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MENNA, JAY H., and RICHARD P. WHEELER. "University of Arkansas for Medical Sciences College of Medicine." Academic Medicine 75, Supplement (September 2000): S11—S13. http://dx.doi.org/10.1097/00001888-200009001-00006.
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Graham, James, Sara Tariq, Karina Clemmons, and Richard Wheeler. "University of Arkansas for Medical Sciences College of Medicine." Academic Medicine 95, no. 9S (September 2020): S30—S32. http://dx.doi.org/10.1097/acm.0000000000003303.
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Newton, Bruce W., and Richard P. Wheeler. "University of Arkansas for Medical Sciences College of Medicine." Academic Medicine 85 (September 2010): S84—S87. http://dx.doi.org/10.1097/acm.0b013e3181e869dd.
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Fiser, Debra H. "The College of Medicine at the University of Arkansas for Medical Sciences." Academic Medicine 83, no. 4 (April 2008): 419. http://dx.doi.org/10.1097/acm.0b013e318166a0e1.
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Ward, Heidi M., Gabriel L. Apple, Lauren R. Thomas, and Kathryn E. Reif. "Extension Contribution to Anaplasmosis Surveillance in Arkansas: A Story of Collaboration." Journal of Animal Science 99, Supplement_2 (May 1, 2021): 8. http://dx.doi.org/10.1093/jas/skab096.012.
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Abstract The emergence of resistant bacteria forced the medical and animal agriculture communities to rethink how antibiotics are used. In Arkansas, medicated feed is mostly used to treat or control Anaplasmosis in beef cattle herds. Bovine Anaplasmosis is a tick-borne disease caused by the rickettsial bacteria, Anaplasma marginale. This disease causes over $300 million in losses annually for the U.S. cattle industry. With beef cattle being the fifth largest agricultural commodity in Arkansas, it is important to know the prevalence of Anaplasmosis infection in the state. The project described is a collaborative effort between the University of Arkansas-Fayetteville campus, the University of Arkansas Extension, and the Kansas State University (KSU) College of Veterinary Medicine. Extension agents from 33 Arkansas counties were trained to recruit producers for the study and to coordinate sample collection. On the day of blood collection, Extension agents discussed the purpose of the project and appropriate disclosures with the producers. A total of 578 mature beef cattle were randomly selected from six geographical regions for sampling between the months of November 2019 and February 2020. Both whole blood and serum samples were collected from each animal. PCR testing was completed at the KSU College of Veterinary Medicine andcELISA testing was completed at the University of Arkansas Veterinary Diagnostic Laboratory. Blood samples from 335 cattle (58.7%) were positive for Anaplasmosis on at least one test with the majority of animals testing positive (229; 68.4%) on both the cELISA and PCR tests. Rates of regional prevalence ranged from 36.7% to 93.8%. The overall results were discussed with Extension agents via Zoom prior to discussing results with individual producers. Data from this study were added to previous surveillance data collected by Kansas State University and will direct Extension education efforts pertaining to Anaplasmosis management in regional beef cattle herds.
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Yaccoby, Shmuel, Joshua Epstein, Sarah K. Johnson, Pingping Qu, Frits van Rhee, Yogesh Jethava, Caleb K. Stein, et al. "The Composition and Clinical Impact of Focal Lesions and Their Impact on the Microenvironment in Myeloma." Blood 126, no. 23 (December 3, 2015): 1806. http://dx.doi.org/10.1182/blood.v126.23.1806.1806.
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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.
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Vuk, Jasna, Steven McKee, Sara Tariq, and Priya Mendiratta. "A Better Learning Community: Mixed-Methods Reveal Medical Student Preferences with Implications for Learning Community Design and Implementation." Journal of Medical Education and Curricular Development 8 (January 2021): 238212052110148. http://dx.doi.org/10.1177/23821205211014895.
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Background: Medical school learning communities benefit students. The College of Medicine (COM) at the University of Arkansas for Medical Sciences (UAMS) provides medical students with academic, professional, and personal support through a learning community (LC) made of 7 academic houses. Objectives: To evaluate the effectiveness of the academic house model at UAMS utilizing a mixed-methods survey. The aims were to: (1) assess student experience and satisfaction with academic houses, (2) describe the realms of advising and guidance, and (3) identify areas for improvement. Method: An online survey was assigned to 723 COM students (all students enrolled, first through fourth years) at UAMS in March 2019. The survey was comprised of 25 items (10 multiple-choice, 8 on the Likert scale, and 7 open-ended questions). Data was depicted using frequency and percentages and/or thematic review of free-form responses. Results: The survey response rate was 31% (227 students). The majority of students responding (132, 58.1%) attended 2 or more face-to-face meetings with the faculty advisor within the preceding year. However, 27 (11.9%) students did not have any meetings. Approximately two-thirds of the respondents were satisfied or very satisfied with the guidance and direction provided by their advisors [very satisfied (n = 83; 36.6%); satisfied (n = 77; 33.9%)]. Themes that emerged from student generated areas for improvement include time constraints, advisor/advisee interest mismatch, and perceived inadequacy of advising content/connections. Conclusions: This study confirms the effectiveness of the LC model for advising and mentoring in the COM at UAMS. Uniquely, this study identifies not only learners’ satisfaction with their LC but also highlights areas for improvement which are widely generalizable and important to consider for institutions with or planning to start an LC.
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Sharma, Shanta, Rita Black Monsen, and Bette Gary. "Comparison of Attitudes toward Death and Dying among Nursing Majors and other College Students." OMEGA - Journal of Death and Dying 34, no. 3 (January 1, 1996): 219–32. http://dx.doi.org/10.2190/wnx7-nfya-mfe9-y064.
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Recent studies of attitudes toward fear of death and dying among under-graduates have been sparse. Hoelter's Multidimensional Fear of Death Scale (MFODS) [1] was developed among undergraduates to discern fear of death or death anxiety. The purposes of this study were to 1) examine the factor structure and reliability estimates of Hoelter's MFODS in a contemporary sample of college students and 2) compare the attitudes of nursing majors with those of other college students at a small liberal arts university in rural, southwestern Arkansas. It was hypothesized that the 1) attitudes of nursing majors would differ from those preparing for other careers and 2) attitudes of nursing majors and other undergraduates would differ at each level of student status (freshman through senior years). This was a descriptive study surveying attitudes among students who were recruited through cooperating faculty in courses serving all undergraduate majors. Informed consents were signed after review of the introductory information by the students. The sample consisted of 405 students, ages eighteen to sixty-four years (mean age 26 years); 27 percent were males and 73 percent females. Nursing students comprised 24 percent of the sample and were marginally different demographically from other students. The MFODS (a 42-item, pencil-and-paper instrument including a demographic questionnaire) was administered in one classroom session. Factor structure was derived using principal components analysis with varimax rotation and revealed eight subscales accounting for 21 percent of the variance. The total scale alpha reliability was .88, with eight subscale alpha reliabilities ranging from .75 to .85. The results of comparisons of nursing students with others revealed differences on three subscales and the total MFODS. Nursing students were less fearful of the dead, less fearful of being conscious while dead, and less fearful of being destroyed after death. Analyses of students by levels of student status revealed that freshman nursing students were most fearful of the dead and junior nursing students were most fearful of discovering a dead body. Other undergraduate freshmen were most fearful of events after death such as treatment of the body after death, being practiced on by medical students, being embalmed, being conscious in a morgue, and the thought of never being found after death. There were no significant findings among comparisons of nursing and other undergraduate majors by level of student status (freshman through senior). It was concluded the MFODS was a reliable instrument. Nursing students displayed significant attitudinal differences as compared to other students examined. Students who study nursing may bring greater acceptance of death and the dying process to health care arenas. Longitudinal comparison studies and qualitative analyses of attitudes were recommended to further elucidate professional socialization processes.
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Kozaczek, Melisa, Walter Bottje, and Reza Hakkak. "Liver Proteomics Analysis After Short- and Long-Term Soy Protein Isolate Feeding Using Obese Zucker Rat Model." Current Developments in Nutrition 5, Supplement_2 (June 2021): 1226. http://dx.doi.org/10.1093/cdn/nzab055_036.
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Abstract Objectives To identify possible mechanisms involved in the development and progression of NAFLD through protein expression (shotgun proteomics) analysis on liver samples of obese Zucker rats fed with either casein (CAS) or soy protein isolate (SPI) during 8 and 16 weeks. Methods 7 weeks old rats (n = 8–9 per group) were randomly assigned to an either CAS-based or a SPI-based diet. Rats were sacrificed after 8 weeks or 16 weeks of SPI feeding. Livers were immediately obtained and stored at −80 C. Ingenuity Pathway Analysis (IPA) software was used to facilitate interpretation of proteomics data. Predictions of activation or inhibition of molecules in the data was made based on activation z-score and P value of overlap (P < 0.05). Activation z-scores > 2.0 indicate that a molecule is activated, whereas activation z-scores of < −2.0 indicate that a target molecule is inhibited. Results Upstream regulator analysis by IPA revealed 6 molecules predicted to be activated (z-scores between 2 and 2.8) and 9 inhibited (z-scores between −2 and −2.6) in SPI vs CAS-fed rats in proteomics data at 8 weeks of SPI feeding. In contrast, at 16 weeks of SPI feeding there were 12 molecules activated (z-scores between 2 and 2.5) and 18 inhibited (z-scores between −2 and −2.8) in SPI vs CAS-fed. All p values were <0.05. Regulator effects analysis also revealed that some of these molecules would be participating, directly or indirectly, in the inhibition of the immune response of cells (such as IL27 and CSF2) and synthesis of lipids (CEBPA, Ins1 and IRF8) in SPI-fed rats. Conclusions These molecules and their downstream target proteins may provide clues by which soy protein produces the observed attenuation of liver steatosis that can be tested in future experiments in this obese rat model. Funding Sources This study was supported in part by the College of Medicine's University Medical Group (RH) and the Arkansas Biosciences Institute (WB, RH).
