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Uzelac, Bojana, Sanja Vasić, Danijela Velikinac e Dušica Gujaničić. "ECG eponymos". ABC - casopis urgentne medicine 21, n.º 3 (2021): 12–18. http://dx.doi.org/10.5937/abc2103012u.
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Eponyms are widely represented in technical, social and natural sciences. Electrocardiography terms, named after the researcher who first described them, have not been summarized in one place until now. Wellens syndrome (Henrick Joan Joost Wellens, Dutch cardiologist) refers to a subgroup of patients with unstable angina who are at risk of developing an anterior myocardial infarction. In 2008, the Dutch cardiologist Robert Jan de Winter described a unique electrocardiographic (ECG) finding for proximal left anterior descending artery occlusion, named de Winter's pattern.Smith-Sgarbossa criteria (Elena Sgarbossa, Stephen Smith) are used to recognize acute myocardial infarction in patients with left bundle branch block. Schamroth's sign (Abraham Leo Schamroth, South African cardiologist) is an indirect ECG finding that indicates chronic obstructive pulmonary disease. Wolff-Parkinson-White syndrome (WPW) was named after the doctors who in 1930. first described the syndrome of short PR interval and abnormal QRS complexes, associated with paroxysmal tachycardia (Louis Wolff, John Parkinson, Paul Dudley White). S1Q3T3 or McGinn-White sign (Sylvester McGinn and Paul White) was first described in 1935. as an ECG finding in support of acute pulmonary heart disease. Second degree AV blocks could be type Wenckebach (Karel Frederik Wenckebach, Dutch anatomist) or type Mobitz (Woldemar Mobitz, Russian-German physician). Ashman's phenomenon (Richard F. Ashman, American physiologist) is a simple ECG manifestation of conduction disturbances, caused by a change in frequency. Bix's rule (Harold Bix) is used to recognize supraventricular tachycardia. Brugada syndrome (Pedro and Josep Brugada) is a congenital channelopathy of sodium channels, with a high risk of sudden cardiac arrest. TP segment's down-sloping in the early stage of pericarditis is called Spodick's sign (David H. Spodick, American cardiologist).
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Quinlivan, Mary. "Dalzell, Enterprising Elite - The Boston Associates And The World They Made". Teaching History: A Journal of Methods 17, n.º 1 (1 de abril de 1992): 33. http://dx.doi.org/10.33043/th.17.1.33.
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In this fine collective biography of the merchants-turned-industrialists who developed the famed Waltham-Lowell system of textile manufacture, Robert F. Dalzell has produced a book of considerable importance in the history of American industrialization, entrepreneurship, and philanthropy. Dalzell presents a well-researched and lucid study of this wealthy, closely knit group of businessmen, a study that appropriately places these men and their activities in the broad sociocultural setting. The Boston Associates, according to Dalzell, were industrial pioneers who introduced integrated innovations on a hitherto unparalleled scale, but whose motivation was essentially conservative.
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Baatz, Simon. "Enterprising Elite: The Boston Associates and the World They Made by Robert F. Dalzell, Jr". Technology and Culture 30, n.º 3 (julho de 1989): 694–95. http://dx.doi.org/10.1353/tech.1989.0085.
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Gaffney, Paul. "Tyson, Radio Free Dixie - Robert F. William & Roots Of Black Power". Teaching History: A Journal of Methods 26, n.º 2 (1 de setembro de 2001): 107–8. http://dx.doi.org/10.33043/th.26.2.107-108.
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Timothy Tyson frames his prize-winning first book with two images. In 1936 an eleven-year old African-American boy in Monroe, North Carolina, witnessed a white police officer, Jesse Helms, Sr., physically assault a black woman and then drag her, dress up over her head, along the pavement to the local jail. White bystanders laughed. African American men hung their heads and hurried away. Sixty years later Robert F. Williams, that black boy who became an advocate of "armed self-reliance," was laid to rest, his body carefully dressed in a gray suit given him by Mao Zedong, his coffin adorned with a red, black, and green pan-African flag, and his eulogy given by Rosa Parks, the embodiment of non-violent resistance.
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Xie, Phil F., Jaeho Chang, Paulina Siejka-Zielińska, Masato Inoue, Magdalena Drożdż, Joseph A. Chadwick, Thomas M. Carroll et al. "Abstract LB131: Association between epigenetic heterogeneity of esophageal adenocarcinoma and response to first-line immunochemotherapy in LUD2015-005 Trial". Cancer Research 83, n.º 8_Supplement (14 de abril de 2023): LB131. http://dx.doi.org/10.1158/1538-7445.am2023-lb131.
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Abstract Immune checkpoint inhibitors (ICI) were recently approved as a first-line treatment for inoperable esophageal adenocarcinomas (EAC) in combination with chemotherapy (CTX). Unfortunately, even though EAC has one of the highest tumor mutation burdens among all cancer types, response to immunochemotherapy (ICI+CTX) is highly variable, and the underlying molecular basis is incompletely understood. While genomic features such as mutations and copy number alterations in EAC are highly variable across samples, DNA methylation array data from numerous studies suggested that EAC can be clustered into a few consistent subtypes. We thus hypothesize that epigenetic heterogeneity of EAC may contribute to or associate with patients’ heterogeneous response to ICI+CTX, possibly through modulation of key genes or neoantigens. To test this hypothesis, we took advantage of a unique ICI+CTX LUD2015-005 trial in which inoperable EAC patients received first-line ICI for four weeks (ICI-4W), followed by ICI+CTX. Instead of methylation array, we also used a new DNA methylation sequencing technology, TET-Assisted Pyridine-Borane Sequencing (TAPS), on 64 tumor and 15 adjacent normal tissue samples collected from 23 EAC patients before and throughout treatment. Unlike prior studies that used methylation arrays which only cover ~2.5% of all CpG sites in the genome, TAPS detects genome-wide, base-resolution DNA methylation information. Furthermore, many previous studies did not account for variability in tumor content between samples, which could impact downstream DNA methylation analyses. In view of this, we proposed an analytical framework that includes tumor content and local copy number as key parameters, which estimates the tumor and stromal methylation and tests for differentially methylated regions (DMR). We also performed unsupervised clustering based on large scale genome-wide methylation pattern and revealed 2 major tumor clusters. Using the whole genome data, we identified a large set of shared tumor-specific DMRs, revealing that hypomethylation across wide regions of the genome and hypermethylation of certain gene bodies are common features in EAC. We also identified a set of shared outcome-associated DMRs in pre-treatment samples, which predicts better progression-free survival at 12 months. We further performed subgroup analysis of the 2 tumor clusters. Interestingly, we found higher numbers of cluster-specific prognostic DMRs with stronger effect sizes. This suggests that tumor subtypes may respond differently to treatment, and should be considered separately in statistical analyses. Altogether, these results indicate that a detailed understanding of tumor epigenetic heterogeneity will improve patient stratification in immunochemotherapy. Citation Format: Phil F. Xie, Jaeho Chang, Paulina Siejka-Zielińska, Masato Inoue, Magdalena Drożdż, Joseph A. Chadwick, Thomas M. Carroll, Richard P. Owen, Michael J. White, Joseph Kaplinsky, Robert Amess, Mark Middleton, Skirmantas Kriaucionis, Chunxiao Song, Benjamin Schuster-Böckler, Xin Lu. Association between epigenetic heterogeneity of esophageal adenocarcinoma and response to first-line immunochemotherapy in LUD2015-005 Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB131.
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Harp, Gillis J. "Enterprising Elite: The Boston Associates and the World They Made, by Robert F. Dalzell, Jr.Enterprising Elite: The Boston Associates and the World They Made, by Robert F. Dalzell, Jr. Cambridge, Mass., Harvard University Press, 1987. xviii, 298 pp. $27.50 U.S." Canadian Journal of History 23, n.º 2 (agosto de 1988): 277–78. http://dx.doi.org/10.3138/cjh.23.2.277.
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Bolton, Charles C. "Robert L. Zangrando and Ronald L. Lewis. Walter F. White: The NAACP’s Ambassador for Racial Justice." American Historical Review 125, n.º 2 (1 de abril de 2020): 673–74. http://dx.doi.org/10.1093/ahr/rhz772.
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Centeno-Girona, Hilmaris, Marievelisse Soto-Salgado, Mariela Bournigal-Feliciano, Sofia F. Contreras-Fernández, Karina Torres-Mojica, Victoria Williams, Arnethea L. Sutton, Katherine Tossas, Robert Winn e Marcia R. Cruz-Correa. "Abstract 2242: Clinical trials knowledge among Hispanic/Latino gastrointestinal cancer survivors in Puerto Rico". Cancer Research 84, n.º 6_Supplement (22 de março de 2024): 2242. http://dx.doi.org/10.1158/1538-7445.am2024-2242.
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Abstract The discovery of innovative cancer prevention and treatment approaches relies on voluntary participation in clinical trials (CTs); however, participation remains low among minorities/ethnic groups. Knowledge of CTs has been reported as a barrier to CT participation. Yet, there is limited understanding regarding CTs knowledge and participation among gastrointestinal (GI) cancer survivors in Puerto Rico (PR). Colorectal cancer is the second leading cause of death in PR, accounting for 13% among men and women. We aimed to describe the knowledge and factors associated with cancer-related CTs among Hispanic/Latino GI cancer survivors in PR. We analyzed preliminary data from an ongoing cross-sectional study targeting Hispanic/Latino GI cancer survivors aged 21+ years in PR. The study employed an interviewer-administered questionnaire to assess participants' awareness, knowledge, and participation in cancer-related CTs, and the social determinants of health (SDoH) associated with CT participation. Descriptive statistics were used to describe the population. Pearson chi-square test or Fisher's exact test were used accordingly to assess significance. A generalized linear model was used to estimate the odds ratios and 95% confidence intervals (CI) for significant variables. As of November 9, 2023, 59 Hispanic/Latino GI cancer survivors had completed the questionnaire. Women accounted for 56% of the sample, and the median age of study participants was 65 years (IQR: 19). Racial identity among participants was primarily white (63%), followed by other races (18%) and African-American (18%). Most participants were in complete or partial remission from cancer (83%). A significant proportion of the respondents reported having at least 12th grade (81%) and an annual income of $20,000 or higher (67%). Most participants (76%) accurately identified the correct definition of a CT. Participants with 12th grade or more had 1.5 (95% CI:1.1-1.9) times the possibility to correctly identify the CT definition compared to to those with less than 12th grade. Similarly, respondents with an annual income equal or higher than $20,000 had 1.4 (95% CI:1.1-1.8) times the possibility to correctly identify the CT definition compared to their counterpart. Furthermore, 93.2% of respondents had a score of at least 80% of correct responses regarding their knowledge of CTs. Although nearly 100% of the respondents knew about CTs, only 20% had participated. Despite a high level of knowledge regarding CTs in PR, a significant gap remains between knowledge and participation. Factors such as education and income might play a role in understanding the CT definition. However, the barriers preventing participation, including SDoH need further exploration. Enhancing participation among Hispanic/Latino GI cancer survivors in PR is essential for advancing cancer research and improving outcomes for this at-risk population. Citation Format: Hilmaris Centeno-Girona, Marievelisse Soto-Salgado, Mariela Bournigal-Feliciano, Sofia F. Contreras-Fernández, Karina Torres-Mojica, Victoria Williams, Arnethea L. Sutton, Katherine Tossas, Robert Winn, Marcia R. Cruz-Correa. Clinical trials knowledge among Hispanic/Latino gastrointestinal cancer survivors in Puerto Rico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2242.
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Xie, Guorong. "Walter F. White: The NAACP's Ambassador for Racial Justice by Robert L. Zangrando and Ronald L. Lewis". Journal of Southern History 86, n.º 3 (2020): 749–50. http://dx.doi.org/10.1353/soh.2020.0238.
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Quaney, Vianey, Benjamin Kroger, Aishwarya Sannareddy, Umar Khan, Fatma Kalkan, Robert H. Collins, Yazan F. Madanat et al. "Abstract 5925: Prevalence of clonal hematopoiesis in patients with monoclonal gammopathy of undetermined significance". Cancer Research 83, n.º 7_Supplement (4 de abril de 2023): 5925. http://dx.doi.org/10.1158/1538-7445.am2023-5925.
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Abstract INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the expansion of progeny derived from hematopoietic stem cells that have acquired somatic mutations at a VAF greater than 2%. CHIP manifests in 10% of patients older than 65 and is associated with an increased risk of progression to malignancies such as the MDS or AML. Although the risk factors for developing CHIP remain incompletely defined, they include prior exposure to chemotherapy and a history of smoking. Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the abnormal growth of clonal plasma cells in the bone marrow and carries a risk of 1% for progression to multiple myeloma (MM) per year. Like CHIP, it becomes more prevalent with age and is associated with smoking. Additionally, patients with MM have demonstrated an increased risk for malignancies. Thus, an examination for a correlation between CHIP and MGUS promises to reveal a link between these two pre-malignant conditions. A recent study did not demonstrate such an association, but this study was performed in a very elderly population and may not be applicable to younger patients. In this study, we aim to assess the relationship between CHIP and MGUS in a population-based cohort of MGUS patients seen at UT Southwestern Medical Center. METHODS: To evaluate an association between CHIP and MGUS, we collected bone marrow samples from 37 patients diagnosed with MGUS. We employed a hybridization capture-based next generation sequencing assay in order to detect CHIP. We identified 24 genes known to cause CHIP in adults. We also evaluated patients risk for developing MM after having been diagnosed with CHIP. RESULTS: The mean age was 68, (range 26-92). 22 patients were white, 8 were black and 3 Hispanic/Latino. 17 patients had IgG, 7 had IgA, 3 had IgM, 3 had biclonal gammopathy and 7 light-chain MGUS. We identified 18 mutations to validate the presence of CHIP in 10 (27%) patients, with the most frequent being DNMT3A (7 patients) and TET2 (5 patients). Other common mutations noted were PPM1D (2), GND1 (1), SF3B1 (1), ASXL1 in (1), and NRAS in (1). 3 out of the 10 patients harbored 2 mutations and 1 harbored 4 mutations. History of chemotherapy (n=6) and smoking (n=14) was taken into consideration to determine the relative risk of patients with MGUS developing CHIP. We found that those who had a prior history of smoking and chemotherapy displayed a higher risk of CHIP. CONCLUSION: There was no significant association between CHIP and MM progression. Our analysis showed 1 patient with CHIP progression and 2 without CHIP progression. Because the rates of CHIP and MGUS are positively correlated with characteristics like aging and a history of smoking, we expected to see high rates of CHIP in patients within our cohort. However, our data suggests that CHIP is frequent (27%) in MGUS patients, but larger future cohorts need to be evaluated to validate this association. Citation Format: Vianey Quaney, Benjamin Kroger, Aishwarya Sannareddy, Umar Khan, Fatma Kalkan, Robert H. Collins, Yazan F. Madanat, Madhuri Vusirikala, Yi Huang, Farrukh T. Awan, Praveen Ramakrishnan, Aimaz Afrough, Larry D. Anderson, Stephen S. Chung, Gurbakhash Kaur. Prevalence of clonal hematopoiesis in patients with monoclonal gammopathy of undetermined significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5925.
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Lamoreaux, Naomi R. "Enterprising Elite: The Boston Associates and the World They Made. By Robert F. DalzellJr, Cambridge: Harvard University Press, 1987. Pp. xviii, 298. $27.50." Journal of Economic History 48, n.º 3 (setembro de 1988): 777–78. http://dx.doi.org/10.1017/s002205070000632x.
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Nunez, Christina, Samantha Spagna, Bailey McDonald e Charles Golden. "A-167 A Comparison of Remotely Administered Verbal Paired Associates Subtests". Archives of Clinical Neuropsychology 36, n.º 6 (30 de agosto de 2021): 1222. http://dx.doi.org/10.1093/arclin/acab062.185.
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Abstract Objective Due to the COVID-19 pandemic, many services attempted to quickly transition to a remote format. A need to validate remote delivery of neuropsychological measures arose. TestMyBrain (TMB) from the Many Brains Project has been utilizing teleneuropsychology in research since 2017. Method Volunteer research participants (N = 147, Mage = 29, Medu = 15 years, 64.7% white, 54.2% female, 83.2% right-handed, 52.1% utilized Mac Operating System) were administered TMB Verbal Paired Associates(TMBVPA) and WMS-IV Verbal Paired Associates I(VPAI) as part of a larger battery of test via zoom. The WMS-IV assessments adhered to standardization as much as possible such as limiting potential distractions. Results A correlation revealed a positive association between TMBVPA and VPAI r(150) = 0.312, p = < 0.001. A linear regression revealed that performance on the TMBVPA positively predicted performance on the VPAI F(3, 144) = 9.344, p < 0.001 accounting for 16.6% of the variability over and above known demographic variables. The rate of agreeance showed that 23.7% of TMBVPA scores were within a one score difference of the VPAI and 37.4% were within two scores. Conclusions The results suggest that the two remote administration formats may not be as congruent as originally thought. With 62.6% of scores outside of a two-point range and the low rate of agreement this suggests little real-world application of the TMBVPA. Although telepsychology has come a long way, remote neuropsychological measures may still not be a reality any time soon. Future research should compare both remote administration versions to a standardized in person administration as well as consider other factors that can influence administration formats.
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Burley, David G. "Dalzell, Robert F., Jr. Enterprising Elite: The Boston Associates and the World They Made. Cambridge, Mass.: Harvard University Press, 1987. Pp. xviii, 298. Illustrations". Urban History Review 18, n.º 1 (1989): 98. http://dx.doi.org/10.7202/1017836ar.
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Golembiewski, Robert T. "Refounding Public Administration.Gary L. Wamsley , Robert N. Bacher , Charles T. Goodsell , Philip S. Kronenberg , John A. Rohr , Camilla M. Stivers , Orion F. White , James F. Wolf". Journal of Politics 53, n.º 4 (novembro de 1991): 1187–90. http://dx.doi.org/10.2307/2131881.
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Rapaport, David. "I seminari di David Rapaport del 1957 sulla metapsicologia". PSICOTERAPIA E SCIENZE UMANE, n.º 3 (setembro de 2020): 357–59. http://dx.doi.org/10.3280/pu2020-003001.
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Nel 1957 David Rapaport (1911-1960) tenne una serie di seminari sulla metapsicologia psicoanalitica agli allievi del primo anno del Western New England Institute for Psychoanalysis (New Haven, Connecticut). Questi seminari, trascritti verbatim, non furono mai pubblicati, ma solo dattiloscritti e divisi in sette volumi curati da Stuart C. Miller nel 1959, i primi tre di "metapsicologia elementare" e gli altri quattro di "metapsicologia avanzata", per un totale di circa 700 pagine. I partecipanti erano, oltre a Rapaport che era sempre presente, Helen G. Gilmore, Nathaniel J. London, Seymour L. Lustman, George F. Mahl, Stuart C. Miller, John P. Plunkett, Herbert S. Sacks, Roy Schafer, Virginia Suttenfield e Robert B. White (in alcuni casi erano presenti Paul E. Emery, Jean Schimek, David Shapiro, Eugene Talbot, Eugene E. Trunnel, Ess A. White Jr.). Qui, dopo una Nota redazionale, vengono pubblicati " per mostrare il metodo di lavoro di Rapaport " i programmi dettagliati dei seminari (con l'elenco dei riferimenti bibliografici da leggere e dei "compiti assegnati") e il testo di una parte di un seminario, le pagine iniziali del primo dei quattro volumi di metapsicologia avanzata.
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Jaher, F. C. "Enterprising Elite. The Boston Associates and the World They Made. By Robert F. Daltzell, Jr. (Cambridge, Massachusetts: Harvard University Press, 1987. xviii plus 298 pp. $27.50)". Journal of Social History 23, n.º 2 (1 de dezembro de 1989): 432–33. http://dx.doi.org/10.1353/jsh/23.2.432.
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Metts, Michael B. "Philology and the Last Supper: A Lesson from Qur’an Prehistory for Gospel Prehistory?" Bulletin for Biblical Research 31, n.º 3 (outubro de 2021): 319–55. http://dx.doi.org/10.5325/bullbiblrese.31.3.0319.
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Abstract Qur’an researchers associated with philology and the recent revisionist paradigm (voices such as Alphonse Mingana, Christoph Luxenberg, John Wansbrough, Fred M. Donner, Andrew Rippin, Gabriel Said Reynolds, Emran Iqbal El-Badawi, Robert M. Kerr, and Ibn Warraq) evidence a methodological disparity with NT researchers. While Qur’an historians allow meaningful input from philology by appropriating a sensible linguistic milieu that can accord with the Qur’an’s linguistic phenomena, particularly Aramaic or Syriac influence on the Qur’an’s Arabic, several voices in Last Supper research (including Matthias Klinghardt, Dennis E. Smith, and Paul F. Bradshaw) pursue Greco-Roman symposial and/or pagan influences contrary to philological findings. This article considers philology in Qur’an studies and in NT studies and examines anew the Aramaic influence evident in Mark’s Last Supper. Research by Raymond A. Martin and Joachim Jeremias is especially noted. This article seeks to pose NT researchers with the following question: Is there a lesson to learn from scholars working in Qur’an studies?
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Felicetti, M., A. Ortolan, A. C. Frigo, R. Padoan, M. Gasparotto, M. Lorenzin, A. Doria, R. Ramonda e F. Schiavon. "SAT0245 RENAL INVOLVEMENT AT ONSET IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS: A MAJOR INDEPENDENT RISK FACTOR FOR RENAL RELAPSE". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 1065.2–1065. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5830.
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Background:In ANCA-associated vasculitis (AAV), renal relapses are cause for concern as they are unpredictable and predictors of end-stage renal disease (ESRD).Objectives:We aimed to assess the frequency of major renal (MR) relapses in AAV in our cohort and identify independent predictors of the first MR relapse at diagnosis.Methods:We performed a retrospective monocentric observational study in our Vasculitis clinic from January 2000 to August 2019. Inclusion criteria were: 1) granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and limited kidney disease (LKD) diagnosis fulfilling EMA algorithm criteria; 2) achievement of a stable remission, defined as absence of vasculitis symptoms or signs and adherence to the prednisone taper during remission-induction treatment. We excluded patients who developed ESRD before remission and those with incomplete data during the follow-up. Major renal (MR) relapses were defined as occurrence of at least one major item of renal Birmingham Vasculitis Activity Score version 3 (BVASv3).All remitted patients were allocated in two subgroups: patients without MR relapse and patients with MR relapse. Univariate and multivariable analysis of first MR relapse predictors was performed with Fine and Gray (F&G) sub distribution hazards model to assess all competitive risks (progression to ESRD without MR relapse and death before MR relapse). Due to the relatively low frequency of events and the risk of overfitting, we performed several multivariable models with three variables, as recommended by Peduzzi e al1. The best multivariable model was selected accordingly to the Akaike information criterion (AIC).Results:96 (53% females) patients met the inclusion criteria: 74 GPA, 21 MPA and 1 LKD. Median age at diagnosis was 54 (44-64) years. ANCA testing was present in 94 patients, 85 were ANCA positive: 56 c-ANCA/PR3, 28 p-ANCA/MPO and 1 double positivity.During a median follow-up (FU) of 54.5 months (29.3-96.5), we observed 19 MR relapses in 17 patients while 2 patients progressed to ESRD, 3 died without events and 76 reported no MR relapse. Density-incidence of MR relapses since remission was 3.6/100 person-year (CI 95% 2.2-5.6). Median time to first MR relapse after remission was 33 months (14-67.5).At first MR relapse, 8 (53.3%) patients were on steroids while 10 (66.7%) were on immunosuppressant (5 azathioprine, 5 mycophenolate). In 2 cases, data about remission-maintenance treatment was not available.MR relapses were observed only in ANCA positive patients with a significantly higher frequency of skin, kidney and nerve involvement at diagnosis (41.2% vs 17.7%, p=0.034, 94.1% vs 57.0% p=0.004, and 52.9% vs 25.3% p=0.024, respectively); while Ear, Nose and Throat (ENT) involvement was significantly lower (35.3% vs 62.0% p=0.043). Mean BVASv3 at diagnosis scored significantly higher in MR relapse group (24.1±6.2 vs 18.1±8.1. p=0.007).At multivariable analysis with F&G model, renal involvement and induction treatment without cyclophosphamide and/or Rituximab at diagnosis were independent predictors of MR relapse (sHR 20.4 (2.6-158.2), p=0.004 and sHR 4.2 (1.5-12.0), p=0.007, respectively). Moreover, there was a trend of higher risk of MR relapse in PR3-ANCA (sHR 2.5 (0.9-7.1), p=0.091).Conclusion:Renal involvement at diagnosis and milder remission-induction treatment regimens resulted in a significantly higher risk of MR relapse during the FU in our cohort. PR3-ANCA specificity was not an independent predictor of MR relapse, even if we observed a trend of higher MR relapse risk with this covariate.References:[1]Peduzzi P et al. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49(12):1373-9.Disclosure of Interests:Mara Felicetti: None declared, Augusta Ortolan: None declared, Anna Chiara Frigo: None declared, Roberto Padoan: None declared, Michela Gasparotto: None declared, Mariagrazia Lorenzin: None declared, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Roberta Ramonda Speakers bureau: Novartis, Celgene, Janssen, Pfizer, Abbvie, Lilly, Franco Schiavon: None declared
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Komanduri, R. "Machining and Grinding: A Historical Review of the Classical Papers". Applied Mechanics Reviews 46, n.º 3 (1 de março de 1993): 80–132. http://dx.doi.org/10.1115/1.3121404.
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Major contributions to machining and grinding research in the US came in the twentieth century. The seminal work by Frederick Winslow Taylor on the Art of Cutting Metals published in 1907 was the beginning of a series of serious and systematic studies on the various aspects of metal cutting and grinding in this century. This monumental work, which became an American classic, continues to inspire many a researcher in this field even today. It was followed by the works of other pioneers, including Orlan W Boston, Hans Ernst, M E Martellotti, Max Kronenberg, M Eugene Merchant, Milton C Shaw, Michael Field, John Kahles, K J Roubik, K Armitage, Ken Trigger, B T Chao, Alfred Schmidt, William W Gilbert, Fran Boulger, Lester Colwell, Carl Oxford, Erich Thomsen, Robert Hahn, and many others. Many of the associates of the pioneers including Nathan Cook, Iain Finnie, B F von Turkovich, Shiro Kobayaski, Inyong Ham, E Loewen, and others including W B Rice, S M Wu, and J Tlusty have made significant contributions to these fields in their own right. There is no doubt that this century will be heralded by the historians as the golden age of metal cutting and grinding research, particularly the period between 1940 and 1960. It was, however, M Eugene Merchant’s paper on the Basic Mechanics of the Metal Cutting Process in 1945 that took a giant step from the art of metal cutting to the science of metal cutting. This work laid the foundation for much of the work that is practiced today. It can be stated unequivocally that because of the significant contributions by the pioneers and their associates, metal cutting and grinding research today is rich in its heritage and contents, and has contributed towards the improvement of manufacturing productivity. It has thereby facilitated the improvement of living standards around the world. In this review, the following ten topics are addressed briefly: Physics of Machining; Mechanics of Machining; Shear and Friction in Machining; Thermal Aspects of Machining and Grinding; Tool Materials, Tool Wear, and Machinability; Multiple Cutting Points; Grinding; Vibrations in Machining; Surface Integrity; and Economics of Machining.
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Zheng, Tong, Xueyan Fu, Xiaohua Shen, Shannon Marschall, Donald Smith, Andrew Tarr, Thomas Biederer, Barbara Shukitt-Hale e Sarah Booth. "Low Vitamin K Intake Negatively Affects C57BL6 Mouse Survival and Cognition". Current Developments in Nutrition 6, Supplement_1 (junho de 2022): 816. http://dx.doi.org/10.1093/cdn/nzac064.035.
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Abstract Objectives Low dietary intake of vitamin K (VK), which is common among older adults, has been associated with age-related dementia and cognitive impairment. Aging and neurodegenerative diseases negatively affect hippocampal neurogenesis, and result in cognitive deficits, such as in learning and memory. The current study investigated the effects of low vitamin K intake on the potential factors affecting the cognitive functions in a C57BL6 mouse model. Methods Middle-aged (7–9 mo) C57BL6 mice (Charles River, n = 60) were randomly assigned by sex and diet (n = 15/group): low vitamin K males (LVKM, 80 μg phylloquinone (PK)/kg diet), control diet males (CM, 1 mg PK/kg diet), low vitamin K females (LVKF), and control diet females (CFM) for 6 months. All animals were fed ad lib, and their body weight were recorded 1–2 times/week. At the completion of the 6-mo feeding period, behavioral tests, including the rotarod, novel object task, and Morris water maze, were performed. Tissue samples were collected at the time of sacrifice (3 weeks after the behavioral tests) and PK content in liver samples were measured by HPLC. Results LVKM had significantly lower survival rate compared to CM (53.3% vs. 93.3% in control, P < 0.05). LVKM/F also had reduced body weight increases compared to the CM/F over the 6 mo feeding period (P < 0.05). The liver PK content in LVKM/F animals was significantly lower than that of CM/F (male:6.2 ± 1.1 vs 30.2 ± 7.0 pmol/g, P < 0.001; female: 10.9 ± 2.4 vs 47.3 ± 10.3 pmol/g, P < 0.001). On the novel object task, LVKM/F showed reduced recognition memory compared to CM/F, while no significant differences were seen between LVKM/F and CM/F on the rotarod test. Additionally, LVKM had a non-statistical trend for a greater time to locate the platform in the Morris water maze, suggesting impaired spatial memory. Conclusions Low vitamin K intake significantly impaired survival and weight gain of C57BL6 mice, especially among males. Additionally, low vitamin K negatively impacted the learning- and memory-related cognitive functions. Future studies are required to establish the mechanisms, underlying these observations. Funding Sources Supported by USDA/ARS intramural grant, and the Robert and Margaret Patricelli Family Foundation
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KITLV, Redactie. "Book Reviews". New West Indian Guide / Nieuwe West-Indische Gids 65, n.º 1-2 (1 de janeiro de 1991): 67–105. http://dx.doi.org/10.1163/13822373-90002017.
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-A. James Arnold, Michael Gilkes, The literate imagination: essays on the novels of Wilson Harris. London: Macmillan, 1989. xvi + 180 pp.-Jean Besson, John O. Stewart, Drinkers, drummers, and decent folk: ethnographic narratives of village Trinidad. Albany, New York: State University of New York Press, 1989. xviii + 230 pp.-Hymie Rubinstein, Neil Price, Behind the planter's back. London: MacMillan, 1988. xiv + 274 pp.-Robert Dirks, Joseph M. Murphy, Santería: an African religion in America. Boston: Beacon Press, 1988. xi + 189 pp.-A.J.R. Russell-Wood, Joseph C. Miller, Way of Death: merchant capitalism and the Angolan slave trade, 1720-1830. Madison, Wisconsin: The University of Wisconsin Press, 1988. xxx + 770 pp.-Anne Pérotin-Dumon, Lawrence C. Jennings, French reaction to British slave Emancipation. Baton Rouge: Louisiana State University Press, 1988. ix + 228 pp.-Mary Butler, Hilary McD. Beckles, White servitude and black slavery in Barbados, 1627-1715. Knoxville: University of Tennesse Press, 1989. xv + 218 pp.-Franklin W, Knight, Douglas Hall, In miserable slavery: Thomas Thistlewod in Jamaica, 1750-1786. London: MacMillan, 1989. xxi + 322 pp.-Ruby Hope King, Harry Goulbourne, Teachers, education and politics in Jamaica 1892-1972. London: Macmillan, 1988. x + 198 pp.-Mary Turner, Francis J. Osbourne S.J., History of the Catholic Church in Jamaica. Chicago: Loyola University Press, 1988. xi + 532 pp.-Christina A. Siracusa, Robert J. Alexander, Biographical dictionary of Latin American and Caribbean political leaders. New York, Westport, London: Greenwood Press, 1988. x + 509 pp.-Sue N. Greene, Brenda F. Berrian ,Bibliography of women writers from the Caribbean (1831-1986). Washington D.C.: Three Continents Press, 1989. 360 pp., Aart Broek (eds)-Romain Paquette, Singaravélou, Pauvreté et développement dans les pays tropicaux, hommage a Guy Lasserre. Bordeaux: Centre d'Etudes de Géographie Tropicale-C.N.R.S./CRET-Institut de Gépgraphie, Université de Bordeaux III, 1989. 585 PP.-Robin Cohen, Simon Jones, Black culture, white youth: the reggae traditions from JA to UK. London: Macmillan, 1988. xxviii + 251 pp.-Bian D. Jacobs, Malcom Cross ,Lost Illusions: Caribbean minorities in Britain and the Netherlands. London: Routledge, 1988. 316 pp., Han Entzinger (eds)
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Murphy, Caryn. "Network television writers and the ‘race problems’ of 1968". Journal of Screenwriting 10, n.º 3 (1 de setembro de 2019): 307–21. http://dx.doi.org/10.1386/josc_00006_1.
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This article examines the development of television scripts in the crime drama genre within the context of US commercial broadcasting in the network era. In 1968, public discourse around race relations, civil rights and violence reached a height following the assassinations of Martin Luther King, Jr and Robert F. Kennedy, and the release of a government study on urban uprisings by the National Advisory Commission on Civil Disorders. Ironside (1967‐75, NBC) and N.Y.P.D. (1967‐69, ABC) are two crime dramas that drew on recent events related to black militants and white supremacy in order to appeal to viewers with socially relevant entertainment during this time. The archival records of screenwriters Sy Salkowitz and Lonne Elder make it possible to trace the development of one episode from each series over the course of multiple drafts. This analysis of the script development process explores the relationship between public discourse, industrial context, commercial agendas and creative priorities. Ironside and N.Y.P.D. are both crime dramas, but an examination of both series yields points of divergence which help to illustrate the norms of the network system in terms of act structure, genre tropes, and the oversight of standards and practices.
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Doucet, Michael J. "Robert F. Harney, ed. Gathering Place: Peoples and Neighbourhoods of Toronto, 1834-1945. Toronto: Multicultural History Society of Ontario, 1985. Pp. 304. 22 black and white plates. $9.95". Urban History Review 14, n.º 3 (1986): 290. http://dx.doi.org/10.7202/1018092ar.
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Susskind, Jacob L., Robert Fischer, Robert B. Luehrs, Joseph M. McCarthy, Pasquale E. Micciche, Bullitt Lowry, Linda Frey et al. "Book Reviews". Teaching History: A Journal of Methods 10, n.º 1 (20 de abril de 2020): 35–45. http://dx.doi.org/10.33043/th.10.1.35-45.
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J. M. MacKenzie. The Partition of Africa, 1880-1900. London and New York: Methuen, 1983. Pp. x, 48. Paper, $2.95. Review by Leslie C. Duly of Bemidji State University. C. Joseph Pusateri. A History of American Business. Arlington Heights, Illinois: Harlan Davidson, Inc., 1984. Pp. xii, 347. Cloth, $25.95; Paper, $15.95. Review by Paul H. Tedesco of Northeastern University. Russell F. Weigley. History of the United States Army. Enlarged edition. Bloomington: Indiana University Press, 1984. Pp. vi, 730. Paper, $10.95. Review by Calvin L. Christman of Cedar Valley College. Jonathan H. Turner, Royce Singleton, Jr., and David Musick. Oppression: A Socio-History of Black-White Relations in America. Chicago: Nelson-Hall, 1984. Cloth, $24.95; Paper, $11.95. Review by Thomas F. Armstrong of Georgia College. H. Warren Button and Eugene F. Provenzo, Jr. History of Education and Culture in America. Englewood Cliffs, New Jersey: Prentice-Hall, Inc., 1983. Pp. xvii, 370. Cloth, $20.95. Review by Peter J. Harder. Vice President, Applied Economics, Junior Achievement Inc. David Stick. Roanoke Island: The Beginnings of English America. Chapel Hill and London: University of North Carolina Press, 1983. Pp. xiv, 266. Cloth, $14.95; Paper, $5.95. Review by Mary E. Quinlivan of the University of Texas of the Permian Basin. John B. Boles. Black Southerners 1619-1869. Lexington: The University Press of Kentucky, 1983. Pp. ix, 244. Cloth, $24.00; Paper, $9.00. Review by Kay King of Mountain View College. Elaine Tyler May. Great Expectations: Marriage and Divorce in Post-Victorian America. Chicago: University of Chicago Press, 1980. Pp. viii, 200. Cloth, $15.00; Paper, $6.95. Review by Barbara J. Steinson of DePauw University. Derek McKay and H. M. Scott. The Rise of the Great Powers, 1648-1815. London: Longman, 1983. Pp. 368. Paper, $13.95. Review by Linda Frey of the University of Montana. Jack S. Levy. War in the Modern Great Power System, 1495-1975. Lexington: The University Press of Kentucky, 1983. Pp. xiv, 215. Cloth, $24.00. Review by Bullitt Lowry of North Texas State University. Lionel Kochan and Richard Abraham. The Making of Modern Russia. Second Edition. New York: Penguin Books, 1983. Pp. 544. Paper, $7.95. Review by Pasquale E. Micciche of Fitchburg State College. D. C. B. Lieven. Russia and the Origins of the First World War. New York: St. Martin's Press, 1983. Pp. 213. Cloth, $25.00. Review by Joseph M. McCarthy of Suffolk University. John F. V. Kieger. France and the Origins of the First World War. New York: St. Martin's Press, 1983. Pp. vii, 201. Cloth, $25.00. Review by Robert B. Luehrs of Fort Hays State University. E. Bradford Burns. The Poverty of Progress: Latin Amerca in the Nineteenth Century. Berkeley: University of California Press, 1980. Pp. 185. Paper, $6.95. Review by Robert Fischer of the Southern Technical Institute. Anthony Seldon and Joanna Pappworth. By Word of Mouth: Elite Oral History. London and New York: Methuen, 1983. Pp. xi, 258. Cloth, $25.00; Paper, $12.95. Review by Jacob L. Susskind of the Pennsylvania State University, The Capitol Campus.
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Thongma-Eng, Punrit, Pokpong Amornvit, Patcharawan Silthampitag, Dinesh Rokaya e Attavit Pisitanusorn. "Effect of Ambient Lights on the Accuracy of a 3-Dimensional Optical Scanner for Face Scans: An In Vitro Study". Journal of Healthcare Engineering 2022 (8 de agosto de 2022): 1–8. http://dx.doi.org/10.1155/2022/2637078.
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Most 3D scanners use optical technology that is impacted by lighting conditions, especially in triangulation with structured-light or laser techniques. However, the effect of ambient lights on the accuracy of the face scans remains unclear. The purpose of this study is to investigate the effect of ambient lights on the accuracy of the face scans obtained from the face scanner (EinScan Pro 2X Plus, Shining 3D Tech. Co., LTD., Hangzhou, China). A head model was designed in Rhinoceros 5 software (Rhino, Robert McNeel and Associates for Windows, Washington DC, USA) and printed with 200 micron resolution of polylactic acid and was dented with 2.0 mm of carbide bur to aid in superimposition in software. The head model was measured by a coordinate-measuring machine (CMM) to generate a reference stereolithography (STL) file as a control. The face model was scanned four times under nine light conditions: cool white (CW), warm white (WW), daylight (DL), natural light (NL), and illuminant (9w, 18w, 22w). Scan data were exported into an STL file. The scan STL files obtained were compared with the reference STL file by 3D inspection software (Geomagic Control X version 17, Geomagic, Morrisville, NC, USA). The deviations and root mean square errors (RMSEs) between the reference model (trueness) and within the group (precision) were selected for the statistical analysis. The statistical analysis was done using SPSS 20.0 (IBM Company, Chicago, USA). The trueness and precision were evaluated with the one-way ANOVA with multiple comparisons using the Tukey method. For trueness, the scanner showed the lowest RMSE under the NL group (77.18 ± 3.22) and the highest RMSE under the 18w-DL group (95.33 ± 6.89). There was a statistically significant difference between the NL group and the 18w-DL group (p < 0.05) for trueness. Similarly, for precision, the scanner showed the lowest RMSE under the NL group (56.92 ± 4.56) and the highest RMSE under the 9w-CW group (78.52 ± 10.61). There was statistically significant difference between NL, 18w-WW, 18w-CW, 18w-DL, 22w-WW, 22w-DL, 9w-CW, 9w-WW, and 9w-DL (p < 0.05) for the precision. Ambient lights affected the face scans. Under the natural light condition, the face scanner had the best accuracy in terms of both trueness and precision. The 18w-DL and 9w-WW conditions showed the least trueness whereasthe 9w-CW and 9w-DL conditions showed the least precision.
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Jeremy, David J. "Robert F. DalzellJr., Enterprising Elite: The Boston Associates and the World They Made, Harvard Studies in Business History, vol XL (Cambridge MA & London: Harvard University Press, 1987, £21.95). Pp. 298. ISBN 0 674 25765 0." Journal of American Studies 23, n.º 3 (dezembro de 1989): 488–89. http://dx.doi.org/10.1017/s0021875800004333.
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Benson, Devyn Spence. "Cuba Calls: African American Tourism, Race, and the Cuban Revolution, 1959–1961". Hispanic American Historical Review 93, n.º 2 (1 de maio de 2013): 239–71. http://dx.doi.org/10.1215/00182168-2077144.
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Abstract This essay explores the role that conversations about race and racism played in forming a partnership between an African American public relations firm and the Cuban National Tourist Institute (INIT) in 1960, just one year after Fidel Castro’s victory over Fulgencio Batista. The article highlights how Cuban revolutionary leaders, Afro-Cubans, and African Americans exploited temporary transnational relationships to fight local battles. Claiming that the Cuban Revolution had eliminated racial discrimination, INIT invited world champion boxer Joe Louis and 50 other African Americans to the island in January 1960 to experience “first class treatment — as first class citizens.” This move benefited Cuban revolutionary leaders by encouraging new tourism as the number of mainstream white American travelers to the island declined. The business venture also allowed African Americans to compare racial violence in the US South to the supposed integrated racial paradise in Cuba and foreshadowed future visits by black radicals, including NAACP leader Robert F. Williams. The politics expressed by Cuban newspapers and travel brochures, however, did not always fit with the lived experiences of Afro-Cubans. This essay uncovers how Afro-Cubans threatened national discourses by invoking revolutionary promises to denounce continued racial segregation in the very facilities promoted to African American tourists. Ultimately, ideas about race did not just cross borders between Cuba and the United States in 1960. Rather, they constituted and constructed those borders as Afro-Cubans used government claims to reposition themselves within the new revolutionary state.
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Nassif, Elise F., Chia-Chin Wu, Kadir Akdemir, Russell G. Witt, Raymond Traweek, Brandon Cope, Prapassorn Thirasastr et al. "Abstract PR002: Antigen presentation and processing pathway is associated with early relapse after neoadjuvant immune checkpoint blockade (ICB) in dedifferentiated liposarcomas (DDLPS)". Clinical Cancer Research 28, n.º 18_Supplement (15 de setembro de 2022): PR002. http://dx.doi.org/10.1158/1557-3265.sarcomas22-pr002.
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Abstract Background: We evaluated the activity of neoadjuvant ICB in localized resectable DDLPS (n=17) and undifferentiated pleomorphic sarcomas (UPS; n=10). DDLPS and UPS patients were randomized to neoadjuvant nivolumab or ipilimumab+nivolumab, with UPS patients receiving concurrent radiotherapy. We assessed genomic markers of early relapse (progression before surgery or relapse within 52 weeks following surgery) using longitudinally acquired tumor samples. Methods: RNA sequencing (RNAseq) and whole genome sequencing (WGS) were performed on longitudinally acquired samples (baseline biopsies and surgical specimens). Differential gene expression between any two groups of patients (i.e., non-early relapse [non-relapsers] vs early relapse [relapsers]) were selected (fold change>1.5 and p value<0.05). Gene set enrichment analyses (GSEA) of KEGG pathways were performed and a network-based approach used to identify genes/pathways associated with MHC-I. Results: At a median follow-up of 23 months, 12 patients (9 DDLPS, 3 UPS) relapsed, including 7 early relapses (relapsers: 5 DDLPS, 2 UPS). The median relapse-free survival was 22 months in DDLPS patients (6 months in relapsers; not reached [NR] in non-relapsers) and NR in UPS patients. At baseline, the most differentially upregulated pathways in non-relapsers compared to relapsers were “graft versus host disease” (GSEA Normalized Enrichment Score[NES]=2.25; False Discovery Rate[FDR] q= 0.009), “natural killer cell mediated cytotoxicity” (NES=2.17; FDR q=0.009), “antigen processing and presentation” (NES=2.16; FDR q=0.009), “allograft rejection” (NES=1.99; FDR q=0.019) and “B-cell receptor signaling pathway” (NES=1.87; FDR q=0.018). In DDLPS patients, the antigen presentation and processing pathway was the most upregulated pathway in non-relapsers compared to relapsers (NES=2.01; FDR q=0.025) while it was not significantly upregulated in UPS (NES=1.15; FDR q=0.62). When looking at pathways longitudinally, the antigen presentation and processing pathway was significantly upregulated at surgery compared to baseline in DDLPS. As antigen presentation and processing was significantly upregulated in DDLPS patients and associated with relapse, we looked for expressed neoantigens that may be processed and presented. Using WGS, we detected 5712 rearrangements at baseline in DDLPS, of which 230 were found in more than one tumor specimen. We also sought to identify genes associated with MHC-I. We selected genes upregulated during ICB comparing baseline to surgical specimens in DDLPS relapsers and looked at the top 10% of genes associated with MHC-I in order to identify potential therapeutic targets for combination. We identified 41 genes upregulated during ICB and associated with MHC-I in relapsers, for which up to 275 inhibitory compounds were found in drug databases. Conclusion: Antigen presentation and processing is a major driver of response to immunotherapy. Future efforts should focus on identifying which antigens are presented to find synergizing compounds in order to increase the clinical benefit of ICB. Citation Format: Elise F. Nassif, Chia-Chin Wu, Kadir Akdemir, Russell G. Witt, Raymond Traweek, Brandon Cope, Prapassorn Thirasastr, Taylor Tate, Grace Mathew, Shadarra Crosby, Randy Chu, Mohammad Mohammad, Kenna Shaw, Ingram Davis, Khalida Wani, Alexander J. Lazar, Wei-Lien Wang, Sheila Duncan, Ashleigh B. Guadagnolo, Andrew J. Bishop, Valerae Lewis, Justin E. Bird, Keila E. Torres, Kelly K. Hunt, Barry W. Feig, Christopher P. Scally, Ravin Ratan, Shreyaskumar Patel, Robert S. Benjamin, Robert Satcher, Kevin McBride, Wolf H. Fridman, Ignacio Wistuba, Andrew Futreal, Jennifer A. Wargo, Neeta Somaiah, Christina L. Roland, Emily Z. Keung. Antigen presentation and processing pathway is associated with early relapse after neoadjuvant immune checkpoint blockade (ICB) in dedifferentiated liposarcomas (DDLPS) [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr PR002.
