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Xiaoming Yuan, G. Orglmeister y I. Barbi. "ARCPI resonant snubber for the neutral-point-clamped inverter". IEEE Transactions on Industry Applications 36, n.º 2 (2000): 586–95. http://dx.doi.org/10.1109/28.833777.
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Viney, Rowena, Antonia Rich, Sarah Needleman, Ann Griffin y Katherine Woolf. "The validity of the Annual Review of Competence Progression: a qualitative interview study of the perceptions of junior doctors and their trainers". Journal of the Royal Society of Medicine 110, n.º 3 (24 de enero de 2017): 110–17. http://dx.doi.org/10.1177/0141076817690713.
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Objective To investigate trainee doctors’ and trainers’ perceptions of the validity of the Annual Review of Competence Progression (ARCP) using Messick’s conceptualisation of construct validity. Design Qualitative semi-structured focus groups and interviews with trainees and trainers. Setting Postgraduate medical training in London, Kent Surrey and Sussex, Yorkshire and Humber, and Wales in November/December 2015. Part of a larger study about the fairness of postgraduate medical training. Participants Ninety-six trainees and 41 trainers, comprising UK and international medical graduates from Foundation, General Practice, Medicine, Obstetrics and Gynaecology, Psychiatry, Radiology, and Surgery, at all levels of training. Main outcome measures Trainee and trainer perceptions of the validity of the ARCP as an assessment tool. Results Participants recognised the need for assessment, but were generally dissatisfied with ARCPs, especially UK graduate trainees. Participants criticised the perceived tick-box nature of ARCPs as measuring clerical rather than clinical ability, and which they found detrimental to learning. Trainees described being able to populate their e-portfolios with just positive feedback; they also experienced difficulty getting assessments signed off by supervisors. ARCPs were perceived as poor at identifying struggling trainees and/or as discouraging excellence by focussing on minimal competency. Positive experiences of ARCPs arose when trainees could discuss their progress with interested supervisors. Conclusions Trainee and trainer criticisms of ARCPs can be conceptualised as evidence that ARCPs lack validity as an assessment tool. Ongoing reforms to workplace-based assessments could address negative perceptions of the ‘tick-box’ elements, encourage constructive input from seniors and allow trainees to demonstrate excellence as well as minimal competency, while keeping patients safe.
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Scrimgeour, DSG, PA Brennan, G. Griffiths, AJ Lee, FCT Smith y J. Cleland. "Does the Intercollegiate Membership of the Royal College of Surgeons (MRCS) examination predict ‘on-the-job’ performance during UK higher specialty surgical training?" Annals of The Royal College of Surgeons of England 100, n.º 8 (noviembre de 2018): 669–75. http://dx.doi.org/10.1308/rcsann.2018.0153.
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Introduction The Intercollegiate Membership of the Royal College of Surgeons (MRCS) is a mandatory examination to enter higher surgical specialty training in the UK. It is designed to help to ensure that successful candidates are competent to practice as higher surgical trainees. The annual review of competence progression (ARCP) assesses trainees’ competence to progress to the next level of training and can be interpreted as a measure of ‘on-the-job’ performance. We investigated the relationship between MRCS performance and ARCP outcomes. Materials and methods All UK medical graduates who passed MRCS (Parts A and B) from 2007 to 2016 were included. MRCS scores, attempts and sociodemographics for each candidate were crosslinked with ARCP outcomes (satisfactory, unsatisfactory and insufficient evidence). Multinomial logistic regression was used to identify potential independent predictors of ARCP outcomes. Results A total of 2570 trainees underwent 11,064 ARCPs; 1589 (61.8%) had only satisfactory outcomes recorded throughout training; 510 (19.9%) had at least one unsatisfactory outcome; and 471 (18.3%) supplied insufficient evidence. After adjusting for age, gender, first language and Part A performance, ethnicity (non-white vs white, OR 1.36, 95% CI 1.08 to 1.71), Part B passing score (OR 0.98, 95% CI 0.98 to 1.00) and number of attempts at Part B (two or more attempts vs one attempt, OR 1.50, 95% CI 1.16 to 1.94) were found to be independent predictors of an unsatisfactory ARCP outcome. Conclusions This is the first study to identify predictors of ARCP outcomes during higher surgical specialty training in the UK and provides further evidence of the predictive validity of the MRCS examination.
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Yang, Xin, Jiang Xu, Shuchang Zhang y Jun Tu. "Debonding Detection in Aluminum/Rigid Polyurethane Foam Composite Plates Using A0 Mode LAMB Wave EMATs". Materials 16, n.º 7 (31 de marzo de 2023): 2797. http://dx.doi.org/10.3390/ma16072797.
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Aluminum/rigid polyurethane foam composite plates (ARCPs) are widely used for thermal insulation. The interface debonding generated during manufacturing degrades the thermal insulation performance of an ARCP. In this study, the debonding of an ARCP, a composite plate with a porous and damped layer of rigid polyurethane foam (RPUF), was detected using A0 mode Lamb wave electromagnetic acoustic transducers (EMATs). The low energy transmission coefficient at the interface caused by the large acoustic impedance difference between aluminum and RPUF made the detection difficult. Based on these structural characteristics, an A0 mode Lamb wave with large out-of-plane displacement was used to detect the debonding. EMATs are preferred for generating A0 mode Lamb waves due to their advantages of being noncontact, not requiring a coupling agent, and providing convenient detection. A finite element simulation model considering the damping of the RPUF layer, the damping of the PU film at the interface, and the bonding stiffness of the interface was established. The simulation results indicated that the Lamb wave energy in the aluminum plate transmits into the RPUF layer in small amounts. However, the transmitted energy rapidly attenuated and was not reflected into the aluminum plate, as the RPUF layer was thick and highly damped. Therefore, energy attenuation was evident and could be used to characterize the debonding. An approximately linear relationship between the amplitude of the received signals and the debonding length was obtained. Experiments were performed on an ARCP using EMATs, and the experimental results were in good agreement with the simulation results.
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Cui, Yi Hua, Stephen Lee, Bahman Noruziaan, Moe M. S. Cheung y Jie Tao. "Fabrication and Properties of Absolutely Recycled Plastic Wood Composites". Key Engineering Materials 334-335 (marzo de 2007): 5–8. http://dx.doi.org/10.4028/www.scientific.net/kem.334-335.5.
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In this study, the absolutely recycled plastic wood (ARCPW) was fabricated with post-consumer high density polyethylene (HDPE) and wood flour from the saw mills. The alkaline, silane and maleic anhydride modified polypropylene (MAPP) were used as modifiers to treat wood fiber and improve the interfacial adhesion of ARCPW. Effects of wood fiber length, weight fraction and surface treatment on the mechanical properties of ARCPW were investigated. The flexural fracture surfaces of ARCPW were examined and the fracture mechanism of ARCPW was also analyzed in this paper. The results indicated that ARCPW with wood fiber simultaneously treated by alkaline, silane and MAPP possesses the best mechanical properties. The higher the content of wood fiber, the better the flexural strength of ARPCW. The interfacial adhesion of prepared ARCPW is ideal and a good compatibility between wood fiber and matrix was obtained.
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Kenzari, Bechir. "Archi-textures". Architectural Theory Review 9, n.º 2 (noviembre de 2004): 16–33. http://dx.doi.org/10.1080/13264820409478515.
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Diaconu, Mădălina. "Archi-texturen". Maske und Kothurn 62, n.º 2-3 (diciembre de 2016): 13–24. http://dx.doi.org/10.7767/muk-2016-2-303.
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Lazerges, Alexandre. "Archi intéressant". Les Grands Dossiers des Sciences Humaines N° 73, n.º 12 (12 de diciembre de 2023): 45. http://dx.doi.org/10.3917/gdsh.073.0045.
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Chumakina, M. "Attributive in Archi". Rhema, n.º 4, 2018 (2018): 166–89. http://dx.doi.org/10.31862/2500-2953-2018-4-166-189.
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In this paper I discuss attributive in Archi (Nakh-Daghestanian). Archi lacks an independent category of adjective and uses attributives instead. Attributives in Archi belong to a transpositional mixed category that can be formed from any of the four main parts of speech: nouns, verbs, ad verbs and postpositions. Based on a detailed analysis of their syntactic and morphological properties, I demonstrated that Archi attributives retain some of the morphosyntactic characteristics of their base category, whilst simultaneously having morphological and syntactic character-istics shared across transposed forms. At the same time, it can be shown that Archi attributives have a unique distribution and agreement pattern that is clearly distinct from any other lexical class. All these make Archi attributive simultaneously possess both morphological and syntactic characteristics of two syntactic categories.
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Yang, Tao, Yang Liang, Chaoyu Wang, Jun Liu, Yan Wu, Haiyan Min, Yunhong Huang et al. "A Prognostic Nomogram Survival Model for Newly Diagnosed Patients with AIDS-Related Diffuse Large B-Cell Lymphoma: A Multicenter Cohort Study in China". Blood 142, Supplement 1 (28 de noviembre de 2023): 4480. http://dx.doi.org/10.1182/blood-2023-179132.