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Hackler, Chris. "University of Arkansas College of Medicine, Division of Medical Humanities." Academic Medicine 78, no. 10 (October 2003): 1059. http://dx.doi.org/10.1097/00001888-200310000-00028.
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Kozaczek, Melisa, Walter Bottje, and Reza Hakkak. "Effects of Short and Long-Term Soy Protein Isolate Intake on Hepatic Cytochrome P450 Expression in Obese Zucker Rats." Current Developments in Nutrition 5, Supplement_2 (June 2021): 1225. http://dx.doi.org/10.1093/cdn/nzab055_035.
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Abstract Objectives To determine the effects feeding for 8 (short-term) and 16 weeks (long-term) soy protein isolate on hepatic CYP gene expression. Methods 7-weeks old rats were randomly assigned to either a casein (CAS) or a soy protein isolate (SPI) diet. They were provided the diets ad libitum for 8 and 16 weeks. Rats were euthanized and livers were stored at − 80°C. RNA was extracted from liver samples, and sequenced to obtain transcriptomic data (RNAseq). Ingenuity Pathway Analysis software (IPA, Qiagen, CA) was used in the analysis of global gene expression data. This analysis includes predictions of activation or inhibition of molecules or upstream regulators and functions based on a generated z-score and p-value of overlap (P = 0.05). Z-scores were consider significant when > 2 (activation) and < −2 (inhibition). Results Comparing short- vs long-term feeding revealed an increase in the number of down-regulated CYP genes from only 3 at 8 weeks of SPI diet to 10 at 16 weeks of same diet (P < 0.05). In contrast, upregulated CYP gene numbers showed a small increase in long-term SPI diet compared to short-term, from 14 genes at 8 weeks to 17 genes at 16 weeks (P < 0.05). In addition, we present a predicted activation of the transcription factor Aryl hydrocarbon receptor (AHR, activation z-score = 2.146, P = 4.20E-11), linked to the subsequent activation or up-regulation of various CYPs genes, indirectly leading to the activation and inhibition of two main metabolic functions under SPI feeding: conversion of lipid (lipid metabolism) –predicted to be activated (z-score = 2.089, P = 2.77E-08), and recruitment of phagocytes (inflammatory response) –predicted to be inhibited (z-score = −2.311, P = 2.10E-05). Conclusions Through global gene expression analysis we showed that gene expression of drug-metabolizing cytochrome P450 genes was modified in genetically obese Zucker rats after being fed a soy-based diet for short- and long-term, and that this change could have an important role in attenuation of liver steatosis. Further research is needed to corroborate these results. Funding Sources This study was supported in part by the College of Medicine's University Medical Group (RH) and the Arkansas Biosciences Institute (WB, RH).
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Zempleni, Janos, J. Steven Stanley, and Donald M. Mock. "Proliferation of peripheral blood mononuclear cells causes increased expression of the sodium-dependent multivitamin transporter gene and increased uptake of pantothenic acid ☆ ☆This work was supported by National Institutes of Health grant DK 36823, USDA/CSREES award 2001-35200-10187, and a grant from the College of Medicine at the University of Arkansas for Medical Sciences." Journal of Nutritional Biochemistry 12, no. 8 (August 2001): 465–73. http://dx.doi.org/10.1016/s0955-2863(01)00162-0.
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Mohan, Meera, Rohan Samant, Larry J. Suva, Corey O. Montgomery, Daisy V. Alapat, Roy Morello, Frits van Rhee, et al. "Re-Mineralization of Large Pelvic Lytic Lesions By CT Imaging in Patients with Multiple Myeloma: The Arkansas Experience." Blood 126, no. 23 (December 3, 2015): 4193. http://dx.doi.org/10.1182/blood.v126.23.4193.4193.
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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.
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Soltis, Denise, and Schwanda K. Flowers. "Expanding Experiential Opportunities Through Patient Care Services." Journal of Pharmacy Practice 23, no. 6 (September 14, 2010): 575–78. http://dx.doi.org/10.1177/0897190010378752.
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A new set of standards, ACPE Standards 2007, adopted by the Accreditation Council for Pharmacy Education (ACPE), required all pharmacy programs to include introductory pharmacy practice experiences (IPPEs) to represent 5% of the curriculum and advance pharmacy practice experiences (APPEs) to represent 25% of the curriculum. This required many pharmacy programs to revise their curriculum to meet these requirements. The challenge of satisfying the increased accreditation requirements along with the increased number of new pharmacy programs in the United States has resulted in increased competition for experiential sites. Drake University College of Pharmacy and Health Sciences and the University of Arkansas for Medical Sciences (UAMS) College of Pharmacy utilized innovative immunization services to help meet the ACPE Standards 2007. Drake utilized P2 and P3 students who were trained to give immunizations in an IPPE patient care elective in order to help experiential sites in their immunization efforts. Senior pharmacy students at UAMS were involved in expanding APPE opportunities by developing immunization clinics and providing immunizations at their experiential sites. Both pharmacy programs were successful in expanding experiential opportunities by focusing on immunizations. Students, preceptors, and patients all benefit from utilizing student pharmacist at experiential sites to provide patient care services.
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Weinhold, Niels, Shweta S. Chavan, Christoph Heuck, Owen W. Stephens, Ruslana Tytarenko, Michael Bauer, Erich Allen Peterson, et al. "High Risk Multiple Myeloma Demonstrates Marked Spatial Genomic Heterogeneity Between Focal Lesions and Random Bone Marrow; Implications for Targeted Therapy and Treatment Resistance." Blood 126, no. 23 (December 3, 2015): 20. http://dx.doi.org/10.1182/blood.v126.23.20.20.
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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.
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ALONSO, DANIEL R. "Cornell University Joan and Sanford I. Weill Medical College and Graduate School of Medical Sciences." Academic Medicine 75, Supplement (September 2000): S235—S238. http://dx.doi.org/10.1097/00001888-200009001-00069.
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Schinke, Carolina, Shayu Deshpande, Alan Mitchell, Malek Faham, Purvi Patel, Sharmilan Thanendrarajan, Meera Mohan, et al. "Impact of Minimal Residual Disease in High and Standard Risk Multiple Myeloma." Blood 126, no. 23 (December 3, 2015): 2979. http://dx.doi.org/10.1182/blood.v126.23.2979.2979.
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Abstract Introduction Achieving complete remission (CR) improves survival outcomes in multiple myeloma (MM). Applying more sensitive flow-cytometry or PCR based minimal residual disease (MRD) testing further improves prognostication and MRD negativity confers better outcomes among CR patients. In our Total Therapy (TT) trials, gene expression profiling based risk (GEP) identifies 15% patients with high risk (HR) MM whose clinical course is characterized by early relapsing disease and prognosis has remained grim despite advances in therapy. Of interest is whether high-risk (HR) patients fail to achieve MRD negativity leading to relapse. We have determined response rates across the total therapy (TT) trials and in this study we report the impact of molecular negativity by MRD assessment in patients who have achieved at least very good partial response (VGPR) or CR at 4-8 months and 12-24 months, respectively, after enrollment in TT3b-TT5 from 2005-2009. We use next-generation sequencing (NGS)-based MRD assessment (Adaptive Biotechnologies) which is sensitive to 1 MM cell in 106 normal cells. Furthermore, we evaluate MRD status in long term relapse-free survivors (>6 years) to determine the importance of MRD status in prolonged remission. Materials and methods Study subjects include 591 patients enrolled in TT3b-TT5 to determine VGPR/nCR/CR by EBMT/IMWG criteria and to analyze PFS and OS of HR and SR patients defined by our GEP model. For MRD testing, we identified 102 patients from the TT3b-TT6 protocols that achieved at least VGPR and had bone marrow (BM) sample available at 4-8 months and 12-24 months after enrollment. Of these 102 patients, 14 patients had HR disease and 88 had SR. Six of 14 HR patients already had clinical relapse between 12-24 months, but were included to determine MRD at 4-8 months. Of all 102 patients, 51 are currently still in CR 6-9 years after protocol enrollment and most recent flow-cytometric MRD status was evaluated. NGS-based MRD Assessment: Genomic DNA was amplified using locus-specific primer sets for immunoglobulin heavy-chain complete (IGH-VDJH) and incomplete (IGH-VDH) as well as for immunoglobulin κ locus (IGκ). The amplified products were subjected to sequencing and clonal gene rearrangements were analyzed. Final MRD measurement was calculated at a sensitivity level of 1 cancer cell per 1 million cell equivalents. Flow Cytometry based MRD assessment: Erythrocyte-lysed BM samples were immunophenotyped by use of 8-color (CD138/CD38/CD19/CD45/CD27/CD81/CD56/CD20) staining technique. Myelomatous Plasmacells (PCs) were separated from healthy PCs by different phenotype expression and MRD was deemed negative when no myelomatous PCs were detectable at a sensitivity of <10-4 to <10-5. Results Response by EBMT/IMWG criteria across our TT3b-TT5 (n=591) protocols showed no significant difference between HR and SR patients by year 1 of enrollment. In the SR group (n=502) 74.9%-77.9% of patients achieve at least nCR/VGPR and 40.3%-50.4% CR. For the HR patients (n=89) the results are similar with 75%-77.9% achieving at least VGPR and 50%-50.4% CR. However, the majority of HR patients start relapsing after one year of enrollment with a relapse rate of 59% for HR at 3 years compared to only 19% for SR at the same time point, indicating that MRD positive disease likely exists at 12-24 months for those patients with relapse. NGS-based MRD assessment will answer this question and data will be available by December 2015. Fifty one patients of the initial 102 patient group continue to be in complete remission to date >6 years after enrollment. Of these, 47 are MRD negative at a MRD level of <10-5 (3 HR and 44 SR), two are MRD negative at <10-4 (SR), leaving only 2 patients (SR) with a detectable MRD burden at >10-4. Conclusions Using conventional response methods, there is no difference between HR and SR MM at 1 year after initiation of treatment. However clinical outcome for HR disease is very poor and characterized by early relapsing disease, indicating that MRD persists even when patients have achieved CR. Sequencing is the most sensitive method for MRD detection and will be used in the present study to evaluate the importance of sequential MRD testing in HR and SR disease. We show that the majority of patients achieving long term remission at 6-8 years are MRD negative indicating the importance of molecular response for long term success. Disclosures Schinke: University of Arkansas for Medical Sciences: Employment. Mitchell:Cancer Research and Biostatistics: Employment. Faham:adaptive biotech: Employment, Other: stockholders. Patel:University of Arkansas for Medical Sciences: Employment. Thanendrarajan:University of Arkansas for Medical Sciences: Employment. Mohan:University of Arkansas for Medical Sciences: Employment. Mathur:University of Arkansas for Medical Sciences: Employment. Matin:University of Arkansas for Medical Sciences: Employment. Radhakrishnan:University of Arkansas for Medical Sciences: Employment. Stephens:University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Zangari:Novartis: Research Funding; Millennium: Research Funding; University of Arkansas for Medical Sciences: Employment; Onyx: Research Funding. Jethava:University of Arkansas for Medical Sciences: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Alapat:University of Arkansas for Medical Sciences: Employment. Johnson:University of Arkansas for Medical Sciences: Employment. Epstein:University of Arkansas for Medical Sciences: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Davies:Celgene: Consultancy; Onyx: Consultancy; Janssen: Consultancy; Millenium: Consultancy; University of Arkansas for Medical Sciences: Employment. Heuck:Millenium: Other: Advisory Board; Celgene: Consultancy; Janssen: Other: Advisory Board; Foundation Medicine: Honoraria; University of Arkansas for Medical Sciences: Employment. Hoering:Cancer Research and Biostatistics: Employment. Weinhold:University of Arkansas for Medical Sciences: Employment; Janssen Cilag: Other: Advisory Board. Morgan: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; 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.
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van Rhee, Frits, Alan Mitchell, Maurizio Zangari, Jeffery Sawyer, Sarah Waheed, Rashid Z. Khan, Christoph Heuck, et al. "A Prognostic 51-Gene Signature Linked to Abnormal Metaphase Cytogenetics Identifies Myeloma Patients Who Benefit from Fractionated Melphalan Dosing and Added Bortezomib, Thalidomide and Dexamethasone As Conditioning for Autologous Stem Cell Transplant." Blood 126, no. 23 (December 3, 2015): 3181. http://dx.doi.org/10.1182/blood.v126.23.3181.3181.
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Abstract Introduction: Total Therapy 4 (TT4) comprises a randomized phase III trial enrolling 289 patients with gene expression profiling defined low-risk MM in which patients were allocated to a standard arm (TT4-S) or a light arm (TT4-L) with as principal goal to reduce toxicity yet maintain efficacy in TT4-L. Methods: The TT4-S regimen was similar to TT3b and utilized 2 cycles of VDTPACE induction, tandem transplantation with melphalan 200mg/m2, 2 cycles of dose reduced VDTPACE consolidation and 3 years maintenance with VRD. In TT4-L the number of induction and consolidation cycles was reduced to one each and melphalan was given in a fractionated fashion (50mg/m2/d x 4days) to avoid peak levels of melphalan and reduce mucosal toxicity. Bortezomib and thalidomide were added to the fractionated melphalan conditioning regimen to explore synergistic effects and compensate for potential loss of efficacy. Results: Grade ≥3 toxicities in TT4-S and L occurred with similar frequencies. With a median follow-up of 4.5 years, the OS and PFS were similar in TT4-S and TT4-L at 90 and 87% respectively. The same applied to PFS (TT4-S 84% versus TT4-L 79%). The presence of metaphase defined cytogenetic abnormalities (CA) affected clinical outcomes. In TT4-S, patient with CA had a strong trend toward inferior OS compared to patients with no CA (2 year estimate 83 versus 94%, p=0.08), while the reverse applied to TT4-L (95 versus 81%, p=0.07). Non-significant trends in similar directions were noted for PFS. Complete remission duration tended to be inferior in patients with CA-type MM in TT4-S (2 year estimate, 79 vs. 92%, p=013) with no significant differences in TT4-L. Time to relapse was significantly shorter for CA patients on the TT4-S arm (2 year estimate, 15.4 versus 3.9%), but was not affected by CA in the TT4-L (15.8 vs 7.9%, p=0.79. The observation of CA's favorable OS impact in TT4-L was not anticipated. We next analyzed whether the presence or absence of metaphase CA was linked to specific gene probes which could help to explain better outcomes in TT4-L. Among a training set of 266 untreated patients enrolled in TT3a with available baseline GEP studies, 90 (34%) exhibited CA. Among a test set of 164 patients with baseline GEP accrued to TT3b, 67 (41%) qualified as having CA. Fifty-one probes were different in patients with and without CA (q<0.0001). Seven of the 51 genes had functions in DNA replication, recombination, and repair; five in nucleic acid metabolism, and 4 in RNA post-translational modification and RNA damage and repair. Pathway analysis identified a network of eight interrelated genes that were overexpressed in the CA group, indicating that these MM cells have a higher proliferative activity. We next examined clinical outcomes by the GEP51-CA prediction model in the 2 arms of TT4. In TT4-S, GEP51/no-CA had superior OS and PFS compared to GEP51/CA, which was not observed in TT4-L (Figure 1A, B). Conclusions: A prognostic CA-linked GEP signature can identify patients who benefit from conditioning with fractionated melphalan dosing together bortezomib, thalidomide and dexamethasone which negates the adverse impact of CA. Patients who lacked a CA-type gene signature were best served with single high dose melphalan. These exploratory findings need to be confirmed in a prospective randomized trial. Figure 1. PFS according to 51-gene model predicting CA versus no-CA according to arm (TT4-S, 1A; TT4-L, 1B) Figure 1. PFS according to 51-gene model predicting CA versus no-CA according to arm (TT4-S, 1A; TT4-L, 1B) Disclosures van Rhee: University of Arkansa for Medical Sciences: Employment. Mitchell:Cancer Research and Biostatistics: Employment. Zangari:Millennium: Research Funding; Novartis: Research Funding; University of Arkansas for Medical Sciences: Employment; Onyx: Research Funding. Sawyer:University of Arkansas for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Heuck:Millenium: Other: Advisory Board; Janssen: Other: Advisory Board; Celgene: Consultancy; Foundation Medicine: Honoraria; University of Arkansas for Medical Sciences: Employment. Thanendrarajan:University of Arkansas for Medical Sciences: Employment. Schinke:University of Arkansas for Medical Sciences: Employment. Jethava:University of Arkansas for Medical Sciences: Employment. Grazziutti:University of Arkansas for Medical Sciences: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Steward:University of Arkansas for Medical Sciences: Employment. Panozzo:University of Arkansas for Medical Sciences: Employment. Bailey:University of Arkansas for Medical Sciences: Employment. Hoering:Cancer Research and Biostatistics: Employment. Crowley:Cancer Research and Biostatistics: Employment. Davies:University of Arkansas for Medical Sciences: Employment; Celgene: Consultancy; Janssen: Consultancy; Onyx: Consultancy; Millenium: Consultancy. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:MMRF: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Weismann Institute: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; CancerNet: Honoraria; University of Arkansas for Medical Sciences: Employment; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Papanikolaou, Xenofon, Carolina Schinke, Sharmilan Thanendrarajan, Adam Rosenthal, Nathan Petty, Maurizio Zangari, Christoph Heuck, et al. "Extending Metronomic Therapy to 28 Days (metro28) for Relapsed Refractory Multiple Myeloma (RRMM)." Blood 126, no. 23 (December 3, 2015): 5395. http://dx.doi.org/10.1182/blood.v126.23.5395.5395.
