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Background: Socioeconomic characteristics are persistently and systematically related to academic outcomes, despite long-standing efforts to reduce educational inequality. Ireland has a strong policy focus on alleviating educational disadvantage and has seen significant improvements in mathematics and science performance in recent years. This study investigates patterns of socioeconomic inequalities in 4th grade students' performance in mathematics and science between 2011 and 2019. Two measures of inequality are examined: (i) inequality of achievement, i.e., the degree of variability in student performance and (ii) inequality of opportunity, i.e., the extent to which student performance is related to background characteristics. Methods: Data for 4th-grade students in Ireland from TIMSS 2011, TIMSS 2015 and TIMSS 2019 were used. Mathematics and science achievement were the main outcome measures. The home resources for learning index was used as a proxy for student-level socioeconomic status. School-level socioeconomic status was examined according to schools' participation in the "Delivering Equality of Opportunity in Schools" (DEIS) programme, which is the Department of Education's main policy initiative addressing educational disadvantage. Descriptive and multilevel regression analyses were conducted to explore variability in student performance and to investigate the variance in achievement explained by socioeconomic factors, across cycles and subjects. Results: Between 2011 and 2015, between-student and between-school differences in mathematics and science performance became smaller, as shown by the decrease in standard deviations and the intraclass correlation coefficients (ICCs). This points to reduced inequality of achievement. Between 2015 and 2019, a small increase in inequality of achievement was observed. Regarding inequality of opportunity, students' home resources for learning and school disadvantaged status were statistically significantly related to mathematics and science achievement across all three cycles. Overall variance explained by these two variables increased from 2011 to 2019. This points towards increasing inequality of opportunity over the period examined. Performance gaps between disadvantaged and non-disadvantaged schools have been reduced over time; however, the relationship between home resources for learning and achievement appears to have strengthened. Findings were consistent for both subjects. Conclusions: The findings indicate that improvements in overall performance do not necessarily reflect improved equality. Ireland's improvements in average mathematics and science performance between 2011 and 2015 were accompanied by reduced inequality of achievement. Performance differences between disadvantaged and non-disadvantaged schools have been reduced over time, suggesting that the DEIS policy is meeting its goal of narrowing achievement gaps based on concentrations of educational disadvantage. However, inequality of opportunity linked to student-level socioeconomic factors (i.e., home resources for learning) appears to have increased over time. These findings are valuable in the context of measuring and tracking educational inequalities.

Wildlife-human relations in the United States are predominantly influenced by Euro-American sociocultural dynamics and (neo)colonial legacies. Humans dominate nonhuman animals through violence, suffering, and death. Wildlife management as a practice is becoming increasingly criticized. Disagreement emerges from epistemological and ontological foundations and remains contentious in theory and practice. Environmental education reinforces the subjugation of nonhumans and particular individuals that are governed by human decision-making, and power assemblages. However, public values have shifted to a mutualism orientation where management practices are challenged by shifting moral standards of society that value the intrinsic rights, welfare, and agency of individual beings. We present two related case studies that showcase posthuman pedagogy and illustrate how 'real-world' field experiences can shape students' ontologies and cosmologies. This work draws from the first author's fieldwork on salmon-sea lion-human relations in the Columbia River Basin of the Pacific Northwest US. This includes over 120 semi-structured interviews, two deployments of the Vertically Integrated Project (VIP) model, participant observation, and archival data. We focus on four specific fieldwork moments captured by student reflection. Posthuman pedagogy allows educators and scholars to rest with the material relations that dictate the lives of nonhuman participants and provides pragmatic openings for more-than-human worlds.

Abstract Wetlands are ecologically and culturally significant ecosystems that are experiencing biodiversity declines globally. Biomonitoring techniques that use environmental DNA (eDNA) to detect and monitor biodiversity are well established in lake, riverine, and marine ecosystems. However, their use in wetlands requires further development due to the presence of sediments that block eDNA filters to limit water filtration, alongside a lack of standardized methodology. In this study, we examined eDNA dynamics to understand spatiotemporal biodiversity patterns in an Aotearoa New Zealand wetland and to optimize their application to wetland‐specific challenges. We sampled four sites across Opuatia Wetland at three time points during an austral spring. We conducted conventional taxonomic surveys, tested three different filter sizes (1.2 μm, 5 μm, and semi‐quantitative dacron filters), and assessed our ability to detect foreign DNA (from kea; Nestor notabilis) at different time points and distances post‐release. We found significant differences in DNA sequence composition across time and space, and when using different sized filters. eDNA data generally complemented (versus replaced) conventional survey and identification methods, with certain species only detected by one method or the other. Taxonomic resolution of conventional sampling and identification methods often exceeded that of eDNA. Foreign DNA was detectable 10 m from its release point for up to 1 week post‐release. Our results provide new considerations for future eDNA research in wetland environments, where rapid biomonitoring techniques are needed to support conservation and preservation.

BackgroundDetailed and invasive clinical investigations are required to identify the causes of haematuria. Highly unbalanced patient population (predominantly male) and a wide range of potential causes make the ability to correctly classify patients and identify patient-specific biomarkers a major challenge. Studies have shown that it is possible to improve the diagnosis using multi-marker analysis, even in unbalanced datasets, by applying advanced analytical methods. Here, we applied several machine learning algorithms to classify patients from the haematuria patient cohort (HaBio) by analysing multiple biomarkers and to identify the most relevant ones.Materials and methodsWe applied several classification and feature selection methods (k-means clustering, decision trees, random forest with LIME explainer and CACTUS algorithm) to stratify patients into two groups: healthy (with no clear cause of haematuria) or sick (with an identified cause of haematuria e.g., bladder cancer, or infection). The classification performance of the models was compared. Biomarkers identified as important by the algorithms were also analysed in relation to their involvement in the pathological processes.ResultsResults showed that a high unbalance in the datasets significantly affected the classification by random forest and decision trees, leading to the overestimation of the sick class and low model performance. CACTUS algorithm was more robust to the unbalance in the dataset. CACTUS obtained a balanced accuracy of 0.747 for both genders, 0.718 for females and 0.803 for males. The analysis showed that in the classification process for the whole dataset: microalbumin, male gender, and tPSA emerged as the most informative biomarkers. For males: age, microalbumin, tPSA, cystatin C, BTA, HAD and S100A4 were the most significant biomarkers while for females microalbumin, IL-8, pERK, and CXCL16.ConclusionsCACTUS algorithm demonstrated improved performance compared with other methods such as decision trees and random forest. Additionally, we identified the most relevant biomarkers for the specific patient group, which could be considered in the future as novel biomarkers for diagnosis. Our results have the potential to inform future research and provide new personalised diagnostic approaches tailored directly to the needs of the individuals.

Objective The objective was to assess the association between nutritional and clinical characteristics and quantitative PCR (qPCR)-diagnosis of bacterial diarrhoea in a multicentre cohort of children under 2 years of age with moderate to severe diarrhoea (MSD).Design A secondary cross-sectional analysis of baseline data collected from the AntiBiotics for Children with Diarrhoea trial (NCT03130114).Patients Children with MSD (defined as >3 loose stools within 24 hours and presenting with at least one of the following: some/severe dehydration, moderate acute malnutrition (MAM) or severe stunting) enrolled in the ABCD trial and collected stool sample.Study period June 2017–July 2019.Interventions None.Main outcome measures Likely bacterial aetiology of diarrhoea. Secondary outcomes included specific diarrhoea aetiology.Results A total of 6692 children with MSD had qPCR results available and 28% had likely bacterial diarrhoea aetiology. Compared with children with severe stunting, children with MAM (adjusted OR (aOR) (95% CI) 1.56 (1.18 to 2.08)), some/severe dehydration (aOR (95% CI) 1.66 (1.25 to 2.22)) or both (aOR (95% CI) 2.21 (1.61 to 3.06)), had higher odds of having likely bacterial diarrhoea aetiology. Similar trends were noted for stable toxin-enterotoxigenic Escherichia coli aetiology. Clinical correlates including fever and prolonged duration of diarrhoea were not associated with likely bacterial aetiology; children with more than six stools in the previous 24 hours had higher odds of likely bacterial diarrhoea (aOR (95% CI) 1.20 (1.05 to 1.36)) compared with those with fewer stools.Conclusion The presence of MAM, dehydration or high stool frequency may be helpful in identifying children with MSD who might benefit from antibiotics.