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Luna-Lupercio, Bianca, Aidan Foley, Nenette A. Caceres, Ergueen Herrera, Galen Wiens-Cook, Vinicius Calsavara, Zul Surani, Sarah-Jeanne Salvy, Robert Haile e Celina H. Shirazipour. "Abstract 1979: Examining stereotype perceptions of colorectal cancer in the Latino community". Cancer Research 83, n.º 7_Supplement (4 de abril de 2023): 1979. http://dx.doi.org/10.1158/1538-7445.am2023-1979.
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Abstract Purpose: Colorectal cancer (CRC) screening is significantly lower in the Hispanic community compared to non-Hispanic whites. Qualitative research has suggested that cultural attitudes towards cancer may be a potential barrier to screening. The purpose of the study was to quantitatively examine explicit stereotypes about CRC and CRC screening within the Hispanic community using the stereotype content model. Methods: A one-time online cross-sectional survey was administered to individuals self-identifying as Hispanic living across the United States. Based on participant preference, the survey was completed in English or Spanish. In counterbalanced order, participants were asked to read brief paragraphs about a control target, a target with CRC, and a target undergoing colonoscopy CRC screening. The target was a Hispanic individual assigned a gender-neutral name. Other than the one sentence with CRC-related information in the CRC and CRC screening paragraphs, all the paragraphs were identical describing the individual, their family, and their hobbies. After each paragraph, participants were asked to rate the target on validated surveys assessing warmth and competence, two indicators of explicit stereotypes. Data was analyzed using linear mixed-effects models, which were fitted to evaluate the effect of each target on warmth and competence, controlling for age, gender, race, Hispanic heritage, cancer exposure, and randomization. Results: The target condition was not statistically significantly associated with the Warmth and Competence outcomes when the models were fitted considering only the main effects. However, in the presence of interactions the condition was associated with the outcomes. Specifically, the analysis yielded a significant fixed effect for the interaction between target condition and participant age, such that younger participants had greater perceptions of warmth [F(2, 511.93)=7.045, p=0.001] and competence [F(2, 522.73)=11.129, p<0.001] towards the target undergoing cancer screening. The analysis also yielded a further significant effect for the interaction between target condition and Hispanic heritage with differences in perceptions of warmth between those born in the USA and participants born in Central and South America or in Europe [(F(2, 520.16)=2.299, p=0.02)]. Conclusion: Findings highlight the importance of understanding the heterogeneity within the Hispanic community when seeking to address stigma towards CRC. First, there are differences in explicit perceptions based on generation, suggesting the need for age-appropriate cancer prevention initiatives. Second, the findings demonstrate the need to account for diverse cultural perspectives of cancer screening based on country of origin. Thus, this research supports the importance of respecting the diversity within the Hispanic community and tailoring cancer prevention interventions accordingly. Citation Format: Bianca Luna-Lupercio, Aidan Foley, Nenette A. Caceres, Ergueen Herrera, Galen Wiens-Cook, Vinicius Calsavara, Zul Surani, Sarah-Jeanne Salvy, Robert Haile, Celina H. Shirazipour. Examining stereotype perceptions of colorectal cancer in the Latino community [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1979.
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Moon, Jesung, Xiaofei Gao, Peiguo Ding, Fnu Bilal, Smita Rindhe, Ning Gao, Digant P. Dave, Mark Henkemeyer, Elizabeth A. Maher e Robert M. Bachoo. "Abstract 3355: Unraveling the molecular mechanisms of glioma migration: Exploring the role of cell intrinsic and stromal ephrin receptor-ligand signaling". Cancer Research 84, n.º 6_Supplement (22 de março de 2024): 3355. http://dx.doi.org/10.1158/1538-7445.am2024-3355.
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Abstract Diffuse invasion, a hallmark of malignant gliomas, makes these tumors surgically incurable and is the ultimate cause of death. While glioma cells can migrate along blood vessels and in neuron-rich regions, their preferred route of migration is along white matter (WM) tracts, which allows tumor cells to spread to the contralateral hemisphere with devastating neurocognitive consequences. The underlying mechanisms of in vivo glioma cell migration are poorly understood. There is emerging evidence that glioblastoma multiforme (GBM) cells may hijack migration mechanisms used during brain development. Accordingly, we used a neonatal plasmid electroporation GBM model (CRISPR-Cas9, -Cre,gRNAs targeting NF1, p53, PTEN, and piggyBac-glast) to generate a highly penetrant diffusely invasive glioma models with preference for migration along myelinated fiber tracts including the corpus callosum (CC). To test the in vivo role of integrin-mediated migration, tumors were generated using conditional integrin β1f/f (ITGB1) or focal adhesion kinase (FAKf/f) mice. Both ITGB1 and FAK null GBM cells (confirmed by western blot analysis) showed diffuse infiltration similar to WT mice, suggesting that integrin signaling is not essential for in vivo GBM cell migration. Next, we tested the role ephrin-signaling using a series of transgenic neonatal mice, including EPH-B1-/-, -B2-/-, -B1/2-/-, -kinase-dead (KD) and a gain-of-function mutant). EPH1/2-/- GBM, but not the other genetic models, consistently formed tumors which showed no diffuse single-cell infiltration, but rather grew as a solid expanding mass. An extensive panel of in vitro studies comparing WT and EPHB1/2-/- GBM patterns of growth and migration, including time-lapse random walk, neurosphere radial migration, migration along patterned surfaces, and laminin-coated confined 3D channels, showed similar patterns of migration, despite the marked differences in vivo. These contrasting in vivo and in vitro results raise the possibility that EPH-B1/2 receptors may require their cognate ephrin ligands to facilitate migration through the WM tracts. To test this hypothesis, we are using Ephrin-B1f/f, B2f/f mice for in vivo cell-type specific deletion in WM tract stroma cells and primary astrocytes derived from these mice for ex vivo co-culture studies. Our preliminary data suggest that EPH/EPHRIN interactions may regulate GBM cell migration. Citation Format: Jesung Moon, Xiaofei Gao, Peiguo Ding, Fnu Bilal, Smita Rindhe, Ning Gao, Digant P. Dave, Mark Henkemeyer, Elizabeth A. Maher, Robert M. Bachoo. Unraveling the molecular mechanisms of glioma migration: Exploring the role of cell intrinsic and stromal ephrin receptor-ligand signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3355.
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Kampf, A. R., J. J. Pluth, Y. S. Chen, A. C. Roberts e R. M. Housley. "Bobmeyerite, a new mineral from Tiger, Arizona, USA, structurally related to cerchiaraite and ashburtonite". Mineralogical Magazine 77, n.º 1 (fevereiro de 2013): 81–91. http://dx.doi.org/10.1180/minmag.2013.077.1.08.
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AbstractBobmeyerite, Pb4(Al3Cu)(Si4 O12)(S0.5Si0.5O4)(OH)7 Cl(H2O)3, is a new mineral from the Mammoth - Saint Anthony mine, Tiger, Pinal County, Arizona, USA. It occurs in an oxidation zone assemblage attributed to progressive alteration and crystallization in a closed system. Other minerals in this assemblage include atacamite, caledonite, cerussite, connellite, diaboleite, fluorite, georgerobinsonite, hematite, leadhillite, matlockite, murdochite, phosgenite, pinalite, quartz, wulfenite and yedlinite. Bobmeyerite occurs as colourless to white or cream-coloured needles, up to 300 m m in length, that taper to sharp points. The streak is white and the lustre is adamantine, dull or silky. Bobmeyerite is not fluorescent. The hardness could not be determined, the tenacity is brittle and no cleavage was observed. The calculated density is 4.381 g cm-3. Bobmeyerite is biaxial (-) with α ≈ β = 1.759(2), γ = 1.756(2) (white light), it is not pleochroic; the orientation is X = c; Y or Z = a or b. Electron-microprobe analyses provided the empirical formula Pb3.80Ca0.04Al3.04Cu2+0.96Cr3+0.13Si4.40S0.58O24.43Cl1.05F0.52H11.83. Bobmeyerite is orthorhombic (pseudotetragonal), Pnnm with unit-cell parameters a = 13.969(9), b = 14.243(10), c = 5.893(4) Å, V = 1172.5(1.4) Å3 and Z = 2. The nine strongest lines in the X-ray powder diffraction pattern, listed as [dobs (Å)(I)(hkl)], are as follows: 10.051(35)(110); 5.474(54)(011,101); 5.011(35)(220); 4.333(43)(121,211); 3.545(34)(040,400); 3.278(77)(330,231,321); 2.9656(88)(141,002,411); 2.5485(93)(051,222,501); 1.873(39)(multiple). Bobmeyerite has the same structural framework as cerchiaraite and ashburtonite. In the structure, which refined to R1 = 0.079 for 1057 reflections with F > 4σF, SiO4 tetrahedra share corners to form four-membered Si4O12 rings centred on the c axis. The rings are linked by chains of edge-sharing AlO6 octahedra running parallel to [001]. The framework thereby created contains large channels, running parallel to [001]. The Cl site is centred on the c axis alternating along [001] with the Si4O12 rings. Two non-equivalent Pb atoms are positioned around the periphery of the channels. Both are elevencoordinate, bonding to the Cl atom on the c axis, to eight O atoms in the framework and to two O (H2O) sites in the channel. The Pb atoms are off-centre in these coordinations, as is typical of Pb2+ with stereo-active lone-electron pairs. A (S, Si, Cr)O4 group is presumed to be disordered in the channel. The name honours Robert (Bob) Owen Meyer, one of the discoverers of the new mineral.
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Ramathal, Cyril, David Masica, Peter Ansell, Bridget Riley-Gillis, Jacob Degner, Thanh Bui, Priya Narayanan et al. "Abstract 5426: Multi-omic characterization and predictive features of advanced ovarian cancer patients in a large phase III cohort". Cancer Research 83, n.º 7_Supplement (4 de abril de 2023): 5426. http://dx.doi.org/10.1158/1538-7445.am2023-5426.
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Abstract Discovery and validation of biomarkers derived from multi-dimensional clinico-genomic datasets have become critical in precision medicine and oncology drug development. The integration of multi-dimensional genomic and imaging datasets from patients in late-stage oncology clinical trials can be difficult, in part due to limited patient enrollment and sample collection, especially tumor tissue biopsies. The objective of this project was to conduct predictive biomarker discovery on integrated clinico-genomics data spanning tumor genomics, germline genetics, tumor imaging, and circulating blood-based biomarkers for a cohort of 800+ advanced ovarian cancer patients enrolled in the phase III trial of the PARP-1 inhibitor Veliparib (VELIA). Genomic (DNA & RNA) and imaging datasets were generated from 800+ patient-matched tumor biopsies, liquid biopsies and whole blood to enable various biomarker analyses for this study, notably in BRCA-deficient and HRD+ subgroups. Pairwise analysis of individual features with clinical outcomes shows that increased tumor-mutation burden (TMB), RNA-based estimates of immune activity (ICR and MIRACLE scores), CA-125 elimination constant (KELIM score), and image-based estimates tumor-infiltrating lymphocytes (TILs) were each significantly associated with longer PFS and less progressive disease (PD). Similarly, homologous recombination deficiency (HRD) and BRCA alteration were associated with better clinical outcomes, while high CA-125 was associated with worse outcomes. To understand the concerted impact of these features on clinical outcome, we developed multivariate classifiers of PD and regressors (Cox Proportional Hazards) of PFS using XGBoost; using a train-test split of 75/25, we trained the models with 500 rounds of 10-fold cross validation hyperparameter tuning, which resulted in fit models. The PD classifier achieved a validation accuracy of 0.71 and F1-score of 0.78, with high immune activation, high TMB, high KELIM, and HRD and BRCA alteration predicting better outcomes. The PFS survival model achieved a validation C-index of 0.61, with a rank importance of features similar to that of PD classification models; for both models, patients receiving Veliparib had clear benefit relative to that of control arms. Collectively, this study illustrates the value of integrating multi-dimensional datasets with predictive machine learning to identify clinically-relevant biomarkers. CR, DM, PA, BR, JD, TB, PN, JS, XH, and JFW are employees of AbbVie. RLC an employee at The University of Texas MD Anderson Cancer Center and has no funding to disclose. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication. Citation Format: Cyril Ramathal, David Masica, Peter Ansell, Bridget Riley-Gillis, Jacob Degner, Thanh Bui, Priya Narayanan, Josue Samayoa, Xin Huang, Robert F. Coleman, Jeffrey F. Waring. Multi-omic characterization and predictive features of advanced ovarian cancer patients in a large phase III cohort. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5426.
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Abogamal, A., G. Harifi, I. Gamal, A. Alansari, A. Azaam e A. Massri. "AB1194 PREVALENCE OF FIBROMYALGIA IN THE RHEUMATOLOGY OPDS DURING COVID19 LOCKDOWN: A CROSS-SECTIONAL STUDY". Annals of the Rheumatic Diseases 81, Suppl 1 (23 de maio de 2022): 1712.1–1712. http://dx.doi.org/10.1136/annrheumdis-2022-eular.130.
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BackgroundIn the challenging times of Covid 19, anxiety increased among the general population. Fibromyalgia patients are more at risk of developing anxiety in these difficult times. This might result in more frequent visits to the rheumatology clinics with an exacerbation of their chronic pain syndrome.ObjectivesThe main objective of this study is to compare the prevalence of FM in the rheumatology outpatients’ clinics during the Covid 19 lockdown period (2020) and during the same period in the previous year (2019).MethodsA cross-sectional study is conducted through 5 rheumatology clinics located in the 3 biggest emirates of the country (3 in Dubai, 1 in Abu Dhabi and 1 in Sharjah) to detect the number and charachteristics of fibromyalgia from March 15 to May 15th2019, and March 15 to May 15th2020.ResultsTotal number of patients seen from march to May 2019 was 3480 out of them 55 were fibromyalgia patients with frequency 0.0158%. While from march to May 2020 total number of patients seen were 1355 out of them 66 were fibromyalgia patients with frequency 0.0487%. Figure 1Figure 1.Total and fibromyalgia patients in March-May 2019 and March-May 2020Descriptive analysis of fibromyalgia patients seen in the lockdown time March to May 2020 shows that; gender was 64 females 97%, 2 males 3%, profession 36 unemployed 54.5%, 28 white collar 42.4%, 2 blue collar 3%, Age minimum was 25 years, maximum 77 years, with mean 48.3±13 years. Table 1Table 1.Descriptive analysis of the fibromyalgia paientsGender(Frequency)Female64 (97%)Male2 (3%)Profession(Frequency)unemployed36 (54.5%)White collar28 (42.4)Blue collar2 (3%)Fibromyalgia severity(Mean±SD)Tender Points15.7±3Pain6.5±2.1Fibromyalgia associates(Frequency)Headache32 (48.5%)Sleep Disturbance47 (71.2%)Fatigue65 (98.5%)IBS26 (39.4%)Anxiety43 (65.2%)Depression37 (56.1%)Tender points were 15.7±3, VAS for pain 6.5±2.1, sleep disturbance was present in 47 patients 71.2%, fatigue 65 patients 98.5%, irritable bowel syndrome in 26 patients 39.4%, headache in 32 patients 48.5%, anxiety in 43 patients 65.2%, and Depression in 37 patients 56.1 %.Comparing frequencies of fibromyalgia between March to May 2019 and 2020 shows a significantly higher frequency of fibromyalgia in March to May 2020, 3.1-fold more than 2019.ConclusionThe prevalence of patients with fibromyalgia seen in the Rheumatology clinics significantly increased during the lockdown time in comparison to the same period of 2019.References[1]Elsevier. “Novel Coronavirus Information Center”. Elsevier Connect. Archived from the original on 30 January 2020.[2]Reynolds, Matt (4 March 2020). “What is coronavirus and how close is it to becoming a pandemic?”. Wired UK. ISSN 1357-0978. Archived from the original on 5 March 2020. Retrieved 5 March 2020.[3]Turak, Natasha (29 January 2020). First Middle East cases of coronavirus confirmed in the UAE CNBC.com. Retrieved 19 March 2020.[4]Coronavirus: UAE confirms 294 new cases, 19 recoveries”. Khaleej Times. Retrieved 5 April 2020.[5]Psychological impact of fibromyalgia: current perspectives. GalvezSánchez CM, Duschek S, Reyes Del Paso GA. Psychol Res Behav Manag. 2019 Feb 13;12:117-127.[6]Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the Multicenter Criteria Committee. Arthritis and Rheumatism. 1990;33(2):160–172.[7]Wolfe F, Clauw DJ, Fitzcharles M, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care and Research. 2010;62(5):600–610.Disclosure of InterestsNone declared
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Rao, Sonia, Samhitha Chava, Christine Chang-Halpenny, Sukhjeet Singh Batth e Jedidiah Mercer Monson. "Fractionated external-beam radiation therapy in elderly patients." Journal of Clinical Oncology 42, n.º 16_suppl (1 de junho de 2024): e13764-e13764. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.e13764.
