Analysis of fragmented piezometric levels records: the ARTE (Antecedent Recharge Temporal Effectiveness) approach

In contrast to climatic data, piezometric records are often fragmented both in time and space continuity, despite their crucial importance in groundwater studies. This work presents a new method for analysis of groundwater level vs. recharge processes relation from fragmented piezometric data, called Antecedent Recharge Temporal Effectiveness (ARTE). The ARTE method was tested on 5 year-long (2016-2020) water table level datasets measured by three automatic piezometers located in the Lucca plain (Tuscany, Italy). For each piezometric level time series, measurements were extracted every 30, 60, and 120 days, and randomly, obtaining fragmented records inlcuding less than 3% of the complete time series. As for recharge processes of the monitored aquifer, rainfall and riverbed infiltration were selected. Hence, daily rainfall and daily mean river stage time series were acquired from different automatic raingauges and hydrometers respectively. The relationship between these recharge processes and the variation of the piezometric level from the artificially fragmented datasets were evaluated with the ARTE method. The ARTE method was potentially able to identify maximum correlation time intervals, for which the recharge processes are most likely to influence the groundwater level. Based on the analysis conducted on the fragmented piezometric datasets, the reconstruction of each piezometric time series was attempted for the study period. The simulated daily groundwater level records have RMSE values between 0.21 m and 0.73 m and NRMSE values between 0.08 and 0.16, which are satisfactory results when compared with other more complex simulation procedures, in which the training datasets are increasingly larger

Steroid treatment of acute graft-versus-host disease grade I: A randomized trial

Patients with acute graft-versus-host disease (GvHD) grade I were randomized to an observation arm (n=85) or to a treatment arm (n=86) consisting of 6-methylprednisolone 1 mg/kg/day, after stratification for age and donor type. The primary end point was development of grade II-IV GvHD. The cumulative incidence of grade II-IV GvHD was 50% in the observation arm and 33% in the treatment arm (P=0.005). However, grade III-IV GvHD was comparable (13% vs. 10%, respectively; P=0.6), and this was true for sibling and alternative donor transplants. Moderate/severe chronic GvHD was also comparable (17% vs. 9%). In multivariate analysis, an early interval between transplant and randomization

Clofarabine and Treosulfan as Conditioning for Matched Related and Unrelated Hematopoietic Stem Cell Transplantation: Results from the Clo3o Phase II Trial

ABSTRACT Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be curative for patients with hematologic malignancies. The ideal conditioning regimen before allo-HSCT has not been established. We conducted a Phase II study to evaluate the tolerability and efficacy of clofarabine and treosulfan as conditioning regimen before allo-HSCT. The primary objective was to evaluate the cumulative incidence of nonrelapse mortality (NRM) on day +100. Forty-four patients (36 with acute myelogenous leukemia, 5 with acute lymphoblastic leukemia, 3 with myelodysplastic syndromes) were enrolled. The median patient age was 47 years, and the median duration of follow-up was 27 months. The conditioning regimen was based on clofarabine 40 mg/m2 (days -6 to -2) and treosulfan 14 g/m2 (days -6 to -4). Allogeneic hematopoietic stem cells were derived from a sibling (n = 22) or a well-matched unrelated donor (n = 22). Graft-versus-host disease (GVHD) prophylaxis consisted of antithymocyte globulin, rituximab, cyclosporine, and a short-course of methotrexate. The regimen allowed for rapid engraftment and a 100-day NRM of 18%, due mainly to bacterial infections. The incidences of grade II-IV acute GVHD and chronic GVHD were 16% and 19%, respectively. The rates of overall survival (OS), progression-free survival, and relapse at 2 years were 51%, 31%, and 50%, respectively. Significantly different outcomes were observed between patients with low-intermediate and patients with high-very high Disease Risk Index (DRI) scores (1-year OS, 78% and 24%, respectively). Our findings show that the use of treosulfan and clofarabine as a conditioning regimen for allo-HSCT is feasible, with a 78% 1-year OS in patients with a low-intermediate DRI score. However, 1-year NRM was 18%, and despite the intensified conditioning regimen, relapse incidence remains a major issue in patients with poor prognostic risk factors

Hydrogeological numerical modeling of the southeastern portion of the Lucca Plain (Tuscany, Italy), stressed by groundwater exploitation

