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Journal articles on the topic "Karel Axel"
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Lauper, K., D. Mongin, S. A. Bergstra, D. Choquette, C. Codreanu, D. De Cock, L. Dreyer, et al. "POS0093 HETEROGENEITY IN ADVERSE EVENT ASSESSMENT BETWEEN COUNTRIES PARTICIPATING IN AN INTERNATIONAL COLLABORATION OF REGISTRIES OF RHEUMATOID ARTHRITIS PATIENTS USING JANUS KINASE INHIBITORS (THE JAK-POT STUDY)." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 256–57. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2216.
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Background:Industry, regulators, and the rheumatology community have recognized the need for observational studies to monitor the safety of new antirheumatic agents. Registries provide a unique opportunity to understand the safety of newer therapies, but pharmacovigilance studies require large number of patients to evaluate rare drug-related adverse-events (AEs). Because JAK-inhibitors (JAKi) have only recently been approved for the treatment of rheumatoid arthritis, it makes sense to combine data from several registries in order to obtain a sufficiently large sample size to promote earlier detection of adverse events.Objectives:The purpose of this analysis was to evaluate how AEs are assessed in the various registries in preparation for a collaborative pharmacovigilance analysis, and present preliminary results.Methods:The “JAK-pot” collaboration includes 19 RA registries. The principal investigators of the participating registries were sent a structured questionnaire on AE assessment and 18 (94%) provided complete responses on the AE assessment procedures of their registries. We present simple descriptive statistics of the AE assessment procedures employed by the participating registries.Results:The 19 registries represent 7186 patients initiating a JAKi (Table 1), who are on average 57 years old, with a mean disease duration 11 years, seropositive (83%), female (82%) and with moderate disease activity at treatment initiation.Table 1.Country, registryN° of patients on JAKi includedAustria, BIOREG87Belgium, TARDIS2113Canada, RHUMADATA363Czech Republic, ATTRA197Denmark, DANBIO506Finland, ROB-FIN229Germany, RABBIT620Italy, GISEA244Israel, I-RECORD96Netherlands, METEOR4Norway, NOR-DMARD97Portugal, REUMA.PT44Romania, RRBR252Russia, ARBITER428Slovenia, biorx.si141Spain, BIOBADASER139Switzerland, SCQM738Turkey, TURKBIO404UK, BSRBR484After ineffectiveness, AEs was the second most common reason for JAKi discontinuation (25.5%), with large differences between registries (Figure 1).Of the participating registries, 2 registries do not collect AEs, while 16 (89%) assess incident AEs, by means of a pre-specified extraction form (3 registries), by free text (5 registries), by a combination of both (6 registries) and/or the use of linkage to external electronic records (3registries). AEs are coded using a predefined coding system by 11 registries (MeDRA (8), other (3)), but nearly all are recording the severity of the AE (15, 94%), AE related-death (15, 94%), or AE-related hospitalisation (15, 94%). AEs of special interest, such as serious infections (15, 94%), thromboembolic events (15, 94%), or shingles (9, 56%), are recorded by most registries. Incident AEs are linked by the treating physician to specific therapies in 11 registries (69%), while the other 5 registries extrapolate potential causal associations based on therapy start and stop dates. A pre-specified adjudication process for AEs is made only by 5 registries (31%).Conclusion:Substantial heterogeneity exists among registries regarding AE assessment within the JAK-pot collaboration. These differences must be taken into account when analysing the safety of JAKi across different countries in collaborative studies. For comparative analyses, stratified analyses by country are required to account for differential AE assessment and varying degrees of potential under-reporting.Disclosure of Interests:Kim Lauper: None declared, Denis Mongin: None declared, Sytske Anne Bergstra: None declared, Denis Choquette: None declared, Catalin Codreanu: None declared, Diederik De Cock: None declared, Lene Dreyer: None declared, Ori Elkayam: None declared, Kimme Hyrich: None declared, Florenzo Iannone: None declared, Nevsun Inanc: None declared, Eirik kristianslund: None declared, Tore K. Kvien: None declared, Burkhard Leeb: None declared, Galina Lukina: None declared, Dan Nordström: None declared, Karel Pavelka: None declared, Manuel Pombo-Suarez: None declared, Ziga Rotar: None declared, Maria Jose Santos: None declared, Anja Strangfeld: None declared, Delphine Courvoisier: None declared, Axel Finckh Speakers bureau: Eli-Lilly, Pfizer, Consultant of: Eli-Lilly, Pfizer, Grant/research support from: BMS, Pfizer.
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Jatav, Vinod, Dk Singh, Nk Singh, and A. Panchbhaiya. "Principal Component Analysis in Bitter Gourd (Momordica Charantia L.)." Bangladesh Journal of Botany 51, no. 1 (March 31, 2022): 1–7. http://dx.doi.org/10.3329/bjb.v51i1.58813.
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Investigation was carried out to assess genetic diversity through principal component analysis (PCA) and D2 analysis. Twenty four genotypes of bitter gourd were grown in RBD with three replications including two checks (Pant karela-1 and Pant karela-2). Principal component analysis showed that the first Eigen root had maximum of 26.83% variation of total variation, while the first six principal component axes together with explained 84.05% variation, which were used for cluster analysis, suggesting first six principal axes are adequate to explain the variation in reduced dimension. Clustering through D2 analysis revealed maximum inter-cluster distance of 498.80 between clusters IV and V followed by cluster III and V (322.81). Thus the genotypes grouped under cluster V, IV and III may yield maximum heterosis upon hybridization and also create wide variability including transgressive segregants in selfed generations. Bangladesh J. Bot. 51(1): 1-7, 2022 (March)
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Lauper, K., D. Mongin, S. A. Bergstra, D. Choquette, C. Codreanu, D. De Cock, L. Dreyer, et al. "OP0231 COMPARATIVE EFFECTIVENESS OF JAK-INHIBITORS, TNF-INHIBITORS, ABATACEPT AND IL-6 INHIBITORS IN AN INTERNATIONAL COLLABORATION OF REGISTERS OF RHEUMATOID ARTHRITIS PATIENTS (THE “JAK-POT” STUDY)." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 146–47. http://dx.doi.org/10.1136/annrheumdis-2020-eular.346.
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Background:In many countries, JAK-inhibitors (JAKi) have only recently been approved as treatment for patients with rheumatoid arthritis (RA).Objectives:To evaluate the effectiveness of JAKi compared to bDMARDs in RA patients in the real-world population in an international collaboration of registers (the “JAK-pot” collaboration).Methods:Patients initiating either JAKi, TNFi, IL-6i or abatacept (ABA) during a time period when JAKi were available in each country (19 registers, Table) were included. We compared the effectiveness of JAKi and bDMARDs in terms of retention using crude and adjusted survival analysis. Missing covariates were imputed using multiple imputation.Results:Among 25521 included patients, 6063 initiated a JAKi, 13879 a TNFi, 2348 ABA, and 3231 an IL-6i. Patients were on average 55 years old, with a mean disease duration 10 years, mostly seropositive (67%), female (77%) and with moderate disease activity at treatment initiation. The main reason of stopping treatment was ineffectiveness (49%), followed by adverse events (21%). Patients on JAKi were treated more often as monotherapy, had higher CRP and disease activity at baseline and had experienced more previous ts/bDMARDs. Crude median retention was 1.4 (95% CI 1.2-1.5) years for JAKi, 1.6 (1.6-1.7) for TNFi, 1.5 (1.3-1.7) for IL6i and 1.1 (1.0-1.3) for ABA. After adjustment, the hazard ratio (HR) for discontinuation tended to be lower for JAKi (HR 0.86 (0.65-1.13)) compared to TNFi, but comparable for ABA (1.02 (0.94-1.10)) and IL6i (0.99 (0.88-1.10)) (Figure 1). HRs differed notably between countries (Figure 2).Table 1.RegistersCountry, registerNJAKi, n (%)Austria, BIOREG*Belgium, TARDIS62882113 (33.6)Canada, RHUMADATA528114 (21.6)Czech Republic, ATTRA374253 (67.6)Denmark, DANBIO4721506 (10.7)Finland, ROB-FIN807234 (29.0)Germany, RABBIT*Italy, GISEA757250 (33.0)Israel, I-RECORD40094 (23.5)Netherlands, METEOR16424 (0.2)Norway, NOR-DMARD50799 (19.5)Portugal, REUMA.PT79744 (5.5)Romania, RRBR593328 (55.3)Russia, ARBITER526483 (91.8)Slovenia, BIORX.SI583146 (25.0)Spain, BIOBADASER781139 (17.8)Switzerland, SCQM2956796 (26.9)Turkey, TURKBIO2150397 (18.5)UK, BSRBR111163 (5.7)*Registers planning to participate in future studies but not included yetConclusion:The adjusted overall drug retention of JAKi tended to be higher than for TNFi, with large variation between countries. Other measures of effectiveness, such as the evaluation of CDAI remission and low disease activity are planned to shape a more comprehensive picture of JAKi effectiveness in the real world.Disclosure of Interests:Kim Lauper: None declared, Denis Mongin: None declared, Sytske Anne Bergstra: None declared, Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Catalin Codreanu Consultant of: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Diederik De Cock: None declared, Lene Dreyer: None declared, Ori Elkayam Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Novartis, Jansen, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Nevsun Inanc: None declared, Eirik kristianslund: None declared, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Burkhard Leeb Grant/research support from: chairman of BioReg, Consultant of: AbbVie, Pfizer, Roche, Lilly, Grünenthal, Gebro,, Paid instructor for: Lilly, Biogen, Speakers bureau: Biogen, Lilly, Pfizer, Grünenthal, Astropharma,, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Dan Nordström Consultant of: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Speakers bureau: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Manuel Pombo-Suarez Consultant of: Janssen, Lilly, MSD and Sanofi., Speakers bureau: Janssen, Lilly, MSD and Sanofi., Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Maria Jose Santos Speakers bureau: Novartis and Pfizer, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Delphine Courvoisier: None declared, Axel Finckh Grant/research support from: Pfizer: Unrestricted research grant, Eli-Lilly: Unrestricted research grant, Consultant of: Sanofi, AB2BIO, Abbvie, Pfizer, MSD, Speakers bureau: Sanofi, Pfizer, Roche, Thermo Fisher Scientific
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López, Marissa. "The Difference latinidad Makes." American Literary History 31, no. 1 (December 21, 2018): 104–21. http://dx.doi.org/10.1093/alh/ajy044.
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AbstractThis essay-review examines three recent works in the study of Chicanx literature, Robert Con Davis-Undiano’s Mestizos Come Home!: Making and Claiming Mexican American Identity (2017), Karen Roybal’s Archives of Dispossession: Recovering the Testimonios of Mexican American Herederas, 1848–1960 (2017), and María Josefina Saldaña-Portillo’s Indian Given: Racial Geographies across Mexico and the United States (2016). López is primarily concerned with how the books position themselves in relation to broader discussions around latinidad. She structures her investigation around three main axes: racial discourse, intersections of politics and form, and periodization in literary studies. The books, she argues, trace an aesthetic and political trajectory leading from concerns over representation and canon formation to wholesale interrogations of genre and political action. López reads this trajectory in the context of theoretical developments in Critical Ethnic studies that privilege difference over diversity.
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Nham, E., R. Aymon, D. Mongin, S. A. Bergstra, D. Choquette, C. Codreanu, O. Elkayam, et al. "OP0266 TREATMENT DISCONTINUATION DUE TO ADVERSE EVENTS AS AN OVERALL MEASURE OF TOLERANCE AND SAFETY OF JAK-INHIBITORS: AN INTERNATIONAL COLLABORATION OF REGISTRIES OF RHEUMATOID ARTHRITIS PATIENTS (THE “JAK-pot” STUDY)." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 177–78. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2342.
