Wavelet Analysis for Wind Fields Estimation

Wind field analysis from synthetic aperture radar images allows the estimation of wind direction and speed based on image descriptors. In this paper, we propose a framework to automate wind direction retrieval based on wavelet decomposition associated with spectral processing. We extend existing undecimated wavelet transform approaches, by including à trous with B3 spline scaling function, in addition to other wavelet bases as Gabor and Mexican-hat. The purpose is to extract more reliable directional information, when wind speed values range from 5 to 10 ms−1. Using C-band empirical models, associated with the estimated directional information, we calculate local wind speed values and compare our results with QuikSCAT scatterometer data. The proposed approach has potential application in the evaluation of oil spills and wind farms

Pemigatinib, a potent inhibitor of FGFRs for the treatment of cholangiocarcinoma

The prognosis of patients affected by cholangiocarcinoma is classically poor. Until recently, chemotherapeutic drugs were the only systemic treatment option available, leading to an overall survival lower than 1 year. In recent decades, different genetic alterations have been identified as playing a key role in the oncogenic signaling. A subgroup of intrahepatic cholangiocarcinoma is characterized byFGFRfamily mutations, more frequently represented by gene fusions ofFGFR2. Based on the results of FIGHT-202 trial, in April 2020 the US FDA approved the FGFR inhibitor pemigatinib in advanced previously treated cholangiocarcinoma patients withFGFR2rearrangements, opening the way to targeted therapy in this disease. This review summarizes the body of evidence about the efficacy of pemigatinib in cholangiocarcinoma.Lay abstract Cholangiocarcinoma is cancer that forms in the slender tubes bile ducts that carry the digestive fluid bile. This condition, also known as bile duct cancer, is a type of tumor that is very difficult to treat with common chemotherapy. Intrahepatic cholangiocarcinoma, those tumors occurring in the parts of the bile ducts within the liver, are frequently caused by alterations of a gene calledFGFR2. Pemigatinib is a novel potent drug that selectively inhibits the function of altered FGFR2 and recently demonstrated to be a valid treatment for patients affected by intrahepatic cholangiocarcinoma. Here, we present results about the efficacy of pemigatinib in this disease

Comparison of 10-m wind forecasts from a regional area model and QuikSCAT scatterometer wind observations over the Mediterranean Sea,

Surface wind forecasts from a limited-area model [the Quadrics Bologna Limited-Area Model (QBOLAM)] covering the entire Mediterranean area at 0.1° grid spacing are verified against Quick Scatterometer (QuikSCAT) wind observations. Only forecasts within the first 24 h in coincidence with satellite overpasses are used. Two years of data, from 1 October 2000 to 31 October 2002, have been considered, allowing for an adequate statistical assessment under different wind conditions. This has been carried out by analyzing the fields of the mean wind vectors, wind speed bias, correlation, difference standard deviation, steadiness, gustiness, and mean wind direction difference, in order to investigate spatial variability. Statistics have been computed on a seasonal basis. A comparison of satellite and forecast winds with measurements from three buoys was also performed. Some critical areas of the Mediterranean Sea where wind forecast quality is lower than average have been identified. Such areas correspond to semienclosed basins surrounded by important orography and to small regions at the lee side of the main islands. In open-sea regions the model underestimates wind strength from about 0.5 m s1 in spring and summer to 1.0 m s1 in winter, as evidenced by the existing biases against scatterometer data. Also, a wind direction bias (scatterometer minus model) generally between 5° and 15° exists. A survey of the identified and likely sources of forecast error is performed, indicating that orography representation plays an important role. Numerical damping is identified as a likely factor reducing forecast wind strength. The need for a correction scheme is envisaged to provide more accurate forcing for numerical sea state forecasting models, wind energy evaluation, and latent and/or sensible heat exchanges

Multicenter Retrospective Analysis of Second-Line Therapy after Gemcitabine Plus Nab-Paclitaxel in Advanced Pancreatic Cancer Patients

Pancreatic cancer is one of the most lethal solid tumors. In many European countries gemcitabine plus nab-paclitaxel is the preferred first-line treatment. An increasing number of patients are eligible for second-line therapy, but the best regimen is still controversial. This study aimed to evaluate the efficacy of oxaliplatin-based compared to irinotecan-based therapies in this setting. 181 advanced pancreatic cancer patients consecutively treated in three centers with a second-line therapy progressed on gemcitabine plus nab-paclitaxel were retrospectively enrolled. OS and PFS were calculated using the Kaplan-Meier method and survival of the two groups was compared using the log-rank test. The median PFS and OS were respectively 3.5 (95%CI 3.2-3.8) and 8.8 months (95%CI 7.9-9.8) from second-line therapy in the overall population. The median PFS and OS were respectively 3.3 (95%CI 3.1-3.5) and 8.2 months (95%CI 7.24-9.34) with an irinotecan-based combination compared to 4.0 (95%CI 2.4-5.7) and 10.3 months (95%CI 8.62-12.02) in patients receiving an oxaliplatin-based combination. We observed a clear trend for longer survival outcomes with platinum-based doublet compared to regimens including irinotecan or nal-IRI. Head-to-head trials are still lacking. The neutrophil-to-lymphocyte ratio and the presence of liver metastases could drive physicians in tailoring the treatment strategy

Clinicogenomic Analysis of FGFR2-Rearranged Cholangiocarcinoma Identifies Correlates of Response and Mechanisms of Resistance to Pemigatinib

Pemigatinib, a selective FGFR1-3 inhibitor, has demonstrated antitumor activity in FIGHT-202, a phase II study in patients with cholangiocarcinoma harboring FGFR2 fusions/rearrangements, and has gained regulatory approval in the United States. Eligibility for FIGHT-202 was assessed using genomic profiling; here, these data were utilized to characterize the genomic landscape of cholangiocarcinoma and to uncover unique molecular features of patients harboring FGFR2 rearrangements. The results highlight the high percentage of patients with cholangiocarcinoma harboring potentially actionable genomic alterations and the diversity in gene partners that rearrange with FGFR2. Clinicogenomic analysis of pemigatinib-treated patients identified mechanisms of primary and acquired resistance. Genomic subsets of patients with other potentially actionable FGF/FGFR alterations were also identified. Our study provides a framework for molecularly guided clinical trials and underscores the importance of genomic profiling to enable a deeper understanding of the molecular basis for response and nonresponse to targeted therapy. SIGNIFICANCE: We utilized genomic profiling data from FIGHT-202 to gain insights into the genomic landscape of cholangiocarcinoma, to understand the molecular diversity of patients with FGFR2 fusions or rearrangements, and to interrogate the clinicogenomics of patients treated with pemigatinib. Our study highlights the utility of genomic profiling in clinical trials.This article is highlighted in the In This Issue feature, p. 211

Use of the ERS-1 scatterometer in the Mediterranean Sea

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Targeting KRAS: The Elephant in the Room of Epithelial Cancers

Mutations of the proto-oncogene KRAS are the most frequent gain-of-function alterations found in cancer. KRAS is mutated in about 30% of all human tumors, but it could reach more than 90% in certain cancer types such as pancreatic adenocarcinoma. Although historically considered to be undruggable, a particular KRAS mutation, the G12C variant, has recently emerged as an actionable alteration especially in non-small cell lung cancer (NSCLC). KRAS(G12C) and pan-KRAS inhibitors are being tested in clinical trials and have recently shown promising activity. Due to the difficulties in direct targeting of KRAS, other approaches are being explored. The inhibition of target upstream activators or downstream effectors of KRAS pathway has shown to be moderately effective given the evidence of emerging mechanisms of resistance. Various synthetic lethal partners of KRAS have recently being identified and the inhibition of some of those might prove to be successful in the future. The study of escape mechanisms to KRAS inhibition could support the utility of combination strategies in overcoming intrinsic and adaptive resistance and enhancing clinical benefit of KRAS(G12C) inhibitors. Considering the role of the microenvironment in influencing tumor initiation and promotion, the immune tumor niche of KRAS mutant tumors has been deeply explored and characterized for its unique immunosuppressive skewing. However, a number of aspects remains to be fully understood, and modulating this tumor niche might revert the immunoresistance of KRAS mutant tumors. Synergistic associations of KRAS(G12C) and immune checkpoint inhibitors are being tested

Safety and activity of the TGF beta receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer

Background We assessed the safety, efficacy, and pharmacokinetics of the transforming growth factor beta (TGF beta) receptor inhibitor galunisertib co-administered with the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab in recurrent/refractory metastatic pancreatic cancer previously treated with <= 2 systemic regimens.Methods This was a two-part, single-arm, multinational, phase Ib study. In a dose-finding phase, escalating oral doses of galunisertib were co-administered on days 1-14 with fixed-dose intravenous durvalumab 1500 mg on day 1 every 4 weeks (Q4W), followed by an expansion cohort phase.Results The galunisertib recommended phase II dose (RP2D) when co-administered with durvalumab 1500 mg Q4W was 150 mg two times per day. No dose-limiting toxicities were recorded. Among 32 patients treated with galunisertib RP2D, 1 patient had partial response, 7 had stable disease, 15 had objective progressive disease, and 9 were not evaluable. Disease control rate was 25.0%. Median overall survival and progression-free survival were 5.72 months (95% CI: 4.01 to 8.38) and 1.87 months (95% CI: 1.58 to 3.09), respectively. Pharmacokinetic profiles for combination therapy were comparable to those published for each drug. There was no association between potential biomarkers and treatment outcomes.Conclusion Galunisertib 150 mg two times per day co-administered with durvalumab 1500 mg Q4W was tolerable. Clinical activity was limited. Studying this combination in patients in an earlier line of treatment or selected for predictive biomarkers of TGF beta inhibition might be a more suitable approach

A phase II study of liposomal irinotecan with 5-fluorouracil, leucovorin and oxaliplatin in patients with resectable pancreatic cancer: the nITRO trial

Background: Up-front surgery followed by postoperative chemotherapy remains the standard paradigm for the treatment of patients with resectable pancreatic cancer. However, the risk for positive surgical margins, the poor recovery after surgery that often impairs postoperative treatment, and the common metastatic relapse limit the overall clinical outcomes achieved with this strategy. Polychemotherapeutic combinations are valid options for postoperative treatment in patients with good performance status. liposomal irinotecan (Nal-IRI) is a novel nanoliposome formulation of irinotecan that accumulates in tumor-associated macrophages improving the therapeutic index of irinotecan and has been approved for the treatment of patients with metastatic pancreatic cancer after progression under gemcitabine-based therapy. Thus, it remains of the outmost urgency to investigate introduction of the most novel agents, such as nal-IRI, in perioperative approaches aimed at increasing the long-term effectiveness of surgery. Methods: The nITRO trial is a phase II, single-arm, open-label study to assess the safety and the activity of nal-IRI with fluorouracil/leucovorin (5-FU/LV) and oxaliplatin in the perioperative treatment of patients with resectable pancreatic cancer. The primary tumor must be resectable with no involvement of the major arteries and no involvement or <180 degrees interface between tumor and vessel wall of the major veins. A total of 72 patients will be enrolled to receive a perioperative treatment of three cycles before and three cycles after surgical resection with nal-IRI 50 mg/m(2), oxaliplatin 60 mg/m(2), leucovorin 200 mg/m(2), and 5-fluorouracil 2400 mg/m(2), days 1 and 15 of a 28-day cycle. The primary objective is to improve from 40% to 55% the proportion of patients achieving R0 resection after preoperative treatment. Discussion: The nITRO trial will contribute to strengthen the clinical evidence supporting perioperative strategies in resectable pancreatic cancer patients. Moreover, this study represents a unique opportunity for translational analyses aimed to identify novel immune-related prognostic and predictive factors in this setting