Letteratura scientifica selezionata sul tema "Appelists"

El presente artículo se centra en una experiencia de propaganda fascista en el extranjero, en concreto sobre la obra de Mario Appellius, Cile e Patagonia. Empezaremos con trazar algunas de las características generales de la propaganda de Mussolini a nivel nacional e internacional, poniendo mayor énfasis sobre el concepto de cultura fascista. En segundo lugar, abordaremos el tema de la cultura fascista en el extranjero, haciendo hincapié sobre los mecanismos utilizados por el Duce para aumentar su consenso. Después, nos centraremos en la figura de Mario Appellius y analizaremos algunos capítulos de su obra dedicada a Chile, focalizándonos en la actitud del autor hacía el pequeño país andino; por último, trazaremos nuestras conclusiones subrayando los aspectos más interesantes de esta experiencia literaria de propaganda fascista en Chile.

During the Fascist ventennio, prominent Italian writers and journalists, such as Mario Appelius, Raffaele Calzini, Arnaldo Cipolla, Arnaldo Fraccaroli, Roberto Suster and Cesco Tommaselli, reported from China, Japan and Korea for Il Popolo d'Italia, Corriere della Sera and La Stampa. Their travel narratives were crucial for the creation and diffusion in Italy of the dominant representation of China and Korea as remote, decadent and exotic societies; and of Japan as a progressive society resonant with Fascist Italy. The narrativisation of these countries in Italian travelogues from the Fascist ventennio was part of a widespread discursive practice by Italian intellectuals willing to subscribe to, and actively disseminate, the guiding principles of Fascism. When emphasising China's and Korea's irreconcilable difference from, and Japan's affinity with, Fascist Italy, these intellectuals extolled the Italian race and culture, justified Italy's position in geopolitical dynamics, and propagandised the exceptionality of the Fascist ideology.

Résumé Zarca (Bernard).- Proximités socioprofessionnelles entre germains et entre alliés : une comparaison dans la moyenne durée Les phénomènes d'héritage de la position socioprofessionnelle du père par chacun des frères aîné et benjamin, ou du statut d'activé de la mère par chacune des sœurs aînée et benjamine (voire les transferts au gendre ou la bru de cette position ou de ce statut), ainsi que la tendance à ce que les frères (resp. les sœurs, les beaux-frères ou les belles-sœurs) héritent ensemble (tendance que nous appelions : complémentarité) avaient été mis en évidence pour l'année 1976 par l'étude des fratries que l'enquête Réseaux familiaux, effectuée par l'Ined cette année-là, permettait d'échantillonner. Ces phénomènes sont-ils stables dans le temps ? L'enquête Proches et parents effectuée par l'Ined en 1990 permettant de composer un échantillon de fratries équivalent au précédent, une comparaison dans la moyenne durée est possible. Les phénomènes d'héritage ou de transfert étudiés persistent dans le temps, dans la quasi-totalité de l'espace social, mais avec une force variable, telle que la tendance soit à une plus grande égalité entre les germains. Par contre, les phénomènes de complémentarité tendent à s'estomper, sauf pour les petits indépendants, c'est-à-dire dans les milieux les plus traditionnels de la société française. Cette constatation est cohérente avec ce que l'on sait des transformations de la famille au cours de la période considérée, notamment avec la plus grande individualisation de ses membres.