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BACKGROUND The prognosis of patients with AIDS-related diffuse large B-cell lymphoma(AR-DLBCL) becomes very poor when the lymphoma relapses or is refractory to first line immunochemotherapy. We aimed to develop a novel ARDPI nomogram prognostic model for risk stratification so as to guide individualized treatment to achieve sustained remission and improve the overall prognosis for newly-diagnosed AR-DLBCL patients. METHODS We interrogated data from 306 patients with newly-diagnosed AR-DLBCL. We filtered variables using LASSO regression and Cox regression to identify prognostic co-variates and develop a survival model, we termed AR-DLBCL Prognostic Index (ARDPI). We evaluated model discrimination, calibration and clinical benefit by Area Under the Receiver-Operator Characteristic (AUROC), calibration plots and decision curve analysis (DCA). Next, we compared the ARDPI model discrimination, calibration and clinical benefit with the IPI and NCCN-IPI models using the same methods. Lastly, we stratified patients into three survival risk cohorts based on ARDPI model by X-tile selecting cutoff point. RESULTS 7 co-variates were independently correlated with survival and were used to develop the ARDPI model including age, lymphocyte monocyte ratio (LMR), CD5 expression on lymphoma cells, blood EBV-DNA copy number, CD4/CD8 ratio, central nervous system (CNS) involvement and anti-HIV therapy (ART). AUROCs of ARDPI model for 1-, 3-, and 5-year were 0.80 (95% Confidence Interval [CI], 0.72, 0.88), 0.78 (0.69, 0.87) and 0.77 (0.63, 0.91). Predicted and calibrated values were concordant. The DCA curve had higher net benefit using the ARDPI model. Prediction accuracy of the ARDPI model was better compared with the IPI and NCCN-IPI models. For example, 3-year survival AUROC in the ARDPI model was 0.78 (0.69, 0.87) compared with the IPI (0.53 [0.43, 0.63] P< 0.001) and the NCCN-IPI (0.52 [0.42, 0.62] P< 0.001). Using the ARDPI model, we identified 3 survival risk cohorts with 3-year survivals of 0.80 , 0.38 and 0.09 ( P<0.001). CONCLUSION The ARDPI has good survival prediction accuracy in newly-diagnosed persons with AIDS-related DLBCL and using it has clinical benefit.Accuracy is better than the IPI and NCCN-IPI models. Validation of our conclusions is needed.
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Jouenne, Noël. "Dys en archi". Cahiers pédagogiques N° 586, n.º 5 (1 de mayo de 2023): 64. http://dx.doi.org/10.3917/cape.586.0064.
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Kiss, Ágnes. "A szamizdat arcai". REGIO 32, n.º 2 (2024): 220–31. http://dx.doi.org/10.17355/rkkpt.v32i2.220.
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Jones, Lisa, Lynn Owens, Andrew Thompson, Ian Gilmore y Paul Richardson. "Informing the development of diagnostic criteria for differential diagnosis of alcohol-related cognitive impairment (ARCI) among heavy drinkers: A systematic scoping review". PLOS ONE 18, n.º 2 (8 de febrero de 2023): e0280749. http://dx.doi.org/10.1371/journal.pone.0280749.
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Background Early detection and diagnosis of alcohol-related cognitive impairment (ARCI) among heavy drinkers is crucial to facilitating appropriate referral and treatment. However, there is lack of consensus in defining diagnostic criteria for ARCI. Uncertainty in attributing a diagnosis of suspected ARCI commonly arises in clinical practice and opportunities to intervene are missed. A systematic scoping review approach was taken to (i) summarise evidence relating to screening or diagnostic criteria used in clinical studies to detect ARCI; and (ii) to determine the extent of the research available about cognitive assessment tools used in ‘point-of-care’ screening or assessment of patients with suspected non-Korsakoff Syndrome forms of ARCI. Methods We searched Medline, PsycINFO, Cinahl and the Web of Science, screened reference lists and carried out forward and backwards citation searching to identify clinical studies about screening, diagnosis or assessment of patients with suspected ARCI. Results In total, only 7 studies met our primary objective and reported on modifications to existing definitions or diagnostic criteria for ARCI. These studies revealed a lack of coordinated research and progress towards the development and standardisation of diagnostic criteria for ARCI. Cognitive screening tools are commonly used in practice to support a diagnosis of ARCI, and as a secondary objective we included an additional 12 studies, which covered a range of settings and patient populations relevant to screening, diagnosis or assessment in acute, secondary or community ‘point-of-care’ settings. Across two studies with a defined ARCI patient sample and a further four studies with an alcohol use disorder patient sample, the accuracy, validity and/or reliability of seven different cognitive assessment tools were examined. The remaining seven studies reported descriptive findings, demonstrating the lack of evidence available to draw conclusions about which tools are most appropriate for screening patients with suspected ARCI. Conclusion This review confirms the scarcity of evidence available on the screening, diagnosis or assessment of patients with suspected ARCI. The lack of evidence is an important barrier to the development of clear guidelines for diagnosing ARCI, which would ultimately improve the real-world management and treatment of patients with ARCI.
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Kolinsky, Michael Paul, Dylan E. O'Sullivan, Devon J. Boyne, Darren R. Brenner, Simran Shokar y Winson Y. Cheung. "A real-world observational study characterizing patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) treated with or without androgen receptor pathway inhibitors (ARPIs)." Journal of Clinical Oncology 42, n.º 4_suppl (1 de febrero de 2024): 59. http://dx.doi.org/10.1200/jco.2024.42.4_suppl.59.
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59 Background: mCSPC treatment is rapidly evolving with androgen deprivation therapy (ADT) plus ARPIs viewed as the standard of care for most pts. Data are needed to understand the real-world characteristics and treatment patterns of mCSPC (PC) pts in this dynamic field. This study aimed to define clinical features of mCSPC pts, estimate the proportion of pts receiving ARPIs, and evaluate clinical and demographic features associated with ARPI use. Methods: This retrospective cohort study used data from electronic health records and administrative databases in the province of Alberta, Canada. All newly diagnosed metastatic PC pts between 2017-2020 were identified. Pts were considered to have mCSPC if they initiated ADT within 30 days prior to, or at any time after diagnosis. ARPI exposure was defined as receiving ARPI within 180 days of initiating ADT. ARPI-naïve pts may have received ADT alone or other non-ARPI therapy (i.e., docetaxel) within 180 days of initiating ADT. Multivariable logistic regression was used to evaluate pt characteristics related to the receipt of ARPI. Overall survival (OS) was defined as the date of diagnosis to death from any cause or last known contact. Results: Of the 976 mCSPC pts identified, 33.5% received an ARPI. In ARPI exposed pts, the median time from ADT to ARPI start was 7.9 weeks and median time on ARPI was 13.1 months (mos). In multivariable analyses, ARPI use was associated with younger pt age, more recent diagnosis, fewer comorbidities, a higher metastatic burden, treatment centre, referral to a medical oncologist, and prior local therapy (all p<0.05). The median time to next therapy was 24.6 mos (95%CI=19.5-33.0) vs. 18.5 mos (95%CI+16.9-21.1), and median OS was 38.5 mos (95%CI=32.8-NA) vs. 34.2 mos (95%CI=33.3-38.8) for APRI exposed vs. ARPI-naive pts, respectively (p=0.03). Conclusions: This study identified factors associated with ARPI use in mCSPC, potentially allowing targeted efforts to improve ARPI uptake for pts in whom use is low. These findings are important as they reflect outcomes seen in real world pts.
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Thomaz, Danilo Y., João N. de Almeida, Odeli N. E. Sejas, Gilda M. B. Del Negro, Gabrielle O. M. H. Carvalho, Viviane M. F. Gimenes, Maria Emilia B. de Souza et al. "Environmental Clonal Spread of Azole-Resistant Candida parapsilosis with Erg11-Y132F Mutation Causing a Large Candidemia Outbreak in a Brazilian Cancer Referral Center". Journal of Fungi 7, n.º 4 (30 de marzo de 2021): 259. http://dx.doi.org/10.3390/jof7040259.
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Clonal outbreaks due to azole-resistant Candida parapsilosis (ARCP) isolates have been reported in numerous studies, but the environmental niche of such isolates has yet to be defined. Herein, we aimed to identify the environmental niche of ARCP isolates causing unremitting clonal outbreaks in an adult ICU from a Brazilian cancer referral center. C. parapsilosis sensu stricto isolates recovered from blood cultures, pericatheter skins, healthcare workers (HCW), and nosocomial surfaces were genotyped by multilocus microsatellite typing (MLMT). Antifungal susceptibility testing was performed by the EUCAST (European Committee for Antimicrobial Susceptibility Testing) broth microdilution reference method and ERG11 was sequenced to determine the azole resistance mechanism. Approximately 68% of isolates were fluconazole-resistant (76/112), including pericatheter skins (3/3, 100%), blood cultures (63/70, 90%), nosocomial surfaces (6/11, 54.5%), and HCW’s hands (4/28, 14.2%). MLMT revealed five clusters: the major cluster contained 88.2% of ARCP isolates (67/76) collected from blood (57/70), bed (2/2), pericatheter skin (2/3), from carts (3/7), and HCW’s hands (3/27). ARCP isolates were associated with a higher 30 day crude mortality rate (63.8%) than non-ARCP ones (20%, p = 0.008), and resisted two environmental decontamination attempts using quaternary ammonium. This study for the first time identified ARCP isolates harboring the Erg11-Y132F mutation from nosocomial surfaces and HCW’s hands, which were genetically identical to ARCP blood isolates. Therefore, it is likely that persisting clonal outbreak due to ARCP isolates was fueled by environmental sources. The resistance of Y132F ARCP isolates to disinfectants, and their potential association with a high mortality rate, warrant vigilant source control using effective environmental decontamination.
