoners has striking similarities to that of enslaved women. Originally, shackling of female slaves was a mechanism of control and dehumanization.[40] This enabled physical and sexual abuses. During the process of intentionally dehumanizing slaves to facilitate subordination, slave owners stripped slave women of their feminine identity.[41] Slave women were unable to exhibit the Victorian model of “good mothering” and people thought they lacked maternal feelings for their children.[42] In turn, societal perception defeminized slave women, and barred them from utilizing the protections of womanhood and motherhood. During the post-Civil War era, black women were reversely depicted as sexually promiscuous and were arrested for prostitution more often than white women.[43] In turn, society excluded black women; they were seen as lacking what the “acceptable and good” women had.[44] Some argue that the historical act of labeling black women sexually deviant influences today’s perception of black women and may lead to labeling them bad mothers.[45] Over two-thirds of incarcerated women are women of color.[46] Many reports document sexual violence and misconduct against prisoners over the years.[47] Male guards have raped, sexually assaulted, and inappropriately touched female prisoners. Some attribute the physical abuse of black female prisoners to their being depicted or stereotyped as “aggressive, deviant, and domineering.”[48] Some expect black women to express stoicism and if they do not, people label them as dangerous, irresponsible, and aggressive.[49] The treatment of these prisoners mirrors the historical oppression endured by black women during and following the era of slavery. The act of shackling incarcerated pregnant women extends the inhumane treatment of these women from the prison setting into the hospital. One prisoner stated that during her thirty-hour labor, while being shackled, she “felt like a farm animal.”[50] Another pregnant prisoner describes her treatment by a guard stating: “a female guard grabbed me by the hair and was making me get up. She was screaming: ‘B***h, get up.’ Then she said, ‘That is what happens when you are a f***ing junkie. You shouldn’t be using drugs, or you wouldn’t be in here.”[51] Shackling goes beyond punishing by isolation from society – it is an additional punishment that is not justified. B. Reproductive Rights and “Bad Mothers” As with slaves not being seen as maternal, prisoners are not viewed as “real mothers.” A female prison guard said the following: “I’m a mother of two and I know what that impulse, that instinct, that mothering instinct feels like. It just takes over, you would never put your kids in harm’s way. . . . Women in here lack that. Something in their nature is not right, you know?”[52] This comment implies that incarcerated women lack maternal instinct. They are not in line with the standards of what society accepts as a “woman” and “mother” and are thought to have abandoned their roles as caretakers in pursuit of deviant behaviors. Without consideration of racial discrimination, poverty issues, trauma, and restricted access to the child right after delivery, these women are stereotyped as bad mothers simply because they are in prison. Reminiscent of the treatment of female black bodies post-civil war and the use of reproductive interventions (for example, Norplant and forced sterilization) in exchange for shorter sentences, I argue that shackles are a form of reproductive control. Justification for the use of shackles even includes their use as a “punitive instrument to remind the prisoner of their punishment.”[53] However, a prisoner’s pregnancy should have no relevance to their sentence.[54] Using shackles demonstrates to prisoners that society tolerates childbirth but does not support it.[55] The shackling is evidence that women are being punished “for bearing children, not for breaking the law.”[56] Physicians and healthcare workers, as a result, are responsible for providing care for the delivery and rectifying any physical problems associated with the restraints. The issues that arise from the use of restraints place physicians in a position more complex than they experience with regular healthy pregnancies. C. Discrimination In the case of Ferguson v. City of Charleston, a medical university subjected black woman to involuntary drug testing during pregnancy. In doing so, medical professionals collaborated with law enforcement to penalize black women for their use of drugs during pregnancy.[57] The Court held the drug tests were an unreasonable search and violated the Fourth Amendment. Ferguson v. City of Charleston further reveals an unjustified assumption: the medical and legal community seemed suspicious of black women and had perhaps predetermined them more likely to use drugs while pregnant. Their fitness to become mothers needed to be proven, while wealthy, white women were presumed fit.[58] The correctional community similarly denies pregnant prisoners’ medical attention. In the case of Staten v. Lackawanna County, an African American woman whose serious medical needs were treated indifferently by jail staff was forced to give birth in her cell.[59] This woman was punished for being pregnant in prison through the withholding of medical attention and empathy. IV. Failure to Follow Anti-Shackling Laws Despite 22 states having laws against shackling pregnant prisoners, officers do not always follow these laws. In 2015, the Correctional Association of New York reported that of the 27 women who gave birth under state custody, officers shackled 23 women in violation of the anti-shackling laws.[60] The lawyer of Tracy Edwards, an inmate who officers shackled unlawfully during her twelve-hour labor stated, “I don’t think we can assume that just because there’s a law passed, that’s automatically going to trickle down to the prison.”[61] Even with more restrictions on shackling, it may still occur, partly due to the stereotype that incarcerated women are aggressive and dangerous. V. Constitutionality The Eighth Amendment protects people from cruel and unusual punishment. In Brown vs. Plata, the court stated, “Prisoners retain the essence of human dignity inherent in all persons.”[62] In several cases, the legal community has held shackling to be unconstitutional as it violates the Eighth Amendment unless specifically justified. In the case of Nelson v. Correctional Medical Services, a pregnant woman was shackled for 12 hours of labor with a brief respite while she pushed, then re-shackled. The shackling caused her physical and emotional pain, including intense cramping that could not be relieved due to positioning and her inability to get up to use a toilet.[63] The court held that a clear security concern must justify shackling. The court cited a similar DC case and various precedents for using the Eighth Amendment to hold correctional facilities and hospitals accountable.[64] An Arkansas law similarly states that shackling must be justified by safety or risk of escape.[65] If the Thirteenth Amendment applied to those convicted of crimes, shackling pregnant incarcerated people would be unconstitutional under that amendment as well as the Eighth. In the Civil Rights Cases, Congress upheld the right “to enact all necessary and proper laws for the obliteration and prevention of slavery with all its badges and incidents.”[66] Section two of the Thirteenth Amendment condemns any trace or acts comparable to that of slavery. Shackling pregnant prisoners, stripping them of their dignity, and justification based on stereotypes all have origins in the treatment of black female slaves. Viewed through the lens of the Thirteenth Amendment, the act of shackling would be unconstitutional. Nonetheless, the Thirteenth Amendment explicitly excludes people convicted of a crime. VI. Justice As a result of the unconstitutional nature of shackling, physicians should have a legal obligation, in addition to their ethical duty, to protect their patients. The principle of justice requires physicians to take a stand against the discriminatory treatment of their patients, even under the eye of law enforcement.[67],[68] However, “badge and gun intimidation,” threats of noncompliance, and the fear of losing one’s license can impede a physician’s willingness to advocate for their patients. The American College of Obstetricians and Gynecologists (ACOG) finds the use of physical restraints interferes with the ability of clinicians to practice medicine safely.[69] ACOG, The American Medical Association, the National Commission on Correctional Health Care, and other organizations oppose using restraints on pregnant incarcerated people.[70] Yet, legislators can adopt shackling laws without consultation with physicians. The ACOG argues that “State legislators are taking it upon themselves to define complex medical concepts without reference to medical evidence. Some of the penalties [faced by OBGYNs] for violating these vague, unscientific laws include criminal sentences.”[71] Legislation that does not consider medical implications or discourages physicians’ input altogether is unjust. In nullifying the voice of a physician in matters pertaining to the patient’s treatment, physicians are prevented from fulfilling the principle of justice, making the act of shackling patients unethical. VII. Principle of Beneficence The principle of beneficence requires the prevention of harm, the removal of harm, and the promotion of good.