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Abstract Introduction: Despite the enormous progress in MM therapy brought about by the rapid development of many novel agents, many patients end up with limited treatment options. We have previously reported on the efficacy and safety of metro16 in RRMM (Papanikolaou, Haematology 2013). Here we are reporting on an extension of such treatment to 28 d (metro28). Patients and Methods: The treatment consisted of a cycle of 28d continuous iv infusions of ADR and DDP each at 1mg/m2/d, along with thalidomide 50 to 100mg/d x 28; bortezomib 0.8 to 1.0mg/m2 on days 1, 4, 7, 10, 13, 16, 19, 22, 25, 28; DEX 8 to 12mg on days 1-4, 7-10, 13-16, 19-22, 25-28; some patients also received vincristine 0.07mg flat dose by CI for 28 days. This was off-protocol therapy that patients provided written informed consent for. The IRB permitted data retrieval and analysis. Results: 150 patients were identified, virtually all had received prior tandem transplants, bortezomib, lenalidomide, carfilzomib and pomalidomide. The median age was 64yr; B2M was elevated >=3.5mg/L in 48%, abnormal cytogenetics (CA) were present in 86%, and 44% had GEP70-defined high risk MM. Figure 1 portrays clinical outcomes. As of April 2015, 60 patients had died, and the 2-yr OS estimate was 45% (Figure 1A); the 6-mo PFS estimate was 31% although 15% had no progression at 18mo (Figure 1B). Analysis by GEP70 and GEP5 risk revealed 18-mo OS estimates of 80% among the 53 patients with low risk in both models, whereas the presence of high risk (HRMM) in either model conferred a significantly reduced 18-mo OS estimate of 25% (p<0.0001) (Figure 1C). On Cox regression analysis, OS was independently adversely affected by GEP5 HRMM (47%, HR=3.43, p<0.001), LDH >=ULN (25%, HR=3.46, p<0.001), low albumin (39%, HR=2.68, p=0.003), B2M >=3.5mg/L (51%, HR+2.63, p=0.014) and thrombocytopenia <50,000/uL (15%, HR=2.3, p=0.043). GEP5 HRMM was the sole adverse variable affecting PFS (HR=2.37, p<0.001). Most patients received metro28 in the outpatient setting, and side effects were mild. Conclusion: Metro28 represents a well-tolerated additional tool in the treatment armamentarium for RRMM. Figure 1. Clinical outcomes A: Overall survival B: Progression-free survival C: Overall survival according to GEP70 and GEP5 risk designations Figure 1. Clinical outcomes. / A: Overall survival. / B: Progression-free survival. / C: Overall survival according to GEP70 and GEP5 risk designations Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Schinke: University of Arkansas for Medical Sciences: Employment. Thanendrarajan:University of Arkansas for Medical Sciences: Employment. Rosenthal:Cancer Research and Biostatistics: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Zangari:University of Arkansas for Medical Sciences: Employment; Onyx: Research Funding; Millennium: Research Funding; Novartis: Research Funding. Heuck:Celgene: Consultancy; Foundation Medicine: Honoraria; Janssen: Other: Advisory Board; University of Arkansas for Medical Sciences: Employment; Millenium: Other: Advisory Board. van Rhee:University of Arkansa for Medical Sciences: Employment. Epstein:University of Arkansas for Medical Sciences: Employment. Yaccoby:University of Arkansas for Medical Sciences: Employment. Morgan:Weismann Institute: Honoraria; CancerNet: Honoraria; 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; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Davies:University of Arkansas for Medical Sciences: Employment; Celgene: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Onyx: Consultancy. Barlogie:University of Arkansas for Medical Sciences: Employment.
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Thanendrarajan, Sharmilan, Caleb K. Stein, Faith E. Davies, Frits van Rhee, Maurizio Zangari, Christoph Heuck, Carolina Schinke, et al. "Defining the Impact of Tandem Autologous Stem Cell Transplantation in Multiple Myeloma: A Case-Match Analysis in the Total Therapy Trials." Blood 126, no. 23 (December 3, 2015): 3182. http://dx.doi.org/10.1182/blood.v126.23.3182.3182.
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Abstract Introduction The introduction of melphalan-based high-dose chemotherapy and autologous stem cell transplantation (MEL-ASCT) has markedly improved the survival of patients with multiple myeloma (MM). The initial clinical studies suggested conditioning with melphalan (MEL) 200 mg/m2 was optimum compared to MEL 140mg/m2 or MEL/TBI. Following on from the introduction of a single MEL-ASCT, the use of tandem transplantation was explored and highlighted the potential of this approach to improve outcome. With the introduction of consolidation and maintenance approaches, questions still remain regarding which patients are most appropriate for the tandem approach and what dose of melphalan should be delivered. The Total Therapy (TT) trials were initiated more than 25 years ago and have used tandem MEL-ASCT since their inception. Not all patients treated in our facility received a 2nd MEL-ASCT due to a number of reasons including adverse events during 1st MEL-ASCT or a lack of funding for 2nd ASCT thus limiting access to a tandem treatment approach. A dose-reduced MEL (140 mg/m2) was given to patients with renal impairment or advanced age at 1st and / or 2nd ASCT. Consolidation/Maintenance chemotherapy was introduced from TT2 onwards. This large data set therefore allows us to perform a retrospective pair-matched analysis to address a number of important clinical questions including the role of single versus tandem MEL-ASCT and standard versus dose-reduced tandem MEL-ASCT in the era of novel agents for induction and consolidation/maintenance therapy. Materials and Methods We have analyzed data from 1918 patients who were enrolled in Total Therapy 1 - 6 trials. Given the changing chemotherapy regimens within TT trials due to the introduction of novel agents coupled with diverse baseline characteristics, we designed a retrospective pair-matched analysis framework in order to account for differences in patient and treatment variables. This was achieved by generating identical treatment and control group subsets from within the full data set that are identical across key covariates including baseline characteristics of ISS stage, age, and creatinine; protocol anti-myeloma treatment regimens such as dexamethasone, thalidomide, bortezomib, and lenalidomide; and variations in transplantation such as melphalan dosage. The majority of the patients in the TT trials completed induction chemotherapy and received the 1st MEL-ASCT (TT1: 88.3%, TT2: 86.0%, TT3: 97.6%, TT4: 95.0%, TT5: 100% and TT6: 95.1%). Fewer patients received the 2nd MEL-ASCT (TT1: 66.7%, TT2: 68.2%, TT3: 85.0%, TT4: 70.0%, TT5: 74.0%, and TT6: 52.4%). MEL 200 mg/m2 was the predominant dose, administered with MEL 140 mg/m2 given to a smaller fraction of patients due to age and renal impairment restrictions. TT3 has the highest percentage of patients receiving a 2nd MEL-ASCT at 85.0% and most of those at standard dose (MEL 200 mg/m2). Results After balancing treatment and control groups with identical treatment, baseline characteristics, and dose of 1st ASCT (140 or 200 mg/m2), we found 289 tandem and 289 single transplant pairs with no significant differences across any of our balancing covariates (all paired Wilcoxon rank test p-values = 1.00). Analysis of these pair-matched cases strongly supported tandem transplantation as superior in outcome-cases with tandem transplantation had 5-year OS rate of 74.8% compared to 54.1% in single transplant cases (logrank p-value: 1.44e-06). For cases with tandem transplantation, we pair-matched 164 cases with tandem 200 mg/m2 transplants to 164 cases with either 140 mg/m2 received as 1st ASCT, 2nd ASCT, or both transplants. Analysis of these pair-matched cases strongly supported tandem 200 mg/m2 over 140 mg/m2 as the 5-year OS rates were 78.5% and 63.6%, respectively (logrank p-value: 1.23e-03). Conclusion MEL-ASCT is the backbone for treatment of MM. From our study, there is overwhelming evidence that application of tandem MEL-ASCT delivers superior clinical outcome compared to single MEL-ASCT. In order to achieve the best clinical results tandem MEL-ASCT should be performed using standard dose MEL 200 mg/m2; dose reduction (140 mg/m2) leads to unfavorable clinical outcome. Ongoing analysis aims to reveal the benefits of MEL-ASCT treatment across specific subgroups to better understand differential response and optimal therapy for patients across distinct molecular and risk subgroups. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Thanendrarajan: University of Arkansas for Medical Sciences: Employment. Stein:University of Arkansas for Medical Sciences: Employment. Davies:Celgene: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Onyx: Consultancy; University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Zangari:Onyx: Research Funding; University of Arkansas for Medical Sciences: Employment; Millennium: Research Funding; Novartis: Research Funding. Heuck:Millenium: Other: Advisory Board; Janssen: Other: Advisory Board; Celgene: Consultancy; Foundation Medicine: Honoraria; University of Arkansas for Medical Sciences: Employment. Schinke:University of Arkansas for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Jethava:University of Arkansas for Medical Sciences: Employment. Weinhold:University of Arkansas for Medical Sciences: Employment; Janssen Cilag: Other: Advisory Board. Matin:University of Arkansas for Medical Sciences: Employment. Mathur:University of Arkansas for Medical Sciences: Employment. Mohan:University of Arkansas for Medical Sciences: Employment. Radhakrishnan:University of Arkansas for Medical Sciences: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:Celgene: 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; CancerNet: Honoraria; MMRF: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Weismann Institute: Honoraria.
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Thanendrarajan, Sharmilan, Daisy V. Alapat, Maurizio Zangari, Carolina Schinke, Christoph Heuck, Frits van Rhee, Adam Rosenthal, et al. "Upfront 28-Day Metronomic Therapy for High-Risk Multiple Myeloma (HRMM)." Blood 126, no. 23 (December 3, 2015): 1843. http://dx.doi.org/10.1182/blood.v126.23.1843.1843.
