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The field of adapted physical activity (APA) and other areas often associated with APA focused on physical activity for people with disabilities, such as adapted physical education (APE) and disability sports (DS), is often marginalized and misunderstood. Little attention has been given to subsets of the general population’s familiarity of this field and related areas. The purpose of this study was to examine college students’ awareness of APA terminology and related organizations. Undergraduate students from 2 U.S. universities (n= 995) completed a survey on their familiarity of APA terminology (APE, DS, and therapeutic recreation [TR]) and related organizations (Paralympics [PL], and Special Olympics [SO]). Students were most familiar with SO, DS, and PL. Familiarity with these terms and organizations, except for TR, were positively associated with being comfortable with people with disabilities (p< .01). Students who reported having a close connection to a person with a disability were significantly more familiar with DS and SO (p= .001). Students with personal connections to people with disabilities appeared to be more aware of APA-related professions and associations. As future leaders, college students can influence the direction of future public policies and resources; thus, because these findings suggests that college students lack the basic familiarity with many APA-related areas, this insinuates that these areas may suffer from a lack of support policies and resources needed to flourish. Further research is needed to fully understand the relationships college students have with people with disabilities and how these may have more awareness of APA-related professions and associations.

Cardiovascular diseases are the leading cause of death globally, and atherosclerosis is the major contributor to the development and progression of cardiovascular diseases. Immune responses have a central role in the pathogenesis of atherosclerosis, with the complement system being an acknowledged contributor. Chronic activation of liver-derived and serum-circulating canonical complement sustains endothelial inflammation and innate immune cell activation, and deposition of complement activation fragments on inflamed endothelial cells is a hallmark of atherosclerotic plaques. However, increasing evidence indicates that liver-independent, cell-autonomous and non-canonical complement activities are underappreciated contributors to atherosclerosis. Furthermore, complement activation can also have atheroprotective properties. These specific detrimental or beneficial contributions of the complement system to the pathogenesis of atherosclerosis are dictated by the location of complement activation and engagement of its canonical versus non-canonical functions in a temporal fashion during atherosclerosis progression. In this Review, we summarize the classical and the emerging non-classical roles of the complement system in the pathogenesis of atherosclerosis and discuss potential strategies for therapeutic modulation of complement for the prevention and treatment of atherosclerotic cardiovascular disease.

ABSTRACTAs health systems emerge from the pandemic, academic medical centres are motivated to have a healthy and resilient workforce. In the face of the collective traumas of the pandemic, we took a systems approach to infuse wellness into our culture by modelling collective recovery in a non-traditional town hall. Over a dozen senior leaders, faculty, staff, and students shared their personal experiences in a virtual forum, nearly 1000 attendees communally supported one another. Since the town hall, a recording of the experience has been broadly viewed, messaging from leaders proliferated, and smaller versions of the same exercise were implemented. At a time when academic medical centres faced multiple challenges, we chose to first value the well-being of our staff at a system-wide level. It is our hope that other academic medical centres leverage our story to hold space for the experiences of the people who make their work possible.

ABSTRACTPartial hospital programs (PHPs) represent an important part of the continuum of care for youth with severe and/or refractory OCD, yet little is known about clinical or utilization outcomes in this setting. The current study aimed to characterize symptom improvement and length of stay (LOS) among 185 youth with OCD treated in a PHP setting and to identify demographic, clinical, and treatment characteristics that predict these outcomes. Results demonstrate a 77.3% treatment response rate and a median LOS of 52 days. Holding other predictors constant, less symptom improvement was observed for youth with lower symptom severity at admission, in a racial or ethnic minoritized group, without comorbid anxiety, and receiving more treatment hours per day. Shorter LOS was observed among youth with public (vs. commercial) insurance, receiving more hours of treatment per day, and not taking a serotonin reuptake inhibitor (SRI). Clinical implications and directions for future research are discussed, including a critical need to understand and improve outcomes for minoritized youth.

Contribution: This study explores industry members’ perceptions about the ABET-based accreditation in a developing country, using the case study of a program in a publicly funded polytechnic university in Ecuador. Background: Engineering programs often seek international accreditations to enhance the education quality, align with the global standards or gain academic reputation. ABET-based accreditation originates in United States, and thus presents some challenges for institutions in developing countries. Intended Outcomes: This study aimed to investigate the significance of international academic accreditation, as seen through the perspective of industry members. It focused on identifying fundamental competencies valued by employers and aimed to provide insights for institutions in similar contexts. Application Design: The research employed an approach informed by a qualitative methodology, involving in-depth interviews with five industry members who had served on the advisory committee board of an engineering program from a higher education institution in Ecuador. Findings: The findings identified three main areas of competencies that the industry members value: communication skills for teamwork, a problem-solving orientation, and an ability for effective task planning. The study also showed that these industry members value international accreditation as a means for enhancing education quality and ensuring graduates develop the necessary skills and competencies, yet the overall awareness with their peers remains relatively low.

