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This study examined the predictive relationship among international students' sense of community, perceived learning, and end-of-course grades in computer-mediated, U.S. graduate-level courses. The community of inquiry (CoI) framework served as the theoretical foundation for the study. Step-wise hierarchical multiple regression showed no statistically significant relationship between the constructs of CoI (social presence, teaching presence, and cognitive presence), perceived learning, and end of course grades. These findings are contrary to previous research findings and initial development of a predictive model utilizing CoI and perceived learning in a non-international population, thus demonstrating that international students may not experience instruction and the instructional environment in the same way as non-international students. Findings hold important implications for the design and delivery of graduate level courses for the international student population and support the need to examine other predictive factors of international student achievement.

Work Integrated Learning is essential for healthcare degrees where students learn to become healthcare professionals. As a complex form of learning the quality of student placement experiences are variable, impacting student wellbeing and development of professional competencies. Getting it right, students enter the workforce ready to practice. Getting it wrong can have deleterious effects on all stakeholders. Although research has examined placement quality for students, less is known about the experiences of other stakeholder groups (e.g. placement educators, university academics and professional support staff). Our research addresses this gap. Using narrative interviewing methods, underpinned by social constructionism, we interviewed fifty-one participants: 19 allied healthcare students, 15 placement educators, 12 university academics and 5 professional staff from a large Australian university. We identified four preparedness themes impacting on placement quality, namely: University, Placement Site, Placement educator and Student preparedness. Within these themes, good practice is highlighted alongside examples of unsettling experiences. Curricula should be reviewed to ensure students are prepared as agentic learners for the complexities of the workplace. Furthermore, universities should co-design placements in partnership with healthcare organisations and educators to enable students to optimise their learning and contribution to patient/client care. [ABSTRACT FROM AUTHOR]

Chronic wounds, defined by their prolonged healing process, significantly impair patients' quality of life and impose a hefty financial burden on healthcare systems worldwide. Sex- and gender-specific mechanisms regulate inflammation and infection, angiogenesis, matrix synthesis and cell recruitment. All of these processes contribute to cutaneous wound healing but remain largely understudied. This review aims to spotlight the innovative realm of bioengineering and nanomedicine, which is at the helm of revolutionizing complex chronic wound care. It underscores the significance of integrating patient sex into the development and (pre)clinical testing of these avant-garde treatment modalities, in order to enhance healing prospects for all patients regardless of sex. Moreover, we explore the representation of male and female patients in clinical trials of bioengineered and nanomedicine products. Finally, we examine the primary reasons for the historical neglect in translating sex-specific wound healing research into clinical practice and propose strategic solutions. By tackling these issues, the article advocates advanced treatment frameworks that could significantly improve healing outcomes for individuals of all sexes, thereby optimizing both efficacy and inclusivity in chronic wound management. [ABSTRACT FROM AUTHOR]

The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goats in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Assembly using PacBio long-reads and Hi-C long-molecule scaffolding together with manual curation resulted in a 573 Mb assembly (N50 = 84 Mb, total scaffolds = 1,286) with five autosomal and one sex-linked chromosomal-scale scaffolds consistent with its karyotype. The genome resource was further improved via annotation of 22,948 genes, with manual curation of over 3,200 of these, resulting in a robust and near complete resource (96.3% complete protein BUSCOs) to support basic and applied research on this important veterinary pathogen. Genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes for benzimidazole, levamisole and ivermectin resistance, as well as novel regions associated with ivermectin and moxidectin resistance. These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance and identifying key loci to prioritise in developing diagnostic markers of anthelmintic resistance to support parasite control. Author summary: Understanding the genetics of anthelmintic resistance is a critical part of the sustainable control of parasitic worms. Here, we have generated a chromosome-scale genome assembly for the gastrointestinal nematode Teladorsagia circumcincta, one of the most important pathogens of sheep and goats in temperate climates worldwide. This genome and its annotation offer a substantial improvement over existing genetic resources and will enable new insight into the biology of this parasite and new opportunities to characterise therapeutic targets such as drug and vaccine candidates. We used this resource to map genetic variation associated with resistance to multiple anthelmintic drug classes used as the primary means of parasite control, confirming known candidate genes and variants (i.e., beta-tubulin isotypes 1 and 2 associated with benzimidazole resistance and acr-8 associated with levamisole resistance, and pgp-9 copy number variation, of which overexpression is associated broadly with anthelmintic resistance) and revealing new regions of the genome associated with drug treatment responses (i.e. 34–38 Mb on chromosome 5 associated with ivermectin resistance). Our results highlight the importance of a contiguous genome assembly and the use of complementary experimental approaches to reveal the impact of drug-mediated selection, both historically and directly in response to treatment, on genome-wide genetic variation. [ABSTRACT FROM AUTHOR]

