How to measure post-error slowing: The case of pre-error speeding

Post-error slowing is one of the most widely employed measures to study cognitive and behavioral consequences of error commission. Several methods have been proposed to quantify the post-error slowing effect, and we discuss two main methods: The traditional method of comparing response times in correct post-error trials to response times of correct trials that follow another correct trial, and a more recent proposal of comparing response times in correct post-error trials to the corresponding correct pre-error trials. Based on thorough re-analyses of two datasets, we argue that the latter method provides an inflated estimate by also capturing the (partially) independent effect of pre-error speeding. We propose two solutions for improving the assessment of human error processing, both of which highlight the importance of distinguishing between initial pre-error speeding and later post-error slowing.

Uncertain reward cues show increased dominance in early phases of binocular rivalry

Binocular rivalry occurs when the eyes are presented with two dissimilar images and visual awareness fluctuates between them. Previous findings suggest that perceptual dominance of a rewarded stimulus may increase relative to an unrewarded stimulus, implying a direct effect of reward on visual representations. Here, we asked how uncertainty about reward occurrence and average reward expectancy affect dominance in binocular rivalry. In three experiments, participants learnt to associate drifting gratings of distinct colors with different levels of uncertainty and expectancy. Uncertainty was manipulated by rewarding each correct trial either with 100% probability (no uncertainty) or with 50% probability (high uncertainty). The amount of reward was either identical per rewarded trial, yielding a lower expectancy in uncertain trials (Experiments 1 and 2), or reward expectancy was matched across uncertainty levels by doubling the award per rewarded trial for uncertain trials (Experiment 3). In Experiment 2, an additional low-reward condition with no uncertainty was included. Using a no-report paradigm, we measured the perceptual dominance of these gratings relative to a grating that was unassociated with reward, before and after associations had been acquired. When the rewarded stimulus feature (color) was task relevant, dominance durations increased for all rewarded gratings after acquisition. In an early phase after rivalry onset we found increased perceptual dominance for cues associated with uncertain reward compared to cues associated with certain reward. This confirms an effect of reward on perceptual dominance, and suggests that reward uncertainty associated with a stimulus has a direct bearing on its visual representation.

“No problem” health-related quality of life (HRQoL) in patients treated with regorafenib (Reg) for relapsed metastatic colorectal cancer (mCRC).

e15593 Background: REG has been shown to improve survival and delay time to quality of life deterioration over placebo (PBO) in two large randomized, double-blind, placebo-controlled multi-center phase III trials CORRECT and CONCUR for the treatment of relapsed mCRC. We report on findings of the five-dimensions of HRQoL in the two trials. Methods: The five key dimensions of HRQoL were captured in the CORRECT and CONCUR trials using EuroQol 5-Dimension questionnaire 3-level version (EQ-5D-3L). The 5 dimensions are mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, severe problems. We calculated the proportion of intent-to-treat (ITT) patients reporting “no problems” (NP) in each of the 5 dimensions by cycle and arm of treatment in the two trials. Results: Detailed descriptions of the trials have been reported previously. Due to space, data below focuses on CORRECT. ITT patients included 760 total in the CORRECT trial, 2:1 randomized to receive REG (N=505) and PBO (N=255). At baseline (BL), 95% of the ITT patients completed the questionnaire (Table), and patients reported the highest percentage of NP in self-care (87%) and lowest in pain/discomfort (35%). EQ-5D completion rates decline with each cycle of treatment, as are the percentages reporting NP in each dimension. The declines however appeared much more rapid for PBO than for REG. Both completion rate and percentages of NP were somewhat higher for PBO than for REG at BL, this continued until only cycle 2 and reversed completely from cycle 3 onward showing increasingly diminished proportion of those on PBO able to complete the questionnaire and reporting NP in each dimension. The differences between arms became larger with each cycle beginning cycle 3. Findings were similar for CONCUR (not shown). Conclusions: REG appeared to enable patients to maintain their mobility, self-care, usual activity, being pain-free and anxiety-free as well as their ability to complete the EQ-5D questionnaire, at much higher rates than PBO. Those whose EQ-5D were no longer available were likely poor performers that discontinued due to progression, death, toxicity or other unfavorable factors associated with their treatments. For PBO, toxicity was unlikely the reason. These findings suggest REG has a positive impact on quality of survival, as well as on length of survival. Further confirmatory analyses are needed.[Table: see text]

Bose-Einstein Condensation and Supersolids

We consider interacting Bose particles in an external potential. It is shown that a Bose-Einstein condensate is possible at finite temperatures that describes a super solid in three dimensions (3D) for a wide range of potentials in the absence of an external potential. However, for 2D, a self-organized super solid exists for finite temperatures provided the interaction between bosons is nonlocal and of infinitely long-range. It is interesting that in the absence of the latter type of potential and in the presence of a lattice potential, there is no Bose-Einstein condensate and so in such a case, a 2D super solid is not possible at finite temperatures. We also propose the correct Bloch form of the condensate wave function valid for finite temperatures, which may be used as the correct trial wave function.

