Testing theories of the vocabulary spurt with monolingual and bilingual infants.

Sometime before their second birthday, many children have a period of rapid expressive vocabulary growth called the vocabulary spurt. Theories of the underlying mechanisms differ: Accumulator models emphasize the accumulation of experience with words over time to yield a spurtlike pattern, while cognitive models attribute the spurt to cognitive changes. To test these theories, English-French monolingual and bilingual children with different exposure to each language were studied. Dense, longitudinal data were analyzed from 45 infants aged 16-30 months, whose expressive vocabulary was measured on a total of 617 occasions in English and/or French. Single-language (English and/or French), concept (number of concepts lexicalized across both languages), and word (sum of both languages) vocabulary scores were computed. Infants' exposure to each language and their exposure balance were measured using a language exposure questionnaire. Logistic curves were fitted to each infant's data to estimate the timing (midpoint) and steepness (slope) of the vocabulary spurt in single-language, concept, and word vocabularies. Seventy-six percent of infants showed a spurt in at least one vocabulary type, and bilinguals were less likely to show one in their nondominant than their dominant language. For single-language vocabulary, infants with more exposure to a language had earlier spurts. For combined vocabularies (concept and word), monolinguals and unbalanced bilinguals had earlier and steeper spurts than balanced bilinguals. Results better support the predictions of accumulator models than cognitive theories and show that infants follow different vocabulary acquisition trajectories based on their language background. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cognates are advantaged over non-cognates in early bilingual expressive vocabulary development.

Bilinguals need to learn two words for most concepts. These words are called translation equivalents, and those that also sound similar (e.g., banana-banane) are called cognates. Research has consistently shown that children and adults process and name cognates more easily than non-cognates. The present study explored if there is such an advantage for cognate production in bilinguals' early vocabulary development. Longitudinal expressive vocabulary data were collected from 47 English-French bilinguals starting at 16-20 months up to 27 months (a total of 219 monthly administrations in both English and French). Children produced a greater proportion of cognates than non-cognates, and the interval between producing a word and its translation equivalent was about 10-15 days shorter for cognates than for non-cognates. The findings suggest that cognate learning is facilitated in early bilingual vocabulary development, such that phonological overlap supports bilinguals in learning phonologically similar words across their two languages.

P29-A135†Impact of COVID-19 on corneal donation and transplantation in Hong Kong.

PURPOSE: With many health and policy issues arising from COVID-19, the Hospital Authority Eye Bank of Hong Kong encountered challenges related to ocular donor suitability and availability. This review aims to analyse the impact of a global pandemic on corneal donation and transplantation in 2020 and 2021, compared to the pre-COVID period in 2019. METHODS: This cohort study evaluated data collected from the Hospital Authority Eye Bank from January 2019 to December 2021. The number of corneas harvested, including voluntary donations initiated by the deceased's relatives and approached cases by Eye Donation Coordinators, tissue distributed, transplanted and disposed, the reason for disposal as well as the usage of the transplanted corneas in 2020 and 2021 were compared to the pre-COVID period of 2019. RESULTS: The number of corneas harvested dropped by 17.6% in 2020 compared to the pre-COVID period of 2019, and rose almost back to baseline in 2021. However, despite having near-normal number of harvested corneas in 2021, the number of corneal transplants using fresh corneas were still reduced by 30% in 2020 and 27% 2021. The observation can be explained by the seven-fold increment in disposal due to suboptimal quality from a cancer donor in 2021. The proportion of corneas used for optical, therapeutic and tectonic purposes remained stable throughout the three years. CONCLUSION: COVID-19 yielded brief periods of service interruption and reduced number of eligible donors, leading to a noticeable rise in solicitation from cancer donors in 2021. The pandemic resulted in a longer corneal transplant waiting time. Nevertheless, The proportion of different corneal transplantation remained stable, with even the development in new techniques such as Descemet's Membrane Endothelial Keratoplasty and enhancement in services such as provision of ultra-fresh Keratolimbal allografts despite the limitations in the COVID-19 era.

The NF-κB multidimer system model: A knowledge base to explore diverse biological contexts.

The nuclear factor κB (NF-κB) system is critical for various biological functions in numerous cell types, including the inflammatory response, cell proliferation, survival, differentiation, and pathogenic responses. Each cell type is characterized by a subset of 15 NF-κB dimers whose activity is regulated in a stimulus-responsive manner. Numerous studies have produced different mathematical models that account for cell type-specific NF-κB activities. However, whereas the concentrations or abundances of NF-κB subunits may differ between cell types, the biochemical interactions that constitute the NF-κB signaling system do not. Here, we synthesized a consensus mathematical model of the NF-κB multidimer system, which could account for the cell type-specific repertoires of NF-κB dimers and their cell type-specific activation and cross-talk. Our review demonstrates that these distinct cell type-specific properties of NF-κB signaling can be explained largely as emergent effects of the cell type-specific expression of NF-κB monomers. The consensus systems model represents a knowledge base that may be used to gain insights into the control and function of NF-κB in diverse physiological and pathological scenarios and that describes a path for generating similar regulatory knowledge bases for other pleiotropic signaling systems.

Patterns of language switching and bilingual children's word learning: An experiment across two communities.

Language switching is common in bilingual environments, including those of many bilingual children. Some bilingual children hear rapid switching that involves immediate translation of words (an 'immediate-translation' pattern), while others hear their languages most often in long blocks of a single language (a 'one-language-at-a-time' pattern). Our two-site experimental study compared two groups of developing bilinguals from different communities, and investigated whether differences in the timing of language switching impose different demands on bilingual children's learning of novel nouns in their two languages: do children learn differently if they hear a translation immediately vs. if they hear translations more separated in time? Using an at-home online tablet word learning task, data were collected asynchronously from 3- to 5-year-old bilinguals from French-English bilingual families in Montreal, Canada (N = 31) and Spanish-English bilingual families in New Jersey, USA (N = 22). Results showed that bilingual children in both communities readily learned new words, and their performance was similar across the immediate-translation and one-language-at-a-time conditions. Our findings highlight that different types of bilingual interactions can provide equal learning opportunities for bilingual children's vocabulary development.

Wavefront aberrometry repeatability and agreement-A comparison between Pentacam AXL Wave, iTrace and OPD-Scan III.

INTRODUCTION: To compare intrasession agreement and repeatability of wavefront aberration measurements from three different aberrometers obtained using Hartmann-Shack, ray tracing and automated retinoscopy methods, as well as their interdevice agreement. METHODS: Three consecutive measurements were obtained using the Pentacam AXL Wave, the iTrace and the OPD-Scan III in 47 eyes of 47 patients. Wavefront refractions, root mean square of total aberrations (RMS total), RMS of higher-order aberrations (HOA) and second-, third- and fourth-order HOAs were exported for 4-mm pupils. Wavefront refractions were converted into vector components: M, J0 and J45 . Intrasession agreement and repeatability were evaluated using intraclass correlation coefficients (ICCs) and repeatability coefficients (RCs); interdevice agreement was assessed using the Bland-Altman method. RESULTS: The intrasession agreement and repeatability of RMS HOA were comparable between the three devices; both the Pentacam AXL Wave and the OPD-Scan III had better intrasession agreement and repeatability for the RMS total than the iTrace (p ≤ 0.02). Intrasession repeatability for the majority of second- and third-order aberrations was better on the Pentacam AXL Wave than on the iTrace (p ≤ 0.01) and OPD-Scan III (p ≤ 0.04), although their agreement and repeatability in spherical aberration were comparable (p ≥ 0.24). Significant systematic differences and proportional bias were detected for almost all refraction power vectors and Zernike coefficients among the three devices. CONCLUSIONS: In this study, all three devices provided good-to-excellent agreement for aberration measurements. Most of the individual Zernike's components were not exchangeable between different aberrometers. Their relative intrasession performance in agreement and repeatability varied significantly across different ocular aberration parameters.

Accelerated corneal collagen cross-linking in progressive keratoconus: Five-year results and predictors of visual and topographic outcomes.

Purpose: To analyze the 5-year results of accelerated corneal collagen crosslinking (CXL) for progressive keratoconus and identify preoperative characteristics predictive of visual and topographic outcomes. Methods: A prospective interventional case series. Nineteen eyes of 19 patients receiving accelerated CXL with settings of 18 mW/cm2 for 5 min were included. Clinical and topographic parameters were assessed. Linear regression and logistic regression were used to compare the R2 and odds ratio (OR), respectively, between baseline characteristics and postoperative outcomes. Results: Corrected distance visual acuity (CDVA) remained stable from 0.28 ± 0.21 to 0.25 ± 0.18 logMAR (P = 0.486). The mean cylindrical refraction was stable (P = 0.119). The maximal keratometry (Kmax) decreased from 61.99 ± 10.37 to 59.25 ± 7.75 D (P < 0.001), flattening in the flattest and steepest meridians and mean keratometry were also observed (P ≤ 0.040). The mean anterior elevation at the apex reduced from 21.42 ± 16.69 to 18.53 ± 12.74 µm (P = 0.013) and changes in posterior elevation were non-significant (P = 0.629). Preoperative Kmax best predicted the postoperative change in Kmax (R2 = 0.55, P < 0.001) compared to the other baseline characteristics (P ≤ 0.028), whereas preoperative CDVA was the only significant predictor of postoperative change in CDVA (R2 = 0.41, P = 0.003). Accelerated CXL is less likely to fail in eyes with a steeper preoperative Kmax (OR = 0.74, P = 0.040) or greater posterior elevation at the apex (OR = 0.91, P = 0.042). Conclusion: Kmax significantly decreased following accelerated CXL. Eyes with worse preoperative CDVA and higher Kmax were more likely to have an improvement in visual acuity and corneal flattening.

Investigation of healthcare-associated SARS-CoV-2 infection: Learning outcomes from an investigative process in the initial phase of the pandemic.

Background: Healthcare-associated (HCA) SARS-CoV-2 infection is a significant contributor to the spread of the 2020 pandemic. Timely review of HCA cases is essential to identify learning to inform infection prevention and control (IPC) policies and organisational response. Aim: To identify key areas for improvement through rapid investigation of HCA SARS-CoV-2 cases and to implement change. Methods: Cases were identified based on date of first positive SARS-CoV-2 PCR sample in relation to date of hospital admission. Cases were reviewed using a structured gap analysis tool to identify key learning points. These were discussed in weekly multidisciplinary meetings to gain consensus on learning outcomes, level of harm incurred by the patient and required actions. Learning was then promptly fed back to individual teams and the organisation. Findings: Of the 489 SARS-CoV-2 cases admitted between 10th March and 23rd June 2020, 114 suspected HCA cases (23.3%) were reviewed; 58/489 (11.8%) were ultimately deemed to be HCA. Five themes were identified: individual patient vulnerability, communication, IPC implementation, policy issues and organisational response. Adaptations to policies based on these reviews were completed within the course of the initial phase of the pandemic. Conclusion: This approach enabled timely learning and implementation of control measures and policy development.

Are translation equivalents special? Evidence from simulations and empirical data from bilingual infants.

The acquisition of translation equivalents is often considered a special component of bilingual children's vocabulary development, as bilinguals have to learn words that share the same meaning across their two languages. This study examined three contrasting accounts for bilingual children's acquisition of translation equivalents relative to singlets (i.e., words that are first labels for a referent): the Avoidance Account whereby translation equivalents are harder to learn, the Preference Account whereby translation equivalents are easier to learn, and the Neutral Account whereby translation equivalents and singlets are learned similarly. To adjudicate between these accounts, Study 1 explored patterns of translation equivalent learning under a novel computational model - the Bilingual Vocabulary Model - which quantifies translation equivalent knowledge as a function of the probability of learning words in each language, and includes a bias parameter that varies the difficulty of learning translation equivalents according to each account. Study 2 tested model-derived predictions against vocabulary data from 200 French-English bilingual children aged 18-33 months. Results showed a close match between the model predictions and bilingual children's patterns of translation equivalent learning. At smaller vocabulary sizes, data matched the Preference Account, while at larger vocabulary sizes they matched the Neutral Account. Our findings show that patterns of translation equivalent learning emerge predictably from the word learning process, and potentially reveal a qualitative shift in translation equivalent learning as bilingual children develop and learn more words.

Experiments from unfinished Registered Reports in the Reproducibility Project: Cancer Biology.

As part of the Reproducibility Project: Cancer Biology, we published Registered Reports that described how we intended to replicate selected experiments from 29 high-impact preclinical cancer biology papers published between 2010 and 2012. Replication experiments were completed and Replication Studies reporting the results were submitted for 18 papers, of which 17 were accepted and published by eLife with the rejected paper posted as a preprint. Here, we report the status and outcomes obtained for the remaining 11 papers. Four papers initiated experimental work but were stopped without any experimental outcomes. Two papers resulted in incomplete outcomes due to unanticipated challenges when conducting the experiments. For the remaining five papers only some of the experiments were completed with the other experiments incomplete due to mundane technical or unanticipated methodological challenges. The experiments from these papers, along with the other experiments attempted as part of the Reproducibility Project: Cancer Biology, provides evidence about the challenges of repeating preclinical cancer biology experiments and the replicability of the completed experiments.

