Near surface quantitative precipitation estimation (QPE) from weather radar measurements is an important task for feeding hydrological models, limiting the impact of severe rain events at the ground ...as well as aiding validation studies of satellite-based rain products. To date, several works have analyzed the performance of various QPE algorithms using actual and synthetic experiments, possibly trained by measurement of particle size distributions and electromagnetic models. Most of these studies support the use of dual polarization radar variables not only to ensure a good level of data quality but also as a direct input to rain estimation equations. One of the most important limiting factors in radar QPE accuracy is the vertical variability of particle size distribution, which affects all the acquired radar variables as well as estimated rain rates at different levels. This is particularly impactful in mountainous areas, where the sampled altitudes are likely several hundred meters above the surface. In this work, we analyze the impact of the vertical profile variations of rain precipitation on several dual polarization radar QPE algorithms when they are tested in a complex orography scenario. So far, in weather radar studies, more emphasis has been given to the extrapolation strategies that use the signature of the vertical profiles in terms of radar co-polar reflectivity. This may limit the use of the radar vertical profiles when dual polarization QPE algorithms are considered. In that case, all the radar variables used in the rain estimation process should be consistently extrapolated at the surface to try and maintain the correlations among them. To avoid facing such a complexity, especially with a view to operational implementation, we propose looking at the features of the vertical profile of rain (VPR), i.e., after performing the rain estimation. This procedure allows characterization of a single variable (i.e., rain) when dealing with vertical extrapolations. In this work, a definition of complex orography is also given, introducing a radar orography index to objectively quantify the degree of terrain complexity when dealing with radar QPE in heterogeneous environmental scenarios. Three case studies observed by the research C-band polarization agility Doppler radar named Polar 55C, managed by the Institute of Atmospheric Sciences and Climate (ISAC) at the National Research Council of Italy (CNR), were used to prove the concept of VPR. Our results indicate that the combined algorithm, which merges together differential phase shift (Kdp), single polarization reflectivity factor (Zhh), and differential reflectivity (Zdr), once accurately processed, in most cases performs better among those tested and those that make use of Zhh alone, Kdp alone, and Zhh, and Zdr. Improvements greater than 25% are found for the total rain accumulations in terms of normalized bias when the VPR extrapolation is applied.
Hematologic patients show lower responses to SARS-CoV-2 vaccines, but predictors of seroconversion are lacking. In this prospective cohort study, hematologic patients undergoing SARS-CoV-2 mRNA ...vaccination at a single center in Milan, Italy, were sampled for anti-Spike and anti-Nucleocapsid IgG titer at 5 ± 1 weeks and at 3 months from the second vaccine dose. Patients (
= 393) received either BNT162b2 (Pfizer-BioNTech, 48%) or MRNA-1273 (Moderna, 52%), and 284 (72%) seroconverted and 100% persisted at 3 months. Non-response was higher in chronic lymphocytic leukemia (CLL) and lymphoma patients, and in those treated with small molecules and monoclonal antibodies. In myeloid neoplasms, lower responses were detected in patients with acute myeloid leukemia treated with venetoclax plus hypomethylating agents and in patients with myelofibrosis receiving ruxolitinib. Multivariable analysis showed that seroconversion was favorably associated with a diagnosis other than indolent lymphoma/CLL OR 8.5 (95% CI 4.1-17.6), lack of B-cell-depleting therapy OR 3.15 (1.7-5.9), and IgG levels within the normal range OR 2.2 (1.2-4.2). We developed a simple algorithm according to these 3 risk factors (A) diagnosis of indolent lymphoma/CLL, (B) B-cell-depleting treatment, and (C) low IgG to predict non-response. IgG levels and treatment may be modifiable risk factors and should be considered for timing of vaccine administration.
Lack of demonstrable mutations affecting
, or
driver genes within the spectrum of
-negative myeloproliferative neoplasms (MPNs) is currently referred to as a triple-negative genotype, which is found ...in about 10% of patients with essential thrombocythemia (ET) and 5-10% of those with primary myelofibrosis (PMF). Very few papers are presently available on triple-negative ET, which is basically described as an indolent disease, differently from triple-negative PMF, which is an aggressive myeloid neoplasm, with a significantly higher risk of leukemic evolution. The aim of the present study was to evaluate the bone marrow morphology and the clinical-laboratory parameters of triple-negative ET patients, as well as to determine their molecular profile using next-generation sequencing (NGS) to identify any potential clonal biomarkers. We evaluated a single-center series of 40 triple-negative ET patients, diagnosed according to the 2017 WHO classification criteria and regularly followed up at the Hematology Unit of our Institution, between January 1983 and January 2019. In all patients, NGS was performed using the Illumina Ampliseq Myeloid Panel; morphological and immunohistochemical features of the bone marrow trephine biopsies were also thoroughly reviewed. Nucleotide variants were detected in 35 out of 40 patients. In detail, 29 subjects harbored one or two variants and six cases showed three or more concomitant nucleotide changes. The most frequent sequence variants involved the
gene (55.0%), followed by
(27.5%). Histologically, most of the cases displayed a classical ET morphology. Interestingly, prevalent megakaryocytes morphology was more frequently polymorphic with a mixture of giant megakaryocytes with hyperlobulated nuclei, normal and small sized maturing elements, and naked nuclei. Finally, in five cases a mild degree of reticulin fibrosis (MF-1) was evident together with an increase in the micro-vessel density. By means of NGS we were able to identify nucleotide variants in most cases, thus we suggest that a sizeable proportion of triple-negative ET patients do have a clonal disease. In analogy with driver genes-mutated MPNs, these observations may prevent issues arising concerning triple-negative ET treatment, especially when a cytoreductive therapy may be warranted.
A specific prognostication score for hepatitis C virus-positive diffuse large B-cell lymphomas is not available. For this purpose, the Fondazione Italiana Linfomi (FIL, Italian Lymphoma Foundation) ...carried out a multicenter retrospective study on a large consecutive series of patients with hepatitis C virus-associated diffuse large B-cell lymphoma to evaluate the prognostic impact of clinical and virological features and to develop a specific prognostic score for this subset of patients. All prognostic evaluations were performed on 535 patients treated with an anthracycline-based induction regimen (with rituximab in 255 cases). Severe hepatotoxicity was observed in 14% of patients. The use of rituximab was not associated with increased rate of severe hepatotoxicity. Three-year overall survival and progression-free survival were 71% and 55%, respectively. At multivariate analysis, ECOG performance status of 2 or over, serum albumin below 3.5 g/dL and HCV-RNA viral load over 1000 KIU/mL retained prognostic significance. We combined these 3 factors in a new "HCV Prognostic Score" able to discriminate 3 risk categories with different overall and progression-free survival (low=0; intermediate=1; high-risk ≥2 factors; P<0.001). This score retained prognostic value in the subgroups of patients treated with and without rituximab (P<0.001). The new score performed better than the International Prognostic Index at multivariate analysis and Harrel C-statistic. With the use of three readily available factors (performance status, albumin level and HCV-RNA viral load), the new "HCV Prognostic Score" is able to identify 3 risk categories with different survival, and may be a useful tool to predict the outcome of hepatitis C virus-associated diffuse large B-cell lymphomas.
Seasonal thermal energy storage is an effective measure to enable a low carbon future through the integration of renewables into the energy system. Borehole thermal energy storage (BTES) provides a ...solution for long-term thermal energy storage and its operational optimization is crucial for fully exploiting its potential. This paper presents a novel linearized control-oriented model of a BTES, describing the storage temperature dynamics under varying operating conditions, such as inlet temperature, mass-flow rate and borehole connection layouts (e.g. in-series, in-parallel or mixed). It supports an optimization framework, which was employed to determine the best operating conditions for a heat pump-driven BTES, subject to different CO2 intensity profiles of the electricity. It was demonstrated that this boundary condition, due to its seasonal variation, is critical for the optimal operation of the system, as increasing heat pump efficiency in winter while accepting a lower one in summer can be beneficial. Results for an exemplary district case, subject to two different CO2 intensity profiles, show that a lower relative intensity in summer compared to the one in winter leads to a higher optimal operating temperature of the storage. The district system studied is heating-dominated, effectively enabling the BTES to cover only 20% of the total heat demand, leading to limited total yearly CO2 emissions savings of 2.2% to 4.3%. When calculating the benefits associated with the heating and cooling demand handled by the BTES, a higher CO2 emission reduction in the range of 12.8%–19.9% was found. This highlights the BTES potential when subject to more balanced loads.
•Linearized modelling of a BTES in different plumbing configurations.•Formulation of a BTES operation optimization framework.•Benchmarking of the proposed operational optimization with baseline controllers.•Assessment of electricity CO2 intensity profile impact on optimal BTES operation.
DIS3 is a catalytic subunit of the human exosome complex, containing exonucleolytic (RNB) and endonucleolytic (PIN) domains, recently found mutated in multiple myeloma (MM), a clinically and ...genetically heterogeneous form of plasma cell (PC) dyscrasia. We analyzed by next-generation sequencing (NGS) the DIS3 PIN and RNB domains in purified bone marrow PCs from 164 representative patients, including 130 cases with MM, 24 with primary PC leukemia and 10 with secondary PC leukemia. DIS3 mutations were found respectively in 18.5%, 25% and 30% of cases. Identified variants were predominantly missense mutations localized in the RNB domain, and were often detected at low allele frequency. DIS3 mutations were preferentially carried by IGH-translocated/nonhyperdiploid patients. Sequential analysis at diagnosis and relapse in a subset of cases highlighted some instances of increasing DIS3 mutation burden during disease progression. NGS also revealed that the majority of DIS3 variants in mutated cases were comparably detectable at transcriptional level. Furthermore, gene expression profiling analysis in DIS3-mutated patients identified a transcriptional signature suggestive for impaired RNA exosome function. In conclusion, these data further support the pathological relevance of DIS3 mutations in plasma cell dyscrasias and suggest that DIS3 may represent a potential tumor suppressor gene in such disorders.
Systemic mastocytosis (SM) is a rare neoplasm resulting from extracutaneous infiltration of clonal mast cells (MC). The clinical features of SM are very heterogenous and treatment should be highly ...individualized. Up to 40% of all SM cases can be associated with another hematological neoplasm, most frequently myeloproliferative neoplasms. Here, we present a patient with indolent SM who subsequently developed a myeloid neoplasm with
rearrangement with complete response to low-dose imatinib. The 63-year-old patient presented with eosinophilia and elevated serum tryptase level. Bone marrow analysis revealed aberrant MCs in aggregates co-expressing CD2/CD25 and
D816V mutation (0.01%), and the
fusion gene was not identified. In the absence of 'B' and 'C' findings, we diagnosed an indolent form of SM. For 2 years after the diagnosis, the absolute eosinophil count progressively increased. Bone marrow evaluation showed myeloid hyperplasia and the
fusion gene was detected. Thus, the diagnosis of myeloid neoplasm with
rearrangement was established. The patient was treated with imatinib 100 mg daily and rapidly obtained a complete molecular remission. The clinical, biological, and therapeutic aspects of SM might be challenging, especially when another associated hematological disease is diagnosed. Little is known about the underlying molecular and immunological mechanisms that can promote one entity prevailing over the other one. Currently, the preferred concept of SM pathogenesis is a multimutated neoplasm in which
mutations represent a "phenotype modifier" toward SM. Our patient showed an evolution from
mutated indolent SM to a myeloid neoplasm with
rearrangement; when the eosinophilic component expanded, a regression of the MC counterpart was observed. In conclusion, extensive clinical monitoring associated with molecular testing is essential to better define these rare diseases and consequently their prognosis and treatment.
