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This paper presents a novel strategy for the synchronization of grid-following Voltage Source Converters (VSCs) in power systems with low rotational inertia. The proposed synchronization unit is based on emulating the physical properties of an induction machine and capitalizes on its inherent grid-friendly properties such as self-synchronization, oscillation damping, and standalone capabilities. To this end, the mathematical model of an induction machine is analyzed and reformulated to obtain the unknown grid frequency by processing the voltage and current measurements at the converter output. This eliminates the need for a Phase-Locked Loop (PLL) unit, traditionally employed in grid-following VSC control schemes, while simultaneously preserving the system- and device-level control. Furthermore, we provide the appropriate steps for obtaining an index-1 DAE representation of the induction-machine-based synchronization unit, suitable for stability analysis. Our analysis shows that replacing the PLL unit with the virtual induction machine-based synchronization may considerably improve the stability of systems with grid-following converters and facilitate the frequency containment. Furthermore, we validate the performance of the proposed synchronization unit through simulations and provide recommendations for its tuning., IEEE Transactions on Power Systems, 38 (3), ISSN:0885-8950, ISSN:1558-0679

Large-scale integration of renewable generation, usually interfaced to the network through power electronics, has led to drastic changes in power system dynamics. This paper presents novel insights into stability properties of such systems. For that purpose, a high-fidelity dynamic model of a generic low-inertia power system has been developed. The full-order, state-of-the-art control schemes of both synchronous and converter-based generators are included, with the latter differentiating between grid-forming and grid-following mode of operation. Furthermore, the dynamics of transmission lines and loads are captured in the model. Using modal analysis techniques such as participation factors and parameter sensitivity, the most vulnerable segments of the system are determined and the adverse effects of timescale coupling and control interference are investigated. More precisely, this work characterizes the maximum permissible penetration levels of inverter-based generation as well as the nature of the associated unstable modes and the underlying dynamics. Finally, potential directions for improving the system stability margin under different generation portfolios are proposed for several benchmark systems.

An increasing penetration of renewable generation has led to reduced levels of rotational inertia and damping in the power network. The consequences are higher vulnerability to disturbances and deterioration of the dynamic response of the system. To overcome these challenges, novel converter control schemes that provide virtual inertia and damping have been introduced, which raises the question of optimal distribution of such devices throughout the network. This paper presents a comprehensive framework for performance-based allocation of virtual inertia and damping to the converter-interfaced generators in a detailed low-inertia system. This is achieved through an iterative, eigensensitivity-based optimization algorithm that determines the optimal controller gains while simultaneously preserving small-signal stability and ensuring that the damping ratio and frequency response after disturbances are kept within acceptable limits. Two conceptually different problem formulations are presented and validated on a modified version of the well known Kundur's two-area system as well as a larger 59-bus South-East Australian network.

The experience of third-generation tyrosine kinase inhibitor ponatinib treatment in Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph'+ ALL) patients post-allogeneic transplantation is limited. We retrospectively collected data on 25 Ph'+ ALL patients who were started on ponatinib after allogeneic transplantation between July 2015 and July 2019 from nine transplantation centers in Italy. Ponatinib was given in prophylaxis in five (20%), as pre-emptive treatment in seven (28%), and as salvage therapy in thirteen (52%) patients. It was combined with donor leukocyte infusions in ten patients. Half of the patients (12/25) harbored T315I mutation of BCR/ABL1, while in the remaining mutational analysis was negative or not performed. Among the 20 patients who received ponatinib as pre-emptive/salvage treatment, complete molecular response was achieved in 15 (75%) patients. Estimated overall survival at 2-year post-initiation of treatment in the whole cohort was 65% (respectively 60%, 60%, and 78% for the prophylaxis, pre-emptive, and salvage therapy groups). In patients with T315I-positive mutational status, the estimated 2-year survival was 40%. Fourteen patients (56%) experienced toxicity, requiring temporary or definitive suspension of treatment. In conclusion, treatment of Ph'+ ALL patients with ponatinib after transplantation is effective, although the question of adequate drug dose and treatment duration remains unanswered.

Among the myeloproliferative diseases, myelofibrosis is a widely heterogeneous entity characterized by a highly variable prognosis. In this context, several prognostic models have been proposed to categorize these patients appropriately. Identifying who deserves more invasive treatments, such as bone marrow transplantation, is a critical clinical need. Age, complete blood count (above all, hemoglobin value), constitutional symptoms, driver mutations, and blast cells have always represented the milestones of the leading models still used worldwide (IPSS, DIPSS, MYSEC-PM). Recently, the advent of new diagnostic techniques (among all, next-generation sequencing) and the extensive use of JAK inhibitor drugs have allowed the development and validation of new models (MIPSS-70 and version 2.0, GIPSS, RR6), which are continuously updated. Finally, the new frontier of artificial intelligence promises to build models capable of drawing an overall survival perspective for each patient. This review aims to collect and summarize the existing standard prognostic models in myelofibrosis and examine the setting where each of these finds its best application.

Acquired hemophilia should be evaluated in pediatric patients with bleeding and isolated prolonged aPTT. Immunosuppressive treatment should be initiated even in minor bleedings. Bypassing agents like rFVIIa can be used in children with success.

Chemotherapy-induced hepatic toxicity is a frequent problem, with some patients developing liver failure. Unfortunately, therapeutic possibilities are still lacking. Here, we describe two patients that developed important liver toxicity in our center following high-dose chemotherapy and were successfully treated with high-dose N-acetylcysteine.

In this paper, the Unit Commitment (UC) problem in a power network with low levels of rotational inertia is studied. Frequency-related constraints, namely the limitation on Rate-of-Change-of-Frequency (RoCoF), frequency nadir and steady-state frequency error, are derived from a uniform system frequency response model that incorporates dynamics and controls of both synchronous generators and grid-forming inverters. These constraints are then included into a stochastic UC formulation that accounts for wind power and equipment contingency uncertainties using a scenario-tree approach. In contrast to the linear RoCoF and steady-state frequency error constraints, the nadir constraint is highly nonlinear. To preserve the mixed-integer linear formulation of the stochastic UC model, we propose a computationally efficient approach that allows to recast the nadir constraint by introducing appropriate bounds on relevant decision variables of the UC model. This method is shown to be generally more accurate and computationally more efficient for medium-sized networks than a piece-wise linearization method adapted from the literature. Simulation results for a modified IEEE RTS-96 system revealed that the inclusion of inertia-related constraints significantly influences the UC decisions and increases total costs, as more synchronous machines are forced to be online to provide inertial response.

Background/aim Imatinib (IM) is the standard-of-care treatment for most chronic myeloid leukemia (CML) patients in chronic phase (CP). However, some patients suffer from low-grade side-effects that, in the long run, severely affect the quality of life and require treatment discontinuation due to toxicities. Fortunately, there are several therapeutic alternatives for these patients. Among them, the second-generation tyrosine kinase inhibitor dasatinib (DAS), used as second-line treatment, has shown to be a valid option in patients with CP-CML after intolerance to prior IM. Patients and methods Herein, we report on seven CP-CML patients who achieved a stable major molecular response (MMR) with IM-therapy, but were shifted to DAS treatment due to recurrent low-grade IM-intolerances (grades 1-2). Results and conclusion All patients received conventional DAS treatment with a median daily dose of 83.3 mg. Treatment was well tolerated and side-effects were mild. In addition, after a median follow-up of 25 months (range=24-43 months) a deep molecular response (DMR) (either MR4 or MR4.5) was achieved in all patients after 24 months of treatment. This finding, although limited to a small cohort of CP-CML patients, supports the view that a therapy switch from IM to DAS induces a reduction of symptom burden, improves patient compliance and shows clinical efficacy in achieving and sustaining deep molecular responses.

The undergoing transition from conventional to converter-interfaced renewable generation leads to significant challenges in maintaining frequency stability due to declining system inertia. In this paper, a novel control framework for Synthetic Inertia (SI) provision from Wind Turbines (WTs) is proposed, which eliminates the secondary frequency dip and allows the dynamics of SI from WTs to be analytically integrated into the system frequency dynamics. Furthermore, analytical system frequency constraints with SI provision from WTs are developed and incorporated into a stochastic system scheduling model, which enables the provision of SI from WTs to be dynamically optimized on a system level. Several case studies are carried out on a Great Britain 2030 power system with different penetration levels of wind generation and inclusion of frequency response requirements in order to assess the performance of the proposed model and analyze the influence of the improved SI control scheme on the potential secondary frequency dip. The results demonstrate that the inclusion of SI provision from WTs into UC can drastically impact the overall system costs., Comment: 10 pages, accepted by IEEE Transaction on Power System

Background: Febrile neutropenia (FN) is a medical emergency that requires urgent evaluation, timely administration of empiric broad-spectrum antibiotics and careful monitoring in order to optimize the patient’s outcome, especially in the setting of both allogeneic and autologous hematopoietic stem cell transplant (ASCT). Methods: In this real-life retrospective study, a total of 49 consecutive episodes of FN were evaluated in 40 adult patients affected by either multiple myeloma (thirty-eight) or lymphoma (eleven), following ASCT, with nine patients having fever in both of the tandem transplantations. Results: Febrile neutropenia occurred a median of 7 days from ASCT. Median duration of FN was 2 days, with 25% of population that had fever for at least four days. Ten patients had at least one fever spike superior to 39 °C, while the median number of daily fever spikes was two. Twenty patients had positive blood cultures with XDR germs, namely Pseudomonas aeruginosa and Klebsiella pneumoniae, present in seven cases. ROC analysis of peak C-reactive protein (CRP) values was conducted based on blood culture positivity and a value of 12 mg/dL resulted significant. Onset of prolonged fever with a duration greater than 3 days was associated with the presence of both a peak number of three or more daily fever spikes (p = 0.02) and a body temperature greater than 39 °C (p = 0.04) based on odds ratio (OR). Blood culture positivity and peak CRP values greater than 12 mg/dL were also associated with prolonged fever duration, p = 0.04, and p = 0.03, respectively. The probability of blood culture positivity was also greater in association with fever greater than 39 °C (p = 0.04). Furthermore, peak CRP values below the cut-off showed less probability of positive blood culture (p = 0.02). Conclusions: In our study, clinical characteristics of fever along with peak CRP levels were associated with a higher probability of both prolonged fever duration and positive blood culture, needing extended antibiotic therapy.

