Evaluation of a flexible NOTA-RGD kit solution using Gallium-68 from different ⁶⁸Ge/⁶⁸Ga-generators : pharmacokinetics and biodistribution in nonhuman primates and demonstration of solitary pulmonary nodule imaging in humans

PURPOSE : Radiopharmaceuticals containing the motive tripeptide arginyl-glycyl-asparatic acid (RGD) are known to target ανβ3 integrins during tumor angiogenesis. A more generic kit radiolabeling procedure accommodating Ga-68 from different generators was developed for NOTA-RGD and evaluated for its versatile use and safety in subsequent in vivo applications. The [⁶⁸Ga]NOTA-RGD kit was further verified for its expected biodistribution and pharmacokinetics in nonhuman primates and its clinical sensitivity to detect solitary pulmonary nodules (SPN) in cancer patients. PROCEDURES : Single vial kits containing 28–56 nmol of NOTA-cyclo-Arg-Gly-Asp-d-Tyr-Lys (NOTA-RGD) and sodium acetate trihydrate buffer were formulated. Versatility of the NOTARGD radiolabeling performance and adaption to a TiO2- and a SnO2-based generator type, characterization and long-term storage stability of the kits were carried out. The blood clearance and urine recovery kinetics as well as the image-guided biodistribution of [⁶⁸Ga]NOTA-RGD was studied in a vervet monkey model. [⁶⁸Ga]NOTA-RGD kits were further tested clinically to target solitary pulmonary nodules. RESULTS : The kits could be successfully formulated warranting integrity over 3–4 months with a good [⁶⁸Ga]NOTA-RGD radiolabeling performance (radiochemical purity 995 %, decay corrected yield 76–94 %, specific activity of 8.8–37.9 GBq/μmol) The kits met all quality requirements to be further tested in vivo. [⁶⁸Ga]NOTA-RGD cleared rapidly from blood and was majorly excreted via the renal route. The liver, spleen, heart and intestines showed initial uptake with steadily declining tissue activity concentration over time. In addition, the [⁶⁸Ga]NOTA-RGD kit allowed for delineation of SPN from non-malignant lung tissue in humans. CONCLUSIONS : A more versatile radiolabeling procedure using kit-formulated NOTA-RGD and different generator types was achieved. The uncompromised in vivo behavior and efficient targeting of SPN warrants further investigations on the clinical relevance of [⁶⁸Ga]NOTA-RGD derivatives to implement initial guidelines and management of patients, with regard to integrin targeted imaging.Nuclear Technologies in Medicine and the Biosciences Initiative (NTeMBIhttps://link.springer.com/journal/113072018-06-30Nuclear Medicin

A New Innovative Spherical Cermet Nuclear Fuel Element to Achieve an Ultra-Long Core Life for use in Grid-Appropriate LWRs

Spherical cermet fuel elements are proposed for use in the Atoms For Peace Reactor (AFPR-100) concept. AFPR-100 is a small-scale, inherently safe, proliferation-resistant reactor that would be ideal for deployment to nations with emerging economies that decide to select nuclear power for the generation of carbon-free electricity. The basic concept of the AFPR core is a water-cooled fixed particle bed, randomly packed with spherical fuel elements. The flow of coolant within the particle bed is at such a low rate that the bed does not fluidize. This report summarizes an approach to fuel fabrication, results associated with fuel performance modeling, core neutronics and thermal hydraulics analyses demonstrating a ~20 year core life, and a conclusion that the proliferation resistance of the AFPR reactor concept is high

Race, Slavery, and the Expression of Sexual Violence in Louisa Picquet, The Octoroon

Historically, victims of sexual violence have rarely left written accounts of their abuse, so while sexual violence has long been associated with slavery in the United States, historians have few accounts from formerly enslaved people who experienced it first-hand. Through a close reading of the narrative of Louisa Picquet, a survivor of sexual violence in Georgia and Louisiana, this article reflects on the recovery of evidence of sexual violence under slavery through amanuensis-recorded testimony, the unintended evidence of survival within the violent archive of female slavery, and the expression of “race” as an authorial device through which to demonstrate the multigenerational nature of sexual victimhood

Hyperemesis gravidarum severity, enteral tube feeding and cardiometabolic markers in offspring cord blood

Publisher Copyright: © The Authors 2022.Peer reviewedPublisher PD

Dissidents and God-Talk in the Johannine Epistles

Peer reviewe

Thyroid-stimulating hormone and free thyroxine fail to predict the severity and clinical course of hyperemesis gravidarum : A prospective cohort study

Funding information: This prospective cohort study was supported by a research grant from North West Hospital Group, Alkmaar, the Netherlands (Grant number: 2013T085) and by a research grant from the Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam UMC, the Netherlands (Project number: 23346). ACKNOWLEDGMENTS We thank Dr. J.P. Bestwick (employed at Queen Mary University of London, London, UK) and Professor Dr. J.H. Lazarus (employed at Cardiff School of Medicine, Cardiff, UK) for providing TSH medians from their study in the UK. Dr. J.P. Bestwick and Professor Dr. Lazarus have nothing to disclose.Peer reviewedPublisher PD

Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery.

BACKGROUND The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. METHODS In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red-cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red-cell transfusion and other clinical outcomes. RESULTS The primary outcome occurred in 11.4% of the patients in the restrictive-threshold group, as compared with 12.5% of those in the liberal-threshold group (absolute risk difference, -1.11 percentage points; 95% confidence interval [CI], -2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive-threshold group and 3.6% in the liberal-threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red-cell transfusion occurred in 52.3% of the patients in the restrictive-threshold group, as compared with 72.6% of those in the liberal-threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between-group differences with regard to the other secondary outcomes. CONCLUSIONS In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .)

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$  < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust