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Cognitive science has demonstrated that we construct knowledge about the world by abstracting patterns from routinely encountered experiences and storing them as semantic memories. This preregistered study tested the hypothesis that caregiving-related early adversities (crEAs) shape affective semantic memories to reflect the content of those adverse interpersonal-affective experiences. We also tested the hypothesis that because affective semantic memories may continue to evolve in response to later-occurring positive experiences, child-perceived attachment security will inform their content. The sample comprised 160 children (ages 6-12 at Visit 1; 87F/73 M), 66% of whom experienced crEAs (n = 105). At Visit 1, crEA exposure prior to study enrollment was operationalized as parental-reports endorsing a history of crEAs (abuse/neglect, permanent/significant parent-child separation); while child-reports assessed concurrent attachment security. A false memory task was administered online [approximately]2.5 years later (Visit 2) to probe the content of affective semantic memories--specifically attachment schemas. Results showed that crEA exposure (vs. no exposure) was associated with a higher likelihood of falsely endorsing insecure (vs. secure) schema scenes. Attachment security moderated the association between crEA exposure and insecure schema-based false recognition. Findings suggest that interpersonal-affective semantic schemas include representations of parent-child interactions that may capture the quality of one's own attachment experiences and that these representations shape how children remember attachment-relevant narrative events. Findings are also consistent with the hypothesis that these affective semantic memories can be modified by later experiences. Moving forward, the approach taken in this study provides a means of operationalizing Bowlby's notion of internal working models within a cognitive neuroscience framework.

Background: Dysphagia affects over half of adults after stroke. Dysphagia rehabilitation aims to improve swallowing and reduce negative outcomes for these adults. However, significant variability exists in dysphagia rehabilitation. Research is needed to explore the underlying clinician-specific and workplace factors that contribute to variability in dysphagia rehabilitation after stroke. Aim: To explore factors influencing speech pathology practice in dysphagia rehabilitation after stroke. Methods & Procedures: We used a phenomenological approach with an interpretivist perspective. Twenty speech pathologists working in dysphagia rehabilitation participated from different workplace settings around Australia. Five semi-structured focus groups were conducted online. Data were inductively analysed using thematic analysis with a coding reliability method. Outcomes & Results: Four themes were discussed within focus groups: (1) relationship between experienced and less experienced clinicians: 'Following what other people have done', (2) need for collaborative learning: 'A safe space to share and train', (3) variation between settings impacts on continuity of care: 'There's a difference between community and acute', and (4) working effectively with multidisciplinary teams (MDT): 'An MDT which can listen to the voice of speech pathology'. Conclusions & Implications: Relationships between senior and junior speech pathologists, within speech pathology and MDT, and across inpatient and community settings influenced speech pathology practice. Flattened hierarchies in speech pathology, collaborative learning in workplaces, mutual respect within teams and connection across inpatient and community settings could improve the quality and consistency of dysphagia rehabilitation after stroke.

EWS fusion oncoproteins underlie several human malignancies including Desmoplastic Small Round Cell Tumor (DSRCT), an aggressive cancer driven by EWS-WT1 fusion proteins. Here we combine chromatin occupancy and 3D profiles to identify EWS-WT1-dependent gene regulation networks and target genes. We show that EWS-WT1 is a powerful chromatin activator controlling an oncogenic gene expression program that characterizes primary tumors. Similar to wild type WT1, EWS-WT1 has two isoforms that differ in their DNA binding domain and we find that they have distinct DNA binding profiles and are both required to generate viable tumors that resemble primary DSRCT. Finally, we identify candidate EWS-WT1 target genes with potential therapeutic implications, including CCND1, whose inhibition by the clinically-approved drug Palbociclib leads to marked tumor burden decrease in DSRCT PDXs in vivo. Taken together, our studies identify gene regulation programs and therapeutic vulnerabilities in DSRCT and provide a mechanistic understanding of the complex oncogenic activity of EWS-WT1.

BACKGROUND: Excision is routinely recommended for atypical ductal hyperplasia (ADH) found on core biopsy given cancer upstage rates of near 20%. Identifying a cohort at low-risk for upstage may avoid low-value surgery. Objectives were to elucidate factors predictive of upstage in ADH, specifically near-complete core sampling, to potentially define a group at low upstage risk. PATIENTS AND METHODS: This retrospective, cross-sectional, multi-institutional study from 2015 to 2019 of 221 ADH lesions in 216 patients who underwent excision or active observation (≥ 12 months imaging surveillance, mean follow-up 32.6 months) evaluated clinical, radiologic, pathologic, and procedural factors for association with upstage. Radiologists prospectively examined imaging for lesional size and sampling proportion. RESULTS: Upstage occurred in 37 (16.7%) lesions, 25 (67.6%) to ductal carcinoma in situ (DCIS) and 12 (32.4%) to invasive cancer. Factors independently predictive of upstage were lesion size ≥ 10 mm (OR 5.47, 95% CI 2.03-14.77, p < 0.001), pathologic suspicion for DCIS (OR 12.29, 95% CI 3.24-46.56, p < 0.001), and calcification distribution pattern (OR 8.08, 95% CI 2.04-32.00, p = 0.003, regional; OR 19.28, 95% CI 3.47-106.97, p < 0.001, linear). Near-complete sampling was not correlated with upstage (p = 0.64). All three significant predictors were absent in 65 (29.4%) cases, with a 1.5% upstage rate. CONCLUSIONS: The upstage rate among 221 ADH lesions was 16.7%, highest in lesions ≥ 10 mm, with pathologic suspicion of DCIS, and linear/regional calcifications on mammography. Conversely, 30% of the cohort exhibited all low-risk factors, with an upstage rate < 2%, suggesting that active surveillance may be permissible in lieu of surgery.

In an ever-changing world of work, workers are expected to maintain currency of changes through lifelong learning to sustain employment and transition into new jobs or occupations - as the need arises. Adult workers rely on affordances from societal, workplace, community and educational institution sources that offer opportunities - intentional or sometimes unintentional. Productive engagement in these opportunities leads to positive outcomes in terms of learning and employment, although adults' personal epistemologies, agency, and intentionality determine which affordances they engage with, in what ways, and for what purposes (Billett, Choy and Le, 2023). Moreover, working age adults' learning is largely and necessarily premised on their own constructive efforts albeit with guidance from those with whom they work closely. According to the Organisation for Economic Co-operation and Development, the working age population is defined as those aged 15 to 64 (OECD, 2023). In Australia, the working age can be extended to 74 (Australian Bureau of Statistics, 2023). Working age adults' worklife learning is sustained through permutations of lifelong learning and lifelong education that enables them to navigate different kinds of transitions that may arise due to institutional or personal factors such as life stages, employment status, occupations, re-locations, health and personal preference or trajectories (Billett, Choy & Le, 2023). This means that lifelong educational provisions need to extend beyond those from educational institutions to include experiences in workplaces and the community. The growing realisation of the potency and importance of learning experiences in workplaces and other social settings is now attracting a greater consideration of these sites for ongoing learning of working age adults. This calls for learning in the course of everyday work to be acknowledged and systematised around work practices. In this paper, we illuminate and elaborate on workplace contributions to learning that support individuals' employability across working life. Drawing on the worklife history interviews (n=66) and a survey (n=678) data from an Australian Research Council funded project [DP 190101519], we report and discuss working age adults' perspectives of workplace affordances. The findings from the interviews indicate that three work-based models suggested by Billett et al. (2016) are most appropriate for supporting workers' learning in their work settings. These are wholly work-based experiences, work-based experiences with direct guidance and work-based experiences with educational interventions. The affordances and practices of workplaces are central to supporting workers' lifelong learning in workplaces, but they also need access to lifelong education provisions to maintain currency of knowledge and skills to sustain employment.

INTRODUCTION: Upadacitinib (UPA) is a Janus kinase inhibitor that has demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA) with an acceptable safety profile. We investigated laboratory parameter changes in UPA RA clinical trials. METHODS: Pooled data from six randomized trials in the SELECT phase 3 program were included. Key laboratory parameters and safety data were measured for UPA 15 and 30 mg once daily (QD), adalimumab (ADA) 40 mg every other week + methotrexate (MTX), and MTX monotherapy. Exposure-adjusted event rates (EAERs) of adverse events were calculated. RESULTS: A total of 3209 patients receiving UPA 15 mg QD (10 782.7 patient-years [PY]), 1204 patients receiving UPA 30 mg QD (3162.5 PY), 579 patients receiving ADA + MTX (1573.2 PY), and 314 patients receiving MTX monotherapy (865.1 PY) were included, representing up to 6.5 years of total exposure. Decreases in mean levels of hemoglobin, neutrophils, and lymphocytes, and increases in mean levels of liver enzymes and creatinine phosphokinase were observed with UPA, with grade 3 or 4 changes observed in some patients. Mean low- and high-density lipoprotein cholesterol ratios remained stable for patients receiving UPA 15 mg QD. EAERs of anemia and neutropenia occurred at generally consistent rates between UPA and active comparators (3.1-4.3 and 1.7-5.0 events [E]/100 PY across treatment groups, respectively). Rates of hepatic disorder were higher with MTX monotherapy, UPA 15 mg and UPA 30 mg (10.8, 9.7, and 11.0 E/100 PY, respectively) versus ADA + MTX (6.4 E/100 PY). Rates of lymphopenia were highest with MTX monotherapy (3.2 E/100 PY). Treatment discontinuations due to laboratory-related events were rare, occurring in 1.1% and 2.2% of patients treated with UPA 15 and 30 mg QD, respectively. CONCLUSIONS: The results of this integrated long-term analysis of laboratory parameters continue to support an acceptable safety profile of UPA 15 mg QD for moderate-to-severe RA.

