second line egfr inhibitors in ras mutant metastatic colorectal cancer the plasma ras wild type window of opportunity

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THGEM operation in Ne and Ne/CH4

The operation of Thick Gaseous Electron Multipliers (THGEM) in Ne and Ne/CH4 mixtures, features high multiplication factors at relatively low operation potentials, in both single- and double-THGEM configurations. We present some systematic data measured with UV-photons and soft x-rays, in various Ne mixtures. It includes gain dependence on hole diameter and gas purity, photoelectron extraction efficiency from CsI photocathodes into the gas, long-term gain stability and pulse rise-time. Position resolution of a 100x100 mm^2 X-rays imaging detector is presented. Possible applications are discussed.Comment: Submitted to JINST, 25 pages, 33 figure

Postmenopausal hormone therapy in BRCA gene mutation carriers: to whom and which?

Introduction: Risk-reducing-salpingo-oophorectomy (RRSO) inevitably leads BRCA mutation carriers to premature menopause. Areas covered: To evaluate the existing evidence for use of postmenopausal hormone therapy (HT) in BRCAmc, after RRSO or menopause occurring naturally, for both breast cancer (BC) survivors and those without BC. Expert opinion: All BC survivors are excluded from any HT treatment: in other BRCAmc, before 51 years of age the benefits of HT overcome the risks after RRSO and/or premature ovarian insufficiency (POF). After 51 years of age, it is important to treat only women with important vasomotor symptoms, after the failure of alternative therapies. Estrogens-only therapy plays a key role in hysterectomized women (HW). In the case of an intact uterus (UW), associations with the lowest dose of progestins/natural progesterone derivatives have to be preferred, as progestins has been shown to play an important role in BC transformation, especially in BRCA1mc. No studies have been performed in BRCAmc with regard to ‘progestin-free’ HT, in particular the old tibolone (both in HW and UW) and the new tissue-selective estrogen complex (in UW). However, preliminary data obtained from the general population are reassuring about the use of these ‘progestin-free’ preparations and BC safety

A Double Fragmentation Approach for Improving Virtual Primary Key-Based Watermark Synchronization

Relational data watermarking techniques using virtual primary key schemes try to avoid compromising watermark detection due to the deletion or replacement of the relation's primary key. Nevertheless, these techniques face the limitations that bring high redundancy of the generated set of virtual primary keys, which often compromises the quality of the embedded watermark. As a solution to this problem, this paper proposes double fragmentation of the watermark by using the existing redundancy in the set of virtual primary keys. This way, we guarantee the right identification of the watermark despite the deletion of any of the attributes of the relation. The experiments carried out to validate our proposal show an increment between 81.04% and 99.05% of detected marks with respect to previous solutions found in the literature. Furthermore, we found out that our approach takes advantage of the redundancy present in the set of virtual primary keys. Concerning the computational complexity of the solution, we performed a set of scalability tests that show the linear behavior of our approach with respect to the processes runtime and the number of tuples involved, making it feasible to use no matter the amount of data to be protected

HQR-Scheme: A High Quality and resilient virtual primary key generation approach for watermarking relational data

Most of the watermarking techniques designed to protect relational data often use the Primary Key (PK) of relations to perform the watermark synchronization. Despite offering high confidence to the watermark detection, these approaches become useless if the PK can be erased or updated. A typical example is when an attacker wishes to use a stolen relation, unlinked to the rest of the database. In that case, the original values of the PK lose relevance, since they are not employed to check the referential integrity. Then, it is possible to erase or replace the PK, compromising the watermark detection with no need to perform the slightest modification on the rest of the data. To avoid the problems caused by the PK-dependency some schemes have been proposed to generate Virtual Primary Keys (VPK) used instead. Nevertheless, the quality of the watermark synchronized using VPKs is compromised due to the presence of duplicate values in the set of VPKs and the fragility of the VPK schemes against the elimination of attributes. In this paper, we introduce the metrics to allow precise measuring of the quality of the VPKs generated by any scheme without requiring to perform the watermark embedding. This way, time waste can be avoided in case of low-quality detection. We also analyze the main aspects to design the ideal VPK scheme, seeking the generation of high-quality VPK sets adding robustness to the process. Finally, a new scheme is presented along with the experiments carried out to validate and compare the results with the rest of the schemes proposed in the literature

Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab

Controversial results on the predictive value of programmed death ligand 1 (PD-L1) status in lung tumor tissue for response to immune checkpoint inhibitors do not allow for any conclusive consideration. Liquid biopsy might allow real-time sampling of patients for PD-L1 through the course of the disease. Twenty-four stage IV NSCLC patients included in the Expanded Access Program with Nivolumab were enrolled. Circulating tumor cells (CTCs) were analyzed by CellSearch with anti-human B7-H1/PD-L1 PE-conjugated antibody. PD-L1 expressing CTCs were assessed at baseline, at 3 and 6 months after starting therapy, and correlated with outcome. At baseline and at 3 months of treatment, the presence of CTCs and the expression of PD-L1 on their surface were found associated to poor patients outcome. Nevertheless, the high frequency of PD-L1 expressing CTCs hampered to discriminate the role of PD-L1 in defining prognosis. Conversely although CTCs were found in all patients 6 months after treatment, at this time patients could be dichotomized into two groups based PD-L1 expression on CTCs. Patients with PD-L1 negative CTCs all obtained a clinical benefit, while patients with PD-L1 (+) CTCs all experienced progressive disease. This suggests that the persistence of PD-L1(+) CTCs might mirror a mechanism of therapy escape

Abiraterone acetate in metastatic castration-resistant prostate cancer after chemotherapy. A retrospective “Real Life” analysis of activity and safety

Abiraterone acetate (AA) is a potent, selective androge (CYP17) biosynthesis inhibitor, which showed to improve overall survival (HR = 0.646) in mCRPC patients progressing after docetaxel. In this retrospective analysis we assessed the safety and efficacy of AA in patients affected with mCRPC progressing after chemotherapy, treated in the normal clinical practice, in several Italian Oncologic Units, after the approval of the drug from the Italian Drug Agency (AIFA)

Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO

Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status

Twinning automata and regular expressions for string static analysis

In this paper we formalize and prove the soundness of Tarsis, a new abstract domain based on the abstract interpretation theory that approximates string values through finite state automata. The main novelty of Tarsis is that it works over an alphabet of strings instead of single characters. On the one hand, such approach requires a more complex and refined definition of the widening operator, and the abstract semantics of string operators. On the other hand, it is in position to obtain strictly more precise results than than state-of-the-art approaches. We implemented a prototype of Tarsis, and we applied it on some case studies taken from some of the most popular Java libraries manipulating string values. The experimental results confirm that Tarsis is in position to obtain strictly more precise results than existing analyses