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Background The treatment of osteoarthritis with knee replacement aims to reduce pain and disability. However, some people experience chronic pain. Objectives To improve outcomes for people with chronic pain after knee replacement by identifying post-surgical predictors and effective interventions, characterising patient pathways and resource use, developing and evaluating a new care pathway, and exploring non-use of services. Design The programme comprised systematic reviews, national database analyses, a cohort study, intervention development, a randomised controlled trial, health economic analyses, qualitative studies and stakeholder engagement. Extensive and meaningful patient and public involvement underpinned all studies. Setting NHS, secondary care, primary care. Participants People with, or at risk of, chronic pain after knee replacement and health-care professionals involved in the care of people with pain. Interventions A care pathway for the management of people with pain at 3 months after knee replacement. Main outcome measures Patient-reported outcomes and cost-effectiveness over 12 months. Data sources Literature databases, the National Joint Registry, Hospital Episode Statistics, patient-reported outcomes, the Clinical Practice Research Datalink, the Clinical Outcomes in Arthroplasty Study, the Support and Treatment After joint Replacement randomised trial, interviews with 90 patients and 14 health-care professionals, and stakeholder events. Review methods Systematic reviews of cohort studies or randomised trials, using meta-analysis or narrative synthesis. Results In the Clinical Outcomes in Arthroplasty Study cohort, 14% of people experienced chronic pain 1 year after knee replacement. By 5 years, 65% reported no pain, 31% fluctuated and 4% remained in chronic pain. People with chronic pain had a worse quality of life, higher primary care costs, and more frequent analgesia prescriptions, particularly for opioids, than those not in chronic pain. People with chronic pain after knee replacement who made little or no use of services often felt nothing more could be done, or that further treatments may have no benefit or cause harm. People described a feeling of disconnection from their replaced knee. Analysis of UK databases identified risk factors for chronic pain after knee replacement. Pre-operative predictors were mild knee pain, smoking, deprivation, body mass index between 35 and 40 kg/m2 and knee arthroscopy. Peri- and post-operative predictors were mechanical complications, infection, readmission, revision, extended hospital stay, manipulation under anaesthetic and use of opioids or antidepressants. In systematic reviews, pre-operative exercise and education showed no benefit in relation to chronic pain. Peri-operative interventions that merit further research were identified. Common peri-operative treatments were not associated with chronic pain. There was no strong evidence favouring specific post-operative physiotherapy content. We evaluated the Support and Treatment After joint Replacement care pathway in a multicentre randomised controlled trial. We randomised 363 people with pain at 3 months after knee replacement from eight NHS Trusts in England and Wales. At 12 months’ follow-up, the intervention group had lower mean pain severity (adjusted difference –0.65, 95% confidence interval –1.17 to -0.13; p = 0.014) and pain interference (adjusted difference –0.68, 95% confidence interval –1.29 to -0.08; p = 0.026), as measured on the Brief Pain Inventory subscales (scale 0–10). People receiving the Support and Treatment After joint Replacement pathway had lower NHS and Personal Social Services costs (–£724, 95% confidence interval –£150 to £51) and higher quality-adjusted life-years (0.03, 95% confidence interval –0.008 to 0.06) than those with usual care. The Support and Treatment After joint Replacement pathway was cost-effective with an incremental net monetary benefit at the £20,000 per quality-adjusted life-year threshold of £1256 (95% confidence interval £164 to £2348), indicating a 98.79% probability that the intervention is the cost-effective option. Participants found the Support and Treatment After joint Replacement pathway acceptable, with opportunities to receive information and discuss concerns while ensuring further treatment and support. In systematic reviews considering treatments for chronic pain after surgery we identified some unifactorial interventions that merit further research after knee replacement. Health-care professionals delivering and implementing the Support and Treatment After joint Replacement pathway valued its focus on neuropathic pain and psychosocial issues, enhanced patient care, formalised referrals, and improved pain management. Stakeholders supported pathway implementation. Limitations Database analyses were limited to factors recorded in data sets. Pain was only measured 6 months after surgery. However, analyses including large numbers of centres and patients should be generalisable across the NHS. In many studies found in systematic reviews, long-term pain was not a key outcome. Conclusions The Support and Treatment After joint Replacement pathway is a clinically effective and cost-effective, acceptable intervention for the management of chronic pain after knee replacement. Unifactorial interventions merit further study before inclusion in patient care. People with pain should be empowered to seek health care, with the support of health-care professionals. Future work Future work should include research relating to the implementation of the Support and Treatment After joint Replacement pathway into the NHS, an assessment of its long-term clinical effectiveness and cost-effectiveness and wider application, and an evaluation of new interventions for incorporation in the pathway. It will also be important to design and conduct research to improve communication between patients and health-care professionals before surgery; explore whether or not education and support can enable earlier recognition of chronic pain; consider research that may identify how to support people’s feelings of disconnectedness from their new knee; and design and evaluate a pre-surgical intervention based on risk factors. Study registration All systematic reviews were registered on PROSPERO (CRD42015015957, CRD42016041374 and CRD42017041382). The Support and Treatment After joint Replacement randomised trial was registered as ISRCTN92545361. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 11, No. 3. See the NIHR Journals Library website for further project information. Plain language summary People with severe knee osteoarthritis may have knee replacement surgery to reduce pain and disability. Although highly successful for many people, some people report long-term pain. Our research looked at why some people are more likely to have long-term pain, its personal and economic consequences, and how to prevent and treat it. We reviewed previous research; analysed UK health-care databases; interviewed and met with patients, surgeons and health-care professionals; and developed and evaluated a new care pathway for patients with pain after knee replacement. We found that about one in seven people experience significant pain 6 months after knee replacement. For many, pain fluctuates over time. Some people with long-term pain feel that nothing more can be done to help and that further treatments may even cause harm. Changes to aspects of patient health and care merit further research as they may prevent the development of long-term pain. The Support and Treatment After joint Replacement pathway comprises a detailed assessment by a trained health-care professional; referral to appropriate services, such as an orthopaedic surgeon, physiotherapist, general practitioner for treatment of depression or anxiety, or pain specialist; and telephone follow-up. A total of 363 people with pain at 3 months after their knee replacement were randomly allocated to receive either the Support and Treatment After joint Replacement pathway or their hospital’s usual care. Participants were followed for 1 year to assess their long-term pain. We also looked at health-care costs and the acceptability of the Support and Treatment After joint Replacement pathway to patients and health-care professionals. This research was supported by a dedicated patient advisory group. For people with pain after knee replacement, the Support and Treatment After joint Replacement pathway leads to reduced long-term pain severity and reduced interference with everyday life, and is acceptable to patients and health-care professionals. NHS, personal social services and patient costs were lower in the group receiving the Support and Treatment After joint Replacement pathway. Scientific summary Background Chronic pain after total knee replacement places considerable burden on individuals, society and the NHS. With nearly 100,000 patients receiving knee replacements in the NHS annually, around 20,000 patients will have chronic post-surgical pain. Pre-operative prediction of who will have chronic pain after knee replacement is of limited value, referral for assessment and care is inconsistent and varies widely, and people do not necessarily receive or seek care. This programme aimed to address these issues and provide evidence on improvements to patient care and service delivery. Objectives The programme aimed to improve outcomes for patients with chronic pain ≥ 3 months after total knee replacement. Specific programme objectives were as follows: 1.synthesise evidence on the effectiveness of interventions for preventing chronic pain after knee replacement and the treatment of chronic pain after diverse surgeries, and identify post-surgical predictors of chronic pain after knee replacement 2.characterise the long-term trajectory of chronic pain, including pain characteristics and resource use up to 5 years after total knee replacement 3.finalise an assessment process and a care pathway for patients with chronic pain after total knee replacement 4.evaluate the clinical effectiveness and cost-effectiveness of a new care pathway for patients with chronic pain after total knee replacement 5.identify reasons for non-use of services 6.make evidence-based suggestions about the best-practice care for patients with chronic pain after total knee replacement and evaluate the implementation of these. Methods To meet the objectives, we conducted six work packages. Work package 1: systematic reviews and analysis of national databases Systematic reviews of the following were carried out: post-surgical predictors of chronic pain after total knee replacement; the effectiveness of pre-, peri- and post-operative interventions for chronic pain after total knee replacement; and the effectiveness of interventions for chronic pain after diverse surgeries. In addition, we undertook an analysis of data from the National Joint Registry (NJR) linked to Hospital Episode Statistics (HES) and Patient Reported Outcome Measures (PROMs) databases to identify post-operative predictors of chronic pain. Work package 2: long-term follow-up and analysis of databases Using the annual follow-up of the Clinical Outcomes in Arthroplasty Study (COASt) cohort of patients with total knee replacement, we were able to collect pain and resource use data for 5 years after surgery. We also analysed the Clinical Practice Research Datalink (CPRD), linked to the Hospital Episode Statistics (HES) and Patient Reported Outcome Measures (PROMs) database, to characterise the natural history of chronic pain after total knee replacement, including resource use. Work package 3: finalisation of an assessment protocol and care pathway Consensus questionnaires completed by and meetings with health-care professionals were used to refine our previously developed intervention. We also tested intervention delivery and acceptability with 10 patients and evaluated the views of 10 health-care professional stakeholders on future implementation using a questionnaire based on the Normalisation Measure Development (NoMAD) instrument. Work package 4: randomised controlled trial The multicentre Support and Treatment After joint Replacement (STAR) randomised controlled trial was carried out with 363 participants to evaluate the clinical effectiveness and cost-effectiveness of a new care pathway for patients with chronic pain after total knee replacement. The primary follow-up time point was 12 months post randomisation and the coprimary outcomes were the Brief Pain Inventory (BPI) severity and interference scales (scored 0–10), with the minimal clinically important difference pre-specified as 1 point on either scale. Two embedded qualitative studies with 56 patients explored trial processes and acceptability of the intervention. Work package 5: qualitative study We undertook a qualitative interview study with 34 people with chronic pain after total knee replacement who made little or no use of formal health-care services and explored reasons for non-use of services. Work package 6: implementation and dissemination Interviews, based on the NoMAD instrument, were carried out with 14 health-care professionals who implemented the intervention within the trial. An online meeting, short animated film and survey were all used to communicate findings to key stakeholders and engage health-care professionals in maximising the embedding of the intervention in practice. A range of dissemination activities to engage health-care professionals, researchers, policy-makers, patients and the public were undertaken. Patient and public involvement Patient and public involvement was integral to the programme’s design and remained at its core during the programme. We worked with an existing patient forum and developed a complementary group focusing exclusively on chronic pain after total knee replacement. Contributions of this group included the design of study materials and processes, research management and dissemination strategies. Results Work package 1: systematic reviews Our systematic review of post-operative risk factors for chronic pain after total knee replacement included 14 studies published up to October 2016, with data from 1168 people. Studies focused on acute pain, function and psychological factors. Risk factor measures and outcomes were heterogeneous. In a narrative synthesis we were unable to draw firm conclusions on potential interventions. The need for further prospective studies in representative populations was clear. Research published up to December 2018 into pre-operative interventions mainly focused on exercise and education. In the eight trials, with a total of 960 people randomised, there was no association with these interventions and long-term pain outcomes. In the peri-operative setting, we identified 44 trials published up to February 2018, with a range of 10 to 280 people randomised. Unifactorial interventions including some forms of analgesia, early rehabilitation, electrical muscle stimulation and anabolic steroids were associated with improved long-term pain outcomes. However, studies were small and merit further evaluation. There was reassurance that some common peri-operative treatments are not associated with chronic pain. Post-operative interventions evaluated in 17 trials published up to November 2016, with a total of 2485 people randomised, mainly focused on physiotherapy. There was no strong evidence favouring one format of therapy over another. There has been little research into treatments for chronic pain after total knee replacement. Considering interventions for general chronic post-surgical pain, we identified 66 randomised trials with a total of 3149 participants in our systematic review with searches up to March 2016. A more focused updated search including treatments for chronic pain after arthroplasty of the large joints was conducted in October 2020. Many unifactorial interventions have been evaluated, and specific nerve-focused treatments deserve further research. Work packages 1 and 2: analysis of national databases We undertook two analyses of linked databases to identify pre-, peri- and post-operative risk factors for chronic pain outcome. In the first analysis with NJR and HES data, the pre- and 6-month-post-operative Oxford Knee Scores (OKS) was available for 258,386 patients, 43,702 (16.9%) of whom were identified as having chronic pain at 6 months post surgery. Post-surgical predictors of chronic pain were mechanical complication of prosthesis, surgical site infection, readmission, reoperation, revision and an extended hospital stay. However, these post-surgical predictors explained only a limited amount of variability in chronic pain outcome. In the second analysis, we analysed primary care data from CPRD and secondary care data from the HES–PROMs database and included 4570 patients. At 6 months after surgery, 10.4% of patients were classified as non-responders to surgery regarding their knee pain. Expressing the effects as absolute risk differences allowed us to quantify the relative importance of individual risk factors in terms of the absolute proportions of patients achieving poor pain outcomes. Pre-operative risk factors were having only mild knee pain symptoms, currently smoking, living in the most deprived areas, having a body mass index between 35 and 40 kg/m2 and having had previous knee arthroscopy surgery. Post-operative risk factors were revision surgery and manipulation under anaesthetic within 3 months after the operation, and use of opioids and antidepressants within 3 months after surgery. Work package 2: long-term follow-up of COASt cohort and analysis of national databases We characterised the long-term trajectory of chronic pain, including pain characteristics and resource use, through the 5-year follow-up of the COASt cohort of 1581 patients with total knee replacement, and analysis of the linked CPRD and HES databases. We applied cluster analysis to data on 128,145 patients with primary total knee replacement included in the English PROMs programme to derive a cut-off point on the pain subscale of the OKS. A high-pain group was identified, defined as those with a score of ≤ 14 points on the OKS pain subscale 6 months after total knee replacement. About one in eight people experienced chronic pain 1 year after total knee replacement. Of these patients with chronic pain after surgery, after imputing significant missing data assumed to be missing at random, 65% experienced no-chronic-pain by year 5, 31% fluctuated and 4% remained in chronic pain. People with chronic pain in year 1 had worse quality of life to start with; this improved, but less rapidly than for those not in chronic pain. People with chronic pain reported slightly higher primary care consultation costs than those not in chronic pain but their prescriptions for analgesia were much more frequent, more costly to the health-care system and continued to grow even after surgery, especially prescriptions for opioids. Work package 3: finalisation of an assessment protocol and care pathway We refined and finalised the novel STAR care pathway and associated training materials. The STAR care pathway involves a clinic appointment for patients who have troublesome pain at 3 months after surgery. A specially trained extended scope practitioner (ESP) conducts a clinic assessment with the patient, comprising history, examination, radiography and questionnaire completion. Based on this assessment, which focuses on understanding the reasons for and impact of the pain, the patient is referred to the appropriate existing services for treatment, such as a surgeon, general practitioner (GP) or specialist, or receives ongoing monitoring. The ESP follows up with patients by telephone for up to 12 months. Work package 4: randomised controlled trial In a multicentre pragmatic, open randomised controlled trial, we evaluated the STAR care pathway. We screened 5036 people, randomised 363 patients with pain at 3 months after knee replacement from eight NHS Trusts in England and Wales and collected 12-month outcomes from 313 (85%) randomised participants. The sample had a mean age of 67 years, was 60% female and 94% white. Our analysis of clinical effectiveness indicated that at 12 months the intervention arm had lower mean pain severity and lower mean pain interference than the usual care arm. For pain interference at 12 months, the adjusted difference in means was –0.68 points on the Brief Pain Inventory pain interference scale [95% CI –1.29, –0.08; p = 0.026]. For pain severity at 12 months, the adjusted difference in means was –0.65 points on the Brief Pain Inventory pain severity scale [95% CI –1.17, –0.13; p = 0.014]. Our analysis of cost-effectiveness indicated that people receiving the STAR pathway from an NHS and personal social services perspective had lower costs (–£724, 95% CI -£1500 to £51) and more quality-adjusted life-years (QALYs) (0.03, 95% CI –0.008 to 0.06) than those receiving usual care. The STAR pathway was the cost-effective option: the incremental net monetary benefit at the £20,000-per-QALY threshold was £1256 (95% CI £164 to £2348). This was also the case from a patient perspective. Embedded qualitative research found that patients thought that the STAR pathway was acceptable, and patients described how it provided an opportunity for them to discuss their concerns and to receive more information about their condition while ensuring they received further treatment and ongoing support. Work package 5: qualitative study In semistructured interviews with 34 people, we found that people with chronic pain after total knee replacement who made little or no use of services did so because they became stuck in a cycle of appraisal of the validity of their need for help and concern that treatment may not be of benefit. Some were concerned that further treatment may even worsen their pain or cause further harm. When describing chronic post-surgical pain, some participants described sensations of discomfort including heaviness, numbness, pressure and tightness associated with the prosthesis, and some also reported a lack of felt connection with their knee as their movement was no longer natural and required deliberate attention, and that they had a lack of confidence in it. Work package 6: implementation and dissemination We found that health-care professionals involved in the delivery and implementation of the STAR care pathway valued its focus on the identification of neuropathic pain and psychosocial issues, enhanced patient care, formalisation and validation of referral practices and an increased knowledge of pain management. Stakeholders supported formal implementation of the STAR pathway. Whether or not this would be supported by hospital management was felt to be dependent on whether or not it was shown to be cost-effective. Conclusions: implications for health care After knee replacement, screening for pain with the OKS pain subscale beginning at 2 months after surgery can facilitate the delivery of targeted care from 3 months. Our findings indicate that the STAR care pathway can provide improved care and outcomes for people who have pain after knee replacement. To our knowledge, the STAR care pathway is the first multifactorial intervention for the treatment of post-surgical pain to have been evaluated in a randomised controlled trial. In database analyses and systematic reviews, we identified risk factors for and univariable interventions to prevent or treat chronic pain. After further research these may provide additional components to the care pathway. Our work also indicates that people with pain could be empowered to seek health care and that health-care professionals can be encouraged provide support. This could include information for people living with chronic pain to inform them that health care may provide benefit and that seeking care is not futile. Informing patients of the likely outcomes after surgery may be a key part of pre- and post-surgical care. Recommendations for research We recommend that further research addresses the following points, numbered in descending order of priority: 1.How to implement the STAR care pathway into the NHS. 2.How to improve communication between patients and professionals before surgery. 3.Whether or not patient education and supportive care can enable earlier recognition of chronic pain. 4.The STAR care pathway showed benefit to patients for both pain and interference at 6 and 12 months. Further follow-up would describe the longer-term outcomes of this intervention and the health-care resources utilised by participants. 5.How to reshape the STAR pathway for other surgeries. 6.The STAR programme focused on care after surgery. Future research could make use of the recently developing evidence base about the time before surgery as an opportunity for intervention. Specifically, we now have a greater understanding of risk factors for poor outcome and using this understanding to design and evaluate pre-surgical intervention may prove of long-term benefit to patients and health-care systems. 7.How to better manage patient’s feelings of disconnectedness from the new knee and sensations of otherness to improve incorporation of the prosthesis. 8.Promising interventions, identified in systematic reviews and suggested by our risk factor studies, should be evaluated in appropriately powered high-quality randomised controlled trials. 9.New interventions with evidence of effectiveness in the treatment of chronic pain after knee replacement should be considered as new components of multifaceted personalised care as delivered in the STAR intervention. Study registration All systematic reviews were registered on PROSPERO (CRD42015015957, CRD42016041374 and CRD42017041382). The STAR randomised trial was registered as ISRCTN92545361. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 11, No. 3. See the NIHR Journals Library website for further project information.

Training the next generation of public health practitioners to promote health equity requires public health graduate programs to cultivate students' skills in community partnership. The Council on Education for Public Health (CEPH) requires Master of Public Health (MPH) students to produce a high-quality written product as part of their culminating Integrative Learning Experience (ILE). Because CEPH recommends that ILE written products be useful to community partners, ILEs can draw lessons from the field of experiential education, especially the social justice aligned principles of critical service-learning (CSL). However, the current literature lacks descriptions of how to operationalize CSL's principles within graduate-level culminating experiences. To help fill this gap, we discuss a CSL ILE for MPH students, called Capstone. We describe CSL's key components and explain and assess how each is operationalized. We hope Capstone's model will help educators engage more deeply with CSL practices to advance health equity.

Interpretative phenomenological analysis was used to explore the simultaneous supervision experiences of counselors-in-training. Simultaneous supervision is when a supervisee receives clinical supervision from multiple supervisors. Sometimes this supervision includes a university supervisor and a site supervisor. Other times this supervision occurs when a student has multiple sites in one semester and receives supervision at each site. Counselors-in-training described their experiences with simultaneous supervision during the course of their education. Four superordinate themes emerged: making sense of multiple perspectives, orchestrating the process, supervisory relationship dynamics, and personal dispositions and characteristics. Results indicated that counselors-in-training experienced compounded benefits and challenges. Implications for supervisors, supervisees, and counselor education programs are provided.

