This edited volume analyses European socialist countries’ strategy of engagement with the West and the European Economic Community in the long 1970s. The book focuses on a time when the socialist ...regimes of Central and Eastern Europe banked their hopes for prosperity and stability on enhanced relations with the West. Crossing the traditional differences among diverse fields of historiography, it assesses the complex influence of European and global processes of transformation on the socialist elites’ reading of the international political and economic environment and their consequent decision-making. The volume also explores the debate in each country among and within the elites involved in policymaking as they elaborated this strategic view and coped with shortcomings and unexpected turns. A comparative analysis of national cases shows a shared logic and common patterns, together with national variations and a plurality of views on the desirability of exchanges with their capitalist neighbours and on the ways to promote them. The multinational coverage of seven countries makes this volume a starting point for anyone interested in each socialist state’s foreign policy, intra-bloc relations, economic strategy, transformation and collapse, relations with the European Community and access to the EU. This book will be of much interest to students and researchers of Cold War Studies, European history, and International Relations. The Open Access version of this book, available at https://www.routledge.com/European-Socialist-Regimes-Fateful-Engagement-with-the-West-National-Strategies/Romano-Romero/p/book/9780367356170, has been made available under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 license.
•We propose a deep learning approach to generate synthetic CT from low tesla MR images.•Synthetic CT was created for pelvic and abdominal lesions enrolling 120 cases.•The images generated show an ...accuracy sufficient to safely calculate IMRT plans.•This study represents the first experience of CT generation from low tesla MR images.•This is the first experience of CT generation in abdomen independently by B intensity.
Artificial intelligence (AI) can play a significant role in Magnetic Resonance guided Radiotherapy (MRgRT), especially to speed up the online adaptive workflow. The aim of this study is to set up a Deep Learning (DL) approach able to generate synthetic computed tomography (sCT) images from low field MR images in pelvis and abdomen.
A conditional Generative Adversarial Network (cGAN) was used for sCT generation: a total of 120 patients treated on pelvic and abdominal sites were enrolled and divided in training (80) and test sets (40).
Intensity modulated radiotherapy (IMRT) treatment plans were calculated on sCT and original CT and then compared in terms of gamma analysis and differences in Dose Volume Histogram (DVH).
The two one-sided test for paired samples (TOST-P) was used to evaluate the equivalence among different DVH parameters calculated for target and organs at risks (OAR) on CT and sCT images.
Using a CPU architecture, the mean time required by the neural network to generate a synthetic CT was 175 ± 43 seconds (s) for pelvic cases and 110 ± 40 s for abdominal ones.
Mean gamma passing rates for the three tolerance criteria analysed (1%/1 mm, 2%/2 mm and 3%/3 mm) were respectively 90.8 ± 4.5%, 98.7 ± 1.1% and 99.8 ± 0.2% for abdominal cases; 89.3 ± 4.8%, 99.0 ± 0.7% and 99.9 ± 0.2% for pelvic ones, while equivalence within 1% was observed among the DVH indicators.
This study demonstrated that sCT generation using a DL approach is feasible for low field MR images in pelvis and abdomen, allowing a reliable calculation of IMRT plans in MRgRT.
MR guided radiotherapy represents one of the most promising recent technological innovations in the field. The possibility to better visualize therapy volumes, coupled with the innovative online ...adaptive radiotherapy and motion management approaches, paves the way to more efficient treatment delivery and may be translated in better clinical outcomes both in terms of response and reduced toxicity. The aim of this review is to present the existing evidence about MRgRT applications for liver malignancies, discussing the potential clinical advantages and the current pitfalls of this new technology.
This article outlines the potential for Research Higher Degree (RHD) supervisors at universities and similar institutions to use ethical review as a constructive, dynamic tool in guiding RHD students ...in the timely completion of effective, innovative research projects. Ethical review involves a bureaucratized process for checking that researchers apply risk management strategies when dealing with human participants. Ethical review can also be a powerful instrument for RHD supervisors in the creative arts if they use it to lead students through processes of imagining, articulating, and improving their methodologies and relationships with research participants. Proposed strategies involve adaptation of theories of visualization and imagination from several disciplines-imagined interaction from the social sciences and psychology, dramatic rehearsal from political science, and creative visualization from the health professions, sports coaching and many other personal-professional development contexts. By using creativity and imagination, supervisors can use ethical review to help students to 'walk through' the potential, progressive phases of proposed research in order to refine or redesign both 'big picture' strategies and specific steps taken to reach research goals. This can stimulate students to unearth possibilities that improve the quality and quantity of knowledge that their research generates and to avoid or manage problems that might disrupt their research.
The use of degrading enzymes in polymer formulation is a very attractive strategy to manage the end-of-life of plastics. However, high temperatures cause the denaturation of enzymes and the loss of ...their catalytic activity; therefore, protection strategies are necessary. Once protected, the enzyme needs to be released in appropriate media to exert its catalytic activity. A successful protection strategy involves the use of layered double hydroxides: cutinase, selected as a highly degrading polyester hydrolytic enzyme, is thermally protected by immobilization in Mg/Al layered double hydroxide structures. Different triggering media are here evaluated in order to find the best releasing conditions of cutinase from LDH. In detail, phosphate and citrate-phosphate buffers, potassium carbonate, sodium chloride, and sodium sulfate solutions are studied. After the comparison of all media in terms of protein release and activity retained, phosphate buffer is selected as the best candidate for the release of cutinase from LDH, and the effect of pH and concentration is also evaluated. The amount of the enzyme released is determined with the Lowry method. Activity tests are performed via spectrophotometry.
Commercial hydrolytic enzymes belonging to different subclasses (several lipases, proteinase k, cutinase) were investigated for their ability to degrade different aliphatic polyesters, i.e., ...poly(butylene succinate) (PBS), poly(butylene succinate-
-adipate) (PBSA), two poly(caprolactone), having two different molecular weights, poly(lactic acid) (PLA) and poly(propylene carbonate) (PPC). The enzyme screening was first carried out by investigating the capacity of fully degrading the target polymers in 24 h, then weight loss measurements of selected polyesters and target enzymes were performed. Solid residues after enzyme degradation were characterized by proton nuclear magnetic resonance (
H NMR), gel permeation chromatography (GPC), infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetry (TGA). Liquid fractions were studied via GPC,
H NMR and high-performance liquid chromatography (HPLC). PCL and PBSA were found to be the most biodegradable polyesters, under the conditions used in this study. PBS was fully degraded only by cutinase, whereas none of the tested enzymes were able to completely degrade PLA and PPC, in the conditions assessed here. Cutinase exhibited the highest hydrolytic activity on PBSA, while lipase from
sp. (CALB) on low molecular weight PCL. Chemical analyses on residual solids showed that the enzymatic degradation occurred homogeneously from the surface through an erosion mechanism and did not significantly affect the macromolecular structure and thermal stability. Cleaving action mode for each enzyme (endo- and/or exo-type) on the different polyesters were also proposed based on the evaluation of the degradation products in the liquid fraction.
Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose ...escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model.
Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11
fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome.
This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients.
ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).
To quantify the overall contribution of mutations in the currently known amyotrophic lateral sclerosis (ALS) genes in a large cohort of sporadic patients and to make genotype-phenotype correlations.
...Screening for SOD1, TARDBP, FUS, ANG, ATXN2, OPTN, and C9ORF72 was carried out in 480 consecutive patients with sporadic ALS (SALS) and in 48 familial ALS (FALS) index patients admitted to a single Italian referral center.
