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This article highlights the use of memes as a tool for creating and conveying meaning through multiple modes of communication in language classrooms. Memes have emerged as a popular form of communication in the digital age, utilizing a combination of images, texts, and cultural references to convey messages and create shared understandings. The Story Memes project in language learning can harness students’ digital literacy skills and leverage the engaging and relatable nature of memes to enhance language-learning experiences. This article explores the interplay among memes, multimodality, and meaning-making, demonstrating how memes can foster intercultural understanding, interpersonal connections, and critical thinking skills in alignment with the 5Cs standards. Additionally, it provides practical guidelines for designing lesson activities that incorporate story memes and cater to learners at different proficiency levels, ranging from beginners to advanced.

Inequality and the lack of inclusion of women in academic higher education (HE) leadership roles persist globally. While inclusivity at the top also applies to ethnicity and disability, the issue of gender is the focus of this article. More specifically, the distinct need is to examine the barriers that slow down and/or obstruct women from advancing in academia and gaining leadership positions. Thus, the purpose of this study is to provide a review of the case in Jordanian Universities. It presents the prevailing situation from the results of a desktop study and a survey questionnaire of the barriers that impede career progression for women in HE. The severity index (SI) formula is used to delineate critical barriers found in the literature in a Jordanian context through a questionnaire. Factor analysis was used to group the critical barriers, which in turn was used to derive an action plan to improve career progression for female academics. The study exposed that women’s participation in leadership was determined to be low, which is attributed to several barriers: sociocultural barriers, gender stereotypes, lack of skill and opportunities, work-life conflicts, social network obstacles, mentoring and support, and poor institutional policies that support women. As a result, several actions are recommended to support an increase in female leaders.

Introduction: The screening mammogram could be a “teachable moment” to improve lung cancer screening (LCS) uptake. The aim of our project was to combine patient self-referral with eligibility identification by providers as a two-pronged approach to increase rates of LCS among eligible women. Methods: LCS education materials were created to stimulate patient education and encourage self-referral. Chart review of patients scheduled for screening mammography was performed to identify patients who met LCS criteria. The primary outcome was rate of acceptance of targeted interventions as measured by qualitative survey material and rate of LCS uptake. Results: Between August 2022 and August 2023, 116 patients were identified by providers for potential eligibility for LCS and 34 patients (29.3%) deemed eligible based on the U.S. Preventative Services Task Force 2021 guidelines. There were 19 patients (56%) who completed LCS with three patients (16%) with screen-detected nodules that led to further workup. Post-implementation qualitative survey results reveal that 100% of the participants rated their shared decision-making visit experience as “very helpful” and 67% responded “very likely” to seek simultaneous breast and LCS in the future. Informational materials were rated as 80% favorable among all respondents; however, the rate of self-referral alone was 0%. The combined rates of eligible patients lost to follow-up or refusal was 24%. Conclusion: The self-referral aspect of the intervention revealed that patients are unlikely to self-refer for LCS. Nevertheless, patients undergoing screening mammograms individually identified for LCS were very responsive to learning more about dual screening.

Zileuton is a leukotriene inhibitor used to treat asthma. As a BCS class II drug it exhibits challenges with solubility which likely impact its absorption. As patient gender significantly impacts the pharmacokinetics of many drugs, this study aimed to investigate potential gender-based pharmacokinetic differences after oral zileuton administration in rats. Male and female Sprague Dawley rats received single oral gavage doses of pure zileuton as an active pharmaceutical ingredient (30 mg/kg body weight (bw)), physical mixture (PM; at 30 mg/kg bw of the formulation contains zileuton, kollidon VA64 fine, dowfax2A1 and trehalose), and nanocrystalline formulation of zileuton (NfZ; at 30 mg/kg bw of the formulation). Plasma, tissue, and urine concentrations were quantified using high performance liquid chromatography (HPLC). Noncompartmental pharmacokinetic analysis showed higher zileuton levels in the plasma of female versus male rats across all evaluated forms of zileuton (API, PM, and NfZ). Female rats demonstrated higher peak plasma concentrations (Cmax) and increased area under the plasma concentration-time curve (AUC) relative to males, regardless of formulation. These findings reveal substantial gender disparities in the pharmacokinetics of zileuton in the rat model. This study emphasizes the critical need to evaluate gender differences during preclinical drug development to enable gender-based precision dosing strategies for equivalent efficacy/safety outcomes in male and female patients. Additional studies are warranted to investigate underlying mechanisms of such pharmacokinetic gender divergences.

