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Purpose: This study describes participant diversity in Williams syndrome (WS) intervention studies. Methods: A literature search was conducted to identify prospective treatment studies including participants with WS. Data was extracted on the reporting of and information provided on age, sex, cognitive ability, socioeconomic status, race, and ethnicity. Results: Eleven eligible articles were identified. Reporting rates of demographic factors varied considerably, with the highest rates for age and sex (100%) and the lowest reporting rates for race (18%) and ethnicity (9%). Combining demographic data from the two studies that reported on race and/or ethnicity (n = 33), 88% of participants were White. The combined participant mean age was 20.9 years. Conclusion: There is a low frequency of reporting on several demographic factors including socioeconomic status, race, and ethnicity in WS intervention studies. There is a need for increased representation of racial and ethnic minority groups, older participants, and more cognitively impaired patients in WS research.

While inclusive pedagogies such as culturally responsive teaching may be common in face-to-face learning, there is little published research regarding culturally responsive teaching and learning in higher education online settings. It is not known whether faculty members employ culturally responsive teaching strategies or what types of strategies they use in online courses. The purpose of this study was to determine whether online faculty members practice culturally responsive teaching and to explore the characteristics of culturally responsive teaching that are reflected in the responses of 12 instructors in a fully online undergraduate general education course required in the first few terms of enrollment. Qualitative methodology was utilized, involving deductive and inductive coding methods of analysis. Data were coded deductively based on four major categories of cultural competence: sociopolitical/cultural consciousness, community of learners, and high academic expectations. Data were coded inductively for culturally nonresponsive interactions. Findings from deductive analysis revealed partial use of culturally responsive teaching strategies in online classrooms. Results for inductive analysis showed themes of nondifferentiated responses, missed opportunities for addressing linguistic or cultural differences, and lack of encouragement for collaboration or sense of community. These findings indicate a need for further research in culturally responsive teaching in online learning as well as faculty professional development that focuses on culturally responsive teaching.

With age, adolescents increasingly demonstrate the ability to forgo immediate, smaller rewards in favor of larger delayed rewards, indicating reduced delay discounting. Adolescence is also a time of social reorientation, where decisions not only involve weighing immediate against future outcomes, but also consequences for self versus those for others. In this functional Magnetic Resonance Imaging study, we examined the neural correlates of immediate and delayed reward choices where the delayed outcomes could benefit self, friends, or unknown others. A total of 196 adolescent twins aged 14–17 completed a social delay discounting task, with fMRI data acquired from 174 participants. Out of these, 156 adolescents had valid fMRI data, and 138 adolescents had observations in every condition. Adolescents more often chose the immediate reward when it was larger, and when the delay was longer. Area-under-the-curve (AUC) comparisons revealed that behavior differed across delay-beneficiaries, with AUC being highest for the self, followed by friends, and lowest for unknown others. This suggests that adolescents are more willing to wait for rewards for self. Neuroimaging analyses showed increased activity in the midline areas medial prefrontal cortex (MPFC) and precuneus, as well as bilateral temporal parietal junction (TPJ) when considering delayed reward for unknown others and friends compared to self. A whole-brain interaction with choice showed that the bilateral insula and right dorsolateral prefrontal cortex (DLPFC) were more active for delayed choices for unknown others and for immediate choices for friends and self. This underscores that the neuro-cognitive processing of how delays reduce the value of rewards depends on closeness of the beneficiary.

The Australian Government, in its Professional Standards for Teachers and Australian Curriculum framework, requires that all secondary teachers actively teach the specific literacy of their learning area. Yet achievement of that goal hinges on teachers having first acquired the pre-requisite literate competencies during their own schooling. There are reasons to doubt that this is the case for some graduate teachers, which means attempts to raise standards in schools are beset by a troubling circularity. Here we illustrate the problem with further findings from a Western Australian ITE Cohort Study (n=393), focussing this time on the word knowledge of secondary teaching graduates. Our analysis suggests that some secondary ITE students carry shortcomings from their own schooling that may hamper their ability to teach word knowledge or to self-correct. Current training and resources may thus have limited efficacy for some graduating teachers, placing limits on what can be achieved in schools. We consider the implications for literacy policies and for initial teacher education at secondary level.

Many states now mandate early screening for dyslexia, but vary in how they address these mandates. There is confusion about the nature of screening versus diagnostic assessments, risk versus diagnosis, concurrent versus predictive validity, and inattention to indices of classification accuracy as the basis for determining risk. To help define what constitutes a screening assessment, we summarize efforts to develop short (3-5 min), teacher-administered screens that used multivariate strategies for variable selection, item response theory to select items that are most discriminating at a threshold for predicting risk, and statistical decision theory. These methods optimize prediction and lower the burden on teachers by reducing the number of items needed to evaluate risk. A specific goal of these efforts was to minimize decision errors that would result in the failure to identify a child as at risk of dyslexia/reading problems (false negatives) despite the inevitable increase in identifications of children who eventually perform in the typical range (false positives). Five screens, developed for different periods during kindergarten, Grade 1, and Grade 2, predicted outcomes measured later in the same school year (Grade 2) or in the subsequent year (Grade 1). The results of this approach to development are applicable to other screening methods, especially those that attempt to predict those children at risk of dyslexia prior to the onset of reading instruction. Without reliable and valid early predictive screening measures that reduce the burden on teachers, early intervention and prevention of dyslexia and related reading problems will be difficult.

Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and metabolic plasticity. Using lymphocytes collected and immortalized from an index proband who carries a truncating variant in one allele of LARP1, we demonstrated that lower cellular levels of LARP1 protein cause reduced rates of aerobic respiration and glycolysis. As expression of LARP1 increases during neurodevelopment, with higher levels in neurons and astrocytes, we propose that LARP1 haploinsufficiency contributes to ASD or related NDDs through attenuated metabolic activity in the developing fetal brain.

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites.org/.

Background/Objectives: Spironolactone (SP), an aldosterone inhibitor widely used to treat androgen-dependent disorders such as acne, hirsutism, and alopecia, has demonstrated therapeutic potential in both oral and topical formulations. However, SP’s low solubility and poor bioavailability in conventional formulations have driven the development of novel nanocarriers to enhance its efficacy. This review systematically examines recent advancements in SP-loaded nanocarriers, including lipid nanoparticles (LNPs), vesicular nanoparticles (VNPs), polymeric nanoparticles (PNPs), and nanofibers (NFs). Methods: A search strategy was developed, and the relevant literature was systematically searched using databases such as Scopus, PubMed, and Google Scholar. The review process, including screening, inclusion, and exclusion criteria, adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A comprehensive analysis of 13 eligible research articles, corresponding to 15 studies, highlights key aspects such as encapsulation efficiency, stability, particle size, and in vitro and in vivo efficacy. Six studies focused on lipid nanoparticles (LNPs), including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), which were found to improve SP’s bioavailability and skin permeation. Another six studies investigated vesicular nanoparticles (VNPs), such as ethosomes and niosomes, demonstrating superior skin targeting and penetration capabilities. Two studies on polymeric nanoparticles (PNPs) showed effectiveness in delivering SP to hair follicles for the treatment of alopecia and acne. Additionally, one study on SP-loaded nanofibers indicated significant potential for topical rosacea therapy. Conclusions: SP-loaded nanocarrier systems represent promising advancements in targeted topical therapy. However, further clinical studies are required to optimize their safety, efficacy, and delivery mechanisms.

Background: Oral anticoagulation (OAC) is the mainstay of treatment for the prevention of strokes in patients with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) account for increasing OAC in patients with AF. However, prescribing DOACs for patients with established AF poses various challenges and general practice pharmacists may have an important role in supporting their management. Aim: To investigate the effectiveness of pharmacist-led interventions in general practice in optimising the use of OAC therapies in AF. Design & setting: A retrospective observational study in general practices in Bradford. Method: The data were collected retrospectively from 1 November 2018–31 December 2019 using electronic health record data. The data were analysed: 1) to identify patients with AF not on OAC; 2) to describe inappropriate DOAC prescriptions; and 3) to calculate HAS-BLED scores. Results: Overall, 76.3% (n = 470) of patients with AF received OAC therapy, and of these, 63.4% received DOACs. Pharmacist-led interventions increased DOAC prescribing by 6.0% (P = 0.03). Inappropriate DOAC use was identified in 24.5% of patients with AF, with underdosed and overdosed identified in 9.7% and 14.8%, respectively. Post-intervention, inappropriate prescribing was reduced to 1.7%. The mean HAS-BLED score decreased from 3.00 to 2.22 (P

