Implementation of the Risk–Need–Responsivity Framework across the Juvenile Justice Agencies in Singapore

The Risk–Need–Responsivity (RNR) framework is regarded as the forefront of offender rehabilitation in guiding youth offender risk assessment and interventions. This article discusses the juvenile justice system in Singapore and the local research that has been conducted in relation to the RNR framework and the associated Youth Level of Service (YLS) measures. It describes a journey that saw the implementation of the RNR framework across the juvenile justice agencies and highlights the challenges that were faced during the implementation process on the ground. Finally, the article concludes by providing future directions for the implementation of the RNR framework in Singapore.     

Substrate topography and size determine the fate of human embryonic stem cells to neuronal or glial lineage

Efficient derivation of neural cells from human embryonic stem cells (hESCs) remains an unmet need for the treatment of neurological disorders. The limiting factors for current methods include being labor-intensive, time-consuming and expensive. In this study, we hypothesize that the substrate topography, with optimal geometry and dimension, can modulate the neural fate of hESCs and enhance the efficiency of differentiation. A multi-architectural chip (MARC) containing fields of topographies varying in geometry and dimension was developed to facilitate high-throughput analysis of topography-induced neural differentiation in vitro. The hESCs were subjected to “direct differentiation”, in which small clumps of undifferentiated hESCs were cultured directly without going through the stage of embryoid body formation, on the MARC with N2 and B27 supplements for 7 days. The gene and protein expression analysis indicated that the anisotropic patterns like gratings promoted neuronal differentiation of hESCs while the isotropic patterns like pillars and wells promoted the glial differentiation of hESCs. This study showed that optimal combination of topography and biochemical cues could shorten the differentiation period and allowed derivation of neurons bearing longer neurites that were aligned along the grating axis. The MARC platform would enable high-throughput screening of topographical substrates that could maximize the efficiency of neuronal differentiation from pluripotent stem cells.     

Use of a Target‐Mediated Drug Disposition Model to Predict the Human Pharmacokinetics and Target Occupancy of GC1118, an Anti‐epidermal Growth Factor Receptor Antibody

GC1118 is an anti‐epidermal growth factor receptor (EGFR) monoclonal antibody that is currently under clinical development. In this study, the pharmacokinetics (PK) of GC1118 were modelled in monkeys to predict human PK and receptor occupancy (RO) profiles. The serum concentrations of GC1118 and its comparator (cetuximab) were assessed in monkeys with a non‐compartmental analysis and a target‐mediated drug disposition (TMDD) model after intravenous infusion (3–25 mg/kg) of these drugs. The scaling exponent of the EGFR synthesis rate was determined using a sensitivity analysis. The human cetuximab exposures were simulated by applying different exponents (0.7–1.0) for the EGFR synthesis rate in the allometric monkey PK model. Simulated C_max and area under the curve values therein were compared with those previously reported in the literature to find the best exponent for the EGFR synthesis rate in human beings. The TMDD model appropriately described the monkey PK profile, which showed a decrease in clearance (CL; 1.2–0.4 ml/hr/kg) as the dose increased. The exponents for CL (0.75) and volume of distribution (Vd; 1.0) were used for the allometric scaling to predict human PK. The allometric coefficient for the EGFR synthesis rate chosen by the sensitivity analysis was 0.85, and the RO profiles that could not be measured experimentally were estimated based on the predicted concentrations of the total target and the drug–target complex. Our monkey TMDD model successfully predicts human PK and RO profiles of GC1118 and can be used to determine the appropriate dose for a first‐in‐human study investigating this drug.     

Socioeconomic Status and Glycemic Index Among Punjabis in Kuala Lumpur,Malaysia: Possible Association with Metabolic Syndrome

There are only limited reports on Punjabi’s health status in Malaysia. This cross-sectional study assessed the prevalence of metabolic syndrome (Mets) and its risk factors among 277 subjects recruited from the Malaysian Punjabi community. Overall prevalence of Mets was 43%, but 61% among females. Subjects classified with Mets had significantly (p?<?0.05) higher body mass index, visceral fat and percentage of body fat. Daily carbohydrate and glycemic index (GI) were also higher among Mets subjects (p?<?0.05). Logistics regression analysis showed that primary level of education (OR 5.57, CI 1.29–23.97, p?=?0.021) was a factor associated with Mets, followed by middle household income (OR 2.30, CI 1.01–5.20, p?=?0.046), GI (OR 1.03, CI 1.00–1.06, p?=?0.026), and age (OR 1.03, CI 1.00–1.05, p?=?0.023). Mets shows high prevalence among the studied Punjabi population, prompting the consideration of adequate preventive measures, primarily among lower socioeconomic groups.