Trends in HIV surveillance data in the EU/EEA, 2005 to 2014: New HIV diagnoses still increasing in men who have sex with men

Human immunodeficiency virus (HIV) transmission remains significant in Europe. Rates of acquired immunodeficiency syndrome (AIDS) have declined, but not in all countries. New HIV diagnoses have increased among native and foreign-born men who have sex with men. Median CD4+T-cell count at diagnosis has increased, but not in all groups, and late diagnosis remains common. HIV infection and AIDS can be eliminated in Europe with resolute prevention measures, early diagnosis and access to effective treatment

Cognition and character traits as determinants of young children’s behaviour in traffic situations

Young children, 3 to 6 years’ old, were observed in two situations: (1) a traffic model, where they used dolls to enact the movements of two children on the way to and from day care; and (2) as they crossed a lightly trafficked, minor road in a situation analogous to that in the model. Atotal of 131 children participated. All were tested in the model situation (a), both on understanding of safety and safety devices and on road-crossing behaviour. The latter was seen as a task consisting of three components (i) using a zebra crossing, (ii) stopping at the curb, and (iii) looking for cars. Asubgroup of 47 children was tested on three character traits, activity, distraction, and impulsivity. Another subgroup of 45 children participated in the roadside situation (b). The results show that although both age and understanding were important predictors of appropriate behaviour in both traffic situations, the behaviour components were differentially related to these factors. Of the character traits, impulsivity was found to be reliably related to traffic behaviour

Developmental Aspects of Children’s Behavior and Safety While Cycling

Objective To examine children's competence while cycling, as demonstrated in mistakes in performance and failure to comply with safety rules. Methods Children in three age groups (8, 10, and 12 years) participated in a realistic yet simulated traffic environment. Results The boys' cycling speed increased steadily with age, while that of the girls increased from 8 to 10 but decreased at age 12. Most children had adequate motor control by age 10, and the youngest compensated for their less developed skills by cycling slowly and braking early at junctions. Serious mistakes, often related to the children's age and gender, consisted of the children failing to stop at signals or stopping too late, especially at short stopping range. Conclusions There are considerable individual differences in children's cycling competence that are related to biological factors, such as age and gender, and psychological factors, such as rule compliance and choice of cycling speed

Efficient multi-objective molecular optimization in a continuous latent space

One of the main challenges in small molecule drug discovery is finding novel chemical compounds with desirable properties. In this work, we propose a novel method that combines in silico prediction of molecular properties such as biological activity or pharmacokinetics with an in silico optimization algorithm, namely Particle Swarm Optimization. Our method takes a starting compound as input and proposes new molecules with more desirable (predicted) properties. It navigates a machine-learned continuous representation of a drug-like chemical space guided by a defined objective function. The objective function combines multiple in silico prediction models, defined desirability ranges and substructure constraints. We demonstrate that our proposed method is able to consistently find more desirable molecules for the studied tasks in relatively short time. We hope that our method can support medicinal chemists in accelerating and improving the lead optimization process

Prioritizing Small Sets of Molecules for Synthesis through in‐silico Tools: A Comparison of Common Ranking Methods

Prioritizing molecules for synthesis is a key role of computational methods within medicinal chemistry. Multiple tools exist for ranking molecules, from the cheap and popular molecular docking methods to more computationally expensive molecular-dynamics (MD)-based methods. It is often questioned whether the accuracy of the more rigorous methods justifies the higher computational cost and associated calculation time. Here, we compared the performance on ranking the binding of small molecules for seven scoring functions from five docking programs, one end-point method (MM/GBSA), and two MD-based free energy methods (PMX, FEP+). We investigated 16 pharmaceutically relevant targets with a total of 423 known binders. The performance of docking methods for ligand ranking was strongly system dependent. We observed that MD-based methods predominantly outperformed docking algorithms and MM/GBSA calculations. Based on our results, we recommend the application of MD-based free energy methods for prioritization of molecules for synthesis in lead optimization, whenever feasible