Determining the Age of Criminal Capacity: Acting in the best interest of children in conflict with the law

This article aims to stimulate critical discourse on the current practices regarding best interest of children in conflict with the law. The issue explored is whether determining the criminal capacity of children in conflict with the law is in the best interest of these children.Findings indicated that logistical and operational challenges are denying child offenders services as intended in the Act. In the light of this finding, the article advocates for keeping a clear vision of the Act’s restorative and rehabilitative intention as opposed to following a pragmatic approach during the upcoming review of the age of criminal capacity

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

Qualification of in-house prepared 68Ga RGD in healthy monkeys for subsequent molecular imaging of avß3 integrin expression in patients

MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014Introduction: Targeted pharmaceuticals for labelling with radio-isotopes for very specific imaging (and possibly later for targeted therapy) play a major role in Theranostics which is currently an important topic in Nuclear Medicine as well as personalised medicine. There was a need for a very specific lung cancer radiopharmaceutical that would specifically be uptaken in integrin avß3 expression cells to image patients using a Positron Emission Tomography- Computed Tomography (PET-CT) scanner. Background and problem statement: Cold kits of c (RGDyK)–SCN-Bz-NOTA were kindly donated by Seoul National University (SNU) to help meet Steve Biko Hospital’s need for this type of imaging. These cold kits showed great results internationally in labelling with a 0.1 M 68Ge/68Ga generator (t1/2 of 68Ge and 68Ga are 270.8 days and 67.6 min, respectively). However the same cold kits failed to show reproducible radiolabeling with the 0.6 M generator manufactured under cGMP conditions at iThemba LABS, Cape Town and distributed by IDB Holland, the Netherlands. Materials and methods: There was therefore a need for producing an in-house NOTA-RGD kit that would enable production of clinical 68Ga-NOTA-RGD in high yields from the IDB Holland/iThemba LABS generator. Quality control included ITLC in citric acid to observe labelling efficiency as well as in sodium carbonate to evaluate colloid formation. HPLC was also performed at iThemba LABS as well as Necsa (South African Nuclear Energy Corporation). RGD was obtained from Futurechem, Korea. Kit mass integrity was determined by testing labelling efficiency of 10, 30 and 60 μg of RGD per cold kit. The RGD was buffered with sodium acetate trihydrate. The original kits were dried in a desiccator and in later studies only freeze dried. Manual labelling was also tested. The radiolabelled in-house kit’s ex vivo biodistribution in healthy versus tumour mice were examined by obtaining xenografts. The normal biodistribution was investigated in three vervet monkeys by doing PET-CT scans on a Siemens Biograph TP 40 slice scanner. Results: Cold kit formulation radiolabeling and purification methods were established successfully and SOPs (standard operating procedures) created. HPLC results showed highest radiochemical purity in 60 μg cold kit vials. 68Ga-NOTA-RGD showed increased uptake in tumours of tumour bearing mouse. The cold kit also showed normal distribution according to literature with fast blood clearance and excretion through kidneys into urine, therefore making it a suitable radiopharmaceutical for clinical studies. Conclusion: The in-house prepared cold kit with a 4 month shelf-life was successfully tested in mice and monkeys.Master

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 nodule

Stability of glomerular and tubular renal injury biomarkers in canine urine after 4 years of storage

Urine biomarkers are sensitive indicators of early-stage renal injury, consequently, research in this area is expanding in both human and veterinary medicine. However, studies investigating the impact of preanalytical factors, such as storage conditions, on urine biomarker concentrations are largely lacking in veterinary medicine. Therefore, we evaluated the stability of several renal injury biomarkers in canine urine after storage for 4 y at -72 degrees C. Urine samples were collected from 26 dogs: 18 dogs with babesiosis and 8 healthy dogs. Concentrations of urine immunoglobulin G (uIgG), urine C-reactive protein (uCRP), and urine retinol-binding protein (uRBP) were measured, using validated commercial immunoassays, at the start of the study and 4 y later. To investigate the effect of long-term storage, absolute and relative differences between both measurements were compared. Additionally, dogs with babesiosis were compared with the healthy controls at both time points. Storage caused significant absolute and relative decreases in concentrations of all 3 biomarkers. Significant differences between dogs with babesiosis and healthy dogs were found in uIgG and uRBP at both times; however, the difference in uCRP between both groups lost significance after storage. Because the main goal of these urine biomarkers is to detect early-stage renal injury, the statistically significant decrease in their concentrations will be clinically relevant when a mild degree of renal injury is present. Our data indicate that the investigated urine biomarkers show significant decay after 4 y of storage at -72 degrees C, adversely affecting their diagnostic utility

Validation of a simple and fast method to quantify in vitro mineralization with fluorescent probes used in molecular imaging of bone

Alizarin Red S staining is the standard method to indicate and quantify matrix mineralization during differentiation of osteoblast cultures. KS483 cells are multipotent mouse mesenchymal progenitor cells that can differentiate into chondrocytes, adipocytes and osteoblasts and are a well-characterized model for the study of bone formation. Matrix mineralization is the last step of differentiation of bone cells and is therefore a very important outcome measure in bone research. Fluorescently labelled calcium chelating agents, e.g. BoneTag and OsteoSense, are currently used for in vivo imaging of bone. The aim of the present study was to validate these probes for fast and simple detection and quantification of in vitro matrix mineralization by KS483 cells and thus enabling high-throughput screening experiments. KS483 cells were cultured under osteogenic conditions in the presence of compounds that either stimulate or inhibit osteoblast differentiation and thereby matrix mineralization. After 21 days of differentiation, fluorescence of stained cultures was quantified with a near-infrared imager and compared to Alizarin Red S quantification. Fluorescence of both probes closely correlated to Alizarin Red S staining in both inhibiting and stimulating conditions. In addition, both compounds displayed specificity for mineralized nodules. We therefore conclude that this method of quantification of bone mineralization using fluorescent compounds is a good alternative for the Alizarin Red S staining.</p

Sexuality and succession law: beyond formal equality

This article endeavours to open up a dialogue between succession law and the field of gender, sexuality and the law. It presents a detailed analysis of five cases concerning inheritance disputes relating to lesbians or gay men. The sexuality of the parties in the cases is ‘doctrinally irrelevant’ but the analysis demonstrates the significance of sexuality in the resolution of the legal disputes. In doing so it identifies how legal discourse remains a critical site for the production of societal norms and in particular how lesbian and gay perspectives reveal the gendered assumptions underlying a number of key succession law doctrines. It emphasises the importance of taking difference seriously and the limits to formal legal equality