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Abstract Introduction: Despite major advances in MM therapy with the inclusion of novel agent combinations for induction prior to and after autotransplant-supported high-dose melphalan, the 15% of patients with GEP-defined HRMM continue to fare poorly with PFS and OS not exceeding 2 and 3 years, respectively. This poor outcome has not been improved with less dose-intense and more dose-dense Total Therapy 5. Having previously reported on 16-day metronomic therapy with low-dose doxorubicin (DOX) and cisplatin (DDP) plus VTD (Papanikolaou, Haematologica), we explored further extension of such metronomic treatment to 28 days (metro-28) also in newly diagnosed HRMM patients. Patients and Methods: All patients signed a written informed consent and data analysis was approved by our IRB. In the outpatient setting, a single cycle of metro-28 comprised DOX and DDP each at 1.0mg/m2/d for 28d by continuous infusion (CI), along with VTD (bortezomib 1.0mg/m2 on days 1-4, 7-10, 13-16, 19-22, 25-28; DEX 12mg on days 1-4, 7-10, 13-16, 19-22, 25-28; thalidomide 50-100mg/d x 28d; some patients also received vincristine [VCR] at a flat daily dose of 0.07mg/d x 28d by CI. Results: Fourteen patients were initiated on metro-28. Their characteristics included age >=65y in 12; albumin <3.5g/dL in 8; B2M >5.5mg/L in 7; cytogenetic abnormalities [CA] were present in 10; GEP70 HRMM in 9/13; PR subgroup in 8/13 (Table 1). The median follow up is 11mo. As portrayed in Figure 1A, no patient has died; the 6mo PFS estimate was 85% (Figure 1B); responses included CR in 3/14, VGPR in 7/14 and PR in 10/14 (Figure 1C); and the PR duration estimate at 6mo is 80% (Figure 1D). Of interest, GEP70 scores morphed to low risk in 3/13. Vascular density (CD34) decreased markedly in most patients evaluated. Toxicities were minor; myelosuppression was virtually absent; alopecia was not encountered. Subsequent salvage therapies included repeat metro-28, combination chemotherapy (PACMED) and autotransplants. Conclusion: We conclude that metro-28 is a promising and safe strategy for elderly patients with HRMM, and we hypothesize an anti-angiogenic mechanism of action in addition to direct anti-MM effects. Table 1. Patient characteristics Factor n/N (%) Age >= 65 yr 12/14 (86%) Albumin < 3.5 g/dL 8/14 (57%) B2M >= 3.5 mg/L 9/12 (75%) B2M > 5.5 mg/L 7/12 (58%) Hb < 10 g/dL 10/14 (71%) Cytogenetic Abnormalities 10/14 (71%) CA within 1 Year of Therapy 10/14 (71%) CA within 90 Days of Therapy 9/14 (64%) GEP 70-Gene High Risk 9/13 (69%) GEP PR Subgroup 8/13 (62%) GEP Proliferation Index >= 10 7/13 (54%) GEP Centrosome Index >= 3 7/13 (54%) n/N (%): n- Number with factor, N- Number with valid data for factor Figure 1. Figure 1. Disclosures Thanendrarajan: University of Arkansas for Medical Sciences: Employment. Alapat:University of Arkansas for Medical Sciences: Employment. Zangari:University of Arkansas for Medical Sciences: Employment; Onyx: Research Funding; Millennium: Research Funding; Novartis: Research Funding. Schinke:University of Arkansas for Medical Sciences: Employment. Heuck:Millenium: Other: Advisory Board; Janssen: Other: Advisory Board; Foundation Medicine: Honoraria; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Rosenthal:Cancer Research and Biostatistics: Employment. Epstein:University of Arkansas for Medical Sciences: Employment. Yaccoby:University of Arkansas for Medical Sciences: Employment. Davies:Janssen: Consultancy; Onyx: Consultancy; University of Arkansas for Medical Sciences: Employment; Millenium: Consultancy; Celgene: Consultancy. Morgan:MMRF: Honoraria; 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; Weismann Institute: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment.
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Heuck, Christoph, Niels Weinhold, Erich Allen Peterson, Michael Bauer, Caleb K. Stein, Timothy Ashby, Shweta S. Chavan, et al. "The Impact of Combination Chemotherapy and Tandem Stem Cell Transplant on Clonal Substructure and Mutational Pattern at Relapse of MM." Blood 126, no. 23 (December 3, 2015): 372. http://dx.doi.org/10.1182/blood.v126.23.372.372.
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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.
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Latiff, AtikahAbdul, Saheera Kamarzaman, NorhafizahAb Manan, KrishnaGopal Rampal, and BalaKrishnian Muniandy. "Students' perception on anatomy education in Cyberjaya University College of Medical Sciences, Malaysia." Journal of the Anatomical Society of India 68, no. 2 (2019): 163. http://dx.doi.org/10.4103/jasi.jasi_46_19.
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Ab Manan, Norhafizah, Nasrin Jahan, Ahmad Munir Qureshi, Muhammad Najib Mohamad Alwi, and Abdul Rashid Abdul Rahman. "Teaching Evidence Based Medicine to Fourth Year Medical Students at Cyberjaya University College of Medical Sciences, Malaysia." Education in Medicine Journal 9, no. 3 (September 30, 2017): 55–62. http://dx.doi.org/10.21315/eimj2017.9.3.6.
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Heuck, Christoph, Shweta S. Chavan, Caleb K. Stein, Ruslana Tytarenko, Niels Weinhold, Siraj Ali, Vincent A. Miller, et al. "Comprehensive Genomic Profiling of Multiple Myeloma in the Course of Clinical Care Identifies Targetable and Prognostically Significant Genomic Alterations." Blood 126, no. 23 (December 3, 2015): 369. http://dx.doi.org/10.1182/blood.v126.23.369.369.
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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.
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Hamdy, Hossam, and M. Brownell Anderson. "The Arabian Gulf University College of Medicine and Medical Sciences: A Successful Model of a Multinational Medical School." Academic Medicine 81, no. 12 (December 2006): 1085–90. http://dx.doi.org/10.1097/01.acm.0000246680.82786.76.
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Garg, Tarun K., Ricky D. Edmondson, Shweta S. Chavan, Katie Stone, Justin M. Stivers, Jessica I. Warden, Veronica Macleod, et al. "Differential ICAM3 Gene Expression Correlates with Susceptibility to Natural Killer Cell-Mediated Lysis in Multiple Myeloma." Blood 126, no. 23 (December 3, 2015): 2990. http://dx.doi.org/10.1182/blood.v126.23.2990.2990.
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Abstract Introduction We previously reported on the generation of highly activated/expanded natural killer cells (ENKs) after coculture with K562 cells modified to express membrane bound IL15 and 41BB-ligand. These cells have potent antimyeloma properties in vitro, in a NGS mouse model, and are safe when given to advanced multiple myeloma (MM) patients. (Szmania et al, J Immunother 2015) A potential obstacle to the effectiveness of ENK-based immunotherapy of MM is the evasion of immune recognition. We have generated 4 MM cell lines (OPM2, JJN3, ANBL6, and INA-6) which are resistant to ENK-mediated lysis to study mechanisms of resistance. These lines were derived from parental lines by repeated challenge with ENKs and maintained resistance long term when cultured without further exposure to ENKs.(Garg et al, Blood 2012, 120:4020) We have shown by stable isotope labeling with amino acids in cell culture-mass spectrometry, gene expression profiling (GEP), and flow cytometry that ICAM3 is downregulated in the ENK-resistant version of OPM2 (OPM2-R) compared to the parental OPM2. (OPM2-P; Garg et al, Blood 2013, 122:3105) We investigated OPM2-P and OPM2-R by whole exome sequencing (WES) and RNA sequencing (RNAseq) with a focus on ICAM3, evaluated ICAM3 cell surface expression on patient myeloma cells, and studied the importance of ICAM3 expression on ENK functionality. Methods DNA and RNA were extracted from OPM2-P and OPM2-R cells using the Qiagen AllPrep kit. WES libraries were prepared with the Agilent qXT and Agilent SureSelect Clinical Research Exome kits with additional baits covering the Ig and MYC loci. RNAseq libraries were prepared using the Illumina TruSeq stranded mRNA kit. Samples were sequenced 100bp PE on an Illumina HiSeq2500. Samples for WES were sequenced to a mean coverage of >120x and RNAseq to a target of >100M reads. WES data were aligned to the Ensembl GRCh37/hg19 human reference using BWA mem. Somatic variants were called MuTect. RNAseq data were analyzed using Tuxedo Suite. Data were aligned to the Ensembl GRCh37/hg19 human reference using TopHat with Bowtie2. Transcriptome reconstruction, quantification and differential analysis was performed using CuffLinks. ENK-mediated lysis of myeloma cells was measured by 4 hour chromium release assay in the presence of isotype or ICAM3 blocking antibody. Bone marrow aspirates were obtained from MM patients after informed consent in accordance with the Declaration of Helsinki. Primary myeloma cells were selected with CD138-coated immunomagnetic beads and ICAM3 expression was assessed by flow cytometry gated on viable CD138 positive cells. Results There was no mutation in ICAM3 in OPM2-R by WES, but RNAseq found a significant reduction in ICAM3 RNA in OPM2-R compared to OPM2-P (p <0.008). Loss of ICAM3 expression on OPM2-R correlated with a reduction in sensitivity to ENK-mediated lysis compared to OPM2-P (mean 83%, range 77-88%, N=7 assays; E:T ratio 10:1). Blocking of ICAM3 on OPM2-P similarly reduced susceptibility to ENK-mediated cytotoxicity (mean 45%, range 30-56%, N=4 assays; E:T ratio 10:1). We next examined ICAM3 expression on primary myeloma cells by flow cytometry (N=49; GEP-defined high-risk n=43) and found that there is considerable biological inter-patient variation in ICAM3 expression (median MFI 922; range 97-5882, Figure 1A). Further, the majority of patients studied exhibited ICAM3-negative myeloma subpopulations (0.01%-19.4% of CD138 positive myeloma cells, Figure 1B). Functional studies will be presented to correlate the level of ICAM3 expression on primary myeloma cells with sensitivity to ENK-mediated lysis and resulting data shall be presented. Conclusion Our findings demonstrate that MM patients harbor ICAM3-negative myeloma populations in varying frequencies, and we hypothesize that these cells may be similarly resistant to ENK-mediated lysis. Functional assays exploring this question are in progress. By understanding the mechanisms of ENK resistance and immune escape in MM, we hope to elucidate a surrogate biomarker which will allow us to select subjects who are most likely to benefit from cellular immunotherapeutic strategies for enrollment in future ENK-based clinical trials. Additionally, the ICAM3/LFA-1 interaction is also important for adhesion of T cells to their targets; therefore, down-regulation of ICAM3 may also have functional implications in the efficacy of T cell-based therapies for MM. Disclosures Garg: University of Arkansas for Medical Sciences: Employment. Chavan:University of Arkansas for Medical Sciences: Employment. Stone:University of Arkansas for Medical Sciences: Employment. Stivers:University of Arkansas for Medical Sciences: Employment. Warden:University of Arkansas for Medical Sciences: Employment. Skinner:University of Arkansas for Medical Sciences: Employment. Lingo:University of Arkansas for Medical Sciences: Employment. Greenway:University of Arkansas for Medical Sciences: Employment. Khan:University of Arkansas for Medical Sciences: Employment. Johann:University of Arkansas for Medical Sciences: Employment. Heuck:Millenium: Other: Advisory Board; Celgene: Consultancy; Janssen: Other: Advisory Board; University of Arkansas for Medical Sciences: Employment; Foundation Medicine: Honoraria. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:University of Arkansas for Medical Sciences: Employment; Weismann Institute: Honoraria; MMRF: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; CancerNet: Honoraria; 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. Epstein:University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment.