Our society faces a great diversity of opportunities for youth. The 10-year Growing Up Together in Society (GUTS) program has the long-term goal to understand which combination of measures best predict societal trajectories, such as school success, mental health, well-being, and developing a sense of belonging in society. Our leading hypothesis is that self-regulation is key to how adolescents successfully navigate the demands of contemporary society. We aim to test these questions using socio-economic, questionnaire (including experience sampling methods), behavioral, brain (fMRI, sMRI, EEG), hormonal, and genetic measures in four large cohorts including adolescents and young adults. Two cohorts are designed as test and replication cohorts to test the developmental trajectory of self-regulation, including adolescents of different socioeconomic status thereby bridging individual, family, and societal perspectives. The third cohort consists of an entire social network to examine how neural and self-regulatory development influences and is influenced by whom adolescents and young adults choose to interact with. The fourth cohort includes youth with early signs of antisocial and delinquent behavior to understand patterns of societal development in individuals at the extreme ends of self-regulation and societal participation, and examines pathways into and out of delinquency. We will complement the newly collected cohorts with data from existing large-scale population-based and case-control cohorts. The study is embedded in a transdisciplinary approach that engages stakeholders throughout the design stage, with a strong focus on citizen science and youth participation in study design, data collection, and interpretation of results, to ensure optimal translation to youth in society.

The issues of bias and racism require that nursing students and healthcare leaders are competent and confident to recognize and effectively address situations that arise in the work setting and community. The American Organization for Nursing Leadership (AONL) stated it is the responsibility of all nurse leaders to address issues related to diversity, equity, inclusion, and belonging (AONL, 2023). To meet this challenge, nurse leaders need to develop the knowledge and skills to manage issues of bias and racism. A 360-degree immersive virtual reality (IVR) simulation was created to provide graduate nursing leadership students and nurse leaders in the health system (n=36) with the opportunity to learn and practice these skills in a safe environment. Effectiveness and acceptability of the IVR simulation were assessed quantitatively and qualitatively through participants' subjective evaluation of their IVR experience, awareness, and confidence to identify and address bias and racism. This innovative simulation demonstrated that the IVR education was impactful, increased participants' confidence, and reinforced the organization's values and commitment to diversity, equity, inclusion, belonging (DEIB), and anti-racism. The IVR experience inspired participants' desire to change behaviors, role model inclusive practices, and influence others to create a culture of inclusion and belonging.

Abstract Background BUP-XR (SUBLOCADE®) is the first buprenorphine extended-release subcutaneous injection approved in the USA for monthly treatment of moderate-to-severe opioid use disorder (OUD). Among patients with OUD, those who inject or use high doses of opioids likely require higher doses of buprenorphine to maximize treatment efficacy. The objective of this analysis was to compare the efficacy and safety of 100-mg versus 300-mg maintenance doses of BUP-XR in OUD patients who inject opioids. Methods This was a secondary analysis of a randomized, double-blind, placebo-controlled study in which adults with moderate or severe OUD received monthly injections of BUP-XR (2 × 300-mg doses, then 4 × 100-mg or 300-mg maintenance doses) or placebo for 24 weeks. Abstinence was defined as opioid-negative urine drug screens combined with negative self-reports collected weekly. Each participant’s percentage abstinence was calculated after the first, second, and third maintenance doses in opioid-injecting and non-injecting participants. The proportion of participants achieving opioid abstinence in each group was also calculated weekly. Treatment retention rate following the first maintenance dose was estimated for opioid-injecting participants with Kaplan–Meier method. Risk-adjusted comparisons were made via inverse propensity weighting using propensity scores. Buprenorphine plasma concentration–time profiles were compared between injecting and non-injecting participants. The percentages of participants reporting treatment-emergent adverse events were compared between maintenance dose groups within injecting and non-injecting participants separately. Results BUP-XR 100-mg and 300-mg maintenance doses were equally effective in non-injecting participants. However, in opioid-injecting participants, the 300-mg maintenance dose delivered clinically meaningful improvements over the 100-mg maintenance dose for treatment retention and opioid abstinence. Exposure–response analyses confirmed that injecting participants would require higher buprenorphine plasma concentrations compared to non-injecting opioid participants to achieve similar efficacy in terms of opioid abstinence. Importantly, both 100- and 300-mg maintenance doses had comparable safety profiles, including hepatic safety events. Conclusions These analyses show clear benefits of the 300-mg maintenance dose in injecting participants, while no additional benefit was observed in non-injecting participants relative to the 100-mg maintenance dose. This is an important finding as opioid-injecting participants represent a high-risk and difficult-to-treat population. Optimal buprenorphine dosing in this population might facilitate harm reduction by improving abstinence and treatment retention. Trial registration: ClinicalTrials.gov, NCT02357901.

The present study aimed to develop a novel temperature and pressure-controlled hybrid system (Cent-Hydro) for large-scale nanofiber production. Nanofibers from a hydrophilic carrier matrix were prepared using the Cent-Hydro system. This study explores the effect of increasing working temperature on the surface tension and viscosity of polymer solutions. The Cent-Hydro system was calibrated through the process of jet formation, and spinning parameters were identified for the jet path. The formation of fingers in front of the thin liquid occurred due to Rayleigh–Taylor instability, and a lower concentration of polymer solution favoured the development of thinner and longer fingers. The critical angular velocity and initial velocity for jet formation were obtained when the balance between surface tension, centrifugal force, and viscous force was achieved. The effect of increasing rotational speed and working temperature on finger velocity and length was experimentally evaluated, concluding that an increase in working temperature increases finger velocity and length. Additionally, the effect of increasing rotational speed, polymer concentration, and working temperature on the diameter of the nanofiber was evaluated. Overall, the Cent-Hydro system presents a compelling proposition for large-scale nanofiber production, offering distinct advantages over conventional methods and paving the way for advancements in various applications.

Arsenic, the 20th most common element in Earth’s crust and historically regarded as the King of Poisons, occurs naturally in two oxidation states, Arsenate (V) and Arsenite (III), and is prevalent worldwide through natural and anthropogenic means. The cations of the metalloid exhibit unique chemical behaviour in water and are found to be components of approximately 245 natural minerals, making its occurrence in drinking water a compelling challenge, especially in groundwater. This comprehensive review collates information regarding the prevalence of arsenic contamination in water worldwide and its impact on human health, its chemical behaviour, methods for detection and quantification, and treatment strategies. A comprehensive search was conducted, and the selection of eligible studies was carried out using the PRISMA (the preferred reporting items for systematic reviews and meta-analyses) guidelines. Essential characteristics of eligible research studies were extracted based on geographical areas, origins, concentration levels and the magnitude of populations vulnerable to arsenic contamination in groundwater sources. Arsenic contamination of water affects over 100 countries including Canada, the United States, Pakistan, China, India, Brazil and Bangladesh, where hydrogeological conditions favour prevalence and groundwater is the primary water source for food preparation, irrigation of food crops and drinking water. This leads to human exposure through absorption, ingestion and inhalation, causing numerous health disorders affecting nearly all systems within the human body, with acute and chronic toxicity including cancers. The presence of arsenic in water poses a considerable challenge to humanity, prompting scientists to devise diverse mitigation approaches categorized as (a) oxidation processes, (b) precipitation methods, (c) membrane technologies, (d) adsorption and ion exchange methods, and (e) social interventions. This comprehensive review is expected to be a valuable source for professionals in the water industry, public management, and policymaking, aiding their ongoing and future research and development efforts.