Abstract Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases.

Gender equality is essential for economic and societal advancement, as outlined in the United Nations’ Sustainable Development Goal 5. This research examines the obstacles that hinder women’s progression from higher education to empowerment in Pakistan. Using a comprehensive descriptive survey questionnaire, we collected quantitative data to gain insights from a diverse sample of various provinces. The survey consisted of two sections: background information and 25 constructs of barriers from the existing literature. Data analysis involving 399 respondents included descriptive and inferential statistics, cross-tabulation, and significance testing using non-parametric tests. The findings highlighted significant sociocultural, familial, and professional barriers, with regional disparities underscoring the need for targeted interventions. Women respondents consistently perceived barriers more keenly than men, underscoring the gender-specific nature of these challenges. This study emphasizes the need for focused policies and educational initiatives to address barriers and promote gender equality in Pakistan’s higher education and professional spheres.

The world has seen unprecedented gains in the global genomic surveillance capacities for pathogens with pandemic and epidemic potential within the last 4 years. To strengthen and sustain the gains made, WHO is working with countries and partners to implement the Global Genomic Surveillance Strategy for Pathogens with Pandemic and Epidemic Potential 2022–2032. A key technical product developed through these multi-agency collaborative efforts is a genomics costing tool (GCT), as sought by many countries. This tool was developed by five institutions – Association of Public Health Laboratories, FIND, The Global Fund to Fight AIDS, Tuberculosis and Malaria, UK Health Security Agency, and the World Health Organization. These institutions developed the GCT to support financial planning and budgeting for SARS-CoV-2 next-generation sequencing activities, including bioinformatic analysis. The tool costs infrastructure, consumables and reagents, human resources, facility and quality management. It is being used by countries to (1) obtain costs of routine sequencing and bioinformatics activities, (2) optimize available resources, and (3) build an investment case for the scale-up or establishment of sequencing and bioinformatics activities. The tool has been validated and is available in English and Russian at https://www.who.int/publications/i/item/9789240090866. This paper aims to highlight the rationale for developing the tool, describe the process of the collaborative effort in developing the tool, and describe the utility of the tool to countries.

Summary: Background: The Paediatric Difficult Intubation Collaborative identified multiple attempts and persistence with direct laryngoscopy as risk factors for complications in children with difficult tracheal intubations and subsequently engaged in initiatives to reduce repeated attempts and persistence with direct laryngoscopy in children. We hypothesised these efforts would lead to fewer attempts, fewer direct laryngoscopy attempts and decrease complications. Methods: Paediatric patients less than 18 years of age with difficult direct laryngoscopy were enrolled in the Paediatric Difficult Intubation Registry. We define patients with difficult direct laryngoscopy as those in whom (1) an attending or consultant obtained a Cormack Lehane Grade 3 or 4 view on direct laryngoscopy, (2) limited mouth opening makes direct laryngoscopy impossible, (3) direct laryngoscopy failed in the preceding 6 months, and (4) direct laryngoscopy was deferred due to perceived risk of harm or poor chance of success. We used a 5:1 propensity score match to compare an early cohort from the initial Paediatric Difficult Intubation Registry analysis (August 6, 2012–January 31, 2015, 785 patients, 13 centres) and a current cohort from the Registry (March 4, 2017–March 31, 2023, 3925 patients, 43 centres). The primary outcome was first attempt success rate between cohorts. Success was defined as confirmed endotracheal intubation and assessed by the treating clinician. Secondary outcomes were eventual success rate, number of attempts at intubation, number of attempts with direct laryngoscopy, the incidence of persistence with direct laryngoscopy, use of supplemental oxygen, all complications, and severe complications. Findings: First-attempt success rate was higher in the current cohort (42% vs 32%, OR 1.5 95% CI 1.3–1.8, p

Abstract Phospho‐ribosyl‐pyrophosphate synthetase 1 (PRPS1) deficiency is secondary to loss of function variants in PRPS1. This enzyme generates phospho‐ribosyl‐pyrophosphate (PRPP), which is utilized in the synthesis of purines, nicotinamide adenine dinucleotide (NAD), and NAD phosphate (NADP), among other metabolic pathways. Arts syndrome, or severe PRPS1 deficiency, is an X‐linked condition characterized by congenital sensorineural hearing loss, optic atrophy, developmental delays, ataxia, hypotonia, and recurrent infections that can cause progressive clinical decline, often resulting in death before 5 years of age. Supplementation of the purine and NAD pathways outside of PRPP‐dependent reactions is a logical approach and has been reported in a handful of patients, two with S‐adenosylmethionine (SAMe) and one with SAMe and nicotinamide riboside (NR). We present the clinical course of a fourth Arts syndrome patient who was started on therapy and review previously reported patients. All patients had stability or improvement of symptoms, suggesting that SAMe and NR can be a treatment option in Arts syndrome, though further studies are warranted.

Polynucleotides, complex molecules composed of nucleotides, have gained attention in aesthetic medicine for their potential to regulate gene expression and promote tissue regeneration. This review aims to provide an overview of the current practices and perceived effectiveness of polynucleotides in aesthetic medicine. A comprehensive search of the literature was conducted using keywords related to polynucleotides, cosmetic application, and aesthetic application. Studies were selected based on their relevance to aesthetic medicine and the inclusion of human subjects. The review found that polynucleotides have been used to improve skin texture, reduce wrinkle depth, and enhance facial appearance. The studies reported varying degrees of efficacy and safety, with some studies demonstrating significant improvements in skin elasticity and hydration. However, others reported limited or no benefits. The review also highlighted the need for further research to establish the optimal use and efficacy of polynucleotides in aesthetic medicine. While the existing literature suggests that polynucleotides may have potential benefits in aesthetic medicine, more research is needed to fully understand their mechanisms of action and optimal use. Clinicians should be aware of the current limitations and potential risks associated with the use of polynucleotides in aesthetic medicine.

Resource consumption in the construction industry is expected to increase globally in the coming years. Additionally, construction and demolition waste (CDW) remains a significant priority within numerous global policies due to its vast volume and the inefficiencies in its management. This situation results in substantial environmental repercussions, primarily due to the low rates of material recovery in the manufacturing processes for new building materials. In response, the concept of the circular economy (CE) emerges as a promising solution across various sectors. CE promotes more resource- and energy-efficient practices, reducing waste generation and mitigating the environmental impacts associated with product life cycles while also unlocking potential economic opportunities. The primary aim of this study is to identify and assess the design practices influencing the adoption of CE principles within the Italian architectural, engineering, and construction (AEC) sector. The study’s main contribution lies in a survey of 77 Italian designers to explore the core strategies driving the development of comprehensive circular approaches. This investigation seeks to understand the constraints and opportunities for CE implementation. The findings will assist in decision-making, inform policy, promote literacy around the CE topic, enable new quality standards, and serve as a baseline reference for businesses regarding sustainability investment indexes and markets.

Abstract Background Systematic description of library quality and sequencing performance of single-cell RNA sequencing (scRNA-seq) data is imperative for subsequent downstream modules, including re-pooling libraries. While several packages have been developed to visualise quality control (QC) metrics for scRNA-seq data, they do not include expression-based QC to discriminate between true variation and background noise. Results We present scQCEA (acronym of the single-cell RNA sequencing Quality Control and Enrichment Analysis), an R package to generate reports of process optimisation metrics for comparing sets of samples and visual evaluation of quality scores. scQCEA can import data from 10X or other single-cell platforms and includes functions for generating an interactive report of QC metrics for multi-omics data. In addition, scQCEA provides automated cell type annotation on scRNA-seq data using differential gene expression patterns for expression-based quality control. We provide a repository of reference gene sets, including 2348 marker genes, which are exclusively expressed in 95 human and mouse cell types. Using scRNA-seq data from 56 gene expressions and V(D)J T cell replicates, we show how scQCEA can be applied for the visual evaluation of quality scores for sets of samples. In addition, we use the summary of QC measures from 342 human and mouse shallow-sequenced gene expression profiles to specify optimal sequencing requirements to run a cell-type enrichment analysis function. Conclusions The open-source R tool will allow examining biases and outliers over biological and technical measures, and objective selection of optimal cluster numbers before downstream analysis. scQCEA is available at https://isarnassiri.github.io/scQCEA/ as an R package. Full documentation, including an example, is provided on the package website.