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e13764 Background: To review the outcome of elderly patients treated with fractionated external-beam radiation therapy (RT) at a privately-owned, multi-disciplinary cancer center. Methods: From January 7, 2019, to August 22, 2023, 63 elderly patients were treated with fractionated RT at California Cancer Associates for Research and Excellence (“cCARE”), a privately-owned, multi-disciplinary cancer center in Fresno, California. The median age at the time of RT was 90 y/o (range, 85-98 y/o). Twenty-three patients were female and 40 were male. Forty-six patients identified as white and 17 as non-white. Treatment sites/histologies included primary lung 10, non-melanomatous skin 6, bone metastases 6, breast 5, esophagus 5, H&N 5, prostate 4, primary CNS 3, brain metastases 3, rectum 3, bladder 2, Merkel tumor 2, sarcoma 2, anus 1, liver 1, melanoma 1, multiple myeloma 1, NHL 1, pancreas 1 and stomach 1. Results: Thirty-two of the patients (51%) were treated with curative intent. The remaining 31 patients were treated for palliation. All patients were treated with fractionated RT. However, 4 patients also received a separate course of single-fraction RT. Twenty-seven patients received more than one course of RT. The median RT course was 10 fractions (range, 1-35 fractions). Most patients had previously been treated with systemic therapy. Nearly one third (31%) received systemic therapy concurrent with their RT. The majority of the patients (73%) completed their prescribed course(s) of RT. Many patients (61%) required one or more treatment breaks. The median duration of a treatment break was 1 day (range, 1-29 days). There were no grade 3 or higher RT toxicities recorded. The median follow-up since RT was 5 months (range, 1-59 months). Twenty-four patients have expired. The mediation duration from RT to death was 5 months (range, 1-32 months ). Of the remaining 39 patients, 92% were scored as clinically stable at the time of their last f/u visit. Conclusions: In our experience at cCARE, fractionated RT was administered to elderly patients and the majority completed their prescribed treatment courses. None of the patients in our review experienced clinically significant side effects (Grade 3 or higher) during their RT even in the cohort (31%) who were treated with concurrent systemic therapy. Clearly, careful patient selection and state-of-the-art RT administration is paramount. It is also highly advantageous for patients to be treated in a multi-disciplinary setting such as cCARE where seamless coordination of cancer care among radiation oncologists, medical oncologists and surgeons excels. A companion study is in process comparing the outcome of similarly matched elderly patients from our center who were treated with systemic therapy alone. We anxiously await the outcome of this vital comparison review.
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Thangavel, Hariprasad, Kezia Lizardo, Robert I. Glazer e Jyothi F. Nagajyothi. "Abstract 293: Distinctive roles of mammary adipomes in breast cancer progression: Insights from functional analysis and differential gene expression". Cancer Research 84, n.º 6_Supplement (22 de março de 2024): 293. http://dx.doi.org/10.1158/1538-7445.am2024-293.
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Abstract Breast Cancer (BC) is a heterogeneous disease that impacts treatment response. This is due in part to the tumor microenvironment (TME), which contributes significantly to BC pathogenesis, including metastasis. Women with higher breast density and reduced breast fat face an increased BC risk across multiple tumor subtypes. This is exemplified by the correlation between increased tumor progression, the appearance of fibrosis and the loss of mature adipocytes. While the role of adipokines in this process has been studied extensively, the contribution of adipocyte-derived extracellular vesicles (EV) or "adipomes" in tumorigenesis and metastasis remains poorly understood. To address this question, we developed a novel technique for isolating intact adipomes from normal mammary fat (MF) obtained from wild-type C57BL/6 mice as well as from tumor-associated MF (TAMF) obtained from mice inoculated orthotopically with EO771 mammary tumor cells. Adipome isolation involved high-speed centrifugation to separate macro- and micro-vesicles, purification using the ExoQuick EV isolation system, and immunomagnetic capture of adipomes. Characterization of adipomes by transmission electron microscopy revealed two adipome populations, large L-adipomes of ~350 nm, and small S-adipomes of ~40 nm. Notably, the quantity of L-adipomes in tumor-associated mammary fat (TAMF) was 10-fold greater than the amount of L-adipomes in the MF of non-tumor-bearing mice. To identify possible functional roles of L-adipomes in the pathogenesis of BC, lipidomic profiling was undertaken. L-Adipomes from TAMF showed significantly altered lipid species in comparison to MF-derived L-adipomes. Adipomes were further characterized by treating EO771 cells for 72 hr with TAMF- or MF-derived adipomes at a cell to adipome ratio of 1:10, followed by RNAseq analysis. Differentially upregulated genes in TAMF-derived L-adipomes included Esr1, Erbb2, Tgfb1, Bcl2, MMP2, and Notch associated with fibrosis, EMT, angiogenesis and invasion and downregulation of genes linked to tumor suppression, apoptosis, and mitochondrial metabolism. Overall, our study illustrates the importance of tumor-associated adipomes in regulating gene expression in tumor cells, which emphasizes the specificity of adipome content relating to the cell-of-origin and the host's pathologic and metabolic state and in modulating signaling pathways involved in BC progression. Citation Format: Hariprasad Thangavel, Kezia Lizardo, Robert I. Glazer, Jyothi F. Nagajyothi. Distinctive roles of mammary adipomes in breast cancer progression: Insights from functional analysis and differential gene expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 293.
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Allred, Kimberly F., Erika L. Garcia-Villatoro, Jennifer DeLuca, Victoria Tepe, Zachary Bomstein, Arinzechukwu Ufondu, Stephen H. Safe, Robert S. Chapkin, Arul Jayaraman e Clinton D. Allred. "Abstract 3443: Aryl hydrocarbon receptor and its ligands influence the formation of colonic tertiary lymphoid tissues". Cancer Research 83, n.º 7_Supplement (4 de abril de 2023): 3443. http://dx.doi.org/10.1158/1538-7445.am2023-3443.
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Abstract Background: In the large intestine, tertiary lymphoid tissues (TLTs) serve as localized centers of adaptive immune responses. These structures often form in response to inflammation and infection during adulthood. However, more recently TLTs have become a focal point of colon caner development and progression as their presence is often associated with positive clinical outcomes. Interestingly, several studies have demonstrated that the aryl hydrocarbon receptor (AhR) influences the development of secondary lymphoid tissues, but minimal studies have focused on its role in TLT formation. The purpose of the presented studies was to test the hypothesis that activation of AhR in intestinal epithelial cells (IECs) induces the formation of TLTs in the colon. Methods: Wild type (WT) and IEC-specific AhR knockout (CDX2PCreT2 x AhRf/f- iAhRKO) mice were used in several different experimental models. In the first study, azoxymethane (AOM) was used to induce precancerous lesions in the colon and TLT formation was evaluated in the presence and absence of AhR. Then, experiments were conducted to determine the necessity of AhR expression in IECs to influence the formation of TLTs following induction of acute inflammation induced by Dextran sodium sulfate (DSS) exposure. Finally, the ability of known, naturally occurring and microbial-derived AhR ligands (indole-3-aldehyde (I3A), 3,3ʹ-diindolylmethane (DIM), and indole-3-acetic acid (IAA)) were tested for their ability to induce TLT formation in the colon. Intestinal permeability (FITC-Dextran), expression of IEC-associated genes (real-time qPCR), and TLT formation/composition (H&E staining/Immunofluorescence) were evaluated. Results: Results from the first study demonstrated that IEC-specific AhR KO mice exposed to AOM developed significantly fewer TLTs when compared to WT controls, while expression of Il-22 and other chemokines involved in TLT formation were also significantly downregulated. In the acute inflammation study, sex specific results were found. In females, loss of AhR activity in IECs reduced the formation of TLTs without significant changes in immune cell composition within their TLTs. Conversely, in males, loss of AhR lowered expression of functional-IEC genes (Ocln, Il-22), increased number of TLTs, increased T-cell density, and lower B: T cell ratio. Finally, in the other experiments, I3A induced TLT formation and DIM promoted intestinal barrier integrity through the upregulation of various tight junction genes and genes involved in the signaling associated with TLT formation. Evaluation of IAA which is a microbial-derived, AhR ligand is ongoing. Conclusion: These data indicate that AhR plays a distinct role in the formation of TLTs in the colon and these effects are likely ligand specific and may have a significant effect on colon tumor formation. Citation Format: Kimberly F. Allred, Erika L. Garcia-Villatoro, Jennifer DeLuca, Victoria Tepe, Zachary Bomstein, Arinzechukwu Ufondu, Stephen H. Safe, Robert S. Chapkin, Arul Jayaraman, Clinton D. Allred. Aryl hydrocarbon receptor and its ligands influence the formation of colonic tertiary lymphoid tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3443.
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Fullerton, Benjamin, Robyn Gartrell, Thomas Enzler, Pan Kim, Ladan Fazlollahi, Andrew Chen, Subha Perni et al. "872 Neoadjuvant chemoradiotherapy enhances T cell infiltration in pancreatic ductal adenocarcinoma but high percentage of regulatory T cells associates with poor survival". Journal for ImmunoTherapy of Cancer 8, Suppl 3 (novembro de 2020): A924—A925. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0872.
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BackgroundCurrently, diagnosis with pancreatic ductal adenocarcinoma (PDAC) renders an almost intrinsically poor patient prognosis. Despite complete surgical resection and intense neoadjuvant and/or adjuvant treatment the great majority of patients will ultimately relapse and die from the disease. Further, PDAC has been characterized as highly immune resistant. It is speculated that radiation, chemotherapy, or chemoradiation cause the release of tumor antigens and inflammatory cytokines eventually leading to increased immunogenicity of PDAC.MethodsWe used computational quantitative multiplex immune fluorescence (qmIF) (n=31) and the NanoString assay (n=34) to quantitatively analyze the effect of neoadjuvant chemoradiation (CRT) on the tumor immune microenvironment (TIME) of PDAC.ResultsWhen comparing non-treated (NT) to neoadjuvant chemoradiation (CRT) tumors, the proportion of tumor within the overall tissue sample was markedly lower in treated tumors (figure 1; Mann Whitney U, U=25, p<0.0001). Additionally, the overall density of Ki67+ cells throughout all tissue was significantly lower in samples that received CRT (figure 1; Mann Whitney U, U=52, p=0.0067). An overall influx of CD3+ cells was noted in CRT samples. T cell influx was accompanied by upregulation of inflammatory genes. When considering T cell subsets, an increase in the CD8+ (Cytotoxic) and CD4+FOXP3+ (Treg) cell densities in the tumor of CRT samples was found. CD4+FOXP3- (T helper) cell density was found to be increased in the tumor, stroma, and overall tissue in CRT samples (figure 2). When comparing samples from patients who lived longer than 2 years to samples from patients who did not within the CRT group, a notably higher ratio of Tregs to CD3+ cells was observed in patients who lived less than 2 years (Mann Whitney U, U=0, p=0.0006). When used as a predictor, the ratio of Tregs to CD3+ cells also correlated closely to patient survival (figure 3); Mantel-Cox, p=0.0121).Abstract 872 Figure 1Representative tissue segmentation and multiplex immune fluorescence (mIF) image of a non-treated patient and a patient who received neoadjuvant chemoradiation and analysis of total tumor density. Tissue segmentation images for A) NT and B) CRT. Blue cells are DAPI (nuclei) positive. Red areas represent tumor tissue, blue areas represent stromal tissue. Processing of slides done in inFormTM (PerkinElmer/Akoya). Multiplex view of the same C) NT and D) CRT images stained using mIF for DAPI (nuclei, blue), Ki67 (tumor, proliferative cells, red), CD3 (T cells, cyan), CD4 (T helper cells, orange), CD8 (cytotoxic T cells (CTLs), magenta), FOXP3 (T regulatory cells (Tregs), yellow), CD68 (macrophages, green). White bars = 100μm. E) Comparison of the proportion of total cells in the tumor tissue to the overall tissue sample between treatment groups (pAbstract 872 Figure 2Density of immune cells in stroma, tumor, and total tissue comparing non-treated to neoadjuvant chemoradiation treated tissue. A) CD3+ cells in tumor (p=0.0006), B) CD3+ cells in stroma (p=0.0078), and C) CD3+ cells in total (p=0.0013). D) CD3+CD8+ cells in tumor (p=0.0079) , E) CD3+CD8+ cells in stroma (p=0.0758), and F) CD3+CD8+ cells in total (p=0.0076). G) CD3+CD4+FOXP3- cells in tumor (p=0.0010), H) CD3+CD4+FOXP3- cells in stroma (p=0.0216), and I) CD3+CD4+FOXP3- cells in total (p=0.0078). J) CD3+CD4+FOXP3+ cells in tumor (p=0.0089), K) CD3+CD4+FOXP3+ cells in stroma (p=0.4211), and L) CD3+CD4+FOXP3+ cells in total (p=0.1464). (*≤0.05, **≤0.01 ***≤0.001, ****≤0.0001)Abstract 872 Figure 3Treg/CD3 differences in CRT PatientsSurvival was analyzed in n=14 patients using qmIF using Kaplan Meier analysis based on median Treg/CD3 value cutoff. Survival was significantly lower in patients with a high CD4+FOXP3+/CD3+ ratio (p=0.0121).ConclusionsWe find that CRT greatly alters the TIME of PDAC, altering distributions of tumor cells within the microenvironment and inducing an overall influx of T cells, including cytotoxic, helper, and Treg T cell subsets. In patients receiving CRT, it appears as though the proportion of T cells infiltrating the tumor that are Tregs is closely associated with patient outcome, with a higher proportion of Treg infiltration correlating with a poor outcome. This data suggests that therapies targeting regulatory T cells should be explored in combination with chemo-radiotherapy in PDAC.Ethics ApprovalThe study was approved by Columbia University’s Ethics Board, approval number AAAQ7337.
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KITLV, Redactie. "Book Reviews". New West Indian Guide / Nieuwe West-Indische Gids 61, n.º 1-2 (1 de janeiro de 1987): 55–114. http://dx.doi.org/10.1163/13822373-90002056.
