Reversing binding sensitivity to A147T translocator protein

The translocator protein (TSPO) is a target for the development of neuroinflammation imaging agents. Clinical translation of TSPO PET ligands, such as [11C]DPA-713, has been hampered by the presence of a common polymorphism (A147T TSPO), at which all second-generation TSPO ligands lose affinity. Little is known about what drives binding at A147T compared to WT TSPO. This study aimed to identify moieties in DPA-713, and related derivatives, that influence binding at A147T compared to WT TSPO. We found changes to the nitrogen position and number in the heterocyclic core influences affinity to WT and A147T to a similar degree. Hydrogen bonding groups in molecules with an indole core improve binding at A147T compared to WT, a strategy that generated compounds that possess up to ten-times greater affinity for A147T. These results should inform the future design of compounds that bind both A147T and WT TSPO for use in neuroinflammation imaging

Does “soft conditionality” increase the impact of cash transfers on desired outcomes? Evidence from a randomized control trial in Lesotho

Cash transfers programs have been shown to have positive effects on a variety of outcomes. While much of the literature focuses on the role of conditionality in achieving desired impact, this paper focuses on the role of ‘soft conditionality’ implemented through both ‘labeling’ and ‘messaging’ in evaluating the impact of the Child Grants Program in Lesotho, an unconditional cash transfer targeting poor households with orphans and vulnerable children. Beneficiary households received a clear message that the transfer should be spent on the interest and needs of children. Our findings are based on a randomized experiment and suggest that ‘soft conditionality’ does play a strong role in increasing expenditure for children, especially on education, clothing and footwear. Results indicate in fact that transfer income is spent differently from general income as it exerts both an income and a substitution effect. This behavioral change is confirmed by comparing the ex-ante expected behaviors with the ex-post actual response to the program. We find that for expenditure categories linked to the wellbeing of children the ex-post response was much higher than the ex-ante expected behavior

Inhaled therapy in paediatrics

In summary, inhalation of aerosols is the mainstay of treatment of asthma and can be useful in treating children with cystic fibrosis. The most efficient method of delivering aerosol to children depends on the age and clinical condition of the child. The most rational dosage schedule for nebulized drugs appears to be to weight-correct the dose added to the nebulizer solution