Introduction/Purpose: Minimally invasive surgical (MIS) techniques for are exponentially increasing as a surgical option for treating midfoot and forefoot conditions. However, performing percutaneous osteotomies using the burr prevents direct visualization to estimate the correct measurements for the resection. This study aimed to evaluate the impact of each burr pass on the degree of correction, gap size, and alignment in MIS Akin and first metatarsal dorsiflexion osteotomies (DFO). It is hoped that this will improve the surgeon's ability to correct the desired amount of deformity and assist in surgical planning. Methods: Minimally invasive Akin and first metatarsal DFO were performed on ten cadaveric specimens using a 2 mm Shannon burr. The lateral (for Akin) and plantar (for 1st DFO) cortices were left intact. A total of 5 passes with the Shannon burr were performed during each osteotomy. The osteotomy gap was manually closed after each pass and held closed while completing the subsequent passes. Fluoroscopy images were obtained before and after each of the five passes, on which two independent reviewers performed measurements and inter-observer reliability was evaluated with ICC analysis. Measurements included the metatarsal dorsiflexion angle (MDA) and dorsal cortical length (MDCL). Likewise, the phalangeal measurements included the first phalangeal medial cortical length (PCML) and proximal to distal phalangeal articular angle (PDPAA) (Figure 1). Results: The average decrease in PCML with each burr pass was as follows: 1.53 mm at the 1st pass, 1.33 mm at the 2nd pass, 1.27 mm at the 3rd pass, 1.23 mm at the 4th pass, and 1.13 mm at the 5th pass. The MDCL sequentially decreased by 1.80 mm, 1.59 mm, 1.35 mm, 0.75 mm, and 0.60 mm. The MDA consistently decreased, and the PDPAA incrementally became more valgus oriented following each consecutive burr pass. Interobserver reliability analysis demonstrated good agreement for all parameters. Conclusion: The results revealed the length and alignment changes trends in the forefoot and midfoot osteotomies with each burr pass. On average, a first metatarsal dorsal wedge resection of 4.7 mm and first phalangeal medial wedge resection of 2.9 mm was achieved after 3 and 2 burr passes, respectively. The first burr pass provided a correction of 76% of the burr diameter, while it decreased to 66%, 63%, 61%, and 56% of the burr diameter with each subsequent pass. This data may aid surgeons determine the optimal number of burr passes required for the amount of resection needed. Overview of the radiographic measurements. A) first metatarsal dorsiflexion angle (MDA), B) first metatarsal dorsal cortical length (MDCL), C) first phalangeal medial cortical length (PCML) and D) proximal to distal phalangeal articular angle (PDPAA). The diameter of the sphere © The Author(s) 2024(Dsphere) was calculated automatically by the MATLAB script for calibration purposes.

