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Catering for the mathematical needs of disabled learners equitably and productively requires the anti-ableist preparation and professional development of teachers. In CAPTeaM (Challenging Ableist Perspectives on the Teaching of Mathematics), we design tasks that emulate inclusion-related challenges from the mathematics classroom, and we engage teachers with these tasks in workshop settings. In this paper, we focus on evidence from one type of task in which participants engage in small groups with solving a mathematical problem while at least one of them is temporarily and artificially deprived of access to a sensory field or familiar channel of communication. In this paper, we focus on evidence of emerging resignification -- discursive and affective shifts in the participating teachers' sense-making about what makes the construction of mathematical meaning possible and valuably different -- as they work on the tasks. By linking Vygotsky's vision about the educational changes required to empower and include disabled learners with more contemporary ideas from embodied cognition and disability studies, our analyses show how engagement with the tasks affects participants' realisation and appreciation of interdependencies between learners, teacher, resources, and emotions, highlights alternative forms of mathematical agency and gives opportunities to turn initial sense of impasse and despair into joy.

This cross-sectional observational study sought to examine the environmental correlates of physical activity and screen-time among youth with autism spectrum disorder (ASD). Parents of youth with ASD (n = 1,165) from seven countries/regions provided responses to an online survey form measuring environmental correlates (i.e., physical activity neighborhood environment, social network, social trust and cohesion, bedroom media, social home environment) and outcomes (i.e., physical activity, screen-time). Multiple linear regression analyses were conducted to determine environmental predictors of the outcomes. Physical activity neighborhood environment (B = 0.15, p = 0.047), social network (B = 0.16, p = 0.02), and social home environment (B = 1.07, p < 0.001) were significantly associated with physical activity, whereas social trust and cohesion and bedroom media were not. Further, social trust and cohesion (B = -0.14, p = 0.001), bedroom media (B = 0.10, p = 0.001), and social home environment (B = -0.16, p < 0.001) were significantly associated with screen-time while neighborhood environment and social network were not. The identified environmental attributes of physical activity and screen-time behaviors should be targeted for health promotion among youth with ASD.

Mary Lou Affronti,1–3 Sarah Woodring,1,2 Katherine B Peters,1,4 James E Herndon II,5 Frances McSherry,5 Patrick N Healy,5 Annick Desjardins,1,4 James J Vredenburgh,6 Henry S Friedman1,2 1The Preston Robert Tisch Brain Tumor Center at Duke, South Hospital, Duke University Medical Center, 2Department of Neurosurgery, Duke University Health System, 3Duke University School of Nursing, 4Department of Neurology, 5Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC, 6Saint Francis Cancer Center, Hartford, CT, USA Purpose: Given that the prognosis of recurrent malignant glioma (MG) remains poor, improving quality of life (QoL) through symptom management is important. Meta-analyses establishing antiemetic guidelines have demonstrated the superiority of palonosetron (PAL) over older 5-hydroxytryptamine 3-receptor antagonists in chemotherapy-induced nausea and vomiting (CINV) prevention, but excluded patients with gliomas. Irinotecan plus bevacizumab is a treatment frequently used in MG, but is associated with low (55%) CINV complete response (CR; no emesis or use of rescue antiemetic) with commonly prescribed ondansetron. A single-arm Phase II trial was conducted in MG patients to determine the efficacy of intravenous PAL (0.25 mg) and dexamethasone (DEX; 10 mg) received in conjunction with biweekly irinotecan–bevacizumab treatment. The primary end point was the proportion of subjects achieving acute CINV CR (no emesis or antiemetic ≤24 hours postchemotherapy). Secondary end points included delayed CINV CR (days 2–5), overall CINV CR (days 1–5), and QoL, fatigue, and toxicity.Materials and methods: A two-stage design of 160 patients was planned to differentiate between CINV CR of 55% and 65% after each dose of PAL–DEX. Validated surveys assessed fatigue and QoL.Results: A total of 63 patients were enrolled, after which enrollment was terminated due to slow accrual; 52 patients were evaluable for the primary outcome of acute CINV CR. Following PAL–DEX dose administrations 1–3, acute CINV CR rates were 62%, 68%, and 70%; delayed CINV CR rates were 62%, 66%, and 70%, and overall CINV CR rates were 47%, 57%, and 62%, respectively. Compared to baseline, there was a clinically meaningful increase in fatigue during acute and overall phases, but not in the delayed phase. There were no grade ≥3 PAL–DEX treatment-related toxicities.Conclusion: Data suggest that PAL–DEX is effective in preventing CINV in MG patients, which ultimately maintains the QoL of patients with glioma. Keywords: chemotherapy, nausea, chemotherapy-induced nausea and vomiting, antiemetic guidelines, evidence-based practice, glioma

With a runtime of 47 years, Saturday Night Live has long served as a societal mirror that captures and creates popular culture. In recent years the show has been criticized for its lack of diverse hosts, cast and staff. Out of 930 episodes only seven episodes have been hosted by an Asian host, four of whom identify as Chinese. This research examined those four episodes through quantitative analysis, finding that the qualities of each of the hosts' characters range from just below neutral to moderately positive. The use of stereotypes and satirical racial humor varied. Jackie Chan and Lucy Liu's episodes had the highest concentration of both overt and covert stereotypes, while Awkwafina had a similar number with a lower concentration. The infrequency of Chinese representation on the show is a social issue. Such a small sample size does not allow for conclusions to be drawn. Rather, this research paints a picture of how the four Chinese hosts are portrayed on SNL as influenced by their own unique identities and the year of their appearance. In addition, the insights this case study offers has implications for shows performed in colleges and K-12 schools. Directors and sponsors of school based shows can learn from this case study how to avoid perpetuating stereotypes and how to advance diversity, equity and inclusion at their institutions.

Abstract Interactions between adipose tissue, liver and immune system are at the center of metabolic dysfunction-associated steatotic liver disease and type 2 diabetes. To address the need for an accurate in vitro model, we establish an interconnected microphysiological system (MPS) containing white adipocytes, hepatocytes and proinflammatory macrophages derived from isogenic human induced pluripotent stem cells. Using this MPS, we find that increasing the adipocyte-to-hepatocyte ratio moderately affects hepatocyte function, whereas macrophage-induced adipocyte inflammation causes lipid accumulation in hepatocytes and MPS-wide insulin resistance, corresponding to initiation of metabolic dysfunction-associated steatotic liver disease. We also use our MPS to identify and characterize pharmacological intervention strategies for hepatic steatosis and systemic insulin resistance and find that the glucagon-like peptide-1 receptor agonist semaglutide improves hepatocyte function by acting specifically on adipocytes. These results establish our MPS modeling the adipose tissue-liver axis as an alternative to animal models for mechanistic studies or drug discovery in metabolic diseases.

Abstract HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes.

Abstract Background Syringe services programs (SSPs) provide harm reduction supplies and services to people who use drugs and are often required by funders or partners to collect data from program participants. SSPs can use these data during monitoring and evaluation (M&E) to inform programmatic decision making, however little is known about facilitators and barriers to collecting and using data at SSPs. Methods Using the Consolidated Framework for Implementation Research (CFIR), we conducted 12 key informant interviews with SSP staff to describe the overall landscape of data systems at SSPs, understand facilitators and barriers to data collection and use at SSPs, and generate recommendations for best practices for data collection at SSPs. We used 30 CFIR constructs to develop individual interview guides, guide data analysis, and interpret study findings. Results Four main themes emerged from our analysis: SSP M&E systems are primarily designed to be responsive to perceived SSP client needs and preferences; SSP staffing capacity influences the likelihood of modifying M&E systems; external funding frequently forces changes to M&E systems; and strong M&E systems are often a necessary precursor for accessing funding. Conclusions Our findings highlight that SSPs are not resistant to data collection and M&E, but face substantial barriers to implementation, including lack of funding and disjointed data reporting requirements. There is a need to expand M&E-focused funding opportunities, harmonize quantitative indicators collected across funders, and minimize data collection to essential data points for SSPs.

Abstract Commander is a multiprotein complex that orchestrates endosomal recycling of integral cargo proteins and is essential for normal development. While the structure of this complex has recently been described, how cargo proteins are selected for Commander-mediated recycling remains unclear. Here we identify the mechanism through which the unstructured carboxy-terminal tail of the cargo adaptor sorting nexin-17 (SNX17) directly binds to the Retriever sub-complex of Commander. SNX17 adopts an autoinhibited conformation where its carboxy-terminal tail occupies the cargo binding groove. Competitive cargo binding overcomes this autoinhibition, promoting SNX17 endosomal residency and the release of the tail for Retriever association. Furthermore, our study establishes the central importance of SNX17-Retriever association in the handover of integrin and lipoprotein receptor cargoes into pre-existing endosomal retrieval sub-domains. In describing the principal mechanism of cargo entry into the Commander recycling pathway we provide key insight into the function and regulation of this evolutionary conserved sorting pathway.

Abstract The impact of adjuvants on malaria vaccine-induced antibody repertoire is poorly understood. Here, we characterize the impact of two adjuvants, Alhydrogel® and AS01, on antibody clonotype diversity, binding and function, post malaria vaccination. We expressed 132 recombinant anti-Pfs230D1 human monoclonal antibodies (mAbs) from participants immunized with malaria transmission-blocking vaccine Pfs230D1, formulated with either Alhydrogel® or AS01. Anti-Pfs230D1 mAbs generated by Alhydrogel® formulation showed higher binding frequency to Pfs230D1 compared to AS01 formulation, although the frequency of functional mAbs was similar between adjuvant groups. Overall, the AS01 formulation induced anti-Pfs230D1 functional antibodies from a broader array of germline sequences versus the Alhydrogel® formulation. All mAbs using IGHV1-69 gene from the Alhydrogel® cohort bound to recombinant Pfs230D1, but did not block parasite transmission to mosquitoes, similar to the IGHV1-69 mAbs isolated from the AS01 cohort. These findings may help inform vaccine design and adjuvant selection for immunization with Plasmodium antigens.

