Electrical and thermal diagnostics for a better understanding of the energy balance of species in technological plasmas

This doctoral thesis explores the investigation of the energy balance of species in technological plasmas through the application of electrical and thermal diagnostics. The research focuses on advancing the understanding of the energy balance of species in plasmas by employing electrical, thermal, and optical diagnostics. Three previously published works are presented, highlighting the use of thermal and electrical diagnostics to analyze magnetron-sputtered thin films with highly specific applications. These publications demonstrate the significance of accurate diagnostic techniques in evaluating the behaviour of plasma-generated species and their effect on thin film properties such as morphology and structure. Additionally, a novel combined diagnostic approach is introduced, combining a thermal probe with a retarding field energy analyzer (RFEA). In this technique, the thermal probe serves as the collector for the RFEA, allowing simultaneous thermal and electrical measurements. The thesis describes the development of a prototype that provides proof of principle for the combined diagnostic and outlines the challenges and limitations encountered during the initial implementation. A new design addresses the limitations identified in the earlier stage and provides enhanced capabilities for studying plasma energy balance. The thesis thoroughly discusses the experimental setup, methodology, and data analysis procedures associated with the new combined diagnostic, illustrating its potential for advancing our understanding of species behaviour in technological plasmas

What is the Impact of the Analysis Method Used for Health State Utility Values on QALYs in Oncology? A Simulation Study Comparing Progression-Based and Time-to-Death Approaches

Background: Health state utility values (‘utilities’) are an integral part of health technology assessment. Though traditionally categorised by disease status in oncology (i.e. progression), several recent assessments have adopted values calculated according to the time that measures were recorded before death. We conducted a simulation study to understand the limitations of each approach, with a focus on mismatches between the way utilities are generated, and analysed. Methods: Survival times were simulated based on published literature, with permutations of three utility generation mechanisms (UGMs) and utility analysis methods (UAMs): (1) progression based, (2) time-to-death based, and (3) a ‘combination approach’. For each analysis quality-adjusted life-years (QALYs) were estimated. Goodness of fit was assessed via percentage mean error (%ME) and mean absolute error (%MAE). Scenario analyses were performed varying individual parameters, with complex scenarios mimicking published studies. The statistical code is provided for transparency and to aid future work in the area. Results: %ME and %MAE were lowest when the correct analysis form was specified (i.e. UGM and UAM aligned). Underestimates were produced when a time-to-death element was present in the UGM but not included in the UAM, while the ‘combined’ UAM produced overestimates irrespective of the UGM. Scenario analysis demonstrated the importance of the volume of available data beyond the initial time period, for example follow-up. Conclusions: We show that the use of an incorrectly or over-specified UAM can result in substantial bias in the estimation of utilities. We present a flowchart to highlight the issues that may be faced

nonprogression with avelumab treatment associated with gains in quality of life in metastatic merkel cell carcinoma

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Dilepton polarization as a signature of plasma anisotropy

We propose the angular distribution of lepton pairs produced in ultrarelativistic heavy-ion collisions as a probe of thermalization of the quark-gluon plasma. We focus on dileptons with invariant masses large enough that they are produced through quark-antiquark annihilation in the early stages of the collision. The angular distribution of the lepton in the rest frame of the pair then reflects the angular distribution of quark momenta. At early times, the transverse pressure of the quark-gluon plasma is larger than its longitudinal pressure as a result of the fast longitudinal expansion, which results in an oblate lepton distribution. By constrast, direct (Drell-Yan) production by quarks and antiquarks from incoming nuclei, whose momenta are essentially longitudinal, results in a prolate distribution. As the invariant mass increases, Drell-Yan gradually becomes the dominant source of dilepton production, and the lepton distribution evolves from oblate to prolate. The invariant mass at which the transition occurs is highly sensitive to the equilibration time of the quark-gluon plasma or, equivalently, the shear viscosity over entropy ratio $\eta/s$ in the early stages of the collision.Comment: 6 pages, 3 figure

Measuring the Abundance of Sub-kilometer-sized Kuiper Belt Objects Using Stellar Occultations

