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To acquire language, learners have to map the language onto the environment, but languages vary as to how much information they include to constrain how a sentence relates to the world. We investigated the conditions under which information within the language and the environment is combined for learning. In a cross-situational artificial language learning study, participants listened to transitive sentences and viewed two scenes, and selected which scene was described by the sentence. There were three conditions, involving different language variants. All variants had free word order but varied as to whether or not they contained morphosyntactic information that defined the subject and object roles of nouns in the sentence. We found that participants were able to learn information about word order and vocabulary from each variant, demonstrating that learners are not reliant on information within a language only, but can combine constraints from language and environment to support acquisition.

Collocations are understood to be integral building blocks of language processing, alongside individual words, but thus far evidence for the psychological reality of collocations has tended to be confined to English. In contrast to English, Turkish is an agglutinating language, utilizing productive morphology to convey complex meanings using a single word. Given this, we expected Turkish speakers to be less sensitive to phrasal frequencies than English speakers. In Study 1, we conducted a corpus analysis of translation-equivalent adjective-noun collocations (e.g., front door) and found differences between the two languages in frequency counts. In Study 2, we conducted a reaction time experiment to determine the sensitivity of native speakers of English and Turkish to the frequency of adjectives, nouns, and whole collocations. Turkish speakers were less sensitive to whole-phrase frequencies, as predicted, indicating that collocations are processed less holistically in Turkish than English. Both groups demonstrated that processing collocations involves combining information about individual words and phrases. Taken together, we show that speakers are sensitive to frequency information at multiple grain sizes that are attuned to the typology of different languages.

Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding difficulties, and gait disturbance. Dysmorphisms and behavioral and/or psychiatric conditions, including autism spectrum disorder, and to a lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision problems, and other organ anomalies, were observed in affected individuals. As a molecular biomarker, a sensitive and specific DNA methylation episignature has been established. Induced pluripotent stem cells (iPSCs) derived from three members of our cohort exhibited reduced MSL2 levels. Remarkably, while NDD-associated variants in two other members of the MSL complex (MOF and MSL3) result in reduced H4K16ac, global H4K16ac levels are unchanged in iPSCs with MSL2 variants. Regardless, MSL2 variants altered the expression of MSL2 targets in iPSCs and upon their differentiation to early germ layers. Our study defines an MSL2-related disorder as an NDD with distinguishable clinical features, a specific blood DNA episignature, and a distinct, MSL2-specific molecular etiology compared to other MSL complex-related disorders.

OBJECTIVES: Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities. METHODS: Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model. RESULTS: Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%-36%; I2 = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%-34%; I2 = 74%]; (b) single CNS anomaly; 16% [95% CI 10%-23%; I2 = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%-40%; I2 = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%-57%; I2 = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus. CONCLUSIONS: Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.

Given the low price of community college relative to need-based aid, last-dollar "free community college" (i.e., Promise) programs often only marginally reduce students' real costs. Given this reality, some claim that these programs impact students largely through "messaging": information conveying the affordability of community college. However, it is unclear how such messaging works in concept or practice. Drawing on a case study, I document the paradoxical ways last-dollar community college Promise programs alter students' understanding of college affordability. Reflecting program marketing, students typically understood the program as simply "free college," with little grasp of last-dollar structure or eligibility criteria. Many believed the Promise program paid their tuition, but administrative data showed the program funded very few students. Student misunderstanding of the program is traceable to a baseline conception of college as "expensive" and to a tenuous grasp of need-based aid. Promise programs' "messaging effects" are predicated upon such prevalent misconceptions. The "message" is a mixture of clarification and misdirection, revealing a factual situation (that community college is often "tuition-free") through an equivocation (that the Promise program is making it free).