Abstract Obstructive sleep apnea (OSA) and hypertension are two important modifiable risk factors for cardiovascular disease and mortality. Numerous studies have highlighted the interplay between these two conditions. We provide a critical review of the current literature on the role of the OSA as a risk factor for hypertension and its effect on blood pressure (BP). We discuss several key topics: the effect of OSA on nocturnal BP, BP response to continuous positive airway pressure (CPAP) treatment, CPAP effect on BP in refractory hypertension, the role of OSA in BP variability (BPV), and maladaptive cardiac remodeling mediated by OSA’s effect on BP. Finally, we discuss the unique aspects of ethnicity and social determinants of health on OSA with a focus on Asian populations and the disparity in BP control and cardiovascular outcomes.

Abstract Aims Currently, there is no reliable biomarker to detect pre‐heart failure in humans. An early risk signal is an elevated left atrial pressure (LAP) and preliminary results from animal studies strongly suggest the neuropeptide neuromedin U (NMU) is released in response to this increase in LAP. However, it is unknown whether NMU is elevated in patients with heart failure. Therefore, the aim of this study was to assess if NMU levels are elevated in human cases of heart failure. Methods and results Twenty‐four serum samples were obtained from patients in stage II and III heart failure from the Royal Papworth Hospital in Cambridge UK and tested using a selective NMU‐ELISA; the data were compared with serum obtained commercially from self‐declared healthy donors. NMU concentrations in serum from heart failure patients were significantly higher (P = 0.0007; unpaired Student's t‐test) than control, 8.48 ± 0.67 ng/mL (mean ± SEM) versus 5.43 ± 0.46 ng/mL. There was no significant difference between NYHA stage II and III patients (P = 0.85, unpaired Student's t‐test), which were 8.33 ± 0.89 ng/mL (n = 9) and 8.6 ± 0.95 ng/mL (n = 15), respectively. Only mean right atrial pressure was found to have a significant correlation with serum NMU (R = 0.81, P

This study aimed to identify the prevalence of current smoking and examine the association between meeting combinations of the 24-h movement guidelines and current smoking in autistic adults. This cross-sectional study administered an electronic survey to a national sample of autistic adults in the United States. The study outcome was current smoking. Independent variables included the 24-h movement behaviors. Multivariable statistical modeling was used to assess the study aims. The study sample (n = 259) had a mean age of 31.05 years (standard deviation = 7.70), 58.7% were male, 11.2% were fully independent, and 35.5% were current smokers. Current smokers met significantly fewer 24-h movement guidelines than non-smokers (mean = 1.52 (standard deviation = 0.73) vs mean= 1.93 (standard deviation = 0.88), respectively, t = 3.77, p < 0.01). Autistic adults with high levels of sedentary behavior were almost three times more likely (odds ratio = 2.784, 95% confidence interval = 1.490, 5.237) to be a current smoker than those who did not meet these guidelines. Autistic adults not meeting sleep and sedentary behavior recommendations had a 1.581 increased odds (odds ratio = 1.581 95% confidence interval = 1.25, 2.001) of being a smoker as compared to those meeting these recommendations. Current smoking was highly prevalent in this sample. Improving sleep health and reducing sedentary time may be viable intervention targets to help promote smoking cessation in autistic adults.

Placement as a form of work-integrated learning is a valued element of undergraduate education. Prior work explores how placement provides a site for developing professional values, skills and competences as well as identifying how students build awareness of professional requirements. Greater focus on how such processes of awareness are realised, negotiated and enacted is still required. This study frames student placement experiences as enabling processes of recursive negotiation between the self and the setting. The empirical contribution is to document and track this with 40 students on accounting placements, interviewed at three points in time (pre-, during, post-placement) exploring their subjective experiences. Findings evidence various trajectories of experience emerging from which a model capturing four distinct forms of fit (personal, reflected, projected, absence of fit) with professional identity is developed. This suggests student placement experiences in all their variations lead to and constitute more than merely technical or academic outcomes. Conceptually framing placement experiences as recursive negotiations between the self and the setting in the professionalisation journey uncovers how professional identity formation processes are constructed and (re)negotiated. As well as providing students with terminology to understand and articulate the multiplicity of possible placement experiences, educators, employers and professional bodies can benefit from the more nuanced possibilities for work-integrated learning that are suggested.

Operational definitions have a significant history in applied behavior analysis. The practice's importance stems from the role operational definitions play in detecting an event, human thought, or action. While operationalizing target behaviors has enjoyed widespread practice, some concerns have recently arisen with translation validity and detection accuracy. Additionally, a review of the literature produces few articles assessing the validity of operational definitions. Pinpoints represent an alternative for describing target behaviors. A pinpoint has a formula for construction that includes using an action verb, an object, or event that receives the action, and a comprehensibly defined context where the observation of the action verb + object or event occurs. Pinpoints also have few empirical studies demonstrating their validity. The following experiment compared the detection accuracy of an operational definition for self-injurious behavior and a corresponding pinpoint across professionals who worked in a school that served clients with autism spectrum disorder. The results indicate lower accuracy scores for the operational definition when compared to the pinpoint. Additionally, the consistency of scores varied more for the operational definition than the pinpoint.