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The LUNEX5 (free electron Laser Using a New accelerator for the Exploitation of X-ray radiation of 5th generation) in France aims at investigating the generation of short, intense, and coherent pulses in the soft x-ray region (with two particular targeted wavelengths of 20 and 13 nm). It consists in a single Free Electron Laser (FEL) line with cryo-ready in-vacuum undulators using a Conventional Linear Accelerator (CLA) using the superconducting technology of 400 MeV or a Laser Wake Field Accelerator (LWFA) ranging from 0.4 to 1 GeV with multi-TW or PW lasers. The FEL line can be operated in the seeded (High order Harmonic in Gas seeding) and Echo Enable Harmonic Generation configurations, which performances will be compared. Two pilot user experiments for time-resolved studies of isolated species and magnetization dynamics will take benefit of LUNEX5 FEL radiation.

A fast multimodal scanning X-ray imaging scheme is prototyped at Soleil Synchrotron. It permits the simultaneous acquisition of complementary information on the sample structure, composition and chemistry by measuring transmission, differential phase contrast, small-angle scattering, and X-ray fluorescence by dedicated detectors with ms dwell time per pixel. The results of the proof of principle experiments are presented in this paper.

The concept of causality remains a controversial issue in social scientific research. For decades, researchers have used the Elaboration Model, established in sociology, and the Validity Typology, established in psychology, as frameworks for analyzing causal inferences. Rubin's Causal Model, developed in statistics and not widely known in the social sciences, offers a system of causal effect equations and a causal variable definition that contribute interesting insights to the evaluation of causal inferences. Each of these three models was applied to three published research articles. The comparison of applications demonstrates some disagreement over what constitutes a valid causal inference, and also highlights areas in each model that could benefit from clarification. A resulting list of guidelines was developed for researchers to consider when designing and interpreting research meant for causal inferences.

PurposePeptide receptor radionuclide therapy (PRRT) is mostly administered using a fixed injected activity (IA) per cycle. This empiric regime results in highly variable absorbed doses to the critical organs and undertreatment of the majority of patients. We conceived a personalized PRRT protocol in which the IA is adjusted to deliver a prescribed absorbed dose to the kidney, with the aim to safely increase tumour irradiation. We herein report on the initial results of our prospective study of personalized PRRT, the P-PRRT Trial (NCT02754297).MethodsPRRT-naïve patients with progressive and/or symptomatic neuroendocrine tumour (NET) were scheduled to receive a four-cycle induction course of 177Lu-octreotate with quantitative SPECT/CT-based dosimetry. The IA was personalized according to the glomerular filtration rate and the body surface area for the first cycle, and according to the prior renal Gy/GBq for the subsequent cycles. The prescribed renal absorbed dose of 23 Gy was reduced by 25–50% in case of significant renal or haematological impairment. Responders were allowed to receive consolidation or maintenance cycles, for each of which 6 Gy to the kidney were prescribed. We simulated the empiric PRRT regime by fixing the IA at 7.4 GBq per cycle, with the same percentage reductions as above. Radiological, molecular imaging, biochemical, and quality of life responses, as well as safety, were assessed.ResultsFifty-two patients underwent 171 cycles. In 34 patients who completed the induction course, a median cumulative IA of 36.1 (range, 6.3–78.6) GBq was administered, and the median cumulative kidney and maximum tumour absorbed doses were 22.1 (range, 8.3–24.3) Gy and 185.7 (range: 15.2–443.1) Gy respectively. Compared with the simulated fixed-IA induction regime, there was a median 1.26-fold increase (range, 0.47–2.12 fold) in the cumulative maximum tumour absorbed dose, which was higher in 85.3% of patients. In 39 assessable patients, the best objective response was partial response in nine (23.1%), minor response in 14 (35.9%), stable disease in 13 (33.3%) and progressive disease in three patients (7.7%). In particular, 11 of 13 patients (84.6%) with pancreatic NET had partial or minor response. The global health status/quality of life score significantly increased in 50% of patients. Acute and subacute side-effects were all of grade 1 or 2, and the most common were nausea (in 32.7% of patients) and fatigue (in 30.8% of patients) respectively. Subacute grade 3 or 4 toxicities occurred in less than 10% of patients, with the exception of lymphocytopenia in 51.9% of patients, without any clinical consequences however. No patient experienced severe renal toxicity.ConclusionsPersonalized PRRT makes it possible to safely increase tumour irradiation in the majority of patients. Our first results indicate a favourable tolerance profile, which appears similar to that of the empiric regime. The response rates are promising, in particular in patients with NET of pancreatic origin.

Background: The extent to which ambient air pollution contributes to the pathogenesis of congenital heart defects remains uncertain. Objective: We investigated whether first trimester exposure to ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) was associated with the risk of critical and noncritical heart defects in a large population-based cohort of births. Methods: We carried out a retrospective cohort study of children conceived between 2000 and 2016 in Quebec, Canada. Heart defects were identified via data from the Maintenance and Use of Data for the Study of Hospital Clientele registry. The main exposures were average concentration of PM2.5 and NO2 in a) the first trimester and b) the month of conception. Exposures were estimated at the residential postal code. Associations with critical and noncritical heart defects were assessed using logistic regression models, adjusted for maternal and infant characteristics. We considered single- and two-pollutant models and assessed modifying effects of maternal comorbidity, including preexisting hypertension, preeclampsia, anemia, and diabetes. Results: The cohort comprised 1,342,198 newborns, including 12,715 with heart defects. Exposure in the first trimester and month of conception yielded similar results; both were associated with a greater risk of heart defects. Adjusted odds ratios (OR) for any heart defect per interquartile range increase were 1.02 (95% CI: 1.00,1.05) for PM2.5 and 1.10 (95% CI: 1.07, 1.13) for N02. Associations with atrial septal defects were 1.08 (95% CI: 1.03,1.14) for PM25 and 1.19 (95% CI: 1.12, 1.25) for NO2. Corresponding ORs for ventricular septal defects and individual critical heart defects were not significant. PM2.5 (OR= 1.11; 95% CI: 1.06, 1.17) and N02 (OR= 1.23; 95% CI: 1.17, 1.31) exposure were associated with a greater risk of heart defects in mothers with comorbidity. Discussion: In this population-based cohort, prenatal exposure to ambient air pollution during the first trimester was associated with an increased risk of heart defects, particularly atrial septal defects. The association with heart defects was greater in mothers with comorbidity.

This study examines the drivers of digital payment adoption across 711 Indian districts within the Unified Payments Interface (UPI) ecosystem from 2020 to 2024. Utilising a multi-method empirical approach—including mixed-effects models, first-differences, and quarterly distributed lag analyses—we investigate whether merchant network development or digital infrastructure represents the primary constraint on adoption. The results reveal that business ecosystem development, measured by formal UDYAM registrations, is a significantly stronger driver of adoption than internet connectivity. Cumulative merchant effects were found to exceed infrastructure effects by a factor of approximately six in quarterly analyses. A quasi-experimental analysis of India’s staggered 5G rollout identifies a structural break in this relationship: once a threshold of high-speed connectivity is reached, incremental infrastructure improvements yield near-zero marginal returns for user onboarding. In this post-5G regime, the merchant network emerges as the nearly exclusive driver of new user registration. On the demand side, our findings reveal a stark cross sectional gender digital divide; while men’s mobile finance participation is a dominant driver of adoption, women’s participation remains statistically insignificant. Interpreted through Rogers’ Diffusion of Innovation curve, women currently occupy the status of late adopters or laggards, facing accessibility barriers and structural constraints rather than demand deficits. These results directly engage with Sustainable Development Goals (SDGs) 5, 8, 9, and 10. We conclude that as connectivity reaches saturation, policymakers must pivot from “providing pipes” to “empowering participants”. This requires prioritising merchant formalisation alongside targeted digital skilling and consumer education for women to mitigate the gender digital divide and achieve inclusive, sustainable economic growth.