The internationalisation of higher education presents an increasingly urgent need to explore how universities can become more welcoming places for all students. Top-down implementation of widening participation and the inclusion of a more diverse and less prepared student population in higher education have led to social and academic exclusion, with systems failing to accommodate this change to support the less prepared intakes. Academic and social/cultural drivers are the key areas for bottom-up implementation of internationalisation strategies to support this influx and change in student profile. However, institutionalised separation of home and international students for academic support and language development provision, and separation of this support from subject disciplines, have increased the obstacles that block inclusive practice. An internationalised campus involves both top-down institutionalised intervention and bottom-up intervention of the academic self, enabling the potential for intercultural construction within and between communities, and promoting agency of the self in connection with others to enact change. Viewing university campuses as intercultural spaces that all students and staff need to navigate and inhabit has implications that this article explores through the lens of social justice and from the bottom-up perspective of language development provision, within the field of English for Academic Purposes, in an arts-based university.

This narrative qualitative study explored how sorority members negotiated their identities within systems of hegemony with their student communities. Sorority members used women's empowerment discourse to rationalize how they consumed alcohol, engaged in frequent consensual sexual relationships, and navigated relationships with fraternity men and across their campus sorority/fraternity communities. Implications for practice included harm reduction, sex education, and supportive policies.

We are a group of teaching-focused academics who share a passion for learning, teaching and the Scholarship of Teaching and Learning (SoTL) in Higher Education (HE). In order to understand how practitioners from a diversity of backgrounds and disciplines came to be in their present LTS (Learning, Teaching & Scholarship) academic roles, we embarked on a Collaborative Autoethnography (CAE). This approach allowed us to use our personal narratives to explore what it means to be a SoTL practitioner in HE, and to analyse these narratives by using textual analysis. This paper unpacks these narratives, focusing on three themes: our rich and diverse backgrounds, influences on our routes to our current academic roles, and how we are loud and proud to be on a teaching-focused career path. It will be of interest to academics who are on, or contemplating, a teaching focused contract. It will also be of relevance to senior staff in HE who wish to understand the nature of these roles, and who wish to consider how to provide appropriate institutional structures to support and nurture these staff.

Understanding students' learning of knowledge components (KCs) is an important educational data mining task and enables many educational applications. However, in the domain of computing education, where program exercises require students to practice many KCs simultaneously, it is a challenge to attribute their errors to specific KCs and, therefore, to model student knowledge of these KCs. In this paper, we define this task as the KC attribution problem. We first demonstrate a novel approach to addressing this task using deep neural networks and explore its performance in identifying expert-defined KCs (RQ1). Because the labeling process takes costly expert resources, we further evaluate the effectiveness of transfer learning for KC attribution, using more easily acquired labels, such as problem correctness (RQ2). Finally, because prior research indicates the incorporation of educational theory in deep learning models could potentially enhance model performance, we investigated how to incorporate learning curves in the model design and evaluated their performance (RQ3). Our results show that in a supervised learning scenario, we can use a deep learning model, code2vec, to attribute KCs with a relatively high performance (AUC > 75% in two of the three examined KCs). Further using transfer learning, we achieve reasonable performance on the task without any costly expert labeling. However, the incorporation of learning curves shows limited effectiveness in this task. Our research lays important groundwork for personalized feedback for students based on which KCs they applied correctly, as well as more interpretable and accurate student models.

The abrupt shift to online instruction that occurred in spring 2020, often referred to as emergency remote teaching (ERT), caught many world language educators off guard. To prepare for future disruptions to face-to-face learning and illustrate promising online teaching practices that emerged during this extended period of time that could serve to expand and enhance world language instruction, it is important to understand how ERT influenced K-12 world language programs around the world. To help the world language teaching community better understand how ERT influenced world language instruction, a team of researchers collected interview data from world language teachers and students in the United States and Germany. Results confirmed that instruction was negatively impacted by the sudden shift to online formats, explained how and why instruction was influenced, and identified promising practices exhibited by teachers to mitigate the negative impact of ERT. World language teachers, stakeholders, and school leaders may wish to consider the results of this study to lessen the impact of future disruptions to on campus learning and to enhance the growing presence of online learning in schools.

Background: Utility-value (UV) classroom interventions typically involve students completing assignments that involve writing about the usefulness of the course material. They are widely recommended and have received some empirical support. Objective: This study tested the effectiveness of a UV intervention in an online research methods course. It was a conceptual replication of a study by Hulleman et al. (2017, Study 2). Method: Students (N = 264) were randomly assigned to complete three assignments that required them to write about the usefulness of course material or three assignments that required them to summarize course material. The groups were compared in terms of their scores on a research methods knowledge test, their final papers, their final exams, and their final point totals, along with measures of the interestingness and usefulness of the course material. Results: There were no differences between conditions on any of the outcome variables. Conclusion: The UV intervention was ineffective. Further research is needed to establish the conditions under which such interventions are and are not effective. Teaching Implications: UV interventions do not necessarily improve student performance. Instructors who use them should consider doing so in a way that allows for an assessment of their effect in their local context.

BACKGROUND: Affirming spaces have been associated with improved mental health outcomes for lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) adolescents. METHODS: With data from adolescents currently enrolled in middle or high school across the United States, this study used topic modeling methods to examine students' reports of what they were looking for in LGBTQ-affirming schools and, separately, the association of LGBTQ-affirming schools with suicide risk reduction. RESULTS: Topic models demonstrated consistent themes in how students determined that their school was affirming, such as LGBTQ clubs, teachers requesting pronouns, pride flags, and accepting peers. Students of color uniquely looked for actionable responses in addressing LGBTQ issues. Transgender and nonbinary students required explicit mention of support for transgender issues. Quantitatively, LGBTQ students who reported that their school was LGBTQ-affirming had 20% lower odds of attempting suicide in the past year (adjusted odds ratio = 0.80). CONCLUSIONS: These findings suggest that schools must be safe for all youth and implementing policies that make LGBTQ students feel seen and supported in their identities is a protective factor for mental health. IMPLICATIONS: School policies must ensure that youth have access to supportive people, symbols of support, and LGBTQ clubs and that they are also salient to LGBTQ students of color and transgender and nonbinary students.

Project INTERprofessional Autism Collaborative Training (INTERACT) is an interprofessional education program designed to prepare graduate students in psychology, special education, and speech-language pathology to work with autistic children with moderate to severe intellectual disabilities. The rising prevalence of autism, coupled with increased appreciation for interprofessional approaches to service delivery, indicates the need for university training programs to prepare graduate students to work interprofessionally with this population; yet descriptions of such programs and their effectiveness are not reported in the literature. In this article, we explain the process through which an interprofessional faculty team developed Project INTERACT, describe the sequence of coursework and team-based clinical experiences that comprise the program, and present preliminary data regarding its effectiveness. Twenty-four graduate students in psychology, special education, and speech-language pathology participated in this quantitative study. We report results from three rating scales that participants completed at program entry, midpoint, and program exit. Participants endorsed positive attitudes toward interprofessional practice and demonstrated high levels of knowledge about autism. Self-rated knowledge and abilities in interprofessional practice increased significantly by program exit. Project INTERACT scholars developed knowledge and skills related to understanding, assessing, and treating autistic children with intellectual disabilities, through the lens of team-based interprofessional collaboration. We discuss implications for practice with Project INTERACT.

The rapid evolution of viruses generates proteins that are essential for infectivity and replication but with unknown functions, due to extreme sequence divergence1. Here, using a database of 67,715 newly predicted protein structures from 4,463 eukaryotic viral species, we found that 62% of viral proteins are structurally distinct and lack homologues in the AlphaFold database2,3. Among the remaining 38% of viral proteins, many have non-viral structural analogues that revealed surprising similarities between human pathogens and their eukaryotic hosts. Structural comparisons suggested putative functions for up to 25% of unannotated viral proteins, including those with roles in the evasion of innate immunity. In particular, RNA ligase T-like phosphodiesterases were found to resemble phage-encoded proteins that hydrolyse the host immune-activating cyclic dinucleotides 3',3'- and 2',3'-cyclic GMP-AMP (cGAMP). Experimental analysis showed that RNA ligase T homologues encoded by avian poxviruses similarly hydrolyse cGAMP, showing that RNA ligase T-mediated targeting of cGAMP is an evolutionarily conserved mechanism of immune evasion that is present in both bacteriophage and eukaryotic viruses. Together, the viral protein structural database and analyses presented here afford new opportunities to identify mechanisms of virus-host interactions that are common across the virome.