Abstract Background Anti-angiogenic, VEGF inhibitors (VEGFi) increase progression-free survival (PFS) and, in some cases, overall survival in many solid tumours. However, their use has been compromised by a lack of informative biomarkers. We have shown that plasma Tie2 is the first tumour vascular response biomarker for VEGFi in ovarian, colorectal and gall bladder cancer: If plasma Tie2 concentrations do not change after 9 weeks of treatment with a VEGFi, the patient does not benefit, whereas a confirmed reduction of at least 10% plasma Tie2 defines a vascular response with a hazard ratio (HR) for PFS of 0.56. The aim of the VALTIVE1 study is to validate the utility of plasma Tie2 as a vascular response biomarker and to optimise the Tie2-definition of vascular response so that the subsequent randomised discontinuation VALTIVE2 study can be powered optimally. Methods VALTIVE1 is a multi-centre, single arm, non-interventional biomarker study, with a sample size of 205 participants (176 bevacizumab-treated participants + 29 participants receiving bevacizumab and olaparib/PARPi), who are 16 years or older, have FIGO stage IIIc/IV ovarian cancer on treatment with first-line platinum-based chemotherapy and bevacizumab. Their blood plasma samples will be collected before, during, and after treatment and the concentration of Tie2 will be determined. The primary objective is to define the PFS difference between Tie2-defined vascular responders and Tie2-defined vascular non-responders in patients receiving bevacizumab for high-risk Ovarian Cancer. Secondary objectives include defining the relationship between Tie2-defined vascular progression and disease progression assessed according to RECIST 1.1 criteria and assessing the impact of PARPi on the plasma concentration of Tie2 and, therefore, the decision-making utility of Tie2 as a vascular response biomarker for bevacizumab during combined bevacizumab-PARPi maintenance. Discussion There is an urgent need to establish a test that tells patients and their doctors when VEGFi are working and when they stop working. The data generated from this study will be used to design a second trial aiming to prove conclusively the value of the Tie2 test. Trial registration ClinicalTrials.gov identifier: NCT04523116. Registered on 21 Aug 2020.

Abstract Adapting to different environments throughout daily activities requires flexibility in allocating attention. Compromised dual-tasking can hinder mobility, increase fall risk, and decrease functional independence in patients with essential tremor, who exhibit both mobility and cognitive impairments. We evaluated motor and cognitive dual-task effects and task prioritization in 15 people with Essential Tremor (ET) and 15 age-matched people without ET during a standard and more challenging water-carry TUG. Task-specific interference was evaluated by calculating motor and cognitive dual-task effects, whereas task prioritization was assessed by contrasting the cognitive dual-task effect with the motor dual-task effect. The simultaneous performance of two tasks did not differentially impact motor or cognitive performance in either group, and both groups prioritized cognitive task performance in standard and water-carry TUG assessments. This study enhances our understanding of motor-cognitive interactions in individuals with essential tremor. These insights could lead to patient-centered approaches to therapy to improve functional performance in dynamic daily environments.

Vibrational spectroscopic techniques, such as Fourier transform infrared (FTIR) absorption and Raman spectroscopy (RS), offer unique and detailed biochemical fingerprints by detecting specific molecular vibrations within samples. These techniques provide profound insights into the molecular alterations induced by ionising radiation, which are both complex and multifaceted. This paper reviews the application of rapid and label-free vibrational spectroscopic methods for assessing biological radiation responses. These assessments span from early compartmentalised models such as DNA, lipid membranes, and vesicles to comprehensive evaluations in various living biological models, including tissues, cells, and organisms of diverse origins. The review also discusses future perspectives, highlighting how the field is overcoming methodological limitations. RS and FTIR have demonstrated significant potential in detecting radiation-induced biomolecular alternations, which may facilitate the identification of radiation exposure spectral biomarkers/profiles.

ABSTRACT: In countries with pasture-based dairy systems and relatively cold winters, such as New Zealand, it is common to manage pregnant, nonlactating cows on forage crop paddocks rather than pasture, due to slow pasture growth rates. Wintering dairy cattle on grazed crops can compromise welfare if wet and muddy underfoot conditions occur, which can reduce lying. This study investigated behavioral and physiological indicators of welfare of cows under 2 wintering practices: cows managed on and grazed kale crop (Brassica oleracea), and cows managed on pasture with baled hay. Following dry-off (d 0), 80 cows were randomly assigned to 1 of the 2 wintering practices (40 cows/practice) and monitored between d 4 and 32 (phase 1). During this period, lying and stepping behavior was continuously recorded using leg-based accelerometers. Blood samples were obtained at d 0 and 32 for measurements of thyroxine (T4), nonesterified fatty acids (NEFA), white blood cells (WBC), and red blood cells. All data for phase 1 were presented descriptively due to the lack of treatment replication. Daily mean air temperature during this period was 5.2°C (range: 0.0–10.7°C), and rainfall was 1.1 mm/d (range: 0–5.6mm/d). Between d 4 and 32, cows in both groups spent similar amounts of time lying (pasture with hay cows: 8.9 h/24 h ± 2.57, kale crop cows: 8.7 h/24 h ± 3.06, mean ± SEM). Both groups reduced their lying on wet and cold days, and there was evidence of rebound lying once unfavorable weather conditions stopped. Cows on kale crop had numerically higher NEFA and lower WBC compared with cows managed on pasture, although most physiological values were within normal ranges. In a second phase of the study (d 34 and 35), cows were managed under controlled, replicated conditions in the 2 wintering practices using typical on-farm stocking rates (2 or 4 cows per group in the pasture with hay and kale crop treatments, respectively; n = 10 groups/treatment). During this period, cow behavior, skin and surface temperatures, hygiene scores, feed intakes, and ground conditions were measured. Weather conditions during the 48-h exposure were mostly cold and dry (mean air temperature: 7.8°C, range: −2.2 to 20.5°C). Cows managed on pasture with hay spent more time lying down on the first day of exposure; however, this was likely due to less space being available to kale cows on this day. Cows managed on pasture with hay ruminated more than cows on kale crop on both days of observations (d 1: 37.9% vs. 30.9% of observations, d 2: 36.8% vs. 28.7% of observations for pasture with hay and kale crop groups, respectively) and were lying more often in postures indicative of greater thermal comfort. Cows managed on pasture with hay had higher skin and surface temperatures compared with cows on kale crop, whereas cows on kale crop had dirtier coats. Results suggest that opportunities for thermal comfort were greater for cows managed on pasture with hay bales, which may be due to increased rumination activities and more insulated lying areas.

In recent decades, it has become the case that leaving school early may no longer be the conclusion of one's educational experiences, with more alternative educational spaces for disenfranchised learners becoming accessible. This qualitative study examines the experiences of 14 young adults in Ireland who, having left their mainstream school prior to receiving a higher secondary qualification, returned to education through an alternative facility called Youthreach. Findings indicated that participants made a distinction between a general appreciation for education, reflective of their aspirational identities, and their feelings towards the specific educational environments they have encountered. A meaningful engagement occurred when their educational aspirations appeared obtainable within the context of a particular setting. Consequently, participants did not reflect on their initial decision to leave as a mistake, as they found that their unsupportive environments provided them with little space to succeed. As a result, participants presented their decision to leave as a sensible response in accordance with what they deemed to be the right course of action for their own development.

Objective: We aimed to examine the psychometric properties of the Scale of Perfectionism and Excellencism (SCOPE) in a novel sample, Australian adolescents. Method: The cross-sectional sample consisted of 350 participants (79 male, 271 female; mean age 17.9 years, age range = 15-20 years) from a secondary 10 school and university who completed a web-based questionnaire. Results: Confirmatory factor analyses showed that the original two-factor structure was replicated and invariant across gender, educational setting, and language (English as first or second language). Cronbach alphas indicated good internal consistency: Excellencism (0.95) and Perfectionism (0.97). We found evidence for divergent and convergent validity. Academic performance was associated with Excellencism, independent of 15 Perfectionism (partial r = 0.32; p < 0.01), with no discernible relationship with Perfectionism. We explored concurrent validity and found mixed results with associations being in the expected direction only for the criterion measures that might be conceptualised as capturing negative-type perfectionism. Conclusions: This study provides valuable insights into SCOPE and the distinct constructs of Excellencism and Perfectionism. Findings indicate Excellencism is associated with more positive 20 academic and mental health outcomes compared to Perfectionism. Further research is warranted to explore long-term outcomes of these constructs to potentially inform educational practice, mental health promotion, and early intervention.

Empirical educational research nearly universally tacitly assumes that people attend college only in order to improve their likely earnings. Thus, it ignores the immense cultural importance ascribed to education (and particularly higher education) in modern culture, or at least proceeds as if this cultural valorization is irrelevant to individuals' educational decision-making. I first review how an economistic model of action informs all dominant theories of educational decision-making, and then suggest how institutional theory can provide a richer account of the college transition. Drawing on in-depth interviews with first-time, first-year community college students, I illustrate this approach through a 'thick description' of individuals' emerging educational orientations. I find that attending college reflects both instrumental goals and moralized conceptions of educational attainment. The decision to attend community college was informed by conceptions of college costs, a limited understanding of grant aid, and loan aversion. And I identify three educational dispositions among entering community college students which map onto institutionalized organizational pathways through the community college itself.

Abstract Background Salmonid species have followed markedly divergent evolutionary trajectories in their interactions with sea lice. While sea lice parasitism poses significant economic, environmental, and animal welfare challenges for Atlantic salmon (Salmo salar) aquaculture, coho salmon (Oncorhynchus kisutch) exhibit near-complete resistance to sea lice, achieved through a potent epithelial hyperplasia response leading to rapid louse detachment. The molecular mechanisms underlying these divergent responses to sea lice are unknown. Results We characterized the cellular and molecular responses of Atlantic salmon and coho salmon to sea lice using single-nuclei RNA sequencing. Juvenile fish were exposed to copepodid sea lice (Lepeophtheirus salmonis), and lice-attached pelvic fin and skin samples were collected 12 h, 24 h, 36 h, 48 h, and 60 h after exposure, along with control samples. Comparative analysis of control and treatment samples revealed an immune and wound-healing response that was common to both species, but attenuated in Atlantic salmon, potentially reflecting greater sea louse immunomodulation. Our results revealed unique but complementary roles of three layers of keratinocytes in the epithelial hyperplasia response leading to rapid sea lice rejection in coho salmon. Our results suggest that basal keratinocytes direct the expansion and mobility of intermediate and, especially, superficial keratinocytes, which eventually encapsulate the parasite. Conclusions Our results highlight the key role of keratinocytes in coho salmon’s sea lice resistance and the diverged biological response of the two salmonid host species when interacting with this parasite. This study has identified key pathways and candidate genes that could be manipulated using various biotechnological solutions to improve Atlantic salmon sea lice resistance.

Abstract Climate change elevates the threat of compound heat and drought events, with their ecological and socioeconomic impacts exacerbated by human ecosystem alterations such as eutrophication, salinization, and river engineering. Here, we study how multiple stressors produced an environmental disaster in a large European river, the Oder River, where a toxic bloom of the brackish-water planktonic haptophyte Prymnesium parvum (the “golden algae”) killed approximately 1000 metric tons of fish and most mussels and snails. We uncovered the complexity of this event using hydroclimatic data, remote sensing, cell counts, hydrochemical and toxin analyses, and genetics. After incubation in impounded upstream channels with drastically elevated concentrations of salts and nutrients, only a critical combination of chronic salt and nutrient pollution, acute high water temperatures, and low river discharge during a heatwave enabled the riverine mass proliferation of B-type P. parvum along a 500 km river section. The dramatic losses of large filter feeders and the spreading of vegetative cells and resting stages make the system more susceptible to new harmful algal blooms. Our findings show that global warming, water use intensification, and chronic ecosystem pollution could increase likelihood and severity of such compound ecoclimatic events, necessitating consideration in future impact models.

Abstract As age increases, a decline in lower extremity strength leads to reduced mobility and increased fall risks. This decline outpaces the age-related reduction in muscle mass, resulting in mobility limitations. Older adults with varying degrees of mobility-disability use different stepping strategies. However, the link between functional lower extremity strength and stepping strategy is unknown. Therefore, understanding how age-related reductions in functional lower extremity strength influence stepping strategy is vital to unraveling mobility limitations. Twenty participants (17F, 72 ± 6 years) were recruited and tested at a local community event. Participants were outfitted with inertial measurement units (IMU) and walked across a pressurized walkway under single and dual motor task conditions (walking with and without carrying a tray with water) at their usual and fast speeds. Participants were dichotomized into normal (11) or low functional strength groups (9) based on age-specific normative cutoffs using the instrumented 5-repetition Sit-to-Stand test duration. Our study reveals that older adults with normal strength prefer adjusting their step time during walking tasks, while those with reduced strength do not exhibit a preferred stepping strategy. This study provides valuable insights into the influence of functional lower extremity strength on stepping strategy in community-dwelling older adults during simple and complex walking tasks. These findings could aid in diagnosing gait deviations and developing appropriate treatment or management plans for mobility disability in older adults.

Abstract Aim To test a serious game intervention about nursing and midwifery perceptions among adolescent school children. Background Nursing and midwifery professions face challenges in recruitment, with persistent gender stereotypes and a lack of clarity regarding the roles contributing to this issue. This study addresses the need for innovative approaches to reshape perceptions and encourage career exploration in adolescent school children. Design Employing a pre/post-test design, this study involved 137 post-primary students aged sixteen or seventeen in the United Kingdom. Methods Data collection occurred between November 2022 to April 2023, involving three post-primary schools. Participants engaged with a digital serious game designed to address misconceptions and promote a more accurate understanding of nursing and midwifery. Participants completed pre- and post-intervention questionnaires, including an adapted version of the Nursing as a Career Choice Questionnaire. Statistical analyses included descriptive statistics, paired t-tests, and independent groups t-tests. Results The serious game intervention resulted in statistically significant improvements in students’ perceptions across multiple domains. Overall, participants showed higher mean post-test scores (M = 139.57, SD = 15.10) compared to their mean pre-test score (M = 131.06, SD = 14.73) on the questionnaire. The domains of self-efficacy (p

Computational models of reading have tended to focus on the cognitive requirements of mapping among written, spoken, and meaning representations of individual words in adult readers. Consequently, the alignment of these computational models with behavioural studies of reading development has to date been limited. Models of reading have provided us with insights into the architecture of the reading system, and these have recently been extended to investigate literacy development, and the early language skills that influence children's reading. These models show us: how learning to read builds on early language skills, why various reading interventions might be more or less effective for different children, and how reading develops across different languages and writing systems. Though there is growing alignment between descriptive models of reading behaviour and computational models, there remains a gap, and I lay out the groundwork for how translation may become increasingly effective through future modelling work.