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Fractional calculus is a mathematical framework that has attracted considerable interest from mathematicians, physicists, and engineers. Among its applications, the use of fractional calculus in the automatic control field has led to interesting results, such as more robust controllers, compared to their integer-order counterparts. The proposed work utilizes the physical realization of a solid-state fractional-order capacitor for the implementation of a fractional-order lead compensator. The proposed capacitor is realized using a carbon black-based dielectric. Therefore, a fully analog closed-loop system implementation is realized. A suitable case study is conducted to validate the controller performance, both from simulations and experimentally. The obtained results further confirm the possibility of realizing and applying a fully analog fractional-order controller. • A realization of a fractional order capacitor is used to realize a Fractional Order Compensator. • The proposed capacitor is realized by using a Carbon-Black-based dielectric. • A fully analog closed loop system implementation is therefore realized. • Results are validated with both simulations and experiments. • The isodamping property has verified. [ABSTRACT FROM AUTHOR]

Fractional-order calculus has been used for generalizing many modern and classical control theories including the well establish PID paradigm. The obtained controllers, of non-integer order, must be approximated with high order integer ones, in order to be realized. Successively, analog or digital implementations are used for the real world applications. This approach offers the hip to a classical criticism to fractional calculus. Why design a fractional-order system, which is usually of low order, if you need a high order system to implement it? In order to face this problem, in this paper, a fractional-order capacitor, more specifically a Constant Phase Device, is applied for implementing a first order fractional transfer function. Due to the intrinsic nature of the realized device, just one capacitor is needed for the implementation, avoiding therefore the need of high order RC approximation. Furthermore a fractional-order Wien oscillator and a chaotic Duffing circuit are presented confirming the potentiality of the proposed device in realizing fractional order circuits. [ABSTRACT FROM AUTHOR]

The article focuses on a study which states that CD34+ selected haematopoietic stem cell (HSC), not preceded by any immunosuppressive therapy, offer an effective treatment for graft failure. The researchers here report a case of graft failure occurring after a T-cell replete allogeneic HSC transplantation that was successfully treated using an infusion of CD34+ immuno-selected HSC without any prior immunosuppression. It was concluded that graft dysfunction may be the result of microenvironment abnormalities pre-existing the transplant or of toxic effects toward HSC from viral infections or drugs. Graft dysfunction may also be due to an immunological reaction.

Objectives: The study aimed to evaluate the utilization of frontline TKI therapy in a large cohort of elderly CP-CML patients., Methods: A retrospective analysis was conducted on 332 CP-CML patients aged 75 years or older among 1929 diagnosed from January 2012 to December 2019 followed at 36 participating Hematology Centers involved in the "Campus CML" project., Results: Among the patients analyzed, 85.8% received imatinib (IM) while 14.2% received second-generation TKIs (2G-TKI), 59.5% dasatinib, and 40.5% nilotinib. Most patients initiated IM at standard dose (67.3%) while 32.7% at reduced dose. A similar trend was observed with 2G-TKIs. The cumulative incidence of permanent TKI discontinuation at 12 months was 28.4%, primarily due to primary resistance (10.1%) and extra-hematologic toxicity (9.5%), with no significant difference between IM and 2G-TKI groups. Following the introduction of generic IM in Italy in 2018, IM usage increased significantly compared with 2G-TKIs., Conclusions: IM was in our Centers the preferred frontline therapy for older CP-CML patients, with increasing utilization after the introduction of generic formulations. However, 2G-TKIs are still used in a substantial proportion of patients, suggesting individualized physician assessments regarding patient suitability and expectations. Further investigation is needed to assess efficacy and safety of reduced TKI doses in this patient population., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: Imatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic-phase chronic myeloid leukemia (CP-CML). The choice of TKI is based on a combined evaluation of the patient's and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP-CML to correlate the choice with the patient's features., Methods: A total of 1967 patients with CP-CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second-generation (2G) TKI., Results: Second-generation TKIs were chosen for most patients aged <45 years (69.2%), whereas imatinib was used in 76.7% of patients aged >65 years (p < .001). There was a predominant use of imatinib in intermediate/high European long-term survival risk patients (60.0%/66.0% vs. 49.7% in low-risk patients) and a limited use of 2G-TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with >3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018-2019 compared to 2012-2017 (53.2%; p = .002). In multivariable analysis, factors correlated with imatinib use were age > 65 years, spleen size, the presence of comorbidities, and ≥3 concomitant medications., Conclusions: This observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP-CML, with 2G-TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first-line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate imatinib responses. Experimental Design: We correlated BCR-ABL/GUS IS and BCR-ABL/ABL transcripts at diagnosis with the outcome-defined by the 2013 European LeukemiaNet recommendations-of 272 patients newly diagnosed with CML receiving imatinib 400 mg/daily. Applying receiver-operating characteristic curves, we defined BCR-ABL/GUS IS and BCR-ABL/ABL levels associated with lower probabilities of optimal response, failure-free (FFS), event-free (EFS), transformation-free (TFS), and overall survival (OS). Results: With a median follow-up of 60 months, 65.4% of patients achieved an optimal response (OR), 5.6% were classified as "warnings," 22.4% failed imatinib, and 6.6% switched to a different TKI because of drug intolerance. We recorded 19 deaths (6.9%), seven (2.5%) attributable to disease progression. We found that higher BCR-ABL/GUS IS levels at diagnosis were associated with inferior rates of OR ( P < 0.001), FFS ( P < 0.001), and EFS ( P < 0.001). Elevated BCR-ABL/GUS IS levels were also associated with lower rates of TFS ( P = 0.029) but not with OS ( P = 0.132). Similarly, high BCR-ABL/ABL levels at diagnosis were associated with inferior rates of OR ( P = 0.03), FFS ( P = 0.001), and EFS ( P = 0.005), but not with TFS ( P = 0.167) or OS ( P = 0.052). However, in internal validation experiments, GUS outperformed ABL in samples collected at diagnosis as the latter produced 80% misclassification rates. Conclusions: Our data suggest that high BCR-ABL transcripts at diagnosis measured using GUS as a reference gene identify patients with CML unlikely to benefit from standard-dose imatinib. Clin Cancer Res; 23(23); 7189-98. ©2017 AACR ., (©2017 American Association for Cancer Research.)

We designed intermediate dose etoposide + G-CSF 16 microg/kg as a Peripheral Blood Stem Cell (PBSC) mobilization schedule suitable for outpatient administration. Forty-one Lymphoma patients received intermediate dose etoposide (200 mg/m(2) i.v. day +1, +2, +3) +G-CSF 16 microg/kg/day. Results of PBSC mobilization in these patients were compared with those of a group of 37 lymphoma patients mobilized using cyclophosphamide (CTX) at dosage of 4 g/m(2) + G-CSF 10 microg/kg/die. Mean peak of CD34+ cells achieved in P.B. and total CD34+ cells harvested were higher in patients mobilized with intermediate dose etoposide (p = 0.003 and p = 0.004, respectively). After transplantation recovery of polymorphonucleate neutrophils (PMN) > 0.5 x 10(9)/L did not differ significantly between groups: 11.7 days in intermediate dose etoposide group and 11.5 days in CTX group (p = 0.7). Intermediate dose etoposide + G-CSF 16 microg/kg resulted in a maximum length of neutropenia (PMN < 0.5 x 10(9)/L) of 2 days and neutropenic fever was registered during only 3/41 courses (7.3%). Intermediate dose etoposide + G-CSF 16 microg/kg is a highly effective mobilizing therapy, further, it has the advantage of low hematologic toxicity and can be easily administered as outpatient treatment.