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Somasekharan, Syam Prakash, Neetu Saxena, Fan Zhang, Eliana Beraldi, Jia Ni Huang, Christina Gentle, Ladan Fazli, Marisa Thi, Poul H. Sorensen y Martin Gleave. "Regulation of AR mRNA translation in response to acute AR pathway inhibition". Nucleic Acids Research 50, n.º 2 (23 de diciembre de 2021): 1069–91. http://dx.doi.org/10.1093/nar/gkab1247.
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Abstract We report a new mechanism of androgen receptor (AR) mRNA regulation and cytoprotection in response to AR pathway inhibition (ARPI) stress in prostate cancer (PCA). AR mRNA translation is coordinately regulated by RNA binding proteins, YTHDF3 and G3BP1. Under ambient conditions m6A-modified AR mRNA is bound by YTHDF3 and translationally stimulated, while m6A-unmodified AR mRNA is bound by G3BP1 and translationally repressed. When AR-regulated PCA cell lines are subjected to ARPI stress, m6A-modified AR mRNA is recruited from actively translating polysomes (PSs) to RNA-protein stress granules (SGs), leading to reduced AR mRNA translation. After ARPI stress, m6A-modified AR mRNA liquid–liquid phase separated with YTHDF3, while m6A-unmodified AR mRNA phase separated with G3BP1. Accordingly, these AR mRNA messages form two distinct YTHDF3-enriched or G3BP1-enriched clusters in SGs. ARPI-induced SG formation is cell-protective, which when blocked by YTHDF3 or G3BP1 silencing increases PCA cell death in response to ARPI stress. Interestingly, AR mRNA silencing also delays ARPI stress-induced SG formation, highlighting its supportive role in triggering this stress response. Our results define a new mechanism for stress adaptive cell survival after ARPI stress involving SG-regulated translation of AR mRNA, mediated by m6A RNA modification and their respective regulatory proteins.
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Monnoyer, Jean-Maurice. "Icnologie et archi-écriture". Rivista di estetica, n.º 50 (1 de julio de 2012): 331–42. http://dx.doi.org/10.4000/estetica.1504.
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Nichols, Rev Aidan. "Archi-Liturgical Culture Wars". New Blackfriars 89, n.º 1023 (septiembre de 2008): 522–42. http://dx.doi.org/10.1111/j.1741-2005.2007.00207.x.
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Daniel, Michael. "Logophoric reference in Archi". Journal of Pragmatics 88 (octubre de 2015): 202–19. http://dx.doi.org/10.1016/j.pragma.2015.07.002.
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Samedov, Jalil. "Converb clauses in Archi". Voprosy Jazykoznanija, n.º 6 (2020): 94. http://dx.doi.org/10.31857/0373-658x.2020.6.94-104.
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Szendy, Peter. "The Archi-Road Movie". Senses and Society 8, n.º 1 (marzo de 2013): 50–61. http://dx.doi.org/10.2752/174589313x13500466750921.
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Patel, Jeetvan, Amrita Sawhney, Clare Byrne, Jackson Tang y Channing Yu. "Real-world treatment patterns and progression-free survival among patients with metastatic castration-resistant prostate cancer: Examining the benefits of sequential androgen receptor pathway inhibitor use." Journal of Clinical Oncology 41, n.º 6_suppl (20 de febrero de 2023): 64. http://dx.doi.org/10.1200/jco.2023.41.6_suppl.64.
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64 Background: Numerous treatments with different mechanisms of action are approved for metastatic castration-resistant prostate cancer (mCRPC), but real-world studies increasingly indicate that androgen receptor pathway inhibitors (ARPIs) are the most common treatment choice at both first- (1L) and second-line (2L). Nonetheless, robust evidence on the clinical effectiveness of ARPIs when used sequentially is lacking. The aim of this study was to examine the real-world treatment patterns and associated progression-free survival (PFS) among patients with mCRPC in the United States (US). Methods: This retrospective cohort study used Flatiron Health electronic health record data from 01/01/2013 to 06/30/2020. Included patients were male, aged ≥18 years, had a confirmed diagnosis of mCRPC within the study period, and received ≥1 systemic therapy post-mCRPC diagnosis. Three treatment subgroups were examined, with ARPI defined as abiraterone or enzalutamide: all 1L ARPI users; all 2L ARPI users irrespective of 1L therapy; and 1L ARPI users who received another ARPI at 2L. Treatment patterns were evaluated descriptively; time to next therapy (TTNT) was measured from the start of the ARPI of interest to the start of the subsequent line of therapy. The Kaplan-Meier method was used to evaluate PFS from the start of the ARPI therapy of interest until progression or death from any cause. Results: The study included 2,588 patients (mean age 72 years). ARPIs were the most prescribed systemic therapy in both the 1L and 2L settings: 63% (1,634/2,588) and 46% (808/1,760), respectively. Among 1L ARPI patients, 28.9% received 2L ARPI, 14.0% 2L taxane, 14.3% 2L combo therapies, and 32% received no further therapy. The median TTNT was 7.6, 6.2, and 5.1 months for 1L ARPIs, 2L ARPIs among all users, and 2L ARPIs among patients who received 1L ARPIs, respectively. The corresponding median PFS was 6.5 months, 4.5 months, and 3.9 months, respectively. Conclusions: Among real-world mCRPC patients in the US, ARPIs remain the most common therapy at both 1L and 2L. However, sequential ARPI use appeared to provide diminishing returns, with a PFS of <4 months seen at 2L in those who had received 1L ARPIs. [Table: see text]
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Fioretti, Tiziana, Luigi Auricchio, Angelo Piccirillo, Giuseppina Vitiello, Adelaide Ambrosio, Fabio Cattaneo, Rosario Ammendola y Gabriella Esposito. "Multi-Gene Next-Generation Sequencing for Molecular Diagnosis of Autosomal Recessive Congenital Ichthyosis: A Genotype-Phenotype Study of Four Italian Patients". Diagnostics 10, n.º 12 (24 de noviembre de 2020): 995. http://dx.doi.org/10.3390/diagnostics10120995.
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Autosomal recessive congenital ichthyoses (ARCI) are rare genodermatosis disorders characterized by phenotypic and genetic heterogeneity. At least fourteen genes so far have been related to ARCI; however, despite genetic heterogeneity, phenotypes associated with mutation of different ARCI genes may overlap, thereby making difficult their clinical and molecular classification. In addition, molecular tests for diagnosis of such an extremely rare heterogeneous inherited disease are not easily available in clinical settings. In the attempt of identifying the genetic cause of the disease in four Italian patients with ARCI, we performed next-generation sequencing (NGS) analysis targeting 4811 genes that have been previously linked to human genetic diseases; we focused our analysis on the 13 known ARCI genes comprised in the panel. Nine different variants including three novel small nucleotide changes and two novel large deletions have been identified and validated in the ABCA12, ALOX12B, CYP4F22, and SULT2B1 genes. Notably, two patients had variants in more than one gene. The identification and validation of new pathogenic ABCA12, ALOX12B, CYP4F22, and SULT2B1 variants through multi-gene NGS in four cases of ARCI further highlight the importance of these genes in proper skin function and development.
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Fizazi, Karim, Michael J. Morris, Neal D. Shore, Kim N. Chi, Michael Crosby, Johann S. De Bono, Ken Herrmann et al. "Health-related quality of life and pain in a phase 3 study of [177Lu]Lu-PSMA-617 in taxane-naïve patients with metastatic castration-resistant prostate cancer (PSMAfore)." Journal of Clinical Oncology 42, n.º 16_suppl (1 de junio de 2024): 5003. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.5003.
