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Estimating the reliability of cognitive task datasets is commonly done via split-half methods. We review four methods that differ in how the trials are split into parts a first-second half split, an odd-even trial split, a permutated split, and a Monte Carlo-based split. Additionally, each splitting method could be combined with stratification by task design. this website These methods are reviewed in terms of the degree to which they are confounded with four effects that may occur in cognitive tasks effects of time, task design, trial sampling, and non-linear scoring. Based on the theoretical review, we recommend Monte Carlo splitting (possibly in combination with stratification by task design) as being the most robust method with respect to the four confounds considered. Next, we estimated the reliabilities of the main outcome variables from four cognitive task datasets, each (typically) scored with a different non-linear algorithm, by systematically applying each splitting method. Differences between methods were interpreted in terms of confounding effects inflating or attenuating reliability estimates. For three task datasets, our findings were consistent with our model of confounding effects. Evidence for confounding effects was strong for time and task design and weak for non-linear scoring. When confounding effects occurred, they attenuated reliability estimates. For one task dataset, findings were inconsistent with our model but they may offer indicators for assessing whether a split-half reliability estimate is appropriate. Additionally, we make suggestions on further research of reliability estimation, supported by a compendium R package that implements each of the splitting methods reviewed here.Decoding the rich temporal dynamics of complex sounds such as speech is constrained by the underlying neuronal-processing mechanisms. Oscillatory theories suggest the existence of one optimal perceptual performance regime at auditory stimulation rates in the delta to theta range ( less then 10 Hz), but reduced performance in the alpha range (10-14 Hz) is controversial. Additionally, the widely discussed motor system contribution to timing remains unclear. We measured rate discrimination thresholds between 4 and 15 Hz, and auditory-motor coupling strength was estimated through a behavioral auditory-motor synchronization task. In a Bayesian model comparison, high auditory-motor synchronizers showed a larger range of constant optimal temporal judgments than low synchronizers, with performance decreasing in the alpha range. This evidence for optimal processing in the theta range is consistent with preferred oscillatory regimes in auditory cortex that compartmentalize stimulus encoding and processing. The findings suggest, remarkably, that increased auditory-motor synchronization might extend such an optimal range towards faster rates.Familial hypercholesterolemia (FH) and chronic kidney disease, especially end-stage renal disease (ESRD), are common and put patients at a high risk of developing atherosclerotic cardiovascular disease (ASCVD). ESRD concomitant with FH may further increase the risk of ASCVD. Achieving target levels of low-density lipoprotein cholesterol (LDL-C) is difficult owing to the limitations of statin administration due to its side effects in ESRD. Therefore, some FH patients with ESRD require lipoprotein apheresis for the prevention of secondary ASCVD events. Although proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors may offer a safe and effective option for lowering lipid levels in such patients, no guidelines are available for their use. Here, we report the case of two male siblings with FH in secondary prevention undergoing hemodialysis combined with PCSK9 inhibitor treatment. The siblings, who showed a heterozygous c.1846-1G>A mutation in the LDLR gene, underwent hemodialysis. In combination with the lipoprotein apheresis, siblings were administered evolocumab, a PCSK9 inhibitor. Both the siblings had coronary artery disease, diabetes, and ESRD, and received hemodialysis. Their LDL-C levels did not reach the target values despite administering statin, ezetimibe, and biweekly lipoprotein apheresis. On the introduction of evolocumab treatment, their LDL-C levels were significantly reduced without any adverse effects, resulting in successful withdrawal from lipoprotein apheresis therapy. Although the effects of switching from lipoprotein apheresis to PCSK9 inhibitors for cardiovascular protection remain unclear in FH patients with and without ESRD, our case report will be helpful in guiding future therapeutic decisions.

Artificial pancreases administering low-dose glucagon in addition to insulin have the scope to improve glucose control in patients with diabetes mellitus type 1. If such a device were to deliver both hormones intraperitoneally, it would mimic normal physiology, which may be beneficial. However, the pharmacokinetic properties of glucagon after intraperitoneal administration are not well known. Hence, the current study aims to evaluate the relationship between the amount of intraperitoneally delivered glucagon and pharmacokinetic variables in a pig model.

Pharmacokinetic data was retrieved from experiments on 19 anaesthetised pigs and analysed post hoc. The animals received a single intraperitoneal bolus of glucagon ranging from 0.30 to 4.46 µg/kg. Plasma glucagon was measured every 2-10 min for 50 min.

Peak plasma concentration and area under the time-plasma concentration curve of glucagon correlated positively with the administered dose, and larger boluses provided a relatively greater increase. The mean (standard deviation) time to maximum glucagon concentration in plasma was 11 (5) min, and the mean elimination half-life of glucagon in plasma was 19 (7) min.

Maximum plasma concentration and area under the time-plasma concentration curve of glucagon increase nonlinearly in relation to the intraperitoneally administered glucagon dose. We hypothesise that the results are compatible with a satiable first-pass metabolism in the liver. Time to maximum glucagon concentration in plasma and the elimination half-life of glucagon in plasma seem independent of the drug dose.

Maximum plasma concentration and area under the time-plasma concentration curve of glucagon increase nonlinearly in relation to the intraperitoneally administered glucagon dose. We hypothesise that the results are compatible with a satiable first-pass metabolism in the liver. Time to maximum glucagon concentration in plasma and the elimination half-life of glucagon in plasma seem independent of the drug dose.

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