[72] Beneficence demands the physician not only avoid harm but benefit patients and promote their welfare.[73] The American Board of Internal Medicine Foundation states that physicians must work with other professionals to increase patient safety and improve the quality of care.[74] In doing so, physicians can adequately treat patients with the goal of prevention and healing. It is difficult to do good when law enforcement imposes on doctors to work around shackles during labor and delivery. Law enforcement leaves physicians and healthcare workers responsible not only to provide care for the delivery, but also rectify any ailments associated with the restraints. The issues arising from using restraints place physicians in a position more complex than they experience with other pregnancies. Doctors cannot prevent the application of the shackles and can only request officers to take them off the patient.[75] Physicians who simply go along with shackling are arguably violating the principle of beneficence. However, for most, rather than violating the principle of beneficence overtly, physicians may simply have to compromise. Given the intricate nature of the situation, physicians are tasked with minimizing potential harm to the best of their abilities while adhering to legal obligations.[76] It is difficult to pin an ethics violation on the ones who do not like the shackles but are powerless to remove them. Some do argue that this inability causes physicians to violate the principle of beneficence.[77] However, promoting the well-being of their patients within the boundaries of the law limits their ability to exercise beneficence. For physicians to fulfill the principle of beneficence to the fullest capacity, they must have an influence on law. Protocols and assessments on flight risks made solely by the officers and law enforcement currently undermine the physician’s expertise. These decisions do not consider the health and well-being of the pregnant woman. As a result, law supersedes the influence of medicine and health care. CONCLUSION People expect physicians to uphold the four major principles of bioethics. However, their inability to override restraints compromises their ability to exercise beneficence. Although pledging to enforce these ethical principles, physicians have little opportunity to influence anti-shackling legislation. Instead of being included in conversations regarding medical complexities, legislation silences their voices. Policies must include the physician's voice as they affect their ability to treat patients. Officers should not dismiss a physician's request to remove shackles from a woman if they are causing health complications. A woman's labor should not harm her or her fetus because the officer will not remove her shackles.[78] A federal law could end shackling pregnant incarcerated people. Because other options are available to ensure the safety of the public and the prisoner, there is no ethical justification for shackling pregnant prisoners. An incarcerated person is a human being and must be treated with dignity and respect. To safeguard the well-being of incarcerated women and the public, it is essential for advocates of individual rights to join forces with medical professionals to establish an all-encompassing solution. - [1] Ferszt, G. G., Palmer, M., & McGrane, C. (2018). Where does your state stand on shackling of Pregnant Incarcerated Women? Nursing for Women’s Health, 22(1), 17–23. https://doi.org/10.1016/j.nwh.2017.12.005 [2] S983A, 2015-2016 Regular Sessions (N.Y. 2015). https://legislation.nysenate.gov/pdf/bills/2015/S983A [3] Chris DiNardo, Pregnancy in Confinement, Anti-Shackling Laws and the “Extraordinary Circumstances” Loophole, 25 Duke Journal of Gender Law & Policy 271-295 (2018) https://scholarship.law.duke.edu/djglp/vol25/iss2/5 [4] Chris DiNardo (2018) [5] U.S. Bureau of Justice Statistics. 1980. " Prisoners in 1980 – Statistical Tables”. Retrieved April 20, 2023 (https://bjs.ojp.gov/content/pub/pdf/p80.pdf). [6] U.S. Bureau of Justice Statistics. 2022. " Prisoners in 2021 – Statistical Tables”. Retrieved April 20, 2023 (https://bjs.ojp.gov/sites/g/files/xyckuh236/files/media/document/p21st.pdf). [7] U.S. Bureau of Justice Statistics (1980) [8] Sufrin C, Jones RK, Mosher WD, Beal L. Pregnancy Prevalence and Outcomes in U.S. Jails. Obstet Gynecol. 2020;135(5):1177-1183. doi:10.1097/AOG.0000000000003834 [9] Kramer, C., Thomas, K., Patil, A., Hayes, C. M., & Sufrin, C. B. (2022). Shackling and pregnancy care policies in US prisons and jails. Maternal and Child Health Journal, 27(1), 186–196. https://doi.org/10.1007/s10995-022-03526-y [10] House, K. T., Kelley, S., Sontag, D. N., & King, L. P. (2021). Ending restraint of incarcerated individuals giving birth. AMA Journal of Ethics, 23(4). https://doi.org/10.1001/amajethics.2021.364 [11] Goshin, L. S., Sissoko, D. R., Neumann, G., Sufrin, C., & Byrnes, L. (2019). Perinatal nurses’ experiences with and knowledge of the care of incarcerated women during pregnancy and the postpartum period. Journal of Obstetric, Gynecologic &amp; Neonatal Nursing, 48(1), 27–36. https://doi.org/10.1016/j.jogn.2018.11.002 [12] Shackling and separation: Motherhood in prison. (2013). AMA Journal of Ethics, 15(9), 779–785. https://doi.org/10.1001/virtualmentor.2013.15.9.pfor2-1309 [13] King, L. (2018). Labor in chains: The shackling of pregnant inmates. Policy Perspectives, 25, 55–68. https://doi.org/10.4079/pp.v25i0.18348 [14] King, L. (2018). [15] AMA Journal of Ethics (2013) [16] Lawrence, A., Lewis, L., Hofmeyr, G. J., & Styles, C. (2013). Maternal positions and mobility during first stage labour. Cochrane database of systematic reviews, (8). [17] Association of Women’s Health, Obstetric and Neonatal Nurses. (2011). AWHONN position statement: Shackling incarcerated pregnant women. Journal of Obstetric, Gynecologic, & Neonatal Nursing, 40(6), 817–818. doi:10.1111/j.1552-6909.2011.01300.x [18] Ferszt, G. G., Palmer, M., & McGrane, C. (2018). Where does your state stand on shackling of Pregnant Incarcerated Women? Nursing for Women’s Health, 22(1), 17–23. https://doi.org/10.1016/j.nwh.2017.12.005 [19] Thompson, E. (2022, August 30). Woman sues NC state prison system for mistreatment while pregnant. North Carolina Health News. Retrieved March 12, 2023, from https://www.northcarolinahealthnews.org/2022/05/25/woman-sues-nc-state-prison-system-for-mistreatment-while-pregnant/ [20] CBS Interactive. (2019, March 13). Shackling pregnant inmates is still a practice in many states. CBS News. Retrieved March 12, 2023, from https://www.cbsnews.com/news/shackling-pregnant-inmates-is-still-a-practice-in-many-states/ [21] Griggs, Claire Louise. "Birthing Barbarism: The Unconstitutionality of Shackling Pregnant Prisoners." American University Journal of Gender Social Policy and Law 20, no. 1 (2011): 247-271. [22] American Civil Liberties Union. (2012, October 12). ACLU briefing paper: The shackling of pregnant women & girls in U.S ... 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UCLA Women's Law Journal, 18(1). https://doi.org/10.5070/l3181017816 [29] Chris DiNardo (2018) [30] Griggs, Claire Louise (2011). [31] Allen, J. E. (2010, October 21). Shackled: Women Behind Bars Deliver in Chains. ABC News. https://abcnews.go.com/Health/WomensHealth/pregnant-shackled-women-bars-deliver-chains/story?id=11933376&page=1 [32] Nelson v. Correctional, 533 F.3d 958 (8th Cir. 2009) [33] Nelson v. Correctional(2009) [34] House, K. T., Kelley, S., Sontag, D. N., & King, L. P. (2021). Ending restraint of incarcerated individuals giving birth. AMA Journal of Ethics, 23(4). https://doi.org/10.1001/amajethics.2021.364 [35] Amnesty International USA. (1999, March). “Not part of my sentence” Violations of the Human Rights of Women in Custody. Amnesty International USA. Retrieved March 12, 2023, from https://www.amnestyusa.org/reports/usa-not-part-of-my-sentence-violations-of-the-human-rights-of-women-in-custody/ [36] Pendleton, V., Saunders, J. B., & Shlafer, R. (2020). 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As 2008 draws to a close, I am pleased to publish Volume 4(2) of the International Journal for Educational Integrity. Having attended the 3rd International Plagiarism Conference at Northumbria University in the UK in June, and recently joined the Advisory Board of the Center for Academic Integrity in the USA, I have gained the sense that there is increasing global interest in the broad field of educational integrity. In parallel with that interest has been an increased number of submissions to the IJEI, and an overall improvement in the quality of those submissions. I am delighted to report that the International Journal for Educational Integrity has been assessed by the European Science Foundation (Standing Committee for the Humanities) as a category 'B' in the ERIH Initial List for 'Pedagogical and Educational Research', and is currently being considered for a change of category to 'A', for confirmation in early 2009. The Asia-Pacific Forum on Educational Integrity (http://apfei.edu.au), the organisation which publishes the IJEI, is currently seeking members, both institutional and individual. Benefits of membership include: Access to the APFEI website and discussion list; Opportunities to contribute to the APFEI wiki/respository of resources; Discounted individual membership; Collaboration with the Center for Academic Integrity (Clemson University, USA, and plagarismadvice.org (Northumbria University, UK); 15% discount on bi-annual APFEI conference registration to all delegates with individual or institutional membership; Networking opportunities with key researchers in the field, including mentoring to publish in the IJEI; Reputational benefit in being associated with the first organisation in the region specifically devoted to issues of educational integrity; and Access to key researchers/speakers/professional developers to conduct seminars and training. The membership application form follows this Editorial. As in previous issues, Volume 4(2) brings together a range of scholars from around the world, each offering a unique perspective on the topic. Kay Fielden and Donald Joyce from Unitec in New Zealand, set the scene by offering an analysis of 125 papers on academic integrity by Australasian authors, published since 1998. Fielden and Joyce use a multi-stakeholder, multi-level theoretical framework to demonstrate that there was a dominant positivist mindset adopted by the authors in the sample, and that academic staff researchers provide the dominant stakeholder view, most often about student behaviour. It is perhaps not surprising, therefore, that the other three papers in the issue are all written by academic researchers and all deal with student behaviour. Amanda Maxwell, Guy Curtis and Lucia Vardanega from the University of Western Sydney in Australia, investigate the perceived seriousness and understanding of plagiarism by local and Asian international students studying at two Australian universities. Based on a sample of 267 undergraduate students from varying disciplinary backgrounds, and using self-report questionnaires, the study challenges commonly held assumptions about cultural differences. No distinction was found between the two groups in terms of perceived seriousness and understanding of plagiarism. This study confirms the findings from other research which indicates that most students demonstrate some difficulty understanding what constitutes plagiarism, and that an educative framework is needed for all students, regardless of cultural or linguistic background. Vidar Gynnild, from the Norwegian University of Science and Technology, and Patricia Gotschalk, from Michigan Technological University in Houghton, report on an institutional study of academic integrity based on reported incidents from 2001-2006, and a campus-wide survey administered in 2008. Although the findings demonstrated that academic dishonesty was widespread, 40% of the academic staff who responded to the survey stated that they had taken no steps to address a suspected breach of academic integrity, due to insufficient proof. Other key findings relating to student breaches of academic integrity indicated that there are cultural and gender differences, as well as differences between schools (disciplines) and levels of study. International students were over-represented in integrity charges, and the most frequent offence generally was collusion. Like many other researchers in the field, Gynnild and Gotschalk conclude that a holistic approach which balances the “punitive and educational aspects of policies” is both the challenge and the goal. The issue concludes with an insightful piece by Sarah Roberts-Cady from Fort Lewis College in Colorado. Roberts-Cady makes the case that while most colleges and universities have adopted two main strategies to address academic integrity – behaviour modification and character development – what is also needed is a program of instruction which teaches students to think critically about values. Roberts - Cady asserts that critical thinking is not only an important element of rationality, but integral to being a morally responsible person. Given the emphasis on critical thinking in higher education, Roberts-Cady concludes that "critical thinking about honesty" is where we need to direct our attention in our daily efforts to address issues of academic integrity. I trust you enjoy the current issue of the International Journal for Educational Integrity and encourage you to submit a paper for review, either through the automatic tracking system, or directly to me at tracey.bretag@unisa.edu.au. The next issue is scheduled to be published in April/May 2009. Tracey Bretag, Editor Reviewers for this issue: Patrick Baughan, City University, UK Mark Brimble, Griffith University, Australia Kate Chanock, La Trobe University, Australia Kathleen Gray, University of Melbourne, Australia Margaret Green, University of South Australia Heather Hancock, University of South Australia Sue Knight, University of South Australia Martin Lipscombe, University of the West of England, UK Helen Marsden, University of Canberra, Australia Stephen Marshall, Victorian University of Wellington, NZ