Background: Electronic cigarettes (ECIGs) have grown in popularity, particularly among adolescents and young adults. Flavored ECIG-liquids (E-liquids) are aerosolized by these ECIGs and inhaled into the respiratory system. Several studies have shown detrimental effects of E-liquids in airway tissues, revealing that flavoring agents may be the most irritating component. However, research on the effects of E-liquids on biological processes of the oral cavity, which is the first site of aerosol contact, is limited. Hence, this study focuses on the effects of E-liquid flavors on oral epithelial cells using the OKF6/TERT-2 cell line model. Methodology: E-liquid was prepared with and without flavors (tobacco, menthol, cinnamon, and strawberry). OKF6/TERT-2 oral epithelial cells, cultured at 37 °C and 5% CO2, were exposed to 1% E-liquid ± flavors for 24 h. Outcomes determined include cell morphology, media pH, wound healing capability, oxidative stress, expression of mucin and tight junction genes, glycoprotein release, and levels of inflammatory cytokines (TNFα, IL-6, and IL-8). Results: Exposure to 1% flavored E-liquids negatively affect cellular confluency, adherence, and morphology. E-liquids ± flavors, particularly cinnamon, increase oxidative stress and production of IL-8, curtail wound healing recovery, and decrease glycoprotein release. Gene expression of muc5b is downregulated after exposure to E-liquids. In contrast, E-liquids upregulate occludin and claudin-1. Conclusions: This study suggests that ECIG use is not without risk. Flavored E-liquids, particularly cinnamon, result in pathophysiological responses of OKF6/TERT-2 cells. The dysregulation of inflammatory responses and cellular biology induced by E-liquids may contribute to various oral pathologies. [ABSTRACT FROM AUTHOR]

The current study sought to examine experiences of gender- and sexual-based harassment and discrimination within the Royal Canadian Mounted Police (RCMP), and what changes, if any, RCMP think are needed to address these issues within the organization. A representative sample of serving RCMP (n = 870; 72.6% men; 83.6% White) answered an open-ended survey question examining participants' perspectives of how the RCMP can work to eliminate harassment and discrimination in RCMP workplaces. Responses were analyzed inductively, using an open-coding approach. Thematic analysis was used to identify themes and frequency analysis was performed to assess for recurrent concrete recommendations. Three themes were identified: Walking the Talk: Broad Accountability; Out with the Old, in with the New: Largescale Cultural Change; and Alternative Perspective: An Exaggerated or Non-Existent Problem. The most common concrete recommendations were to enforce actual consequences (n = 172), to have more effective leadership (n = 138), and to change the promotion process (n = 116). The current results indicate that many RCMP conceptualize gender- and sexual-based harassment and discrimination within the RCMP as a two-tiered problem, involving the actions of individual perpetrators and insufficient organizational responses to those actions. Results further evidence individual and structural hegemonically masculine elements within the RCMP organizational culture. Participant suggestions provide possible actionable solutions. [ABSTRACT FROM AUTHOR]

The microtubule-associated protein Tau is a driver of neuronal dysfunction in Alzheimer's disease and other tauopathies. In this process, Tau initially undergoes subtle changes to its abundance, subcellular localization and a vast array of post-translational modifications including phosphorylation that progressively result in the protein's somatodendritic accumulation and dysregulation of multiple Tau-dependent cellular processes. Given the various loss- and gain-of-functions of Tau in disease and the brain-wide changes in the proteome that characterize tauopathies, we asked whether targeting Tau would restore the alterations in proteostasis observed in disease. Therefore, by phage display, we generated a novel pan-Tau antibody, RNJ1, that preferentially binds human Tau and neutralizes proteopathic seeding activity in multiple cell lines and benchmarked it against a clinically tested pan-Tau antibody, HJ8.5 (murine version of tilavonemab). We then evaluated both antibodies, alone and in combination, in the K3 tauopathy mouse model, showing reduced Tau pathology and improvements in neuronal function following 14 weekly treatments, without obtaining synergy for the combination. These effects were more pronounced in female mice. To investigate the molecular mechanisms contributing to improvements in neuronal function, we employed quantitative proteomics, phosphoproteomics and kinase prediction analysis to first establish alterations in K3 mice relative to wild-type controls at the proteome level. In female K3 mice, we found 342 differentially abundant proteins, which are predominantly involved in metabolic and microtubule-associated processes, strengthening previously reported findings of defects in several functional domains in multiple tauopathy models. We next asked whether antibody-mediated Tau target engagement indirectly affects levels of deregulated proteins in the K3 model. Importantly, both immunotherapies, in particular RNJ1, induced abundance shifts towards a restoration to wild-type levels (proteostasis). A total of 257 of 342 (∼75%) proteins altered in K3 were closer in abundance to wild-type levels after RNJ1 treatment, and 73% after HJ8.5 treatment. However, the magnitude of these changes was less pronounced than that observed with RNJ1. Furthermore, analysis of the phosphoproteome showed an even stronger restoration effect with RNJ1, with ∼82% of altered phosphopeptides in K3 showing a shift to wild-type levels, and 75% with HJ8.5. Gene set over-representation analysis further confirmed that proteins undergoing restoration are involved in biological pathways affected in K3 mice. Together, our study suggests that a Tau immunotherapy-induced restoration of proteostasis links target engagement and treatment efficacy. [ABSTRACT FROM AUTHOR]

Soluble programmed death ligand‐1 (sPD‐L1), a pivotal immune checkpoint protein, serves as a biomarker for evaluating the efficacy of cancer therapies. Aptamers, as highly stable and specific recognition elements, play an essential role in emerging point‐of‐care diagnostic technologies. Yet, crucial advancements rely on engineering the intricate interaction between aptamers and sensor substrates to achieve specificity and signal enhancement. Here, a comprehensive physicochemical characterization and performance optimization of a sPD‐L1 aptamer‐based biosensor by a complementary set of state‐of‐the‐art methodologies is presented, including atomic force microscopy‐based infrared spectroscopy and high‐resolution transmission electron microscopy, providing critical insights on the surface coverage and binding mechanism. The optimal nanoaptasensors detect sPD‐L1 across a wide concentration range (from am to μm) with a detection limit of 0.76 am in both buffer and mouse serum samples. These findings, demonstrating superior selectivity, reproducibility, and stability, pave the way for engineering miniaturized point‐of‐care and portable biosensors for cancer diagnostics. [ABSTRACT FROM AUTHOR]

Disruptive change in urban landscapes, such as large-scale tree planting, is complicated by the different priorities of the wide range of urban stakeholders. Here, we demonstrate an approach to the planning of urban green spaces using virtual reality simulations. We evaluate the health benefits (restorative benefits) and safety concerns of participants using virtual reconstructions of 10 urban parks in Bradford, UK, to simulate changes in woodland cover. Participants experienced each of the 10 parks as immersive environments with each of three scenarios: (i) no trees, (ii) real tree distribution, and (iii) doubling of tree numbers. Participants answered a short questionnaire while in each virtual park to quantify their feelings of safety and the restorative benefit that they thought they would experience. The results show that our VR approach produces reported restorative benefits that are not significantly different from those reported in the physical parks during visits by participants. We then demonstrate that increased tree cover is associated with significant increases in perceived restorative benefit, with some evidence of saturation at higher tree densities. Reductions in tree cover lead to a reduction in reported restorative benefit. We suggest that immersive technologies present a useful tool for the consultation and co-design of urban landscapes.

The Community of Inquiry framework has been widely supported by research to provide a model of online learning that informs the design and implementation of distance learning courses. However, the relationship between elements of the CoI framework and perceived learning warrants further examination as a predictive model for online graduate student success. A predictive correlational design and hierarchical multiple regression was used to investigate relationships between community of inquiry factors and perceived learning to determine the predictive validity of these variables for students' course points (N = 131), while controlling for demographic and course variables. The results of this study clearly supported the foundational constructs of Community of Inquiry (CoI) theory (Garrison et al., 2000) and the role of perceived learning to predict final course points. The entire predictive model explained 55.6% of the variance in course points. Implications, limitations, and recommendations are discussed.

Abstract Understanding how different online communities engage with COVID-19 misinformation is critical for public health response. For example, misinformation confined to a small, isolated community of users poses a different public health risk than misinformation being consumed by a large population spanning many diverse communities. Here we take a longitudinal approach that leverages tools from network science to study COVID-19 misinformation on Twitter. Our approach provides a means to examine the breadth of misinformation engagement using modest data needs and computational resources. We identify a subset of accounts from different Twitter communities discussing COVID-19, and follow these ‘sentinel nodes’ longitudinally from July 2020 to January 2021. We characterize sentinel nodes in terms of a linked domain preference score, and use a standardized similarity score to examine alignment of tweets within and between communities. We find that media preference is strongly correlated with the amount of misinformation propagated by sentinel nodes. Engagement with sensationalist misinformation topics is largely confined to a cluster of sentinel nodes that includes influential conspiracy theorist accounts. By contrast, misinformation relating to COVID-19 severity generated widespread engagement across multiple communities. Our findings indicate that misinformation downplaying COVID-19 severity is of particular concern for public health response. We conclude that the sentinel node approach can be an effective way to assess breadth and depth of online misinformation penetration.

Abstract Background There is a need for effective health service solutions to provide greater structure and support for implementing evidence‐based practice in back pain care. Patient involvement in developing these solutions is crucial to increase relevance, acceptability and uptake. Objectives To determine patients' perceived needs and barriers to best‐practice back pain care, and potential solutions to better address care needs. The study is the third in a series of needs assessment studies feeding into the ‘idea generation’ for service design in a large teaching hospital in a culturally and linguistically diverse community in metropolitan Sydney, Australia. Design We conducted a combination of focus groups and in‐depth interviews using an interpretive description approach. We used inductive thematic analysis to identify the main themes. Setting and Participants We purposively sampled patients with diverse characteristics from the neurosurgery and physiotherapy outpatient clinics, in particular those whose primary language was English, Arabic, Persian or Mandarin. Non‐English audio recordings were translated and transcribed by bilingual researchers. Results There were 24 participants (focus groups = 9; individual interviews = 15) when data saturation was reached. The analysis identified three key themes with several subthemes around what service designers needed to understand in helping people with back pain in this setting: (1) This is who I am; (2) It's not working for me; and (3) What I think I need. Discussion and Conclusion This study highlights that perceived unmet needs of patients are underpinned by unhelpful beliefs about the causes of and solutions for back pain, misaligned care expectations, unclear expectations of the hospital role and fragmentations in the health system. To design and implement a service that can deliver better back pain care, several solutions need to be integrated around: developing new resources that challenge unhelpful beliefs and set realistic expectations; improving access to education and self‐management resources; focusing on individualized care; using a collaborative multidisciplinary approach within the hospital; and better connecting with and directing primary health care services. Patient or Public Contribution A consumer representative of the Western Sydney Local Health District provided input during study conceptualisation and is duly recognized in the Acknowledgements section.

Ceftibuten, C15H14N4O6S2, with the systematic name (6R,7R)-7-{[(Z)-2-(2-amino-1,3-thiazol-4-yl)-4-carboxybut-2-enoyl]amino}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, is a third generation, orally administered cephalosporin antibiotic with broad antimicrobial activity and stability against extended spectrum β-lactamases. Ceftibuten can exist in various hydration states and to better understand the location of the water molecules of crystallization and their effect on the structure, the crystal structures of anhydrous (I) and hydrated (II) ceftibuten were determined and both occur as zwitterions with proton transfer from the carboxylate group adjacent to the β-lactam ring to the N atom of the thiazole ring. The β-lactam ring in (I) is almost planar but the equivalent grouping in (II) is slightly buckled. In the extended structure of (I), O—H...O and N—H...O hydrogen bonds link the molecules into a three-dimensional network. In (II), O—H...Oc, N—H...Oc, O—H...Ow, N—H...Ow and Ow—H...Ow (c = ceftibuten, w = water) hydrogen bonds link the components into a three-dimensional network. A large void space is present within the anhydrous crystal structure that can accommodate between two and three molecules of water.

Background: To refine an on-hen mite feeding device, an ethogram was employed to measure the reactions of hens during a routine experimental procedure (feather plucking) and to assess effects of analgesic cream on those reactions. Methods: Three experimental groups were used; one treated with EMLA 5% before plucking (“EMLA group”); one with aqueous cream (“placebo group”) and a “no treatment” group. Behaviours were measured and compared on three days: ‘dummy handling day’ i.e. no plucking; ‘plucking day’, plucking the left thigh; and ‘treatment day’ i.e with right thighs plucked post-treatment. Poultry red mite feeding assays were performed to examine effect of creams on mite feeding rates, mortality and fecundity. All data were analysed using generalised linear (mixed) modelling approaches. Results: Use of the ethogram demonstrated no significant difference in hen behaviours in the EMLA group between dummy handling day and treatment day (p = 0.949) alongside a significant reduction in measured behaviours between plucking day and treatment day in the same group (p = 0.028). There was a statistically significant increase in measured behaviours from the dummy handling day to the plucking day in both placebo (p = 0.011) and no treatment group (p < 0.001). Effect sizes and directions were similar between dummy handling and treatment days in the ‘placebo’ and ‘no treatment’ groups, though not statistically significant (placebo, p = 0.064; no treatment p = 0.069). Mite feeding in the EMLA group was significantly lower than in the no treatment group in feeding assay 1 (p = 0.029) only. Mite mortality and fertility were unaffected. Conclusions: The ethogram successfully measured changes in observed behaviours between the dummy handling session and procedures. No adverse effects of EMLA cream on hens were demonstrated at 3mg/kg in hens. Use of analgesia for this routine procedure improves hens’ experiences during experimental trials.

ObjectiveRoyal Canadian Mounted Police report experiencing extremely frequent potentially psychologically traumatic events (PPTE). In a recent study, approximately half of participating RCMP screened positive for one or more mental disorders, which is approximately five times the diagnostic proportion for the general Canadian population. Increased reporting of mental health symptoms been linked to PPTE exposures. Programs promoting physical activity may be useful interventions to supplement or pair with mental health interventions, providing anxiolytic, antidepressant, and stress-buffering effects. The current study was designed to assess the relationship between physical activity behaviors and reported mental health disorder symptoms of cadets during the Royal Mounted Canadian Police (RCMP) Cadet Training Program (CTP). The current study also examined the relationship between exercise and mental health disorder symptoms of cadets during the CTP.MethodsThe study included data from 394 cadets (76.1% male). An analysis of variance (ANOVA) and a series of t-tests were used to assess several differences across sociodemographic groups. Bivariate Spearman’s Rank correlations were performed between the average number of active calories burned per day, as recorded by Apple Watches, and changes in self-reported mental health disorder symptoms (i.e., Generalized Anxiety Disorder [GAD], Major Depressive Disorder [MDD], Posttraumatic Stress Disorder [PTSD], Social Anxiety Disorder [SAD]. Alcohol Use Disorders [AUD], Panic Disorder [PD]) from pre-training (starting the CTP) to pre-deployment (completing the CTP) 26 weeks later.ResultsThere were statistically significant correlations between physical activity and self-reported mental health disorder symptom scores during CTP. Cadets who performed more physical activity from pre-training to pre-deployment had statistically significantly greater decreases in symptoms of GAD (ρ = −0.472, p 0.05). There were also no statistically significant relationships between pre-CTP mental health disorder symptom scores and the volume of physical activity performed during CTP.ConclusionThere was evidence of a significant relationship between reductions in mental health disorder symptom scores and physical activity during the 26-week CTP. The results highlight the role that exercise can play as an important tool for reducing mental health disorder symptoms, considering there was no relationship between pre-CTP baseline mental health scores and physical activity performed during CTP. Further research is needed to understand differences in physical activity behaviours among cadets and serving RCMP.

Intro: New Zealand has a low burden of Tuberculosis (TB) with a mortality of 0.26 per 100,000. The aim of this audit was to review the cause of mortality, classify whether the death was TB-related and identify any associated factors for patients with TB who died prior to completion of treatment for TB in Auckland. Methods: A retrospective audit of clinical notes for adult TB patients (aged >15) who died prior to commencing or during TB treatment between 2009-2019 was performed. Cause of death was classified as a TB-related death if it was found to be directly related to TB. Findings: Of the 1738 TB cases notified, 86 (4.9%) patients died prior to completion of TB treatment; 6 were excluded from further analysis due to incomplete documentation. Of the remaining 80 patients, 60% were male and the median age was 70 (range 25-97). 45% patients were of Asian ethnicity, 31% Pacific Island, 13% Maori and 8% European. 45% were smear positive at presentation, 29% had disseminated TB disease and 5% had central nervous system TB disease. 41% of patients had diabetes, 36% had renal impairment and 23% had malignancy. 30% died prior to commencing TB treatment, with the majority having TB confirmed after death. Death was felt to be directly related to TB disease in 31 (39%) patients or in 31/1738 (1.8%) of the total cohort. Discussion: TB mortality, which is potentially preventable with early detection and treatment, continues to be significant in our low TB incidence setting. More data is needed to understand the role of older age, male sex, smear positivity, and diabetes as contributing factors for increasing mortality. Conclusion: This audit highlights the need for clinicians to be vigilant and consider a diagnosis of TB to enable timely diagnosis, especially in low TB burden settings.

The ratio of forage to concentrate in cattle feeding has a major influence on the composition of the microbiota in the rumen and on the mass of methane produced. Using methane measurements and microbiota data from 26 cattle we aimed to investigate the relationships between microbial relative abundances and methane emissions, and identify potential biomarkers, in animals fed two extreme diets - a poor quality fresh cut grass diet (GRASS) or a high concentrate total mixed ration (TMR). Direct comparisons of the effects of such extreme diets on the composition of rumen microbiota have rarely been studied. Data were analyzed considering their multivariate and compositional nature. Diet had a relevant effect on methane yield of +10.6 g of methane/kg of dry matter intake for GRASS with respect to TMR, and on the centered log-ratio transformed abundance of 22 microbial genera. When predicting methane yield based on the abundance of 28 and 25 selected microbial genera in GRASS and TMR, respectively, we achieved cross-validation prediction accuracies of 66.5 ± 9% and 85 ± 8%. Only the abundance of Fibrobacter had a consistent negative association with methane yield in both diets, whereas most microbial genera were associated with methane yield in only one of the two diets. This study highlights the stark contrast in the microbiota controlling methane yield between animals fed a high concentrate diet, such as that found on intensive finishing units, and a low-quality grass forage that is often found in extensive grazing systems. This contrast must be taken into consideration when developing strategies to reduce methane emissions by manipulation of the rumen microbial composition.

Abstract Room‐temperature detection of volatile organic compounds in particle‐per‐billion concentrations is critical for the development of wearable and distributed sensor networks. However, sensitivity and selectivity are limited at low operating temperatures. Here, a strategy is proposed to substantially improve the performance of semiconductor sensors. Tunable oxygen vacancies in thick 3D networks of metal oxide nanoparticles are engineered using deep ultraviolet photoactivation. High selectivity and sensitivity are achieved by optimizing the electronic structure and surface activity while preserving the 3D morphology. Cross‐sectional depth analysis reveals oxygen vacancies present at various depths (≈24% at a depth of 1.13 µm), with a uniform distribution throughout the thick films. This results in ≈58% increase in the sensitivity of ZnO to 20‐ppb ethanol at room temperature while ≈51% and 64% decrease in the response and recovery times, respectively. At an operating temperature of 150 °C, oxygen‐vacant nanostructures achieve a lower limit of detection of 2 ppb. Density functional theory analysis shows that inducing oxygen vacancies reduces activation energy for ethanol adsorption and dissociation, leading to improved sensing performance. This scalable approach has the potential for designing low‐power wearable chemical and bio‐sensors and tuning the activity and band structure of porous, thick oxide films for multiple applications.