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BackgroundThe recently presented “ORAL Surveillance Study” has suggested increased risk of serious adverse events (AEs) with tofacitinib, a JAK-inhibitor (JAKi), compared to a comparator TNF-inhibitor (TNFi). Currently, there is limited real world evidence for the tolerability and safety of JAKi (1).ObjectivesTo assess the safety of JAKi compared to other biologic agents in rheumatoid arthritis (RA) patients in a real-world population, by evaluating treatment discontinuation for AEs.MethodsPooled patient database from 16 national RA registries from across Europe, Québec (Canada), Turkey, and Israel were used. Treatment discontinuation due to AEs by treatment groups, JAKi versus (vs) TNFi and JAKi vs bDMARDs with other modes of action (OMA), were compared as an overall measure of tolerability and safety of JAKi. Standard descriptive statistics were used for baseline characteristics. We plotted unadjusted cumulative incidence, then the cause-specific Cox model was used to account for competing risks, and to obtain association between covariates and the instantaneous hazard rate for AEs. Variables listed in Table 1 were used for adjustment in the fully-adjusted cause-specific Cox model.Table 1.Baseline characteristics of the study populationJAKi1(BARI, FILGO,TOFA,UPA)OMA2(ABA, ANAK, SARI, TOCI)TNFi3(ADA, CERT, ETAN, GOL, INFL)n = 9208n = 16737n = 64533Treatment duration* (yrs)0.7 [0.2, 1.7]1.1 [0.4, 2.8]1.5 [0.5, 3.9]Age57.556.853.2Female (%)81.380.773.2Disease duration (yrs)9.913.110.7Seropositivity (%)78.775.969.8Previous b/tsDMARD (%) 034.030.859.7 120.925.924.3 216.621.710.4 3 or more28.521.55.6Concomitant GC (%)44.650.741.3Concomitant CsDMARD (%) MTX22.622.028.8 MTX + other9.59.713.1 None50.552.543.5 Other17.415.914.7CRP13.2 (24.1)13.3 (25.6)12.3 (24.1)CDAI23.7 (13.8)22.9 (13.5)22.6 (14.0)DAS 284.7 (1.5)4.7 (1.6)4.6 (1.6)HAQ1.2 (0.7)1.2 (0.7)1.1 (0.7)BMI27.1 (5.9)26.8 (5.8)26.8 (5.8)Patients with at least one Comorbidity (%)51.753.949.6csDMARDs = classical synthetic DMARDs, MTX = methotrexate, GC = glucocorticoids, CRP = C-reactive protein, CDAI = Clinical Disease Activity Index, DAS 28 = Disease Activity Score 28, HAQ = Health Assessment Questionnaire, BMI = Body Mass Index, *Treatment duration (median [IQR]) = Last visit date – start date (if treatment is ongoing), treatment stop date – treatment start date (if treatment has stopped). 1BARI (baricitinib; 44.41 %), FILGO (filgotinib; 0.23%), TOFA (tofacitinib; 49.59%), UPA (upadacitinib; 5.78%); 2ABA (abatacept; 39.96%), ANAK (anakinra; 2.64%), SARI (sarilumab; 3.14%), TOCI (tocilizumab; 52.55%); 3ADA (adalimumab; 31.00%), CERT (certolizumab; 8.33%), ETAN (etanercept; 38.83%), GOLI (golimumab; 9.36%), INFL (infliximab; 12.56%)Results90,478 treatment courses were included in the analysis (Table 1). We observed similar crude incidence rate of treatment discontinuation due to AEs between JAKi and TNFi, but less in JAKi vs OMA (Figure 1). The fully adjusted hazard rate of treatment stop for AEs was also similar in JAKi vs TNFi (HR = 1.02 (95% CI 0.92 – 1.13)), and in JAKi vs OMA (HR= 1.08 (95% CI 0.97 – 1.20)). The rate of treatment stop for AEs was higher in women (HR = 1.29 (95% CI 1.21 – 1.37)) and with an increasing number of previous b/tsDMARDs (HR = 1.50; 1.48; 1.68 for 1, 2, and 3 or more previous b/ts DMARDs, respectively).Figure 1.Comparison of cumulative incidence of treatment discontinuation for adverse events in JAKi, TNFi, and OMA groupConclusionAfter adjusting for potential confounders, the rate of treatment discontinuation for AEs was comparable between JAKi and OMA or TNFi. Treatment discontinuation for AEs comprises a wide range of AEs; future analyses will be performed to investigate specific AEs, such as cancer, serious infections or major adverse cardiovascular events.References[1]Ann Rheum Dis 2022. doi: 10.1136/annrheumdis-2021-221915.Disclosure of InterestsEric Nham: None declared, Romain Aymon: None declared, Denis Mongin: None declared, Sytske Anne Bergstra: None declared, Denis Choquette Speakers bureau: DC reports speaker or consultant fees from Abbvie, Amgen, Eli Lilly, Fresenius-Kabi,Pfizer, Novartis, Sandoz, Tevapharm, Consultant of: Stated above, Catalin Codreanu Speakers bureau: CC reports speaker/consulting fees from AbbVie, Amgen, Astra Zeneca, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Richter, Consultant of: Stated above, Ori Elkayam Consultant of: OE has received consultant and honorary fees from Pfizer, Lilly, Abbvie, Novartis, Jansen, BI, Kimme Hyrich Speakers bureau: KLH has received speaker honoraria from Abbvie, Grant/research support from: KLH has received grant income from Pfizer and BMS, Florenzo Iannone Speakers bureau: FI has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, SOBI, Roche and UCB, Consultant of: Stated above, Nevsun Inanc Speakers bureau: NI has received consultant and speaker/honoraria from Abbvie, Lilly, MSD, Novartis, Pfizer, Roche, Amgen, Celltrion,UCB., Consultant of: Stated above, Lianne Kearsley-Fleet: None declared, Eirik kristianslund: None declared, Tore K. Kvien Speakers bureau: TKK has received fees for speaking and/or consulting from several companies among them Pfizer, AbbVie, Lilly and Galapagos/Gilead, Consultant of: Stated above, Burkhard Leeb Speakers bureau: BFL has received speaker honoraria from Sandoz, Abbvie, Eli-Lilly, Pfizer, Roche, Grünenthal, Biogen, Celgene, Galina Lukina Speakers bureau: GVL has