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-Sidney W. Mintz, Mats Lundahl, The Haitian economy: man, land and markets. New York: St. Martins Press, 1983. 290 pp.-Regine Altagrace Latortue, Léon-Francois Hoffmann, Essays on Haitian Literature. Washington D.C.: Three Continents Press, 1984. 184 pp.-Robert Forster, Lieutenant Howard, The Haitian journal of lieutenant Howard, York Hussars, 1796-1798. Edited with an introduction by Roger Norman Buckley. Knoxville: University of Tennessee Press, 1985. liv + 194.-David Bray, Bernardo Vega, Los Estados Unidos y Trujillo, año 1930. Santo Domingo: Fundación Cultural Dominicano, 1986. 2 vols. xi + 1120 pp.-David Bray, Bernardo Vega, Los Estados Unidos y Trujillo, año 1947. Santo Domingo: Fundación Cultural Dominicana, 1984. 2 vols. xi + 1018 pp.-David Bray, Bernardo Vega, Nazismo, fascismo y falangismo en la Republica Dominicana. Santo Domingo: Fundación Cultural Dominicana, 1985. 415 pp.-Tony Thorndike, Bruce J. Calder, The impact of intervention: The Dominican Republic during the US occupation of 1916-1924. Austin: University of Texas Press, 1984. 358 pp.-Marcella M. Little, Jacques Barbier ,The North American role in the Spanish imperial economy 1760-1819. Manchester, England, 1984: Manchester University Press. pp. 232., Allan J. Kuethe (eds)-Janette Forte, Peter Riviere, Individual and society in Guiana: a comparative study of Amerindian social organisation. Cambridge, London, New York: Cambridge University Press, 1984. 127 pp.-Stephen D. Glazier, Jay D. Dobbin, The Jombee dance of Montserrat: a study of trance ritual in the West Indies. Columbus: Ohio State University Press, 1986. 202 pp.-Robert J. Stewart, Stephen D. Glazier, Marchin' the Pilgrims home: leadership and decision-making in an Afro-Caribbean faith. Connecticut and London: Greenwood Press, 1983. xv + 165 pp.-Sidney M. Greenfield, Karen Fog Olwig, Cultural adaptation and resistance on St. John: three centuries of Afro-Caribbean life. Gainesville: University of Florida Press, 1985. xii + 226 pp.-Adam Kendon, William Washabaugh, Five fingers for survival. Ann Arbor: Karoma Publishers, Inc., 1986. xiv + 198 pp.-Evelyne T. Menard, Carnot (F. Moloen), Alors ma chére...Propos d'un musicien guadeloupéen recueillis et traduits par Marie-Céline Lafontaine. Paris: Editions Caribéennes, 1986. 159 pp.-Sally Price, Suzanne Slesin ,Caribbean style. Authors include Daniel Rozensztroch. Photographs by Gilles de Chabaneix. New York: Clarkson N. Potter, 1985. 290 pp., Stafford Cliff, Jack Berthelot (eds)-Allison Blakely, Gert Oostindie ,In het land van de overheerser. Deel II. Antillianen en Surinamers in Nederland, 1634/1667-1954. Dordrecht (Holland) and Providence RI (U.S.A.): Foris Publications, 1986. xi + 255 pp., Emy Maduro (eds)-Rosemarijn Hoefte, E. van de Boogaart ,Overzee: Nederlandse koloniale geschiedenis, 1590-1975. Haarlem: Fibula-van Dishoek, 1982. 291 pp., P.J. Drooglever et al (eds)-Frederick J. Conway, P.I. Gomes, Rural development in the Caribbean. London: C. Hurst and Company. New York: St. Martins Press, 1985. xxi + 246 pp.-Steve M. Slaby, Charles Edquist, Capitalism, socialism and technology: a comparative study of Cuba and Jamaica. London: Zed Books Ltd., 1985. xiii + 182 pp.-Joan D. Mandle, June Nash ,Women and social change in Latin America. South Hadley, Mass.: Bergin and Garvey Publishers, 1986. 372 pp., Helen Safa (eds)-Bonham C. Richardson, Michael L. Conniff, Black labor on a white canal: Panama, 1904-1981. Pittsburgh, Pa.: University of Pittsburgh Press, 1985. xv + 221 pp.-Brackette F. Williams, Stephen Glazier, Caribbean ethnicity revisited. A special edition of Ethnic Groups, International periodical of ethnic studies. New York, London, Paris, Montreaux, Tokyo: Gordon Breach Science Publishers, 1985. 164 pp.-Gert J. Oostindie, Frauke Gewecke, Die Karibik; zur Geschichte, Politik und Kultur einer Region. Frankfurt/M: Verlag Klaus Dieter Vervuert 1984. 165 pp.
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LaMorte, Joseph, Nicholas Bateman, Thomas Conrads, Robert F. Browning, Craig D. Shriver, Robert L. Kortum e Matthew D. Wilkerson. "Abstract 4944: Divergent proteogenomic gene expression is driven by microenvironment across tumor types". Cancer Research 84, n.º 6_Supplement (22 de março de 2024): 4944. http://dx.doi.org/10.1158/1538-7445.am2024-4944.
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Abstract Solid tumors develop through a complex series of genome and downstream expression alterations that interact with the local tissue microenvironment, leading to a transformed cell and malignant phenotype. With massive multi-omic data, recent proteogenomics studies have jointly analyzed RNA and protein expression to uncover new gene regulatory relationships; however, many of these studies focused on single tumor types and lack a generalizable view of joint RNA and protein expression. Here, we present the first pan-cancer analysis of sample-wise RNA to protein correlation (SRPC). We re-analyzed over 1,000 tumors across 10 tumor types from published proteogenomic data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) Research Network. We identified a wide range of SRPC across all tumors (ρ range: -0.08 to 0.70, median: 0.45). We then analyzed tumor pathologic and molecular characteristics versus the range of SRPC. High SRPC tumors had high tumor purity by pathology review, by somatic DNA whole exome sequencing, and by RNA and protein purity scores. In contrast, low SRPC tumors had high immune cell and stromal cell expression scores as inferred by either protein or RNA based signatures. We observed marked differences in cell type populations estimated by expression in different SRPC tumor tranches (low SRPC: macrophages, endothelial cells, cancer-associated fibroblasts; high SRPC: CD4+ Th2 cells). Tumors expressed signaling pathways depending on their SRPC (low SRPC: hypoxia, inflammatory response, and KRAS signaling; high SRPC: DNA repair and E2F targets). SRPC also stratifies tumors with distinct somatic DNA alterations (low SRPC: HRAS and NF2; high SRPC: TP53, MEN1, high Tumor Mutational Burden and high DNA chromosomal instability). Finally, we found that cancer driver genes displayed divergent gene-wise RNA to protein correlations (GRPC) among tumor types with a median absolute deviation interquartile range of 0.1 - 0.2, suggesting tumor-type-specific regulation. In summary, divergent RNA and protein expression is driven, in part, by tumor microenvironment composition across tumor types. Tumors with a diverse cellular microenvironment display a summation of RNA and protein expression resulting from this cell type diversity leading to a low SRPC, while tumors predominated by tumor cells display coordinated RNA and protein expression levels resulting from a pure clonal or cell type leading to a high SRPC. This first deep analysis into sample-wise RNA to protein correlation represents a large proteogenomic community resource for informing biomarker analysis by modality and by tranches of tumor microenvironment. The views expressed in this abstract are solely of the authors and do not reflect the official policy of the Departments of Army/Navy/Air Force, Department of Defense, USUHS, HJF, or U.S. Government. Citation Format: Joseph LaMorte, Nicholas Bateman, Thomas Conrads, Robert F. Browning, Craig D. Shriver, Robert L. Kortum, Matthew D. Wilkerson. Divergent proteogenomic gene expression is driven by microenvironment across tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4944.
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Torrelli-Diljohn, Alex B., Svetlana Komarova, Vipul Sheth, Benjamin Lin, Paran Goel, Ryan Miller, Robert Welner e Erwin G. Van Meir. "Abstract 15: Investigating the spectrum of brain tumors associated with Adgrb3 and Tp53 loss in a mouse model of Li-Fraumeni syndrome". Cancer Research 83, n.º 7_Supplement (4 de abril de 2023): 15. http://dx.doi.org/10.1158/1538-7445.am2023-15.
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Abstract Adhesion G protein-coupled receptor 3 (ADGRB3), also known as brain specific angiogenesis inhibitor (BAI3) is a member of the ADGRB1-3 subfamily of adhesion transmembrane proteins, which are highly expressed in the brain specifically in cerebellum and hippocampal neurons. ADGRB3 has been shown to play diverse roles under physiological and pathological conditions which include dendritic morphogenesis, synaptic plasticity, synaptogenesis, and myogenesis. Loss of ADGRB3 expression and point mutations in the gene have been observed in sporadic tumors, including brain tumors, but the significance of this observation has not been investigated. Moreover, no mouse models to understand the role of ADGRB3 in brain tumor susceptibility and pathobiology have been developed thus far. Li-Fraumeni syndrome (LFS) is a rare inherited autosomal dominant disorder caused by a germline mutation in one TP53 allele, predisposing patients to the development of a variety of tumors from a pediatric age, including gliomas and medulloblastoma. The secondary molecular alterations that predispose LFS patients to brain tumors are currently unknown. Interestingly, a LFS patient was reported to carry a translocation in ADGRB3 and HGMLL genes. To investigate the molecular mechanisms underlying brain tumor formation in LFS patients and the role of p53 and ADGRB3 in the process, we have generated a LFS mouse model. The mice harbor a germline p53 deleted allele and a second floxed allele. Loss of the second allele is induced in the brain by crossing with mice harboring a Nestin promoter driven Cre recombinase, since Nestin is expressed along the craniospinal axis and in glial precursor cells. We observed that the majority of nestin-Cre p53m/f mice all died between 8 and 10 months of age while nestin-Cre p53m/+ mice did not. About 20% of the mice developed hind leg paralysis and harbored large gliomas, which likely caused their demise. The remainder mice lacked brain tumors, but had other malignancies (sarcomas, etc.) as observed in patients. Remarkably, the addition of Adgrb3 deletion to the genotype led to a dramatic increase (from 20% to 60%??) in the number of brain tumors, including medulloblastoma formation, which are also reported in LFS patients. The Adgrb3-/- p53+/- Nestin-Cre mouse model constitutes a useful tool to understand the tumorigenic landscape caused by the loss of Adgrb3. We are now performing genomic analyses on the excised tumors and derived neurosphere cultures to further study the transformation process and the molecular changes induced by Adgrb3 loss. Citation Format: Alex B. Torrelli-Diljohn, Svetlana Komarova, Vipul Sheth, Benjamin Lin, Paran Goel, Ryan Miller, Robert Welner, Erwin G. Van Meir. Investigating the spectrum of brain tumors associated with Adgrb3 and Tp53 loss in a mouse model of Li-Fraumeni syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 15.
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Day, Melissa E., Miguel E. Mejia Sang, Yonairy Collado Puello, Elvira J. Diaz Brockmans, Stephanie Rivera Defillo, Karla M. Taveras Cruz, Javier O. Santiago Perez et al. "725. Complete Blood Count Values Vary in Degree of Change with Day of Fever in Children with Dengue Fever". Open Forum Infectious Diseases 8, Supplement_1 (1 de novembro de 2021): S461—S462. http://dx.doi.org/10.1093/ofid/ofab466.922.
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Abstract Background Dengue fever (DF) is an acute viral disease which can lead to severe illness, including dengue hemorrhagic fever, marked by thrombocytopenia and hemolytic anemia, as well as end-organ damage. Despite the well-known presentation and prevalence, changes in hematologic markers across the DF course have not been well-described in children. We sought to investigate the association of clinical laboratory values over time with dengue disease progression and outcome in a pediatric population in the Dominican Republic. Methods Pediatric participants were enrolled at Hospital Infantil Dr. Robert Reid Cabral in Santo Domingo, Dominican Republic, in a prospective, observational case-based study. Laboratory values, including complete blood count (CBC) indices and dengue titer results, were collected over the course of hospital stay. Using linear mixed models, we assessed whether 13 different CBC values and time trajectories differed by dengue status, including age and sex as covariates. To account for multiple testing, p≤0.0033 was considered significant. Results A total of 575 children ages 0 to 211 months met inclusion criteria; 51.8% (n=298) were male, and the median (IQR) age was 59 (14-93) months. Eighty-two percent (n=472) of participants had DF. CBC values across days 1 to 10 of fever in those with and without DF are depicted in Figure 1. Those with DF showed levels dropping more quickly across days of fever for hematocrit and hemoglobin (p≤ 0.002), with a more rapid decline in those with severe DF (p < 0.0001). Those with DF had levels increasing more quickly for mean corpuscular hemoglobin concentration (MCHC), monocyte number, and white blood cell counts (p ≤ 0.003), with those with severe DF having a more rapid increase (p < 0.001). The direction of the change across time differed by DF status for mean corpuscular volume and red blood cell distribution width (RDW) (p ≤ 0.0003), with those with severe DF showing an increase in RDW across day of fever (p= 0.0004). Figure 1. CBC values across day of fever in dengue (blue) and non-dengue (purple) patients. The graph above depicts the following CBC values across day of fever in dengue (blue) and non-dengue (purple) patients: a) white blood cell (WBC) count, b) platelet count, c) monocyte number, d) hemoglobin, e) mean corpuscular hemoglobin concentration (MCHC), and f) mean corpuscular volume (MCV). Values with an asterisk (*) represent significant values (p < 0.0033). Conclusion The trajectory of CBC measures differs between those with and without DF, despite similar clinical presentations. These laboratory differences may facilitate a better understanding of the clinical course of DF and may aid in earlier identification of DF in resource-limited settings. Disclosures Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member)
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Gray, Joshua P., Gamze E. Bildik, Margie N. Sutton, Yong Zhou, Steven Millward, John F. Hancock, Zhen Lu e Robert C. Bast. "Abstract 3599: Helical stapled peptides derived from DIRAS3 block KRAS dimerization and downstream MEK/ERK signaling in pancreatic and ovarian carcinomas". Cancer Research 82, n.º 12_Supplement (15 de junho de 2022): 3599. http://dx.doi.org/10.1158/1538-7445.am2022-3599.
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Abstract The overall 5-year survival for pancreatic ductal adenocarcinoma (PDAC) has changed little over the past few decades, and PDAC is predicted to become the second leading cause of cancer-related mortality in the next decade in Western countries. Low grade serous ovarian cancer (LGSOC) is a slow-growing but generally chemo-resistant cancer with few effective treatments for recurrent disease. More than 90% of PDAC and up to 40% of LGSOC express mutationally activated KRAS that drives persistent cell division, anti-apoptosis, cell migration and metastasis. Preventing signaling from the KRAS oncoprotein has been challenging. While recent studies have shown promising results by targeting the binding pocket in Switch II for development of KRAS mutant-specific inhibitors for the G12C mutant and G12D mutant, targeting other mutations remains a work in progress. We have discovered that DIRAS3, a novel endogenous physiological RAS inhibitor, blocks KRAS activity by directly binding KRAS with high affinity, inhibiting KRAS dimerization/nanoclustering and blocking effector activation. In this study we have developed drug-like, helical 10-mer stapled peptides derived from DIRAS3 α5 domain. Preliminary studies show that these lead compounds associate with KRAS with low nanomolar affinity, are largely resistant to serum proteases, and rapidly cross the cellular membrane. Functionally, DIRAS3 peptides—but not control peptides—block KRAS homodimers in ReBiL split luciferase assays of KRAS dimerization and disrupt nanoclustering by TEM analysis of GFP-KRAS(G12V)-labeled gold nanoparticles on the inner leaflet of the plasma membrane of cells. Moreover, DIRAS3 peptides significantly inhibit phospho-ERK, decrease cell viability and induce apoptosis in pancreatic and low-grade ovarian cancer cells with KRAS mutations. Finally, daily treatment with stapled DIRAS3-derived peptides inhibited growth of ASPC-1 (KRAS G12D) PDAC xenografts and improved survival. Thus, our study suggests that development of DIRAS3 stapled peptides may provide a novel therapeutic approach to target mutant KRAS-driven cancers. Citation Format: Joshua P. Gray, Gamze E. Bildik, Margie N. Sutton, Yong Zhou, Steven Millward, John F. Hancock, Zhen Lu, Robert C. Bast. Helical stapled peptides derived from DIRAS3 block KRAS dimerization and downstream MEK/ERK signaling in pancreatic and ovarian carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3599.
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Spinelli, F. R., M. S. Chimenti, M. Vadacca, C. Iannuccelli, P. Conigliaro, S. L. Bosello, F. Ceccarelli et al. "SAT0153 GENDER DOES NOT INFLUENCE CLINICAL RESPONSE TO JAK INHIBITORS IN RHEUMATOID ARTHRITIS: AN ITALIAN MULTICENTRE ANALYSIS". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 1016.2–1017. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5978.