Mutations were detected in 53 patients, with a cumulative frequency of 11. Seven of them were novel. The highest frequencies of positive cases were obtained in TARDBP (2.7%), C9ORF72 (2.5%), and SOD1 (2.1%). The overall group of mutated patients was indistinguishable from that without mutations as no significant differences were observed with regard to age and site of onset, frequency of clinical phenotypes, and survival. However, by separately evaluating genotype-phenotype correlation in single genes, clinical differences were observed among different genes. Duration of disease was significantly shorter in patients harboring the C9ORF72 expansion and longer in the SOD1 group. A high frequency of predominant upper motor neuron phenotype was observed among patients with TARDBP mutations. Two patients, 1 with C9ORF72 and 1 with SOD1 mutation, had concurrent ANG mutations. Mutations were detected in 43.7% of patients with FALS.
A considerable proportion of patients with SALS harbored mutations in major ALS genes. This result has relevant implications in clinical practice, namely in genetic counseling. The detection of double mutations in 2 patients raises the hypothesis that multiple mutations model may explain genetic architecture of SALS.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nervous system. Despite the established diagnostic criteria, monitoring ...disease activity and treatment remains challenging. To address this limitation, we investigated serum neurofilament light chain (sNfL) and serum free light chains (sFLCs) as potential biomarkers. A total of 32 CIDP patients undergoing immunoglobulin therapy and 32 healthy controls enrolled in the present study, and agreed to have their blood plasma sNfL and sFLCs analyzed, while CIDP severity was assessed through the modified Rankin Scale (mRS) and the Overall Neuropathy Limitations Scale (ONLS). In line with the immunoglobulin treatment aimed at limiting neuronal damage administered to the majority of patients, sNfL levels did not exhibit significant differences between the two groups. However, CIDP patients showed significantly elevated sFLC and sFLC ratios, while the marker levels did not correlate with the clinical scores. The study confirms the potential of sFLCs as a sensitive biomarker of inflammatory processes in CIDP. Additionally, the present study results regarding neurofilaments strengthen the role of sNfL in monitoring CIDP treatments, confirming the effectiveness of immunoglobulin therapy. Overall, our results demonstrate how combining these markers can lead to better patient characterization for improved treatment.
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•Locally Advanced Pancreatic Cancer is one of most aggressive tumors.•Limitations of SABR are represented by the possible toxicity to the OARs surrounding the lesion.•MRgRT offers ...better soft tissue contrast and accurate management of organ motion during RT.•Online adaptive RT allows to adapt the treatment plan based on the daily anatomical changes.•Feasibility and the benefit of the online adaptive procedures has been demonstrated.
Magnetic Resonance-guided Radiation Therapy (MRgRT) allows online adaptations (OA) of the treatment plan to optimize daily dose distribution based on patient's anatomy, just before fraction delivery. The aim of this study is to evaluate feasibility and the dosimetric improvement of the OA workflow implemented in our institution for locally advanced pancreatic cancer (LAPC) patients, in terms of target coverage and organs at risk (OARs) sparing.
We retrospectively analysed 8 LAPC patients treated with MRgRT in combination with the OA approach, using video-assisted inspiratory breath-hold for a total of 38 fractions with a dose ranging from 30 Gy to 40 Gy in 5 fractions.
Dose distribution of the baseline plan was first calculated based on daily anatomy, obtaining a “predicted” plan to assess the dosimetric improvement. If the dose distribution did not meet the constraints set in the planning phase, PTV, GTV and OARs were re-contoured within a distance of 3 cm from the PTV external edge and a new online “adaptive” plan was generated. Other clinical and planning parameters were also evaluated to assess the feasibility and the dosimetic benefit of the online adaptive workflow.
Out of 38 total fractions, 26 (68.4%) were adapted online and 12 (31.6%) were delivered using the baseline plan. The use of the adaptive workflow resulted to be feasible in our clinical practice and advantageous in all the patients: mean PTV V95% increased by 10.8% (5.7–20.8) while mean CTV V98% of 12.6% (7.3–17.7). Also OARs V33 and V25 showed a positive trend avoiding unnecessary irradiation.
OA workflow improves the dosimetric benefit of MRgRT, preventing the occurrence of high-doses to OARs and increasing the safety of stereotactic treatment for LAPC, without any drawback for our daily clinical practice routine.
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