BACKGROUND: After many decades of stagnation, several promising novel therapies have recently been approved for the management of patients (pts) with Acute Myeloid Leukemia (AML). Many of these target pts in specific clinical and molecular subsets such as midostaurin/gilteritinib for FLT3-mutated AML, liposomal daunorubicin-cytarabine for secondary AML, and fractionated gemtuzumab ozogamicin (GO) for good risk AML. To address the dismal outlook for elderly AML patients, we now have venetoclax or glasdegib combinations. Single agent FLT3 inhibitors (resulting in ~4 m improvement in overall survival (OS)) and IDH inhibitors (response rate 40%, doubled OS in responders) have shown to be superior to traditional approaches in the relapsed setting. Although these agents are exciting, a majority of pts with AML present with intermediate and high-risk disease and only a small subset will have actionable mutations. In order to determine the impact of these newer therapies on outcome for our pts, we investigated AML outcomes for pts diagnosed and treated since 2017 and compared these with survival for similar pts treated in the prior two years (y). METHODS: We performed a retrospective chart review to identify newly diagnosed pts treated with chemotherapy over a 2y period (2015-17) prior to the first FDA approval of Midostaurin in April, 2017 (old AML era or group 1) and the 2y since approval (2017-19; new AML era or group 2). We reviewed charts of 138 AML pts meeting these criteria at our institution: 79 in group 1 and 59 in group 2. Demographics, disease-specific variables, as well as outcomes of interest (overall survival (OS), overall response rate (CR/CRi)) were collected on an IRB-approved protocol. Responses were defined according to the 2003 International Working Group (IWG) criteria. Demographics, baseline characteristics, and treatment responses were analyzed using descriptive statistics. Overall survival was estimated utilizing Kaplan-Meier (KM) survival analysis. RESULTS: Clinical characteristics were comparable in both groups. Median age was 65y with slight differences in gender distribution (Table 1). ELN risk categories (Döhner, Blood. 2017) across the groups were similarly distributed; a majority of pts had intermediate and adverse risk characteristics. As expected, more pts received newer therapies in group 2. 6 pts (7.6%) in group 1 received new drugs (as part of clinical trials), while 31 (52%) received newer therapies in group 2. Newer therapies were mostly GO (28%), midostaurin (11%) and venetoclax (11%) with lesser percentages of the more specific targeted therapies. Median follow-up was 10m for group 1 and 8m for group 2. Median OS was 13m for group 1 and 20m for group 2, but the difference was not statistically significant (p=0.29) [Figure 1]. OS was significantly better in the subgroup of older AML pts (age ≥ 60y); median OS was 7m vs. 11m in groups 1 and 2 respectively (p=0.01).Rates of CR from induction therapy were comparable in both groups (68% in group 1 versus 65% in group 2). A larger number of pts (especially older pts) in group 2 went on to allogeneic bone marrow transplant (allo-HCT). This was perhaps due to increased recognition of performance status over age in selection of pts for allo-HCT and increased utilization of reduced intensity and non-myeloablative conditioning regimens. CONCLUSIONS: Our results indicate a positive impact on survival for pts diagnosed in the era of novel therapies in a real world setting, specifically for pts presenting at older ages. A larger cohort analysis to further evaluate these findings is currently underway. The expansion of the therapeutic armamentarium as well as expanded transplant options is encouraging and offers new hope for pts diagnosed with AML Disclosures Griffiths: Onconova Therapeutics: Other: PI on a clinical trial; Partner Therapeutics: Consultancy; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Appelis Pharmaceuticals: Other: PI on a clinical trial; Onconova Therapeutics: Other: PI on a clinical trial; Appelis Pharmaceuticals: Other: PI on a clinical trial; Boston Scientific: Consultancy; Genentech, Inc.: Research Funding; Genentech, Inc.: Research Funding; New Link Genetics: Consultancy; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Celgene, Inc: Consultancy, Research Funding; Celgene, Inc: Consultancy, Research Funding; Abbvie, Inc.: Consultancy, PI on a clinical trial; Abbvie, Inc.: Consultancy; New Link Genetics: Consultancy; Persimmune: Consultancy; Persimmune: Consultancy; Boston Scientific: Consultancy; Novartis Inc.: Consultancy; Partner Therapeutics: Consultancy; Novartis Inc.: Consultancy. Wang:Kite: Other: Advisory role; Jazz: Other: Advisory role; Amgen: Other: Advisory role; Agios: Other: Advisory role; Abbvie: Other: Advisory role; Daiichi: Other: Advisory role; Stemline: Other: Advisory role, Speakers Bureau; Pfizer: Other: Advisory role, Speakers Bureau; celyad: Other: Advisory role; Astellas: Other: Advisory role, Speakers Bureau. Thota:Incyte, Inc.: Speakers Bureau.