Terbium-161 (161Tb) emits beta-radiation similar to lutetium-177 (177Lu), with additional radiation over ultra-short path lengths from Auger electrons. 161Tb has shown superior in-vitro and in-vivo efficacy compared with 177Lu. We aimed to evaluate the safety of [161Tb]Tb-PSMA-I&T in patients with metastatic castration-resistant prostate cancer (mCRPC). VIOLET was an investigator-initiated, single-centre, phase 1/2 trial, conducted at the Peter MacCallum Cancer Centre (Melbourne, VIC, Australia). Eligible patients were men aged 18 years or older with progressive mCRPC (histologically or cytologically confirmed adenocarcinoma of the prostate or unequivocal diagnosis of metastatic prostate cancer with an elevated serum prostate specific antigen) previously treated with an androgen receptor pathway inhibitor and taxane chemotherapy (unless medically unsuitable), Eastern Cooperative Oncology Group performance status of 0–2, and prostate-specific membrane antigen (PSMA) positivity (maximum standardised uptake value ≥20 on PSMA PET-CT) without discordance on 2-[18F]fluoro-2-deoxy-D-glucose (FDG) PET-CT. Dose escalation (3 + 3 design) had three prespecified radioactivities (4·4 GBq, 5·5 GBq, and 7·4 GBq). Up to six cycles of [161Tb]Tb-PSMA-I&T were administered intravenously every 6 weeks, reduced by 0·4 GBq for each cycle. Primary endpoints of phase 1 were dose-limiting toxicities, the maximum tolerated dose, and the recommended phase 2 dose, and the primary objective of phase 2 was evaluation of adverse events as defined by Common Terminology Criteria for Adverse Events version 5.0. We present here an interim analysis, with follow-up ongoing and recruitment reopened for an additional dose level (9·5 GBq). The trial is registered at ClinicalTrials.gov (NCT05521412). Between Oct 14, 2022 and Feb 15, 2024, 30 eligible patients were enrolled. Median age was 69·0 years (IQR 66·0–74·8), screening PSA 26·9 ng/mL (10·1–70·0), PSMA mean standardised uptake value 8·2 (7·4–10·8), and 20 (67%) of 30 patients had received previous docetaxel. There were no dose-limiting toxicities. The maximum administered dose and recommended phase 2 dose was 7·4 GBq. Grade 3 treatment-related adverse events (TRAEs) were limited to pain (one [3%] of 30; the only serious TRAE) and lymphopenia (one [3%] of 30). No grade 4 TRAEs or treatment-related deaths occurred. No dose reductions or treatment discontinuation occurred for toxicity. [161Tb]Tb-PSMA-I&T is safe at the maximum administered dose of 7·4 GBq. Further investigation of this promising radionuclide is warranted in larger, randomised clinical trials. Prostate Cancer Foundation, Peter MacCallum Cancer Foundation, National Health and Medical Research Council Investigator Grant, Isotopia Molecular Imaging.

BackgroundTumour 18F-FDG-uptake is of prognostic value in high-risk and metastatic prostate cancer (PCa). The aim of this study is to investigate the underlying glucose metabolism mechanisms of 18F-FDG-uptake on PET/CT imaging in PCa.MethodsRetrospective analysis was conducted for 94 patients diagnosed with a Gleason sum ≥8 adenocarcinoma of the prostate at biopsy between July 2011 and July 2014 who underwent 18F-FDG-PET/CT imaging before radical prostatectomy (RP). 18F-FDG-uptake in primary lesion was measured by a blinded reader using maximum standardised uptake value (SUVmax). GLUT1, GLUT12 and HK2 expression were blindly scored after immunohistochemistry on specimens RP by three pathologists. Correlations between GLUT1, GLUT12 and HK2, and SUVmax were assessed using Spearman’s rank correlation test. Survival probabilities were based on the Kaplan–Meier method.ResultsWith a median follow-up of 4.5 years, 56% (n = 53) of patients had biochemical recurrence (BCR), 7% (n = 7) progressed to castration-resistant prostate cancer (CRPC) disease, 13% (n = 12) developed metastasis and 6% (n = 6) died. Correlation was found between GLUT1 expression and SUVmax level (r = 0.25, p = 0.02). In addition, SUVmax was significantly higher in tumours with high GLUT1 expression (n = 17, 5.74 ± 1.67) than tumours with low GLUT1 expression (n = 71, 2.68 ± 0.31, p = 0.004). Moreover, a significant association was found between GLUT1 expression levels and SUVmax level (p = 0.005), lymph node status (p = 0.05), volume of cancer (p = 0.01), CRPC disease progression (p = 0.02) and metastasis development (p = 0.04). No significant difference between GLUT12 and HEX2 expression and SUVmax have been found.ConclusionsGLUT1 expression in PCa tumours correlates with 18F-FDG-uptake and poor prognostic factors. These results suggest that this transporter is involved in the molecular mechanism of 18F-FDG-uptake in high-risk PCa and raise interest in targeting metabolic dependencies of PCa cells as a selective anticancer strategy.

Lutetium-177 [177Lu]Lu-PSMA-I&T (177Lu-PSMA-I&T) and the bone-seeking α-emitter radium-223 (223Ra) are established life-extending therapies for patients with metastatic castration-resistant prostate cancer; however, resistance and progression are inevitable. We aimed to evaluate the safety and preliminary antitumour activity of 177Lu-PSMA-I&T combined with 223Ra in this patient group. We conducted an investigator-initiated, single-centre, single-arm, phase 1/2 trial (AlphaBet) at the Peter MacCallum Cancer Centre in Melbourne, Australia. Adults (aged ≥18 years) with a diagnosis of progressive, metastatic castration-resistant prostate cancer, an Eastern Cooperative Oncology Group performance status score of 0–2, at least two visible bone metastases not treated with radiotherapy, previous exposure to an androgen receptor pathway inhibitor, prostate-specific membrane antigen (PSMA)-positive disease (defined by maximum standardised uptake value ≥20 at a site of disease), and no discordant sites (ie, avid on 2-[18F]fluoro-2-deoxy-D-glucose-PET–CT with minimal PSMA expression and no uptake on bone scintigraphy) were eligible for inclusion. Phase 1 dose-escalation assessed two dose levels of 223Ra (27·5 kBq/kg and 55·0 kBq/kg) combined with 7·4 GBq 177Lu-PSMA-I&T, administered intravenously every 6 weeks for up to six cycles. Phase 2 dose expansion continued with the recommended phase 2 dose. Co-primary endpoints were the maximum tolerated or administered dose and the recommended phase 2 dose (phase 1), and the PSA response rate (phase 2), analysed in all patients treated at the maximum tolerated or administered dose in either phase. Safety was assessed in all patients who received at least one dose of either protocol treatment in phase 1 or 2. Herein, we report the results of an interim analysis, which was added to the protocol following an amendment on May 30, 2024. This trial is registered at ClinicalTrials.gov (NCT05383079) and follow-up is ongoing. Between Nov 3, 2022, and Nov 5, 2024, 37 patients were enrolled, of whom 36 (97%; median age 72·5 years [IQR 67·0–78·0]) were included in the safety analysis and 33 (89%) were included in the preliminary activity analysis. No dose-limiting toxicities were observed. The recommended phase 2 dose of 223Ra was 55·0 KBq/kg combined with 7·4 GBq 177Lu-PSMA-I&T, administered every 6 weeks. With a median follow-up of 13·3 months (IQR 8·7–17·1), 11 (31%) patients completed all six cycles of both treatments. 18 (50%) patients discontinued treatment early, primarily due to unequivocal disease progression (11 [61%]) or adverse events (three [17%]). A reduction in PSA of at least 50% was observed in 18 (55%; 95% CI 36–72) patients. Grade 3 or higher treatment-related adverse events occurred in five (14%) of 36 patients, including anaemia (four [11%]) and neutropenia (three [8%]), with no treatment-related deaths. Non-clinically significant grade 3 lymphopenia occurred in ten (28%) patients. The combination of 177Lu-PSMA-I&T and 223Ra is safe and feasible in patients with metastatic castration-resistant prostate cancer and bone metastases. These findings warrant further evaluation of combined α-emitting and β-emitting approaches. Prostate Cancer Foundation, Bayer, and National Health and Medical Research Council.