The development of gaze following in monolingual and bilingual infants: A multi-laboratory study.

Determining the meanings of words requires language learners to attend to what other people say. However, it behooves a young language learner to simultaneously encode relevant non-verbal cues, for example, by following the direction of their eye gaze. Sensitivity to cues such as eye gaze might be particularly important for bilingual infants, as they encounter less consistency between words and objects than monolingual infants, and do not always have access to the same word-learning heuristics (e.g., mutual exclusivity). In a preregistered study, we tested the hypothesis that bilingual experience would lead to a more pronounced ability to follow another's gaze. We used a gaze-following paradigm developed by Senju and Csibra (Current Biology, 18, 2008, 668) to test a total of 93 6- to 9-month-old and 229 12- to 15-month-old monolingual and bilingual infants, in 11 laboratories located in 8 countries. Monolingual and bilingual infants showed similar gaze-following abilities, and both groups showed age-related improvements in speed, accuracy, frequency, and duration of fixations to congruent objects. Unexpectedly, bilinguals tended to make more frequent fixations to on-screen objects, whether or not they were cued by the actor. These results suggest that gaze sensitivity is a fundamental aspect of development that is robust to variation in language exposure.

Fluctuation in straylight measurements during the visual recovery phase after small incision lenticule extraction.

PURPOSE: To investigate the postoperative straylight changes during the visual recovery phase after small incision lenticule extraction (SMILE) and their association. METHODS: Seventy consecutive eyes from 37 patients with a mean age of 30.92 ± 7.26 years and a mean preoperative spherical equivalent of -5.24 ± 1.90 dioptres undergoing myopic or myopic astigmatism SMILE correction were included in this prospective study. Patients were followed up at days 1, 3, 7, 14, 21 and 28 after standard SMILE. Straylight was measured using the C-Quant straylight meter (Oculus GmbH, Germany) preoperatively and at each postoperative visit. RESULTS: Preoperatively, the mean straylight measurement was 1.16 ± 0.16. After SMILE, the mean straylight values were 1.12 ± 0.14 and 1.13 ± 0.13 at days 7 and 14, which were significantly reduced compared to preoperative values (p ≤ 0.028). Straylight returned to baseline by week 3 (p = 0.160) and remained stable onwards (p = 0.651). A lower ablation ratio was associated with less straylight level at days 1, 3, 14 and 21 (p ≤ 0.0497) in the multivariable regression model. Likewise, better visual acuity was associated with lower straylight at days 7, 14 and 28 postoperatively (p ≤ 0.038). A small proportion of eyes (range: 0-12.86%) had ≥0.30 log(s) increase in postoperative straylight within the first month after SMILE. CONCLUSIONS: SMILE induced a temporary decrease in straylight. It gradually returned to the preoperative level, which could be related to a number of dynamic processes during corneal healing. In the small proportion of patients with an increase in straylight postoperatively, this can affect their visual recovery during the early postoperative period.

Replication study: androgen receptor splice variants determine taxane sensitivity in prostate cancer.

In 2015, as part of the Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative, we published a Registered Report (Shan et al., 2015) that described how we intended to replicate selected experiments from the paper "Androgen Receptor Splice Variants Determine Taxane Sensitivity in Prostate Cancer" (Thadani-Mulero et al., 2014). Here we report the results of those experiments. Growth of tumor xenografts from two prostate cancer xenograft lines, LuCaP 86.2, which expresses wild-type androgen receptor (AR) and AR variant 567, and LuCaP 23.1, which expresses wild-type AR and AR variant 7, were not affected by docetaxel treatment. The LuCaP 23.1 tumor xenografts grew slower than in the original study. This result is different from the original study, which reported significant reduction of tumor growth in the LuCaP 86.2. Furthermore, we were unable to detect ARv7 in the LuCaP 23.1, although we used the antibody as stated in the original study and ensured that it was detecting ARv7 via a known positive control (22rv1, Hörnberg et al., 2011). Finally, we report a meta-analysis of the result.

IκBß enhances the generation of the low-affinity NFκB/RelA homodimer.

The NFκB family of dimeric transcription factors regulate inflammatory and immune responses. While the dynamic control of NFκB dimer activity via the IκB-NFκB signalling module is well understood, there is little information on how specific dimer repertoires are generated from Rel family polypeptides. Here we report the iterative construction-guided by in vitro and in vivo experimentation-of a mathematical model of the Rel-NFκB generation module. Our study reveals that IκBß has essential functions within the Rel-NFκB generation module, specifically for the RelA:RelA homodimer, which controls a subset of NFκB target genes. Our findings revise the current dogma of the three classical, functionally related IκB proteins by distinguishing between a positive 'licensing' factor (IκBß) that contributes to determining the available NFκB dimer repertoire in a cell's steady state, and negative feedback regulators (IκBα and -ɛ) that determine the duration and dynamics of the cellular response to an inflammatory stimulus.

Studying NF-κB signaling with mathematical models.

Mathematical modeling of NF-κB signaling can be employed to understand how the network of molecular interactions leads to signaling phenomena observed experimentally. Model construction is a challenging process; however, existing models can be utilized and can provide a great deal of insight quickly and inexpensively. The simulation of various inputs and the identification of potential therapeutic targets using the mathematical model are detailed here.

A pathway switch directs BAFF signaling to distinct NFκB transcription factors in maturing and proliferating B cells.

BAFF, an activator of the noncanonical NFκB pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NFκB family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, whereas at high synthesis rates, p100 assembles into multimeric IκBsome complexes, which BAFF neutralizes in order to potentiate cRel activity and B cell expansion. Indeed, moderation of p100 expression or disruption of IκBsome assembly circumvented the BAFF requirement for full B cell expansion. Our studies emphasize the importance of p100 in determining distinct NFκB network states during B cell biology, which causes BAFF to have context-dependent functional consequences.

IκBε is a key regulator of B cell expansion by providing negative feedback on cRel and RelA in a stimulus-specific manner.

The transcription factor NF-κB is a regulator of inflammatory and adaptive immune responses, yet only IκBα was shown to limit NF-κB activation and inflammatory responses. We investigated another negative feedback regulator, IκBε, in the regulation of B cell proliferation and survival. Loss of IκBε resulted in increased B cell proliferation and survival in response to both antigenic and innate stimulation. NF-κB activity was elevated during late-phase activation, but the dimer composition was stimulus specific. In response to IgM, cRel dimers were elevated in IκBε-deficient cells, yet in response to LPS, RelA dimers also were elevated. The corresponding dimer-specific sequences were found in the promoters of hyperactivated genes. Using a mathematical model of the NF-κB-signaling system in B cells, we demonstrated that kinetic considerations of IκB kinase-signaling input and IκBε's interactions with RelA- and cRel-specific dimers could account for this stimulus specificity. cRel is known to be the key regulator of B cell expansion. We found that the RelA-specific phenotype in LPS-stimulated cells was physiologically relevant: unbiased transcriptome profiling revealed that the inflammatory cytokine IL-6 was hyperactivated in IκBε(-/-) B cells. When IL-6R was blocked, LPS-responsive IκBε(-/-) B cell proliferation was reduced to near wild-type levels. Our results provide novel evidence for a critical role for immune-response functions of IκBε in B cells; it regulates proliferative capacity via at least two mechanisms involving cRel- and RelA-containing NF-κB dimers. This study illustrates the importance of kinetic considerations in understanding the functional specificity of negative-feedback regulators.

A single NFκB system for both canonical and non-canonical signaling.

Two distinct nuclear factor κB (NFκB) signaling pathways have been described; the canonical pathway that mediates inflammatory responses, and the non-canonical pathway that is involved in immune cell differentiation and maturation and secondary lymphoid organogenesis. The former is dependent on the IκB kinase adaptor molecule NEMO, the latter is independent of it. Here, we review the molecular mechanisms of regulation in each signaling axis and attempt to relate the apparent regulatory logic to the physiological function. Further, we review the recent evidence for extensive cross-regulation between these two signaling axes and summarize them in a wiring diagram. These observations suggest that NEMO-dependent and -independent signaling should be viewed within the context of a single NFκB signaling system, which mediates signaling from both inflammatory and organogenic stimuli in an integrated manner. As in other regulatory biological systems, a systems approach including mathematical models that include quantitative and kinetic information will be necessary to characterize the network properties that mediate physiological function, and that may break down to cause or contribute to pathology.