Background: Patients with myelodysplastic syndromes (MDS) present across a clinical spectrum from mild disease to profound bone marrow failure and transformation to acute myeloid leukemia (AML). Those with lower risk disease are generally managed with watchful waiting and best supportive care (growth factors, blood and platelet transfusions and iron chelation; BSC), while those with higher risk disease are treated with repeated cycles of low dose "hypomethylating" chemotherapy (such as azacitidine or decitabine; HMA). A majority of patients with MDS, even those with lower risk disease, are likely to die of complications related to their diagnosis, mostly infections and bleeding but also leukemic transformation. As part of our standard approach to infection prevention, current clinical guidelines suggest annual vaccination against influenza. Patients with these disorders and their family members are advised to receive inactivated protein based vaccines rather than live vaccination approaches to limit infection risk. Most will receive high dose trivalent vaccination due to age. Despite these recommendations, limited data exist on the ability of patients with MDS across the spectrum of risk groups to respond to standard seasonal influenza vaccination. In light of the growing literature suggesting that patients with MDS have an altered immune environment, we hypothesized that they would show inferior response to standard vaccination. We sought to determine the response to influenza vaccination in patients with MDS receiving standard therapeutic management. Methods: A non-randomized study is currently ongoing at the Roswell Park Comprehensive Cancer Center for patients with MDS. Age-relevant family members are enrolled as a comparator population for vaccine response. Cohorts were stratified into 3 groups: healthy volunteers (Cohort 1), MDS patients receiving BSC (Cohort 2) and MDS patients actively receiving HMA (Cohort 3; Table 1). All participants are administered the yearly preparation of Sanofi Pasteur's Fluzone High-Dose Vaccine (containing trivalent inactivated strains: Influenza virus A (H1N1 and H3N2) and Influenza virus B). Baseline blood samples were collected prior to vaccination (day 0), and between days 25-90 and 115-185 post-vaccination. Serological responses to vaccination were determined by viral-neutralizing activity analyzed via microneutralization assay. Neutralizing antibody titers for the first year of the study were measured against seasonal influenza vaccine strains based upon the 2017-2018 vaccine product. Samples from the 2018-19 flu season are being analyzed. Results: To date 56 individuals have been recruited to the study over 2 years. Neutralizing antibody titers following vaccination are available for 20 individuals vaccinated in the 2017-18 flu season. Humoral immune responses to vaccination against different strains of Influenza virus A (H1N1 and H3N2) and Influenza virus B were observed across all cohorts (Figure 1). Response was deemed adequate if the titer for any vaccine component increased by >4 fold comparing the baseline to the day 25-90 time point. Cohort 1: 4/4 responded (100%); cohort 2: 4/4 responded (100%); cohort 3: 11/12 responded (92%). To better understand the effect of standard treatment for MDS on influenza vaccine response we are currently profiling immune cells pre and post vaccination using multi-parameter flow cytometry. Additional analyses are planned based on the number of HMA cycles received (<6, or ≥6) and cycle timing relative to vaccination. Conclusion: Patients with MDS respond to vaccination with Fluzone High Dose. Responses in patients with MDS were not statistically different from those seen in an age-relevant population of healthy family members. Additional individuals are being enrolled in order to assess whether standard HMA therapy impacts the response to influenza vaccination. These data suggest that MDS patients receiving BSC respond adequately to viral vaccination. Our preliminary data also show that patients receiving HMA therapy respond adequately to influenza vaccination. These data support the value of influenza vaccination in all patients with MDS and highlight the potential for anti-MDS immunotherapeutic vaccination strategies. Disclosures Vachhani: Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Astellas: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Przespolewski:Jazz Pharmaceuticals: Other: PI on clinical trial. Thota:Incyte, Inc.: Speakers Bureau. Wang:Amgen: Other: Advisory role; Agios: Other: Advisory role; Pfizer: Other: Advisory role, Speakers Bureau; Stemline: Other: Advisory role, Speakers Bureau; Daiichi: Other: Advisory role; Astellas: Other: Advisory role, Speakers Bureau; celyad: Other: Advisory role; Jazz: Other: Advisory role; Abbvie: Other: Advisory role; Kite: Other: Advisory role. Griffiths:Boston Scientific: Consultancy; Genentech, Inc.: Research Funding; Abbvie, Inc.: Consultancy; Boston Scientific: Consultancy; Novartis Inc.: Consultancy; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; New Link Genetics: Consultancy; Genentech, Inc.: Research Funding; Onconova Therapeutics: Other: PI on a clinical trial; Appelis Pharmaceuticals: Other: PI on a clinical trial; Abbvie, Inc.: Consultancy, PI on a clinical trial; Onconova Therapeutics: Other: PI on a clinical trial; Persimmune: Consultancy; Partner Therapeutics: Consultancy; Persimmune: Consultancy; Novartis Inc.: Consultancy; Celgene, Inc: Consultancy, Research Funding; Celgene, Inc: Consultancy, Research Funding; Appelis Pharmaceuticals: Other: PI on a clinical trial; Partner Therapeutics: Consultancy; New Link Genetics: Consultancy.

