Ruffle&Riley: Towards the Automated Induction of Conversational Tutoring Systems

Conversational tutoring systems (CTSs) offer learning experiences driven by natural language interaction. They are known to promote high levels of cognitive engagement and benefit learning outcomes, particularly in reasoning tasks. Nonetheless, the time and cost required to author CTS content is a major obstacle to widespread adoption. In this paper, we introduce a novel type of CTS that leverages the recent advances in large language models (LLMs) in two ways: First, the system induces a tutoring script automatically from a lesson text. Second, the system automates the script orchestration via two LLM-based agents (Ruffle&Riley) with the roles of a student and a professor in a learning-by-teaching format. The system allows a free-form conversation that follows the ITS-typical inner and outer loop structure. In an initial between-subject online user study (N = 100) comparing Ruffle&Riley to simpler QA chatbots and reading activity, we found no significant differences in post-test scores. Nonetheless, in the learning experience survey, Ruffle&Riley users expressed higher ratings of understanding and remembering and further perceived the offered support as more helpful and the conversation as coherent. Our study provides insights for a new generation of scalable CTS technologies.Comment: NeurIPS'23 GAIED, Camera-read

Examining Food Tourists’ Intentions to Consume Local Cuisine

The current study applied an extended model of goal-directed behavior to examine food tourists’ intentions to consume local cuisine. The structural model reveals significant and positive impact of food involvement and food tourist motivation on attitude, as well as significant and positive influence of attitude, perceived behavioral control, anticipated positive and negative emotions, frequency of past behavior, and self-identity on food tourists’ desires of consuming local cuisine. Furthermore, Desire significantly and positively predicts intention of consuming local cuisine. The findings provide theoretical contributions on both the model of goal-directed behavior and the research of food tourist behavior. Practical implications are also provided

Counter-selectable marker for bacterial-based interaction trap systems

Counter-selectable markers can be used in two-hybrid systems to search libraries for a protein or compound that interferes with a macromolecular interaction or to identify macromolecules from a population that cannot mediate a particular interaction. In this report, we describe the adaptation of the yeast URA3/5-FOA counter-selection system for use in bacterial interaction trap experiments. Two different URA3 reporter systems were developed that allow robust counter-selection: (i) a single copy F\u27 episome reporter and (ii) a co-cistronic HIS3-URA3 reporter vector. The HIS3-URA3 reporter can be used for either positive or negative selections in appropriate bacterial strains. These reagents extend the utility of the bacterial two-hybrid system as an alternative to its yeast-based counterpart

455 Pegasus Lung, a platform study of SAR444245 (THOR-707, a pegylated recombinant non-alpha IL-2) with anti-cancer agents in patients with non-small cell lung cancer (NSCLC) and mesothelioma

BackgroundSAR444245 (THOR-707) is a recombinant human IL-2 molecule that includes a PEG moiety irreversibly bound to a novel amino acid via click chemistry to block the alpha-binding domain while retaining near-native affinity for the beta/gamma subunits. In animal models, SAR444245 showed anti-tumor benefits, but with no severe side effects, both as single agent and when combined with anti-PD1 comparing with historical data from aldesleukin. The HAMMER trial, which is the FIH study shows preliminary encouraging clinical results: initial efficacy and safety profile with SAR444245 monotherapy and in combination with pembrolizumab support a non-alpha preferential activity, validating preclinical models. The Pegasus Lung Ph2 study will evaluate the clinical benefit of SAR444245 in combination with other anticancer therapies for the treatment of patients with lung cancer or pleural mesotheliomaMethodsThe Pegasus Lung (NCT04914897) will enroll approximately 354 patients in 6 separate cohorts concurrently or sequentially. In cohorts A1 & A2, patients with first line (L) NSCLC will receive SAR444245 + pembrolizumab. In cohort A3, patients with 1L non-squamous NSCLC will receive SAR444245 + pembrolizumab + pemetrexed + carboplatin/cisplatin. In cohort B1 & B2 patients with 2/3L NSCLC who have progressed on a checkpoint inhibitor (CPI)-based therapy will receive SAR444245 + pembrolizumab, or SAR444245 + pembrolizumab + nab-paclitaxel. In cohort C patients with 2/3L CPI naïve mesothelioma will receive SAR444245 + pembrolizumab. SAR444245 is administered IV at a dose of 24 ug/kg Q3W in an outpatient setting until disease progression or completion of 35 cycles. Pembrolizumab is administered at a dose of 200 mg Q3W until PD or completion of 35 cycles. The study primary objective is to determine the antitumor activity of SAR444245 in combination with other anticancer therapies. Secondary objectives include confirmation of dose and safety profile, assess other indicators of antitumor activity, and assess the pharmacokinetic profile and immunogenicity of SAR444245. The study will be conducted in the US, Australia, France, Italy, Japan, Poland, South Korea, Spain, and Taiwan.AcknowledgementsThe Pegasus Lung study is sponsored by Sanofi.Trial RegistrationNCT04914897Ethics ApprovalThis study has been approved by applicable ethics committees or institutional review boards. All participants gave informed consent before taking part.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal

435 Pegasus HNSCC, a platform study of SAR444245 (THOR-707, a pegylated recombinant non-alpha IL-2) with anti-cancer agents in patients with recurrent/metastatic head and neck squamous cell carcinoma

BackgroundSAR444245 (THOR-707) is a recombinant human IL-2 molecule that includes a PEG moiety irreversibly bound to a novel amino acid via click chemistry to block the alpha-binding domain while retaining near-native affinity for the beta/gamma subunits. In animal models, SAR444245 showed anti-tumor benefits, but with no severe side effects, both as single agent and when combined with anti-PD1 comparing with historical data from aldeslukin. Preclinical study demonstrated SAR444245 enhances ADCC function of cetuximab. The HAMMER trial, which is the FIH study shows preliminary encouraging clinical results: initial efficacy and safety profile with SAR444245 monotherapy and in combination with pembrolizumab or with cetuximab support a non-alpha preferential activity, validating preclinical models. The Pegasus Head and Neck Ph 2 study will evaluate the clinical benefit of SAR444245 in combination with other anticancer therapies for the treatment of patients with R/M HNSCC.MethodsThe Pegasus Head and Neck will enroll approximately 272 patients in 4 separate cohorts concurrently. In cohorts A1 & A2, 1L R/M HNSCC patients will receive SAR444245 + pembrolizumab, or SAR444245+ pembrolizumab+ cetuximab respectively. In cohort B1 & B2 patients with 2/3L R/M HNSCC failed a checkpoint based regimen & a platinum containing regimen will receive SAR444245 + pembrolizumab, or SAR444245 + cetuximab. Patients to be enrolled in cohort B2 need to be cetuximab-naïve in R/M setting. SAR444245 is administered intravenously IV at a dose of 24 ug/kg Q3W until disease progression (PD) or completion of 35 cycles. Pembrolizumab is administered at a dose of 200 mg Q3W until PD or completion of 35 cycles. Cetuximab is administered at a dose of 400/250 mg/m2 QW until PD. The study primary objective is to determine the antitumor activity of SAR444245 in combination with other anticancer therapies. Secondary objectives include confirmation of dose and safety profile, assess other indicators of antitumor activity, and assess the pharmacokinetic profile and immunogenicity of SAR444245. The study will be conducted in the US, Canada, France, Germany, Italy, Netherlands, Poland, South Korea, Spain and Taiwan.AcknowledgementsThe Pegasus Head and Neck study is sponsored by Sanofi

Effects of minimum unit pricing for alcohol on different income and socioeconomic groups: a modelling study

Background: Several countries are considering a minimum price policy for alcohol, but concerns exist about the potential effects on drinkers with low incomes. We aimed to assess the effect of a £0·45 minimum unit price (1 unit is 8 g/10 mL ethanol) in England across the income and socioeconomic distributions. Methods: We used the Sheffield Alcohol Policy Model (SAPM) version 2.6, a causal, deterministic, epidemiological model, to assess effects of a minimum unit price policy. SAPM accounts for alcohol purchasing and consumption preferences for population subgroups including income and socioeconomic groups. Purchasing preferences are regarded as the types and volumes of alcohol beverages, prices paid, and the balance between on-trade (eg, bars) and off-trade (eg, shops). We estimated price elasticities from 9 years of survey data and did sensitivity analyses with alternative elasticities. We assessed effects of the policy on moderate, hazardous, and harmful drinkers, split into three socioeconomic groups (living in routine or manual households, intermediate households, and managerial or professional households). We examined policy effects on alcohol consumption, spending, rates of alcohol-related health harm, and opportunity costs associated with that harm. Rates of harm and costs were estimated for a 10 year period after policy implementation. We adjusted baseline rates of mortality and morbidity to account for differential risk between socioeconomic groups. Findings: Overall, a minimum unit price of £0·45 led to an immediate reduction in consumption of 1·6% (−11·7 units per drinker per year) in our model. Moderate drinkers were least affected in terms of consumption (−3·8 units per drinker per year for the lowest income quintile vs 0·8 units increase for the highest income quintile) and spending (increase in spending of £0·04 vs £1·86 per year). The greatest behavioural changes occurred in harmful drinkers (change in consumption of −3·7% or −138·2 units per drinker per year, with a decrease in spending of £4·01), especially in the lowest income quintile (−7·6% or −299·8 units per drinker per year, with a decrease in spending of £34·63) compared with the highest income quintile (−1·0% or −34·3 units, with an increase in spending of £16·35). Estimated health benefits from the policy were also unequally distributed. Individuals in the lowest socioeconomic group (living in routine or manual worker households and comprising 41·7% of the sample population) would accrue 81·8% of reductions in premature deaths and 87·1% of gains in terms of quality-adjusted life-years. Interpretation: Irrespective of income, moderate drinkers were little affected by a minimum unit price of £0·45 in our model, with the greatest effects noted for harmful drinkers. Because harmful drinkers on low incomes purchase more alcohol at less than the minimum unit price threshold compared with other groups, they would be affected most by this policy. Large reductions in consumption in this group would however coincide with substantial health gains in terms of morbidity and mortality related to reduced alcohol consumption. Funding: UK Medical Research Council and Economic and Social Research Council (grant G1000043)

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P

Bicontinuous minimal surface nanostructures for polymer blend solar cells

This paper presents the first examination of the potential for bicontinuous structures such as the gyroid structure to produce high efficiency solar cells based on conjugated polymers. The solar cell characteristics are predicted by a simulation model that shows how the morphology influences device performance through integration of all the processes occurring in organic photocells in a specified morphology. In bicontinuous phases, the surface de. ning the interface between the electron and hole transporting phases divides the volume into two disjoint subvolumes. Exciton loss is reduced because the interface at which charge separation occurs permeates the device so excitons have only a short distance to reach the interface. As each of the component phases is connected, charges will be able to reach the electrodes more easily. In simulations of the current-voltage characteristics of organic cells with gyroid, disordered blend and vertical rod (rods normal to the electrodes) morphologies, we find that gyroids have a lower than anticipated performance advantage over disordered blends, and that vertical rods are superior. These results are explored thoroughly, with geminate recombination, i.e. recombination of charges originating from the same exciton, identified as the primary source of loss. Thus, if an appropriate materials choice could reduce geminate recombination, gyroids show great promise for future research and applications

The effect of collagen fibril orientation on the biphasic mechanics of articular cartilage

The highly inhomogeneous distribution of collagen fibrils may have important effects on the biphasic mechanics of articular cartilage. However, the effect of the inhomogeneity of collagen fibrils has mainly been investigated using simplified three-layered models, which may have underestimated the effect of collagen fibrils by neglecting their realistic orientation. The aim of this study was to investigate the effect of the realistic orientation of collagen fibrils on the biphasic mechanics of articular cartilage. Five biphasic material models, each of which included a different level of complexity of fibril reinforcement, were solved using two different finite element software packages (Abaqus and FEBio). Model 1 considered the realistic orientation of fibrils, which was derived from diffusion tensor magnetic resonance images. The simplified three-layered orientation was used for Model 2. Models 3–5 were three control models. The realistic collagen orientations obtained in this study were consistent with the literature. Results from the two finite element implementations were in agreement for each of the conditions modelled. The comparison between the control models confirmed some functions of collagen fibrils. The comparison between Models 1 and 2 showed that the widely-used three-layered inhomogeneous model can produce similar fluid load support to the model including the realistic fibril orientation; however, an accurate prediction of the other mechanical parameters requires the inclusion of the realistic orientation of collagen fibrils.</p