Pulsed CW laser for long-term spectroscopic measurements at high power in deep-UV

We present a novel technique for in-vacuum cavity-enhanced UV spectroscopy that allows nearly continuous measurements over several days, minimizing mirror degradation caused by high-power UV radiation. Our method relies on pulsing of the cavity's internal power, which increases the UV intensity to maximum only for short periods when the studied atom is within the cavity mode volume while keeping the average power low to prevent mirror degradation. Additionally, this method significantly decreases laser-induced background on charged particle detectors. The described 244 nm laser system is designed for 1S-2S two-photon CW spectroscopy of muonium in the Mu-MASS project. It was tested to provide intracavity powers above 20 W, requiring maintenance only a few times a day. The pulsing technique demonstrates minimal impact on the radiation frequency, with no observed shifts exceeding 15 kHz. Our approach represents a promising new technique for high-precision spectroscopy of atoms in harsh UV environments and demonstrates the feasibility of CW spectroscopy of muonium.Comment: 10 pages, 5 figure

Pulsed CW laser for long-term spectroscopic measurements at high power in deep-UV

We present a novel technique for in-vacuum cavity-enhanced UV spectroscopy that allows nearly continuous measurements over several days, minimizing mirror degradation caused by high-power UV radiation. Our method relies on pulsing of the cavity’s internal power, which increases the UV intensity to maximum only for short periods when the studied atom is within the cavity mode volume while keeping the average power low to prevent mirror degradation. Additionally, this method significantly decreases laser-induced background on charged particle detectors. The described 244 nm laser system is designed for 1S-2S two-photon CW spectroscopy of muonium in the Mu-MASS project. It was tested to provide intracavity powers above 20 W, requiring maintenance only a few times a day. The pulsing technique demonstrates minimal impact on the radiation frequency, with no observed shifts exceeding 15 kHz. Our approach represents a promising new technique for high-precision spectroscopy of atoms in harsh UV environments and demonstrates the feasibility of CW spectroscopy of muonium.ISSN:1094-408

Update of Muonium 1S–2S transition frequency

We present an updated value of the Muonium 1S–2S transition frequency, highlighting contributions from different QED corrections as well as the large uncertainty in the Dirac contribution, stemming from the uncertainty of the electron to muon mass ratio. Improving the measurement of this spectral line would allow to extract a more accurate determination of fundamental constants, such as the electron to muon mass ratio or, combined with the Muonium hyperfine splitting, an independent value of the Rydberg constant. Furthermore, we report on the current status of the Mu-MASS experiment, which aims at measuring the Muonium 1S–2S transition frequency at a 10kHz uncertainty level.ISSN:1434-6060ISSN:1434-607

Validation and Analysis of the European Quality Questionnaire in Italian Language

The European Quality Questionnaire (euroQ2) is the culturally-adapted version to the European context of the Family Satisfaction in Intensive Care Unit (FS-ICU) and Quality of Dying and Death (QODD) tools in a single instrument divided into three parts (the last is optional). These tools were created for an adult setting. The aim of this study was the Italian validation and analysis of the euroQ2 tool. The Italian version of euroQ2 questionnaire was administered to the relatives, over 18 years of age, of adult intensive care unit patients, with the Hospital Anxiety and Depression Scale (HADS) and the Impact of Event Scale—Revised (IES-r). For the re-test phase the questionnaire was administered a second time. One hundred questionnaires were filled in. The agreement between test and retest was between 17–19 out of 20 participants with an upward trend in the re-test phase. A measure of coherence and cohesion between the euroQ2 variables was given by Cronbach’s alpha: in the first part of the questionnaire alpha was 0.82, in the second part it was 0.89. The linear Pearson’s correlation coefficients between all questions showed a weak positive correlation. The results obtained agreed with the original study. This study showed a good stability of the answers, an indication of an unambiguous understanding of the Italian translation

Short communication: Alteration in blood parameters induced by enrofloxacin in juvenile lesser spotted dogfish (Scyliorhinus canicula, Linnaeus, 1758) after intramuscular injection.

Enrofloxacin (EF) is a veterinary drug for respiratory, gastrointestinal and urinary tract infections. Parenteral administration at doses higher than the manufacturer recommended dosage has induced cartilage lesions in juvenile mammals and poultry. In elasmobranchs EF is commonly used for the treatment of infectious diseases, however only one study has been performed previously to evaluate pharmacokinetics and the potential chondrotoxicity of a fluoroquinolone in adult skates. In present study juvenile lesser spotted dogfish (Scyliorhinus canicula, Linnaeus, 1758) were treated with low (LD, 5mg/kg) and high dose (HD, 10mg/kg) of EF daily via intramuscular injection for 15 consecutive days, as indicated in a recognized treatment. Hematological parameters, oxidative stress and histology of vertebral cartilage were evaluated. No cartilage damage was observed. Hematological parameters evaluation underlined a significant (p=0.035), dose-dependent reduction in red blood cell count and in hematocrit (40% and 6%, respectively). Anyway, the biological significance of this reduction is doubtful, due to limited decrease observed. The evaluation of oxidative stress parameters underlined that glutathione levels, as well as glutathione S-transferase and catalase activities, were significantly increased in HD group animals, with respect to untreated and solvent control groups. Obtained data do not support a toxic effect of EF on dogfish cartilage, while concern arises from hematological and oxidative stress data

Measurement of the transition frequency from 2S1/2, F = 0 to 2P1/2, F = 1 states in Muonium

Muons are puzzling physicists since their discovery when they were first thought to be the meson predicted by Yukawa to mediate the strong force. The recent result at Fermilab on the muon g-2 anomaly puts the muonic sector once more under the spotlight and calls for further measurements with this particle. Here, we present the results of the measurement of the 2S1/2, F = 0 → 2P1/2, F = 1 transition in Muonium. The measured value of 580.6(6.8) MHz is in agreement with the theoretical calculations. A value of the Lamb shift of 1045.5(6.8) MHz is extracted, compatible with previous experiments. We also determine the 2S hyperfine splitting in Muonium to be 559.6(7.2) MHz. The measured transition being isolated from the other hyperfine levels holds the promise to provide an improved determination of the Muonium Lamb shift at a level where bound state QED recoil corrections not accessible in hydrogen could be tested. This result would be sensitive to new physics in the muonic sector, e.g., to new bosons which might provide an explanation of the g-2 muon anomaly and allow to test Lorentz and CPT violation. We also present the observation of Muonium in the n = 3 excited state opening up the possibility of additional precise microwave measurements.ISSN:2041-172

Precision Measurement of the Lamb Shift in Muonium

We report a new measurement of the n = 2 Lamb shift in Muonium. Our result of 1047.2(2.3)stat(1.1)syst MHz comprises an order of magnitude improvement upon the previous best measurement. This value matches the theoretical calculation within 1 standard deviation allowing us to set limits on Lorentz and CPT violation in the muonic sector, as well as on new physics coupled to muons and electrons which could provide an explanation of the muon g − 2 anomaly.ISSN:0031-9007ISSN:1079-711

Metabolic Parameters as Biomarkers of Response to Immunotherapy and Prognosis in Non-Small Cell Lung Cancer (NSCLC): A Real World Experience

Immune-checkpoint inhibitors (ICIs) have been proven to have great efficacy in non-small cell lung cancer (NSCLC) as single agents or in combination therapy, being capable to induce deep and durable remission. However, severe adverse events may occur and about 40% of patients do not benefit from the treatment. Predictive factors of response to ICIs are needed in order to customize treatment. The aim of this study is to evaluate the correlation between quantitative positron emission tomography (PET) parameters defined before starting ICI therapy and responses to treatment and patient outcome. We retrospectively analyzed 92 NSCLC patients treated with nivolumab, pembrolizumab or atezolizumab. Basal PET/computed tomography (CT) scan parameters (whole-body metabolic tumor volume—wMTV, total lesion glycolysis—wTLG, higher standardized uptake volume maximum and mean—SUVmax and SUVmean) were calculated for each patient and correlated with outcomes. Patients who achieved disease control (complete response + partial response + stable disease) had significantly lower MTV median values than patients who had not (progressive disease) (77 vs. 160.2, p = 0.039). Furthermore, patients with MTV and TLG values lower than the median values had improved OS compared to patients with higher MTV and TLG (p = 0.03 and 0.05, respectively). No relation was found between the other parameters and outcome. In conclusion, baseline metabolic tumor burden, measured with MTV, might be an independent predictor of treatment response to ICI and a prognostic biomarker in NSCLC patients

p65BTK is a novel potential actionable target in KRAS-mutated/EGFR-wild type lung adenocarcinoma

Background: Lung cancer is still the main cause of cancer death worldwide despite the availability of targeted therapies and immune-checkpoint inhibitors combined with chemotherapy. Cancer cell heterogeneity and primary or acquired resistance mechanisms cause the elusive behaviour of this cancer and new biomarkers and active drugs are urgently needed to overcome these limitations. p65BTK, a novel isoform of the Bruton Tyrosine Kinase may represent a new actionable target in non-small cell lung cancer (NSCLC). Methods: p65BTK expression was evaluated by immunohistochemistry in 382 NSCLC patients with complete clinico-pathological records including smoking habit, ALK and EGFR status, and in metastatic lymph nodes of 30 NSCLC patients. NSCLC cell lines mutated for p53 and/or a component of the RAS/MAPK pathway and primary lung cancer-derived cells from Kras/Trp53 null mice were used as a preclinical model. The effects of p65BTK inhibition by BTK Tyrosine Kinase Inhibitors (TKIs) (Ibrutinib, AVL-292, RN486) and first-generation EGFR-TKIs (Gefitinib, Erlotinib) on cell viability were evaluated by MTT. The effects of BTK-TKIs on cell growth and clonogenicity were assessed by crystal violet and colony assays, respectively. Cell toxicity assays were performed to study the effect of the combination of non-toxic concentrations of BTK-TKIs with EGFR-TKIs and standard-of-care (SOC) chemotherapy (Cisplatin, Gemcitabine, Pemetrexed). Results: p65BTK was significantly over-expressed in EGFR-wild type (wt) adenocarcinomas (AdC) from non-smoker patients and its expression was also preserved at the metastatic site. p65BTK was also over-expressed in cell lines mutated for KRAS or for a component of the RAS/MAPK pathway and in tumors from Kras/Trp53 null mice. BTK-TKIs were more effective than EGFR-TKIs in decreasing cancer cell viability and significantly impaired cell proliferation and clonogenicity. Moreover, non-toxic doses of BTK-TKIs re-sensitized drug-resistant NSCLC cell lines to both target- and SOC therapy, independently from EGFR/KRAS status. Conclusions: p65BTK results as an emerging actionable target in non-smoking EGFR-wt AdC, also at advanced stages of disease. Notably, these patients are not eligible for EGFR-TKIs-based therapy due to a lack of EGFR mutation. The combination of BTK-TKIs with EGFR-TKIs is cytotoxic for EGFR-wt/KRAS-mutant/p53-null tumors and BTK-TKIs re-sensitizes drug-resistant NSCLC to SOC chemotherapy. Therefore, our data suggest that adding BTK-TKIs to SOC chemotherapy and EGFR-targeted therapy may open new avenues for clinical trials in currently untreatable NSCLC