Archaea are widespread in the environment and play fundamental roles in diverse ecosystems; however, characterization of their unique biology requires advanced tools. This is particularly challenging when characterizing gene function. Here, we generate randomly barcoded transposon libraries in the model methanogenic archaeon Methanococcus maripaludis and use high-throughput growth methods to conduct fitness assays (RB-TnSeq) across over 100 unique growth conditions. Using our approach, we identified new genes involved in nutrient utilization and response to oxidative stress. We identified novel genes for the usage of diverse nitrogen sources in M. maripaludis including a putative regulator of alanine deamination and molybdate transporters important for nitrogen fixation. Furthermore, leveraging the fitness data, we inferred that M. maripaludis can utilize additional nitrogen sources including ʟ-glutamine, ᴅ-glucuronamide, and adenosine. Under autotrophic growth conditions, we identified a gene encoding a domain of unknown function (DUF166) that is important for fitness and hypothesize that it has an accessory role in carbon dioxide assimilation. Finally, comparing fitness costs of oxygen versus sulfite stress, we identified a previously uncharacterized class of dissimilatory sulfite reductase-like proteins (Dsr-LP; group IIId) that is important during growth in the presence of sulfite. When overexpressed, Dsr-LP conferred sulfite resistance and enabled use of sulfite as the sole sulfur source. The high-throughput approach employed here allowed for generation of a large-scale data set that can be used as a resource to further understand gene function and metabolism in the archaeal domain.IMPORTANCEArchaea are widespread in the environment, yet basic aspects of their biology remain underexplored. To address this, we apply randomly barcoded transposon libraries (RB-TnSeq) to the model archaeon Methanococcus maripaludis. RB-TnSeq coupled with high-throughput growth assays across over 100 unique conditions identified roles for previously uncharacterized genes, including several encoding proteins with domains of unknown function (DUFs). We also expand on our understanding of carbon and nitrogen metabolism and characterize a group IIId dissimilatory sulfite reductase-like protein as a functional sulfite reductase. This data set encompasses a wide range of additional conditions including stress, nitrogen fixation, amino acid supplementation, and autotrophy, thus providing an extensive data set for the archaeal community to mine for characterizing additional genes of unknown function.

In the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome.

PURPOSE: Minimal residual disease (MRD) detection can identify the recurrence in patients with colorectal cancer (CRC) following definitive treatment. We evaluated a plasma-only MRD assay to predict recurrence and survival in patients with metastatic CRC who underwent curative intent procedures (surgery and/or radiotherapy), with or without (neo)adjuvant chemotherapy. The primary objective of this study was to assess the correlation of postprocedure tumor cell-free DNA detection status with radiographic disease recurrence. EXPERIMENTAL DESIGN: Preprocedure and postprocedure longitudinal samples were collected from 53 patients and analyzed with a multiomic MRD assay detecting circulating tumor DNA (ctDNA) from genomic and epigenomic signals. Preprocedure and postprocedure ctDNA detection correlated with recurrence-free and overall survival (OS). RESULTS: From 52 patients, 230/233 samples were successfully analyzed. At the time of data cutoff, 36 (69.2%) patients recurred with median follow-up of 31 months. Detectable ctDNA was observed in 19/42 patients (45.2%) with ctDNA analyzed 3 weeks postprocedure. ctDNA detection 3 weeks postprocedure was associated with shorter median recurrence-free survival (RFS; HR, 5.27; 95% CI, 2.31-12.0; P < 0.0001) and OS (HR, 12.83; 95% CI, 3.6-45.9; P < 0.0001). Preprocedure ctDNA detection status was not associated with RFS but was associated with improved OS (HR, 4.65; 95% CI, 1.4-15.2; P = 0.0111). Undetectable ctDNA preprocedure had notable long-term OS, >90% 3 years postprocedure. CONCLUSIONS: In this cohort of oligometastatic CRC, detection of ctDNA preprocedure or postprocedure was associated with inferior outcomes even after accounting for known prognostic clinicopathologic variables. This suggests ctDNA may enhance current risk stratification methods helping the evaluation of novel treatments and surveillance strategies toward improving patient outcomes.