Are post-error adjustments influenced by beliefs in free will? A failure to replicate Rigoni, Wilquin, Brass and Burle, 2013

In this pre-registered study, we tried to replicate the study by Rigoni et al. 2013 Cognition 127 , 264–269. In the original study, the authors manipulated the participants’ belief in free will in a between-subject design and subsequently measured post-error slowing (i.e. slower responses after an incorrect trial compared with a correct trial) as a marker of cognitive control. They found less post-error slowing in the group with reduced belief in free will (anti-free will group) compared with a control group in which belief in free will was not manipulated. In the present study, we used the same task procedure and the same free will manipulation (Crick text) in an attempt to replicate these findings. However, we used an online procedure and a larger sample size in order to address concerns about statistical power. Similar to the original study, we also used a questionnaire to measure beliefs in free will as an independent manipulation check. We found a difference in the scores on the questionnaire, thus a reduced belief in free will, after reading the Crick text. However, we did not find any difference in post-error slowing between the anti-free will and control groups. Our findings are in line with several other recent findings suggesting that the Crick text manipulation affects the participants’ self-reported belief in free will but not their behaviour. The present study can be considered a high-powered failed replication attempt.

Machine Perfusion: Cold versus Warm, versus Neither. Update on Clinical Trials

Machine perfusion (MP) preservation is potentially one of the most significant improvements in the field of liver transplantation in the last 20 years, and it has been considered a promising strategy for improved preservation and ex situ evaluation of extended criteria donor (ECD) organs. However, MP preservation adds significant cost and logistical considerations to liver transplantation. MP protocols are mainly classified according to the perfusion temperature with hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) being the two categories most studied so far. After extensive preclinical work, MP entered the clinical setting, and there are now several studies that demonstrated feasibility and safety. However, because of the limited quality of clinical trials, there is no compelling evidence of superiority in preservation quality, and liver MP is still considered experimental in most countries. MP preservation is moving to a more mature phase, where ongoing and future studies will bring new evidence in order to confirm their superiority in terms of clinical outcomes, organ utilization, and cost-effectiveness. Here, we present an overview of all preclinical MP studies using discarded human livers and liver MP clinical trials, and discuss their results. We describe the different perfusion protocols, pitfalls in MP study design, and provide future perspectives. Recent trials in liver MP have revealed unique challenges beyond those seen in most clinical studies. Randomized trials, correct trial design, and interpretation of data are essential to generate the data necessary to prove if MP will be the new gold standard method of liver preservation.

Regorafenib dose escalation therapy for patients with refractory metastatic colorectal cancer (RECC Study).

116 Background: Regorafenib, a multi-kinase inhibitor, significantly improved overall survival in previously treated metastatic colorectal cancer (mCRC) patients in the phase 3 CORRECT trial. Despite its significant benefits, various toxicities such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited regorafenib use. The toxicities occur soon after treatment initiation, typically within the first cycle, and later improve. Although the standard daily dose of regorafenib is 160 mg, physicians have adopted various dosing regimens in clinical practice, indicating the need to optimize the dosing strategy to maintain the antitumor benefits. The ReDOS study demonstrated the effectiveness of a weekly dose-escalating strategy (WDES) of regorafenib starting with a lower daily dose. We conducted the phase II RECC study to evaluate the safety and efficacy of WDES for regorafenib in an Asian population. Methods: Patients with sufficient organ function who had previously received more than two lines of chemotherapy were included. Regorafenib was started at 80 mg/day and escalated to 120 mg/day in Week 2 and 160 mg/day in Week 3 if no severe drug-related toxicities were observed. The primary endpoint was progression-free survival (PFS) and secondary endpoints were time to treatment failure (TTF), response rate (RR), overall survival (OS), and safety. Tumor response and progression were assessed radiologically every 8 weeks. Results: From March 2017 to November 2018, 57 eligible patients were enrolled and all started regorafenib at 80 mg/day. Thirty-five patients (61%) were subsequently escalated to 120 mg/day and 16 (28%) to 160 mg/day. Forty patients (70.2%) finished Cycle 2 at 8 weeks. Only 8 patients (14%) discontinued treatment because of adverse events. The median PFS was 1.9 months, RR was 0%, and disease control rate was 32%. The most frequent adverse event ≥grade 3 was hypertension (17.5%), followed by HFSR (14%). No treatment-related deaths occurred. Conclusions: Regorafenib dose escalation was well tolerated with PFS similar to that reported in the CORRECT study, indicating that WDES may represent an option for regorafenib administration. Clinical trial information: UMIN000028933.