Ten years ago, this series of seven previous publications announced the practical realization of the true unification of all domains of traditional physics under the new paradigm of the quantized Universe. The aim of this series is to present the main theoretical and practical consequences of the unification in physics to a wider scientific community, especially to astrophysicists, geophysicists, and biophysicists. Nevertheless, even today, ten years later, the scientific community seems to be completely unaware of this fundamental progress in science. Therefore, the present part of the series shows once more an overview of the most important achievements of the new-paradigm scientific description of the Universe and of life in it, and of the both creation and evolution from the very beginning until today. Moreover, we are able today, for the first time in human history, to predict the future evolution of the Solar System and of ourselves over the coming millennia. VC 2026 Physics Essays Publication.
Red yeast rice (RYR) is marketed as a dietary supplement because it contains natural 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), including monacolin K. However, there is concern that some RYR supplements may be adulterated with the pharmaceutical drug lovastatin to enhance health claims. We have developed an optimized method to isolate monacolin K/lovastatin from complex RYR dietary supplement matrices to then test for adulteration in RYR supplements using stable carbon isotope (delta C-13) analysis. Samples were initially screened for monacolin K/lovastatin using liquid chromatography with mass spectrometric detection (LC-MS). To ensure the extraction process did not affect the measured isotopic values (i.e., isotopic fractionation effects), neat lovastatin standards were spiked into two types of blank RYR matrices (powder and gel). The monacolin K/lovastatin peaks were detected using high performance liquid chromatography with ultraviolet detection (HPLC-UV) and isolated using fraction collection. Residual matrix components were removed from targeted fractions by solid phase extraction (SPE) using graphitized carbon black cartridges. The resulting isolates were then analyzed using elemental analyzer-isotope ratio mass spectrometry (EA-IRMS) to measure delta C-13 values. The delta C-13 values of the extracted lovastatin standards were compared to their respective neat lovastatin delta C-13 values and demonstrated negligible isotopic fractionation effects. Using this optimized clean up method and carbon isotope analysis, thirty-one samples were screened. Eight RYR dietary supplement samples had >0.8 mg/g of monacolin K/lovastatin, our minimum threshold for analyzing samples using this method. Four of these eight samples had delta C-13 values greater than -28.3 parts per thousand, a previously proposed cutoff value for natural monacolin K, indicating likely adulteration. Additionally, five RYR powder samples were analyzed as part of a collaborative study using in-house methods from two laboratories and the data shows acceptable agreement in the delta C-13 values of monacolin K/lovastatin (differences ranging from +/- 0.02 parts per thousand to +/- 0.76 parts per thousand). This optimized method represents a robust, reproducible procedure for detecting lovastatin adulteration in dietary supplements with minimal isotopic fractionation.
4020 Background: 212Pb-DOTAMTATE is a Targeted Alpha Therapy (TAT) in clinical development for subjects with SSTR+ neuroendocrine tumors. A phase I dose-escalation study has already been completed (Delpassand et al. J Nucl Med 2022). TAT holds the promise to improve outcomes versus Peptide Receptor Radionuclide Therapy (PRRT) with beta-emitters like 177Lu-DOTATATE, currently considered the standard of care for subjects with GEP-NETs. Methods: ALPHAMEDIX 02 is a Phase II, open-label, multicenter study evaluating the safety, tolerability and efficacy of 212Pb-DOTAMTATE in PRRT-naïve (Cohort 1, N = 36) and PRRT-refractory (Cohort 2, Target N = 30) subjects with histologically confirmed unresectable or metastatic GEP-NETs, positive somatostatin analogue imaging and at least 1 site of measurable disease per RECIST 1.1. 212Pb-DOTAMTATE was administered at 67.6 μCi/kg per cycle, with a maximum activity administered per cycle of 5.5 mCi every 8 weeks, for up to 4 cycles. Primary endpoints include overall response rate (ORR) per RECIST1.1, and incidence and severity of adverse events (AEs). Secondary endpoints include progression free survival, overall survival , and health-related quality of life. Initial results of the already completed cohort 1 are presented. Results: In cohort 1, 17 out of 36 subjects with metastatic SSTR+ GEP-NETs achieved a confirmed response (ORR 47.2% (32.0-63.0%)). In the Phase I trial, five out of eight PRRT- naïve subjects with SSTR+ GEP-NETs treated with the same regimen of 212Pb-DOTAMTATE achieved a response (ORR 62.5% (30.6-86.3%)): the combined ORR from both studies is 50% (22 out of 44, 95%-CI:36% - 64%). Median Duration of Response (DOR) has not been reached in both studies. Four out of five subjects (80%) with confirmed response in Phase I had a DOR of ≥ 12 months. In the ongoing Phase II study the response follow-up for 10 subjects with confirmed response is currently shorter than 6 months: so far 7 out of 17 subjects (41%) with confirmed response had a DOR of ≥ 6 months, and one of these subjects had a DOR of ≥ 12 months. Lymphocytopenia is a lead cause of the 59% grade 3 and 4 AEs reported in subjects in cohort 1. Overall, 4 fatal AEs were reported: death / progressive disease (N = 2), carcinoid syndrome (N = 1) and sepsis (N = 1). Conclusions: In PRRT-naïve subjects with SSTR+ unresectable or metastatic GEP-NETs treatment with up to 4 cycles of ²¹²Pb-DOTAMTATE (67.6 μCi/kg/cycle) was well-tolerated, with a safety profile consistent with the underlying disease and expected toxicities of radioligand therapy, similar to 177Lu-DOTATATE. The ORR of 47.2% in cohort 1 (50% in the pooled dataset) appears to be substantially higher than the ORR previously reported for 177Lu-DOTATATE in the pivotal NETTER-1 study (ORR 18% (10–25%)). Clinical trial information: NCT05153772 .
Fuel cycle design approaches vary significantly across the globe for LWR plants. This is driven by unique approaches to economic models, different operational modes, and variations in the regional safety criteria. Cycle length can vary from a few months up to 2 years. Other factors such as taxonomy, technical requirements and regulations have a strong influence as well. This paper assimilates available information to compare the various approaches worldwide and evaluate their impact on operational and safety analysis. In addition, there is a lot of technical work underway to evaluate increasing burnup and enrichment beyond currently approved limits. Environmental and political reasons such as lowering CO2 production or reducing independence on other energy sources – both foreign and domestic can play an important role. Current fuel cycles as well as future evolution owing to ongoing improvements will be considered. This paper will be based on Framatome’s global experience for nuclear core design and safety analysis for PWRs and BWRs. Clearly this paper focuses on the technical part and shows how flexible nuclear power plants are today and how they will open the door to address emerging special requirements. With this operating space of nuclear power, it contributes to low carbon dioxide production, security of supply of electricity, highest safety standards and strong economic value for Nuclear Power Plant (NPP) operators.
