Results of a research regarding the variability of spring depletion curves

Springs, no recharge periods, discharge process, depletion coefficient

Using flood water in Managed Aquifer Recharge schemes as a solution for groundwater management in the Cornia valley (Italy)

The lower Cornia valley aquifer system (Tuscany, Italy) provides the only source of water for drinking, irrigation, industrial purposes and it also contributes to the water needs of the nearby Elba island. Since 60 years, intensive exploitation of groundwater resulted in consistent head lowering and water balance deficit, causing subsidence, reduction of groundwater dependent ecosystems, and salinization of freshwater resources. Rebalancing the water budget of the hydrologic system is the main objective of the LIFE REWAT project (sustainable WATer management in the lower Cornia valley through demand REduction, aquifer Recharge and river REstoration; http://www.liferewat.eu). Here, five demonstration measures (river restoration; Managed Aquifer Recharge; reuse of treated wastewater for irrigation; high irrigation efficiency scheme; leakage management in water distribution systems) are set in place for promoting water resource management, along with capacity building and participatory actions. A pilot Managed Aquifer Recharge (MAR) infiltration basin for using flood-water was designed and set in operation in Suvereto, testing the new-issued Italian regulation on artificial recharge of aquifers (DM 100/2016). The infiltration basin is located at a pre-existing topographical low near the Cornia River. The river, having intermittent flow, provides the recharge water during high flow periods, including floods, and when discharge is above the minimum ecological flow. The infiltration basin is set in a groundwater recharge area where the aquifer is constituted by gravel and sands. A preliminary project and an executive one were prepared and discussed with the relevant authorities, following one-year long monthly monitoring of surface- and ground-water. The project was supported by a groundwater flow modelling-based approach using the FREEWAT platform (www.freewat.eu). The facility consists of the following elements: i) intake work on the River Cornia; ii) the inlet structure control system, managed by quality (mass spectrometer defining surface water spectral signature) and level probes, and allowing pumping into the facility at predefined head and chemical quality thresholds; iii) a sedimentation basin; iv) the infiltration area (less than 1 ha large); v) the operational monitoring system, based on a network of piezometers where both continuous data (head, T, EC, DO) are gathered and discrete measurements/sampling performed. The cost of construction of the plant is about 300000 C well below the cost of a surface water reservoir for a similar storage. Depending on the climatic conditions, the estimated volume of diverted surface water may vary between 300000 m3/year and 2 Mm3/year. Being the facility a pilot one, diverted water discharge ranges between 20 to 50 l/s. Minimal site development and modification was required, resulting in a no-impact water-work, while providing ecosystem benefits by reconnecting and inundating former abandoned riverbeds. The effectiveness of such pilot may demonstrate the potential for Flood-MAR schemes to increase water availability in scarcity prone areas

Water planning and management in the Cornia river plain by means of the gis-integrated freewat platform

Coastal aquifer, Cornia valley, Tuscany, Managed Aquifer Recharge, FREEWAT platform

SWIPE: a bolometric polarimeter for the Large-Scale Polarization Explorer

The balloon-borne LSPE mission is optimized to measure the linear polarization of the Cosmic Microwave Background at large angular scales. The Short Wavelength Instrument for the Polarization Explorer (SWIPE) is composed of 3 arrays of multi-mode bolometers cooled at 0.3K, with optical components and filters cryogenically cooled below 4K to reduce the background on the detectors. Polarimetry is achieved by means of large rotating half-wave plates and wire-grid polarizers in front of the arrays. The polarization modulator is the first component of the optical chain, reducing significantly the effect of instrumental polarization. In SWIPE we trade angular resolution for sensitivity. The diameter of the entrance pupil of the refractive telescope is 45 cm, while the field optics is optimized to collect tens of modes for each detector, thus boosting the absorbed power. This approach results in a FWHM resolution of 1.8, 1.5, 1.2 degrees at 95, 145, 245 GHz respectively. The expected performance of the three channels is limited by photon noise, resulting in a final sensitivity around 0.1-0.2 uK per beam, for a 13 days survey covering 25% of the sky.Comment: In press. Copyright 2012 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibite

The Large-Scale Polarization Explorer (LSPE)

The LSPE is a balloon-borne mission aimed at measuring the polarization of the Cosmic Microwave Background (CMB) at large angular scales, and in particular to constrain the curl component of CMB polarization (B-modes) produced by tensor perturbations generated during cosmic inflation, in the very early universe. Its primary target is to improve the limit on the ratio of tensor to scalar perturbations amplitudes down to r = 0.03, at 99.7% confidence. A second target is to produce wide maps of foreground polarization generated in our Galaxy by synchrotron emission and interstellar dust emission. These will be important to map Galactic magnetic fields and to study the properties of ionized gas and of diffuse interstellar dust in our Galaxy. The mission is optimized for large angular scales, with coarse angular resolution (around 1.5 degrees FWHM), and wide sky coverage (25% of the sky). The payload will fly in a circumpolar long duration balloon mission during the polar night. Using the Earth as a giant solar shield, the instrument will spin in azimuth, observing a large fraction of the northern sky. The payload will host two instruments. An array of coherent polarimeters using cryogenic HEMT amplifiers will survey the sky at 43 and 90 GHz. An array of bolometric polarimeters, using large throughput multi-mode bolometers and rotating Half Wave Plates (HWP), will survey the same sky region in three bands at 95, 145 and 245 GHz. The wide frequency coverage will allow optimal control of the polarized foregrounds, with comparable angular resolution at all frequencies.Comment: In press. Copyright 2012 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibite

Comparison and combination of a hemodynamics/biomarkers-based model with simplified PESI score for prognostic stratification of acute pulmonary embolism: findings from a real world study

Background: Prognostic stratification is of utmost importance for management of acute Pulmonary Embolism (PE) in clinical practice. Many prognostic models have been proposed, but which is the best prognosticator in real life remains unclear. The aim of our study was to compare and combine the predictive values of the hemodynamics/biomarkers based prognostic model proposed by European Society of Cardiology (ESC) in 2008 and simplified PESI score (sPESI).Methods: Data records of 452 patients discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. The ESC model and sPESI were retrospectively calculated and compared by using Areas under Receiver Operating Characteristics (ROC) Curves (AUCs) and finally the combination of the two models was tested in hemodinamically stable patients. All cause and PE-related in-hospital mortality and fatal or major bleedings were the analyzed endpointsResults: All cause in-hospital mortality was 25% (16.6% PE related) in high risk, 8.7% (4.7%) in intermediate risk and 3.8% (1.2%) in low risk patients according to ESC model. All cause in-hospital mortality was 10.95% (5.75% PE related) in patients with sPESI score ≥1 and 0% (0%) in sPESI score 0. Predictive performance of sPESI was not significantly different compared with 2008 ESC model both for all cause (AUC sPESI 0.711, 95% CI: 0.661-0.758 versus ESC 0.619, 95% CI: 0.567-0.670, difference between AUCs 0.0916, p=0.084) and for PE-related mortality (AUC sPESI 0.764, 95% CI: 0.717-0.808 versus ESC 0.650, 95% CI: 0.598-0.700, difference between AUCs 0.114, p=0.11). Fatal or major bleedings occurred in 4.30% of high risk, 1.60% of intermediate risk and 2.50% of low risk patients according to 2008 ESC model, whereas these occurred in 1.80% of high risk and 1.45% of low risk patients according to sPESI, respectively. Predictive performance for fatal or major bleeding between two models was not significantly different (AUC sPESI 0.658, 95% CI: 0.606-0.707 versus ESC 0.512, 95% CI: 0.459-0.565, difference between AUCs 0.145, p=0.34). In hemodynamically stable patients, the combined endpoint in-hospital PE-related mortality and/or fatal or major bleeding (adverse events) occurred in 0% of patients with low risk ESC model and sPESI score 0, whilst it occurred in 5.5% of patients with low-risk ESC model but sPESI ≥1. In intermediate risk patients according to ESC model, adverse events occurred in 3.6% of patients with sPESI score 0 and 6.65% of patients with sPESI score ≥1.Conclusions: In real world, predictive performance of sPESI and the hemodynamic/biomarkers-based ESC model as prognosticator of in-hospital mortality and bleedings is similar. Combination of sPESI 0 with low risk ESC model may identify patients with very low risk of adverse events and candidate for early hospital discharge or home treatment.

Pathologic response and survival after neoadjuvant chemotherapy with or without pertuzumab in patients with HER2-positive breast cancer: the Neopearl nationwide collaborative study

PurposeClinical trials have shown a significant increase in pathologic complete response (pCR) with the addition of pertuzumab to neoadjuvant chemotherapy for patients with early-stage HER-2 positive breast cancer. To date, limited studies have examined comparative outcomes of neoadjuvant pertuzumab in real-world setting. The Neopearl study aimed to assess comparative real-life efficacy and safety of neoadjuvant pertuzumab for these patients.MethodsWe conducted a nationwide retrospective analysis involving 17 oncology facilities with a certified multidisciplinary breast cancer treatment committee. We identified patients with HER-2 positive stage II-III breast cancer treated with neoadjuvant chemotherapy based on trastuzumab and taxanes with or without pertuzumab. All patients underwent breast surgery and received a comprehensive cardiologic evaluation at baseline and after neoadjuvant treatment. Patients who received the combination of pertuzumab, trastuzumab, and chemotherapy constituted case cohort (PTCT), whereas those treated with trastuzumab and chemotherapy accounted for control cohort (TCT). The pCR rate and 5-year event free survival (EFS) were the primary outcomes. Secondary end-points were rates of conversion from planned modified radical mastectomy (MRM) to breast conservation surgery (BCS) and cardiotoxicities.ResultsFrom March 2014 to April 2021, we included 271 patients, 134 (49%) and 137 (51%) in TCT and PTCT cohort, respectively. Positive axillary lymph nodes and stage III were more frequent in PTCT cohort. The pCR rate was significantly increased in patients who received pertuzumab (49% vs 62%; OR 1.74, 95%CI 1.04-2.89) and with HER-2 enriched subtypes (16% vs 85%; OR 2.94, 95%CI 1.60-5.41). After a median follow-up of 5 years, the 5-year EFS was significantly prolonged only in patients treated with pertuzumab (81% vs 93%; HR 2.22, 95%CI 1.03-4.79). The same analysis performed on propensity score matched population showed concordant results. On univariate analysis, only patients with positive lymph nodes were found to benefit from pertuzumab for both pCR and 5-year EFS. The rates of conversion from MRM to BCS and cardiologic toxicities did not differ between the cohorts.ConclusionOur findings support previous data on improved outcomes with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy. This benefit seems to be more significant in patients with clinically positive lymph nodes

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19