Children's working understanding of knowledge sources : confidence in knowledge gained from testimony

In three experiments children aged between 3 and 5 years (N = 38; 52; 94; mean ages 3;7 to 5;2) indicated their confidence in their knowledge of the identity of a hidden toy. With the exception of some 3-year-olds, children revealed working understanding of their knowledge source by showing high confidence when they had seen or felt the toy, and lower confidence when they had been told its identity by an apparently well-informed speaker, especially when the speaker subsequently doubted the adequacy of his access to the toy. After a 2-minute delay, 3-to 4- year olds, unlike 4- to 5-year-olds, failed to see the implications of the speaker’s doubt about his access

Children's working understanding of the knowledge gained from seeing and feeling

In three Experiments, (N = 48 3- to 4-year olds; 100 3- to 5-year olds; 54 4-yearolds), children who could see or feel a target toy, recognized when they had sufficient information to answer “Which one is it?” and when they needed additional access. They were weaker at taking the informative modality of access when the choice was between seeing more of a partially visible toy and feeling it; at doing so when the target was completely hidden; and at reporting seeing or feeling as their source of knowledge of the target’s identity having experienced both. Working understanding of the knowledge gained from seeing and feeling (identifying the target efficiently) was not necessarily in advance of explicit understanding (reporting the informative source)

Can one written word mean many things? Prereaders’ assumptions about the stability of written words’ meanings

Results of three experiments confirmed previous findings that in a moving word task, prereaders 3 to 5 years of age judge as if the meaning of a written word changes when it moves from a matching to a nonmatching toy (e.g., when the word “dog” moves from a dog to a boat). We explore under what circumstances children make such errors, we identify new conditions under which children were more likely correctly to treat written words’ meanings as stable: when the word was placed alongside a nonmatching toy without having been alongside a matching toy previously, when two words were moved from a matching toy to a nonmatching toy, and when children were asked to change what the print said. Under these conditions, children more frequently assumed that physical forms had stable meanings as they do with other forms of external representation

Gaia, White Dwarfs, and the Age of the Galaxy

The Milky Way is composed of four major stellar populations: the thin disk, thick disk, bulge, and halo. At present, we do not know the age of any of these populations to better than one or two billion years. This lack of knowledge keeps us from answering fundamental questions about the Galaxy: When did the thin disk, thick disk, and halo form? Did they form over an extended period, and if so, how long? Was star formation continuous across these populations or instead occur in distinct episodes? The Gaia satellite is providing precise trigonometric parallaxes for a plethora of white dwarfs in each of these populations. We combine these parallaxes (and hence, distances) with photometry and analyze them using a modeling technique that relies on Bayesian statistics. This allows us to derive precise ages for individual white dwarfs and determine the age distribution and star formation history for each of the constituents of our Galaxy. Here we will present current progress in this endeavor, with emphasis on the ages of individual white dwarfs in the Hyades. Measuring the ages of individual white dwarfs in well-studied clusters provides proof of concept for our technique, as well exploration of any systematic offsets caused from timescales from main sequence models, as well as the initial-final mass relation

Conformationally restricted calpain inhibitors

The cysteine protease calpain-I is linked to several diseases and is therefore a valuable target for inhibition. Selective inhibition of calpain-I has proved difficult as most compounds target the active site and inhibit a broad spectrum of cysteine proteases as well as other calpain isoforms. Selective inhibitors might not only be potential drugs but should act as tools to explore the physiological and pathophysiological roles of calpain-I. α-Mercaptoacrylic acid based calpain inhibitors are potent, cell permeable and selective inhibitors of calpain-I and calpain-II. These inhibitors target the calcium binding domain PEF(S) of calpain-I and -II. Here X-ray diffraction analysis of co-crystals of PEF(S) revealed that the disulfide form of an α-mercaptoacrylic acid bound within a hydrophobic groove that is also targeted by a calpastatin inhibitory region and made a greater number of favourable interactions with the protein than the reduced sulfhydryl form. Measurement of the inhibitory potency of the α-mercaptoacrylic acids and X-ray crystallography revealed that the IC50 values decreased significantly on oxidation as a consequence of the stereo-electronic properties of disulfide bonds that restrict rotation around the S–S bond. Consequently, thioether analogues inhibited calpain-I with potencies similar to those of the free sulfhydryl forms of α-mercaptoacrylic acids

Influence of cardiac autonomic neuropathy on cardiac repolarisation during incremental adrenaline infusion in type 1 diabetes

Aims/hypothesis We examined the effect of a standardised sympathetic stimulus, incremental adrenaline (epinephrine) infusion on cardiac repolarisation in individuals with type 1 diabetes with normal autonomic function, subclinical autonomic neuropathy and established autonomic neuropathy. Methods Ten individuals with normal autonomic function and baroreceptor sensitivity tests (NAF), seven with subclinical autonomic neuropathy (SAN; normal standard autonomic function tests and abnormal baroreceptor sensitivity tests); and five with established cardiac autonomic neuropathy (CAN; abnormal standard autonomic function and baroreceptor tests) underwent an incremental adrenaline infusion. Saline (0.9% NaCl) was infused for the first hour followed by 0.01 μg kg−1 min−1 and 0.03 μg kg−1 min−1 adrenaline for the second and third hours, respectively, and 0.06 μg kg−1 min−1 for the final 30 min. High resolution ECG monitoring for QTc duration, ventricular repolarisation parameters (T wave amplitude, T wave area symmetry ratio) and blood sampling for potassium and catecholamines was performed every 30 min. Results Baseline heart rate was 68 (95% CI 60, 76) bpm for the NAF group, 73 (59, 87) bpm for the SAN group and 84 (78, 91) bpm for the CAN group. During adrenaline infusion the heart rate increased differently across the groups (p = 0.01). The maximum increase from baseline (95% CI) in the CAN group was 22 (13, 32) bpm compared with 11 (7, 15) bpm in the NAF and 10 (3, 18) bpm in the SAN groups. Baseline QTc was 382 (95% CI 374, 390) ms in the NAF, 378 (363, 393) ms in the SAN and 392 (367, 417) ms in the CAN groups (p = 0.31). QTc in all groups lengthened comparably with adrenaline infusion. The longest QTc was 444 (422, 463) ms (NAF), 422 (402, 437) ms (SAN) and 470 (402, 519) ms (CAN) (p = 0.09). T wave amplitude and T wave symmetry ratio decreased and the maximum decrease occurred earlier, at lower infused adrenaline concentrations in the CAN group compared with NAF and SAN groups. AUC for the symmetry ratio was different across the groups and was lowest in the CAN group (p = 0.04). Plasma adrenaline rose and potassium fell comparably in all groups. Conclusions/interpretation Participants with CAN showed abnormal repolarisation in some measures at lower adrenaline concentrations. This may be due to denervation adrenergic hypersensitivity. Such individuals may be at greater risk of cardiac arrhythmias in response to physiological sympathoadrenal challenges such as stress or hypoglycaemia