Defining the clinical and cognitive phenotype of child savants with autism spectrum disorder

Objective: Whilst savant syndrome is most commonly observed in individuals with Autism Spectrum Disorder (ASD), it has historically been associated with intellectual impairment, and little is known about the clinical and cognitive characteristics of intellectually able individuals with ASD and savant skills. Methods: Participants with ASD and validated savant skills were compared with age and intelligence matched non-savants with ASD using a range of diagnostic and standardised tests. Results: Although the analysis of the clinical data revealed few differences between the groups, striking differences emerged during cognitive testing. Children with savant skills exhibited highly superior working memory and their scores on tests of analytic skills were also superior to those of non-savants. Conclusion: We propose that obsessionality, focused attention, superior working memory and analytic skills facilitate veridical mapping and pattern perception abilities characteristic in savant syndrome

The impact of haptic and visual secondary tasks on drivers' visual behaviour and driving performance : a qualitative analysis

Godkänd; 2008; 20100428 (pebn

Identification, Characterization, and Optimization of 2,8-Disubstituted-1,5-naphthyridines as Novel <i>Plasmodium falciparum</i> Phosphatidylinositol-4-kinase Inhibitors with in Vivo Efficacy in a Humanized Mouse Model of Malaria

A novel 2,8-disubstituted-1,5-naphthyridine hit compound stemming from the open access Medicines for Malaria Venture Pathogen Box formed a basis for a hit-to-lead medicinal chemistry program. Structure–activity relationship investigations resulted in compounds with potent antiplasmodial activity against both chloroquine sensitive (NF54) and multidrug resistant (K1) strains of the human malaria parasite <i>Plasmodium falciparum</i>. In the humanized <i>P. falciparum</i> mouse efficacy model, one of the frontrunner compounds showed in vivo efficacy at an oral dose of 4 × 50 mg·kg^–1. In vitro mode-of-action studies revealed <i>Plasmodium falciparum</i> phosphatidylinositol-4-kinase as the target

Identification, Characterization, and Optimization of 2,8-Disubstituted-1,5-naphthyridines as Novel <i>Plasmodium falciparum</i> Phosphatidylinositol-4-kinase Inhibitors with in Vivo Efficacy in a Humanized Mouse Model of Malaria

A novel 2,8-disubstituted-1,5-naphthyridine hit compound stemming from the open access Medicines for Malaria Venture Pathogen Box formed a basis for a hit-to-lead medicinal chemistry program. Structure–activity relationship investigations resulted in compounds with potent antiplasmodial activity against both chloroquine sensitive (NF54) and multidrug resistant (K1) strains of the human malaria parasite <i>Plasmodium falciparum</i>. In the humanized <i>P. falciparum</i> mouse efficacy model, one of the frontrunner compounds showed in vivo efficacy at an oral dose of 4 × 50 mg·kg^–1. In vitro mode-of-action studies revealed <i>Plasmodium falciparum</i> phosphatidylinositol-4-kinase as the target

Identification, Characterization, and Optimization of 2,8-Disubstituted-1,5-naphthyridines as Novel <i>Plasmodium falciparum</i> Phosphatidylinositol-4-kinase Inhibitors with in Vivo Efficacy in a Humanized Mouse Model of Malaria

A novel 2,8-disubstituted-1,5-naphthyridine hit compound stemming from the open access Medicines for Malaria Venture Pathogen Box formed a basis for a hit-to-lead medicinal chemistry program. Structure–activity relationship investigations resulted in compounds with potent antiplasmodial activity against both chloroquine sensitive (NF54) and multidrug resistant (K1) strains of the human malaria parasite <i>Plasmodium falciparum</i>. In the humanized <i>P. falciparum</i> mouse efficacy model, one of the frontrunner compounds showed in vivo efficacy at an oral dose of 4 × 50 mg·kg^–1. In vitro mode-of-action studies revealed <i>Plasmodium falciparum</i> phosphatidylinositol-4-kinase as the target

Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4‑Aminoquinoline-Based Compounds

A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds <b>3c</b>–<b>3e</b> had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P450 enzymes in vitro. Pharmacokinetic studies on <b>3d</b> and <b>3e</b> in mice showed that they had moderate half-life (4–6 h) and low oral bioavailability. The front runner compound <b>3d</b> exhibited moderate inhibition of the malaria parasite on <i>P. berghei</i> infected mice following oral administration (5 mg/kg), achieving reduction of parasitemia population by 47% on day 7

Identification of Fast-Acting 2,6-Disubstituted Imidazopyridines That Are Efficacious in the in Vivo Humanized <i>Plasmodium falciparum</i> NODscidIL2Rγ^<i>null</i> Mouse Model of Malaria

Optimization of a chemical series originating from whole-cell phenotypic screening against the human malaria parasite, <i>Plasmodium falciparum</i>, led to the identification of two promising 2,6-disubstituted imidazopyridine compounds, <b>43</b> and <b>74</b>. These compounds exhibited potent activity against asexual blood stage parasites that, together with their in vitro absorption, distribution, metabolism, and excretion (ADME) properties, translated to in vivo efficacy with clearance of parasites in the <i>Pf</i>SCID mouse model for malaria within 48 h of treatment

Identification of Fast-Acting 2,6-Disubstituted Imidazopyridines That Are Efficacious in the in Vivo Humanized <i>Plasmodium falciparum</i> NODscidIL2Rγ^<i>null</i> Mouse Model of Malaria

Optimization of a chemical series originating from whole-cell phenotypic screening against the human malaria parasite, <i>Plasmodium falciparum</i>, led to the identification of two promising 2,6-disubstituted imidazopyridine compounds, <b>43</b> and <b>74</b>. These compounds exhibited potent activity against asexual blood stage parasites that, together with their in vitro absorption, distribution, metabolism, and excretion (ADME) properties, translated to in vivo efficacy with clearance of parasites in the <i>Pf</i>SCID mouse model for malaria within 48 h of treatment

Novel Antitubercular 6‑Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure–Activity Relationship and Target Identification Studies

A BioFocus DPI SoftFocus library of ∼35 000 compounds was screened against <i>Mycobacterium tuberculosis</i> (Mtb) in order to identify novel hits with antitubercular activity. The hits were evaluated in biology triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome <i>bc</i>₁ complex, disruption of cell–wall homeostasis, and DNA damage. Among the hits that passed this screening cascade, a 6-dialkylamino­pyrimidine carboxamide series was prioritized for hit to lead optimization. Compounds from this series were active against clinical Mtb strains, while no cross-resistance to conventional antituberculosis drugs was observed. This suggested a novel mechanism of action, which was confirmed by chemoproteomic analysis leading to the identification of BCG_3193 and BCG_3827 as putative targets of the series with unknown function. Initial structure–activity relationship studies have resulted in compounds with moderate to potent antitubercular activity and improved physicochemical properties