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Background:Gender medicine aims at describing how diseases differ between men and women in terms of epidemiology, clinical feature, therapeutic approach, treatment response and prognosis, psychological and social impact. Rheumatoid Arthritis (RA) affects women 2-3 times more than men. Female gender seems to be independently associated to a more refractory disease and a worst response to conventional synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs) and biological DMARDs. Male patients achieve remission more often than females probably due to the higher number of tender joints reported by the latter.Objectives:In the light of the effect of Janus kinases inhibitors (JAKi) on pain, the objective of the study was to investigate whether gender might affect the achievement of remission or low disease activity in RA patients treated with baricitinib and tofacitinib.Methods:We performed a multicentric, prospective study on consecutive patients starting one of the two available JAKi: baricitinib and tofacitinib. Demographic and clinical data were recorded in a dedicate database and included: gender, age, disease duration, serological status (Rheumatoid Factor – RF; anti-citrullinated peptide antibodies, ACPA) number of previous csDMARDs and bDMARDs, number of tender joints (TJ) and swollen joints (SJ), C reactive protein (CRP); patient global assessment (PGA) and pain were recorded on a 0-100 mm visual-analogue scale (VAS). Disease activity score (DAS) 28 was calculated at baseline and at two follow-up visits (after 3-4 months and after 6-8 months). Data were expressed as mean±standard deviation or median (interquartile range) according to variables’ distribution. Continuous variables were compared by Mann Whitney test while dichotomous ones by Chi-squared test; p value < 0.05 were considered statistically significant.Results:We enrolled 182 RA patients (149 F:33 M) with similar age (F 58±12 vs M 60±10) and disease duration (F 143±101 vs M 147±105 months). Females and males were previously treated with the same number of csDMARDs [2(2)] but female have previously received numerically more bDMARDs [2(3) vs 1(2)]. At the 3 timepoints females and males showed similar number of TJ, SJ, similar values of CRP, PGA and pain. We did not observe any difference in percentage of males and females achieving remission or low disease activity according to gender (figure 1A) nor in terms of reduction of TJ, SJ and PGA; only pain decreased significantly more in male than in female patients at both timepoints (figure 1B).Conclusion:In RA patients treated with JAK inhibitors, even if the effect of JAKi on pain seems to be more relevant in male than in female, gender seems not to influence the overall clinical response, allowing men and women the same probability of reaching the therapeutic targetReferences:Disclosure of Interests:Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Maria Sole Chimenti: None declared, Marta Vadacca: None declared, Cristina Iannuccelli: None declared, Paola Conigliaro: None declared, Silvia Laura Bosello: None declared, Fulvia Ceccarelli: None declared, Cristina Garufi: None declared, Giulia Raffone: None declared, Paola Di Noi: None declared, Dario Bruno: None declared, Antonella Afeltra: None declared, Roberto Perricone: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB
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Krausman, Paul R. "The Ecology of Large Mammals in central Yellowstone; sixteen years of integrated field studies. Robert H. Garrott, P. J. White, and F. G. R. Watson. editors. 2009. Academic Press, San Diego, California, USA. 693 pp. ISBN 13: 978‐0‐12‐374174‐5". Journal of Wildlife Management 75, n.º 3 (abril de 2011): 747–48. http://dx.doi.org/10.1002/jwmg.87.
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KITLV, Redactie. "Book Reviews". New West Indian Guide / Nieuwe West-Indische Gids 71, n.º 3-4 (1 de janeiro de 1997): 317–91. http://dx.doi.org/10.1163/13822373-90002612.
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-Leslie G. Desmangles, Joan Dayan, Haiti, history, and the Gods. Berkeley: University of California Press, 1995. xxiii + 339 pp.-Barry Chevannes, James T. Houk, Spirits, blood, and drums: The Orisha religion in Trinidad. Philadelphia: Temple University Press, 1995. xvi + 238 pp.-Barry Chevannes, Walter F. Pitts, Jr., Old ship of Zion: The Afro-Baptist ritual in the African Diaspora. New York: Oxford University Press, 1993. xvi + 199 pp.-Robert J. Stewart, Lewin L. Williams, Caribbean theology. New York: Peter Lang, 1994. xiii + 231 pp.-Robert J. Stewart, Barry Chevannes, Rastafari and other African-Caribbean worldviews. London: Macmillan, 1995. xxv + 282 pp.-Michael Aceto, Maureen Warner-Lewis, Yoruba songs of Trinidad. London: Karnak House, 1994. 158 pp.''Trinidad Yoruba: From mother tongue to memory. Tuscaloosa: University of Alabama Press, 1996. xviii + 279 pp.-Erika Bourguignon, Nicola H. Götz, Obeah - Hexerei in der Karibik - zwischen Macht und Ohnmacht. Frankfurt am Main: Peter Lang, 1995. 256 pp.-John Murphy, Hernando Calvo Ospina, Salsa! Havana heat: Bronx Beat. London: Latin America Bureau, 1995. viii + 151 pp.-Donald R. Hill, Stephen Stuempfle, The steelband movement: The forging of a national art in Trinidad and Tobago. Philadelphia: University of Pennsylvania Press, 1995. xx + 289 pp.-Hilary McD. Beckles, Jay R. Mandle ,Caribbean Hoops: The development of West Indian basketball. Langhorne PA: Gordon and Breach, 1994. ix + 121 pp., Joan D. Mandle (eds)-Edmund Burke, III, Lewis R. Gordon ,Fanon: A critical reader. Oxford: Blackwell, 1996. xxi + 344 pp., T. Denean Sharpley-Whiting, Renée T. White (eds)-Keith Alan Sprouse, Ikenna Dieke, The primordial image: African, Afro-American, and Caribbean Mythopoetic text. New York: Peter Lang, 1993. xiv + 434 pp.-Keith Alan Sprouse, Wimal Dissanayake ,Self and colonial desire: Travel writings of V.S. Naipaul. New York : Peter Lang, 1993. vii + 160 pp., Carmen Wickramagamage (eds)-Yannick Tarrieu, Moira Ferguson, Jamaica Kincaid: Where the land meets the body: Charlottesville: University Press of Virginia, 1994. xiii + 205 pp.-Neil L. Whitehead, Vera Lawrence Hyatt ,Race, discourse, and the origin of the Americas: A new world view. Washington DC: Smithsonian Institution Press, 1995. xiii + 302 pp., Rex Nettleford (eds)-Neil L. Whitehead, Patricia Seed, Ceremonies of possession in Europe's conquest of the new world, 1492-1640. Cambridge: Cambridge University Press, 1995. viii + 199 pp.-Livio Sansone, Michiel Baud ,Etnicidad como estrategia en America Latina y en el Caribe. Arij Ouweneel & Patricio Silva. Quito: Ediciones Abya-Yala, 1996. 214 pp., Kees Koonings, Gert Oostindie (eds)-D.C. Griffith, Linda Basch ,Nations unbound: Transnational projects, postcolonial predicaments, and deterritorialized nation-states. Langhorne PA: Gordon and Breach, 1994. vii + 344 pp., Nina Glick Schiller, Cristina Szanton Blanc (eds)-John Stiles, Richard D.E. Burton ,French and West Indian: Martinique, Guadeloupe and French Guiana today. Charlottesville: University Press of Virginia; London: Macmillan Caribbean, 1995. xii + 202 pp., Fred Réno (eds)-Frank F. Taylor, Dennis J. Gayle ,Tourism marketing and management in the Caribbean. New York: Routledge, 1993. xxvi + 270 pp., Jonathan N. Goodrich (eds)-Ivelaw L. Griffith, John La Guerre, Structural adjustment: Public policy and administration in the Caribbean. St. Augustine: School of continuing studies, University of the West Indies, 1994. vii + 258 pp.-Luis Martínez-Fernández, Kelvin A. Santiago-Valles, 'Subject People' and colonial discourses: Economic transformation and social disorder in Puerto Rico, 1898-1947. Albany: State University of New York Press, 1994. xiii + 304 pp.-Alicia Pousada, Bonnie Urciuoli, Exposing prejudice: Puerto Rican experiences of language, race, and class. Boulder: Westview Press, 1996. xiv + 222 pp.-David A.B. Murray, Ian Lumsden, Machos, Maricones, and Gays: Cuba and homosexuality. Philadelphia: Temple University Press, 1996. xxvii + 263 pp.-Robert Fatton, Jr., Georges A. Fauriol, Haitian frustrations: Dilemmas for U.S. policy. Washington DC: Center for strategic & international studies, 1995. xii + 236 pp.-Leni Ashmore Sorensen, David Barry Gaspar ,More than Chattel: Black women and slavery in the Americas. Bloomington: Indiana University Press, 1996. xi + 341 pp., Darlene Clark Hine (eds)-A. Lynn Bolles, Verene Shepherd ,Engendering history: Caribbean women in historical perspective. Kingston: Ian Randle; London: James Currey, 1995. xxii + 406 pp., Bridget Brereton, Barbara Bailey (eds)-Bridget Brereton, Mary Turner, From chattel slaves to wage slaves: The dynamics of labour bargaining in the Americas. Kingston: Ian Randle; Bloomington: Indiana University Press; London: James Currey, 1995. x + 310 pp.-Carl E. Swanson, Duncan Crewe, Yellow Jack and the worm: British Naval administration in the West Indies, 1739-1748. Liverpool: Liverpool University Press, 1993. x + 321 pp.-Jerome Egger, Wim Hoogbergen, Het Kamp van Broos en Kaliko: De geschiedenis van een Afro-Surinaamse familie. Amsterdam: Prometheus, 1996. 213 pp.-Ellen Klinkers, Lila Gobardhan-Rambocus ,De erfenis van de slavernij. Paramaribo: Anton de Kom Universiteit, 1995. 297 pp., Maurits S. Hassankhan, Jerry L. Egger (eds)-Kevin K. Birth, Sylvia Moodie-Kublalsingh, The Cocoa Panyols of Trinidad: An oral record. London & New York: British Academic Press, 1994. xiii + 242 pp.-David R. Watters, C.N. Dubelaar, The Petroglyphs of the Lesser Antilles, the Virgin Islands and Trinidad. Amsterdam: Foundation for scientific research in the Caribbean region, 1995. vii + 492 pp.-Suzannah England, Mitchell W. Marken, Pottery from Spanish shipwrecks, 1500-1800. Gainesville: University Press of Florida, 1994. xvi + 264 pp.
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Mamounas, Eleftherios, Hanna Bandos, Julia White, Thomas Julian, Atif Khan, Simona Shaitelman, Mylin Torres et al. "Abstract GS02-07: Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304". Cancer Research 84, n.º 9_Supplement (2 de maio de 2024): GS02–07—GS02–07. http://dx.doi.org/10.1158/1538-7445.sabcs23-gs02-07.
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Abstract Background: The benefit of adjuvant regional nodal irradiation including the chest wall after mastectomy (CWI+RNI) and with whole breast irradiation (WBI+RNI) after breast conserving surgery (BCS) is well established in pts with pathologically positive axillary nodes (pN+). Pts who present with axillary node involvement (cN+), receive neoadjuvant chemotherapy (NC), and are found to be pathologically node-negative at surgery (ypN0), have lower loco-regional recurrence (LRR) rates compared to those who remain pathologically node-positive (ypN+). This phase III, randomized trial aimed to evaluate whether CWI+RNI after mastectomy or addition of RNI to WBI after BCS significantly improves invasive breast cancer recurrence-free interval (IBC-RFI) in cN+ pts found to be ypN0 after NC. Methods: Eligible pts had clinical cT1-3, N1, M0 invasive breast cancer (biopsy-proven N+ by FNA/core needle bx), completed ≥8 wks of NC (and anti-HER2 therapy if HER2+), and were ypN0 after mastectomy or BCS and sentinel node biopsy (SLNB, ≥2 nodes), axillary lymph node dissection (ALND), or both. Pts were randomized to “No RNI” (i.e., observation after mastectomy or WBI after BCS) vs. “RNI” (i.e., CWI+RNI after mastectomy or WBI+RNI after BCS). Primary endpoint was IBC-RFI. Secondary endpoints reported here: LRR-free interval (LRRFI), distant recurrence-free interval (DRFI), disease-free survival (DFS), and overall survival (OS). Study was designed to have 80% power to detect 35% reduction in annual rate of IBC-RFI for an absolute risk reduction of 4.6% (5-yr cumulative rate). Per protocol, final analysis was to occur after 172 events or 10 yrs after study initiation.Here we report the time-driven analysis prespecified in the protocol. Results: From 9/13-12/20, 1,641 pts were enrolled; 1,556 pts were available for primary event analysis; median f/u time 59.5 mos (IQR 40.7-74.1). Pt/tumor characteristics were well balanced between groups. Median age 52 yrs (range 21-84); 31% non-white; 21% cT1, 60% cT2, 19% cT3; 23% triple-negative, 21% HR+/HER2-, 56% HER2+; 58% BCS; 55% SLNB, 45% ALND+/-SLNB; and 78% had breast pathologic complete response. At the time of the analysis, 109 IBC-RFI events (63% of the planned 172) were confirmed (“No RNI”: 59, “RNI”: 50). There was no statistically significant difference between groups for IBC-RFI (HR=0.88, 95%CI 0.60-1.29; p=0.51), 5-yr point estimates: 91.8% for “No RNI” and 92.7% for “RNI.” There were no statistically significant differences between the treatment groups for secondary endpoints. There were no study-related deaths and no unexpected toxicities.Grade 4 toxicity was rare (0.1% with “No RNI”, 0.5% with “RNI”); 6.5% of pts developed grade 3 toxicity in “No RNI” and 10% in “RNI” group. Most common grade 3 toxicity was radiation dermatitis (3.3% in “No RNI,” 5.7% in “RNI”). Conclusion: In pts who present with biopsy-proven axillary node involvement and convert their axillary nodes to ypN0 after NC, CWI+RNI after mastectomy, or WBI+RNI after BCS, did not significantly improve IBC-RFI, LRRFI, DRFI, DFS, or OS. These findings suggest that downstaging involved axillary nodes with NC can result in optimization of adjuvant radiotherapy without adversely affecting oncologic outcomes. Follow-up of pts for long-term outcomes continues. NCT01872975 *EPM and JW are co-first authors. Table 1 Citation Format: Eleftherios Mamounas, Hanna Bandos, Julia White, Thomas Julian, Atif Khan, Simona Shaitelman, Mylin Torres, Frank Vicini, Patricia Ganz, Susan McCloskey, Nilendu Gupta, X. Allen Li, Peter Lucas, Nadeem Abu-Rustum, Saumil Gandhi, Rahul Tendulkar, Robert Coleman, Keiichi Fujiwara, Samantha Seaward, William Irvin, Kristin Higgins, Robert Mutter, Jean-Francois Boileau, Andrew Muskovitz, Reshma Jagsi, Anna Weiss, Curran Walter Jr., Norman Wolmark. Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-07.
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Graves, Diana, Aleksandar Obradovic, Michael Korrer, Yu Wang, Sohini Roy, Yaomin Xu, Adam Luginbuhl et al. "903 Human cancer-associated fibroblast subsets can predict immune checkpoint response in head and neck cancer patients". Journal for ImmunoTherapy of Cancer 9, Suppl 2 (novembro de 2021): A947. http://dx.doi.org/10.1136/jitc-2021-sitc2021.903.
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BackgroundUse of anti-PD-1 immune checkpoint inhibitors (ICI) is currently the first line therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but critical work remains in identifying factors guiding resistance mechanisms.1 2 While recent studies have specifically implicated cancer-associated fibroblasts (CAFs) as potential mediators of immunotherapy response, the immunoregulatory role of CAFs in head and neck cancer has not been thoroughly explored.3–5MethodsTo determine if there are changes in cell populations associated with anti-PD-1 therapy in head and neck cancer patients, we performed high dimensional single-cell RNA sequencing (scRNA-SEQ) from a neoadjuvant trial of 50 advanced-stage head and neck squamous cell carcinoma (HNSCC) patients that were treated with the anti-PD-1 therapy, nivolumab, for the duration of one month. Tumor specimens were analyzed pre- and post-treatment with single-cell RNA sequencing performed on 4 patients as well as bulk RNA sequencing on 40 patients. Matched scRNA-SEQ data was analyzed using the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) and Virtual Inference of Protein-activity by Enriched Regulon (VIPER) bioinformatic analysis platform to determine TME cells that correlated with response and resistance to nivolumab.6 For CAF functional studies, surgical tumor specimens were processed and enriched for CAF subtypes, and these were co-cultured with T cells from peripheral blood and tumor infiltrating lymphocytes.ResultsWe identified 14 distinct cell types present in HNSCC patients. Of these 14 cell types, the fibroblast subtype showed significant changes in abundance following nivolumab treatment. We identified 5 distinct clusters of cancer-associated fibroblast subsets (HNCAF-0, 1, 2, 3, and 4) of which, two clusters, HNCAF-0 and HNCAF-3 were predictive of patient response to anti-PD-1 therapy. To determine the significance of these CAF subsets’ function, we isolated HNCAF-0/3 cells from primary HNSCC tumor specimens and co-cultured with primary human T cells. Analysis by flow cytometry showed that HNCAF-0/3 reduced TGFβ-dependent PD-1+TIM-3+ exhaustion of T cells and increased CD103+NKG2A+ resident memory phenotype and cytotoxicity to enhance overall function.ConclusionsTo our knowledge, we are the first to characterize CAF heterogeneity within the head and neck TME and show direct immunostimulatory activity of CAFs. Our findings demonstrate the functional importance of CAF subsets in modulating the immunoregulatory milieu of the human HNSCC, and we have identified clinically actionable CAF subtypes that can be used as a biomarker of response and resistance in future clinical trials.Trial RegistrationNCT03238365ReferencesFerris RL, Blumenschein Jr G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016;375:1856–1867.Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016;17:956–965.Dominguez CX, Muller S, Keerthivasan S, Koeppen H, Hung J, Gierke S, Breart B, Foreman O, Bainbridge TW, Castiglioni A, et al. Single-cell RNA sequencing reveals stromal evolution into LRRC15(+) myofibroblasts as a determinant of patient response to cancer immunotherapy. Cancer Discov 2020;10:232–253.Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A 2013;110:20212–20217.Kieffer Y, Hocine HR, Gentric G, Pelon F, Bernard C, Bourachot B, Lameiras S, Albergante L, Bonneau C, Guyard A, et al. Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer. Cancer Discov 2020;10:1330–1351.Obradovic A, Chowdhury N, Haake SM, Ager C, Wang V, Vlahos L, Guo XV, Aggen DH, Rathmell WK, Jonasch E, et al. Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages. Cell 2021;184:2988–3005.Ethics ApprovalPatients provided informed consent for this work. All experimental procedures were approved by the Institutional Review Board of Vanderbilt University Medical Center (IRB: 171883).
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Shmunk, Irina, Olga Korobitsyna, Marina Zakharova, Mikhail Lyubchenko, Alexander Korobkin, Alexandra Burmistrova e Marina Konopleva. "Association Of FLT3 Mutations With Unfavorable Factors In AML and APL Patients". Blood 122, n.º 21 (15 de novembro de 2013): 4967. http://dx.doi.org/10.1182/blood.v122.21.4967.4967.
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Abstract Background Mutations in the fms-like tyrosine kinase 3 (FLT3) gene have been considered to predict a poor prognosis in acute myeloid leukemia (AML). Internal tandem duplication (ITD) of the FLT3 is one of the most frequent mutations activating aberrant signal-transduction in AML. The impact of D835 point mutations in tyrosine kinase domain (TKD) on prognosis is less clear. Aims Characterization of AML and APL (acute promyelocytic leukemia) patients with FLT3 mutations. Methods FLT3 status in bone marrow samples of adult patients (pts) with AML (63 pts) (m\28; f\35; median 53 yrs, 19-73 yrs) and APL (14 pts) (m\3; f\11; median 43 yrs, 25-62 yrs) at diagnosis was examined. Genomic PCR amplification of ITD and TKD containing regions of the FLT3 gene was performed. The TKD amplicon product was restricted with the EcoRV enzyme. Results were detected by gel electrophoresis. Results FLT3\ITD was found in 8 AML pts (12.7%) and in 5 APL pts (35.7%), p=0.053 (Fisher Exact test). FLT3\TKD was found in 4 AML pts (6.4%) and in 1 APL pt (7.1%). In AML group there were 1 pt with t(6;9) in FLT3\ITD+ subgroup and 1 pt with inv16 in FLT3\TKD+. There were 1 pt with t(6;11), 1 with dupMLL, 3 with t(8;21), 7 with inv16 in AML pts without FLT3 mutations (FLT3-). There were no significant differences in sex, age, WT1 expression at diagnosis between AML pts with FLT3\ITD, FLT3\TKD and without FLT3 mutations. But the presence of FLT3 mutations was related to high peripheral white blood cell (WBC) count in AML pts at diagnosis. The median value (m) of WBC was 49.2 x109\L (range 2.75-191) in FLT3\ITD+; m= 81 x109\L (range 7.2-153) in FLT3\TKD+; m= 5.4 x109\L (range 0.2-230) in FLT3-. The differences are statistically significant between subgroups with FLT3\ITD+ and FLT3- (p<0.05, Mann–Whitney U test); FLT3\ITD+TKD and FLT3- (p<0.01, Mann–Whitney U test). In FLT3\ITD+TKD subgroup 66.7% of pts had WBC over 30 x109\L, whereas in subgroup without FLT3 mutations only 23.4% of pts had the same unfavorable factor, p=0.012 (Fisher Exact test). In APL group the t(15;17) translocation was detected in 11 pts. 3 pts were without PML\RARa, NPM1\RARa, PLZF\RARa fusions. One FLT3\TKD+ pt had bcr1 PML breakpoint. In FLT3\ITD+ subgroup 4 pts (80%) had bcr3 PML breakpoint, whereas in FLT3- subgroup only 1 pt (12.5%) had bcr3, p=0.032 (Fisher Exact test). In FLT3\ITD+ subgroup all pts had WBC >10 x109\L; moreover, 3 pts (60%) had two unfavorable factors in combination (WBC >10 x109\L plus platelet count < 40 x109\L) at diagnosis, and in FLT3- subgroup nobody had the same combination, p=0.035, (Fisher Exact test). Out of 5 pts with FLT3\ITD 2 ones had death in induction, 1 pt had late molecular remission, 1 had molecular persistence and 1 pt without RARa fusion had failure in WT1 reduction after induction (under 2 log). One FLT3\TKD+ pt had the early relapse. Summary The results confirm previous reports. FLT3\ITD mutations are seen more frequently in APL than in other subtypes of AML. FLT3 mutations in AML have association with such unfavorable prognostic factor as high WBC count at diagnosis. FLT3\ITD in APL associates with bcr3 and with combination of high WBC count plus low platelet count. The presence of FLT3 mutations is related to unfavorable events in APL pts. Disclosures: No relevant conflicts of interest to declare.
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Vitko, Alexandra S., Pamela A. Martin, Sheng Zhang, Adam F. Johnston, Robert L. Ohsfeldt, Shen Zheng e Astra M. Liepa. "Abstract P6-07-01: Costs of breast cancer recurrence after initial treatment for high risk early breast cancer using SEER-Medicare linked data". Cancer Research 83, n.º 5_Supplement (1 de março de 2023): P6–07–01—P6–07–01. http://dx.doi.org/10.1158/1538-7445.sabcs22-p6-07-01.
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Abstract Background: Despite the good prognosis with treatment for most patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) early breast cancer (EBC), ~ 20–30% of patients experience locoregional or distant disease recurrence. To assist in value assessments of novel therapies in the adjuvant setting, this study aimed to determine the costs of treated breast cancer recurrence following treated EBC. Methods: This retrospective study analyzed linked patient data from the US Surveillance Epidemiology and End Results (SEER) registry (2010-2014) and Medicare claims (2009 to 2019, which included data from Part A, B, and Prescription Drug Events [Part D]). Data were analyzed for patients aged ≥65 years with HR+, HER2-, node-positive EBC at high risk of recurrence (consistent with monarchE trial high risk criteria). Treated recurrences were defined based on treatment events/procedure codes, including surgery, radiation and systemic therapy, after a 90-day gap following the last treatment for initial EBC. Recurrences were classified based on Medicare claim diagnosis codes or SEER registry data. Extra cost was defined as cost attributable to treated recurrence. Cumulative extra costs were estimated by calculating cost differences between patients with treated vs non/untreated recurrence. Cumulative extra costs were analyzed over the first 6 years following first treated recurrence, a duration which ensured adequate sample size. Costs were inflated to 2021-US$. Results: We identified 3081 eligible patients (mean age at diagnosis 74.5±7.1 years, 97.4% female, 87.8% White). We identified 964 patients with treated recurrence (distant=432, locoregional=128, contralateral=9, unclassified=347) and 2117 patients with non/untreated recurrence. Six-year cumulative extra costs were higher for patients with distant recurrences ($168,656) than for patients with locoregional recurrences ($96,465) (Table 1). Conclusions: Cost of recurrence in patients with high risk EBC is considerable, particularly in patients with distant recurrences. Most patients who recurred in this population experienced distant recurrence. Delaying or preventing recurrence may reduce long term costs in these high risk EBC patients. Table 1. Mean cumulative extra costs attributable to treated recurrence. Citation Format: Alexandra S. Vitko, Pamela A. Martin, Sheng Zhang, Adam F. Johnston, Robert L. Ohsfeldt, Shen Zheng, Astra M. Liepa. Costs of breast cancer recurrence after initial treatment for high risk early breast cancer using SEER-Medicare linked data [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-07-01.
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Borges, Regilson Maciel, e José Carlos Rothen. "Abordagens de avaliação educacional: a constituição do campo teórico no cenário internacional (Educational evaluation approaches: constitution of the theoretical field in the international scenario)". Revista Eletrônica de Educação 13, n.º 2 (10 de maio de 2019): 749. http://dx.doi.org/10.14244/198271992481.
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This article presents a theoretical review of the main evaluation approaches that marked the trajectory of educational evaluation in the international scenario. This is a bibliographical research that, based on the assessment literature, aimed at studying the various dimensions and different meanings that have historically constituted the educational evaluation field. Seven evaluation approaches are described: goal-based evaluation, evaluation based on scientific logic, value-based evaluation, decision-making evaluation, consumer-oriented evaluation, participant-centered evaluation, and qualitative evaluation. Each one of them is characterized according to its protagonists, objectives, conceptual approaches, theoretical orientations deriving from methodological assumptions, and the scholars who continued their respective approaches. Such international literature had a strong influence on Brazilian evaluation researchers who, based on these references, sought to support a field of knowledge that is still in the process of constitution and strengthening in our country.ResumoEste artigo apresenta uma revisão teórica das principais abordagens de avaliação que marcaram a trajetória da avaliação educacional no cenário internacional. Trata-se de uma pesquisa bibliográfica que, referenciada na literatura da avaliação, busca estudar as variadas dimensões e os diferentes sentidos que constituíram historicamente o campo da avaliação educacional. São descritas sete abordagens de avaliação: a avaliação baseada em objetivos, a avaliação baseada na lógica científica, a avaliação baseada no valor agregado, a avaliação a serviço da decisão, a avaliação orientada para consumidores, a avaliação centrada nos participantes e a avaliação qualitativa. Cada uma dessas abordagens é caracterizada segundo seus protagonistas, objetivos, enfoques conceituais, orientações teóricas decorrentes de pressupostos metodológicos e os estudiosos que deram continuidade nas suas respectivas abordagens. Essa literatura internacional exerceu forte influência sobre os pesquisadores brasileiros da avaliação que, fundamentados nesses referenciais, buscaram sustentar uma área de conhecimento que ainda se encontra em processo de constituição e fortalecimento em nosso país.Keywords: Educational evaluation, Evaluation approaches, Theories on evaluation.Palavras-chave: Avaliação educacional, Abordagens de avaliação, Teorias em avaliação.ReferencesALKIN, Marvin C.; CHRISTIE, Christina A. An evaluation theory tree. In: ALKIN, Marvin C. (Ed.). Evaluation roots: tracing theorists’ views and influences. London: Sage, 2004. p. 381-392.CAMPBELL, Donald T.; STANLEY, Julian C. Experimental and quasi-experimental designs for research on teaching. In: GAGE, N. L. (Ed.). Handbook of research on training. Chicago: Rand McNally, 1963. p. 1-84.DE KETELE, Jean-Marie. L’évaluation conjuguée en paradigmes. Revue Française de Pédagogie, Lyon, n. 103, p. 59-80, 1993.DIAS SOBRINHO, José. Campo e caminhos da avaliação: a avaliação da educação superior no Brasil. In: FREITAS, Luiz Carlos (Org.). Avaliação: construindo o campo e a crítica. Florianópolis: Insular, 2002. p. 13-62.FERNANDES, Domingos. Acerca da articulação de perspectivas e da construção teórica em avaliação educacional. In: ESTEBAN, Maria Teresa; AFONSO, Almerindo Janela (Orgs.). Olhares e interfaces: reflexões críticas sobre a avaliação. São Paulo: Cortez, 2010. p. 15-44.GUBA, Egon G.; LINCOLN, Yvonna S. Avaliação de quarta geração. Trad. Beth Honorato. Campinas: Editora da Unicamp, 2011.HOUSE, Ernest; HOWE, Kenneth R. Deliberative democratic evaluation in practice. In: STUFFLEBEAM, Daniel L.; MADAUS, George F.; KELLAGHAN, Thomas (Eds.). Evaluation models: viewpoints on educational and human services evaluation. Boston: Kluwer Academic Publishers, 2000. p. 409-422.MACDONALD, Barry. Uma classificação política dos estudos avaliativos. In: GOLDBERG, Maria Amélia Azevedo; SOUSA, Clarilza Prado de (Orgs.). Avaliação de programas educacionais: vicissitudes, controvérsias, desafios. São Paulo: EPU, 1982. p. 16-17.OWSTON, Ron. Models and Methods for Evaluation. In: SPECTOR, J. Michael et al. (Eds.). Handbook of Research on Educational Communications and Technology. New York: Lawrence Erlbaum Associates, 2008. p. 605-618.PARLETT, Malcolm; HAMILTON, David. Avaliação Iluminativa: uma nova abordagem no estudo de programas inovadores. In: GOLDBERG, Maria Amélia Azevedo; SOUSA, Clarilza Prado de (Orgs.). Avaliação de programas educacionais: vicissitudes, controvérsias, desafios. São Paulo: EPU, 1982. p. 38-45.SANDERS, William L.; HORN, Sandra P. The Tennessee value-added assessment system (TVAAS): mixed model methodology in educational assessment. Journal of Personnel Evaluation in Education, New York, v. 8, n. 3, p. 299-311, 1994.SANDERS, William L.; RIVERS, June C. Cumulative and residual effects of teachers on future student academic achievement. Knoxville: University of Tennessee Value-Added Research and Assessment Center, 1996.STAKE, Robert E. Evaluation the arts in education: a responsive approach. Columbus: Merril, 1975a.STAKE, Robert E. Program evaluation, particularly responsive evaluation. Kalamazoo: Western Michigan University Evaluation Center, 1975b. (Occasional paper n. 5).STUFFLEBEAM, Daniel L. Evaluation models. New directions for evaluation, San Francisco, n. 89, p. 7-98, 2001.STUFFLEBEAM, Daniel L.; SHINKFIELD, Anthony L. Evaluación sistemática: guía teórica y práctica. Trad. Carlos Losilla. Barcelona: Paidós, 1987.WORTHEN, Blaine R.; SANDERS, James S.; FITZPATRICK, Jody L. Avaliação de programas: concepções e práticas. Trad. Dinah de Abreu Azevedo. São Paulo: Gente, 2004.