The microsomal metabolism of phenol (11 °C) over an annual reproductive cycle from June to December was studied using fall spawning adult brook trout (Salvelinus fontinalis). Hepatic microsomes were isolated from three male and three female fish each month. Incubations were optimized for time, cofactor concentration, pH, and microsomal protein concentration. The formation of phase I ring-hydroxylation metabolites, i.e., hydroquinone (HQ) and catechol (CAT), was quantified by HPLC with dual-channel electrochemical detection. Sample preparation and chromatographic conditions were optimized to achieve the separation and sensitivity required for the analysis of these labile products. Biotransformation of phenol over a range of substrate concentrations (1 to 150 mM) was quantified for the calculation of Michaelis–Menten constants (Km and Vmax) for each month. Results indicate a nearly equal production of HQ and CAT among males and females in late June. At the peak of maturity in October, there was an approximate ten-fold greater production of ring-hydroxylation metabolites noted in females in comparison with males on a total liver basis. In vitro phase II biotransformation of phenol glucuronidation was assessed by determining the Michaelis–Menten constants (Km, Vmax) using brook trout hepatic microsomes over a range of substrate concentrations (1 to 60 mM). Initially, there were no significant differences in the glucuronide rate of formation (pmol/min/mg protein) or total capacity (nmol/min/liver) between females and males. At the peak of maturation, the maximum rate of glucuronide formation was 4-fold less in females; however, the total capacity was 2-fold less in females due to the increased liver size in the females. The alterations in biotransformation coincided with increases in the hepatic and gonadal somatic indices and with changes in plasma hormone concentrations. These experiments provide insight into the metabolic deactivation of xenobiotics and to provide data for the prediction of altered hepatic biotransformation rates and pathways during the reproductive cycle.

The purpose of this study was to review the research literature on online learning to identify effective instructional practices. We narrowed our scope to empirical studies published 2013-2019 given that studies earlier than 2013 had become quickly outdated because of changes in online pedagogies and technologies. We also limited our search to studies with undergraduate and graduate students, application of an empirical methodological design, and descriptions of methodology, data analysis, and results with sufficient detail to assure verifiability of data collection and analysis. Our analysis of the patterns and trends in the corpus of 104 research studies led to identification of five themes: course design factors, student support, faculty pedagogy, student engagement, and student success factors. Most of the strategies with promising effectiveness in the online environment are the same ones that are considered to be effective in face-to-face classrooms including the use of multiple pedagogies and learning resources to address different student learning needs, high instructor presence, quality of faculty-student interaction, academic support outside of class, and promotion of classroom cohesion and trust. Unique to the online environment are user-friendly technology tools, orientation to online instruction, opportunities for synchronous class sessions, and incorporation of social media. Given the few studies utilizing methodological designs from which claims of causality can be made or meta-analyses could be conducted, we identified only faculty feedback as an evidence-based practice and no specific intervention that we could identify as research-based in online instruction.

This study was designed to investigate the applicability of the IES/NSF pipeline-of-evidence protocol in ascertaining why two notable educational initiatives spearheaded and financially supported by the Bill and Melinda Gates Foundation achieved or not the goal of improved academic outcomes for K-12 public school students. Our interest was not whether there is a sufficient body of high quality research evidence to support the two initiatives but whether the research considered by the Gates Foundation established the likelihood that the initiatives would be successful and worth the decision to dedicate substantial funding, time, and effort required for each versus the many competing programs seeking sponsorship. We found that in the case of Intensive Partnerships for Effective Teaching, foundational, efficacy, and effectiveness research were absent and the Gates foundation discontinued grant support because the initiative had not achieved the goal of improved high school graduation and college attendance among low-income minority students. In the case of Early College High School, we found empirical evidence was manifest at all but the effectiveness stage of the pipeline and the initiative continued to receive funding. Our findings support the importance of widening the net of methodologies that constitute a framework for elements needed to make predictions of effectiveness for any given intervention before investing in scale-up initiatives and the need for private foundations to be transparent in their decision-making process to enable others to scrutinize the research that informs the design of initiatives.