We present here the analysis of about 19,500 new star hours of low ecliptic latitude observations (|b| ≤ 20°) obtained by the Hubble Space Telescope's Fine Guidance Sensors over a time span of more than nine years, which is in addition to the ~12, 000 star hours previously analyzed by Schlichting et al. Our search for stellar occultations by small Kuiper Belt Objects (KBOs) yielded one new candidate event corresponding to a body with a 530 ± 70 m radius at a distance of about 40 AU. Using bootstrap simulations, we estimate a probability of ≈5% that this event is due to random statistical fluctuations within the new data set. Combining this new event with the single KBO occultation reported by Schlichting et al. we arrive at the following results: (1) the ecliptic latitudes of 6º.6 and 14º.4 of the two events are consistent with the observed inclination distribution of larger, 100-km-sized KBOs. (2) Assuming that small, sub-kilometer-sized KBOs have the same ecliptic latitude distribution as their larger counterparts, we find an ecliptic surface density of KBOs with radii larger than 250 m of N(r > 250 m) = 1.1^(+1.5)_(–0.7) × 10^7 deg^(–2); if sub-kilometer-sized KBOs have instead a uniform ecliptic latitude distribution for –20° 250 m) = 4.4^(+5.8)_(–2.8) × 10^6 deg^(–2). This is the best measurement of the surface density of sub-kilometer-sized KBOs to date. (3) Assuming the KBO size distribution can be well described by a single power law given by N(> r) ∝ r^(1–q) , where N(> r) is the number of KBOs with radii greater than r, and q is the power-law index, we find q = 3.8 ± 0.2 and q = 3.6 ± 0.2 for a KBO ecliptic latitude distribution that follows the observed distribution for larger, 100-km-sized KBOs and a uniform KBO ecliptic latitude distribution for –20° 4.0 at 2σ, confirming a strong deficit of sub-kilometer-sized KBOs compared to a population extrapolated from objects with r > 45 km. This suggests that small KBOs are undergoing collisional erosion and that the Kuiper Belt is a true analog to the dust producing debris disks observed around other stars

A Rapid Population Assessment Method for Wild Pigs Using Baited Cameras at 3 Study Site

Reliable and efficient population estimates are a critical need for effective management of invasive wild pigs (Sus scrofa). We evaluated the use of 10‐day camera grids for rapid population assessment (RPA) of wild pigs at 3 study sites that varied in vegetation communities and wild pig densities. Study areas included Buck Island Ranch, Florida; Tejon Ranch, California; and the Savannah River Site, South Carolina, USA, during 2016–2018. Rapid population assessments grids were composed of baited camera traps spaced approximately 500 or 750 m apart. Two RPA grids were deployed per study site and each grid was deployed twice (4–6 months apart) to assess changes in response to season or population control efforts. We assessed the ability of RPA grids to track population trends, how camera number influenced estimate precision, and how relative abundance indices related to density estimates. We detected changes in occupancy probability, detection probability, and N‐mixture estimates following removal operations and between seasons, but the ability of RPA grids to track population trends was dependent on the statistical method used and number of cameras traps. Increasing the number of cameras traps used in RPA grids increased precision, and these results can be used in determining survey design and estimate choice. We found that estimates of occupancy probability, detection probability, and N‐mixture estimates were positively correlated with spatially explicit capture-recapture density estimates. Thus, these less labor‐intensive estimates from RPA grids showed potential to index the relative abundance of wild pigs in some systems. Our evaluation of RPAs indicates that using study‐specific combinations of statistical method and number of cameras can provide a useful tool for monitoring wild pig presence, tracking population trends, and evaluating the effectiveness of management actions

Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma

Background: Response rates are primary endpoints in many oncology trials; however, correlation with overall survival (OS) is not uniform across cancer types, treatments, or lines of therapy. This study explored the association between objective response (OR) and OS in patients with chemotherapy-refractory metastatic Merkel cell carcinoma who received avelumab (anti-PD-L1). Methods: Eighty-eight patients enrolled in JAVELIN Merkel 200 (part A; NCT02155647) received i.v. avelumab 10 mg/kg every 2 weeks until confirmed progression, unacceptable toxicity, or withdrawal. Using conditional landmark analyses, we compared OS in patients with and without confirmed OR (RECIST v1.1). We applied a Cox model that included OR as a time-varying covariate and adjusted for age, visceral disease, and number of previous therapies. Results: Twenty-nine patients had confirmed OR; 20 by study week 7 and 7 more between study weeks 7 and 13. Survival probabilities 18 months after treatment initiation were 90% [95% confidence interval (CI) 65.6-97.4] in patients with OR at week 7 and 26.2% (95% CI 15.7-37.8) in patients without OR but who were alive at week 7. Median OS was not reached in patients with OR and was 8.8 months (95% CI 6.4-12.9) in patients without. Similar results were observed for the week 13 landmark. The adjusted Cox model showed OR was associated with a 95% risk reduction of death [hazard ratio 0.052 (95% CI 0.018-0.152)] compared with a nonresponse. Conclusions: Patients with OR by 7 or 13 weeks had significantly longer OS than patients without, confirming that early OR is an endpoint of major importance

Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study

Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1-associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1-positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC