The "Automated Welding Machine" in the integration process of the Detection Units of the KM3Net experiment: general description

This note describes one of the tools used during Process-1 of the integration of the Detection Units (DUs) in the KM3NeT experiment. In particular, the device is designed to seal the Break-out-box (BOB). The BOB is a box interface between a Digital Optical Module (DOM) and the electrooptical cable (VEOC) for power and optical connection of each optical module (DOM) to the DU. The original manual version of the tool developed by NIKHEF was automatized by INFN-LNS in order to guarantee a reproducible operation in the recursive process of the DU integration and two samples have been realized for the integration sites at LNS and Genova respectively

The system to fill with oil the empty Break Out Boxes (BOBs) of the KM3NeT Detection Units

The KM3NeT collaboration aims to construct the largest underwater neutrino telescope in the Mediterranean sea. The detector is located in two sites, one in front of Toulon at 2500m sea depth and one SE Capo Passero in Sicily at 3500m depth. On both sites, one or two blocks of 115 Detection Units (DU) are connected to shore , each Du being composed by a Vertical Electro-Optical Cable (VEOC) connecting 18 Digital Optical Modules (DOMs). In this report we describe the integration of the DU carried out in our INFN laboratory in Genova, in particular one important phase of the process where some components in the VEOC have to be carefully filled with oil before connection to the DOMs

A phase I study of PankoMab-GEX, a humanised glyco-optimised monoclonal antibody to a novel tumour-specific MUC1 glycopeptide epitope in patients with advanced carcinomas

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Single Institution trial of anthracycline- and taxane-based chemotherapy for operable breast cancer: The ASTER study

The efficacy of anthracycline- and taxane-based chemotherapy for perioperative treatment of breast cancer (BC) has been established. No superiority of a cytotoxic regimen has been demonstrated, provided that administration of an anthracycline and a taxane is warranted. The ASTER study was designed to investigate the safety of 6 months of perioperative chemotherapy with Doxorubicin and Paclitaxel, followed by Cyclophosphamide, Methotrexate, and 5-Fluorouracil. ASTER enrolled patients with cT2-3 N0-1 or pT1-2 N1-3 BC, from November 2008 to August 2011. Treatment consisted of Doxorubicin 60 mg/sm, Paclitaxel 200 mg/sm q21 (AT) for three cycles followed by Cyclophosphamide 600 mg/sm, Methotrexate 40 mg/sm, 5-Fluorouracil 600 mg/sm d1,8 q28 (CMF) for three cycles, in either neo-adjuvant or adjuvant setting. All HER-positive patients received targeted therapy with Trastuzumab for 1 year. Disease-free and overall survival (DFS and OS, respectively) were estimated according to Kaplan-Meier method. Three hundred and thirty patients were enrolled, where 77.9% of cases were treated in an adjuvant setting; 65.5% received breast conservative surgery, 72.4% axillary dissection. 75.5% of cases presented estrogen receptor positivity, 66.7% progesterone receptor positivity; 18.5% of patients presented HER2-positive BC, 16.1% triple negative disease. Twenty-eight (8.5%) developed grade III-IV hematologic toxicity; nine patients (2.7%) developed grade III neurological toxicity. Loco-regional DFS was 99.6% at 1 year, 97.1% at 5 years, 95.9% at 7 years. Corresponding distant DFS was 98.4%, 90.2%, and 88.8%. One, 5, and 7-year OS was 99.6%, 94.9%, and 91.2%, respectively. Chemotherapy with ATx3 -> CMFx3 is confirmed safe and effective at 6.7 years follow-up. These results appear comparable to those reported in regulatory trials of most commonly prescribed anthracycline and taxane-based regimens

Combination of baseline LDH, performance status and age as integrated algorithm to identify solid tumor patients with higher probability of response to anti PD-1 and PD-l1 monoclonal antibodies

Predictive biomarkers of response to immune-checkpoint inhibitors (ICIs) are an urgent clinical need. The aim of this study is to identify manageable parameters to use in clinical practice to select patients with higher probability of response to ICIs. Two-hundred-and-seventy-one consecutive metastatic solid tumor patients, treated from 2013 until 2017 with anti-Programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) ICIs, were evaluated for baseline lactate dehydrogenase (LDH) serum level, performance status (PS), age, neutrophil-lymphocyte ratio, type of immunotherapy, number of metastatic sites, histology, and sex. A training and validation set were used to build and test models, respectively. The variables\u2019 effects were assessed through odds ratio estimates (OR) and area under the receive operating characteristic curves (AUC), from univariate and multivariate logistic regression models. A final multivariate model with LDH, age and PS showed significant ORs and an AUC of 0.771. Results were statistically validated and used to devise an Excel algorithm to calculate the patient\u2019s response probabilities. We implemented an interactive Excel algorithm based on three variables (baseline LDH serum level, age and PS) which is able to provide a higher performance in response prediction to ICIs compared with LDH alone. This tool could be used in a real-life setting to identify ICIs in responding patients

A phase 1 study of mTORC1/2 inhibitor BI 860585 as a single agent or with exemestane or paclitaxel in patients with advanced solid tumors

This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5–300 mg/day; Arm A), BI 860585 (40–220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80–220 mg/day; Arm C) with 60–80 mg/m2 /week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD. Forty-one, 25, and 24 patients were treated (Arms A, B, and C). DLTs were observed in four (rash (n = 2), elevated alanine aminotransferase/aspartate aminotransferase, diarrhea), four (rash (n = 3), stomatitis, and increased gamma-glutamyl transferase), and two (diarrhea, increased blood creatine phosphokinase) patients in cycle 1. The BI 860585 MTD was 220 mg/day (Arm A) and 160 mg/day (Arms B and C). Nine patients achieved an objective response (Arm B: Four partial responses (PRs); Arm C: Four PRs; one complete response). The disease control rate was 20%, 28%, and 58% (Arms A, B, and C). The most frequent treatment-related adverse events (AEs) were hyperglycemia (54%) and diarrhea (39%) (Arm A); diarrhea (40%) and stomatitis (40%) (Arm B); fatigue (58%) and diarrhea (58%) (Arm C). The MTD was determined in all arms. Antitumor activity was observed with BI 860585 monotherapy and in combination with exemestane or paclitaxel

Cutaneous Involvement in Diseases with Plasma Cell Differentiation: Diagnostic Approach

Neoplasms with plasma cell differentiation may occasionally involve the skin. Cutaneous lesions may represent the first sign of an underlying systemic plasma cell malignancy, such as multiple myeloma, or the skin itself may be the primary site of occurrence of a hematological tumor with plasma cell differentiation. Starting from examples encountered in our daily practice, we discussed the diagnostic approach pathologists and clinicians should use when faced with cutaneous lesions with plasma cell differentiation. Cases of primary cutaneous marginal zone lymphoma, localized primary amyloidosis/amyloidoma, and cutaneous manifestations (secondary either to multiple myeloma or to plasmablastic lymphoma) are discussed, focusing on the importance of the adequate patient’s work-up and precise clinicopathological correlation to get to the correct diagnosis and appropriate treatment. The pertinent literature has been reviewed, and the clinical presentation, pathological findings, main differential diagnoses, treatment, and outcome of neoplasms with plasma cell differentiation involving the skin are discussed

Exploring food system resilience to the global polycrisis in six Asian countries

The world is currently in the midst of a global food crisis brought about and exacerbated by a series of mutually reinforcing shocks to food systems This study investigated the resilience of food systems in six Asian countries (Bangladesh, Kyrgyz Republic, Lao PDR, Pakistan, Philippines, and Sri Lanka) amidst the global ‘polycrisis’ caused by COVID-19, geopolitical conflicts, and climate change. Trend analyses were performed for 19 indicators sourced from global databases and World Food Programme national data, representing the four domains of food system resilience: exposure to shocks; resilience capacities and agro- and food diversity, resilience responses and strategies; and long-term resilience outcomes. The analysis revealed that all six countries experienced the effects of the ‘polycrisis’, leading to diverse impacts on exchange rates, with Sri Lanka, Pakistan, and Lao PDR facing significant currency depreciation. While most countries increased crop production and decreased food imports during the crisis, government economic support during the pandemic varied widely. Resilience outcomes, including national food price inflation and the proportion of populations facing food insecurity, witnessed upward variations. Overall, countries with higher resilience capacities at the start of the ‘polycrisis’ showed less severe long-term resilience outcomes. Our findings highlight the varied challenges and resilience capacities across each country, influenced by a complex interplay of economic, political, agricultural, and food affordability factors crucial for determining long-term resilience in their food systems. Recommendations for future research include focusing on resilience assessment in food systems, integrating climate change adaptation measures, and developing early intervention strategies

A three-scale domain decomposition method for the 3D analysis of debonding in laminates

The prediction of the quasi-static response of industrial laminate structures requires to use fine descriptions of the material, especially when debonding is involved. Even when modeled at the mesoscale, the computation of these structures results in very large numerical problems. In this paper, the exact mesoscale solution is sought using parallel iterative solvers. The LaTIn-based mixed domain decomposition method makes it very easy to handle the complex description of the structure; moreover the provided multiscale features enable us to deal with numerical difficulties at their natural scale; we present the various enhancements we developed to ensure the scalability of the method. An extension of the method designed to handle instabilities is also presented