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Atrash, Shebli, Bart Barlogie, Maurizio Zangari, Frits van Rhee, Sarah Waheed, Clyde Bailey, Nathan Petty, Christoph Heuck, Gareth J. Morgan, and Yogesh Jethava. "Outcomes of Autologous Transplantation for Treatment-Related AML and MDS in Previously Treated Multiple Myeloma Patients (pts)." Blood 126, no. 23 (December 3, 2015): 1997. http://dx.doi.org/10.1182/blood.v126.23.1997.1997.
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Abstract Introduction: Therapy related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) are significant long-term complications of MM treatment. We have treated pts on standard therapy protocols including TT2, TT3, TT4 and TT5. These protocols include an induction, tandem melphalan-based ASCT and consolidation, followed by three years of maintenance. As a part of the protocols, multiple bone marrow examinations including metaphase cytogenetics are performed at regular intervals, giving us the unique opportunity to examine the development of t-MDS/t-AML and understand the efficacy of subsequent treatment. Here we investigate the outcome of t-AML and t-MDS treated with autologous stem cell transplantation (ASCT) in MM patients. Materials and Methods, Results: During the period between 1998 to 2015, a total of 1558 pts were treated for MM with standard therapy protocols. We identified 68 pts out of 1558 who developed t-AML + t-MDS. Thirty-one had a confirmed diagnosis of t-AML, and thirty-seven had a diagnosis of t-MDS. The median age at diagnosis was 60 years (range 45-76). The median time from diagnosis MM of t-AML and t-MDS was 66 months (range, 9.6-155.4) and 63 months (range, 8-130), respectively. Baseline cytogenetics were as follows: complex cytogenetics in 34 pts out of 68, del(7) in 24 pts, del(5) in 17 pts, and del(17p) in 5 pts. Eighteen out of thirty-one t-AML pts were treated with ASCT. The remaining 13 pts did not receive ASCT. The treatment related mortality (TRM) at day100 (D100) in the ASCT group was 33% (6/18 pts). Neutrophil and platelet engraftment was achieved in all 18 pts by D21. Complete remission was achieved in 50% (9 out of 18) of pts. When we compared pts who received ASCT to those who were treated with chemotherapy only, the median overall survival (OS) was 11.28 months after ASCT vs 1.32 months without ASCT (p < 0.05). Nineteen out of thirty seven t-MDS pts were treated with ASCT. When we compared pts who received ASCT to chemotherapy only for t-MDS, there was no difference in survival between the groups. A mortality rate of 47% (9/19) was recorded at D200 after transplantation due to severe infections and lack of engraftment. Conclusion: t-AML and t-MDS treatment is a significant therapeutic challenge for the elderly, who often have poor risk cytogenetic markers, significant comorbidities and a compromised performance status. In our case series of post MM therapy t-AML, ASCT prolonged survival. In contrast, there was no change in survival of t-MDS pts, most likely due to high rate of infectious complications seen in this group. To our knowledge, this is the first analysis suggesting a survival benefit from ASCT in treating t-AML. Although the numbers in our study are small, we recommend that ASCT can be safely considered for t-AML patients who are physically fit, have autologous stem cells in storage and are overseen by a good supportive care team. These results need to be validated in large prospective studies. Disclosures Atrash: University of Arkansas for Medical Sciences: Employment. Barlogie:Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; European School of Haematology- International Conference on Multiple Myeloma: Other: Travel Stipend; ComtecMed- World Congress on Controversies in Hematology: Other: Travel Stipend; International Workshop on Waldenström's Macroglobulinemia: Other: Travel Stipend; Dana Farber Cancer Institute: Other: Travel Stipend; Multiple Myeloma Research Foundation: 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. Zangari:Onyx: Research Funding; Novartis: Research Funding; Millennium: Research Funding; University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Bailey:University of Arkansas for Medical Sciences: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Heuck:Celgene: Consultancy; Janssen: Other: Advisory Board; Millenium: Other: Advisory Board; Foundation Medicine: Honoraria; 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; Weismann Institute: Honoraria; CancerNet: Honoraria; University of Arkansas for Medical Sciences: Employment; 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. Jethava:University of Arkansas for Medical Sciences: Employment.
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Chung, Q.-En, Surajudeen Abiola Abdulrahman, Mohamad Khan Jamal Khan, Hassan Basri Jahubar Sathik, and Abdul Rashid. "The Relationship between Levels of Physical Activity and Academic Achievement among Medical and Health Sciences Students at Cyberjaya University College of Medical Sciences." Malaysian Journal of Medical Sciences 25, no. 5 (2018): 88–102. http://dx.doi.org/10.21315/mjms2018.25.5.9.
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McDonald, James E., Marcus M. Kessler, Michael Gardner, Amy Buros, Sarah Waheed, James Ntambi, Frits van Rhee, et al. "Assessment of Total Lesion Glycolysis and Metabolic Tumor Volume Improve the Clinical Value of Focal Lesion Assessment By FDG PET/CT in Myeloma." Blood 126, no. 23 (December 3, 2015): 724. http://dx.doi.org/10.1182/blood.v126.23.724.724.
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Abstract Introduction: Focal lesions are important anatomical features seen in the bone marrow of multiple myeloma patients that contribute to drug resistance and disease relapse. Fluroine-18 fluorodexyglucose positron emission tomography with CT attenuation correction (18F-FDG PET/CT) is useful in the detection and enumeration of focal lesions and in semi-quantitative characterization of metabolic activity by calculation of glucose uptake reported as a standardized uptake value (SUV). Lesion count and SUV are predictors of outcome. Two additional variables, total lesion glycolysis (TLG) and metabolic tumor volume (MTV) can also be assessed and have the potential to improve the value of this approach. The purpose of this study was to determine whether TLG and MTV can predict progression free survival (PFS) and overall survival (OS), and to determine whether they are superior to traditional assessment methods. Materials and Methods: 191 patients underwent whole body PET/CT in the Total Therapy 3A trial and were evaluated using 3 dimensional region of interest analysis with TLG, MTV, and standard measurement parameters derived for all focal lesions with peak SUV above the background red marrow signal. Survival analysis was performed using Kaplan-Meier and log-rank tests. Univariate and multivariate analyses were performed using Cox proportional hazards regression. Results: Baseline characteristics show that 43/191 patients (23%) had no detectable lesions by PET. 1-3 lesions were present in 55/191 (28%) of patients and over 3 lesions in 93/191 (49%) of patients. A baseline TLG >205g was seen in 18% (34/191) of patients, with a TLG >620g being seen in 7% (14/191). A baseline MTV >210cm3 was seen in 7% (14/191). The distribution of patients with high TLG scores between molecular subgroups was not even with patients in the PR, MF and HY subgroups having higher scores. The 3 year PFS and OS for patients with no PET focal lesions was 83.1% and 88.3%, for patients with 1-3 lesions was 83.9%, and 85.5%, and for patients with >3 lesions 59.6% and 63.5% (p<0.0001). The 3 year PFS and OS for patients with a baseline TLG of less than 205g was 82.8% and 86.0%, compared to patients with a baseline TLG between 205g and 620g of 75.0% and 80.0%, and to patients with a baseline TLG of greater than 620g of 14.3% and 21.4% (p<0.0001). A similar pattern was seen for complete response (CR) duration. The MTV also had prognostic importance with 3 year PFS and OS for patients with a baseline MTV of less than 210cm3 at 81.4% and 84.7%, compared to patients with a baseline MTV of greater than 210cm3 of 21.4% and 28.6% (p<0.0001). Pearson Correlation Coefficient (r) between MTV and TLG was 0.94232 (p-value <.0001). On univariate analysis baseline PET/CT with >3 focal lesions (HR 1.92, 95% CI 1.22-3.04, p=0.004), TLG >205g (HR 2.99, 95% CI 1.83-4.88, p<0.0001), baseline TLG > 620g (HR 6.90, 95% CI 3.67-12.97, p<0.0001), and MTV >210cm3 (HR 6.20, 95% CI 3.33-11.54, p<0.0001) were statistically significant in predicting OS and PFS. In multivariate analysis baseline TLG>620g retained prognostic significance for predicting PFS and OS together with high B2M, LDH and GEP based proliferation. Importantly baseline TLG >620g and baseline MTV >210cm3 were statistically more predictive of poor PFS and OS than baseline PET with >3 focal lesions in both univariate and multivariate models. Conclusion : TLG assessment is superior to counting the number of focal lesions. It is the optimum method for evaluating the extent of focal lesions and to predict clinical outcome. As this measurement can be standardized using FDA approved software, it should be utilized clinically and in trials going forward. Disclosures McDonald: University of Arkansas for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Ntambi:University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Zangari:University of Arkansas for Medical Sciences: Employment; Novartis: Research Funding; Onyx: Research Funding; Millennium: Research Funding. Heuck:Janssen: Other: Advisory Board; Millenium: Other: Advisory Board; Foundation Medicine: Honoraria; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Schinke:University of Arkansas for Medical Sciences: Employment. Thanendrarajan:University of Arkansas for Medical Sciences: Employment. Mitchell:Cancer Research and Biostatistics: Employment. Hoering:Cancer Research and Biostatistics: Employment. Barlogie: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; Dana Farber Cancer Institute: Other: Travel Stipend; Multiple Myeloma Research Foundation: Other: Travel Stipend. Morgan:Weisman Institute: Honoraria; CancerNet: Honoraria; MMRF: Honoraria; University of Arkansas for Medical Sciences: Employment; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: 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, Research Funding. Davies:Array-Biopharma: Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; Onyx-Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.
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Tomczak, RL. "College of Podiatric Medicine and Surgery in Des Moines." Journal of the American Podiatric Medical Association 82, no. 6 (June 1, 1992): 304–10. http://dx.doi.org/10.7547/87507315-82-6-304.
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The College of Podiatric Medicine and Surgery was established in 1981 as a fully integrated college of the University of Osteopathic Medicine and Health Sciences, Des Moines, Iowa, becoming the only school in the profession to be part of an academic health science center. Thus, this college provides a unique opportunity for the students and the podiatric medical profession to receive a multidisciplinary education, preparing them for podiatric medical practice as an integral part of total health care.
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Waheed, Sarah, Hongwei Wang, Pingping Qu, Christoph Heuck, Aasiya Matin, Yogesh Jethava, Frits van Rhee, et al. "Gene Expression Profiling of Extramedullary Disease-Related Toward Identification of a Terminal Disease Pathway in Multiple Myeloma." Blood 126, no. 23 (December 3, 2015): 1777. http://dx.doi.org/10.1182/blood.v126.23.1777.1777.
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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.
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Al Wadry, Nadia. "Faculty Development Initiatives at the College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman." Sultan Qaboos University Medical Journal [SQUMJ] 20, no. 3 (October 5, 2020): 271. http://dx.doi.org/10.18295/squmj.2020.20.03.005.
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Faculty development is necessary to improve and update teaching and learning methodologies. As such, a variety of learning activities have been designed to improve teaching competencies of individual teachers. The College of Medicine & Health Sciences at Sultan Qaboos University, Muscat, Oman, recognised the need for teacher training in order to bring faculty up-to-date in teaching and assessment methodologies. A programme of regular and one-time interventions consisting of short courses, workshops and a series of lectures was offered. Feedback from the participants and facilitators led to programme expansion and enhancement. This special contribution discusses the impact of the programme on faculty and the college.Keywords: Teacher Training; Medical Education; Oman.
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Qureshi, Shoeb, Abdullah Alanazi, Farhan Al Enezi, MohammdMesfer Alqahtani, Saleh Al-Oraibi, TurkiFaleh Alshammari, and MumtazAhmed Ansari. "Effects of passive smoking on students at College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, Riyadh." Journal of Natural Science, Biology and Medicine 6, no. 1 (2015): 100. http://dx.doi.org/10.4103/0976-9668.149100.
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Stein, Caleb K., Faith E. Davies, Christoph Heuck, Niels Weinhold, Shweta S. Chavan, Brian A. Walker, Sharmilan Thanendrarajan, et al. "Molecular Subtyping and Risk Stratification for the Classification of Myeloma." Blood 126, no. 23 (December 3, 2015): 4173. http://dx.doi.org/10.1182/blood.v126.23.4173.4173.
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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.
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Lown, Debbie, and Kenneth Lown. "Effects of enteral nutrition and ethanol on cytochrome P450 distribution in small intestine of male rats R HAKKAK, M RONIS, AND T BADGER University of Arkansas for Medical Sciences; Arkansas Children's Hospital Research Center, Little Rock." Nutrition in Clinical Practice 8, no. 6 (December 1993): 291. http://dx.doi.org/10.1177/088453369300800608.
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Watts, Chris, and Ijeoma Ibegbulam. "Access to Electronic Healthcare Information Resources in Developing Countries: experiences from the Medical Library, College of Medicine, University of Nigeria." IFLA Journal 32, no. 1 (March 2006): 54–61. http://dx.doi.org/10.1177/0340035206063903.
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Bindayna, Khalid Mubarak, and Abdelhalim Deifalla. "The Curriculum at the College of Medicine and Medical Sciences at Arabian Gulf University: A Way Forward to Meet the Future Medical Education Needs." Journal of Medical Education and Curricular Development 7 (January 2020): 238212052093290. http://dx.doi.org/10.1177/2382120520932904.
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Arabian Gulf University (AGU) follows a curriculum based on Problem Based Learning (PBL). PBL is a learner-centered approach that empowers students for life-long learning. Students are taught through problems that are designed based on global health problems customized to the local needs. The classroom teaching is complemented through adjunct programs like community health activities and professional skills program. Medical education aims to meet the changing needs of society. Demographics, disease epidemiology and healthcare needs of the gulf countries have changed over 38 years since the inception of AGU. To keep pace with the changing demands, it is imperative that the curriculum is reviewed in the light of advances in technology and newer techniques of medical education.In the present article the curriculum at AGU is reviewed based on the predictors for future medical education and alternative teaching methods that can be integrated to optimize the student outputs are explored.
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Yaccoby, Shmuel, Joshua Epstein, Pingping Qu, Frits van Rhee, Maurizio Zangari, Christoph Heuck, Faith E. Davies, et al. "Melphalan Affects Genes Critical for Myeloma Survival, Homing, and Response to Cytokines and Chemokines." Blood 126, no. 23 (December 3, 2015): 1808. http://dx.doi.org/10.1182/blood.v126.23.1808.1808.
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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.
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Tian, Erming, Joshua Epstein, Pingping Qu, Christoph Heuck, Frits van Rhee, Maurizio Zangari, Antje Hoering, Jeffery Sawyer, Bart Barlogie, and Gareth J. Morgan. "Deletion of TP53 (17p13) Is Associated with Poor Outcome for Newly Diagnosed High-Risk Multiple Myeloma." Blood 126, no. 23 (December 3, 2015): 2982. http://dx.doi.org/10.1182/blood.v126.23.2982.2982.
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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.
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Lee, Joan. "Reviewer Acknowledgements for Journal of Plant Studies, Vol. 7, No. 1." Journal of Plant Studies 7, no. 1 (February 27, 2018): 73. http://dx.doi.org/10.5539/jps.v7n1p73.
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Journal of Plant Studies wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal are greatly appreciated.Journal of Plant Studies is recruiting reviewers for the journal. If you are interested in becoming a reviewer, we welcome you to join us. Please find the application form and details at http://www.ccsenet.org/reviewer and e-mail the completed application form to jps@ccsenet.org.Reviewers for Volume 7, Number 1Adriana F. Sestras, University of Agricultural Sciences and Veterinary Medicine, RomaniaAlireza Valdiani, University of Copenhagen, DenmarkAmi Lokhandwala, University of Mississippi, Department of Biology, USAIsabel Desgagné-Penix, Université du Québec à Trois-Rivières, CanadaKirandeep Kaur Mani, California seed and Plant Labs, Pleasant Grove, CA, USAMartina Pollastrini, University of Florence, ItalyMassimo Zacchini, Institute of Agroenvironmental and Forest Biology, ItalyMatteo Busconi, Università Cattolica del Sacro Cuore, ItalyMelekber Sulusoglu, Arslanbey Vocational School Kocaeli University, TurkeyMilana Trifunovic-Momcilov, Institute for Biological Research “Sinisa Stankovic”, SerbiaMohamed Trigui, Sfax Preparatory Engineering Institute and CBS, TunisiaMohammad Nurul Amin, Noakhali Science and Technology University, BangladeshMontaser Fawzy Abdel-Monaim, Plant Pathology Res. Instatute, Agric. Res. Center, EgyptNina Ivanovska, Institute of Microbiology, BulgariaPanagiotis Madesis, Centre for Research and Technology Hellas/Institiute of Applied Biosciences, GreeceRajiv Ranjan, T. P. Varma College, IndiaRaksha Singh, University of Arkansas, USASlawomir Borek, Adam Mickiewicz University, PolandSuheb Mohammed, University of Virginia, USA
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Hamdy, H., M. GREALLY, I. N. GRANT, H. EL-SHAZALI, U. NAYAR, K. RAJAB, K. AL-ROOMI, et al. "Professional skills programme in a problem-based learning curriculum: experience at the College of Medicine & Medical Sciences, Arabian Gulf University." Medical Teacher 23, no. 2 (January 2001): 214–16. http://dx.doi.org/10.1080/014215901750177604.