ARL is the bimonthly report on research library issues and actions from ARL (Association of Research Libraries), CNI (Coalition of Networked Information), and SPARC (Scholarly Publishing and Academic Resources Coalition). ARL reports on current issues of interest to academic and research library administrators, staff, and users; higher education administrators and faculty; information technologists and those who depend on networked information; as well as anyone concerned with the future of scholarly communication or information policy developments. Each issue explores a broad range of education topics of particular importance to research institutions and academic librarians. This August 2004 issue consists of the following two articles: (1) A Snapshot in Time: ARL Libraries and Electronic Journal Resources (Mary M. Case); and (2) ARL Membership Examines Systemic Change at 144th Meeting (Judith Matz).

Prescription opioids are used for managing pain in persons with cancer, however, there are socioeconomic and racial disparities in medication access. Cannabis is increasingly used for cancer symptom management and as an opioid alternative. Limited data are available about patterns of opioid and cannabis use among patients with cancer. We used survey data from 4 National Cancer Institute–designated cancer centers in 3 states (n = 1220) to assess perceptions, use of cannabis and opioids for pain, their substitution, and racial and ethnic differences in each outcome. Compared with White patients, Black patients were less likely to use opioids for pain (odds ratio [OR] = 0.66; P =.035) and more likely to report that cannabis was more effective than opioids (OR = 2.46; P =.03). Race effects were mitigated (P> .05) after controlling for socioeconomic factors. Further research is needed to understand cannabis and opioid use patterns and how overlapping social determinants of health create a disadvantage in cancer symptom management for Black patients.

Although patients with systemic lupus erythematosus (SLE) experience high levels of depression and anxiety disorders, evidence concerning patient perceptions of facilitators and barriers to effective uptake of mental health services (eg, referral to therapists and psychiatrists, psychoeducational interventions, or support groups) is limited. We conducted semistructured qualitative interviews with 15 adults with SLE to explore patient experiences and perceptions of mental health services to identify facilitators and barriers to accessing mental health care among patients with SLE. Qualitative interviews were conducted via telephone and audio recorded for transcription and directed content analysis using NVivo software by two coders. The median age of the 15 participants was 48 years, 87% were female, 33% identified as Black or African American, and 33% identified as Hispanic or Latino. Qualitative themes were organized into three domains: barriers, facilitators, and preferences for mental health services. Barriers to the use of mental health services include mental health stigma, sociodemographic factors, lack of autonomy, and time commitment. Facilitators to the use of mental health services included strong relationships with their rheumatologists and mental health care clinician experience with patients with SLE. Preferences for mental health services included education‐based formats, mental health providers who work with patients with SLE, peer group formats, demographically and disease‐matched psychological resources, and an emphasis on non–disease‐related activities. In the setting of persistent unmet psychosocial needs of patients living with SLE, data from this qualitative study will inform the development and refinement of mental health interventions that bolster psychological wellbeing in the SLE population.

The adaptive immune system plays an important role in the development and progression of atherosclerotic cardiovascular disease. B cells can have both proatherogenic and atheroprotective roles, making treatments aimed at modulating B cells important therapeutic targets. The innate-like B-cell response is generally considered atheroprotective, while the adaptive response is associated with mixed consequences for atherosclerosis. Additionally, interactions of B cells with components of the adaptive and innate immune system, including T cells and complement, also represent key points for therapeutic regulation. In this review, we discuss therapeutic approaches based on B-cell depletion, modulation of B-cell survival, manipulation of both the antibody-dependent and antibody-independent B-cell response, and emerging immunization techniques.

To determine the proportion of people in New South Wales towns at high risk of Japanese encephalitis virus (JEV) infections during the 2022 outbreak; to identify risk factors for JEV infection. Cross‐sectional serosurvey study of the seroprevalence of JEV‐specific antibodies in NSW. Convenience sample of people (all ages) from five regional NSW towns deemed to be at high risk of JEV infections after first outbreak of Japanese encephalitis in southeastern Australia in early 2022 (Balranald, Corowa, Dubbo, Griffith, Temora), 21 June – 22 July 2022. Proportion of people seropositive for JEV total antibody, assayed by defined epitope‐blocking enzyme‐linked immunosorbent assay; prevalence odds ratios for exposure risk factors and protective behaviours. Eighty of 917 eligible participants (559 girls or women, 61%; 42 Aboriginal and Torres Strait Islander people, 4.6%; median age, 52 years [IQR, 37–62 years]) were seropositive for JEV‐specific total antibody (8.7%); the median age of seropositive people was 61 years (IQR, 48–70 years). The seropositivity proportion was largest for people aged 65 years or more (30 of 192; weighted proportion, 13.7%) and larger for male than female participants (30 of 358, 10.6% v50 of 559, 7.5%). Five of 42 samples from Aboriginal and Torres Strait Islander participants were seropositive (12%). We found mixed associations with a range of potential risk factors. We found evidence for a substantial number of JEV infections in five regional NSW towns during a single arbovirus season in 2022. Public health responses, including effective surveillance, vaccination against JEV, and mosquito management, are critical for controlling outbreaks. Promoting behaviours that reduce exposure to mosquitoes is a core component of prevention, particularly when the vaccine supply is limited.

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs1–3and revealed how quickly viral escape can curtail effective options4,5. When the SARS-CoV-2 Omicron variant emerged in 2021, many antibody drug products lost potency, including Evusheld and its constituent, cilgavimab4–6. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination4and is challenging to replace with existing approaches. Rapidly modifying such high-value antibodies to restore efficacy against emerging variants is a compelling mitigation strategy. We sought to redesign and renew the efficacy of COV2-2130 against Omicron BA.1 and BA.1.1 strains while maintaining efficacy against the dominant Delta variant. Here we show that our computationally redesigned antibody, 2130-1-0114-112, achieves this objective, simultaneously increases neutralization potency against Delta and subsequent variants of concern, and provides protection in vivo against the strains tested: WA1/2020, BA.1.1 and BA.5. Deep mutational scanning of tens of thousands of pseudovirus variants reveals that 2130-1-0114-112 improves broad potency without increasing escape liabilities. Our results suggest that computational approaches can optimize an antibody to target multiple escape variants, while simultaneously enriching potency. Our computational approach does not require experimental iterations or pre-existing binding data, thus enabling rapid response strategies to address escape variants or lessen escape vulnerabilities.

IMPORTANCE: Dermatologists prescribe more oral antibiotics per clinician than clinicians in any other specialty. Despite clinical guidelines that recommend limitation of long-term oral antibiotic treatments for acne to less than 3 months, there is little evidence to guide the design and implementation of an antibiotic stewardship program in clinical practice. OBJECTIVE: To identify salient barriers and facilitators to long-term antibiotic prescriptions for acne treatment. DESIGN, SETTING, AND PARTICIPANTS: This qualitative study assessed data collected from stakeholders (including dermatologists, infectious disease physicians, dermatology resident physicians, and nonphysician clinicians) via an online survey and semistructured video interviews between March and August 2021. Data analyses were performed from August 12, 2021, to January 20, 2024. MAIN OUTCOMES AND MEASURES: Online survey and qualitative video interviews developed with the Theoretical Domains Framework. Thematic analyses were used to identify salient themes on barriers and facilitators to long-term antibiotic prescriptions for acne treatment. RESULTS: Among 30 participants (14 [47%] males and 16 [53%] females) who completed the study requirements and were included in the analysis, knowledge of antibiotic guideline recommendations was high and antibiotic stewardship was believed to be a professional responsibility. Five salient themes were to be affecting long-term antibiotic prescriptions: perceived lack of evidence to justify change in dermatologic practice, difficulty navigating patient demands and satisfaction, discomfort with discussing contraception, iPLEDGE-related barriers, and the absence of an effective system to measure progress on antibiotic stewardship. CONCLUSIONS AND RELEVANCE: The findings of this qualitative study indicate that multiple salient factors affect long-term antibiotic prescribing practices for acne treatment. These factors should be considered in the design and implementation of any future outpatient antibiotic stewardship program for clinical dermatology.

The article focuses on the ongoing debate regarding deep-sea mining for critical minerals, addressing the increasing interest in seabed exploitation, environmental concerns, and the dilemma policymakers face in balancing resource extraction with conservation efforts. It also mentions arguments for the necessity of deep-sea mining, concerns about its potential ecological impacts, and the need for precautionary measures in policymaking.

Engineering culture research to date has described the culture as rigid, chilly, and posing many barriers to entry. However, the COVID‐19 pandemic provided an important opportunity to explore how engineering culture responds to a major disruption. The purposes of this study are to understand how elements of engineering culture emerged in mechanical engineering students' perceptions of their classroom experiences during the pandemic and how their experiences varied across two national contexts. This qualitative comparative case study examines undergraduate mechanical engineering students' perceptions of their experiences taking courses during the pandemic at two universities—one in the United States and one in South Africa. Semistructured interviews were conducted across both sites with 21 students and contextualized with 3 faculty member interviews. Student interviews were analyzed using an iterative process of deductive coding, inductive coding, and pattern coding. We identified two key themes that characterized participants' experiences during the pandemic: hardness and access to resources. We found that students at both sites experienced two types of hardness—intrinsic and constructed—and were more critical of constructed forms of hardness. We found that the South African university's response to facilitating student access to resources was viewed by students as more effective when compared with the US university. We found that hardness remained a central feature of engineering culture, based on student perceptions, and found that students expressed awareness of resource‐related differences. A key distinction emerged between intrinsic and constructed hardness.

A single center had a collaborative, multidisciplinary review to determine how to best implement new acute ischemic stroke trials involving large vessel occlusions. A flow diagram process map was created for clinical decision support. Patients were divided into four groups based upon size of infarct and timing of presentation. The process map, available in the electronic health record (EHR) for clinicians to reference, guides the selection of patients for endovascular therapy with neuroimaging. In addition, the process map offers guidance for discussions with families and patients experiencing large vessel occlusions with both small and large core infarcts. This manuscript describes the process of creating the process map through a multidisciplinary review and discussion, with points of controversy and how these were addressed.

Background: No prior racial disparities studies in total knee arthroplasty (TKA) and total hip arthroplasty (THA) have specifically evaluated outcomes among American Indian or Alaska Native (AIAN) patients. We hypothesized that AIAN patients have worse outcomes than White patients after controlling for demographics and comorbidities. Methods: This was a retrospective cohort study comparing White and AIAN patients undergoing primary TKA/THA from 2012–2019 using the American College of Surgeons National Surgical Quality Improvement Program. Race, demographics, and comorbidities were analyzed for correlations with 30-day outcomes and complications using multivariable logistic and linear regression analyses. Results: Comparing 422,215 White and 2,676 AIAN patients, AIAN patients had higher American Society of Anesthesiologist (ASA) classifications, body mass index (BMI), and were younger at the time of surgery. AIAN patients more often stayed inpatient > 2 days (49.4% vs 36.2%, p&lt; 0.001), underwent reoperation (2.1% vs 1.4%, p&lt; 0.01), and were discharged home (91.4% vs 81.7%, p&lt; 0.01). Regression analyses controlling for age, BMI, sex, ASA classification, and functional status found that AIAN race was significantly positively correlated with a length of stay > 2 days (OR 1.6), reoperation (OR 1.4), and discharging home (OR 2.0). Conclusion: AIAN patients undergoing TKA/THA present with a greater comorbidity burden compared to White patients and experience multiple worse outcome metrics including increased hospital length of stay and reoperation rates. Interestingly, AIAN patients were more likely to discharge home, representing a unique racial disparity which warrants further study.

There remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by an increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (Mpro, 3CLpro) of SARS-CoV-2 is an attractive target due to its homology within the coronaviral family, and lack thereof toward human proteases. In this disclosure, we outline the advent of a novel SARS-CoV-2 3CLproinhibitor, CMX990, bearing an unprecedented trifluoromethoxymethyl ketone warhead. Compared with the marketed drug nirmatrelvir (combination with ritonavir = Paxlovid), CMX990has distinctly differentiated potency (∼5× more potent in primary cells) and human in vitroclearance (>4× better microsomal clearance and >10× better hepatocyte clearance), with good in vitro-to-in vivocorrelation. Based on its compelling preclinical profile and projected once or twice a day dosing supporting unboosted oral therapy in humans, CMX990advanced to a Phase 1 clinical trial as an oral drug candidate for SARS-CoV-2.

The red fox (Vulpes vulpes) is a generalist mesopredator found throughout the UK. It has been linked to national declines in native wildlife, especially ground-nesting birds such as waders. In the New Forest National Park, nest predation and poor chick survival is primarily responsible for low breeding success of Eurasian curlew (Numenius arguata), a species of high conservation concern. To reduce predation losses, foxes are lethally controlled by wildlife managers. Here, we identified the major food resources that are being exploited by foxes in the New Forest area and examined temporal and spatial patterns in the presence of specific food categories, with special reference to anthropogenic food. Stomachs from foxes culled in curlew breeding areas were collected from April 2021 - July 2022 and the contents of these stomachs were quantified. Foxes exhibited a highly varied diet with no single food category predominating. Anthropogenic food comprised 14% of the overall diet, with its presence predicted by proximity to human settlements and other infrastructure. We also estimated the total annual volume of anthropogenic food consumed by the fox population and by extension how many individual foxes this volume of food could support in isolation. According to these calculations, at present the number of foxes subsidised by anthropogenic food is approximately 64.8% (50.2–79.7%) of those removed by culling per year. Our findings highlight that better local food sanitation and education should become important parts of a more holistic management approach to reduce the burden of fox predation experienced by breeding waders.

A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1–BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG and IgA responses and, unlike the intramuscular mRNA vaccine, induced spike-specific B cells in the lungs. IgG, IgA and T cell responses correlated with protection in the lungs, whereas mucosal IgA alone correlated with upper airway protection. This study highlights differential mucosal and serum correlates of protection and how mucosal vaccines can durably prevent infection against SARS-CoV-2.

Immune imprinting is a phenomenon in which prior antigenic experiences influence responses to subsequent infection or vaccination1,2. The effects of immune imprinting on serum antibody responses after boosting with variant-matched SARS-CoV-2 vaccines remain uncertain. Here we characterized the serum antibody responses after mRNA vaccine boosting of mice and human clinical trial participants. In mice, a single dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike protein minimally imprinted serum responses elicited by Omicron boosters, enabling generation of type-specific antibodies. However, imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron vaccine. In both SARS-CoV-2-infected and uninfected humans who received two Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with Omicron variants as well as more distantly related sarbecoviruses. Because serum neutralizing responses against Omicron strains and other sarbecoviruses were abrogated after pre-clearing with Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes targeted by the antecedent mRNA-1273 primary series. Thus, the antibody response to Omicron-based boosters in humans is imprinted by immunizations with historical mRNA-1273 vaccines, but this outcome may be beneficial as it drives expansion of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and distantly related sarbecoviruses.

An important part of STEM education is students’ acquisition of knowledge, skills, and abilities needed for career success, all of which emerge from a combination of classroom and co-curricular activities. Work-related experiential activities (WREAs) offer the opportunity for students to engage in experiential activities before degree completion, and these experiences provide students with an important way to refine their skills that facilitate career success. Generally, prior research confirms the benefits of work-related experiential activities in students’ transition to the workforce, but more evidence is needed to examine the contribution of WREA participation in the development of career competencies. This paper focuses on engineering and computer science students’ perceptions of skills related to career competence that were enhanced during WREA participation. Sixty-three percent of the students surveyed in spring 2021 and spring 2022 at five institutions in one U.S. state said they completed one or more WREAs during their baccalaureate studies. With only a few significant differences by students’ gender, race/ethnicity, or financial aid status, student responses indicated high value in developing skills related to career competence, and in particular, professionalism and communication. Student perceptions are detailed, and implications for STEM research and education are discussed.

Objective Faith leaders often serve as health-related role models yet many struggle with obesity and self-care engagement. The purpose of this scoping review was to examine how the faith leader literature has defined self-care and examined obesity and obesity-related chronic disease.Data Source Studies were identified through database (eg, PubMed, CINAHL, PsycINFO), backward, and grey literature (eg, dissertations) searches.Inclusion/Exclusion Criteria Studies published in English with participants who were 18 years or older and examined leaders across all faiths. Studies also included an examination of self-care behaviors among faith leaders within the context of obesity or obesity-related chronic diseases.Data Extraction/Synthesis Data synthesis was qualitative and informed by the six-step framework developed by Arksey and O’Malley (2005) as well as updated recommendations by Daudt et al (2013). Of the 418 studies identified and screened, 20 met the eligibility criteria.Results Studies were primarily cross-sectional and participants Christian faith-leaders in the US. Most studies did not define self-care or incorporate theory, but focused on vegetarian diets and physical activity engagement. Other self-care related behaviors (eg, sleep, days off), some unique to faith leaders (eg, sabbatical), were included but not systematically.Conclusions Research with more diverse faith leaders and that uses theory is needed to guide development of strategies for engaging this population in self-care to reduce obesity and related chronic diseases.

DHX9 is a DExH-box RNA helicase that utilizes hydrolysis of all four nucleotide triphosphates (NTPs) to power cycles of 3′ to 5′ directional movement to resolve and/or unwind double stranded RNA, DNA, and RNA/DNA hybrids, R-loops, triplex-DNA and G-quadraplexes. DHX9 activity is important for both viral amplification and maintaining genomic stability in cancer cells; therefore, it is a therapeutic target of interest for drug discovery efforts. Biochemical assays measuring ATP hydrolysis and oligonucleotide unwinding for DHX9 have been developed and characterized, and these assays can support high-throughput compound screening efforts under balanced conditions. Assay development efforts revealed DHX9 can use double stranded RNA with 18-mer poly(U) 3′ overhangs and as well as significantly shorter overhangs at the 5′ or 3′ end as substrates. The enzymatic assays are augmented by a robust SPR assay for compound validation. A mechanism-derived inhibitor, GTPγS, was characterized as part of the validation of these assays and a crystal structure of GDP bound to cat DHX9 has been solved. In addition to enabling drug discovery efforts for DHX9, these assays may be extrapolated to other RNA helicases providing a valuable toolkit for this important target class.

A market-released deep brain stimulation (DBS) lead and burr hole device (BHD) have been used for more than ten years to provide stable DBS therapy using leads with four equally distributed cylindrical electrodes along the distal lead length. Newer directional leads cluster segmented electrodes at the center of the electrode array. This work tests the hypothesis that improved chronic translational and rotational stability through enhanced BHD design may ensure that these newer directional electrodes remain in a stable orientation near the stimulation target to maintain therapy and maximize opportunities to adjust therapy, if needed.

Engineering education research is a relatively new field focused on improving engineering education to support the success of a broader range of students and be more relevant to the needs of contemporary society. In this article, we look closely at the impact of a pioneer in this field, the late Professor Duncan McKenzie Fraser, who began a focused and scholarly programme of work during late apartheid in South Africa, looking closely at the challenges experienced by chemical engineering students at the University of Cape Town (UCT), where he worked. We analyse Duncan’s early experiments in improving teaching and curriculum which led into a recognized body of engineering education research. These research findings informed a programme of curriculum reform at UCT, the first phase of which involved the creation of some new courses and the modification of parts of the curriculum, and the second phase of which involved a full-scale reform of the entire curriculum. The analysis shows how engineering education research was used to inform innovative curriculum design that was closely attuned to contextual needs, specifically regarding stark racial disparities in student success, and also evolved later to embody a focus on sustainable development. Overall, there are significant lessons for the growing field of engineering education, which continues to grapple with the disjoint between research and improved practice—crucially showing the need for long term engagement, as exemplified in this programme of work which spanned over three decades.

Objective: We tested the feasibility and effectiveness of a percutaneous atrial transseptal extracorporeal membrane oxygenation (ECMO) cannulation strategy in a right ventricular failure (RVF) model.Methods: We performed 4 nonsurvival porcine experiments. Percutaneous transseptal access was achieved using a steerable introducer. For guidance, we used fluoroscopy, transesophageal echocardiogram (TEE), and intracardiac echocardiography (ICE). A ProtekDuo rapid deployment cannula (LivaNova, London, UK) was advanced across the septum into the left atrium by 2 to 3 cm. Pulmonary hypertension (PH) was induced by partially clamping the pulmonary artery. ECMO flow was cycled from high (2 to 3 L/min) to low (0.2 to 0.3 L/min) over 2 to 3 hours.Results: Transseptal access using TEE and fluoroscopy was successful in 1 animal and unsuccessful in 1 animal. ICE provided optimal visualization for the remaining 2 animals. Mean arterial pressure (MAP) was associated immediately and consistently with high versus low ECMO flow rate (mean difference: 29 ± 3.1 mm Hg, P= 0.004) but was not restored to baseline values. RV pressure values were dynamic. Given time to equilibrate, mean RV pressure was restored to a baseline level.Conclusions: Percutaneous right atrium to left atrium transseptal cannulation relieved PH-RVF. MAP was restored to a viable level, and mean RV pressure was restored to a baseline level. Transseptal ECMO shows promise as a cannulation strategy to bridge patients with PH-RVF to lung transplant.

Although interleukin‐1 (IL‐1)/IL‐6 inhibitors are effective therapies for systemic juvenile idiopathic arthritis (JIA), some patients develop eosinophilia and lung disease during treatment. This study was undertaken to retrospectively evaluate incidence and risk factors for eosinophilia and describe lung disease outcomes in IL‐1/IL‐6 inhibitor–exposed patients with systemic JIA. Among JIA patients at our institution exposed to interleukin‐1 (IL‐1)/IL‐6 inhibitors (1995–2022), we compared incidence rate of eosinophilia in systemic JIA compared to other JIA, stratified by medication class (IL‐1/IL‐6 inhibitors, other cytokine inhibitors, methotrexate). We used Cox models to identify predictors of eosinophilia during IL‐1/IL‐6 inhibitor use and summarized treatment changes and outcomes after eosinophilia, including lung disease. HLA typing was performed on a clinical or research basis. There were 264 new medication exposures in 75 patients with systemic JIA and 41 patients with other JIA. A total of 49% of patients with systemic JIA with HLA typing (n = 45) were positive for HLA–DRB1*15 alleles. Eosinophilia was common during IL‐1/IL‐6 inhibitor use and did not differ by systemic JIA compared to other JIA (0.08 and 0.07 per person‐year, respectively; P= 0.30). Among systemic JIA patients, pretreatment macrophage activation syndrome (MAS) was associated with a higher rate of subsequent eosinophilia on biologic therapy (unadjusted hazard ratio 3.2 [95% confidence interval 1.2–8.3]). A total of 4 of 5 patients who switched therapy within 10 weeks of eosinophilia experienced disease flare compared to none of the patients who continued the original therapy. A total of 8 of 25 patients with pulmonary evaluations had lung disease, and all had severe manifestations of systemic JIA (MAS, intensive care unit stay). One death was attributed to systemic JIA–lung disease. Eosinophilia is common in JIA patients using IL‐1/IL‐6 inhibitors. Severe disease may be associated with eosinophilia and lung disease in systemic JIA.

AbstractMolar morphologies of the latest Oligocene genera, Chuniaand Ektopodon, are easy to distinguish, but species determinations are more difficult. As more specimens have been collected, more maxillary fragments with molars and/or alveoli and a portion of the rostrum preserved are available. With a suite of maxillae now known, new ektopodontid features have revealed themselves, including the shortening of the rostrum compared to other families of contemporary possums. The facial angulation represented by the flexure of the rostrum at the boundary between P3 and the molar row results in the rostrum being angled differently than the molar row. Ektopodontids have a significantly greater angulation and thus shorter faces, compared to that seen in contemporary phalangeriform possums. Two new species of the genus Chunia, from the lower Etadunna Formation, South Australia, can be distinguished from the type species, Chunia illuminata, of the Ditjimanka Local Fauna. Differences in molar morphologies and the degree of facial angulation distinguish a new species of Chuniafrom the lowest faunal zone and the Minkina Local Fauna (facial angulation of 52°) from C. illuminatafrom the next higher faunal zone (Ditjimanka Local Fauna), which has a greater facial angulation of 63°, while a second new species of Chunia, also from the Dijimanka Local Fauna, has a facial angulation of 58° and intermediate molar traits. The degree of facial shortening is a valid discriminator between species of ektopodontid marsupials as it coincides with the species level differences in dental morphology. Additionally, C. omegafrom the Tarkarooloo Local Fauna is placed in new genus, Ngathachunia, as it is outside of the hypodigms for both of the previously described genera, Chuniaand Ektopodon. A well-supported phylogenetic hypothesis for the family indicates the species of Ektopodonform a monophyletic clade, while the species of Chuniaare paraphyletic.Judd A. Case [jcase@ewu.edu], Department of Biology, Eastern Washington University, Cheney, WA 99004, USA. Case, J.A., Month, 202X. Two new species of ektopodontid marsupial from the lower deposits of the Etadunna Formation (latest Oligocene), South Australia and a phylogenetic hypothesis for the Ektopodontidae. Alcheringa XXX, X–X. ISSN 0311-5518.

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain1(RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting.

Minority stress theory offers an explanation of how discrimination, marginalization, harassment, and violence against sexual minority and transgender women are connected to mental health disparities. Particularly, these groups are vulnerable to body image issues, disordered eating, higher rates of mood and anxiety disorders, suicide and nonsuicidal self-injury, and substance use. Discrimination is also experienced within clinical settings, which may lead this population to postpone or avoid treatment. Clinicians play a crucial role in reducing barriers to health care by developing cultural competency and ensuring safe and affirming spaces within their practice.

Tropical savannas have been increasingly targeted for carbon sequestration by afforestation, assuming large gains in soil organic carbon (SOC) with increasing tree cover. Because savanna SOC is also derived from grasses, this assumption may not reflect real changes in SOC under afforestation. However, the exact contribution of grasses to SOC and the changes in SOC with increasing tree cover remain poorly understood. Here we combine a case study from Kruger National Park, South Africa, with data synthesized from tropical savannas globally to show that grass-derived carbon constitutes more than half of total SOC to a soil depth of 1 m, even in soils directly under trees. The largest SOC concentrations were associated with the largest grass contributions (>70% of total SOC). Across the tropics, SOC concentration was not explained by tree cover. Both SOC gain and loss were observed following increasing tree cover, and on average SOC storage within a 1-m profile only increased by 6% (s.e. = 4%, n= 44). These results underscore the substantial contribution of grasses to SOC and the considerable uncertainty in SOC responses to increasing tree cover across tropical savannas.

Gene therapy with an adeno-associated virus serotype 8 (AAV8) vector (AAV8-LSPhGAA) could eliminate the need for enzyme replacement therapy (ERT) by creating a liver depot for acid α-glucosidase (GAA) production. We report initial safety and bioactivity of the first dose (1.6 × 1012vector genomes/kg) cohort (n = 3) in a 52-week open-label, single-dose, dose-escalation study (NCT03533673) in patients with late-onset Pompe disease (LOPD). Subjects discontinued biweekly ERT after week 26 based on the detection of elevated serum GAA activity and the absence of clinically significant declines per protocol. Prednisone (60 mg/day) was administered as immunoprophylaxis through week 4, followed by an 11-week taper. All subjects demonstrated sustained serum GAA activities from 101% to 235% of baseline trough activity 2 weeks following the preceding ERT dose. There were no treatment-related serious adverse events. No subject had anti-capsid T cell responses that decreased transgene expression. Muscle biopsy at week 24 revealed unchanged muscle glycogen content in two of three subjects. At week 52, muscle GAA activity for the cohort was significantly increased (p < 0.05). Overall, these initial data support the safety and bioactivity of AAV8-LSPhGAA, the safety of withdrawing ERT, successful immunoprophylaxis, and justify continued clinical development of AAV8-LSPhGAA therapy in Pompe disease.

Deep brain stimulation (DBS) is an important clinical therapeutic tool to control motor symptoms of Parkinson’s disease (PD) for many patients whose symptoms are not well controlled by medication alone (Malek, 2019 [1]). DBS therapy involves the delivery of an electrical current through an electrode that is surgically placed in the brain, traditionally in the subthalamic nucleus (STN) or globus pallidus internus (GPi). Recent technology has allowed these devices to not only deliver an electrical current, but also measure local field potentials (LFPs). LFPs are electrical potentials, produced by the activation of neurons, that act as markers for the frequency and severity of specific motor symptoms in PD (Neumann et al., 2017 [2], Swann et al., 2016 [3]). These markers can give insight into the efficacy of a given treatment regiment, by providing data to use as clinical benchmarks for the treatment team. The utility of LFPs in the treatment of PD is illustrated in this case series of three patients with complex motor fluctuations such as dyskinesias, Levodopa wearing-off and muscle rigidity. Here we demonstrate how we used LFP sensing through Timeline, Streaming and Event Capture to gain insight to the patients’ symptoms and offer data driven therapy optimization. The first case is a 72-year-old y/o female patient with PD, who presented with severe dyskinesias and motor fluctuations. By monitoring real-time LFPs, the treatment team was able to identify significant dyskinesias and optimize medication and stimulation frequency, which led to more personalized and efficacious treatment. The second case is a 66 y/o male patient with PD, hoping to achieve more on time without troublesome dyskinesias. Using chronic LFP data the treatment team was able to adjust therapy amplitude and pulse width to better manage the patient’s symptoms. In addition, the LFP data was used to educate the patient on when the patient programmer could be used situationally for changing programming groups. The third case is a 65 y/o male patient with a ten-year history of PD, experiencing abrupt and unpredictable medication wearing off times and severe dyskinesias, which compromised gait and activities of daily living. Real time and chronic LFP sensing supported the optimization of his stimulation amplitude and pulse width and medication regimen, ultimately decreasing his fluctuations and greatly improving his gait and quality of life.

Epidemiological monitoring of HIV among transgender women is minimal despite prioritisation of this group in the US National HIV/AIDS Strategy (2022–2025). We aimed to estimate HIV incidence in a multisite cohort of transgender women in the eastern and southern USA. Participant deaths were identified during follow-up; thus, we felt it was an ethical imperative to report mortality alongside HIV incidence.