WRF wind field assessment under multiple forcings using spatialized aircraft data

AbstractThe performances of limited area weather models are affected by the choice of core solvers, domain resolutions, and initial and boundary conditions. To understand the extent of such differences on simulated wind fields, weather research and forecast (WRF) simulations initialized by different forcings were extensively compared with an aircraft‐derived high‐resolution data set. The two used forcings were the European Centre for Medium‐Range Weather Forecasts (ECMWF) ERA‐Interim reanalysis and the National Centers for Environmental Predictions (NCEP) Climate Forecast System Reanalysis (CFSR). The model domain covered a large portion of central western Italy (including part of the Tyrrhenian coast) encompassing the aircraft track and allowed the characterization of their performance across the simulation domain rather than a small set of point‐based observations. The WRF results show good agreement with the aircraft data across the whole flight track with both forcings (root mean square errors (RMSEs) < 2.3 m·s−1 and an average r2 = 0.7). Orography and coasts show an effect on simulated wind fields. The presence of a strong orography (which is smoothed by the model internal terrain elevation model) is associated with increased errors. Distance from the coast is also associated with a variation in RMSE (even if in a non‐straightforward manner) because of potential breeze effects. No forcing data set clearly outperforms the other, while the ECMWF has higher correlation co‐efficients when considering wind direction

Lamotrigine versus valproic acid as first-line monotherapy in newly diagnosed typical absence seizures: an open-label,randomized, parallel-group study

Purpose: To compare the efficacy of lamotrigine (LTG) and valproic acid (VPA) in newly diagnosed children and adolescents with typical absence seizures. Methods: A randomized, open-label parallel-group design was used. After undergoing an awake video-EEG recording, which included one to two trials of 3 min of hyperventilation and intermittent photic stimulation, eligible patients were randomized to receive LTG or VPA. LTG was initiated at a daily dose of 0.5 mg/kg for 2 weeks in two divided doses, followed by 1.0 mg/kg/day for an additional 2 weeks. Thereafter, doses were increased in 1-mg/kg/day increments every 5 days until seizures were controlled, intolerable adverse effects occurred, or a maximum dose of 12 mg/kg/day had been reached. VPA was equally uptitrated according to clinical response, starting at 10 mg/kg and increasing by 5 mg/kg/24 h every 3 days, if required, to a maximum of 30 mg/kg/day in three divided doses. Patients were seen in the clinic every month for ≤12 months.The primary efficacy end point at each visit was seizure freedom, defined as lack of clinically observed seizures since the previous visit and lack of electroclinical seizures during ambulatory 24-h EEG testing and a video-EEG session with hyperventilation. Results: Thirty-eight children (17 boys, 21 girls), aged from 3 to 13 years (mean, 7.5 years), all newly diagnosed with childhood or juvenile typical absence seizures, were enrolled. After 1 month of treatment, 10 (52.6%) of 19 children taking VPA and one (5.3%) of 19 taking LTG were seizure free (p = 0.004). By the 3-month follow-up, 12 (63.1%) children taking VPA and seven (36.8%) taking LTG were controlled (p = 0.19). After 12 months, 13 children taking VPA (dose range, 20–30 mg/kg/day; mean serum level, 76.8 mg/L; range, 51.4–91 mg/L) and 10 taking LTG (dose range, 2–11 mg/kg/day; mean serum level, 8.1 mg/L; range, 1.1–18 mg/L) were seizure free (p=0.51). Side effects were mostly mild and transient and were recorded in two (10.6%) children treated with VPA and in six (31.8%) treated with LTG. Conclusions: Both VPA and LTG can be efficacious against absence seizures, although VPA shows a much faster onset of action, at least in part because of its shorter titration schedule. KeyWords: Lamotrigine—Valproic acid—Typical absences— Monotherapy. Valproic acid (VPA) and ethosuximide (ESM) have been shown to be equally effective as monotherapy for typical absence seizures (1,2), and, at present, they are generally considered first-choice drugs for this seizure type. VPA controls absences in∼75% of patients, in addition to being effective against generalized tonic–clonic seizures (70%) and myoclonic seizures (75%). However, its use may involve safety risks for postmenarchal women (3). ESM produces complete control of absences in 70% of treated patients (4,5), but it is unsuitable as monotherapy Accepted Ma

CCNU, vinblastine, procarbazine and prednisone (CVPP) with extended-field radiotherapy in the treatment of early unfavorable Hodgkin's disease - A prospective study on behalf of the Gruppo Italiano per lo Studio dei Linfomi (GISL)

Purpose. To test the adequacy of the CVPP four-drug regimen as ancillary chemotherapy associated with extended-field radiotherapy in the treatment of early, unfavorable, clinically staged Hodgkin's disease. Patients and Methods. The population of this prospective, multicenter study consisted of 49 patients with stage I-II disease, associated with bulky involvement or unfavorable histology (lymphocyte-depleted nodular sclerosis or lymphocyte depletion), systemic symptoms or extranodal involvement, or presenting with stage III A favorable-histology disease, with or without extranodal involvement. Results. Complete remission was achieved in 39 patients, partial remission in 2, while 8 patients did not respond. Four patients have relapsed so far (median follow-up: 43 months), all of whom were subsequently rescued with different salvage treatments. Dose intensity (mean+/-SD: 0.83+/-0.12) and hematological toxicity (including 2 deaths from infection) were higher when RT followed CT than when it was interposed in the middle of the 6 cycles. No growth factors were used. Nonhematological toxicity was very low and fully tolerable. Conclusions. Results confirmed the mild neurological and gastroenteric side effects of CVPP that make it an interesting MOPP-variant regimen. This combination seems most indicated when a regimen devoid of cardiac and pulmonary toxicity is required for association with full-dosage mediastinal radiotherapy, as is often the case in early, unfavorable Hodgkin's disease. The optimal sequence consists of radiotherapy administered after completion of the chemotherapy program. The use of growth factors for correction (or prevention) of marked leukopenia seems appropriate

Long-term results from MOPPEBVCAD chemotherapy with optional limited radiotherapy in advanced Hodgkin's disease

The purpose was to verify the 5-year results of the MOPPEBVCAD chemotherapy regimen with limited radiotherapy in relation to the promising preliminary data. Mechlorethamine, vincristine, procarbazine, prednisone, epidoxorubicin, bleomycin, vinblastine, lomustine, melphalan, and vindesine were delivered according to a schedule derived through hybridization, intensification, and shortening of the corresponding alternating CAD/MOPP/ABV regimen. Radiotherapy was restricted to sites of bulky involvement or to areas that responded incompletely to chemotherapy. This multicenter, controlled, nonrandomized trial involved 145 eligible patients. Radiotherapy was administered to 47 patients, 46 of whom were in complete remission after chemotherapy. Remissions were complete in 137 patients (94%), partial in 4 (3%), and null in the remaining 4. Tumor-specific, overall, relapse-free, and failure-free survival at 5 years were 0.89, 0.86, 0.82, and 0.78, respectively. Hematologic toxicity was considerable, whereas nonhematologic side effects were fully acceptable. Most of the unfavorable prognostic factors lost their clinical weight. Only age and lymphocyte depletion histologic type were statistically correlated with major follow up endpoints; performance status and bone marrow involvement were subordinate to age. Seven patients developed a second cancer (including 3 myelodysplasias). MOPPEBVCAD with selected radiotherapy is a highly effective regimen in advanced Hodgkin\ub4s disease. Early and late toxicity are no more severe than what would be expected with other alternating or hybrid regimens. A comparison with ABVD, which is currently considered the standard regimen for advanced Hodgkin\ub4s disease, is needed

Efficacy of two different ProMACE-CytaBOM derived regimens in advanced aggressive non-Hodgkin's lymphoma. Final report of a multicenter trial conducted by GISL

Background and Objective. To compare the efficacy of ProME(Epidoxorubicin)CE-CytaBOM (PE-C) and ProMI(Idarubicin)CE-CytaBOM (PIG) in the treatment of adult patients with aggressive non Hodgkin's lymphoma in a multicenter randomized controlled trial performed by 18 centers of the Italian Lymphoma Study Group (GISL). Design and Methods. One hundred and twenty-eight and 122 patients were randomly assigned to receive either 6 courses of PE-C or PI-C, respectively. Some patients achieving complete remission with induction therapy participated in another randomized study comparing no further therapy versus maintenance therapy consisting of four blocks of two drugs. Results. The rate of CRs was 62% and 64% for patients treated with PE-C and PI-C, respectively (p=0.51). The 5-year relapse-free survival was 60% for PE-C and 53% for PI-C (p=0.29). The estimated relapse-free disease survival rates at 4 years were 75% for patients in the consolidation group and 57% for those in the observation group (p=0.11). Patients alive In first complete remission 4 years after study entry were estimated to be 39% in the PE-C arm and 38% in the PI-C arm (p=0.90). The 3-year and 5-year estimated survival rates were 61% and 55% for the PE-C group and 56% and 47% for the PI-C group (p=0.26). Fatal toxicities occurred in 7 patients (2.9%) with active disease and in 4 patients (1.7%) in complete remission. Stage (p=0.04), bulky disease (p=0.02), serum LDH (p=0.0006), serum albumin (p=0.0051), hemoglobin (p=0.0011), performance status (p=0.0001), International prognostic index (p<0.0001) and the index proposed by the French group G.E.L.A. (p<0.0001) were of prognostic value. In a multivariate analysis (Cox regression model) alternatively IPI alone or G.E.L.A, index plus performance status emerged as independent prognostic factors. Interpretation and Conclusions. The present study indicates that epirubicin and idarubicin in a combined chemotherapy regimen, have similar activities. The toxic profile also indicates the safety of both anthracyclines at the dosages employed, suggesting their possible dose escalation in a combined chemotherapy setting. PE-C and PI-C were both effective and feasible regimens in an outpatient setting, with acceptable cardiovascular toxicity. The trend toward a better outcome in patients undergoing consolidation therapy after the achievement of a complete remission, warrants further investigation. (C)1998, Ferrata Storti Foundation

Apoptosis Therapy in Cancer: The First Single-molecule Co-activating p53 and the Translocator Protein in Glioblastoma

In the complex scenario of cancer, treatment with compounds targeting multiple cell pathways has been emerging. In Glioblastoma Multiforme (GBM), p53 and Translocator Protein (TSPO), both acting as apoptosis inducers, represent two attractive intracellular targets. On this basis, novel indolylglyoxylyldipeptides, rationally designed to activate TSPO and p53, were synthesized and biologically characterized. The new compounds were able to bind TSPO and to reactivate p53 functionality, through the dissociation from its physiological inhibitor, murine double minute 2 (MDM2). In GBM cells, the new molecules caused Δψm dissipation and inhibition of cell viability. These effects resulted significantly higher with respect to those elicited by the single target reference standards applied alone, and coherent with the synergism resulting from the simultaneous activation of TSPO and p53. Taken together, these results suggest that TSPO/MDM2 dual-target ligands could represent a new attractive multi-modal opportunity for anti-cancer strategy in GBM

Rest Rust ! Physical active for active and healthy ageing

The aim of this paper is to give an insight on how physical activity can be defined, parameterized and measured in older adults and on different options to deal with citizen physical activity promotion at European level. Three relevant aspects are highlighted: When talking about physical activity, two different aspects are often unfairly mixed up: "physical activity" and "physical capacity". Physical activity, is referred to as the level of physical activity someone is actually performing in daily life.Physical capacity is referred to as the maximum physical activity a person can perform.Both physical activity and physical capacity can be expressed in different dimensions such as time, frequency, or type of activity with the consequence that there are many tools and techniques available. In order to support people to choose an appropriate instrument in their everyday practice a list of 9 criteria that are considered important is defined.Older adults score differently across the various physical dimensions, so strategies to promote physical activity should consider individual differences, in order to adapt for these variations

H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC.

H-Prune hydrolyzes short-chain polyphosphates (PPase activity) together with an hitherto cAMP-phosphodiesterase (PDE), the latest influencing different human cancers by its overexpression. H-Prune promotes cell migration in cooperation with glycogen synthase kinase-3 (Gsk-3β). Gsk-3β is a negative regulator of canonical WNT/β-catenin signaling. Here, we investigate the role of Gsk-3β/h-Prune complex in the regulation of WNT/β-catenin signaling, demonstrating the h-Prune capability to activate WNT signaling also in a paracrine manner, through Wnt3a secretion. In vivo study demonstrates that h-Prune silencing inhibits lung metastasis formation, increasing mouse survival. We assessed h-Prune levels in peripheral blood of lung cancer patients using ELISA assay, showing that h-Prune is an early diagnostic marker for lung cancer. Our study dissects out the mechanism of action of h-Prune in tumorigenic cells and also sheds light on the identification of a new therapeutic target in non-small-cell lung cancer

I stay at home with headache. A survey to investigate how the lockdown for COVID-19 impacted on headache in Italian children

ObjectiveThe present Italian multicenter study aimed at investigating whether the course of primary headache disorders in children and adolescents was changed during the lockdown necessary to contain the COVID-19 emergency in Italy.MethodsDuring the lockdown, we submitted an online questionnaire to patients already diagnosed with primary headache disorders. Questions explored the course of headache, daily habits, psychological factors related to COVID-19, general mood and school stress. Answers were transformed into data for statistical analysis. Through a bivariate analysis, the main variables affecting the subjective trend of headache, and intensity and frequency of the attacks were selected. The significant variables were then used for the multivariate analysis.ResultsWe collected the answers of 707 patients. In the multivariate analysis, we found that reduction of school effort and anxiety was the main factor explaining the improvement in the subjective trend of headache and the intensity and frequency of the attacks (p &lt; 0.001). The greater the severity of headache, the larger was the clinical improvement (p &lt; 0.001). Disease duration was negatively associated with the improvement (p &lt; 0.001). It is noteworthy that clinical improvement was independent of prophylaxis (p &gt; 0.05), presence of chronic headache disorders (p &gt; 0.05) and geographical area (p &gt; 0.05).ConclusionsOur study showed that lifestyle modification represents the main factor impacting the course of primary headache disorders in children and adolescents. In particular, reduction in school-related stress during the lockdown was the main factor explaining the general headache improvement in our population