Choice biases in no-sample and delay testing in pigeons (Columba livia)

In experimental tasks that involve stimuli that vary along a quantitative continuum, some choice biases are commonly found. Take, for instance, a matching-to-sample task where animals must, following the presentation of sample stimuli (that differ in duration), choose between two or more comparison stimuli. In tests where no sample is presented there is usually a bias towards the comparison that is correct following the shortest sample. To examine some aspects of these choice biases, pigeons were trained in a symbolic matching-to-sample task with two durations of keylight as samples, where key pecking had to be maintained during sample presentation. Firstly, even though animals were required to attend to the sample, a preference for the "short" comparison in no-sample testing was found. This result disproves an account where this effect was hypothesized to happen due to non-programmed learning resulting from the animals failing to attend to some trials. Secondly, even though a bias for "short" was found in both no-sample and delay testing, the extent of the biases differed between tasks, thus suggesting that forgetting the sample presented during a delay does not necessarily land the animal in a state similar to presenting no sample at all to begin with.The present study was supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education through national funds. It was also co-financed by the European Regional Development Fund (FEDER)-through COMPETE2020-under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653)

L-Plastin nanobodies perturb matrix degradation, podosome formation, stability and lifetime in THP-1 macrophages

Podosomes are cellular structures acting as degradation ‘hot-spots’ in monocytic cells. They appear as dot-like structures at the ventral cell surface, enriched in F-actin and actin regulators, including gelsolin and L-plastin. Gelsolin is an ubiquitous severing and capping protein, whereas L-plastin is a leukocyte-specific actin bundling protein. The presence of the capping protein CapG in podosomes has not yet been investigated. We used an innovative approach to investigate the role of these proteins in macrophage podosomes by means of nanobodies or Camelid single domain antibodies. Nanobodies directed against distinct domains of gelsolin, L-plastin or CapG were stably expressed in macrophage-like THP-1 cells. CapG was not enriched in podosomes. Gelsolin nanobodies had no effect on podosome formation or function but proved very effective in tracing distinct gelsolin populations. One gelsolin nanobody specifically targets actin-bound gelsolin and was effectively enriched in podosomes. A gelsolin nanobody that blocks gelsolin-G-actin interaction was not enriched in podosomes demonstrating that the calcium-activated and actin-bound conformation of gelsolin is a constituent of podosomes. THP-1 cells expressing inhibitory L-plastin nanobodies were hampered in their ability to form stable podosomes. Nanobodies did not perturb Ser5 phosphorylation of L-plastin although phosphorylated L-plastin was highly enriched in podosomes. Furthermore, nanobody-induced inhibition of L-plastin function gave rise to an irregular and unstable actin turnover of podosomes, resulting in diminished degradation of the underlying matrix. Altogether these results indicate that L-plastin is indispensable for podosome formation and function in macrophages

A Rescorla-Wagner Drift-Diffusion Model of Conditioning and Timing

Computational models of classical conditioning have made significant contributions to the theoretic understanding of associative learning, yet they still struggle when the temporal aspects of conditioning are taken into account. Interval timing models have contributed a rich variety of time representations and provided accurate predictions for the timing of responses, but they usually have little to say about associative learning. In this article we present a unified model of conditioning and timing that is based on the influential Rescorla-Wagner conditioning model and the more recently developed Timing Drift-Diffusion model. We test the model by simulating 10 experimental phenomena and show that it can provide an adequate account for 8, and a partial account for the other 2. We argue that the model can account for more phenomena in the chosen set than these other similar in scope models: CSC-TD, MS-TD, Learning to Time and Modular Theory. A comparison and analysis of the mechanisms in these models is provided, with a focus on the types of time representation and associative learning rule used

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease