Predictive coding in ASD: inflexible weighting of prediction errors when switching from stable to volatile environments

Individuals with autism spectrum disorder (ASD) have been widely reported to show atypicalities in predictive coding, though there remains a controversy regarding what causes such atypical processing. Suggestions range from overestimation of volatility to rigidity in the reaction to environmental changes. Here, we tested two accounts directly using duration reproduction of volatile and non-volatile interval sequences. Critically, both sequences had the same set of intervals but differed in their stimulus presentation orders. Comparing individuals with ASD vs. their matched controls, we found both groups to respond to the volatility in a similar manner, albeit with a generally reduced prior in the ASD group. Interestingly, though, relative to the control group, the ASD group exhibited a markedly reduced trust in the prior in the volatile trial session when this was performed after the non-volatile session, while both groups performed comparably in the reverse session order. Our findings suggest that it is not the learning of environmental volatility that is compromised in ASD. Rather, it is their response to a change of the volatility regimen from stable to volatile, which causes a highly inflexible weighting of prediction errors.Competing Interest StatementThe authors have declared no competing interest

Acquisition and Use of 'Priors' in Autism: Typical in Deciding Where to Look, Atypical in Deciding What Is There

Individuals with Autism Spectrum Disorder (ASD) are thought to under-rely on prior knowledge in perceptual decision-making. This study examined whether this applies to decisions of attention allocation, of relevance for 'predictive-coding' accounts of ASD. In a visual search task, a salient but task-irrelevant distractor appeared with higher probability in one display half. Individuals with ASD learned to avoid 'attentional capture' by distractors in the probable region as effectively as control participants-indicating typical priors for deploying attention. However, capture by a 'surprising' distractor at an unlikely location led to greatly slowed identification of a subsequent target at that location-indicating that individuals with ASD attempt to control surprise (unexpected attentional capture) by over-regulating parameters in post-selective decision-making

The effect of harvest time of forage on carbohydrate digestion in horses quantified by in vitro and mobile bag techniques

publishedVersio

Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells

Background: Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties. Methods: hiPSC were differentiated into spontaneously beating clusters by co-culturing with visceral endoderm-like cells in a serum-free medium. Subsequent culturing in a specified fetal bovine serum (FBS)-enriched cell medium produced a pacemaker-type phenotype that was studied in detail using quantitative real-time polymerase chain reaction (qRT-PCR), immunocytochemistry, and patch-clamp electrophysiology. Further investigations comprised pharmacological stimulations and co-culturing with neonatal cardiomyocytes. Results: hiPSC co-cultured in a serum-free medium with the visceral endoderm-like cell line END-2 produced spontaneously beating clusters after 10–12 days of culture. The pacemaker-specific genes HCN4, TBX3, and TBX18 were abundantly expressed at this early developmental stage, while levels of sarcomeric gene products remained low. We observed that working-type cardiomyogenic differentiation can be suppressed by transfer of early clusters into a FBS-enriched cell medium immediately after beating onset. After 6 weeks under these conditions, sinoatrial node (SAN) hallmark genes remained at high levels, while working-type myocardial transcripts (NKX2.5, TBX5) were low. Clusters were characterized by regular activity and robust beating rates (70–90 beats/min) and were triggered by spontaneous Ca2+ transients recapitulating calcium clock properties of genuine pacemaker cells. They were responsive to adrenergic/cholinergic stimulation and able to pace neonatal rat ventricular myocytes in co-culture experiments. Action potential (AP) measurements of cells individualized from clusters exhibited nodal-type (63.4%) and atrial-type (36.6%) AP morphologies, while ventricular AP configurations were not observed. Conclusion: We provide a novel culture media-based, transgene-free approach for targeted generation of hiPSC-derived pacemaker-type cells that grow in clusters and offer the potential for disease modeling, drug testing, and individualized cell-based replacement therapy of the SAN

Clinical use of lithium salts: guide for users and prescribers

Lithium has been used clinically for 70 years, mainly to treat bipolar disorder. Competing treatments and exaggerated impressions about complexity and risks of lithium treatment have led to its declining use in some countries, encouraging this update about its safe clinical use. We conducted a nonsystematic review of recent research reports and developed consensus among international experts on the use of lithium to treat major mood disorders, aiming for a simple but authoritative guide for patients and prescribers

The P3^3 Experiment: A Positron Source Demonstrator for Future Lepton Colliders

The PSI Positron Production (P$^3$ or P-cubed) experiment is a demonstrator for a e+ source and capture system with potential to improve the state-of-the-art e+ yield by an order of magnitude. The experiment is driven by the FCC-ee injector study and will be hosted in the SwissFEL facility at the Paul Scherrer Institute in Switzerland. This paper is an overview of the P$^3$ design at an advanced stage, with a particular emphasis on a novel e+ capture system and its associated beam dynamics. Additionally, a concept for the experiment diagnostics is presented, as well as the key points of the ongoing installation works

Efficient Terahertz Generation by Tilted-Pulse-Front Pumping in Lithium Niobate for the Split-Ring Resonator Experiment at FLUTE

A compact, longitudinal diagnostics for fs-scale electron bunches using a THz electric-field transient in a split-ring resonator (SRR) for streaking will be tested at the Ferninfrarot Linac- Und Test- Experiment (FLUTE). For this new streaking technique, intensive THz pulses are required, which will be generated by laser-based optical rectification. We present a setup for generating THz pulses using tilted-pulse-front pumping in lithium niobate at room temperature. Excited by an 800 nm Ti:Sa pump laser with 35 fs bandwidth-limited pulse length, conversion efficiencies up to 0.027% were achieved. Furthermore, the status of the SRR experiment is shown

Lithium induced hypercalcemia:an expert opinion and management algorithm

Background: Lithium is the gold standard prophylactic treatment for bipolar disorder. Most clinical practice guidelines recommend regular calcium assessments as part of monitoring lithium treatment, but easy-to-implement specific management strategies in the event of abnormal calcium levels are lacking. Methods: Based on a narrative review of the effects of lithium on calcium and parathyroid hormone (PTH) homeostasis and its clinical implications, experts developed a step-by-step algorithm to guide the initial management of emergent hypercalcemia during lithium treatment. Results: In the event of albumin-corrected plasma calcium levels above the upper limit, PTH and calcium levels should be measured after two weeks. Measurement of PTH and calcium levels should preferably be repeated after one month in case of normal or high PTH level, and after one week in case of low PTH level, independently of calcium levels. Calcium levels above 2.8 mmol/l may require a more acute approach. If PTH and calcium levels are normalized, repeated measurements are suggested after six months. In case of persistent PTH and calcium abnormalities, referral to an endocrinologist is suggested since further examination may be needed. Conclusions: Standardized consensus driven management may diminish the potential risk of clinicians avoiding the use of lithium because of uncertainties about managing side-effects and consequently hindering some patients from receiving an optimal treatment