Reading proficiency is crucial for academic, vocational, and economic success and has been closely linked to health outcomes. Unfortunately, in the United States, a concerning 63% of fourth-grade children are reading below grade level, with approximately 7%–10% exhibiting a disability in word reading, developmental dyslexia. Research in developmental cognitive neuroscience indicates that individuals with dyslexia show functional and structural brain alterations in regions processing reading and reading-related information, with some of these differences emerging as early as preschool and even infancy. This suggests that some children start schooling with less optimal brain architecture for learning to read, emphasizing the need for preventative education practices. This article reviews educational policies impacting children with dyslexia and highlights a decentralized parent-led grassroots movement, Decoding Dyslexia, which centers the voices of those directly impacted by dyslexia. It utilizes civic engagement practices, advocacy and lobbying on local, federal, and social media platforms, and strong partnerships with scientists to drive systems-level change in educational practices, leading to dyslexia prevention legislation across the U.S. The ongoing partnership continues to address the profound gaps between scientific findings and policymaking to drive systems-level change for contemporary challenges in educational practices within a learning disabilities framework.

A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. We further found that muscular protein O-GlcNAcylation was regulated by hypoxia and lactate through HIF1A-dependent OGT promoter activation and was elevated after exercise. Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. This was associated with reduced skeletal muscle mass and contractility in tumour-bearing mice. Our findings link O-GlcNAcylation to muscular protein homoeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation.

BACKGROUND: Genetic variation in one-carbon metabolism may affect nutrient concentrations and biological functions. However, data on genetic variants associated with blood biomarkers of one-carbon metabolism in US postmenopausal women are limited, and whether these associations were affected by the nationwide folic acid (FA) fortification program is unclear. OBJECTIVES: We investigated associations between genetic variants and biomarkers of one-carbon metabolism using data from the Womens Health Initiative Observational Study. METHODS: In 1573 non-Hispanic White (NHW) and 282 Black/African American, American Indian/Alaska Native, Asian/Pacific Islander, and Hispanic/Latino women aged 50-79 y, 288 nonsynonymous and tagging single-nucleotide variants (SNVs) were genotyped. RBC folate, plasma folate, pyridoxal-5-phosphate (PLP), vitamin B-12, homocysteine, and cysteine concentrations were determined in 12-h fasting blood. Multivariable linear regression tested associations per variant allele and for an aggregated genetic risk score. Effect modifications before, during, and after nationwide FA fortification were examined. RESULTS: After correction for multiple comparisons, among NHW women, 5,10-methylenetetrahydrofolate reductase (MTHFR) rs1801133 (677C→T) variant T was associated with lower plasma folate (-13.0%; 95% CI: -17.3%, -8.6%) and higher plasma homocysteine (3.5%; 95% CI: 1.7%, 5.3%) concentrations. Other associations for nonsynonymous SNVs included DNMT3A rs11695471 (T→A) with plasma PLP; EHMT2 rs535586 (G→A), TCN2 rs1131603 (L349S A→G), and TCN2 rs35838082 (R188W G→A) with plasma vitamin B-12; CBS rs2851391 (G→A) with plasma homocysteine; and MTHFD1 rs2236224 (G→A) and rs2236225 (R653Q G→A) with plasma cysteine. The influence of FA fortification on the associations was limited. Highest compared with lowest quartiles of aggregated genetic risk scores from SNVs in MTHFR and MTRR were associated with 14.8% to 18.9% lower RBC folate concentrations. Gene-biomarker associations were similar in women of other races/ethnicities. CONCLUSIONS: Our findings on genetic variants associated with several one-carbon metabolism biomarkers may help elucidate mechanisms of maintaining B vitamin status in postmenopausal women.

Abstract Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p

Abstract Background Low birthweight (LBW) infants are at increased risk of morbidity and mortality. Exclusive breastfeeding up to six months is recommended to help them thrive through infection prevention, growth improvements, and enhancements in neurodevelopment. However, limited data exist on the feeding experiences of LBW infants, their caregivers and key community influencers. The qualitative component of the Low Birthweight Infant Feeding Exploration (LIFE) study aimed to understand practices, facilitators, and barriers to optimal feeding options in the first six months for LBW infants in low-resource settings. Methods This study was conducted in four sites in India, Malawi, and Tanzania from July 2019 to August 2020. We conducted 37 focus group discussions with mothers and family members of LBW infants and community leaders and 142 in-depth interviews with healthcare providers, government officials, and supply chain and donor human milk (DHM) experts. Data were analyzed using a framework approach. Results All participants believed that mother’s own milk was best for LBW infants. Direct breastfeeding was predominant and feeding expressed breast milk and infant formula were rare. DHM was a new concept for most. Adequate maternal nutrition, lactation support, and privacy in the facility aided breastfeeding and expression, but perceived insufficient milk, limited feeding counseling, and infant immaturity were common barriers. Most believed that DHM uptake could be enabled through community awareness by overcoming misconceptions, safety concerns, and perceived family resistance. Conclusion This study fills an evidence gap in LBW infant feeding practices and their facilitators and barriers in resource-limited settings. LBW infants face unique feeding challenges such as poor latching and tiring at the breast. Similarly, their mothers are faced with numerous difficulties, including attainment of adequate milk supply, breast pain and emotional stress. Lactation support and feeding counseling could address obstacles faced by mothers and infants by providing psychosocial, verbal and physical support to empower mothers with skills, knowledge and confidence and facilitate earlier, more and better breast milk feeding. Findings on DHM are critical to the future development of human milk banks and highlight the need to solicit partnership from stakeholders in the community and health system.

There is a scarcity of literature relating to post-bariatric hypoglycaemia (PBH) in pregnancy. Recurrent hyperglycaemia and hypoglycaemia can have significant consequences for both the mother and the developing fetus. We describe a case of a young pregnant woman who was diagnosed with symptomatic PBH in the second trimester of pregnancy using continuous glucose monitoring (CGM) 3 years after Roux-en-Y gastric bypass (RYGB) surgery. Instigating a low glycaemic index and complex carbohydrate diet significantly improved the patient’s glycaemic excursions. Given that this condition is likely underdiagnosed as a complication of RYGB surgery, a greater awareness of this complication is needed. Patients should be adequately consented pre-operatively for this relatively frequent late surgical complication to enable patients to identify symptoms of this condition at an early stage and seek medical treatment.

Abstract Background Governments internationally have invested hugely in the implementation and scale-up of school-based physical activity interventions, but have little evidence of how to best sustain these interventions once active implementation support ceases. This study will assess the effectiveness of a multi-strategy sustainability intervention on classroom teachers’ sustainment of energisers (short 3–5 min physical activity breaks during class-time) scheduled across the school day from baseline to 12 and 24-month follow-up. Methods A cluster randomised controlled trial will be conducted in 50 primary schools within the Hunter New England, Illawarra Shoalhaven, Murrumbidgee and Northern New South Wales (NSW) Local Health Districts of NSW Australia. Schools will be randomly allocated to receive either usual support or the multi-strategy sustainability intervention that includes: centralised technical assistance from a trained project officer; formal commitment and mandated change obtained from school principals; training in-school champions; reminders for teachers; educational materials provided to teachers; capturing and sharing local knowledge; and engagement of parents, carers and the wider school community. The primary trial outcome will be measured via a teacher logbook to determine the between-group difference in the change in mean minutes of energisers scheduled across the school day at 12 and 24-month follow-up compared to baseline. Analyses will be performed using an intention to treat framework. Linear mixed models will be used to assess intervention effects on the primary outcome at both follow-up periods. Discussion This study will be one of the first randomised controlled trials to examine the impact of a multi-strategy sustainability intervention to support schools’ sustainment of a physical activity intervention. The proposed research will generate new evidence needed for the partnering organisations to protect their considerable investments to date in physical activity promotion in this setting and will provide seminal evidence for the field globally. Trial registration ACTRN12620000372987 version 1 registered 17th March 2020. Version 3 (current version) updated 4th August 2023.

Abstract Background Growth hormone deficiency (GHD) has been implicated in increased cardiovascular and cerebrovascular disease risk seen in hypopituitarism, however the mechanism remains speculative. We hypothesise that platelet abnormalities may play a contributory role. Herein we examined platelet behaviour in GHD hypopituitary patients, pre- and post-growth hormone (GH) replacement. Methods This study utilizes a physiological flow-based assay to quantify platelet function in whole blood from patient cohorts under arterial shear. Thirteen GH Naïve hypopituitary adults with GHD and thirteen healthy matched controls were studied. Patients were assessed before and after GH treatment. All other pituitary replacements were optimised before the study. In addition to a full endocrine profile, whole blood was labelled and perfused over immobilised von Willibrand factor (vWF). Seven parameters of dynamic platelet-vWF interactions were recorded using digital image microscopy and analysed by customised platelet tracking software. Results We found a significantly altered profile of platelet-vWF interactions in GHD individuals compared to healthy controls. Specifically, we observed a marked increase in platelets shown to form associations such as tethering, rolling and adherence to immobilized vWF, which were reduced post GH treatment. Speed and distance platelets travelled across vWF was similar between controls and pre-therapy GHD patients, however, this was considerably increased post treatment. This may indicate reduced platelet signaling resulting in less stable adhesion of platelets post GH treatment. Conclusions Taken together observed differences in platelet behaviour may contribute to an increased risk of thrombosis in GHD which can in part be reversed by GH therapy.

Abstract The analysis of microbial genomes from human archaeological samples offers a historic snapshot of ancient pathogens and provides insights into the origins of modern infectious diseases. Here, we analyze metagenomic datasets from 38 human archaeological samples and identify bacterial genomic sequences related to modern-day Clostridium tetani, which produces the tetanus neurotoxin (TeNT) and causes the disease tetanus. These genomic assemblies had varying levels of completeness, and a subset of them displayed hallmarks of ancient DNA damage. Phylogenetic analyses revealed known C. tetani clades as well as potentially new Clostridium lineages closely related to C. tetani. The genomic assemblies encode 13 TeNT variants with unique substitution profiles, including a subgroup of TeNT variants found exclusively in ancient samples from South America. We experimentally tested a TeNT variant selected from an ancient Chilean mummy sample and found that it induced tetanus muscle paralysis in mice, with potency comparable to modern TeNT. Thus, our ancient DNA analysis identifies DNA from neurotoxigenic C. tetani in archaeological human samples, and a novel variant of TeNT that can cause disease in mammals.

The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration. It has thus been proposed that the oxytosis/ferroptosis pathway can be used to identify novel drug candidates for the treatment of age-associated neurodegenerative diseases that act by preserving mitochondrial function. Previously, we identified cannabinol (CBN) as a potent neuroprotector. Here, we demonstrate that not only does CBN protect nerve cells from oxytosis/ferroptosis in a manner that is dependent on mitochondria and it does so independently of cannabinoid receptors. Specifically, CBN directly targets mitochondria and preserves key mitochondrial functions including redox regulation, calcium uptake, membrane potential, bioenergetics, biogenesis, and modulation of fusion/fission dynamics that are disrupted following induction of oxytosis/ferroptosis. These protective effects of CBN are at least partly mediated by the promotion of endogenous antioxidant defenses and the activation of AMP-activated protein kinase (AMPK) signaling. Together, our data highlight the potential of mitochondrially-targeted compounds such as CBN as novel oxytotic/ferroptotic inhibitors to rescue mitochondrial dysfunction as well as opportunities for the discovery and development of future neurotherapeutics.

Chronic metabolic diseases such as diabetes are characterized by delayed wound healing and a dysregulation of the inflammatory phase of wound repair. Our study focuses on changes in the payload of extracellular vesicles (EVs) communicating between immune cells and stromal cells in the wound bed, which regulate the rate of wound closure. Adoptive transfer of EVs from genetically defined mouse models are used here to demonstrate a functional and molecular basis for differences in the pro-reparative biological activity of diabetic (db/db) vs. wildtype EVs in wound healing. We identify several members of the Serpin family of serine protease inhibitors that are absent in db/db EVs, then we overexpress Serpin A1, F2 and G1 in EVs to evaluate their effect on wound healing in db/db mice. Serpins have an important role in regulating levels of elastase, plasmin and complement factors that coordinate immune cell signaling in full thickness wounds in a diabetic model. Here, we establish a novel therapeutic approach by engineering the payload of EVs based on proteomic analysis. Serpin-loaded EVs were used to rescue the Serpin deficiency identified by proteomics and promote wound healing in db/db mice, as well as evaluated how EVs affected extracellular matrix remodeling and the resolution of tissue injury. Therefore, we propose that the identification of EV payloads that are downregulated in diabetic wounds can be systematically analyzed for their functional activity and potential as a therapeutic, based on whether their re-expression in engineered EVs restores normal kinetics of tissue repair in chronic wounds.

Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9 (CRISPR/Cas9) has transformed our ability to edit the human genome selectively. This technology has quickly become the most standardized and reproducible gene editing tool available. Catalyzing rapid advances in biomedical research and genetic engineering, the CRISPR/Cas9 system offers great potential to provide diagnostic and therapeutic options for the prevention and treatment of currently incurable single-gene and more complex human diseases. However, significant barriers to the clinical application of CRISPR/Cas9 remain. While in vitro, ex vivo, and in vivo gene editing has been demonstrated extensively in a laboratory setting, the translation to clinical studies is currently limited by shortfalls in the precision, scalability, and efficiency of delivering CRISPR/Cas9-associated reagents to their intended therapeutic targets. To overcome these challenges, recent advancements manipulate both the delivery cargo and vehicles used to transport CRISPR/Cas9 reagents. With the choice of cargo informing the delivery vehicle, both must be optimized for precision and efficiency. This review aims to summarize current bioengineering approaches to applying CRISPR/Cas9 gene editing tools towards the development of emerging cellular therapeutics, focusing on its two main engineerable components: the delivery vehicle and the gene editing cargo it carries. The contemporary barriers to biomedical applications are discussed within the context of key considerations to be made in the optimization of CRISPR/Cas9 for widespread clinical translation.

Introduction: Pain scales are often used in peripheral nerve block studies but are problematic due to their subjective nature. Ultrasound-measured diaphragmatic excursion is an easily learned technique that could provide a much-needed objective measure of pain control over time with serial measurements.Case Series: We describe three cases where diaphragmatic excursion was used as an objective measure of decreased pain and improved respiratory function after serratus anterior plane block in emergency department patients with anterior or lateral rib fractures.Conclusion: Diaphragmatic excursion may be an ideal alternative to pain scores to evaluate serratus anterior plane block efficacy. More data will be needed to determine whether this technique can be applied to other ultrasound-guided nerve blocks.

The aim of the current investigation was to examine the locomotor performance profile of elite ladies Gaelic football (LGF) players in relation to playing position and quarters of play. Thirty (n = 30) elite LGF players (age: 24 ± 4 years, height: 169 ± 5 cm, body mass: 61 ± 4 kg) were monitored using 10 Hz GPS technology (Playertek; Catapult Sports; Australia) resulting in 145 individual samples collected over 18 competitive matches across the 2021 and 2022 LGF seasons. Locomotor performance was determined across the following variables: total distance covered (TD, m), relative distance (m·min−1), high-speed running (HSR, ≥ 4.4 m·s−1), very high-speed running (VHSR, ≥ 5.5 m·s−1), relative HSR (RHSR; m·min−1), peak velocity (m·s−1), percentage peak velocity (%PeakV), accelerations (n; ≥ 3 m·s−2), and decelerations (n; ≤ −3 m·s−2). Data were classified based on playing position and quarter of play. The greatest TD was covered by half-backs, midfielders, and half-forwards, with these positions covering significantly greater distances than full-backs (p < 0.05). Similarly, half-backs, midfielders, and half-forwards covered the greatest high-speed distance (HSR). When running performance was analysed across quarters, a significant position by quarter interaction was observed for all running performance variables, except peak velocity and percentage peak velocity. A consistent trend for reduced locomotor performance was evident in the second and fourth quarters across all positional lines. The current data provide coaches with the position-specific locomotor requirements of LGF match-play, which can inform the design of training content for LGF players, along with match-day strategies. Given the reduction in locomotor performance observed across the match, performance staff may consider the use of nutritional interventions, rewarm-up strategies, or specific substitution policies to mitigate the decrement in locomotor performance observed across match-play.

The goal of creating evidence-based programs is to scale them at sufficient breadth to support population-level improvements in critical outcomes. However, this promise is challenging to fulfill. One of the biggest issues for the field is the reduction in effect sizes seen when a program is taken to scale. This paper discusses an economic perspective that identifies the underlying incentives in the research process that lead to scale up problems and to deliver potential solutions to strengthen outcomes at scale. The principles of open science are well aligned with this goal. One prevention program that has begun to scale across the USA is early childhood home visiting. While there is substantial impact research on home visiting, overall average effect size is 0.10 and a recent national randomized trial found attenuated effect sizes in programs implemented under real-world conditions. The paper concludes with a case study of the relevance of the economic model and open science in developing and scaling evidence-based home visiting. The case study considers how the traditional approach for testing interventions has influenced home visiting's evolution to date and how open science practices could have supported efforts to maintain impacts while scaling home visiting. It concludes by considering how open science can accelerate the refinement and scaling of home visiting interventions going forward, through accelerated translation of research into policy and practice.

The politics of children's literature and the actors surrounding it have never been more visible than they are now, in the digital age. As one of the first children's series to gain widespread popularity concurrently with the spread of the internet, the Harry Potter septet arrived on the global stage at the perfect moment to develop an avid, connected fandom. But the fandom has laid bare the many conflicting ideologies of the fans themselves and of the actors surrounding the texts. This article examines the contentious issue of gender nonnormativity and its relation to the Harry Potter texts, the queer/trans reading practices and political resistance common to the fandom, and the ongoing disagreements over gender, made visible on social media, between Rowling and the fans of her series. The article discusses the Harry Potter novels' varied and conflicting ideologies; queer/trans readings of the Potter septet, including both invitations and resistances to queer/trans reading by Rowling herself; how gender is queered and queried in and through fan fiction; and finally, the recent hostilities between Rowling and her fans. It concludes by discussing the worsening relationship between Rowling and her fans and highlighting how fans are using their collective power to undermine Rowling's gender politics through fan fiction. By doing so, the article traces the complex politics of the reception of books for young people in the digital age, demonstrating that authors' powerful voices continue to shape readers' responses to texts long after their publication but showing, too, that readers often resist authors' attempts to influence not only their textual interpretations but their politics.

Young people's relationship to the digital economy is a key site of popular and policy attention within the context of shifts in labour market conditions globally. The massification of digital media and rapid growth of digital markets globally have brought significant challenges for policy makers in what counts as work and how best to prepare young people to engage with it. This has manifest in a proliferation of initiatives and policy orientations across much of the global North which have tended to focus on the importance of science, technology, engineering, and mathematics occupations, and, in particular, computing aimed at preparing young people for jobs of the future. The formalization of learn to code programs in school curriculum has been one such initiative. Despite the proliferation of coding and computational thinking curriculum across many countries, there remains a relative paucity of scholarship examining their embedding in educational policy debates. This article follows the announcement of the 'coding in schools' policy in Australia since its formal announcement by Opposition Leader Bill Shorten in his Budget Reply speech in May 2015. The announcement followed similar moves in other countries and has cemented 'coding in schools' as a literacy of 'the future' in the Australian political landscape. This article suggests that, while a policy focus on technical and instrumental skills such as computer coding may help young people to interact with dominant technologies of the present, they also risk weakening a more substantive conversation around educational participation and purpose in the present, and for the future.