The construction industry accounts for approximately one-third of the total waste generation globally. With the United Nations projecting a population increase of 2 billion within the next three decades, there is a heightened demand for building stock, generating unprecedented volumes of construction and demolition waste (CDW). To combat this, circular economy strategies are purported to help alleviate the prevailing situation. But a number of challenges are jeopardizing their implementation in the construction industry and preventing from achieving the UN Sustainable Development Goals, net zero carbon and zero avoidable waste targets. This paper systematically analyzes 54 research articles, published in the past decade within major peer-reviewed English-language scholarly publications in the form of a systematic research review. In doing so, it aims to identify and classify the challenges that prevent improved CDW management by assimilating previous research results in support of a circular economy. The classification and analysis using a PESTLE model offers insights into gaps and differences between categories, as well as regions and countries. This initial step could contribute to a better understanding of these barriers, along with associated solutions, which could result in a significant reduction on the impact of construction activities, therefore facilitating the development of an effective circular economy in the sector.

Education is the foundation of culture and the engine of economies; it is an essential part of life. However, it remains inaccessible or unavailable in some parts of developing nations. Moreover, such barriers for girls and women can extend beyond education and into the workplace, and this is a bone of contention based on erroneous beliefs and other factors. Barriers for girls’ and women’s education are debatable in the literature; however, there is a sparsity of literature that focuses on the bridge to the workplace. Therefore, through a focus group study, this study explores the barriers that prohibit the transition for women from higher education to employment in Egypt. Based on qualitative data from focus group participants, the barriers to girls’ and women’s education are related to cultural, economic, family, and structural–educational barriers. In addition, stereotypical thinking and discrimination are factors hindering girls and women from ‘decent’ employment in Egypt. Based on this study’s results, some practical recommendations were elicited, which centre around awareness enhancement, formulation of laws and policies, and development of employability skills and entrepreneurship skills. The managerial and societal implications of this study are illustrated. It is anticipated that the results of this study will serve to create an inherent need to undertake a larger survey to investigate the barriers from a wider number of respondents.

The persistent underrepresentation of women in leadership positions within the construction industry remains a global concern. In Jordan, despite comprising 60.45% and 22.4% of the total workforce of architects and civil engineers, respectively, women’s contribution to management roles is significantly low. Therefore, there is an urgent necessity to examine the factors hindering women’s advancement in the construction sector and their ability to attain leadership positions. This research aims to provide an overview of the current situation in Jordan, focusing specifically on the architectural and civil engineering professions. It presents findings from a desktop study, a survey questionnaire, and focus groups. The Severity Index (SI) formula is utilised to identify critical barriers in the Jordanian context, derived from both the literature review and questionnaire responses. Additionally, the Interpretive Structural Modelling (ISM) technique is employed to establish a hierarchy of critical barriers and analyse their interrelationships. The study reveals that the obstacles impeding women from assuming leadership roles in the Jordanian construction sector primarily stem from 20 critical barriers categorised across 11 levels in ISM. Notably, the lack of childcare programmes is identified as a fundamental barrier at the lower level, while informal networks formed by men emerge as the highest-rated barrier at level 11. Addressing and mitigating these challenges is crucial to facilitating women’s progression into leadership positions within the sector and is anticipated to contribute significantly to addressing the growing complexity of modern construction projects.

The issue of gender equality demands attention from governments, policymakers, and the community at large. It requires continuous redefinition due to its complex technical, professional, economic, and social dimensions, all aimed at empowering women to claim their position within society. Jordan is no exception to this, as women encounter numerous hurdles in accessing equal opportunities in the professional sphere despite their increasing levels of education. This underscores the necessity for a thorough examination of the factors influencing this discussion. This research is targeted at identifying and categorising relevant gender equality indicators within the architectural practice in Jordan, as part of the construction sector. This research adopts a quantitative approach, utilising the Delphi Technique and Analytical Hierarchy Process through engagement with experts from academia and practice to ensure appropriate sourcing, filtration, and rating of the most relevant indicators. It concludes with the identification of fifty-nine indicators grouped into the categories of Education, Employability, Enablement, Inclusion, Professionalism, Facilitation, and Support. This research reveals a higher emphasis on the practical aspects of gender equality by the participants, prioritising particular categories and indicators. The findings offer essential insights to effectively address such an important issue across the policy, economic, social, and professional levels.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Abstract The long-term impact of COVID-19 among those with mild infections is not well characterized. Among 81 adults who completed online assessments at 3- and 12-months following infection, quality of life scores did not significantly improve over time. Among 62 subjects who also completed telephone interviews, respiratory symptoms or exercise limitation were reported by 42% at a median follow-up of 387 days (IQR 251–402 days). Those with persistent respiratory symptoms scored lower on the EQ-5D visual analog score compared to those without. Persistent respiratory symptoms were associated with a lower likelihood of full-time employment at 1 year (aOR 0.09, 95%CI 0.01–0.91; P = 0.041). In an adjusted linear regression, persistent respiratory symptoms (P = 0.037) and female sex (P = 0.016) were both independent risks for increased visits to a primary care provider. This cohort study demonstrates that respiratory symptoms are frequent at 1 year following COVID-19 and more importantly, are associated with negative impacts on employment, quality of life, and health care utilization. Further research is needed to determine the pathophysiology and risk factors for persistent symptoms as well as optimal management strategies to improve the level of functioning and quality of life.

Abstract Background Hereditary transthyretin amyloidosis is an uncommon multisystem disorder caused by mutation of the transthyretin protein, leading to peripheral neuropathy often with autonomic features, cardiomyopathy, or a mixed phenotype. Multiple other organ systems can be involved with ophthalmologic, renal, hematologic, gastrointestinal, and/or genitourinary symptoms and signs. This often results in assessments by multiple specialists and significant delays before the diagnosis is recognized. With the recent advent of potentially lifesaving therapies, early diagnosis has become even more important. Our case highlights the protean aspects of this disease as well as the difficulty of making this diagnosis, especially in the absence of a clear family history. Case presentation We report the case of a 64-year-old man of East-Asian descent who presented with diarrhea, mild anemia, and symptoms of peripheral neuropathy. Numerous investigations and specialist evaluations did not identify a cause. Progression of neurologic symptoms and the development of new hematologic abnormalities ultimately led to consideration of hereditary transthyretin amyloidosis. The diagnosis was confirmed after re-examining previously acquired gastrointestinal biopsies and pursuing genetic testing, which confirmed a pathogenic mutation in the transthyretin gene. He was subsequently started on a novel gene-silencing therapy. On clinical follow-up 8 months after initiation of therapy, the patient described stabilization of previously progressive numbness, weakness, and weight loss with an unchanged neurologic examination and stable repeat electrophysiologic testing. Conclusions Hereditary transthyretin amyloidosis is a challenging disease to recognize in early stages owing to its multisystem and nonspecific manifestations. Recent approval of novel therapies highlights the importance of early diagnosis before irreversible organ damage occurs.

This article explores how music and lyrics serve as modes of storytelling in the language classroom, integrating a multimodal approach and the World-Readiness Standards for Learning Languages. In the 'Sing My Story' project, language students creatively write their own lyrics, which are subsequently performed by either student musicians or target language-speaking musicians within the school community. This initiative encourages students at the Intermediate or Advanced proficiency levels to collaboratively produce a music album, creating narrative lyrics for existing songs. Through this project, students are provided with opportunities for meaningful language application, fostering creative and transformative language learning experiences.

Korean language programs in US higher education are experiencing noticeable and continuous growth. While students’ interest in Korea may initially be driven by Korean pop culture, Korean language educators need to expose these students to advanced-level language study and content. This paper addresses content-based project modules designed by interweaving the multiliteracies- and Standards-based frameworks. These modules enable students to connect with other disciplines and acquire information and diverse perspectives in order to use the language to function in academic- and career-related contexts.

Non-pharmaceutical interventions including physical distancing and restriction on public gatherings were the cornerstone in controlling the COVID-19 pandemic, in the absence of effective vaccines and available treatment options. Many sport mega-events and sport leagues were canceled or indefinitely postponed, leaving stadiums globally empty or converted to be used as part of the COVID-19 response. There were calls for exit strategies to be developed. With the early containment of COVID-19 in South Australia, various restrictions were lifted in a staged and controlled manner, including the reopening of the Adelaide Oval for recommencement of sport leagues with spectator attendance. This involved the collaboration between public health authorities, other governmental agencies, Adelaide Oval Stadium Management Authority, various sporting leagues etc. Recommencement of sport leagues with staged increase in number of attending spectators allowed various measures to be introduced, revisited, and implemented accordingly, demonstrating that a case-by-case risk assessment can be conducted for mega-events during COVID-19, accounting for the epidemiological context at the time. Economic impacts and non-economic benefits of this recommencement were documented. This globally unprecedented, staged and controlled approach in returning spectators to sporting events during the COVID-19 pandemic could inform the reopening strategy of stadiums, recommencement of sport leagues and mega-events all over the world before herd immunity is achieved or in the event of future outbreaks.

An effective communication process is an important element in distributing information to various project teams. The previous study demonstrates the importance of communication in the project management process in order to encourage project delivery processes successfully. Unfortunately, the issue of communication still dominates Industrialization Building System (IBS) because the project development process are still based on traditional methods. This research aims to explore the cause of communication challenges between construction players in managing IBS projects. The research methodology implemented for this paper was a semi-structured interview approach used to investigate the communication problem. Five experienced project managers were chosen from across the industry. The findings of this study are valuable for improving the communication level of project teams, which will indirectly increase the level of the IBS project delivery process and strengthen team integration on IBS projects in Malaysia.

Phospholipidosis, the excessive accumulation of phospholipids within lysosomes, is a pathological response observed following exposure to many drugs across multiple therapeutic groups. A clear mechanistic understanding of the causes and implications of this form of drug toxicity has remained elusive. We previously reported the discovery and characterization of a lysosome-specific phospholipase A2 (PLA2G15) and later reported that amiodarone, a known cause of drug-induced phospholipidosis, inhibits this enzyme. Here, we assayed a library of 163 drugs for inhibition of PLA2G15 to determine whether this phospholipase was the cellular target for therapeutics other than amiodarone that cause phospholipidosis. We observed that 144 compounds inhibited PLA2G15 activity. Thirty-six compounds not previously reported to cause phospholipidosis inhibited PLA2G15 with IC50 values less than 1 mM and were confirmed to cause phospholipidosis in an in vitro assay. Within this group, fosinopril was the most potent inhibitor (IC50 0.18 μM). Additional characterization of the inhibition of PLA2G15 by fosinopril was consistent with interference of PLA2G15 binding to liposomes. PLA2G15 inhibition was more accurate in predicting phospholipidosis compared with in silico models based on pKa and ClogP, measures of protonation, and transport-independent distribution in the lysosome, respectively. In summary, PLA2G15 is a primary target for cationic amphiphilic drugs that cause phospholipidosis, and PLA2G15 inhibition by cationic amphiphilic compounds provides a potentially robust screening platform for potential toxicity during drug development.

OBJECTIVES/GOALS: 1. To characterize domains of maternal psychosocial stress from the Edinburgh Postnatal Depression Scale (EPDS) and Cohens Perceived Stress Scale (PSS) administered during pregnancy using principal components analysis (PCA). 2. To identify sociodemographic, perinatal, and lifestyle correlates of maternal psychosocial stress domains. METHODS/STUDY POPULATION: Using data from 1,079 pregnant women in the Healthy Start Study who completed both the EPDS and PSS in early pregnancy, we ran PCA and retained factors representative of uncorrelated domains of maternal psychosocial stress based on the Scree plot and Eigenvalues >1. We then used linear regression to identify sociodemographic, perinatal, and lifestyle correlates of each maternal stress domain, followed by multivariable models that mutually adjusted for all characteristics that were statistically significant at alpha = 0.10. RESULTS/ANTICIPATED RESULTS: We identified three domains of maternal psychosocial stress based on PCA results: Feeling Overwhelmed (Domain 1), Anhedonia (Domain 2), and Lack of Control (Domain 3). In unadjusted analyses, lower household income and poor diet quality were associated with higher scores for all three domains. In adjusted analyses, lower household income, being multiparous, inadequate or excessive GWG, and poor diet quality were associated with Feeling Overwhelmed. Older age, Hispanic ethnicity, and poor diet quality were associated with Anhedonia. Non-Hispanic, Black race/ethnicity, lower educational attainment, having a partner born outside the US, larger household size, receiving public assistance, and smoking during pregnancy were associated with Lack of Control. DISCUSSION/SIGNIFICANCE: We identify three unique domains of maternal psychosocial stress that are differentially related to sociodemographic, perinatal, and lifestyle characteristics. Correlates of stress domains shed light on upstream determinants and biological and psychosocial mechanisms through which experiences of stress manifest.

New food technologies are touted by some to be an indispensable part of the toolkit when it comes to feeding a growing population, especially when factoring in the growing appetite for animal products. To this end, technologies like genetically engineered (GE) animals and in vitro meat are currently in various stages of research and development, with proponents claiming a myriad of justificatory benefits. However, it is important to consider not only the technical attributes and promissory possibilities of these technologies, but also the worldviews that are being imported in turn, as well as the unanticipated social and environmental consequences that could result. In addition to critiquing dominant paradigms, the inclusive, intersectional ecofeminist perspective presented here offers a different way of thinking about new food technologies, with the aim of exposing inherent biases, rejecting a view of institutions like science and law as being objective, and advancing methods and rationales for a more explicitly ethical form of decision-making. Alternative and marginalized perspectives are especially valuable in this context, because careful reflection on the range of concerns implicated by new food technologies is necessary in order to better evaluate whether or not they can contribute to the building of a more sustainable and just food system for all.

The thermalization of hot carriers and phonons gives direct insight into the scattering processes that mediate electrical and thermal transport. Obtaining the scattering rates for both hot carriers and phonons currently requires multiple measurements with incommensurate timescales. Here, transient extreme-ultraviolet (XUV) spectroscopy on the silicon 2p core level at 100 eV is used to measure hot carrier and phonon thermalization in Si(100) from tens of femtoseconds to 200 ps, following photoexcitation of the indirect transition to the Δ valley at 800 nm. The ground state XUV spectrum is first theoretically predicted using a combination of a single plasmon pole model and the Bethe-Salpeter equation with density functional theory. The excited state spectrum is predicted by incorporating the electronic effects of photo-induced state-filling, broadening, and band-gap renormalization into the ground state XUV spectrum. A time-dependent lattice deformation and expansion is also required to describe the excited state spectrum. The kinetics of these structural components match the kinetics of phonons excited from the electron-phonon and phonon-phonon scattering processes following photoexcitation. Separating the contributions of electronic and structural effects on the transient XUV spectra allows the carrier population, the population of phonons involved in inter- and intra-valley electron-phonon scattering, and the population of phonons involved in phonon-phonon scattering to be quantified as a function of delay time.

As a developing country, Malaysian is currently driving for implementing a new or modern construction method, the Industrialised Building System (IBS), as an alternative towards enhancing construction performance. Currently, most of the IBS project developments in Malaysia are still conducted by using the traditional construction process approach. This traditional construction process has been widely criticised for its fragmented approach to project delivery and its failure to form effective teams thus created a number of issues such as reworks, time delay, rising costs, lack of communication and coordination, and wastages. This paper through literature review aims to highlight this fragmentation issue and clarify how far it affects the process of IBS implementation. Suggestions on how an integrated approach in design and construction in order to minimise the fragmentation gaps will be concluded.

In this investigation, we test whether temporal discounting is domain-specific (i.e., compared to other people, can an individual have a relatively high discount rate for one type of reward but a relatively low discount rate for another?), and we examine whether individual differences in the types of rewards one finds tempting explain domain-specificity in discount rates. Adults discounted delayed rewards they found particularly tempting (defined as the visceral attraction to and enjoyment of a reward) more steeply than did adults who did not find the rewards as tempting, contrary to what might be expected from the magnitude effect. Furthermore, we found significant group by domain interactions (e.g., chip lovers who do not like beer have relatively high discount rates for chips and relatively low discount rates for beer, whereas beer lovers who do not like chips showed the opposite pattern). These results suggest that domain-specificity in temptation partially accounts for corresponding domain-specificity in temporal discounting.

Remaining committed to goals is necessary (albeit not sufficient) to attaining them, but very little is known about domain-general individual differences that contribute to sustained goal commitment. The current investigation examines the association between grit, defined as passion and perseverance for long-term goals, other individual difference variables, and retention in four different contexts: the military, workplace sales, high school, and marriage. Grit predicted retention over and beyond established context-specific predictors of retention (e.g. intelligence, physical aptitude, Big Five personality traits, job tenure) and demographic variables in each setting. Grittier soldiers were more likely to complete an Army Special Operations Forces (ARSOF) selection course, grittier sales employees were more likely to keep their jobs, grittier students were more likely to graduate from high school, and grittier men were more likely to stay married. The relative predictive validity of grit compared to other traditional predictors of retention is examined in each of the four studies. These findings suggest that in addition to domain-specific influences, there may be domain-general individual differences which influence commitment to diverse life goals over time.

The importance of self-control to a wide range of developmental outcomes prompted the current investigation of negative life events and self-control in early adolescence. In three prospective, longitudinal studies, negative life events reported by the mother (in Study 1) or child (in Studies 2 and 3) predicted rank-order decreases in self-control over time. In all studies, self-control was measured at two different time points using questionnaires completed by three separate raters, including a classroom teacher who knew the child well and two other raters (parents, caregivers, and/or the child himself/herself). Psychological distress measured in Studies 2 and 3 mediated the deleterious effects of negative life events on self-control. These findings extend prior experimental laboratory research documenting the acute effects of stress on self-control.

Amyloid is a complex pathology associated with a growing number of diseases including Alzheimer's disease, type 2 diabetes, rheumatoid arthritis, and myeloma. The distribution and extent of amyloid deposition in body organs establishes the prognosis and can define treatment options; therefore, determining the amyloid load by using non-invasive molecular imaging is clinically important. We have identified a heparin-binding peptide designated p5 that, when radioiodinated, was capable of selectively imaging systemic visceral AA amyloidosis in a murine model of the disease. The p5 peptide was posited to bind effectively to amyloid deposits, relative to similarly charged polybasic heparin-reactive peptides, because it adopted a polar α helix secondary structure. We have now synthesized a variant, p5R, in which the 8 lysine amino acids of p5 have been replaced with arginine residues predisposing the peptide toward the α helical conformation in an effort to enhance the reactivity of the peptide with the amyloid substrate. The p5R peptide had higher affinity for amyloid and visualized AA amyloid in mice by using SPECT/CT imaging; however, the microdistribution, as evidenced in micro-autoradiographs, was dramatically altered relative to the p5 peptide due to its increased affinity and a resultant "binding site barrier" effect. These data suggest that radioiodinated peptide p5R may be optimal for the in vivo detection of discreet, perivascular amyloid, as found in the brain and pancreatic vasculature, by using molecular imaging techniques; however, peptide p5, due to its increased penetration, may yield more quantitative imaging of expansive tissue amyloid deposits.

Human FTO gene variants are associated with body mass index and type 2 diabetes. Because the obesity-associated SNPs are intronic, it is unclear whether changes in FTO expression or splicing are the cause of obesity or if regulatory elements within intron 1 influence upstream or downstream genes. We tested the idea that FTO itself is involved in obesity. We show that a dominant point mutation in the mouse Fto gene results in reduced fat mass, increased energy expenditure, and unchanged physical activity. Exposure to a high-fat diet enhances lean mass and lowers fat mass relative to control mice. Biochemical studies suggest the mutation occurs in a structurally novel domain and modifies FTO function, possibly by altering its dimerisation state. Gene expression profiling revealed increased expression of some fat and carbohydrate metabolism genes and an improved inflammatory profile in white adipose tissue of mutant mice. These data provide direct functional evidence that FTO is a causal gene underlying obesity. Compared to the reported mouse FTO knockout, our model more accurately reflects the effect of human FTO variants; we observe a heterozygous as well as homozygous phenotype, a smaller difference in weight and adiposity, and our mice do not show perinatal lethality or an age-related reduction in size and length. Our model suggests that a search for human coding mutations in FTO may be informative and that inhibition of FTO activity is a possible target for the treatment of morbid obesity.

Conscientiousness has been shown to predict healthy behaviors, healthy social relationships, and physical health and longevity. The causal links, however, are complex and not well elaborated. Many extant studies have used comparable measures for conscientiousness, and a systematic endeavor to build cross-study analyses for conscientiousness and health now seems feasible. Of particular interest are efforts to construct new, more comprehensive causal models by linking findings and combining data from existing studies of different cohorts. Although methodological perils can threaten such integration, such efforts offer an early opportunity to enliven a life course perspective on conscientiousness, to see whether component facets of conscientiousness remain related to each other and to relevant mediators across broad spans of time, and to bolster the findings of the few long-term longitudinal studies of the dynamics of personality and health. A promising approach to testing new models involves pooling data from extant studies as an efficient and heuristic prelude to large-scale testing of interventions.