A Multidisciplinary Approach to Improve the Management of Immune-Checkpoint Inhibitor-Related Pneumonitis

Purpose: Treatment with immune-checkpoint inhibitors (ICIs) can be associated with a wide spectrum of immune-related adverse events (irAEs). Among irAEs, immune-mediated pneumonitis (im-PN) is a rare but potentially life-threatening side effect. TPrompt multidisciplinary diagnosis and effective management of im-PN may be essential to avoid severe complications and allowing resumation of therapy. Patients and Methods: We collected a case series of skin (melanoma, cutaneous squamous cell carcinoma-CSCC), lung, and mesothelioma cancer patients (pts), treated with ICI at the Center for Immuno-Oncology University Hospital of Siena, Italy, and diagnosed with im-PN. Clinical and radiologic data were thoroughly collected, as well as bronchoalveolar lavage (BAL) samples; imPN was graded using CTCAE v. 5.0. Radiological patterns were reported according to the Fleischner Society classification. Results: From January 2014 to February 2023, 1004 patients with melanoma (522), CSCC (42), lung (342) or mesothelioma (98) were treated with ICI (619 monotherapy; 385 combination). Among treated patients, 24 (2%) developed an im-PN and 58% were symptomatic. Im-PN were classified as grades G1 (10) and G2 (14). Prompt steroid treatment led to complete resolution of im-PN in 21 patients, with a median time to resolution of 14 weeks (range: 0.4-51). Twelve patients resumed ICI therapy once fully-recovered and 2 experienced a recurrence that completely resolved with steroids after resumption of treatment. Three radiologic patterns were identified: organizational pneumonia-like (67%), pulmonary eosinophilia (29%), and hypersensitivity pneumonitis (4%). Furthermore, BAL analysis performed in 8 (33%) patients showed an inflammatory lymphocytic infiltrate, predominantly consisting of foam celllike macrophage infiltrates in 6 cases. Notably, transmission electron microscopy evaluation performed in 2 patients revealed a scenario suggestive of a drug-mediated toxicity. Conclusion: Im-PN is a rare but challenging side effect of ICI therapy, with variable time of onset and with heterogeneous clinical and radiological presentations. A multidisciplinary assessment is mandatory to optimize the clinical management of im-PN

Determination of the b quark mass at the M_Z scale with the DELPHI detector at LEP

An experimental study of the normalized three-jet rate of b quark events with respect to light quarks events (light= \ell \equiv u,d,s) has been performed using the CAMBRIDGE and DURHAM jet algorithms. The data used were collected by the DELPHI experiment at LEP on the Z peak from 1994 to 2000. The results are found to agree with theoretical predictions treating mass corrections at next-to-leading order. Measurements of the b quark mass have also been performed for both the b pole mass: M_b and the b running mass: m_b(M_Z). Data are found to be better described when using the running mass. The measurement yields: m_b(M_Z) = 2.85 +/- 0.18 (stat) +/- 0.13 (exp) +/- 0.19 (had) +/- 0.12 (theo) GeV/c^2 for the CAMBRIDGE algorithm. This result is the most precise measurement of the b mass derived from a high energy process. When compared to other b mass determinations by experiments at lower energy scales, this value agrees with the prediction of Quantum Chromodynamics for the energy evolution of the running mass. The mass measurement is equivalent to a test of the flavour independence of the strong coupling constant with an accuracy of 7 permil.Comment: 24 pages, 10 figures, Accepted by Eur. Phys. J.

Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance

This paper presents DELPHI measurements and interpretations of cross-sections, forward-backward asymmetries, and angular distributions, for the e+e- -> ffbar process for centre-of-mass energies above the Z resonance, from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are consistent with the predictions of the Standard Model and are used to study a variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering and several models which include physics beyond the Standard Model: the exchange of Z' bosons, contact interactions between fermions, the exchange of gravitons in large extra dimensions and the exchange of sneutrino in R-parity violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.

A Determination of the Centre-of-Mass Energy at LEP2 using Radiative 2-fermion Events

Using e+e- -> mu+mu-(gamma) and e+e- -> qqbar(gamma) events radiative to the Z pole, DELPHI has determined the centre-of-mass energy, sqrt{s}, using energy and momentum constraint methods. The results are expressed as deviations from the nominal LEP centre-of-mass energy, measured using other techniques. The results are found to be compatible with the LEP Energy Working Group estimates for a combination of the 1997 to 2000 data sets.Comment: 20 pages, 6 figures, Accepted by Eur. Phys. J.

Evidence for an Excess of Soft Photons in Hadronic Decays of Z^0

Soft photons inside hadronic jets converted in front of the DELPHI main tracker (TPC) in events of qqbar disintegrations of the Z^0 were studied in the kinematic range 0.2 < E_gamma < 1 GeV and transverse momentum with respect to the closest jet direction p_T < 80 MeV/c. A clear excess of photons in the experimental data as compared to the Monte Carlo predictions is observed. This excess (uncorrected for the photon detection efficiency) is (1.17 +/- 0.06 +/- 0.27) x 10^{-3} gamma/jet in the specified kinematic region, while the expected level of the inner hadronic bremsstrahlung (which is not included in the Monte Carlo) is (0.340 +/- 0.001 +/- 0.038) x 10^{-3} gamma/jet. The ratio of the excess to the predicted bremsstrahlung rate is then (3.4 +/- 0.2 +/- 0.8), which is similar in strength to the anomalous soft photon signal observed in fixed target experiments with hadronic beams.Comment: 37 pages, 9 figures, Accepted by Eur. Phys. J.

A Measurement of the Tau Hadronic Branching Ratios

The exclusive and semi-exclusive branching ratios of the tau lepton hadronic decay modes (h- v_t, h- pi0 v_t, h- pi0 pi0 v_t, h- \geq 2pi0 v_t, h- \geq 3pi0 v_t, 2h- h+ v_t, 2h- h+ pi0 v_t, 2h- h+ \geq 2pi0 v_t, 3h- 2h+ v_t and 3h- 2h+ \geq 1pi0 v_t) were measured with data from the DELPHI detector at LEP.Comment: 53 pages, 18 figures, Accepted by Eur. Phys. J.

Energy dependence of Cronin momentum in saturation model for p+Ap+A and A+AA+A collisions

We calculate $\sqrt{s}$ dependence of Cronin momentum for $p+A$ and $A+A$ collisions in saturation model. We show that this dependence is consistent with expectation from formula which was obtained using simple dimentional consideration. This can be used to test validity of saturation model (and distinguish among its variants) and measure $x$ dependence of saturation momentum from experimental data.Comment: LaTeX2e, 12 pages, 8 figure

CP asymmetry in B→ϕKSB \to \phi K_S in a general two-Higgs-doublet model with fourth-generation quarks

We discuss the time-dependent CP asymmetry of decay $B \to \phi K_S$ in an extension of the Standard Model with both two Higgs doublets and additional fourth-generation quarks. We show that although the Standard Model with two-Higgs-doublet and the Standard model with fourth generation quarks alone are not likely to largely change the effective $\sin 2 \beta$ from the decay of $B \to \phi K_S$, the model with both additional Higgs doublet and fourth-generation quarks can easily account for the possible large negative value of $\sin 2 \beta$ without conflicting with other experimental constraints. In this model, additional large CP violating effects may arise from the flavor changing Yukawa interactions between neutral Higgs bosons and the heavy fourth generation down type quark, which can modify the QCD penguin contributions. With the constraints obtained from $b \to s \bar{s} s$ processes such as $B \to X_s \gamma$ and $\Delta m_{B_s^0}$, this model can lead to the effective $\sin 2 \beta$ to be as large as $- 0.4$ in the CP asymmetry of $B \to \phi K_S$.Comment: 13 pages, 5 figures, references added, to appear in Eur.Phys.J.

A Precise Measurement of the Tau Lifetime

The tau lepton lifetime has been measured with the e+e- -> tau+tau- events collected by the DELPHI detector at LEP in the years 1991-1995. Three different methods have been exploited, using both one-prong and three-prong tau decay channels. Two measurements have been made using events in which both taus decay to a single charged particle. Combining these measurements gave tau_tau (1 prong) = 291.8 +/- 2.3 (stat) +/- 1.5 (sys) fs. A third measurement using taus which decayed to three charged particles yielded tau_tau (3 prong) = 288.6 +/- 2.4 (stat) +/- 1.3 (sys) fs. These were combined with previous DELPHI results to measure the tau lifetime, using the full LEP1 data sample, to be tau_tau = 290.9 +/- 1.4 (stat) +/- 1.0 (sys) fs.Comment: 27 pages, 7 figure

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio