Anti-CD19 monoclonal antibodies for the treatment of relapsed or refractory B-cell malignancies: a narrative review with focus on diffuse large B-cell lymphoma

Purpose: CD19 is a cell surface protein that is found on both healthy and malignant B cells. Accordingly, it has become an important target for novel treatments for non-Hodgkin lymphomas and B-cell leukaemia. Three anti-CD19 monoclonal antibodies with distinct mechanisms of action have been developed for the treatment of B-cell malignancies. Methods: We reviewed the preclinical and clinical data on the development of the newly approved anti-CD19 monoclonal antibodies blinatumomab, tafasitamab and loncastuximab tesirine, and consider their place in the treatment of relapsed or refractory B-cell malignancies. Results: Blinatumomab is a bispecific T-cell engager that binds to both CD19 on B cells and CD3 on T cells, facilitating antibody-dependent cytotoxicity. Blinatumomab significantly prolongs overall survival in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, although cytokine release syndrome and severe neurotoxicity may necessitate discontinuation. Tafasitamab, which has modified anti-CD19 Fab and Fc regions, has significantly enhanced affinity for both CD19 and effector cell receptors compared with unmodified anti-CD19. In L-MIND, tafasitamab plus lenalidomide provided an overall response rate (ORR) of 57.5% in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients non-transplant eligible. Loncastuximab tesirine is an antibody–drug conjugate that has been studied as monotherapy and in combination with ibrutinib in 3L + relapsed or refractory DLBCL. The ORR was 48.3% in a phase II trial of loncastuximab tesirine. The optimal place of anti-CD19 monoclonal antibodies in therapy has yet to be determined, but the prospect of improved outcomes for at least some patients with treatment-resistant B-cell malignancies appears likely, particularly in those with limited therapeutic options and poor prognosis

Effect of stators geometry on the resonance sensitivity of capacitive MEMS

open4openFrangi, A.; Laghi, G.; Minotti, P.; Langfelder, G.Frangi, ATTILIO ALBERTO; Laghi, Giacomo; Minotti, Paolo; Langfelder, Giacom

A new anti-neutrino detection technique based on positronium tagging with plastic scintillators

The main signature for anti-neutrino detection in reactor and geo-neutrino experiments based on scintillators is provided by the space-time coincidence of positron and neutron produced in the Inverse Beta Decay reaction. Such a signature strongly suppresses backgrounds and allows for measurements performed underground with a relatively high signal-to-background ratio. In an aboveground environment, however, the twofold coincidence technique is not sufficient to efficiently reject the high background rate induced by cosmogenic events. Enhancing the positron-neutron twofold coincidence efficiency has the potential to pave the way future aboveground detectors for reactor monitoring. We propose a new detection scheme based on a threefold coincidence, between the positron ionization, the ortho-positronium (o-Ps) decay, and the neutron capture, in a sandwich detector with alternated layers of plastic scintillator and aerogel powder. We present the results of a set of dedicated measurements on the achievable light yield and on the o-Ps formation and lifetime. The efficiencies for signal detection and background rejection of a preliminary detector design are also discussed.Comment: 18 pages, 10 figure

Modello coesivo per l’avanzamento di fratture mediante rilascio nodale di strutture discretizzate con elementi finiti

La simulazione numerica della propagazione di una frattura in MODO I, viaggiante ad elevatavelocità in un acciaio a comportamento duttile è realizzata attraverso un modello coesivo che governa ladistribuzione delle forze di rilascio nodale. Come noto, la ricerca di un valore di tensione all’apice non ha alcunsenso nel caso elastico; infatti, la tensione può essere valutata solo mediante fattori di campo. Nel caso elasto-plastico, incrudimento e softening di origine geometrica o legato al progressivo danneggiamento influisconodecisamente sull’andamento esponenziale del campo tensionale. È possibile comunque individuare un valore diriferimento, di entità finita, mediante estrapolazione delle tensioni elasto-plastiche nella zona di inizio softeningdella frattura. Tale grandezza può essere presa come fattore di riferimento per il calcolo delle forze di rilasciocoesive e quindi dell’energia dissipata. Nel lavoro viene discusso come determinare, dal campo di tensioneelasto-plastico locale, il valore che governa la zona coesiva al variare del T-stress