Background: Immunotherapeutic approaches for myelodysplastic syndrome (MDS) show promise, but progress is limited by our incomplete understanding of the immunologic milieu. In a recent Phase I trial, we found that MDS patients with higher numbers of CD141Hi conventional dendritic cells (cDCs) were more likely to respond to NY-ESO-1 vaccination. In solid tumor models, the CD141Hi cDC is critical for initiating anti-tumor immune responses but its impact in myeloid malignancies is unknown. In studies of primary human specimens and mouse models, we tested the hypothesis that MDS patients exhibit decreased quantity and quality of CD141Hi cDCs due to impaired myeloid differentiation. Methods: Bone marrow (BM) cells were collected from MDS patients (pre-treatment) and age matched healthy donors (HD; defined as absence of hematologic malignancy). We quantified DC populations, stem, progenitor cells and interferon regulatory factor-8 (IRF-8) expression using flow cytometry and RT-qPCR. Histone modifications were assessed by chromatin immunoprecipitation. To assess DC differentiation of progenitors, human CD34+ and mouse c-kit+ cells were expanded and differentiated in vitro. Results: We found fewer CD141Hi cDCs (p<0.0001), CD1c+ cDCs (p<0.005) and plasmacytoid DCs (CD123+ pDCs; p<0.005) overall in BM samples from MDS patients (n=71) compared to HD (n=17). We stratified MDS patients based on the relative number of DCs and found that only those patients with highest number of CD141Hi cDCs had superior survival (p < 0.05). No differences in survival were seen in patients stratified by the CD1c+ cDCs (p = 0.96) and CD123+ pDCs (p = 0.32) populations. We hypothesized that decreased numbers of CD141Hi cDCs and adverse survival in MDS patients resulted from impaired differentiation of DC progenitors. We showed that MDS patients (n=19) have fewer monocyte-DC progenitors (MDP) and common DC progenitors (CDP) compared to HD (n=11; p<0.01). We then hypothesized that MDS progenitors express lower levels of IRF8, a master regulator of CD141Hi cDC differentiation. IRF8 expression was significantly lower in CDPs from MDS patients compared to HD (p<0.05). Furthermore, MDS patients with lower levels of IRF8 (n=8) in their MDPs showed a trend towards production of fewer CDPs and significantly fewer CD141Hi cDCs compared to those with higher levels of IRF8 (n=10; p<0.005). These results suggest that approaches to increase IRF8 expression could enhance CD141Hi cDC differentiation. We hypothesized that inhibition of lysine-specific histone demethylase 1A (LSD1), which increases IRF8 expression in myeloid leukemia cells, would induce CD141Hi cDC differentiation. Pharmacologic inhibition of LSD1 increased IRF8 expression (both mRNA and protein) in KG-1 cells, a model of human CD34+ cells, and in HD and MDS CD34+ progenitors (p<0.05). LSD1 inhibition in KG-1 cells resulted in increased H3K27 acetylation (3861-fold change) and H3K4 dimethylation (922.4-fold change) compared to PBS (p<0.05) at a region -70 kb to the IRF8 transcriptional start site, a putative regulatory element that demonstrated the highest level of LSD1 binding. These data indicate that LSD1 inhibition alters histone modifications at the IRF8 locus, resulting in increased expression of IRF8. Pharmacologic inhibition of LSD1 in HD CD34+ cells increased the number of mature CD141Hi cDCs in 92% of specimens (n = 12; 3.4 fold-change) compared to PBS. Similarly, LSD1 inhibition in MDS CD34+ cells increased the number of CD141Hi cDCs (n = 12) in 75% of patient specimens (16.8 fold-change) compared to PBS. IRF8 function is conserved between mice and humans. To test whether the effect of LSD1 inhibition