A Trade-Off Study Revealing Nested Timescales of Constraint

This study investigates human performance in a cyclic Fitts task at three different scales of observation, either in the presence (difficult condition) or in the absence (easy condition) of a speed–accuracy trade-off. At the fastest scale, the harmonicity of the back and forth movements, which reflects the dissipation of mechanical energy, was measured within the timeframe of single trials. At an intermediate scale, speed and accuracy measures were determined over a trial. The slowest scale pertains to the temporal structure of movement variability, which evolves over multiple trials. In the difficult condition, reliable correlations across each of the measures corroborated a coupling of nested scales of performance. Participants who predominantly emphasized the speed-side of the trade-off (despite the instruction to be both fast and accurate) produced more harmonic movements and clearer 1/f scaling in the produced movement time series, but were less accurate and produced more random variability in the produced movement amplitudes (vice versa for more accurate participants). This implied that speed–accuracy trade-off was accompanied by a trade-off between temporal and spatial streams of 1/f scaling, as confirmed by entropy measures. In the easy condition, however, no trade-offs nor couplings among scales of performance were observed. Together, these results suggest that 1/f scaling is more than just a byproduct of cognition. These findings rather support the claim that interaction-dominant dynamics constitute a coordinative basis for goal-directed behavior

Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial†

We examined the effect of MSI status in a trial-based cohort of 1254 stage II and III colon cancer (CC) patients treated with 5-FU/LV or FOLFIRI. We confirm that for stage II CC MSI is strongly prognostic for RFS and OS. No significant differences were found between treatment arms. Adding irinotecan to 5-FU did not benefit MSI-H tumors. RFS was better for MSI-H CC both in the right and left colo

The placebo response rate in pharmacological trials in patients with irritable bowel syndrome: a systematic review and meta-analysis

Findings Between June 16, 2014, and July 28, 2017, 122 patients were eligible for screening and a total of 95 patients were randomly assigned to the infliximab-continued group (n=48) or the infliximab-discontinued group (n=47). 92 patients (n=46 for both groups) were included in the full analysis set. 37 (80.4% [95% CI 66.1-90.6]) of 46 patients in the infliximab-continued group and 25 (54.3% [39.0-69.1]) of 46 patients in the infliximab-discontinued group were in remission at week 48. The between-group difference was 26.1% (95% CI 7.7-44.5; p=0.0076) before adjustment and 27.3% (95% CI 8.0-44.1; p=0.0059) after adjustment for stratification factors. Eight (17%) of 48 patients in the infliximab-continued group and six (13%) of 47 in the infliximab-discontinued group developed adverse events (between-group difference 3.9% [95% CI -10.3 to 18.1]; p=0.59). In the infliximab-continued group, one patient had an infusion reaction and two patients had psoriatic skin lesions. Eight (66.7%, 95% CI 34.9-90.1) of the 12 patients in the infliximab-discontinuation group who were re-treated with infliximab after relapsing were in remission within 8 weeks of re-treatment; none had infusion reactions.Background Anti-tumour necrosis factor (TNF) agents are the mainstay of long-term treatment for refractory ulcerative colitis. However, long-term use of anti-TNF therapy might lead to an increased risk of malignancy or infection. To date, no randomised controlled trial has evaluated whether anti-TNF agents can be safely discontinued in patients with ulcerative colitis in remission. We therefore aimed to compare outcomes in these patients who continued infliximab with those who discontinued infliximab.Methods We did a multicentre, open-label randomised controlled trial at 24 specialist centres in Japan. We enrolled patients with ulcerative colitis who were in remission, had been treated with intravenous infliximab (5 mg/kg) every 8 weeks, and had started infliximab at least 14 weeks before study enrolment. No restrictions regarding age and comorbidities were used to exclude participation. Patients who were confirmed to be in remission for more than 6 months, to be corticosteroid-free, and to have a Mayo Endoscopic Subscore (MES) of 0 or 1 were centrally randomised. An independent organisation randomly assigned patients (1:1) into either the infliximab-continued group or infliximab-discontinued group, using a computer-generated stratified randomisation procedure. The stratified factors were the use of immunomodulators (yes or no) and MES (0 or 1). Neither patients nor health-care providers were masked to the randomisation. The primary endpoint was the remission rate at week 48 in the full analysis set, which was based on the intention-to-treat principle and excluded participants with no efficacy data after randomisation. This study was registered with the University Hospital Medical Information Network Center Trials registry, UMIN000012092. Findings Between June 16, 2014, and July 28, 2017, 122 patients were eligible for screening and a total of 95 patients were randomly assigned to the infliximab-continued group (n=48) or the infliximab-discontinued group (n=47). 92 patients (n=46 for both groups) were included in the full analysis set. 37 (80.4% [95% CI 66.1-90.6]) of 46 patients in the infliximab-continued group and 25 (54.3% [39.0-69.1]) of 46 patients in the infliximab-discontinued group were in remission at week 48. The between-group difference was 26.1% (95% CI 7.7-44.5; p=0.0076) before adjustment and 27.3% (95% CI 8.0-44.1; p=0.0059) after adjustment for stratification factors. Eight (17%) of 48 patients in the infliximab-continued group and six (13%) of 47 in the infliximab-discontinued group developed adverse events (between-group difference 3.9% [95% CI & minus;10.3 to 18.1]; p=0.59). In the infliximab-continued group, one patient had an infusion reaction and two patients had psoriatic skin lesions. Eight (66.7%, 95% CI 34.9-90.1) of the 12 patients in the infliximab-discontinuation group who were re-treated with infliximab after relapsing were in remission within 8 weeks of re-treatment; none had infusion reactions.Interpretation Maintenance of remission was significantly more common in patients who continued infliximab than in those who discontinued. Discontinuing infliximab should therefore be discussed with caution, taking both risk of relapse and efficacy of re-treatment into account.Funding Mitsubishi Tanabe Pharma Corporation and the Intractable Disease Project of the Ministry of Health, Labour and Welfare of Japan.Copyright (c) 2021 Elsevier Ltd. All rights reserved

Uncorking the potential of wine language for young wine tourists

Effective communication with consumers underpins growth in wine knowledge that, in turn, contributes to growth in wine consumption. Indeed, tasting notes may enhance consumers’ experiences of wine. Yet wine language is full of fuzzy concepts. In this chapter, we consider the language used to talk about wine, specifically the humanlike features of wine (e.g., wine is described as honest, sexy, shy, or brooding). We demonstrate that metaphoric language is integral to the experience of wine and influences consumer behaviour. We discuss practical implications for the cellar door experience, and for effective and ethical wine communication. We conclude that metaphoric language is a pedagogical and cultural platform for engaging younger wine tourists in the cellar door experience, which is a significant revenue source for micro, small, and medium wineries

Relative Sea-Level Rise Projections and Flooding Scenarios for 2150 CE for the Island of Ustica (Southern Tyrrhenian Sea, Italy)

The island of Ustica (Italy) is constantly exposed to the effects of sea-level rise, which is threatening its coastal zone. With the aim of assessing the sea levels that are anticipated by 2150 CE under the climatic projections shown in the AR6 report from the IPCC, a detailed evaluation of potential coastal flooding under different climatic scenarios and the ongoing land subsidence has been carried out for three coastal zones. Scenarios are based on the determination of the current coastline position, a high-resolution digital terrain and marine model, and the SSP1-2.6, SSP3-7.0, and SSP5-8.5 climatic projections. Relative sea-level rise projections allowed the mapping of the potential inundated surfaces for 2030, 2050, 2100, and 2150. The results show rising sea levels for 2150, ranging from a minimum of 66 ± 40 cm (IPCC AR6 SSP2.6 scenario) to a maximum of 128 ± 52 cm (IPCC AR6 SSP8.5 scenario). In such conditions, considering the SSP8.5 scenario during storm surges with return times (RTs) of 1 and 100 years, the expected maximum wave run-up along the island may vary from 3 m (RT = 1) to 14 m (RT = 100), according to the coastal morphology. Our results show that adaptation and mitigation actions are required to protect the touristic and harbor installations of the island

Kalman filter density reconstruction in ICRH discharges on ASDEX Upgrade

Plasma density is one of the key quantities that need to be controlled in real-time as it scales directly with fusion power and, if left uncontrolled, density limits can be reached leading to a disruption. On ASDEX Upgrade (AUG), the real-time measurements are the line-integrated density, measured by the interferometers, and the average density derived from the bremsstrahlung measured by spectroscopy. For control, these measurements are used to reconstruct the radial density profile using an extended Kalman filter (EKF). However, in discharges where ion cyclotron resonance heating (ICRH) is used, the measurements from the interferometers are corrupted and the reconstructed density is false. In this paper, the existing EKF implementation is improved, implemented and experimentally verified on AUG. The new EKF includes a new particle transport model in the prediction model RAPDENS as well as a new representation of ionization and recombination. Furthermore, an algorithm was introduced that is capable of detecting the corrupt diagnostics; this algorithm is based on the rate of change of the innovation residual. The changes to the RAPDENS observer resulted in better density reconstruction in ICRH discharges where corrupt measurement occur. The new version has been implemented on the real-time control system at AUG and functions properly in ICRH discharges.</p

Approximation algorithms for replenishment problems with fixed turnover times

We introduce and study a class of optimization problems we coin replenishment problems with fixed turnover times: a very natural model that has received little attention in the literature. Nodes with

Cell Line Derived 5-FU and Irinotecan Drug-Sensitivity Profiles Evaluated in Adjuvant Colon Cancer Trial Data.

This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. To test if an irinotecan signature and a SN-38 signature could identify patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer patients enrolled in the PETACC-3 prospective randomized clinical trial. A 5-FU profile developed similarly was assessed by comparing the PETACC-3 cohort with a cohort of 359 stage II colon cancer patients who underwent surgery but received no adjuvant therapy. There was no statistically significant association between the irinotecan or SN-38 profiles and benefit from irinotecan. The 5-FU sensitivity profile showed a statistically significant association with relapse free survival (RFS) (hazard ratio (HR) = 0.54 (0.41-0.71), p&lt;1e-05) and overall survival (HR = 0.47 (0.34-0.63), p&lt;1e-06) in the PETACC-3 subpopulation. The effect of the 5-FU profile remained significant in a multivariable Cox Proportional Hazards model, adjusting for several relevant clinicopathological parameters. No statistically significant effect of the 5-FU profile was observed in the untreated cohort of 359 patients (relapse free survival, p = 0.671). The irinotecan predictor had no predictive value. The 5-FU predictor was prognostic in stage III patients in PETACC-3 but not in stage II patients with no adjuvant therapy. This suggests a potential predictive ability of the 5-FU sensitivity profile to identify colon cancer patients who may benefit from 5-FU, however, any biomarker predicting benefit for adjuvant 5-FU must be rigorously evaluated in independent cohorts. Given differences between the two study cohorts, the present results should be further validated

Gas temperature structure across transition disk cavities

[Abridged] Most disks observed at high angular resolution show substructures. Knowledge about the gas surface density and temperature is essential to understand these. The aim of this work is to constrain the gas temperature and surface density in two transition disks: LkCa15 and HD 169142. We use new ALMA observations of the $^{13}$CO $J=6-5$ transition together with archival $J=2-1$ data of $^{12}$CO, $^{13}$CO and C$^{18}$O to observationally constrain the gas temperature and surface density. Furthermore, we use the thermochemical code DALI to model the temperature and density structure of a typical transition disk. The $6-5/2-1$ line ratio in LkCa15 constrains the gas temperature in the emitting layers inside the dust cavity to be up to 65 K, warmer than in the outer disk at 20-30 K. For the HD 169142, the peak brightness temperature constrains the gas in the dust cavity of HD 169142 to be 170 K, whereas that in the outer disk is only 100 K. Models also show that a more luminous central star, a lower abundance of PAHs and the absence of a dusty inner disk increase the temperature of the emitting layers and hence the line ratio in the gas cavity. The gas column density in the LkCa15 dust cavity drops by a factor >2 compared to the outer disk, with an additional drop of an order of magnitude inside the gas cavity at 10 AU. In the case of HD 169142, the gas column density drops by a factor of 200$-$500 inside the gas cavity, which could be due to a massive companion of several M$_{\mathrm{J}}$. The broad dust-depleted gas region from 10-68 AU for LkCa15 may imply several lower mass planets. This work demonstrates that knowledge of the gas temperature is important to determine the gas surface density and thus whether planets, and if so what kind of planets, are the most likely carving the dust cavities.Comment: Accepted for publication in Astronomy and astrophysic