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5003 Background: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged radiographic progression-free survival vs change of androgen receptor pathway inhibitor (ARPI) in taxane-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) in PSMAfore (NCT04689828). We now present health-related quality of life (HRQoL) and pain outcomes at second interim analysis. Methods: Eligible patients had mCRPC, were candidates for change of ARPI after progression on one prior ARPI, and had ≥1 PSMA-positive and no exclusionary PSMA-negative metastatic lesions by [68Ga]Ga-PSMA-11 PET/CT. Ineligible patients were candidates for PARP inhibition or had received prior systemic radiotherapy, immunotherapy or chemotherapy. Patients were randomized 1:1 to open-label 177Lu-PSMA-617 (7.4 GBq/6 weeks; 6 cycles) or ARPI change (abiraterone/enzalutamide). Patients with confirmed radiographic progression on ARPI change could cross over to 177Lu-PSMA-617. Secondary endpoints included time to worsening (TTW) in self-reported HRQoL (FACT-P, EQ-5D-5L) and pain (BPI-SF), defined as a composite of score worsening (prespecified thresholds), clinical progression (including new anti-cancer treatment) or death. Post hoc analyses of TTW in FACT-P and BPI-SF excluded clinical progression and death. The study was not powered for these endpoints and type I error was not controlled. Results: We randomized 468 patients (234/arm) with a median age of 72 years (range, 43–94). Median duration of exposure was 8.4 months for 177Lu-PSMA-617 and 6.5 months for ARPI change. 177Lu-PSMA-617 delayed TTW in FACT-P, EQ-5D-5L and BPI-SF scales and subscales vs ARPI change (Table). Results were similar in non-composite analyses. Incidence of grade ≥3 adverse events (AEs), serious AEs and AEs leading to discontinuation for 177Lu-PSMA-617 and ARPI change were 34% vs 44%, 20% vs 28% and 5.7% vs 5.2%, respectively. Conclusions: 177Lu-PSMA-617 delayed TTW in self-reported pain and HRQoL vs change of ARPI in taxane-naïve patients with PSMA-positive mCRPC. Clinical trial information: NCT04689828 . [Table: see text]
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Muzenda, Muredzwa Adelina, Olusegun Sodiya y Baxi Sinha. "Evaluation of the Quality of the Pre-ARCP (Pre-Annual Review of Competency Progression) Corporate Report for Postgraduate Doctors (Core Trainees) in Relation to Their Postgraduate Teaching Attendance and Audit Involvement". BJPsych Open 9, S1 (julio de 2023): S138. http://dx.doi.org/10.1192/bjo.2023.379.
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AimsThis evaluation was done with the focus to improve the quality of pre-ARCP corporate report for core-trainees. The pre-ARCP corporate report is a document compiled by the medical education department guided by other departments to capture certain competencies. The area of interest was how the report could be up-to-date and accurate. This would ultimately lead to a fair and objective summation of facts for the Psychiatric and Educational Supervisor report which will be reviewed by the ARCP panel.MethodsThis evaluation included all full-time core trainees within the Northern training scheme of the Trust who have undergone ARCP in January and July 2022. Exclusion criteria included less-than full-time trainees and core trainees who did not take part in an ARCP panel in January and July 2022. The questionnaire was designed by the Project Team and approved by the Trust Audit Team prior to data collection. The data were collected from 11th July to 31st July 2022. Electronic questionnaires were sent out to 33 postgraduate doctors.ResultsA total of 12 postgraduate doctors responded (36%). Out of the 12 doctors that responded, 11 (92%) had taken part in the ARCP panel in July 2022. 11/12 (92%) reported having received their pre-ARCP corporate report prior to the ARCP and in adequate time. Similarly, 11/12 (92%) of postgraduate doctors agreed with the record of both the RCPsych teaching attendance and audit involvement recorded on their pre-ARCP corporate report. In relation to capturing locality teaching attendance, 58% of postgraduate doctors reported the information as accurate. Inaccurate capturing of leaves, on-calls and/or rest days were pointed out by respondents as reasons for the discrepancy in attendance. Of those who contacted medical education, 10/10 (100%) reported that the issue was resolved before the portfolio submission date for ARCP. Of those who did not take action, 50% (1/2) reported the reason as being “I did not see the need to take action”.ConclusionWe found that core trainees felt that capturing accurate RCPsych teaching attendance as well as accurate audit involvement before ARCP are areas that required improvement. There is room for improvement regarding recording locality teaching attendance and absences due to leaves, on-calls, and compensatory rest. It brings us back to reflect on the time spent by each affected postgraduate doctor to clarify their records when discrepancies are noted. Results were discussed with Medical Education department and suggestions for improvement implemented. A re-evaluation is scheduled to take place in July 2023.
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Hope, Carla, Jonathan Lund, Gareth Griffiths y David Humes. "Differences in progression by surgical specialty: a national cohort study". BMJ Open 12, n.º 2 (febrero de 2022): e053391. http://dx.doi.org/10.1136/bmjopen-2021-053391.
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The aim of surgical training across the 10 surgical specialties is to produce competent day 1 consultants. Progression through training in the UK is assessed by the Annual Review of Competency Progression (ARCP).ObjectiveThis study aimed to examine variation in ARCP outcomes within surgical training and identify differences in outcomes between specialties.DesignA national cohort study using data from the UK Medical Education Database was performed. ARCP outcome was the primary outcome measure. Multilevel ordinal regression analyses were performed, with ARCP outcomes nested within trainees.ParticipantsHigher surgical trainees (ST3–ST8) from nine UK surgical specialties were included (vascular surgery was excluded due to insufficient data). All surgical trainees across the UK with an ARCP outcome between 2010 and 2017 were included.ResultsEight thousand two hundred and twenty trainees with an ARCP outcome awarded between 2010 and 2017 were included, comprising 31 788 ARCP outcomes. There was substantial variation in the proportion of non-standard outcomes recorded across specialties with general surgery trainees having the highest proportion of non-standard outcomes (22.5%) and urology trainees the fewest (12.4%). After adjustment, general surgery trainees were 1.3 times more likely to receive a non-standard ARCP outcome compared with trainees in trauma and orthopaedics (T&O) (OR 1.33, 95% CI 1.21 to 1.45, p=0.001). Urology trainees were 36% less likely to receive a non-standard outcome compared with T&O trainees (OR 0.64, 95% CI 0.54 to 0.75, p<0.001). Female trainees and older age were associated with non-standard outcomes (OR 1.11, 95% CI 1.02 to 1.22, p=0.020; OR 1.04, 95% CI 1.03 to 1.05, p<0.001).ConclusionThere is wide variation in the training outcome assessments across surgical specialties. General surgery has higher rates of non-standard outcomes compared with other surgical specialties. Across all specialties, female sex and older age were associated with non-standard outcomes.
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Aslet, Margaret, Lewis W. Paton, Thomas Gale y Paul A. Tiffin. "Evaluating the recruitment process into UK anaesthesia core training: a national data linkage study of doctors’ performance at selection and subsequent postgraduate training". Postgraduate Medical Journal 96, n.º 1131 (24 de julio de 2019): 14–20. http://dx.doi.org/10.1136/postgradmedj-2019-136390.
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Purpose of the studyTo explore which factors increase the likelihood of being deemed appointable to core anaesthesia training in the UK and whether those factors subsequently predict performance in postgraduate training.Study designObservational study linking UK medical specialty recruitment data with postgraduate educational performance, as measured by Annual Review of Competence Progression (ARCP) outcomes. Data were available for 2782 trainee doctors recruited to anaesthesia core training from 2012 to 2016 with at least one subsequent ARCP outcome.ResultsBoth higher interview and shortlisting scores were independent and statistically significant (p≤0.001) predictors of more satisfactory ARCP outcomes, even after controlling for the influence of postgraduate exam failure. It was noted that a number of background variables (eg, age at application) were independently associated with the odds of being deemed appointable at recruitment. Of these, increasing age and experience were also negative predictors of subsequent ARCP rating. These influences became statistically non-significant once ARCP outcomes associated with exam failure were excluded.ConclusionsThe predictors of ‘appointability’ largely also predict subsequent performance in postgraduate training, as indicated by ARCP ratings. This provides evidence for the validity of the selection process. Our results also suggest that greater weight could be applied to shortlisting scores within the overall process of ranking applicants for posts.
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Parrish, Joshua, Thomas J. Polascik, Agnes Hong, Nader N. El-Chaar, Amanda Marie De Hoedt, Janet Kim, Claire Trustram Eve et al. "Real-world (RW) survival and outcomes with androgen receptor pathway inhibitor (ARPI) –doublet therapy in patients (pts) with de novo metastatic castration-sensitive prostate cancer (mCSPC)." Journal of Clinical Oncology 42, n.º 4_suppl (1 de febrero de 2024): 145. http://dx.doi.org/10.1200/jco.2024.42.4_suppl.145.