on cDC differentiation was dependent on IRF8, we compared the effect of LSD1 inhibition on BM c-kit+ cells from Irf8 knock-out mice (Irf8-KO) and littermate controls (WT). LSD1 inhibition in WT c-kit+ cells resulted in increased numbers of CD141Hi cDCs in vitro (p<0.05). By contrast, LSD1 inhibition of Irf8-KO c-kit+ cells did not result in differentiation of CD141Hi cDCs. These data suggest that LSD1 inhibition drives CD141Hi cDCs differentiation through IRF8. Conclusion: These data reveal a previously unrecognized determinant of the immune microenvironment in MDS. The opportunity for epigenetic regulation of CD141Hi cDC differentiation in MDS offers an opportunity for intervention and a potential adjunct to immunotherapy for patients. Disclosures Sait: Celgene: Consultancy. Griffiths:Boston Scientific: Consultancy; Boston Scientific: Consultancy; Genentech, Inc.: Research Funding; Persimmune: Consultancy; Persimmune: Consultancy; Abbvie, Inc.: Consultancy; Genentech, Inc.: Research Funding; Novartis Inc.: Consultancy; Celgene, Inc: Consultancy, Research Funding; New Link Genetics: Consultancy; New Link Genetics: Consultancy; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Novartis Inc.: Consultancy; Partner Therapeutics: Consultancy; Partner Therapeutics: Consultancy; Appelis Pharmaceuticals: Other: PI on a clinical trial; Onconova Therapeutics: Other: PI on a clinical trial; Appelis Pharmaceuticals: Other: PI on a clinical trial; Onconova Therapeutics: Other: PI on a clinical trial; Celgene, Inc: Consultancy, Research Funding; Abbvie, Inc.: Consultancy, PI on a clinical trial.

BACKGROUND: Patient reported outcomes (PROs) are increasingly being used as key outcome measures in management of patients with chronic hematologic malignancies. Use of PROs in routine clinical care in hematology has been associated with improved patient-physician communication, enhanced shared decision making, better symptom management, and greater satisfaction with care as well as improved quality of life (QoL) (Breccia M, et al. 2015; Hirji I, et al. 2013). With a therapeutic landscape shifting towards long-term use of oral therapies in chronic myeloid malignancies (myelofibrosis (MF) and chronic myeloid leukemia (CML)), the potential for serious medication adverse events rises. Due to these concerns, pharmacists are increasingly functioning, as integral members of the healthcare team, responsible for the management of oral anticancer agents. The effectiveness and value of pharmacists in the management of oral medications for hematologic malignancies from a patient perspective is limited. Here we designed a prospective patient survey study to assess PROs of a pharmacist-led medication therapy management (MTM) program to monitor adverse events and improve adherence in adults with hematologic malignancies. METHODS: Adult patients (pts) (≥ 18 years old) prescribed an oral targeted therapy for a hematologic malignancy and who were seen by a clinical pharmacist for a MTM session were eligible. A modified validated questionnaire consisting of 22 multiple choice questions and 3 comment questions and incorporating both CTSQ & FACT-Leu (Abetz L, et al. 2005; Cella D, et al. 2012) was completed by each participant. Individual questions and responses were pooled into the following categories: education, monitoring and support. Demographics, disease-specific variables and questionnaire responses were also collected. RESULTS: 66 pts seen in the adult leukemia clinic at Roswell Park Comprehensive Cancer Center in 2019 participated in the study. Baseline characteristics for this cohort are outlined in Table 1. Median age of the cohort was 64 years old (range 31-89 yrs) and 52% were male. Hematologic malignancies included CML (64%), MF (11%), acute myeloid leukemia (AML) (8%), Ph+ acute lymphoblastic leukemia (Ph+ALL) (6%), myeloproliferative neoplasm (MPN) (6%), polycythemia vera (PV) (3%), mastocytosis (1%) and hypereosiniophilic syndrome (1%). The most common oral agents were imatinib (21%), ruxolitinib (18%), and dasatinib (17%). This cohort also included patients off BCR-ABL inhibitors as part of treatment free remission monitoring (8%) and those on novel therapies such as enasidenib (3%). Majority of pts had been on their oral agent for at least 1-5 years (55%). For each pooled category i.e., education, monitoring and support, involvement of a pharmacist was associated with positive or very positive benefits: education (98%), monitoring (96%), and support (91%) (Figure 1). There was no difference in questionnaire response by number of years on oral chemotherapy (&lt; 1 year vs. &gt; 1 year into therapy). In addition, there was no difference in questionnaire response based on diagnosis (CML vs. non-CML) or gender. For question "I feel that I have missed fewer doses of my medication due to interacting with my pharmacist", non-CML patients tend to be more positive (p = 0.0695) (Figure 2). For question "The pharmacist has provided me with tools to help me remember to take my oncology medication", patients with &gt; 1 year TKI therapy are more positive (p = 0.052) (Figure 3). CONCLUSIONS: Our study demonstrates that the involvement of subspecialty pharmacists as part of a formal MTM program, for adult pts on oral therapy for hematologic malignancies was overwhelmingly associated with positive pt reported outcomes in the areas of education, monitoring and support. The greatest positive role of the pharmacist was on education of pts at start of therapy. Pts also perceived benefits in increased long term drug compliance and improved toxicity management. These data support further investigation of pharmacist-led MTM programs as part of the care continuum for pts with hematological malignancies at high risk of non-compliance and medication-related adverse events. For instance, adolescent/young adult (AYA), ALL or APL pts on maintenance, or geriatric individuals with multiple comorbidities may particularly benefit from improved medication compliance and overall care. Disclosures Przespolewski: Jazz Pharmaceuticals: Other: PI on clinical trial. Griffiths:Celgene, Inc: Consultancy, Research Funding; Novartis Inc.: Consultancy; Genentech, Inc.: Research Funding; Persimmune: Consultancy; New Link Genetics: Consultancy; New Link Genetics: Consultancy; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Celgene, Inc: Consultancy, Research Funding; Genentech, Inc.: Research Funding; Abbvie, Inc.: Consultancy; Abbvie, Inc.: Consultancy, PI on a clinical trial; Onconova Therapeutics: Other: PI on a clinical trial; Persimmune: Consultancy; Boston Scientific: Consultancy; Boston Scientific: Consultancy; Partner Therapeutics: Consultancy; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Appelis Pharmaceuticals: Other: PI on a clinical trial; Partner Therapeutics: Consultancy; Novartis Inc.: Consultancy; Onconova Therapeutics: Other: PI on a clinical trial; Appelis Pharmaceuticals: Other: PI on a clinical trial. Thota:Incyte, Inc.: Speakers Bureau. Wang:Pfizer: Other: Advisory role, Speakers Bureau; Stemline: Other: Advisory role, Speakers Bureau; Daiichi: Other: Advisory role; celyad: Other: Advisory role; Astellas: Other: Advisory role, Speakers Bureau; Jazz: Other: Advisory role; Kite: Other: Advisory role; Abbvie: Other: Advisory role; Agios: Other: Advisory role; Amgen: Other: Advisory role.