Trait-based frameworks are increasingly used for predicting how ecological communities respond to ongoing global change. As species range shifts result in novel encounters between predators and prey, identifying prey guilds, based on a suite of shared traits, can distill complex species interactions, and aid in predicting food web dynamics. To support advances in trait-based research in open-ocean systems, we present the Pelagic Species Trait Database, an extensive resource documenting functional traits of 529 pelagic fish and invertebrate species in a single, open-source repository. We synthesized literature sources and online resources, conducted morphometric analysis of species images, as well as laboratory analyses of trawl-captured specimens to collate traits describing 1) habitat use and behavior, 2) morphology, 3) nutritional quality, and 4) population status information. Species in the dataset primarily inhabit the California Current system and broader NE Pacific Ocean, but also includes pelagic species known to be consumed by top ocean predators from other ocean basins. The aim of this dataset is to enhance the use of trait-based approaches in marine ecosystems and for predator populations worldwide.

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.

Environmental DNA (eDNA) is an increasingly useful method for detecting pelagic animals in the ocean but typically requires large water volumes to sample diverse assemblages. Ship-based pelagic sampling programs that could implement eDNA methods generally have restrictive water budgets. Studies that quantify how eDNA methods perform on low water volumes in the ocean are limited, especially in deep-sea habitats with low animal biomass and poorly described species assemblages. Using 12S rRNA and COI gene primers, we quantified assemblages comprised of micronekton, coastal forage fishes, and zooplankton from low volume eDNA seawater samples (n = 436, 380-1800 mL) collected at depths of 0-2200 m in the southern California Current. We compared diversity in eDNA samples to concurrently collected pelagic trawl samples (n = 27), detecting a higher diversity of vertebrate and invertebrate groups in the eDNA samples. Differences in assemblage composition could be explained by variability in size-selectivity among methods and DNA primer suitability across taxonomic groups. The number of reads and amplicon sequences variants (ASVs) did not vary substantially among shallow (600 m), but the proportion of invertebrate ASVs that could be assigned a species-level identification decreased with sampling depth. Using hierarchical clustering, we resolved horizontal and vertical variability in marine animal assemblages from samples characterized by a relatively low diversity of ecologically important species. Low volume eDNA samples will quantify greater taxonomic diversity as reference libraries, especially for deep-dwelling invertebrate species, continue to expand.

Lactation insufficiency affects many women worldwide. During lactation, a large portion of mammary gland alveolar cells become polyploid, but how these cells balance the hyperproliferation occurring during normal alveologenesis with terminal differentiation required for lactation is unknown. Here, we show that DNA damage accumulates due to replication stress during pregnancy, activating the DNA damage response. Modulation of DNA damage levels in vivo by intraductal injections of nucleosides or DNA damaging agents reveals that the degree of DNA damage accumulated during pregnancy governs endoreplication and milk production. We identify a mechanism involving early mitotic arrest through CDK1 inactivation, resulting in a heterogeneous alveolar population with regards to ploidy and nuclei number. The inactivation of CDK1 is mediated by the DNA damage response kinase WEE1 with homozygous loss of Wee1 resulting in decreased endoreplication, alveologenesis and milk production. Thus, we propose that the DNA damage response to replication stress couples proliferation and endoreplication during mammary gland alveologenesis. Our study sheds light on mechanisms governing lactogenesis and identifies non-hormonal means for increasing milk production.

Abstract While operational stability has evolved to be the primary issue for the practical applications of perovskite solar cells (PSCs), the understanding of the origins of device degradation is still limited. Hysteresis is known as a unique and significant feature of PSCs. The hysteresis behavior of the current density-voltage (J–V) curves, governed by the interaction between the evolving ion-induced electric field and the carrier transport/recombination, offers rich and important information about the physical properties of the device. Herein, we propose to establish hysteresis as a diagnostic key to unveil and remedy degradation issues with device physics. With a custom-made ion-incorporated drift-diffusion simulator, we comprehensively investigate the relations between characteristic J–V hysteresis features and critical device issues such as bulk and surface defects, and low mobility of each layer in the PSCs. Ultimately, we derive a fundamental understanding and unveil the origins of the device degradation during the continuous operation of PSCs. This work therefore offers a new way to address and optimize PSC operational stability.