In the hydrogeological field, the numerical modeling is well known as a powerful tool to set up a management strategy that can prevent groundwater mining. To overcome its somehow “exoteric fame”, it needs as many as possible of local field tests in order to become real world common practice in groundwater management. The Lucca Plain aquifer shows a severe piezometric drop associated to an unregulated competition between agriculture, industry, public and private drinking water wells. It was chosen to test a finite difference numerical model capability as a crisis analysis and forecasting tool and as a regulatory action technical support benchmark. The southern Lucca Plain geological and hydrogeological conceptual model was translated into a MODFLOW grid. Public and private pumping wells were monthly surveyed from January 2007 to October 2008. Calibration allowed the numerical model to achieve a good statistical correspondence with reality. The resulting virtual reality highlighted the heavy hydrogeological stress affecting the area, where pumping rate significantly exceeds the recharge in the studied period. The sensibility analysis highlighted rainfall recharge and pumping rate as the more sensitive values among the input data. Since the calibration process implied a remarkable increase of the officially declared pumping rate, numerical modeling, when a lot of calibration data are available, showed promising capability of back-analysis to estimate the real pumping rate for a given area

Mesenchymal stem/stromal cells: a new ''cells as drugs'' paradigm. Efficacy and critical aspects in cell therapy

Mesenchymal stem cells (MSCs) were first isolated more than 50 years ago from the bone marrow. Currently MSCs may also be isolated from several alternative sources and they have been used in more than a hundred clinical trials worldwide to treat a wide variety of diseases. The MSCs mechanism of action is undefined and currently under investigation. For in vivo purposes MSCs must be produced in compliance with good manufacturing practices and this has stimulated research on MSCs characterization and safety. The objective of this review is to describe recent developments regarding MSCs properties, physiological effects, delivery, clinical applications and possible side effects

Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair

Acute myelogenous leukemias (AMLs) are genetically heterogeneous and characterized by chromosomal rearrangements that produce fusion proteins with aberrant transcriptional regulatory activities. Expression of AML fusion proteins in transgenic mice increases the risk of myeloid leukemias, suggesting that they induce a preleukemic state. The underlying molecular and biological mechanisms are, however, unknown. To address this issue, we performed a systematic analysis of fusion protein transcriptional targets. We expressed AML1/ETO, PML/RAR, and PLZF/RAR in U937 hemopoietic precursor cells and measured global gene expression using oligonucleotide chips. We identified 1,555 genes regulated concordantly by at least two fusion proteins that were further validated in patient samples and finally classified according to available functional information. Strikingly, we found that AML fusion proteins induce genes involved in the maintenance of the stem cell phenotype and repress DNA repair genes, mainly of the base excision repair pathway. Functional studies confirmed that ectopic expression of fusion proteins constitutively activates pathways leading to increased stem cell renewal (e.g., the Jagged1/Notch pathway) and provokes accumulation of DNA damage. We propose that expansion of the stem cell compartment and induction of a mutator phenotype are relevant features underlying the leukemic potential of AML-associated fusion proteins

"Disturbed immagination" e "true political econony". Aspirazioni e sfide tra Architettura e Politica in John Ruskin

Nella sua riflessione sulla politica Ruskin indaga il rapporto tra la libert\ue0 individuale e i meccanismi legati ai processi di industrializzazione. In questa prospettiva solleva questioni e dilemmi di larga portata culturale che pongono l'uomo di fronte al problema della Tecnica, al dinamismo "senza sedimenti memoria" che segna la sua esistenza, alla questione cruciale del limite della sua azione di fronte alla natura e al costruito. Nella medesima prospettiva richiama la necessit\ue0 della cura in luogo del dominio delle cose del mondo, della parsimonia in luogo di un consumo non rispendente alle reali esigenze dell\u2019uomo. Per contro richiama la necessit\ue0 di un impegno attivo verso l'affermazione di quelle spinte vitali - come l\u2019Amore, la Bellezza, Immaginazione \u2013 fonti di inventiva ,che spingono l\u2019azione e la ricerca dell\u2019Umanit\ue0. Queste sono solo alcune delle aspettative e delle sfide, ingenue e necessarie, che Ruskin lascia in eredit\ue0 alla contemporaneit\ue0, su cui si \ue8 inteso riflettere