A five-year survey for plastic surgery malpractice claims in Rome, Italy

(1) Introduction: Medical malpractice claims against both health institutions and physicians are a crucial topic in Italy, as well as in other countries, particularly regarding civil proceedings. Our study reports an analysis of all of the malpractice judgments concerning plastic surgery decided in the Civil Court of Rome between 2012 and 2016. (2) Methods: the database of the Observatory Project on Medical Responsibility (ORMe) was analyzed, which collects all of the judgments of the Civil Court of Rome, that is, the first instance district court. Therefore, neither the jurisprudence of the second level court nor that of the Supreme Court was taken into account. (3) Results: 144 judgments concerning plastic surgery were delivered in the five-year period of 2012–2016 (corresponding to 10.6% of total professional liability verdicts of the Civil Court of Rome in the same period). In 101/144 cases (70.14%), the claim was accepted. A total of €4,727,579.00 was paid in compensation for plastic surgery malpractice claims, with a range from a minimum amount of €1555.96 to a maximum amount of €1,425,155.00 and an average compensation of €46,807.71 per claim that was significantly lower compared to other surgical disciplines. (4) Conclusions: Our data confirm that the analyzed branch has a high litigation rate, with a prevalence of convictions for cosmetic procedures over reconstructive ones, both for malpractice and for violation of the informed consent. Plastic surgery is also confirmed among those branches in which the professionals are more frequently sued compared to health institutions

Modello coesivo per l’avanzamento di fratture mediante rilascio nodale di strutture discretizzate con elementi finiti

La simulazione numerica della propagazione di una frattura in MODO I, viaggiante ad elevatavelocità in un acciaio a comportamento duttile è realizzata attraverso un modello coesivo che governa ladistribuzione delle forze di rilascio nodale. Come noto, la ricerca di un valore di tensione all’apice non ha alcunsenso nel caso elastico; infatti, la tensione può essere valutata solo mediante fattori di campo. Nel caso elasto-plastico, incrudimento e softening di origine geometrica o legato al progressivo danneggiamento influisconodecisamente sull’andamento esponenziale del campo tensionale. È possibile comunque individuare un valore diriferimento, di entità finita, mediante estrapolazione delle tensioni elasto-plastiche nella zona di inizio softeningdella frattura. Tale grandezza può essere presa come fattore di riferimento per il calcolo delle forze di rilasciocoesive e quindi dell’energia dissipata. Nel lavoro viene discusso come determinare, dal campo di tensioneelasto-plastico locale, il valore che governa la zona coesiva al variare del T-stress

Optical properties of highly n-doped germanium obtained by in situ doping and laser annealing

High n-type doping in germanium is essential for many electronic and optoelectronic applications especially for high performance Ohmic contacts, lasing and mid-infrared plasmonics. We report on the combination of in situ doping and excimer laser annealing to improve the activation of phosphorous in germanium. An activated n-doping concentration of 8.8  ×  1019 cm−3 has been achieved starting from an incorporated phosphorous concentration of 1.1  ×  1020 cm−3. Infrared reflectivity data fitted with a multi-layer Drude model indicate good uniformity over a 350 nm thick layer. Photoluminescence demonstrates clear bandgap narrowing and an increased ratio of direct to indirect bandgap emission confirming the high doping densities achieved

Análisis de imágenes satelitales con R: patrones espaciales de la correlación cruzada de series temporales de imágenes Modis de temperatura y productividad vegetal

R se perfila como uno de los entornos más completos para realizar análisis de datos espacio-temporales de grandes bases de datos abiertos satelitales. Presentamos un ejemplo de análisis de series temporales de productos MODIS para identificar áreas con distinto patrón de funcionamiento ecológico, usando medidas de correlación cruzada de series de tiempo y agrupamiento con redes neuronales autoorganizadas.Sociedad Argentina de Informática e Investigación Operativ

Análisis de imágenes satelitales con R: patrones espaciales de la correlación cruzada de series temporales de imágenes Modis de temperatura y productividad vegetal

R se perfila como uno de los entornos más completos para realizar análisis de datos espacio-temporales de grandes bases de datos abiertos satelitales. Presentamos un ejemplo de análisis de series temporales de productos MODIS para identificar áreas con distinto patrón de funcionamiento ecológico, usando medidas de correlación cruzada de series de tiempo y agrupamiento con redes neuronales autoorganizadas.Sociedad Argentina de Informática e Investigación Operativ

Análisis de imágenes satelitales con R: patrones espaciales de la correlación cruzada de series temporales de imágenes Modis de temperatura y productividad vegetal

R se perfila como uno de los entornos más completos para realizar análisis de datos espacio-temporales de grandes bases de datos abiertos satelitales. Presentamos un ejemplo de análisis de series temporales de productos MODIS para identificar áreas con distinto patrón de funcionamiento ecológico, usando medidas de correlación cruzada de series de tiempo y agrupamiento con redes neuronales autoorganizadas.Sociedad Argentina de Informática e Investigación Operativ