Abstract Background The efficacy of Seprafilm® in preventing clinically significant adhesive small bowel obstruction (ASBO) is controversial and deserves further review. The aim of this review was to assess the utility of Seprafilm® in preventing clinically significant adhesive bowel obstruction after abdominal operations, with separate focus on colorectal resections. The secondary aim was to provide an updated literature review on the safety profile of this implant. Methods An up-to-date systematic review was performed on the available literature between 2000 and 2023 on PubMed, EMBASE, Medline, and Cochrane Library databases. The main outcome measures were rates of adhesive bowel obstruction, as well as rates of intervention. The secondary outcome was the clinical safety profile of Seprafilm® as described in current literature. Results A total of 17 observational studies were included, accounting for 62,886 patients. Use of Seprafilm® was associated with a significant reduction in adhesive bowel obstruction events (OR 0.449, 95% CI: 0.3271 to 0.6122, p

Structural modularization, lightweight and functional integration are the urgent development directions for next generation high-performance aeroengines. Heat concentration during aeroengine operation would lead to local high temperature, which tremendously negative impacts on aeroengine structural life and performance. Therefore, the design and optimization of radiator structures are significant for the efficiency and reliability of aeroengine. The structural geometry design and layout optimization of radiators is promising to improve the heat dissipation efficiency and reduce aerodynamic loss. The purpose of this study is to investigate the state of the art and perspectives of aeroengine radiator structural design by a comprehensive literature review. The main contents involve the review on the structural design and layout optimization technologies of radiator structures, the analyses of the structural features, design theory and methods of existed radiator structures, the induction of the theory and method of different radiators structural optimization design, and the discussion on the application perspectives of advanced structures in aeroengine radiators, the report on the current challenges and development directions of the design of radiator structures, including smart materials, lattice structures, variable structures, advanced optimization theories and methods, heat dissipation methods and so forth. The efforts of this study are promising to support the high-performance and lightweight design of aeroengine structures besides radiators, and thermal management system.

Partnerships with local public sector agencies, enterprises and tertiary institutions offer a means to inform young people about post-school pathways into working life and occupations that schools alone cannot achieve. Informing about those pathways is an important, yet, complex educational goal for schooling. This is because much of schooling effort privileges and is directed towards higher education entry. Often advice provided to young people through schools is by teachers and administrators who are, understandably, unacquainted with the range of post-school pathways other than higher education. School guidance officers report being ill-equipped and unable to provide students personalised advice. Consequently, sources of advice and experiences beyond the school are now being utilised, particularly through the growing role of partnerships. These partnerships take diverse forms and comprise different kinds of institutional alignments and are increasingly being viewed as essential bases for supporting effective and informed post-school transitions. This article presents and discusses a review of literature and a recent investigation to advance principles and practices of how such partnerships can be best initiated, enacted, and sustained over time and they can meet the goals of informing and guiding young people's pathways, including options other than progression to higher education.

Purpose: This study aims to develop a self-reflection scale useful for teachers to improve their skills and to clarify the Japanese teachers' characteristics during mathematics lesson observation (MLO). In MLO, it is important to understand the lesson plan in advance to clarify observation points, and we aim to develop a scale including these points. Design/methodology/approach: Based on the pre-questionnaire survey, nine perspectives and two situations for MLO were extracted. From these, a questionnaire for MLO was created. The results obtained from 161 teachers were examined, and exploratory factor analysis was conducted. ANOVA was conducted to analyze the effect of differences across the duration of teaching experience on the identified factors. Findings: We developed a self-reflection scale consisting of 14 items with three factors: [B1] focus on instructional techniques and evaluation, [B2] focus on proactive problem-solving lesson development and [B3] focus on the mathematical background of the learning content. While duration of teaching experience showed no effect, three factors of the self-reflection scale for MLO showed a significant effect. Further multiple comparisons revealed the degree of focus was [B2]>[B1]>[B3]. Originality/value: Teachers who use this developed scale may grasp the strengths and weaknesses of their own MLO, which leads to self-improvement. The perspectives emphasized in lesson observation are the same when creating lesson plans and implementing lessons, leading to lesson improvement. Furthermore, based on the characteristics of teachers revealed, new training programs regarding MLO can lead to higher-quality lesson studies.

Dyslexia and developmental language disorders are important learning difficulties. However, their genetic basis remains poorly understood, and most genetic studies were performed on Europeans. There is a lack of genome-wide association studies (GWAS) on literacy phenotypes of Chinese as a native language and English as a second language (ESL) in a Chinese population. In this study, we conducted GWAS on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; total N = 1046). We performed association tests at the single-variant, gene, and pathway levels. In addition, we tested genetic overlap of these phenotypes with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. Totally 5 independent loci (LD-clumped at r[superscript 2] = 0.01; MAF > 0.05) reached genome-wide significance (p < 5e-08; filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs (r[superscript 2] > 0.5) with p < 1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with EA and other neuropsychiatric phenotypes, such as "MANEA" and "PLXNC1." In PRS analysis, EA and CP showed the most consistent and significant polygenic overlap with a variety of language traits, especially English literacy skills. To summarize, this study revealed the genetic basis of Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings.