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14 result(s) for "Bore, Paul"
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Paclitaxel–bevacizumab combination in advanced non-squamous non-small-cell lung cancer (NSCLC): AVATAX, a retrospective multicentric study
Introduction: Compared with docetaxel, the phase-III trial, ULTIMATE, showed a significant improvement of progression-free survival (PFS) with paclitaxel–bevacizumab combination (PB) as second- or third-line treatment in advanced non-small cell lung cancer (NSCLC). With the increase of immunotherapy treatment in first-line settings, the optimal treatment after first-line failure must be redefined. Methods: This multicentric retrospective study identified all advanced NSCLC patients treated with PB as second-line therapy and beyond. The main efficacy outcomes assessed were objective response rate (ORR), disease control rate (DCR), PFS, and overall survival (OS). The adverse events were reported according to Common Terminology Criteria for Adverse Events (CTCAE). Results: From January 2010 to February 2020, 314 patients in 16 centers received the PB combination. Most patients were male (55%), with a median age of 60 years (19–82), 95% had adenocarcinoma, 27% had a performance status ⩾2, 45% had brain metastases at the time of inclusion. They mostly received the PB combination either in second (20%) or in third-line (39%), and 28% were treated just after ICI failure. ORR and DCR were 40% and 77%, respectively; median PFS and OS were 5.7 [interquartile range (IQR): 3.2–9.6] and 10.8 [IQR: 5.3–19.6] months, respectively. All grade adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued monotherapy (mostly with bevacizumab) alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compared with those not previously treated with ICI (ICI−): 7.0 [IQR: 4.2–11.0] versus 5.2 [IQR: 2.9–8.8] months, p = 0.01, without statistically significant difference for OS between these two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment and performance status of 0–1. Only a performance status of 0–1 was associated with superior OS. Conclusion: PB combination as second-line treatment or beyond for advanced non-squamous NSCLC had acceptable toxicity and a clinically relevant efficacy and is an option as salvage treatment for these patients, more particularly after ICI progression.
False Positive 18F-FDG Positron Emission Tomography Findings in Schwannoma—A Caution for Reporting Physicians
Schwannoma is a rare source of false-positive 18F-fluorodeoxyglucose (18F-FDG) uptake in Positron-emission tomography (PET/CT), inducing potential errors in staging of several solid cancer, with implications for patient management. This clinical case reports the situation of a patient undergoing an 18F-FDG-PET/CT for initial staging of an ovarian adenocarcinoma. We found a high paramediastinal hypermetabolic mass suspicious of remote extension or secondary synchronous primitive tumor. The biopsy finally reveals a histopathology of Schwannoma, allowing the patient to be eligible for a surgical procedure of her ovarian adenocarcinoma by rejecting the hypothesis of malignancy.
Abscopal Response in Metastatic Melanoma: Real-World Data of a Retrospective, Multicenter Study
Objective: To evaluate the incidence of the abscopal response (AR) in patients with metastatic melanoma requiring palliative radiotherapy (RT). Patients and methods: Patients treated for metastatic melanoma between January 1998 and February 2020 in four oncology departments were screened. Patients with progression under immune checkpoint inhibitors or without ongoing systemic treatment, and requiring palliative RT were considered. The AR was defined as an objective response according to RECIST and/or iRECIST for at least one non-irradiated metastasis at distance (≥10 cm) from the irradiated lesion. Primary endpoint was the rate of AR. Secondary endpoints were overall survival (OS), progression-free survival (PFS), local control (LC) of the irradiated lesion, and toxicity as assessed by CTCAE v5. Results: Over the period considered, 118 patients were included and analyzed. Fifteen patients (12.7%) had an AR. With a median follow-up of 7.7 months (range, 0.2–242.2), median OS and PFS after RT were significantly longer in patients with an AR compared to those without: 28 vs. 6.6 months (p < 0.01) and not reached vs. 3.2 months, respectively. No grade ≥2 toxicity was reported. Patients who developed an AR were more likely to be treated with immunotherapy (93.3% vs. 55.9%, p = 0.02). In multivariate analysis, they had a higher number of irradiated metastases treated concomitantly (HR = 16.9, p < 0.01) and a higher rate of mild infections during RT (HR = 403.5, p < 0.01). Conclusions: AR in metastatic melanoma seems to be highly prognostic of overall survival, although it is a rare phenomenon. It may be promoted by multiple concomitant treatments with RT and immunotherapy and by acute inflammatory events such as infection.
Paclitaxel–bevacizumab combination in advanced non-squamous non-small-cell lung cancer (NSCLC): AVATAX, a retrospective multicentric study
Introduction: Compared with docetaxel, the phase-III trial, ULTIMATE, showed a significant improvement of progression-free survival (PFS) with paclitaxel-bevacizumab combination (PB) as second-or third-line treatment in advanced non-small cell lung cancer (NSCLC). With the increase of immunotherapy treatment in first-line settings, the optimal treatment after first-line failure must be redefined. Methods: This multicentric retrospective study identified all advanced NSCLC patients treated with PB as second-line therapy and beyond. The main efficacy outcomes assessed were objective response rate (ORR), disease control rate (DCR), PFS, and overall survival (OS). The adverse events were reported according to Common Terminology Criteria for Adverse Events (CTCAE). Results: From January 2010 to February 2020, 314 patients in 16 centers received the PB combination. Most patients were male (55%), with a median age of 60 years (19-82), 95% had adenocarcinoma, 27% had a performance status ⩾2, 45% had brain metastases at the time of inclusion. They mostly received the PB combination either in second (20%) or in thirdline (39%), and 28% were treated just after ICI failure. ORR and DCR were 40% and 77%, respectively; median PFS and OS were 5.7 [interquartile range (IQR): 3.2-9.6] and 10.8 [IQR: 5.3-19.6] months, respectively. All grade adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued monotherapy (mostly with bevacizumab) alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compared with those not previously treated with ICI (ICI-): 7.0 [IQR: 4.2-11.0] versus 5.2 [IQR: 2.9-8.8] months, p = 0.01, without statistically significant difference for OS between these two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment and performance status of 0-1. Only a performance status of 0-1 was associated with superior OS. Conclusion: PB combination as second-line treatment or beyond for advanced non-squamous NSCLC had acceptable toxicity and a clinically relevant efficacy and is an option as salvage treatment for these patients, more particularly after ICI progression.
Mobility, food and housing: responsibility, individual consumption and demand-side policies in European deep decarbonisation pathways
The Brundtland Commission report ‘Our Common Future’ highlighted that residents in high-income countries lead lifestyles incompatible with planetary boundaries. Three decades later, consumption-related greenhouse gas (GHG) emissions have continued to increase. To achieve ‘well below 2°C’ and 1.5 °C goals, consumption-related emissions must be substantially reduced in the coming decades. This paper provides insights on how to pursue 1.5 °C pathways through changes in household consumption. It draws on original data gathered in the project ‘HOusehold Preferences for reducing greenhouse gas Emissions in four European High Income Countries’ (HOPE) to analyse policies targeting and affecting direct and indirect GHG emissions in three household consumption categories (mobility, housing and food) in four countries (France, Germany, Norway and Sweden) and four medium-sized cities. This paper demonstrates discrepancies and similarities between current governmental policy approaches in the four countries and household perceptions of consumption changes with respect to policy mechanisms, responsibilities and space for acting on mitigation. Current demand-side policy strategies rely heavily on instruments of self-governance and nudging behaviour. Whilst some of our data suggests that households broadly accept this, it also suggests that governments could more actively lead and steer demand-side mitigation via adjusting and supplementing a comprehensive list of 20 climate policy measures currently in place in one or more of the case countries. The paper concludes by suggesting areas for more effective policy change and household-level climate change mitigation to feed the next update of climate pledges under the Paris Agreement.
Methods for conducting trends analysis: roadmap for comparing outcomes from three national HIV Population-based household surveys in Kenya (2007, 2012, and 2018)
Background For assessing the HIV epidemic in Kenya, a series of independent HIV indicator household-based surveys of similar design can be used to investigate the trends in key indicators relevant to HIV prevention and control and to describe geographic and sociodemographic disparities, assess the impact of interventions, and develop strategies. We developed methods and tools to facilitate a robust analysis of trends across three national household-based surveys conducted in Kenya in 2007, 2012, and 2018. Methods We used data from the 2007 and 2012 Kenya AIDS Indicator surveys (KAIS 2007 and KAIS 2012) and the 2018 Kenya Population-based HIV Impact Assessment (KENPHIA 2018). To assess the design and other variables of interest from each study, variables were recoded to ensure that they had equivalent meanings across the three surveys. After assessing weighting procedures for comparability, we used the KAIS 2012 nonresponse weighting procedure to revise normalized KENPHIA weights. Analyses were restricted to geographic areas covered by all three surveys. The revised analysis files were then merged into a single file for pooled analysis. We assessed distributions of age, sex, household wealth, and urban/rural status to identify unexpected changes between surveys. To demonstrate how a trend analysis can be carried out, we used continuous, binary, and time-to-event variables as examples. Specifically, temporal trends in age at first sex and having received an HIV test in the last 12 months were used to demonstrate the proposed analytical approach. These were assessed with respondent-specific variables (age, sex, level of education, and marital status) and household variables (place of residence and wealth index). All analyses were conducted in SAS 9.4, but analysis files were created in Stata and R format to support additional analyses. Results This study demonstrates trends in selected indicators to illustrate the approach that can be used in similar settings. The incidence of early sexual debut decreased from 11.63 (95% CI: 10.95–12.34) per 1,000 person-years at risk in 2007 to 10.45 (95% CI: 9.75–11.2) per 1,000 person-years at risk in 2012 and to 9.58 (95% CI: 9.08–10.1) per 1,000 person-years at risk in 2018. HIV-testing rates increased from 12.6% (95% CI: 11.6%–13.6%) in 2007 to 56.1% (95% CI: 54.6%–57.6%) in 2012 but decreased slightly to 55.6% [95% CI: 54.6%–56.6%) in 2018. The decrease in incidence of early sexual debut could be convincingly demonstrated between 2007 and 2012 but not between 2012 and 2018. Similarly, there was virtually no difference between HIV Testing rates in 2012 and 2018. Conclusions Our approach can be used to support trend comparisons for variables in HIV surveys in low-income settings. Independent national household surveys can be assessed for comparability, adjusted as appropriate, and used to estimate trends in key indicators. Analyzing trends over time can not only provide insights into Kenya’s progress toward HIV epidemic control but also identify gaps.
Acute coronary syndrome rule-out strategies in the emergency department: an observational evaluation of clinical effectiveness and current UK practice
BackgroundNumerous strategies have been developed to rapidly rule-out acute coronary syndrome (ACS) using high-sensitivity troponin. We aimed to establish their performance in terms of emergency care length of stay (LOS) in real-world practice.MethodsA multicentre observational cohort study in 94 UK sites between March and April 2023. Recruitment was preferably prospective, with retrospective recruitment also allowed. Adults presenting to the ED with chest pain triggering assessment for possible ACS were eligible. Primary outcome was emergency care LOS. Secondary outcomes were index rate of acute myocardial infarction (MI), time to be seen (TTBS), disposition and discharge diagnosis. Details of ACS rule-out strategies in use were collected from local guidelines. Mixed effects linear regression models tested the association between rule-out strategy and LOS.Results8563 eligible patients were recruited, representing 5.3% of all ED attendances. Median LOS for all patients was 333 min (IQR 225, 510.5), for admitted patients was 460 min (IQR 239.75, 776.25) and for discharged patients was 313 min (IQR 221, 451). Heterogeneity was seen in the rule-out strategies with regard to recommended troponin timing. There was no significant difference in LOS in discharged patients between rule-out strategies defined by single and serial troponin timing (p=0.23 and p=0.41). The index rate of acute MI was 15.2% (1301/8563). Median TTBS was 120 min (IQR 57, 212). 24.4% (2087/8563) of patients were partly managed in a same day emergency care unit and 70% (5934/8563) of patients were discharged from emergency care.ConclusionDespite heterogeneity in the ACS rule-out strategies in use and widespread adoption of rapid rule-out approaches, this study saw little effect on LOS in real-world practice. Suspected cardiac chest pain still accounts for a significant proportion of UK ED attendances. ED system pressures are likely to be explanatory, but further research is needed to understand the reasons for the unrealised potential of these strategies.
Measurement Duration but Not Distance, Angle, and Neighbour-Proximity Affects Precision in Enteric Methane Emissions when Using the Laser Methane Detector Technique in Lactating Dairy Cows
The laser methane detector (LMD), is a proprietary hand-held open path laser measuring device. Its measurements are based on infrared absorption spectroscopy using a semiconductor laser as a collimated excitation source. In the current study, LMD measurements were carried out in two experiments using 20 and 71 lactating dairy cows in Spain and Scotland, respectively. The study aimed at testing four assumptions that may impact on the reliability and repeatability of the LMD measurements of ruminants. The study has verified that there is no difference in enteric methane measurements taken from a distance of 3 m than from those taken at a distance of 2 m; there was no effect to the measurements when the measurement angle was adjusted from 90° to 45°; that the presence of an adjacent animal had no effect on the methane measurements; and that measurements lasting up to 240 s are more precise than those taken for a shorter duration. The results indicate that angle, proximity to other animals, and distance had no effects and that measurements need to last a minimum of 240 s to maintain precision.
ICARUS-Q: Integrated Control and Readout Unit for Scalable Quantum Processors
We present a control and measurement setup for superconducting qubits based on Xilinx 16-channel radio-frequency system-on-chip (RFSoC) device. The proposed setup consists of four parts: multiple RFSoC boards, a setup to synchronise every digital to analog converter (DAC), and analog to digital converter (ADC) channel across multiple boards, a low-noise direct current (DC) supply for tuning the qubit frequency and cloud access for remotely performing experiments. We also design the setup to be free of physical mixers. The RFSoC boards directly generate microwave pulses using sixteen DAC channels up to the third Nyquist zone which are directly sampled by its eight ADC channels between the fifth and the ninth zones.
The STRANDS Project: Long-Term Autonomy in Everyday Environments
Thanks to the efforts of the robotics and autonomous systems community, robots are becoming ever more capable. There is also an increasing demand from end-users for autonomous service robots that can operate in real environments for extended periods. In the STRANDS project we are tackling this demand head-on by integrating state-of-the-art artificial intelligence and robotics research into mobile service robots, and deploying these systems for long-term installations in security and care environments. Over four deployments, our robots have been operational for a combined duration of 104 days autonomously performing end-user defined tasks, covering 116km in the process. In this article we describe the approach we have used to enable long-term autonomous operation in everyday environments, and how our robots are able to use their long run times to improve their own performance.