received speaker fees from Abbvie, Lilly, Novartis, MSD, Roche, Pfizer, Dan Nordström Consultant of: DCN has acted as consultant for AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Karel Pavelka Speakers bureau: KP has received honoraria for lectures: MSD, Pfizer, Roche, Eli Lilly, Medac, UCB, SOBI, Biogen, Sandoz, Viatris, Manuel Pombo-Suarez Speakers bureau: MPS reports advisor and speaker honoraria from Janssen, Lilly, MSD, Novartis, Sanofi, Consultant of: Stated above, Ziga Rotar Speakers bureau: ZR has received fees for speaking/consulting from several companies among them Pfizer, AbbVie, and Eli Lilly, Consultant of: Stated above, Maria Jose Santos Speakers bureau: MJS has received speaker fees from Abbvie, AstraZeneca, Lilly, Novartis and Pfizer, Delphine Courvoisier: None declared, Kim Lauper Speakers bureau: KL reports speakers fees for Pfizer, Viatris and Celltrion, Consultant of: KL reports consulting fees for Pfizer, Axel Finckh Speakers bureau: AF reports honoraria and consultancies from Pfizer, BMS, MSD, Eli-Lilly, AbbVie, Galapagos, Mylan, UCB, Viatris, Consultant of: Stated above, Grant/research support from: AF reports grants from Pfizer INC, AbbVie, Galapagos, Eli Lilly
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Ortiz-Ortiz, Karen J., Axel Gierbolini-Bermúdez, Ana P. Ortiz, Karen Pabón-Cruz, Chi-Fang Wu, Jeslie Ramos-Cartagena, Reydi Morales-Martínez, and Ashish A. Deshmukh. "Abstract A052: Lifetime cost of care associated with squamous cell carcinoma of the anus in Puerto Rico." Cancer Epidemiology, Biomarkers & Prevention 32, no. 1_Supplement (January 1, 2023): A052. http://dx.doi.org/10.1158/1538-7755.disp22-a052.
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Abstract Background: Squamous cell carcinoma of the anus (SCCA), caused by human papillomavirus infection (HPV), is the most frequently diagnosed form of anal cancer (85%-90%). SCCA incidence has increased dramatically among the general population in Puerto Rico (nearly 5% annually) and the risk is disproportionately elevated among patients living with HIV. SCCA is preventable through HPV vaccination and screening. Therefore, the study of the cost of anal cancer care could have significant implications for understanding preventable economic burden in Puerto Rico. Objective: Determine the lifetime and phase-specific cost of SCCA cases aged ≥21 diagnosed during 2009-2016 in Puerto Rico. Method: This population-based study used the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database (PRCCR-HILD), which links PRCCR data with health insurance claim data from the principal health insurance companies and the government health plan. PRCCR-HILD has information for almost 90% of Puerto Rico's cancer cases from 2008. We matched SCCA cases and non-cancer control (1:1) by age and sex for each phase of care (initial, continuation, and terminal). SCCA-related costs were calculated by subtracting the costs between SCCA patients and the control group. We used the phase-specific monthly cost estimates combined with survival data, stratified by age and cancer stage (localized, regional, and distance), to calculate the lifetime and average annual cost (discount at 3%) for SCCA. The cost was adjusted to 2019 US dollars using the consumer price index. We used the number of SCCA incident cases for 2019, stratified by age group and multiplied by the lifetime SCCA cost estimates, to calculate the SCCA-related lifetime economic burden for Puerto Rico. Results: Of the 351 patients with SCCA included in this study, the mean age at diagnosis was 64 years, 66.4% were women, 57.6% were diagnosed at a localized stage, and 23.1% were enrolled in private insurance. The overall survival after cancer diagnosis was 18 years. Meanwhile, the average monthly costs per patient were higher in the initial phase ($4,755), followed by the terminal phase ($3,499). The main cost driver in all phases was the outpatient costs. However, inpatient costs increased substantially at the terminal phase of care. The average lifetime cost for patient with SCCA was $137,343 (95% CI: $130,873-$145,241) (2019 US dollars). The average SCCA per year cost was $9,193 (95% CI: $8,744-$9,895), while the SCCA-related lifetime economic burden for 2018 in Puerto Rico was nearly $8.7 million. Conclusion: To our knowledge, this is the first study to describe the cost of SCCA management in Puerto Rico. Although SCCA continues to be relatively rare among the general population, our study shows that the SCCA-related lifetime economic burden is substantial and could continue to rise due to the rising SCCA burden in Puerto Rico. These findings could support the evaluation of the impact of strategies to reduce the SCCA burden through HPV vaccination and anal cancer screening for high-risk populations. Citation Format: Karen J. Ortiz-Ortiz, Axel Gierbolini-Bermúdez, Ana P. Ortiz, Karen Pabón-Cruz, Chi-Fang Wu, Jeslie Ramos-Cartagena, Reydi Morales-Martínez, Ashish A. Deshmukh. Lifetime cost of care associated with squamous cell carcinoma of the anus in Puerto Rico [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A052.
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Liu, Cheng-Chien, Yueh-Cheng Chang, Stefani Huang, Frank Wu, An-Ming Wu, Soushi Kato, and Yasushi Yamaguchi. "First space-borne high-spatial-resolution optical imagery of the Antarctic from Formosat-2." Antarctic Science 20, no. 6 (May 16, 2008): 605–6. http://dx.doi.org/10.1017/s0954102008001338.
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Coordinating and collecting satellite data of changing polar environments is one of the prime activities of International Polar Year (IPY) 2007–08 (Rapley et al. 2004). Within this framework, the requirements to obtain spaceborne snapshots of the Polar Regions and key high latitude processes have been prepared by the international cryospheric community under the auspices of the approved IPY project titled the Global Inter-agency IPY Polar Snapshot Year (GIIPSY). Earlier efforts in manoeuvring Radarsat-1 in a special mode provided radar images with a spatial resolution of 30 m over the entirety of Antarctica during September–October 1997 (Jezek et al. 1998). Limited to their altitude (AL), swath (SW) and pointing capability (PC), however, the operation of optical satellites with high-spatial-resolution sensors is generally restricted to certain latitudes. For example, Landsat (AL:705 km/SW:185 km/PC:0°) mission has been able to provide high-spatial-resolution optical imagery only to ~81°N to ~81°S since the 1980s. The coverage is now extended to ~86° by ASTER (AL:705 km/SW:60 km/PC:24°) (Kargel et al. 2005), but there has been no availability of space-borne optical image of the polar regions with a resolution equivalent or higher than Landsat type sensors with latitudes higher than 86°, until the successful operation of Formosat-2 (AL:891 km/SW:24 km/PC: ± 45° across and along track). Equipped with two-axes high torque reaction wheels, Formosat-2 is able to point not only to ± 45° across track, but also to ± 45° along track (Liu et al. 2007). Figure 1 shows the accessible areas (longer lines: along track ± 0°, across track ± 45°; shorter lines: along track ± 0°, across track ± 30°) and the corresponding ground tracks (solid curves) of Formosat-2 in the Polar Regions. Note that the accessible areas would be even greater if the pointing direction is also set to ± 45° along track. The detailed comparison of Formosat-2 with other similar sensors, including the multi-spectral bands and imaging repeat period, can be found in table I in Liu et al. (2007). To support IPY 2007–08, the National Space Organization (NSPO) of Taiwan launched a Polar Imaging Campaign (PIC) in March 2006. Up to September 2007, a total of 1 131 624 km2 in the North Polar Region and a total of 57 408 km2 in the South Polar Region had been imaged by Formosat-2. All Formosat-2 images taken during the NSPO PIC are available from the authors.
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Barghi, Farinaz, Pankita H. Pandya, M. Reza Saadatzadeh, Khadijeh Bijangi-Vishehsaraei, Barbara J. Bailey, Erika A. Dobrota, Courtney Young, et al. "Abstract 2011: Targeting CDK4/6 inhibitor resistance in relapsed RB-proficient osteosarcoma patient-derived xenografts via PI3 Kinase/mTOR inhibition." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2011. http://dx.doi.org/10.1158/1538-7445.am2022-2011.
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Abstract In children, adolescents, and young adults (AYA), osteosarcoma (OS) is the most common type of bone cancer and ~35% patients relapse following frontline cytotoxic therapy. Thus, there is a critical need to identify therapies targeting specific molecular signatures in OS. Hyperactivation of cyclin-dependent kinases 4 and 6 (CDK4/6) has been identified by us and others as a top actionable marker in OS. CDK4/6 binds to cyclin D resulting in a complex that mediates RB phosphorylation leading to cell cycle progression. While CDK4/6 inhibitors (CDK4/6i) have shown promise clinically, one drawback is that CDK4/6i induces cell cycle arrest rather than cell death. Furthermore, prolonged CDK4/6 inhibitor therapy can confer therapeutic resistance in RB1-proficient (RB+) tumors where compensatory pathways such as PI3K/mTOR are activated. To mitigate such CDK4/6i resistance in OS, we hypothesized that dual inhibition of CDK4/6 and PI3K pathways will promote cytotoxicity in hyperactivated CDK4/6 OS models. RB+ OS cell lines and a TT2-77 xenoline were evaluated in vitro. Combination index and Bliss independence analyses indicated that inhibition of OS growth by exposure to CDK4/6i (Palbociclib or Abemaciclib) and PI3K/mTOR inhibitor (PI3K/mTORi-Voxtalisib or LY3023414) was additive-to-synergistic and lead to increased apoptosis at clinically relevant concentrations. Short-term pharmacodynamic study of vehicle- versus Palbociclib-treated TT2-77 patient-derived xenograft (PDX) was analyzed by global/phospho-proteomics and kinome profiling. RB1 and MKI67 phosphopeptides as well as the total protein levels of CDK1 were reduced by Palbociclib, thus, confirming modulation of the cell cycle. Kinome profiling analysis of PDX from Palbociclib-treated mice indicated increased activity of AXL, a receptor tyrosine kinase linked to PI3K pathway activation. Increased activity of the autophagy marker PIK3C3 was also evident. OS PDX models TT2-77 and HT96 (RB+, CDKN2Anull, CCND3 amplified) were treated with Palbociclib (50 mg/kg), Voxtalisib (50 mg/kg) or Palbociclib + Voxtalisib. In TT2-77 PDXs treated for four weeks, tumor growth was significantly reduced in single-agent and combo groups compared to vehicle (p<0.05, Two-way ANOVA; Holm-Sidak). We observed a trend that the combo was more efficacious than single agent, but statistical differences were not evident. Increasing the dosing timeline to six weeks may be beneficial. In HT96 PDXs, tumor growth was significantly decreased in single-agent and combo groups compared to vehicle. Notably, Palbociclib + Voxtalisib was more efficacious than single-agent (p<0.05, Two-way ANOVA; Holm-Sidak). These data highlight the need to optimize CDK4/6i+PI3K/mTORi dosing schedules and provide evidence that Palbociclib + Voxtalisib therapy is safe, efficacious, and can decrease CDK4/6i resistance in aggressive PDX models of OS. Citation Format: Farinaz Barghi, Pankita H Pandya, M. Reza Saadatzadeh, Khadijeh Bijangi-Vishehsaraei, Barbara J. Bailey, Erika A. Dobrota, Courtney Young, Melissa A. Trowbridge, Kathryn L. Coy, Henry Mang, Reagan K. Wohlford, Anthony L. Sinn, Emily C. Sims, Matt J. Repass, Nuri Damayanti, Niknam Riyahi, Harlan E. Shannon, Steve P Angus, Michael J Ferguson, Jamie L. Renbarger, Karen E. Pollok. Targeting CDK4/6 inhibitor resistance in relapsed RB-proficient osteosarcoma patient-derived xenografts via PI3 Kinase/mTOR inhibition [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 2011.
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Schroeder, Mark A., Jonathan D. Ricks, Jaebok Choi, Julie Ritchey, Matthew Holt, Brian K. Dieckgraefe, and John F. DiPersio. "Pegylated Recombinant Murine GM-CSF Is a Potent Mobilizer of Murine Bone Marrow Progenitors, Synergizes with BIO5192 and Plerixafor (AMD3100), and Skews Mobilized Cells to a Tolerogenic Phenotype." Blood 114, no. 22 (November 20, 2009): 2432. http://dx.doi.org/10.1182/blood.v114.22.2432.2432.
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Abstract Abstract 2432 Poster Board II-409 Granulocyte-macrophage colony stimulating factor (GM-CSF) is a naturally occurring acidic glycoprotein growth factor that regulates proliferation and differentiation of hematopoietic stem and progenitor cells. Inflammation results in the release of GM-CSF from numerous cell types including T-cells, macrophages, and neutrophils. Murine GM-CSF (mGM-CSF), unlike human GM-CSF, has a very short half-life in vivo. Pegylation of mGM-CSF (peg-mGM-CSF) has been shown to prolong its half-life. There are numerous reports of GM-CSF use in humans to mobilize stem cells. It was observed by our group that patients who were transplanted with stem cell products mobilized by GM-CSF had a lower incidence of acute GVHD (Devine et al. BBMT 2005; 36:531). The reason for this is unclear. A recent report suggested that regulatory T-cells (T-regs) express the low affinity alpha subunit of the mGM-CSF receptor and can be expanded ex vivo in the presence of GM-CSF and independent of IL-2 (Kared et al. Blood 2008;112:2575). We hypothesized that peg-mGM-CSF may expand T-regs in vivo and act synergistically with the CXCR4 antagonist Plerixafor (AMD3100) and a small molecule inhibitor of VLA-4, BIO5192, to generate optimal peripheral blood stem cell products enriched in hematopoietic progenitors and T-regs. Peg-mGM-CSF was manufactured in a bioreactor as previously described (Sainathan et al. Prot Express and Purification 2005;44:94). C57/Bl6 mice were injected with peg-mGM-CSF 5ug IP, daily x 4 days then bled and analyzed for CFU progenitor assays (CFU-C) and FACS analysis. The same mice were then injected with AMD3100 (5mg/kg SC) with or without BIO5192 (1mg/kg IV) and serially bled at 30 minutes, 1 hour, 3 hours, and 6 hours. CFU-C were performed and blood and spleen were analyzed for T-cell and dendritic cell subsets by FACS. We observed that peg-mGM-CSF was a potent mobilizer of hematopoietic progenitors and resulted in leukocytosis (mean difference 17.98 K/uL +/- 2.15, 95%CI 13.4 - 22.53, p<0001, n=6) and splenomegally. Peg-mGM-CSF increased CFU-C by 26.5 fold compared to PBS treated mice (n=6, 95% CI = 10.25-42.73). Peg-mGM-CSF had synergistic effects on progenitor mobilization when combined with AMD3100 (89.8 fold, 95% CI 61.6-118, n=6) or BIO5192 (94 fold, 95% CI 46.5-141.6, n=6) compared to PBS treated mice. The combination of peg-mGM-CSF, AMD3100 and BIO5192 resulted in 119.7 fold (95% CI 63.7-175.6, n=6) increase in progenitor mobilization over PBS treated mice and peaked at 30 minutes. In addition, peg-mGM-CSF increased circulating CD4+ FoxP3+ T-regs from a mean of 10.66% +/- 2.65 to 23.86% +/- 4.7 at 5 days (n=15, p=0.001 by paired t-test). Splenic T-regs were also increased from 16.09% +/- 2.7 to 31.56% +/- 4.34 (n=9, p=0.001 by paired t-test). This effect was sustained out to 4 days after the last dose of peg-mGM-CSF. Furthermore, there was no significant change in thymic T-regs, and this effect was not significantly affected by the addition of AMD3100 or BIO5192. The function of these peg-mGM-CSF T-regs, as measured in a MLR was found to be equivalent to T- regs from PBS treated control mice (n=3, p=0.27, by paired t-test). Interestingly, analysis of the spleens from animals on day 5 after peg-mGM-CSF demonstrated an increase in absolute CD11c+ cells, as expected, and a 4 fold increase in the absolute number of plasmacytoid dendritic cells as determined by CD11c+ SiglecH+ staining. Additional studies are underway to assess the functional impact of murine peripheral blood stem cells mobilized with peg-mGM-CSF in combination with small molecule inhibitors of the CXCR4 and VLA-4 axes on engraftment and graft versus host disease in a murine acute GVHD parent to F1 model. Disclosures: DiPersio: Genzyme Corporation: Honoraria.
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Minguzzi, Isabella Rodrigues, Joverlany Pessoa de Albuquerque, and Julicristie Machado de Oliveira. "culinária e o cuidado." Temas em Educação e Saúde, November 30, 2022, e022008. http://dx.doi.org/10.26673/tes.v18i00.16189.
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O objetivo deste trabalho foi avaliar um processo pedagógico, alicerçado em “A Festa de Babette”, para estudantes de Nutrição, da Universidade Estadual de Campinas. Primeiramente, analisou-se o conto “A Festa de Babette”, de Karen Blixen, e o filme homônimo, de Gabriel Axel, com base em conceitos e obras de referência. Posteriormente, foi elaborado, aplicado e analisado um processo pedagógico na disciplina Educação Alimentar e Nutricional. Na coleta de dados, foram realizados dois grupos focais com sete estudantes voluntárias e discutidos os principais temas identificados: o choque de cultura entre a alimentação francesa e as práticas restritivas religiosas, a dedicação de Babette ao jantar e a relevância da comensalidade. Em conclusão, a culinária e o cuidado, atrelados ao cozinhar e ao comer, fomentaram rotas para a compreensão de conceitos trabalhados na disciplina, a sensibilização sobre essas dimensões e as possibilidades de atuação profissional que considerem outros matizes da vida social.
Dissertations / Theses on the topic "Karel Axel"
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Fischer, Axel Verfasser], Karl [Akademischer Betreuer] [Leo, and Henning [Akademischer Betreuer] Sirringhaus. "A Vertical C60 Transistor with a Permeable Base Electrode / Axel Fischer. Betreuer: Karl Leo. Gutachter: Karl Leo ; Henning Sirringhaus." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://d-nb.info/1078205035/34.
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Fischer, Axel [Verfasser], Karl [Akademischer Betreuer] Leo, and Henning [Akademischer Betreuer] Sirringhaus. "A Vertical C60 Transistor with a Permeable Base Electrode / Axel Fischer. Betreuer: Karl Leo. Gutachter: Karl Leo ; Henning Sirringhaus." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-180780.
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Neumann, Kai Verfasser], Karl [Akademischer Betreuer] [Nienhaus, and Axel [Akademischer Betreuer] Preuße. "Ultra-Wideband-Technologie für den Einsatz im Schwermaschinenbau / Kai Neumann ; Karl Nienhaus, Axel Preuße." Aachen : Universitätsbibliothek der RWTH Aachen, 2017. http://d-nb.info/1162845651/34.
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Hartmann, Tobias [Verfasser], Karl [Akademischer Betreuer] Nienhaus, and Axel [Akademischer Betreuer] Preuße. "Ein Beitrag zur untertägigen Navigation von mobilen Maschinen / Tobias Hartmann ; Karl Nienhaus, Axel Preuße." Aachen : Universitätsbibliothek der RWTH Aachen, 2021. http://d-nb.info/124076572X/34.
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Neumann, Kai W. [Verfasser], Karl [Akademischer Betreuer] Nienhaus, and Axel [Akademischer Betreuer] Preuße. "Ultra-Wideband-Technologie für den Einsatz im Schwermaschinenbau / Kai Neumann ; Karl Nienhaus, Axel Preuße." Aachen : Universitätsbibliothek der RWTH Aachen, 2017. http://nbn-resolving.de/urn:nbn:de:101:1-2018071607584375050609.
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Hunger, Andrea [Verfasser], Karl-Heinrich [Akademischer Betreuer] Baumann, Joachim [Akademischer Betreuer] Ulrich, and Axel [Akademischer Betreuer] König. "Zum Stofftransportprozess über eine Flüssig-Flüssig-Phasengrenze / Andrea Hunger. Betreuer: Karl-Heinrich Baumann ; Joachim Ulrich ; Axel König." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2015. http://d-nb.info/1069532517/34.
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Mellert, Karl Heinz [Verfasser], Axel [Akademischer Betreuer] Göttlein, and Hermann [Akademischer Betreuer] Rodenkirchen. "Erfassung von Indikatoren zur Beurteilung des Nitrataustragsrisikos in Bayerns Wäldern sowie Lösungsansätze zur räumlichen Bewertung auf verschiedenen Skalenebenen / Karl Heinz Mellert. Gutachter: Axel Göttlein ; Hermann Rodenkirchen. Betreuer: Axel Göttlein." München : Universitätsbibliothek der TU München, 2014. http://d-nb.info/1048428796/34.
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Kunze, Karl-Philipp Gerhart Friedrich [Verfasser], Axel [Akademischer Betreuer] Haase, Julia [Gutachter] Herzen, and Axel [Gutachter] Haase. "Quantitative Cardiac PET/MRI: Studies on Validation and Synergies in Clinical Applications of Perfusion Imaging and Tissue Characterization / Karl-Philipp Gerhart Friedrich Kunze ; Gutachter: Julia Herzen, Axel Haase ; Betreuer: Axel Haase." München : Universitätsbibliothek der TU München, 2018. http://d-nb.info/1169304206/34.
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Maier, Stefan Karl [Verfasser], Bernhard [Akademischer Betreuer] Küster, and Axel [Akademischer Betreuer] Walch. "Towards Comprehensive Identification of Proteins from MALDI imaging / Stefan Karl Maier. Gutachter: Bernhard Küster ; Axel Walch. Betreuer: Bernhard Küster." München : Universitätsbibliothek der TU München, 2014. http://d-nb.info/1054752931/34.
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Kröner, Axel W. H. [Verfasser], Boris [Akademischer Betreuer] Vexler, Michael [Akademischer Betreuer] Ulbrich, and Karl [Akademischer Betreuer] Kunisch. "Numerical Methods for Control of Second Order Hyperbolic Equations / Axel Kröner. Gutachter: Michael Ulbrich ; Karl Kunisch. Betreuer: Boris Vexler." München : Universitätsbibliothek der TU München, 2011. http://d-nb.info/1019587903/34.
Full textBooks on the topic "Karel Axel"
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Düring, Diana, Hans-Ullrich Krause, Friedhelm Peters, Regina Rätz, Nicole Rosenbauer, and Matthias Vollhase, eds. Kritisches Glossar - Hilfen zur Erziehung. WALHALLA Fachverlag, 2018. http://dx.doi.org/10.5771/9783802949708.
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Kritisches Glossar Hilfen zur Erziehung Im neu erschienenen Kritischen Glossar Hilfen zur Erziehung werden 54 Begriffe, die im öffentlichen und fachlichen Diskurs der Hilfen zur Erziehung eine zentrale Rolle spielen, kritisch analysiert und diskutiert. Die Leser_innen erhalten auf diese Weise einen umfassenden Einblick in aktuelle Entwicklungen, theoretische Zugänge und methodische Herangehensweisen in verschiedenen Feldern der Hilfen zur Erziehung. Der Band widmet sich zentralen Schlüsselbegriffen, die die Diskussion in der Kinder- und Jugendhilfe und insbesondere in den Erziehungshilfen prägen. Diese beeinflussen die Art und Weise, in der Fachkräfte ihr Denken und Handeln einordnen, reflektieren und deuten. Die einzelnen Stichworte in diesem Band sind auf unterschiedlichen Ebenen angesiedelt und betreffen neben Begriffen, die auf gesellschaftlich übergreifende Entwicklungen eingehen, konzeptionelle Entwürfe im engeren Feld der Hilfen zur Erziehung wie auch Techniken und Verfahren oder methodische Zugänge. Insgesamt ergibt sich eine kritische Bestandsaufnahme der bestehenden Diskurse in den Hilfen zur Erziehung und gleichzeitig ein progressiver Ausblick auf neue Ansätze und Entwicklungen, die neue Handlungsmöglichkeiten erkennbar werden lassen. Aus dem Inhalt: ADHS (Aufmerksamkeitsdefizit-/Hyperaktivitätsstörungen) - Charlotte Köttgen Arbeitsbedingungen - Gunther Fleischmann Armut - Karl-August Chassé Aufarbeitung der Heimerziehungsgeschichte - Carola Kuhlmann Aufwachsen in privater und öffentlicher Verantwortung - Timm Kunstreich Intensivpädagogische Auslandsmaßnahmen - Holger Wendelin Bildung und Demokratie - Michael Winkler Care Leaver - Dirk Nüsken Case Management - Heiko Kleve Diagnostik - Kira Gedick Dienstleistungsorientierung - Gaby Flösser / Matthias Vollhase Eigenverantwortung - Peter Schruth Elternarbeit - Michael Winkler Empowerment - Josef Bakic Familialisierung - Luise Hartwig Flexibilisierung - Nicole Rosenbauer Geschlecht - Nicole Rosenbauer Governance - Diana Düring Grenzen - Annegret Wigger Geschlossene Unterbringung - Michael Lindenberg / Tilmann Lutz Professionelle Haltung - Hans-Ullrich Krause / Dirk Schäfer Inklusion - Benedikt Hopmann Intensivpädagogik - Werner Freigang Kinderrechte - Peter Hansbauer / Martina Kriener Kinderschutz - Reinhart Wolff Kooperation - Andreas Matzner Managerialisierung - Andreas Polutta Markt und Wettbewerb - Friedhelm Peters Mediatisierung - Nadia Kutscher Migration - Chantal Munsch Modularisierung - Friedhelm Peters Nachhaltigkeit - Norbert Struck Ökonomisierung - Martin Schröder / Samuel Keller / Nicole Rosenbauer Ombudschaft und Beschwerdeverfahren - Ulrike Urban-Stahl Partizipation - Hans-Ullrich Krause / Martin Schröder Prävention - Katja Wohlgemuth Qualität - Kay Biesel Rechte und Pflichten - Regina Rätz Responsibilisierung - Simon Mohr / Eva Schone / Holger Ziegler Risiko, Risikofaktoren und Risikoverhalten - Axel Groenemeyer Schutzkonzepte - Reinhold Schone ‚Schwierige Jugendliche’ - Samuel Keller / Regina Rätz Sozialraumorientierung - Christian Reutlinger / Fabian Kessl Spezialisierung - Werner Freigang Steuerung - Friedhelm Peters / Diana Düring (Teilhabe-)Gerechtigkeit - Stefanie Albus Time-out - Hannelore Häbel Training(s), Elterntraining(s) - Matthias Euteneuer Vernetzung - Jörg Fischer Verwahrlosung - Regina Rätz / Jana Kuhnle Wirkungsorientierung - Friedhelm Peters Wohlfahrtsstaat - Hans-Jürgen Dahme / Norbert Wohlfahrt Zwang (und Zwangskontexte) - Tillmann Lutz / Michael Lindenberg Dieser Titel ist eine Veröffentlichung der Internationalen Gesellschaft für erzieherische Hilfen (IGfH).
Reports on the topic "Karel Axel"
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Laroche, Hervé, and Véronique Steyer. L’apport des théories du sensemaking à la compréhension des risques et des crises. Fondation pour une culture de sécurité industrielle, October 2012. http://dx.doi.org/10.57071/208snv.
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Les théories du sensemaking, ou fabrication de sens, analysent la manière dont ceux qui participent à une action, et qui sont confrontés à une interruption, répondent à deux questions: Que se passe-t-il? Que faut-il faire maintenant? Les personnes plongées dans l’action ont souvent des difficultés à rester au contact du monde, et cette faillite de la fabrication du sens peut avoir des conséquences dramatiques. En s’appuyant sur de nombreuses études de cas, les auteurs présentent les fondements de la théorie du sensemaking — due au célèbre psychosociologue américain Karl Weick — et ses principaux apports. Le document s’intéresse aux différents facteurs et éléments influençant la capacité des participants à une action à rester en «contact» avec ce qu’il se passe dans «le monde». Notamment, il examine les difficultés à détecter des signes de dégradations de la sécurité, à signaler des anomalies, à adapter son action et à improviser de façon appropriée face à des situations imprévues. Il souligne notamment l’importance de la qualité des interactions entre membres d’un collectif de travail, à adapter les processus de décision pour que expertise et expérience priment sur hiérarchie (et permettre que les décisions à fort impact soient prises par les personnes disposant de la meilleure connaissance de la situation), ainsi que la manière dont le cadre et la culture organisationnels peuvent faciliter ou entraver la fabrication d’un sens menant à une action adaptée. Les facteurs pouvant influer sur le sensemaking sont analysés selon quatre axes: les facteurs individuels, les caractéristiques de la situation de travail, les facteurs liés au collectif de travail, et l’impact des processus d’organisation. En fin de document, cinq principes d’organisation visant à contrer les différents phénomènes négatifs liés à la perte de sens face à une situation risquée sont exposés.