Laser-driven production with advanced targets of Copper-64 for medical applications

Radionuclides are of paramount importance in nuclear medicine both for clinical uses and radiopharmaceutical production. Among the others, nuclides suitable for theranostics like Copper-64 are particularly attractive since they can play both a diagnostic and therapeutic role. In the last years, the growing demand for these nuclides stimulated the research of new solutions, along with cyclotrons already in use, for their production. In this respect, a promising alternative is laser-driven proton accelerators based on the interaction of superintense laser pulses with target materials. Because of their potential compactness and flexibility, they are under investigation for several applications ranging from materials science to nuclear medicine. Moreover, the use of advanced Double-Layer targets (DLTs) was identified as a viable route to increase the number and energy of the accelerated protons to satisfy the requirements of demanding applications. In this contribution, we numerically investigate the use of DLT-based laser-driven sources for Copper-64 production. We show that activities relevant to pre-clinical studies can be achieved with an existing 150 TW laser and DLTs. Moreover, we extend the discussion by considering a broad range of laser systems by exploiting a theoretical model. Our results can guide the choice of laser and target parameters for future experimental investigations

Ultra-intense laser interaction with nanostructured near-critical plasmas

Near-critical plasmas irradiated at ultra-high laser intensities (I > 1018W/cm2) allow to improve the performances of laser-driven particle and radiation sources and to explore scenarios of great astrophysical interest. Near-critical plasmas with controlled properties can be obtained with nanostructured low-density materials. By means of 3D Particle-In-Cell simulations, we investigate how realistic nanostructures influence the interaction of an ultra-intense laser with a plasma having a near-critical average electron density. We find that the presence of a nanostructure strongly reduces the effect of pulse polarization and enhances the energy absorbed by the ion population, while generally leading to a significant decrease of the electron temperature with respect to a homogeneous near-critical plasma. We also observe an effect of the nanostructure morphology. These results are relevant both for a fundamental understanding and for the foreseen applications of laser-plasma interaction in the near-critical regime

Laser cleaning of diagnostic mirrors from tokamak-like carbon contaminants

This paper presents a laboratory-scale experimental investigation of laser cleaning of diagnostic First Mirrors (FMs). Redeposition of contaminants sputtered from tokamak first wall onto FMs surface could dramatically decrease their reflectivity in an unacceptable way for the functioning of the plasma diagnostic systems. Laser cleaning is a promising solution to tackle this issue. In this work, pulsed laser deposition was exploited to produce rhodium films functional as FMs and to deposit onto them carbon contaminants with tailored features, resembling those found in tokamaks. The same laser system was also used to perform laser cleaning experiments by means of a sample handling procedure that allows to clean some cm(2) in few minutes. The cleaning effectiveness was evaluated in terms of specular reflectivity recovery and mirror surface integrity. The effect of different laser wavelengths (lambda = 1064, 266 nm) on the cleaning process is also addressed

CD22 expression in b-cell acute lymphoblastic leukemia: Biological significance and implications for inotuzumab therapy in adults

CD22 is a surface molecule expressed early during the ontogeny of B cells in the bone marrow and spleen, and can be found on B cells isolated from the different lymphoid compartments in humans. CD22 is expressed by most blasts from the majority (60–90%) of B-cell acute lymphoblastic leukemia (B-ALL). Current therapies in adults with newly diagnosed B-ALL are associated with complete remission (CR) rates of 50–90%. However, 30–60% of these patients relapse, and only 25–40% achieve disease-free survival of three years or more. Chemotherapy regimens for patients with refractory/relapsed B-ALL are associated with CR rates ranging from 31% to 44%. Novel immune-targeted therapies, such as blinatumomab and inotuzumab (a humanized anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic agent calicheamicin), provide potential means of circumventing chemo-refractory B-ALL cells through novel mechanisms of action. Eighty percent of inotuzumab-treated B-ALL patients may achieve a CR state. This review is focused on the biological and clinical activities of CD22 antibodies in BALL, and provides evidence about the potential role played by qualitative and quantitative analysis of the CD22 molecule on individual B-ALL blasts in predicting the depletion of leukemic cells, and, ultimately, leading to better clinical response rates

2q37 deletions in patients with an albright hereditary osteodystrophy phenotype and PTH resistance

Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects. PHP subtypes are defined by the presence/absence of specific clinical/biochemical features. PHP1A is characterized by resistance to multiple hormones with features of Albright hereditary osteodystrophy (AHO), while pseudopseudohypoparathyroidism (PPHP) is characterized by AHO in the absence of PTH resistance. Small subsets of PHP and PPHP patients without known molecular defects have been re-diagnosed as being affected by the brachydactyly-mental retardation syndrome (BDMR), also known as the AHO-like syndrome. This study aimed to analyse 24 PHP1A and 51 PPHP patients without a molecular diagnosis for the presence of BDMR-associated 2q37 deletions to improve the differential diagnosis and to identify features that might help to avoid a misdiagnosis. Molecular investigations identified 4 deletions in 4 unrelated patients. The affected patients showed a combination of the most pathognomonic AHO features. Of note, 3 of the patients also displayed mild PTH resistance, and none of the patients developed ectopic ossifications. Our work confirmed the rarity of the misdiagnosis of BDMR in PHP patients through the identification of 4 patients bearing a 2q37 deletion in a cohort of 73 PHP patients (5.3%). Three patients with the deletion presented a PHP1A phenotype in the absence of any BDMR-specific findings. Further studies on larger case series are needed to elucidate the overlap between these clinical entities and to allow the early identification of patients

In situ cleaning of diagnostic first mirrors: An experimental comparison between plasma and laser cleaning in ITER-relevant conditions

This paper presents an experimental comparison between the plasma cleaning and the laser cleaning techniques of diagnostic first mirrors (FMs). The re-deposition of contaminants sputtered from a tokamak first wall onto FMs could dramatically decrease their reflectance in an unacceptable way for the proper functioning of plasma diagnostic systems. Therefore, suitable in situ cleaning solutions will be required to recover the FMs reflectance in ITER. Currently, plasma cleaning and laser cleaning are considered the most promising solutions. In this work, a set of ITER-like rhodium mirrors contaminated with materials tailored to reproduce tokamak redeposits is employed to experimentally compare plasma and laser cleaning against different criteria (reflectance recovery, mirror integrity, time requirement). We show that the two techniques present different complementary features that can be exploited for the cleaning of ITER FMs. In particular, plasma cleaning ensures an excellent reflectance recovery in the case of compact contaminants, while laser cleaning is faster, gentler, and more effective in the case of porous contaminant. In addition, we demonstrate the potential benefits of a synergistic solution which combines plasma and laser cleaning to exploit the best features of each technique

First case of typhoid fever due to extensively drug-resistant Salmonella enterica serovar typhi in Italy

Typhoid fever is a potentially severe and occasionally life-threatening bacteraemic illness caused by Salmonella enterica serovar Typhi (S. Typhi). In Pakistan, an outbreak of extensively drug-resistant (XDR) S. Typhi cases began in November 2016. We report on a five-year-old boy who contracted enteric fever while travelling in Pakistan and was diagnosed after returning to Italy in September 2019. Blood culture isolated Salmonella enterica serovar Typhi that was XDR to all first-line antibiotics, including ceftriaxone and fluoroquinolones. Empiric therapy was switched to meropenem, and the patient recovered completely. Whole-genome sequencing showed that this isolate was of haplotype H58. The XDR S. Typhi clone encoded a chromosomally located resistance region and harbored a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum β-lactamase and the qnrS fluoroquinolone resistance gene. This is the first case of typhoid fever due to XDR S. Typhi detected in Italy and one of the first paediatric cases reported outside Pakistan, highlighting the need to be vigilant for future cases. While new vaccines against typhoid are in development, clinicians should consider adapting their empiric approach for patients returning from regions at risk of XDR S. Typhi outbreak with typhoid symptoms

Improved Molecular Diagnosis of McCune-Albright Syndrome and Bone Fibrous Dysplasia by Digital PCR

McCune-Albright syndrome (MAS) is a rare congenital disorder characterized by the association of endocrine and nonendocrine anomalies caused by somatic activating variants of GNAS. The mosaic state of variants makes the clinical presentation extremely heterogeneous depending on involved tissues. Biological samples bearing a low level of mosaicism frequently lead to false-negative results with an underestimation of causative molecular alterations, and the analysis of biopsies is often needed to obtain a molecular diagnosis. To date, no reliable analytical method for the noninvasive testing of blood is available. This study was aimed at validating a novel and highly sensitive technique, the digital PCR (dPCR), to increase the detection rate of GNAS alterations in patients with a clinical suspicion of MAS and, in particular, in blood. We screened different tissues (blood, bone, cutis, ovary, and ovarian cyst) collected from 54 MAS patients by different technical approaches. Considering blood, Sanger was unable to detect mutations, the allele-specific PCR and the co-amplification at lower denaturation temperature had a 9.1% and 18.1% detection rate, respectively, whereas the dPCR reached a 37.8% detection rate. In conclusion, the dPCR resulted in a cost-effective, reliable, and rapid method allowing the selective amplification of low-frequency variants and able to improve GNAS mutant allele detection, especially in the blood