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145 Background: With multiple phase 3 trials showing improved overall survival (OS) with doublet therapy (androgen-deprivation therapy [ADT]+ARPI), it has become the standard of care for pts with mCSPC. However, data on RW effectiveness of ARPI doublets are limited. This study assessed OS, time to progression to metastatic castration-resistant prostate cancer (mCRPC), and PSA decline to <0.2 ng/mL in pts with de novo mCSPC on ADT alone vs ADT+ARPI doublets or ADT+first-generation nonsteroidal antiandrogens (NSAAs). Methods: Men in the Veteran’s Health Administration with ≥1 ICD code for PC and de novo mCSPC diagnosis confirmed by clinical chart review were identified and categorized into first-line (1L) ADT alone, ADT+NSAA, or ADT+ARPI cohorts (study period: Feb 2018−Mar 2023). Target recruitment quotas ensured representation of each treatment (Tx) regimen. Index date was the ADT initiation date. OS and time to mCRPC were calculated using inverse probability of Tx weighting (IPTW)-adjusted Cox regression. IPTW-adjusted incidence rate ratios (IRR) of the proportion of pts with PSA decline to <0.2 ng/mL at any time during 1L Tx were estimated using Poisson regression. Results: 384 men with de novo mCSPC were identified (Table). Median follow-up range was 34.8–38.1 mo. 1L Tx duration for ADT+ARPI was over twice as long as ADT alone (Table). Importantly, pts on ADT+ARPI had a 39% lower risk of death vs ADT alone (HR: 0.61, 95% CI: 0.43–0.87); while OS was similar between ADT+NSAA vs. ADT alone (HR: 1.09, 95% CI: 0.79–1.49). Consistent with the improved OS, ADT+ARPI showed a 54% lower risk of progression to mCRPC (HR: 0.46, 95% CI: 0.33–0.66) and significant superiority in achieving PSA <0.2 ng/mL (57% vs 17%; Table) than ADT alone. Conclusions: This is one of the first RW studies to validate clinical trial findings of the effectiveness of ARPI-doublets for de novo mCSPC as evidenced by significantly improved OS, time to mCRPC, and PSA response. ADT+NSAA may have limited value vs ADT alone, and ARPI-doublet is an effective Tx for de novo mCSPC. [Table: see text]
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Oyen, Meredith. "“Thunder without Rain”: ARCI, the Far East Refugee Program, and the U.S. Response to Hong Kong Refugees". Journal of Cold War Studies 16, n.º 4 (octubre de 2014): 189–221. http://dx.doi.org/10.1162/jcws_a_00520.
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During the early Cold War, a refugee crisis in Hong Kong captured international attention. The failure of the United Nations to respond gave rise to a complicated cooperative relief effort involving British authorities, the U.S. government, and many private voluntary organizations. This article focuses on the history of one organization, Aid Refugee Chinese Intellectuals (ARCI), and demonstrates how its work with the U.S. Refugee Relief Program (RRP) contributed to the politicization of the migrants and became a mutually beneficial collaboration for both bodies: ARCI facilitated RRP's claims to be aiding Chinese refugees, and RRP funded ARCI. Although both ARCI and the RRP fulfilled some of their own goals and aided some refugees, their history shows that Cold War politics still usually won out over strictly humanitarian concerns.
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Hotz, Alrun, Julia Kopp, Emmanuelle Bourrat, Vinzenz Oji, Kira Süßmuth, Katalin Komlosi, Bakar Bouadjar et al. "Mutational Spectrum of the ABCA12 Gene and Genotype–Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis". Genes 14, n.º 3 (15 de marzo de 2023): 717. http://dx.doi.org/10.3390/genes14030717.
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Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mutations in ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, SDR9C7, SULT2B1, and TGM1. The most severe form of ARCI, harlequin ichthyosis, is caused by mutations in ABCA12. Mutations in this gene can also lead to congenital ichthyosiform erythroderma or lamellar ichthyosis. We present a large cohort of 64 patients affected with ARCI carrying biallelic mutations in ABCA12. Our study comprises 34 novel mutations in ABCA12, expanding the mutational spectrum of ABCA12-associated ARCI up to 217 mutations. Within these we found the possible mutational hotspots c.4541G>A, p.(Arg1514His) and c.4139A>G, p.(Asn1380Ser). A correlation of the phenotype with the effect of the genetic mutation on protein function is demonstrated. Loss-of-function mutations on both alleles generally result in harlequin ichthyosis, whereas biallelic missense mutations mainly lead to CIE or LI.
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Grimm, Marc-Oliver, Matthew Raymond Smith, Maha H. A. Hussain, Fred Saad, Karim Fizazi, Natasha Littleton, Noman Paracha, Shankar Srinivasan, Frank Verholen y Bertrand F. Tombal. "Post-progression survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who received darolutamide or placebo: Post hoc analysis of ARASENS." Journal of Clinical Oncology 42, n.º 16_suppl (1 de junio de 2024): 5083. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.5083.
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5083 Background: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor pathway inhibitor (ARPI). In ARASENS (NCT02799602), the addition of DARO to androgen-deprivation therapy (ADT) and docetaxel (DOC) significantly reduced the risk of death by 32.5% in patients (pts) with mHSPC, despite most placebo (PBO) pts (75.6%) receiving subsequent therapy. DARO also delayed time to progression to metastatic castration-resistant prostate cancer (mCRPC; median, not reached vs 19.1 months for PBO), resulting in a longer time in mHSPC, which is associated with improved quality of life vs mCRPC. We report post-progression subsequent anticancer therapies and related survival from ARASENS. Methods: Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or PBO in addition to ADT + DOC. After treatment discontinuation, pts entered active and long-term survival follow-up periods during which assessments included subsequent therapies and survival outcomes. Post-progression survival was defined as time from first subsequent therapy to death using Kaplan-Meier estimates. Results: Of 1305 treated pts (DARO n=651; PBO n=654), 315 receiving DARO and 495 receiving PBO entered follow-up. Of these, 57% (n=179) and 76% (n=374), respectively, received subsequent therapy; abiraterone and enzalutamide were the most frequent first subsequent therapy (Table). In the DARO arm, 90% of first subsequent therapies were ARPI or chemotherapy. Minimal difference was observed in post-progression survival between subsequent therapies, suggesting subsequent therapy with another ARPI does not provide further survival benefit vs non-ARPI options (mainly chemotherapy). In contrast, in the PBO arm where the majority (78%) received first subsequent therapy with an ARPI, a survival benefit was observed vs non-ARPI subsequent therapies (median, 23.0 vs 13.5 months). Conclusions: DARO+ADT+DOC increased overall survival vs PBO+ADT+DOC and also delayed time to progression to mCRPC. DARO pts had similar survival with all post-progression therapies. Pts receiving PBO+ADT+DOC quickly progressed to mCRPC and treatment with an ARPI in ARPI-naïve pts improved survival. Clinical trial information: NCT02799602 . [Table: see text]
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Guérineau, Julie. "Ils sont archi(s)-humains !" DARD/DARD N° 3, n.º 1 (2 de noviembre de 2020): 136–43. http://dx.doi.org/10.3917/dard.003.0136.
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Antonenko, Andrei y Alice C. Harris. "Multiple Exponence on Archi Pronouns". LSA Annual Meeting Extended Abstracts 1 (2 de mayo de 2010): 30. http://dx.doi.org/10.3765/exabs.v0i0.509.
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In this paper we consider multiple exponence in Archi pronouns. We investigate the morphological structure of pronominal forms with several class markers, and demonstrate how the schema-based approach advocated by Harris (2009) can account for their occurrence. We show that pronominal forms with multiple class markers consist of a number of independent morphemes, each taking a class marker. Finally we show that concord is responsible for obligatory co-occurrence of the morphemes on the sequences of reflexive pronouns in Archi. This paper provides additional arguments for a layered structure of words in languages with multiple exponence based on morphological schemas.
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Patel, Jeetvan, Jennifer Nguyen, Vamsi Bollu, Barinder Kang, Amrita Sawhney, Clare Byrne, Jackson Tang, Magdaliz Gorritz, Chi-Chang Chen y Neal D. Shore. "Real-world clinical outcomes and economic burden of early discontinuation of taxane therapy among patients with metastatic castration-resistant prostate cancer." Journal of Clinical Oncology 42, n.º 16_suppl (1 de junio de 2024): e17043-e17043. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.e17043.
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e17043 Background: Despite comprising an important part of the treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC) for over a decade, real-world use of taxanes is hindered by adverse events (AEs). AEs may lead to early treatment discontinuation, which may adversely affect outcomes. The two goals of this study were to determine the proportion of mCRPC patients who discontinue taxanes early (defining the early discontinuation threshold relative to efficacy results associated with androgen receptor pathway inhibitors [ARPIs]) and to evaluate the impact of early discontinuation on clinical outcomes, AEs, and healthcare costs. Methods: This was a retrospective, observational study of adult men with mCRPC treated with an ARPI as their first-line (1L) therapy and who initiated second-line (2L) therapy with another ARPI or a taxane. The Flatiron Health electronic health record database (07/01/2012–06/30/2020) was used to estimate Kaplan-Meier overall survival (OS) curves for the taxane cohort by the number of cycles received; these were compared with patients who received ARPI at 2L. Cox regression modeling and median PFS and OS values were used to identify the number of taxane cycles needed to achieve comparable OS to ARPI. The number of taxane cycles with similar OS outcomes to ARPI was then considered the threshold for early discontinuation. In addition, the IQVIA PharMetrics Plus claims database (01/01/2013–08/31/2021) was used to estimate taxane-related AEs (based on product information) and associated healthcare costs among patients who did and did not discontinue taxanes early. Results: From Flatiron, 473 2L ARPI patients and 214 2L taxane patients were included. Similar clinical characteristics – e.g., prostate-specific antigen level, ECOG performance status, and Gleason score – were observed between the two cohorts. Overall, 2L ARPI was associated with longer median OS (15.4 vs. 13.6 months) than 2L taxane. The number of taxane cycles needed to reach comparable OS to ARPI was determined to be 8. Patients receiving >8 cycles (n=48; 22%) compared to those receiving ≤8 cycles (n=166; 78%) had longer median OS (18.4 vs. 11.9 months, respectively) and PFS (9.0 vs. 4.3 months, respectively). From PharMetrics, 158 2L taxane patients were included. Patients receiving >8 cycles (n=20; 13%) were more likely to experience an AE (95% vs. 88%) than those receiving ≤8 cycles (n=138; 87%) but had lower mean AE-related total healthcare costs per patient per month ($3,429 vs. $6,334). Conclusions: These results suggest that mCRPC patients need to receive >8 cycles of taxane at 2L to receive more clinical benefit than 2L ARPI. However, the vast majority of patients in the study discontinued taxane early, resulting in shorter survival outcomes compared to ARPI.
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Nikesitch, Nicholas, Eliana Beraldi, Fan Zhang, Hans Adomat, Robert Bell, Ladan Fazli, Christopher Wells, Nicholas Pinette, Yuzhuo Wang y Martin Gleave. "Abstract 395: Characterizing the role of chaperone-mediated autophagy in prostate cancer treatment resistance". Cancer Research 82, n.º 12_Supplement (15 de junio de 2022): 395. http://dx.doi.org/10.1158/1538-7445.am2022-395.
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Abstract Androgen deprivation therapy (ADT) and androgen receptor pathway inhibition (ARPI) remains the standard of care for advanced prostate cancer (PCa). As part of its canonical activities, the androgen receptor (AR) plays an important role in PCa metabolism. AR inhibition with ARPI subjects PCa cells to acute metabolic stress caused by reduced biosynthesis and energy production. The upregulation of ARPI-induced stress response mechanisms is essential adaptive mechanism for cell proliferation and survival. This process requires PCa cells undergoing rapid phenotypic changes to adapt to their environment and circumvent lethal outcomes. By profiling the proteomic pathway alterations associated with the ARPI stress response in LNCaP cells, we noted a significant upregulation of chaperone mediated autophagy (CMA), a stress response mechanism yet to be defined in PCa. CMA, a selective protein degradation pathway, specifically targets protein substrates via a CMA recognition motif and is an essential survival mechanism in cancer cells during energy depleted metabolic stress. Within in-vitro and in-vivo PCa models, ARPI induced CMA is reflected through the increased activity of CMA lysosomes and specifically by the increased expression of the CMA marker, lysosomal associated membrane protein 2a (L2A). L2A knockdown using shRNA not only elicited a strong anti-proliferative effect in PCa cells, but also compromised PCa metabolism with decreases in ATP levels and mTORC1 signaling. Proteomic analysis by mass spectrometry further identified that CMA promotes chromatin silencing, and the suppression of pathways associated with transcription. Conversely, L2A overexpression not only promoted PCa cell proliferation during Enza treatment, but upregulated of hallmark target genes of AR-indifferent PCa growth. The upregulation of CMA facilitated proteome remodeling during ARPI, leading to increased mTORC1 signaling and biosynthesis. In summary, our data illustrates the importance of CMA in mediating the ARPI stress response in PCa, providing novel insights into the mechanisms of ARPI treatment resistance. Citation Format: Nicholas Nikesitch, Eliana Beraldi, Fan Zhang, Hans Adomat, Robert Bell, Ladan Fazli, Christopher Wells, Nicholas Pinette, Yuzhuo Wang, Martin Gleave. Characterizing the role of chaperone-mediated autophagy in prostate cancer treatment resistance [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 395.
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Ghantoji, Shashank, Channing Yu, Amrita Sawhney, Clare Byrne, Jackson Tang, Kyle Runeckles y Jeetvan Patel. "Real-world treatment patterns in the U.S. and trends pre-post CARD trial among patients with metastatic castration-resistant prostate cancer." Journal of Clinical Oncology 40, n.º 16_suppl (1 de junio de 2022): e17024-e17024. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e17024.
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e17024 Background: Numerous treatments with different mechanisms of action are approved for metastatic castration-resistant prostate cancer (mCRPC). The sequencing for management of these patients has been evolving post availability of trials such as the CARD trial, looking at clinical outcomes post androgen receptor pathway inhibitor (ARPI) and docetaxel. This study examined real-world treatment patterns and sequencing among United States patients with mCRPC. Methods: This retrospective cohort study used Flatiron Health electronic health record data from Jan 1, 2013 to June 30, 2020 (study period). Included patients were male aged ≥18 years, had a confirmed diagnosis of mCRPC within the study period, and received ≥1 systemic therapy post-mCRPC diagnosis. Index date was the date of first-line (1L) therapy initiation post-mCRPC diagnosis. Patient characteristics and treatment patterns were evaluated descriptively. Across analyses, treatments were grouped as follows: ARPI (abiraterone, enzalutamide), taxane (docetaxel, cabazitaxel), sipuleucel-T, radium-223, targeted therapy (TT; olaparib, rucaparib), mitoxantrone, combo therapy (any combination regimen containing ≥1 of the preceding therapies), and other (any other therapy or combination of therapies). Results: 2,588 patients were included in the study; mean±SD age was 72±8 years and 66% were White. The most common 1L therapy was ARPI (63%), followed by taxane (11%), combo therapy (11%), radium-223 (6%), sipuleucel-T (6%), and other therapy (2%). No patient received TT or mitoxantrone alone in 1L. Median time to next treatment post-1L was longest for combo therapy (8.1 months) and ARPI (7.6 months) and shortest for sipuleucel-T (3.4 months). The most common sequence of treatment for mCRPC patients was 1L ARPI to another ARPI at second-line (2L) (29%); taxane and combo therapy (both 14%) were the next most common (Table). Treatment patterns were similar pre- and post- read-out of the CARD trial. Conclusions: The majority of mCRPC patients who receive 1L ARPI will receive another at 2L rather than switching to an alternative type of treatment.[Table: see text]
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Khan, Muhammad Ali, Syed Arsalan Ahmed Naqvi, Manal Imran, Aneeta Channar, Akshat Saxena, Ammad Raina, Kaneez Zahra Rubab Khakwani et al. "First-line PARP inhibitors (PARPi) with androgen receptor pathway inhibitors (ARPi) in metastatic castration-resistant prostate cancer (mCRPC): A systematic review and meta-analysis." Journal of Clinical Oncology 42, n.º 4_suppl (1 de febrero de 2024): 173. http://dx.doi.org/10.1200/jco.2024.42.4_suppl.173.
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173 Background: The data for combining PARPi and ARPi in mCRPC have shown conflicting results. Here, we report a quantitative summary of benefits by clinically meaningful subgroups (HRR mutation status, BRCA mutation status) to guide the use of PARPi and ARPi combination in mCRPC setting. Methods: MEDLINE, EMBASE, and CENTRAL were systematically searched from each database’s inception through September 7, 2023. Phase III studies comparing PARPi + ARPi with ARPi + placebo in mCRPC were included. Radiographic progression-free survival (rPFS) and overall survival (OS) in patient subgroups based on HRR and BRCA mutation status were assessed. Hazard ratios for rPFS and OS with 95% CI were collected at the level of each trial, and a random-effects meta-analysis was conducted using an inverse variance approach. Subgroup differences were assessed and p-value of interaction <0.1 was considered statistically significant. Results: The literature search identified 4976 studies from which 3 trials (11 references) – TALAPRO2, PROpel and MAGNITUDE met the inclusion criteria. A total of 2254 participants were eligible for analysis. PARPi + ARPi prolonged rPFS in patients with HRR mutations (HR: 0.55, 95%CI: 0.38-0.78) as well as in patients without HRR mutations (HR: 0.74, 95%CI: 0.63-0.88). There is no evidence of treatment interaction by HRR mutation status (p = 0.14). In patients harboring HRR mutations, improved rPFS was observed in those with BRCA mutations (HR: 0.28, 95%CI: 0.13-0.62) as well as those without BRCA mutations (HR: 0.72, 95%CI: 0.59-0.87). However, there is evidence that patients with BRCA mutations derived greater rPFS benefit as compared to patients without BRCA mutations (p =0.02). PARPi + ARPi showed no significant improvement in overall survival either in patients with HRR mutations (HR: 0.79, 95%CI: 0.59-1.05) or in patients without HRR mutations (HR: 0.92, 95%CI: 0.74-1.14). Conclusions: Genomic testing for HRR genes is mandatory to guide clinical decision making in mCRPC patients. Patients harboring BRCA mutations are most likely to derive clinically meaningful benefit from combination PARPi + ARPi treatment. [Table: see text]
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Li, Ting, Yan Wei, Meihua Qu, Lixian Mou, Junye Miao, Mengqi Xi, Ying Liu y Rongqiao He. "Formaldehyde and De/Methylation in Age-Related Cognitive Impairment". Genes 12, n.º 6 (13 de junio de 2021): 913. http://dx.doi.org/10.3390/genes12060913.
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Formaldehyde (FA) is a highly reactive substance that is ubiquitous in the environment and is usually considered as a pollutant. In the human body, FA is a product of various metabolic pathways and participates in one-carbon cycle, which provides carbon for the synthesis and modification of bio-compounds, such as DNA, RNA, and amino acids. Endogenous FA plays a role in epigenetic regulation, especially in the methylation and demethylation of DNA, histones, and RNA. Recently, epigenetic alterations associated with FA dysmetabolism have been considered as one of the important features in age-related cognitive impairment (ARCI), suggesting the potential of using FA as a diagnostic biomarker of ARCI. Notably, FA plays multifaceted roles, and, at certain concentrations, it promotes cell proliferation, enhances memory formation, and elongates life span, effects that could also be involved in the aetiology of ARCI. Further investigation of and the regulation of the epigenetics landscape may provide new insights about the aetiology of ARCI and provide novel therapeutic targets.
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Kashif, Muhammad, Ahsan Naseem, Nouman Iqbal, Pieter De Winne y Hans De Backer. "Evaluating the Early-Age Crack Induction in Advanced Reinforced Concrete Pavement Using Partial Surface Saw-Cuts". Applied Sciences 11, n.º 4 (12 de febrero de 2021): 1659. http://dx.doi.org/10.3390/app11041659.
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The technological innovation of continuously reinforced concrete pavement (CRCP) that contains a significantly reduced amount of reinforcement and the same fundamental behavior as CRCP is called advanced reinforced concrete pavement (ARCP). This new concept of a rigid pavement structure is developed to eliminate unnecessary continuous longitudinal steel bars of CRCP by using partial length steel bars at predetermined crack locations. In Belgium, partial surface saw-cuts are used as the most effective crack induction method to eliminate the randomness in early-age crack patterns by inducing cracks at the predetermined locations of CRCP. The reinforcement layout of ARCP is designed based on the distribution of steel stress in continuous longitudinal steel bar in CRCP and the effectiveness of partial surface saw-cuts as a crack induction method. The 3D finite element (FE) model is developed to evaluate the behavior of ARCP with partial surface saw-cuts. The early-age crack characteristics in terms of crack initiation and crack propagation obtained from the FE simulation are validated with the field observations of cracking characteristics of the CRCP sections in Belgium. The finding indicates that there is fundamentally no difference in the steel stress distribution in the partial length steel bar of ARCP and continuous steel bar of CRCP. Moreover, ARCP exhibits the same cracking characteristics as CRCP even with a significantly reduced amount of continuous reinforcement.
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Ahmed, Md Razu, Md Shajadul Islam, Md Dipu Islam y Maruf Hossain. "Circulating Capital Management and Its Impact on Profitability: Evidence From Selected Food and Beverage Companies Listed in DSE". International Journal of Accounting and Financial Reporting 13, n.º 2 (20 de junio de 2023): 23. http://dx.doi.org/10.5296/ijafr.v13i2.21020.
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Circulating capital management and its impact on profitability seek an empirical relationship between circulating capital and profitability. The study is based on secondary data collected from the websites of food and beverage companies. Because of the availability of data, this study covers six food and beverage companies from 2016 to 2020. The circulating capital components are cash conversion cycle (CCC), inventory turnover (IT), accounts payable payment period (APPP), accounts receivable collection periods (ARCP), and profitability, which involves return on assets (ROA) and net profit margin (NPM). This study implicates descriptive statistics and inferential statistics, which have analyzed mean, standard deviation, correlation, and regression to summarize the inverse connection between CCC, IT, ARCP, APPP, and ROA. The study also summarizes the significant relationship between CCC, ARCP, and NPM and the insignificant impact of IT and APPP on NPM. I have found both positive and negative connections between circulating capital components and profitability. So, CCC, IT, ARCP, and APPP should be well communicated with ROA and inventory turnover, and the accounts payable payment period should be optimal with NPM.
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Sartor, A. Oliver, Michael J. Morris, Kim N. Chi, Johann S. De Bono, Neal D. Shore, Michael Crosby, Teri Nguyen Kreisl y Karim Fizazi. "PSMAfore: A phase 3 study to compare 177Lu-PSMA-617 treatment with a change in androgen receptor pathway inhibitor in taxane-naïve patients with metastatic castration-resistant prostate cancer." Journal of Clinical Oncology 40, n.º 6_suppl (20 de febrero de 2022): TPS211. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.tps211.
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TPS211 Background: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) is a high-affinity prostate-specific membrane antigen (PSMA)-targeted radioligand therapy that delivers β-particle radiation to PSMA-expressing cells and their surrounding microenvironment. In the phase 3 VISION trial, 177Lu-PSMA-617 significantly prolonged radiographic progression-free survival (rPFS) and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with ≥1 androgen receptor pathway inhibitor (ARPI) and 12 taxanes. PSMAfore is investigating the effect on rPFS in taxane-naïve patients with mCRPC treated with either 177Lu-PSMA-617 or a change in ARPI. Methods: PSMAfore (NCT04689828) is a multicenter, open-label, randomized phase 3 trial in adults with progressive mCRPC and confirmed PSMA expression by [68Ga]Ga-PSMA-11 PET/CT. Eligible patients are taxane-naïve in the metastatic setting and have: received one prior ARPI and are candidates for a change in ARPI; an Eastern Cooperative Oncology Group performance status of 0 or 1; a castrate level of serum/plasma testosterone ( < 50 ng/dL or < 1.7 nmol/L); and recovered to grade ≤2 from toxicities related to prior therapies. Approximately 450 patients will be randomized 1:1 to receive 177Lu-PSMA-617 (7.4 GBq i.v. every 6 weeks for 6 cycles) or a change in ARPI to either abiraterone or enzalutamide. Best supportive care is allowed in both arms. Stratification factors are prior ARPI use in castration-resistant vs hormone-sensitive prostate cancer settings and pain symptomatology (score 03 vs 410 on the worst pain intensity item of the Brief Pain InventoryShort Form). The primary endpoint is rPFS according to PCWG3-modified RECIST v1.1 criteria. Participants with blinded independent centrally confirmed radiographic progression in the ARPI arm can crossover to the 177Lu-PSMA-617 arm. The planned sample size provides 95% power to detect a hazard ratio of 0.56 for rPFS after 156 events with an overall one-sided significance level of 0.025. The key secondary endpoint is OS; other secondary endpoints include safety and tolerability of 177Lu-PSMA-617 and health-related quality of life. Previously presented at the 2021 European Society for Medical Oncology Congress, FPN 942, Morris M et al. Reused with permission. Clinical trial information: NCT04689828.
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Naito, Yushi, Jun Nagayama, Yuta Sano, Satoshi Inoue, Kazuna Matsuo, Tomoyasu Sano, Shohei Ishida, Yoshihisa Matsukawa, Masashi Kato y Shusuke Akamatsu. "Optimal sequential therapy for metastatic castration-resistant prostate cancer after androgen receptor pathway inhibitors in the up-front era." Journal of Clinical Oncology 42, n.º 4_suppl (1 de febrero de 2024): 168. http://dx.doi.org/10.1200/jco.2024.42.4_suppl.168.
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168 Background: The optimal sequential therapy for metastatic castration-resistant prostate cancer (mCRPC) following the use of up-front androgen receptor pathway inhibitors (ARPIs) for metastatic hormone-sensitive prostate cancer (mHSPC) is still unclear. Methods: A total of 220 patients who received systemic therapy for de novo mHSPC at Nagoya University Hospital and its affiliated institutions between 2014 and 2022 were included in the study. Patients who received up-front therapy with ARPI as first-line therapy for mHSPC, followed by ARPI as primary therapy for mCRPC were defined as the AA group, followed by docetaxel (DOC) as primary therapy for mCRPC were defined as the AD group. On the other hand, the vAA group was defined as patients who received androgen deprivation therapy alone or combined androgen blockade as “vintage” first-line therapy for mHSPC, followed by two consecutive ARPIs as sequential therapy for mCRPC, and the vAD group was defined as patients who received ARPI followed by DOC as sequential therapy for mCRPC. Patient characteristics and progression-free survival (PFS) of the second agent after the first ARPI were compared in each group. Results: We identified 14 patients in the AA group, 16 in the AD group, 84 in the vAA group, and 59 in the vAD group. There were no differences in patient background such as initial PSA, Gleason score, and metastatic burden between the groups, while patient age was lower in the AD and vAD groups compared to the AA and vAA groups. The PFS of the second agent in the AA group was significantly shorter than that in the vAA group (median, 6.8 vs. 1.9 months; hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.25-0.87; p=0.017). In contrast, there was no significant difference in PFS of the second agent in the vAD and AD groups (median, 7.0 vs. 4.0 months; HR, 0.63; 95%CI, 0.29-1.34; p=0.235). Conclusions: The effect of each agent after ARPI therapy in the UP-FRONT era may be poorer than that in the VINTAGE era. In the setting after up-front ARPI, sequential therapy with DOC may be more appropriate than sequential therapy with ARPI.
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Turco, Fabio, Isabella Saporita, Mariangela Calabrese, Federica Maria Carfi, Andrea Mogavero, Giorgio Treglia, Silke Gillessen et al. "Maximal androgen blockade therapy (MAB) for prostate cancer (PC) and risk of bone fractures: A systematic literature review and meta-analysis." Journal of Clinical Oncology 42, n.º 16_suppl (1 de junio de 2024): e17111-e17111. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.e17111.
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e17111 Background: Androgen deprivation therapy (ADT) increases the risk of fractures. The addition of an androgen receptor pathway inhibitor (ARPI) to ADT (MAB) has shown to improve outcomes compared to ADT monotherapy in patients (pts) with metastatic castration-resistant PC (mCRPC), non-mCRPC (nmCRPC), metastatic hormone-sensitive PC (mHSPC), high-risk localized disease and high-risk biochemical relapse. There is no definitive evidence whether MAB increases the risk of fractures compared to ADT alone. Methods: We conducted a systematic review of all clinical trials assessing treatment with an ARPI plus ADT for pts with PC having placebo plus ADT as control arm, using the PubMed/Medline and Cochrane library databases. We also performed a meta-analysis to compare the risk of fractures of each ARPI versus placebo. Further we assessed the number of pts receiving bone protecting agents (BPA) in the studies selected. The comparison between ARPI and placebo in terms of risk of fractures was performed using odds ratio (OR) as meta-analytic outcome. Results: We identified 15 studies comprising 15183 pts (8638 treated with an ARPI and 6545 with placebo), of which 3 studies evaluated abiraterone, 3 apalutamide, 3 darolutamide and 6 enzalutamide. Each ARPI resulted in a statistically significant increase in the risk of fractures compared to placebo (see table), but without statistical differences among the different ARPIs since there is an overlap between the confidence intervals (CI) of the pooled outcome measure of different ARPIs compared to placebo. Only 7/15 studies reported the number (n°) of pts treated with a BPA of which 4 were in mCRPC, 2 in nmCRPC and one in the mHSPC setting. The highest percentage was found in studies including mCRPC pts, of which 35-50% received a BPA. In the studies in the nmCRPC setting, 10-11% of pts received a BPA while in the only mHSPC study reporting data on the use of BPA only two pts (0.4%) in the ARPI group received BPA and no patient in the placebo group. Conclusions: In our meta-analysis MAB resulted in a statistically significant increase in fracture risk compared to ADT regardless of the ARPI used. Data on the use of BPA should be properly reported in future clinical trials. Since long term MAB represents the standard of care in various settings of PC, the use of a BPA should be generally recommended. Dosing and frequency of BPA needs to be adapted according to the specific PC setting. [Table: see text]
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DEMİRKAN, Özgür, Ayhan USTA y Emre ENGİN. "ARCHI-MIMESIS AS A DESIGN DOCTRINE". TURKISH ONLINE JOURNAL OF DESIGN ART AND COMMUNICATION 9, n.º 2 (1 de abril de 2019): 207–15. http://dx.doi.org/10.7456/10902100/013.
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Thoiron, Philippe, Pierre Arnaud, Henri Béjoint y Claude Pierre Boisson. "Notion d'« archi-concept » et dénomination". Meta 41, n.º 4 (30 de septiembre de 2002): 512–24. http://dx.doi.org/10.7202/004486ar.
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Résumé Cette étude se place dans le cadre d'une approche multilingue de la terminologie. Les termes équivalents (i.e. désignant des concepts homologues dans plusieurs langues) font l'objet d'une analyse exhaustive en éléments de nomination. Tous les éléments de nomination sont regroupés en un ensemble panlinguistique qui est vu comme le correspondant d'un ensemble de traits conceptuels, lui-même représentation d'un "archi-concept" englobant la totalité des caractéristiques (i.e. traits conceptuels) de chacun des concepts homologues dans les langues utilisées. L'archi-concept, parce qu'il est placé au seul niveau cognitif, peut avoir son utilité dans le cadre d'une représentation "conceptuelle" affinée, non strictement dépendante d'une seule langue naturelle. La procédure explicite que nous proposons s'appuie sur les dénominations dans diverses langues et sur les mécanismes inférentiels susceptibles de donner accès aux traits conceptuels non désignés. La même approche multilingue permet de mettre en place, après confrontation de plusieurs conceptologies, une conceptologie enrichie non tributaire d'une seule langue et non dépourvue d'intérêt dans le cadre des études cognitives.
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Adiyanto, Johannes. "Archi-text-ture: Architecting Through Writing". Architectural Research Journal (ARJ) 1, n.º 1 (12 de mayo de 2021): 1–7. http://dx.doi.org/10.22225/arj.1.1.3296.1-7.
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Architecture is often understood as a real and tangible science, in the form of space and form. This understanding is associated with the origin of the word ‘techne’ which refers to the engineering in the construction process of a building, an architectural work. Writing on new architecture developed around 1968, at a time when architectural criticism by Louis Huxtable became known although the form of writing, identification both in pictures and description, had been done since the time of the Roman Empire by Vitruvius and later interpreted by Leon Battista in the Renaissance. This paper describes descriptively several examples and categories of writing about architecture, especially in Indonesia. The study uses an exploratory study approach with reference to the theory of architectural criticism from Attoe’s understanding. The descriptive exploration of this paper shows there are at least four categories of architectural writing in Indonesia, from those aimed at creating architectural narratives to making architectural texts which are then called archi-text-ture in the paper. The paper is not a final paper, because it is the start of a long textual journey, so it is made as an archi-text-ture construction process and to open up opportunities for further interpretation and development
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Krochmalnik, Daniel. "Amaleq ou l�archi-antis�mite". Le Genre humain N�56-57, n.º 1 (2016): 319. http://dx.doi.org/10.3917/lgh.056.0319.
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Fröhlich, Ida. "Dávid változó arcai a deuteronomiumi történetírásban". Belvedere Meridionale 31, n.º 1 (2019): 25–38. http://dx.doi.org/10.14232/belv.2019.1.2.
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Studies in anthropology and cultural memory evidenced the common concept in several cultures that possessing the land by the community living on it is conditioned by the ethical conduct of their rulers. The legitimacy of kings depends on their ethical conduct and devotion to the deity who is the patron of the country and their group. Legitimacy of a new dynasty is interconnected in historical memory with the erection of a new sanctuary built by the founding member of the dynasty and consecrated to the patron deity. However, perpetrating certain sins like cultic offenses, homicide and bloodshed, sexual sins, breaking oaths call for punishment in the form of plagues, attacks of foreign hordes, the fall of the dynasty, or the exile of the people. Ancient Near Eastern historiographies – including biblical Deuteronomistic historiography – are in line with this principle, and use special narrative forms to express it. The present study aims at examining the use of the elements of this ethical language in the Deuteronomistic historiography and demonstrating how they served – the exilic redactors being aware of the fall of the Judean kingdom and the fate of its dynasty – to reshape an originally ideal image of David, the founder of a dynasty, and how to make his portrait ambiguous by eliminating from and adding to the narrative elements with ethical portent.
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Raval, Amit D., Orsolya Lunacsek, Matthew J. Korn, Natasha Littleton, Niculae Constantinovici y Daniel J. George. "Real-world intensification beyond androgen deprivation therapy (ADT) in metastatic hormone sensitive prostate cancer (mHSPC) in the United States 2017-2023: An administrative claims database study." Journal of Clinical Oncology 42, n.º 16_suppl (1 de junio de 2024): e17082-e17082. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.e17082.
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e17082 Background: Severalguidelines recommended the use of androgen receptor pathway inhibitors (ARPIs) and/or docetaxel along with ADT for mHSPC based on improved clinical outcomes demonstrated in clinical trials. Given the evolving treatment landscape since 2016, there is a need to understand the translation of clinical evidence and guidelines into clinical practice. Therefore, we examined the use of, and factors associated with intensification beyond ADT in men with mHSPC. Methods: A retrospective cohort of men treated for mHSPC was selected from private insurance claims of the Komodo Research Dataset (Jan 2017-Sep 2023). Men with mHSPC were identified based on their earliest claim for metastasis on or after prostate cancer diagnosis date without evidence of castration resistance. Index date was the earliest claim of ADT following mHSPC. Continuous insurance coverage for ≥ 12 months pre- (baseline) and ≥ 4 months post-index was required. Intensification beyond ADT was defined as the addition of ARPIs, docetaxel or both within ±4 months of the index date. Multinomial regression was conducted to examine factors associated with ADT intensification. Results: The study cohort comprised of 10,717 men with mHSPC with a median age of 65 years. Most had de novo mHSPC (62%), bone-only metastases (49%), hypertension (68%), diabetes (29%), and received opioids (59%) at baseline. Overall, in addition to ADT, 28% received ARPI (abiraterone: 18%, androgen receptor inhibitors: 10%), 9% docetaxel and 2.5% ARPI + docetaxel. From 2017 to 2023, there has been an increase in the intensification of ADT with ARPI from 13% to 47% and with docetaxel + ARPI from 0.8% to 15%, while the use of ADT + docetaxel declined from 12% to 3% and ADT alone from 74% to 36%. Key factors (age, comorbidity, de novo mHSPC, bone metastases) associated with intensification with either docetaxel or ARPI are listed in Table. Conclusions: There was a linear increase in intensification with ARPI and/or docetaxel in mHSPC between 2017-2023 in the US. Findings highlight a gradual uptake of guideline-recommended treatment for men with mHSPC, while over a third are still receiving ADT alone. [Table: see text]
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Yamamoto, Masayoshi, Hisanori Morii y Shigeyuki Funabiki. "Novel Smoothing Capacitor-less ARCP Scheme Soft Switching Inverter". IEEJ Transactions on Industry Applications 130, n.º 2 (2010): 258–59. http://dx.doi.org/10.1541/ieejias.130.258.
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