Background: Clinical course of COVID-19 depends on several patient-specific risk factors, including immune function, that is largely compromised in cancer patients. Methods: We prospectively evaluated 120 adult consecutive patients (including 34 cases of COVID-19 breakthrough after two full doses of BNT162b2 vaccine) with underlying hematological malignancies and a SARS-CoV-2 infection, in terms of patient’s clinical outcome. Results: Among fully vaccinated patients the achievement of viral clearance by day 14 was more frequent than in unvaccinated patients. Increased 30-day mortality was associated with presence of active/progressing disease and absolute monocyte count lower than 400 cells/uL. Results of multivariable analysis in unvaccinated patients showed that the pre-infection absolute count of monocytes less or equal to 400 cells/mmc, active or progressive disease of the underlying hematological malignancy, the COVID-19 severity identified by hospitalization requirement and lack of viral clearance at 14 days were independent predictors of 1-year overall survival. Conclusions: Taken together, our results indicate that absolute monocyte count determined one month before any documented SARS-CoV-2 infection could identify patients affected by hematological neoplasms with increased risk of inferior overall survival.

Deferasirox (DFX) is used for the management of iron overload (IOL) in many haematological malignancies including myelofibrosis (MF). The ‘RUX-IOL’ study retrospectively collected 69 MF patients treated with ruxolitinib (RUX) and DFX for IOL to assess: safety, efficacy in term of iron chelation response (ICR) and erythroid response (ER), and impact on overall survival of the combination therapy. The RUX–DFX therapy was administered for a median time of 12.4months (interquartile range 3.1–71.2). During treatment, 36 (52.2%) and 34 (49.3%) patients required RUX and DFX dose reductions, while eight (11.6%) and nine (13.1%) patients discontinued due to RUX- or DFX-related adverse events; no unexpected toxicity was reported. ICR and ER were achieved by 33 (47.8%) and 32 patients (46.4%) respectively. Thirteen (18.9%) patients became transfusion-independent. Median time to ICR and ER was 6.2 and 2months respectively. Patients achieving an ER were more likely to obtain an ICR also (p=0.04). In multivariable analysis, the absence of leukocytosis at baseline (p=0.02) and achievement of an ICR at any time (p=0.02) predicted improved survival. In many MF patients, the RUX–DFX combination provided ICR and ER responses that correlated with improved outcome in the absence of unexpected toxicities. This strategy deserves further clinical investigation.

Simple Summary According to the International Myeloma Working Group diagnostic criteria serum free light chain (sFLC) assay is recommended for disease monitoring in oligo-secretory and micromolecular multiple myeloma (MM). However, normo-secretory patients could suffer from oligo-secretory/micromolecular escape at disease relapse, making it difficult to monitor disease relapse with serum protein electrophoresis alone. The possibility of a simple and manageable biochemical exam able to predict either future treatment response at disease relapse or relapse type in the course of treatment could be of great aid. In this work, we retrospectively analyzed the occurrence of oligo-secretory/micromolecular escape at disease relapses and its impact on disease outcome. Moreover, we have retrospectively evaluated the role of sFLC ratio and involved sFLC at disease relapse in a historical real-life single-center cohort of MM patients that underwent at least three lines of treatment. Abstract Background: In the era of novel drugs a growing number of multiple myeloma (MM) patients are treated until disease progression. Serum free light chain (sFLC) assay is recommended for disease monitoring in oligo-secretory and micromolecular MM. Methods: In this real-life survey, a total of 130 relapsed/refractory MM patients treated at our center with at least three lines were investigated as a retrospective cohort. Results: The median age at diagnosis was 64 years and more than half of patients were male. A total of 24 patients (18%) had oligo-secretory/micromolecular disease at diagnosis. More than 20% of 106 normo-secretory patients had oligo-secretory/micromolecular escape. In order to evaluate potential role of sFLC assay before (“pre”) and after (“post”) every treatment line, involved serum free light chain values (iFLC) less than 138 mg/mL and serum free light chain ratios (FLCr)