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Althubaiti, Suha, and Norah Althubaiti. "Saudi Medical Students’ Interest in Basic Medical Sciences and the Factors Affecting It." Global Journal of Health Science 10, no. 3 (February 28, 2018): 30. http://dx.doi.org/10.5539/gjhs.v10n4p30.
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OBJECTIVES: To evaluate medical students’ interest in basic sciences and identify perceived obstacles for choosing a career in basic science.METHODS: A cross-sectional survey study was conducted and carried out between March and May 2016 with 600 undergraduate medical students at the College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. Students’ interest towards basic medical sciences was evaluated using a questionnaire.RESULTS: A total of 352 medical students (180 male and 172 female) responded. The leading reasons for not pursuing a career in basic sciences were that medical students aimed primarily to become clinicians (71.6%), would prefer to engage in clinical research (40.4%), were concerned about salaries in basic sciences (36.6%), and had not experienced exciting practical training in basic sciences (26.2%).CONCLUSION: Integrating basic sciences and clinical medicine and increasing research participation will result in more positive attitudes towards basic sciences. Furthermore, reducing the students’ concerns will encourage medical students to engage more with basic medical science.
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Henriksen, Erik J., Anne E. Atwater, Nicholas A. Delamere, and William H. Dantzler. "The Physiology undergraduate major in the University of Arizona College of Medicine: past, present, and future." Advances in Physiology Education 35, no. 2 (June 2011): 103–9. http://dx.doi.org/10.1152/advan.00089.2010.
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The American Physiological Society (APS) and APS Council encourage the teaching of physiology at the undergraduate, graduate, and medical school levels to support the continued prominence of this area of science. One area identified by the APS Council that is of particular importance for the development of future physiologists (the “physiology pipeline”) is the teaching of physiology and physiology-related topics at the undergraduate level. In this article, we describe the historical development and implementation of an undergraduate program offered through the Department of Physiology, a basic science department in the College of Medicine at the University of Arizona, culminating in a Bachelor of Science in Health Sciences degree with a major in Physiology. Moreover, we discuss the current Physiology curriculum offered at our institution and explain how this program prepares our students for successful entry into a variety of postbaccalaureate professional programs, including medical school and numerous other programs in health professions, and in graduate study in the Masters and Doctoral programs in biomedical sciences. Finally, we cover the considerable challenges that we have faced, and continue to face, in developing and sustaining a successful physiology undergraduate major in a college of medicine. We hope that the information provided on the Physiology major offered by the Department of Physiology in the College of Medicine at the University of Arizona will be helpful for individuals at other institutions who may be contemplating the development and implementation of an undergraduate program in Physiology.
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Memon, Ismail, Abdulmohsen Alkushi, Dur E. Shewar, Irfan Anjum, and Zeeshan Feroz. "Approaches used for teaching anatomy and physiology in the university pre-professional program at King Saud bin Abdulaziz University for Health Sciences." Advances in Physiology Education 44, no. 2 (June 1, 2020): 188–91. http://dx.doi.org/10.1152/advan.00167.2019.
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Many medical schools offer pre-professional programs to undergraduate students. The main purpose of the university pre-professional program (UPPP) is to equip students with the necessary knowledge and skills required to successfully cope with the academic demands of further education provided by professional colleges. The aim of this commentary article is to describe the role of UPPP at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) in preparing students to continue studies at the College of Medicine (COM) and other health-related colleges. The anatomy and physiology course is presented as a representative model. An outline of the UPPP in the context of the curriculum, teaching strategies, learning facilities, and assessment is presented. The pre-professional program at KSAU-HS prepares school graduates to become self-learners and enable them to learn effectively in the clinical context in a problem-based learning curriculum at COM.
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Momeni, Maryam, Azam Ghorbani, and Zahra Arjeini. "Disordered eating attitudes among Iranian university students of medical sciences: The role of body image perception." Nutrition and Health 26, no. 2 (April 1, 2020): 127–33. http://dx.doi.org/10.1177/0260106020912657.
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Background: Disordered eating attitudes and behaviors have become an issue of worldwide concern. Aim: This research was designed to investigate the role of body image satisfaction in the relationship with eating attitudes among students of Qazvin University of Medical Sciences in Iran. Methods: In this cross-sectional study, 385 Qazvin university students of medical sciences were recruited by randomized stratified sampling in 2014. The students completed a three-part questionnaire (socio-demographic, Eating Attitudes Test and Body Shape Questionnaire) in their classrooms. We used hierarchical generalized linear models to identify variables significantly associated with Eating Attitudes Test scores. Results: The mean age of the students was 21.80 ± 2.98 years. Mean scores for the Eating Attitudes Test and Body Shape Questionnaire were 66.75 ± 29.8 and 11.86 ± 10.97 respectively; 18.5% of students had a score of 20 and above (≥ 20) that indicated disordered eating attitudes or as being at risk of eating disorders. In the multiple regression model, the Eating Attitudes Test was related to screening body image dissatisfaction (β = 0.122, P < 0.001). Body mass index was negatively related to the Eating Attitudes Test score (β= -0.488, P < 0.016), and diet was significantly correlated with an increased Eating Attitudes Test score (β = 5.803, P < 0.001). Conclusions: The risk of eating disorders is relatively high among Iranian university students. It can be a warning to health policy makers and should be the focus of special attention. In the present study, the most important factor related to abnormal eating attitudes was body image dissatisfaction. Regarding the complexity of the causes of eating disorders, various preventive and therapeutic interventions are necessary to avoid the dissemination in society of an idealized view of excessive thinness and further unfavorable outcomes in college students.
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Lazerson, Jack, Judith Rosenthal, Carolyn Glaubensklee, Thomas Hunt, Bruce Morgenstern, Jayabala Pamidimukkala, David M. Penn, Ken Rosenthal, Mira Sarsekeyeva, and Stephanie Wragg. "Adaptation of the Roseman 6-Point Mastery Learning Model to the College of Medicine Program." Journal of Medical Education and Curricular Development 5 (January 2018): 238212051880311. http://dx.doi.org/10.1177/2382120518803111.
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Medical education has evolved over time toward a model which integrates clinical medicine with the basic sciences. More recently, medical education has put an emphasis on outcome-based education. Other areas of health care education have had a similar emphasis which can provide models to inform a new model for medical education. The Roseman University of Health Sciences has developed and implemented a model based on underlying tenets of mastery learning since 1999. The model has been implemented in pharmacy, nursing, and dental education. It was conceived as an integration of 6 key points which reinforce each other and interrelate to support learning. The model has been modified for application to medical education in support of medical education’s outcome-based emphasis and to address the educational demands of the changing environment of the practice of medicine.
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Esan, OluwaseunTaiwo, AyodejiPatrick Akinyemi, OluwafemiMoses Ayegbusi, ToheebAdemuyiwa Bakare, YakubLekan Balogun, and AlexanderOdunayo Ogunwusi. "Determinants of uptake of periodic medical examination among students of college of health sciences, Obafemi Awolowo University Ile-Ife, South-West Nigeria." Nigerian Journal of Medicine 29, no. 4 (2020): 575. http://dx.doi.org/10.4103/njm.njm_150_20.
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Parve, Swapnil, Ali Ershadi, Alexandr Karimov, Anne Dougherty, Chiratidzo E. Ndhlovu, Midion M. Chidzonga, and Majid Sadigh. "Access, attitudes and training in information technologies and evidence-based medicine among medical students at University of Zimbabwe College of Health Sciences." African Health Sciences 16, no. 3 (October 18, 2016): 860. http://dx.doi.org/10.4314/ahs.v16i3.29.
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Annet Kinengyere, Alison, Julie Rosenberg, Olivia Pickard, and Moses Kamya. "Utilization and uptake of the UpToDate clinical decision support tool at the Makerere University College of Health Sciences (MakCHS), Uganda." African Health Sciences 21, no. 2 (August 2, 2021): 904–11. http://dx.doi.org/10.4314/ahs.v21i2.52.
Full textAbstract:
Background: The use of point-of-care, evidence-based tools is becoming increasingly popular. They can provide easy-to- use, high-quality information which is regularly updated and has been shown to improve clinical outcomes. Integrating such tools into clinical practice is an important component of improving the quality of health care. However, because such tools are rarely used in resource-limited settings, there is limited research on uptake especially among medical students.
Objective: This paper explores the uptake of one such tool, Up-To-Date, when provided free of cost at a medical school in Africa.
Methods: In partnership with the Better Evidence at Ariadne Labs free access to UpToDate was granted through the MakCHS IP address. On-site librarians facilitated training sessions and spread awareness of the tool. Usage data was aggre- gated, based on log ins and content views, presented and analyzed using Excel tables and graphs.
Results: The data shows evidence of meaningful usage, with 43,043 log ins and 15,591 registrations between August 2019 and August 2020. The most common topics viewed were in obstetrics and gynecology, pediatrics, drug information, and infectious diseases. Access occurred mainly through the mobile phone app.
Conclusion: Findings show usage by various user categories, but with inconsistent uptake and low usage. Librarians can draw upon these results to encourage institutions to support uptake of point-of-care tools in clinical practice.
Keywords: UpToDate clinical decision support tool; Makerere University College of Health Sciences; Uganda.