Objectives/Goals: We assessed the feasibility of using a large language model (LLM) to create lay language descriptions of study protocols for recruitment, which has the potential to improve accessibility and transparency of clinical studies and enable participants to make informed decisions. Methods/Study Population: All studies from a clinical research recruitment platform were included, which features human-written lay descriptions and titles for study recruitment. Corresponding protocol summaries in the IRB system were extracted and translated into lay language using a LLM (gpt-35-turbo-0613). A subset was used to develop prompt variations through an iterative process. Prompt strategies evaluated include chain-of-thought and few-shot prompting techniques. LLM-generated and human-written descriptions were compared for readability using Flesch–Kincaid and Simple Measure of Gobbledygook (SMOG) reading grade levels and information completeness using Word Movers’ Distance (WMD). Results/Anticipated Results: A total of 55 study descriptions were included – 10 were used to develop prompts and 45 were used for evaluation. The final LLM instructions included multistep prompts. The LLM was first instructed to produce a two- to three-sentence long description without using scientific jargon and included two pairs of examples. The LLM was then asked to shorten the description and finally to provide an engaging title. LLM-generated and human-written summaries were similar in length (median (IQR) 328 (278.5–360.5) vs. 342 (203–532.5) characters, respectively). LLM-generated summaries had lower Flesch-Kincaid grade level (5.15 vs. 8.28, p Discussion/Significance of Impact: An LLM can be used to generate lay language summaries that are readable at a lower grade level while maintaining semantic similarity. This approach can be used to improve the drafting of summaries for recruitment, thereby improving accessibility to potential participants. Future work includes human evaluation and implementation into practice.

Background: In phase 3 ADVANCE, atogepant 60mg reduced mean monthly migraine days (MMDs) from 7.8 days (baseline) to 3.0 (weeks 9-12; Δ=−4.7) in the overall episodic migraine population [treatment responders and nonresponders (i.e., marked benefit and minimal benefit)], which obscures information regarding magnitude of treatment effect in these populations. Here, magnitude of treatment effect in atogepant responders and nonresponders is characterized. Methods: Mean MMDs, acute medication use-days (MUDs), and Migraine-Specific Quality of Life-Role Function-Restrictive (MSQ-RFR) scores were calculated in treatment responders (based on MMD percentage reduction) and nonresponders from ADVANCE participants. Results: From baseline to weeks 9-12, ≥50% improvement was achieved by 71% (139/195) of participants. In these responders, MMDs reduced from 7.6 to 1.3 (Δ=−6.3). 50% (97/195) of participants achieved ≥75% response. In this group, MMDs reduced from 7.7 to 0.6 (Δ=−7.1). Atogepant 60mg nonresponders (<25% reduction in MMDs; 15% [30/195 participants]) showed MMD change from 7.7 to 9.1 (Δ=+1.4). Acute MUDs in ≥50% MMD responders decreased 7.1 to 1.6 (Δ=−5.5). In treatment-nonresponders, acute MUDs were 7.3 (baseline) and 7.2 (weeks 9-12; Δ=−0.1). Similar mean MSQ-RFR score changes were observed in both populations. Conclusions: Of participants who experienced ≥50% reduction in MMDs, 71% had substantial treatment effect (ΔMMD=−6.3), representing 83% reduction in MMDs.

Background: Children with pathogenic variations in SCN8A can present with early infantile epileptic encephalopathy-13, benign familial infantile seizures-5 or intellectual disability alone without epilepsy. In this case series, we discuss six children with variants in SCN8A managed at BC Children’s Hospital. Methods: We describe clinical and genetic results on six individuals with SCN8A variants identified via clinical or research next-generation sequencing. Functional consequences of two SCN8A variants were assessed using electrophysiological analyses in transfected cells. Results: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Phenotypes and genotypes in our cohort are described in the table below. Functional analysis supported gain-of-function in P2 and loss-of-function in P4. Conclusions: Our cohort expands the clinical and genotypic spectrum of SCN8A-related disorders. We establish functional evidence for two missense variants in SCN8A, including LoF variant in a patient with intellectual disability, and autism spectrum disorder without seizures.

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History, Maths and Astronomy are all mixed up in an innovative educational project that is being carried out in the Faculty of Education of the Universidad de La Laguna, in Spain. Students learn how to teach (to primary school students) about the shape of the Earth, the distances to the Moon, the Sun and other planets, collecting their own data with simple instrumentation and, most important, to connect ideas and different disciplines. The structure and contents of this project are presented, as well as examples of the activities that are carried out.

Knowledge about marine reptile diversity and disparity during the Late Jurassic is increasing. This contribution describes marine reptile skeletal elements (ichthyosaur and plesiosaur) from Kingofjeld mountain in NE Greenland. The assemblage is early Late Oxfordian (Late Jurassic) in age, and consists of c. 100 disarticulated skeletal elements. The location is of biogeographic importance as it was at the time situated between the Boreal realm and the Tethys Sea and is promising in terms of future prospecting.

According to the European Convention on Nationality (1997), nationality-or the term “citizenship” used as synonymous with nationality-means a legal bond between a person and a state. As such, nationality is linked to nation building. Nationality can also be defined as equal membership in a political community, and as a status to which rights and duties, participatory practices and a sense of national identity are attached. In other words, nationality constitutes an important element of a person's identity.

European Union citizenship is linked to nationality in an EU Member State. Union citizenship grants rights to the Member State nationals and may be defined as membership in a larger political community, the EU. Union citizenship is meant to foster a feeling of European identity. The third report of the Commission on Citizenship of the Union described citizenship as “both a source of legitimation of the process of European integration, by reinforcing the participation of citizens, and a fundamental factor in the creation among citizens of a sense of belonging to the European Union and of having a genuine European identity.”

Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.

The object of this paper is to uncover the nature of the destabilising coupling that is the major cause of body-freedom flutter and to see whether a simple cure for the flutter can be found. To do this frequency-coalesence theory is applied to a simple aircraft. It is shown that the aircraft is liable to flutter if it has a sweptforward wing and a positive ‘tail-off’ cg margin or a sweptback wing and a negative cg margin but a simple cure for the flutter does not appear to exist.

Coordination infrastructures play a central role in the engineering of multiagent systems. Since the advent of agent technology, research on coordination infrastructures has produced a significant number of infrastructures with varying features. In this paper, we review the the state-of-the-art coordination infrastructures with the purpose of identifying open research challenges that next generation coordination infrastructures should address. Our analysis concludes that next generation coordination infrastructures must address a number of challenges: (i) to become socially aware, by facilitating human interaction within a MAS; (ii) to assist agents in their decision making by providing decision support that helps them reduce the scope of reasoning and facilitates the achievement of their goals; and (iii) to increase openness to support on-line, fully decentralised design and execution. Furthermore, we identify some promising approaches in the literature, together with the research issues worth investigating, to cope with such challenges.

This paper addresses the problem of designing low-order and linear robust feedback controllers that provide a priori guarantees with respect to stability and performance when applied to a fluid flow. This is challenging, since whilst many flows are governed by a set of nonlinear, partial differential–algebraic equations (the Navier–Stokes equations), the majority of established control system design assumes models of much greater simplicity, in that they are: firstly, linear; secondly, described by ordinary differential equations (ODEs); and thirdly, finite-dimensional. With this in mind, we present a set of techniques that enables the disparity between such models and the underlying flow system to be quantified in a fashion that informs the subsequent design of feedback flow controllers, specifically those based on the $\mathscr{H}_{\infty }$ loop-shaping approach. Highlights include the application of a model refinement technique as a means of obtaining low-order models with an associated bound that quantifies the closed-loop degradation incurred by using such finite-dimensional approximations of the underlying flow. In addition, we demonstrate how the influence of the nonlinearity of the flow can be attenuated by a linear feedback controller that employs high loop gain over a select frequency range, and offer an explanation for this in terms of Landahl’s theory of sheared turbulence. To illustrate the application of these techniques, an $\mathscr{H}_{\infty }$ loop-shaping controller is designed and applied to the problem of reducing perturbation wall shear stress in plane channel flow. Direct numerical simulation (DNS) results demonstrate robust attenuation of the perturbation shear stresses across a wide range of Reynolds numbers with a single linear controller.

Two experiments on replacement heifers (175±12 days of age) assessed the effects of forage particle length and moisture on feeding behavior. Both experiments used a replicated 3×3 Latin square design, with nine heifers per replication and three periods of 9 days each. Each group of nine heifers was housed in one pen with access to three electronic feed bins. In Experiment 1, hay chopped at different lengths was incorporated into three total mixed rations (TMR) all having the same ingredient and nutrient composition but differing in the percentage of long particles (>19 mm): 60% (Short), 64% (Medium) and 72% (Long). In Experiment 2, heifers were fed a TMR with the same ingredient and nutrient composition but differing in moisture content: 65% DM (Dry), 50% DM (Moderate), and 35% DM (Wet). In both experiments, feeding behavior during the last 5 days of each period was analyzed using a mixed model accounting for the fixed effects of treatment and period, and the random effects of replication and animal. In Experiment 1, dry matter intake (DMI) and eating rate (DMI/min) tended to increase, whereas daily eating time decreased as the feed particle size decreased. Heifers fed the Long diet selected in favor of long particles (>19 mm) and against Short (1.18 to 8 mm) and fine (<1.18 mm) particles; heifers fed the Short diet selected against long particles and in favor of short and fine particles. Heifers fed the Medium diet showed a preference for medium particles with no preference for the other particle sizes. In Experiment 2, heifers fed the Dry diet tended to consume more feed than those fed the Moderate and Wet diets, with no differences in feeding behavior or sorting activity. In conclusion the Medium diet minimized sorting without reducing eating rates and intake, and adding water to TMR to achieve a dry matter less than 65% tended to decrease DMI without reducing sorting.