Precipitation retrievals exploiting the available passive microwave (PMW) observations by cross-track and conically scanning satellite-borne radiometers in the Global Precipitation Measurement (GPM) ...mission era are used to monitor and characterize heavy precipitation events that occurred during the Fall 2014 in Italy. Different physically based PMW precipitation retrieval algorithms are used: the Cloud Dynamics and Radiation Database (CDRD) and Passive microwave Neural network Precipitation Retrieval (PNPR), used operationally in the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT) Satellite Application Facility on support to Operational Hydrology and Water Management (H-SAF), and the National Aeronautics and Space Administration (NASA) Goddard PROFiling algorithm (GPROF). Results show that PMW precipitation retrievals from the GPM constellation of radiometers provide a reliable and quantitative description of the precipitation (instantaneous and on the daily scale) throughout the evolution of the precipitation systems in the Mediterranean region. The comparable relative errors among gauges, radar, and combination of radiometer overpasses legitimize the use of PMW estimates as a valuable and independent tool for monitoring precipitation. The pixel-based comparison with dual-polarization radars and raingauges indicates the ability of the different sensors to identify different precipitation areas and regimes (0.60 <; POD <; 0.76; 0.28 <; FAR <; 0.45; 0.42 <; ETS <; 0.59;-1.6 mm/h <; ME <; 1.1 mm/h}, with values depending on the radiometer and on the precipitation product). This is particularly relevant in the presence of complex orography in proximity of coastal areas, as for the analyzed cases. The different characteristics of the radiometers (i.e., viewing geometry, spatial resolution, channel assortment) and of retrieval techniques, as well as the limitations of the ground-based reference datasets, are taken into consideration in the evaluation of the accuracy and consistency of the retrievals.
Mechanisms underlying the pathophysiology of primary Plasma Cell Leukemia (pPCL) and intramedullary multiple myeloma (MM) need to be further elucidated, being potentially relevant for improving ...therapeutic approaches. In such a context, the MM and pPCL subgroups characterized by t(11;14) deserve a focused investigation, as the presence of the translocation is mainly associated with sensitivity to venetoclax. Herein, we investigated a proprietary cohort of MM and pPCL patients, focusing on the transcriptional signature of samples carrying t(11;14), whose incidence increases in pPCL in association with an unfavorable outcome. In addition, we evaluated the expression levels of the BCL2-gene family members and of a panel of B-cell genes recently reported to be associated with sensitivity to venetoclax in MM. Moreover, transcriptional analysis of lncRNAs in the two clinical settings led to the identification of several differentially expressed transcripts, among which the SNGH6 deregulated lncRNA might be relevant in the pathogenesis and prognosis of pPCL with t(11;14). Overall, our data suggest that MMs and pPCLs with t(11;14) might be responsive to venetoclax based on different molecular programs, prompting further studies to elucidate better novel potential predictive biomarkers.
Antigen stimulation may be important for splenic marginal zone lymphoma pathogenesis. To address this hypothesis, the occurrence of stereotyped B-cell receptors was investigated in 133 SMZL (26 HCV+) ...compared with 4,414 HCDR3 sequences from public databases. Sixteen SMZL (12%) showed stereotyped BCR; 7 of 86 (8%) SMZL sequences retrieved from public databases also belonged to stereotyped HCDR3 subsets. Three categories of subsets were identified: i) "SMZL-specific subsets" (n=5), composed only of 12 SMZL (9 HCV-from our series); ii) "Non-Hodgkin's lymphoma-like subsets" (n=5), comprising 5 SMZL (4 from our series) clustering with other indolent lymphomas; iii) "CLL-like subsets" (n=6), comprising 6 SMZL (3 from our series) that belonged to known CLL subsets (n=4) or clustered with public CLL sequences. Immunoglobulin 3D modeling of 3 subsets revealed similarities in antigen binding regions not limited to HCDR3. Overall, data suggest that the pathogenesis of splenic marginal zone lymphoma may involve also HCV-unrelated epitopes or an antigenic trigger common to other indolent lymphomas.
PDF
