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IntroductionThere is a paucity of data on immune checkpoint inhibitors (ICIs) plus doublet chemotherapy (C) in patients with advanced lung cancer whose tumor harbors an actionable mutation. We sought to provide insight into the role of this combination in relation to chemotherapy alone in this patient population.MethodsWe conducted a retrospective study at the five University of California National Cancer Institute-designated Comprehensive Cancer Centers. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and significant adverse events. Adverse events in patients who received a tyrosine kinase inhibitor (TKI) post-ICI were also captured.ResultsA total of 246 patients were identified, 170 treated with C plus ICI and 76 treated with C alone. Driver alterations included EGFR (54.9%), KRAS (32.9%), ALK (5.3%), HER2/ERBB2 (2.9%), ROS1 (1.2%), MET (1.2%), RET (0.8%), and BRAF non-V600 (0.8%). The overall PFS and OS hazard ratios were not significant at 1.12 (95% confidence interval 0.83-1.51; p = 0.472) and 0.86 (95% confidence interval: 0.60-1.24, p = 0.429), respectively. No significant differences in PFS or OS were observed in the mutational subgroups. Grade 3 or greater adverse events were lower in the C plus ICI group. The multivariate analysis for PFS and OS revealed a performance status (Eastern Cooperative Oncology Group) score of 2, and previous TKI treatment was associated with poorer outcomes with C plus ICI.ConclusionsOur study suggests that patients with oncogenic-driven NSCLC, primarily those with EGFR-driven tumors, treated with a TKI should not subsequently receive C plus ICI. Analysis from prospective clinical trials will provide additional information on the role of ICIs in this group of patients.

IntroductionChildren who are HIV-exposed uninfected (HEU), that is, children who do not acquire HIV infection despite being born to mothers with HIV, have a higher risk of mortality, infectious morbidity and growth deficits than children who are HIV-unexposed uninfected (HUU). Prior research has focused on breast feeding and has pointed to changes in human milk oligosaccharides (HMOs) associated with maternal HIV that may influence the infant microbiome and thereby lead to these adverse outcomes. However, to our knowledge, no study has attempted to intervene along this pathway to reduce the occurrence of the adverse outcomes in children HEU. We will conduct a double-blind, randomised trial of a synbiotic intervention, which combines an HMO and probiotic, in breastfed infants HEU in South Africa to evaluate whether this intervention has promise to reduce excess infectious morbidity and growth faltering compared with controls.Methods and analysisOne hundred and forty-four breastfed infants HEU, aged 4 weeks, will be 1:1 randomised to receive either a daily synbiotic or an identical-looking placebo through age 24 weeks. Infants will be followed until age 48 weeks and outcomes of infectious morbidity, growth and biological measurements (eg, microbiota, inflammation and metabolome) will be assessed. Analyses will follow intention-to-treat principles comparing the cohorts as randomised. Infants HEU will be compared across arms with respect to the occurrence of infectious morbidity and growth outcomes through 4-24 weeks and 4-48 weeks using appropriate parametric and non-parametric statistical tests. Additionally, an observational cohort of 40 breastfed infants HUU will be recruited as a comparator group with no intervention.Ethics and disseminationEthical approval for this study has been obtained from the ethics committees at Columbia University and Stellenbosch University. The findings will be disseminated in publications.Trial registration numberClinicalTrials.gov Identifier: NCT05282485. SANCTR ID number: DOH-27-122021-6543.

The coronavirus disease 2019 (COVID-19) pandemic has created a global health crisis, with disproportionate effects on vulnerable sociodemographic groups. Although the pandemic is showing potential to increase suicide ideation (SI), we know little about which sociodemographic characteristics or COVID-19 experiences are associated with SI. Our United States-based sample (n = 837 adults [mean age = 37.1 years]) completed an online survey during August-September 2020. The study utilized an online convenience sample from a prior study, which was enriched for exposure to trauma and experiences of posttraumatic stress symptoms. We assessed SI using the Beck Depression Inventory-II. Traditional (i.e., logistic regression) and machine learning (i.e., LASSO, random forest) methods evaluated associations of 148 self-reported COVID-19 factors and sociodemographic characteristics with current SI. 234 participants (28.0%) reported SI. Twenty items were significantly associated with SI from logistic regression. Of these 20 items, LASSO identified seven sociodemographic characteristics (younger age, lower income, single relationship status, sexual orientation other than heterosexual as well as specifically identifying as bisexual, non-full-time employment, and living in a town) and six COVID-19 factors (not engaging in protective COVID-19 behaviors, receiving mental health treatment (medication and/or psychotherapy) due to the COVID-19 pandemic, socializing during the pandemic, losing one's job due to COVID-19, having a friend with COVID-19, and having an acquaintance with COVID-19) associated with SI. Random forest findings were largely consistent with LASSO. These findings may inform multidisciplinary research and intervention work focused on understanding and preventing adverse mental health outcomes such as SI during and in the aftermath of the pandemic.

BackgroundDuring the COVID-19 pandemic within the United States, much of the responsibility for diagnostic testing and epidemiologic response has relied on the action of county-level departments of public health. Here we describe the integration of genomic surveillance into epidemiologic response within Humboldt County, a rural county in northwest California.MethodsThrough a collaborative effort, 853 whole SARS-CoV-2 genomes were generated, representing ~58% of the 1,449 SARS-CoV-2-positive cases detected in Humboldt County as of March 12, 2021. Phylogenetic analysis of these data was used to develop a comprehensive understanding of SARS-CoV-2 introductions to the county and to support contact tracing and epidemiologic investigations of all large outbreaks in the county.ResultsIn the case of an outbreak on a commercial farm, viral genomic data were used to validate reported epidemiologic links and link additional cases within the community who did not report a farm exposure to the outbreak. During a separate outbreak within a skilled nursing facility, genomic surveillance data were used to rule out the putative index case, detect the emergence of an independent Spike:N501Y substitution, and verify that the outbreak had been brought under control.ConclusionsThese use cases demonstrate how developing genomic surveillance capacity within local public health departments can support timely and responsive deployment of genomic epidemiology for surveillance and outbreak response based on local needs and priorities.

BackgroundRecent studies have reignited the tinderbox of debate surrounding the use of race and ancestry in medicine. These controversial studies have argued for a strong correlation between genetic ancestry and race, justifying continued use of genetic ancestry measures in studies of disease. These studies contend that increased use of continental ancestry estimates can inform clinical risk assessments and management. Further, recent studies of racial corrections used in clinical algorithms, such as those used to estimate 'normal' lung function, also advocate for use of genetic ancestry in place of race for refining risk algorithms.Main bodyThese positions are misleading, harmful, and reflect superficial interpretations of population genetics. In this Perspective, we argue that continental genetic ancestry, often proxied by race, serves as a poor indicator of disease risk, and reinforces racialized inequities.ConclusionInstead, we endorse that racial disparities in disease should be investigated by rigorous measures of structural racism alongside careful measures of genetic factors in relevant disease pathways, rather than relying on genetic ancestry or race as a crude proxy for disease-causing alleles.

Over the course of human life, health care decision-making is often interdependent. In this article, we use "interdependence" to refer to patients' engagement of nonclinicians-for example, family members or trusted friends-to reach health care decisions. Interdependence, we suggest, is common for patients in all stages of life, from early childhood to late adulthood. This view contrasts with the common bioethical assumption that medical decisions are either wholly independent or dependent and that independence or dependence is tightly coupled with a person's decision-making capacity. In this article, we array various approaches to decision-making along a continuum of interdependence. An appreciation of this continuum can empower patients and elucidate ethical challenges that arise when people transition between different kinds of interdependence across the life span.

Sleep disturbance has emerged as an independent, mechanistic, and modifiable risk factor for suicide. Sexual and gender minority (SGM) people disproportionately experience sleep disturbance and are at higher risk of death by suicide relative to cisgender and/or heterosexual individuals. The present narrative review evaluates nascent research related to sleep disturbance and suicide-related thoughts and behaviors (STBs) among SGM populations, and discusses how experiences of minority stress may explain heightened risk among SGM people. Although there is a growing understanding of the link between sleep disturbance and STBs, most research has not been conducted in SGM populations or has not examined suicide as an outcome. Research is needed to examine whether and how aspects of sleep disturbances relate to STBs among SGM people in order to better tailor sleep treatments for SGM populations.

AbstractOxygen bioavailability is declining in aquatic systems worldwide as a result of climate change and other anthropogenic stressors. For aquatic organisms, the consequences are poorly known but are likely to reflect both direct effects of declining oxygen bioavailability and interactions between oxygen and other stressors, including two-warming and acidification-that have received substantial attention in recent decades and that typically accompany oxygen changes. Drawing on the collected papers in this symposium volume ("An Oxygen Perspective on Climate Change"), we outline the causes and consequences of declining oxygen bioavailability. First, we discuss the scope of natural and predicted anthropogenic changes in aquatic oxygen levels. Although modern organisms are the result of long evolutionary histories during which they were exposed to natural oxygen regimes, anthropogenic change is now exposing them to more extreme conditions and novel combinations of low oxygen with other stressors. Second, we identify behavioral and physiological mechanisms that underlie the interactive effects of oxygen with other stressors, and we assess the range of potential organismal responses to oxygen limitation that occur across levels of biological organization and over multiple timescales. We argue that metabolism and energetics provide a powerful and unifying framework for understanding organism-oxygen interactions. Third, we conclude by outlining a set of approaches for maximizing the effectiveness of future work, including focusing on long-term experiments using biologically realistic variation in experimental factors and taking truly cross-disciplinary and integrative approaches to understanding and predicting future effects.

Inclusive sports have emerged as a potential tool for building social inclusion within diverse populations. The Special Olympics Unified Sports programs are an example of inclusion initiatives specific to students with intellectual disability and sports that can be reevaluated with new understandings of inclusion. This systematic mixed studies review aimed to capture athlete Unified Sports experiences and identify what athletes reported about their participation. The systematic review identified nine original studies conducted by six unrelated research groups. Results across the studies are synthesized and suggestions for future research are presented. Athletes in all nine studies reviewed reported positive experiences with Unified Sports leading to increased social inclusion and/or self-concepts.

Educational leaders, including directors of special education (DSE), often lack the depth and breadth of knowledge, skills, and dispositions needed to effectively manage the nuanced needs of special education. It is critically important, both legally and morally, for DSEs to have skills and mindsets to be effective in their roles. It is imperative that the field identify effective methods of training, developing, and supporting DSEs in the competencies they need to successfully serve all learners. This piece shares one Institute of Higher Education's (IHE's Council for Exceptional Children) process for revising an existing preparation program through an innovative partnership with statewide, practicing DSEs. Results of statewide program reviews and DSE surveys and focus groups highlight the critical capacities needed for DSEs to be effective on the job as well as ways to rethink what effective DSE licensure programs could and should look like.

Upholding critical race theory (CRT)'s transdisciplinary approach to unveil the educational violence against Students of Color, we apply W.E.B. Du Bois's story of John from the chapter "Of the Coming of John" in "The Souls of Black Folk." In doing so, we expose the problematic ideological and practical structures used for the identification and retention of Students of Color within gifted and talented programming. Examining the concepts of the Veil and double consciousness through the analogous relationship of Du Bois's John to a contemporary John, we parallel the insidious educational experiences of Students of Color that has remained relatively constant over time.

First-generation immigrants (FGIs) are eager to achieve the American dream and acquire the advantages a bachelor's degree affords. FGIs compared to their second-generation, third-generation and native peers fare better educationally. But, this comparison obscures across racial variation within a single-nativity status. As such, it is important to understand what mechanisms might produce inequality in college access among FGIs. One mechanism may be differences in how schools support students for college-going. The content of support may vary if racial stereotypes affect how support is given. Such variations could be decisive for FGIs' educational trajectories. We find that Latinx and black FGIs are less likely than other FGIs to enroll in bachelor-degree programs. The content of school support is a mechanism that can help partially explain this differential for black FGIs. Our findings indicate that how schools support black FGIs for college-going is different and is likely at least implicitly racially biased.

Objective: Human papillomavirus vaccination coverage is suboptimal, especially among males. Social networks influence young adults' health behaviors and could be leveraged to promote vaccination. We sought to describe how young sexual minority men communicate about human papillomavirus (HPV) vaccination with their sexual partners. Participants: National (U.S.) sample of sexual minority men ages 18-26 (n = 42) from January 2019. Methods: We conducted four online focus groups and identified salient themes using inductive content analysis. Results: Across groups, participants described that HPV vaccination is not a focus of their conversations with sexual partners. Other key themes related to HPV vaccine communication included: varying discussions based on relationship type, and valuing conversations with partners about safer sex. Conclusions: Findings provide novel insight into how young sexual minority men communicate with their sexual partners about HPV vaccination and identify potential areas for interventions to promote communication. Future research is needed to investigate associations between partner communication and HPV vaccine uptake.

This study examines how parents' mental health symptoms, emotion regulation and mindfulness relate to parent-child reminiscing conversations about past emotional events. Fifty-four children aged 8-12 years and their parents were recruited from a child psychology clinic (n = 28) and local schools (n = 26). Dyad's reminiscing conversations were recorded, transcribed, and coded for elaboration style, emotion content and emotion closure. Child language ability and mental health symptoms were measured, as was parent mindfulness, emotion regulation and mental health symptoms. Mindfulness acting with awareness was a unique predictor of dyad emotion closure. Depression, anxiety, and stress symptoms were not directly related to elaborative reminiscing, however, moderation by clinical status revealed a negative relationship for the community children only. These findings suggest a more complex relationship at play between parent and child mental health in reminiscing within clinical populations. Implications of these findings for a growing body of reminiscing interventions are discussed.

Purpose: Families and professionals often consider augmentative and alternative communication (AAC) a "last resort" for persons with communication challenges; however, speaking autistic adults have reported that they would have benefited from access to AAC as children. This tutorial discusses the history of this "last resort" practice and its perpetuation within the medical model of disability. The tutorial focuses on communication access, choice, and agency for autistic students. Method: We provide a brief overview of the AAC community and their preferred terminology, review the history of traditional approaches to research on AAC and autism, and then examine the relationship between disability models and ableism to views of spoken language as a priority of intervention. Studies on this topic are rare, and resisting ableism requires acknowledging and honoring disabled people's experiences and expertise. Therefore, we promote autistic expertise within the framework of evidence-based practice and discuss the experiences of autistic people and spoken language. Finally, we consider the role of the speech-language pathologist (SLP) in assessment and offer autistic-based strategies and recommendations for communication support. Conclusions: Speaking autistic students who could benefit from AAC may not have access to AAC due to the prioritization of spoken language and lack of awareness of the benefit of AAC. We recommend that SLPs and school-based professionals support and facilitate access, communicative choice, and agency by implementing multimodal communication strategies to include AAC use for autistic students regardless of their spoken language status. Promoting all types of communication and ensuring opportunities for communication across multiple modalities are paramount to a child's agency and self-determination, as is normalization of AAC.

The United States has a higher rate of teen pregnancy than any other developed country with 30% of American girls becoming pregnant before the age of 20. Laws regarding the inclusion and content of sexuality education vary across the country, which are associated with differences in pregnancy and sexually transmitted infection (STI) rates between states. This systematic review aims to determine whether comprehensive sexuality education (CSE) is more effective than abstinence-only or no sexuality education at reducing teenage pregnancy. Secondary objectives include analyzing the effect of CSE on STI incidence, sexual activity, safe-sex behaviors, and social discomfort. We searched multiple databases for studies published from 1990 to 2021. Twenty-nine studies met our inclusion criteria. Seven included pregnancy as an outcome, with three fitting our meta-analysis criteria. There was a decrease in pregnancy rates for participants in the CSE intervention compared to the control (n = 3, risk ratio = 0.89, 95%CI 0.79-1.00, I[superscript 2] = 0%). We found that CSE is likely to reduce pregnancy rates; however, there was limited data available on this outcome. CSE increased safe-sex behaviors but did not have a notable impact on sexual activity or STIs. This review can serve as evidence for the implementation of CSE in the US.

Purpose: Access to communication is a basic human right, yet autistic adults have reported challenges fully and effectively expressing themselves throughout childhood. This may be due to the historical (and ongoing) focus and prioritization of speech skills as a barometer of communicative success. The result is a lack of support for other forms of communication for children who may speak but still require support to fully meet their communication needs. This study aimed to examine the knowledge, experience, and training of school-based professionals in order to better understand one possible barrier to early communication access for autistic children. Method: Using a participatory research method, we designed and administered a 35-question online survey. A total of 567 participants completed the survey, including 465 special educators, 71 speech-language pathologists (SLPs), and 31 other professionals. A segment of the survey data was analyzed in R. Comparisons between and within the largest groups (SLPs and special educators) were made with nonparametric statistics, including Fisher's exact, Wilcoxon signed-ranks, and Quade tests. Results: SLPs and special educators differed significantly on a variety of survey measures, including undergraduate coursework in augmentative and alternative communication (AAC) and autism, caseloads, and confidence related to working with autistic students and AAC users. Regardless of profession, most respondents reported completing what they considered to be an AAC assessment. Conclusions: Increasing school-based professionals' knowledge related to autism and AAC, as well as opportunities to improve skills, is critical to resolving access and opportunity barriers for autistic children who speak but may benefit from AAC. Partnering with autistic people to better understand autistic speech and careful collaboration among team members are recommended.

Objective: This study explored how COVID-related mental health and well-being varied between undergraduate and graduate students. Relationships with physical health behaviors were also examined. Participants: Undergraduate (n = 897) and graduate (n = 314) students were recruited from three US universities between mid-April and late-May 2020. Methods: Participants in this cross-sectional survey self-reported perceived stress, financial stress, resilience, repetitive negative thinking, mood, anxiety, diet, sleep, and physical activity using validated instruments. Results: Undergraduate students reported more perceived stress, more repetitive negative thinking, less positive mood, and less support from professors than graduate students. Perceived stress, repetitive negative thinking, negative mood, and anxiety increased among all students (p < 0.05 for all). Correlations between mental health outcomes and physical health behaviors were weak to moderate (r = 0.08 to 0.49). Conclusions: College students, particularly undergraduates, perceived negative mental health impacts during COVID. Creative approaches for meeting student needs are necessary.

Visual (perceptual) reasoning is a critical skill in many medical specialties, including pathology, diagnostic imaging, and dermatology. However, in an ever-compressed medical curriculum, learning and practicing this skill can be challenging. Previous studies (including work with pigeons) have suggested that using reward-feedback-based activities, novices can gain expert levels of visual diagnostic accuracy in shortened training times. But is this level of diagnostic accuracy a result of image recognition (categorization) or is it the acquisition of diagnostic expertise? To answer this, the authors measured electroencephalographic data (EEG) and two components of the human event-related brain potential (reward positivity and N170) to explore the nature of visual expertise in a novice-expert study in pathology visual diagnosis. It was found that the amplitude of the reward positivity decreased with learning in novices (suggesting a decrease in reliance on feedback, as in other studies). However, this signal remained significantly different from the experts whose reward positivity signal did not change over the course of the experiment. There were no changes in the amplitude of the N170 (a reported neural marker of visual expertise) in novices over time. Novice N170 signals remained statistically and significantly lower in amplitude compared to experts throughout task performance. These data suggest that, while novices gained the ability to recognize (categorize) pathologies through reinforcement learning as quantified by the change in reward positivity, increased accuracy, and decreased time for responses, there was little change in the neural marker associated with visual expertise (N170). This is consistent with the multi-dimensional and complex nature of visual expertise and provides insight into future training programs for novices to bridge the expertise gap.

Lesbian, gay, bisexual, and queer (LGBQ) youth experience more heterosexist bullying victimization than their straight peers, which contributes to mental health disparities. However, LGBQ youth may simultaneously experience other types of bias-based bullying (e.g., racist, cis-sexist, and able-ist bullying). Informed by intersectionality theory, this study describes intersections of LGBQ students' experiences of multiple forms of bias-based bullying and explores demographic correlates of individual types and typologies of bias-based bullying. This study uses 2016 state-wide survey data from 9th and 11th grade students in Minnesota schools. The analytic sample was limited to students who reported a LGBQ sexual orientation and responded to bullying items (N = 8313). Typology indicators were six items assessing bias-based bullying in the previous 30 days (race, gender, gender expression, sexual orientation, ability, weight). Covariates (age, sexual orientation, assigned sex, gender identity, race, perceived gender presentation, individualized education program (IEP), weight status) also predicted class membership. A latent class analysis (LCA) was conducted, and the three-class model was best fitting, with classes characterized by high levels of all types of bias-based bullying (6.3%), gender expression and sexual orientation bullying (35.2%), and low levels of bias-based bullying (58.4%). LGBQ youth who also identified as transgender or gender diverse, had an IEP, reported perceived nonconforming gender presentation, and youth of color were more likely to belong to the multiple bias-based bullying typology. Future work should leverage an intersectional lens to design multilevel interventions and strategies to prevent bias-based bullying that attend to broader issues of stigma within school systems.

Research suggests the need to assess both positive and negative forms of student engagement. The purpose of this study was to pilot disaffection items with the Student Engagement Instrument (SEI) with a sample of middle school students from a rural area in the Southeastern U.S. This study explored the factor structure of the piloted items alongside the SEI, measurement invariance, and associations between student engagement and disaffection with educational outcomes such as mathematics and reading test scores, discipline referrals, and absences. Results hold implications for our theoretical understanding of engagement, suggesting that engagement and disaffection dimensions are theoretically and psychometrically distinct.

Background Data sharing in developmental science is increasingly encouraged, supported by funder and publisher mandates for open data access. Data sharing can accelerate discovery, link researchers with high quality analytic expertise to researchers with large datasets and democratise the research landscape to enable researchers with limited funding to access large sample sizes. However, there are also significant privacy and security concerns, in addition to conceptual and ethical considerations. These are particularly acute for developmental science, where child participants cannot consent themselves. As we move forward into a new era of data openness, it is essential that we adequately represent the views of stakeholder communities in designing data sharing efforts. Methods We conducted a comprehensive survey of the opinions of 195 parents on data sharing in developmental science. Survey themes included how widely parents are willing to share their child’s data, which type of organisations they would share the data with and the type of consent they would be comfortable providing. Results Results showed that parents were generally supportive of curated, but not open, data sharing. In addition to individual privacy and security concerns, more altruistic considerations around the purpose of research were important. Parents overwhelmingly supported nuanced consenting models in which preferences for particular types of data sharing could be changed over time. This model is different to that implemented in the vast majority of developmental science research and is contrary to many funder or publisher mandates. Conclusions The field should look to create shared repositories that implement features such as dynamic consent and mechanisms for curated sharing that allow consideration of the scientific questions addressed. Better communication and outreach are required to build trust in data sharing, and advanced analytic methods will be required to understand the impact of selective sharing on reproducibility and representativeness of research datasets.

Rift Valley fever virus (RVFV) is an encephalitic bunyavirus that can infect neurons in the brain. There are no approved therapeutics that can protect from RVFV encephalitis. Innate immunity, the first line of defense against infection, canonically antagonizes viruses through interferon signaling. We found that interferons did not efficiently protect primary cortical neurons from RVFV, unlike other cell types. To identify alternative neuronal antiviral pathways, we screened innate immune ligands and discovered that the TLR2 ligand Pam3CSK4 inhibited RVFV infection, and other bunyaviruses. Mechanistically, we found that Pam3CSK4 blocks viral fusion, independent of TLR2. In a mouse model of RVFV encephalitis, Pam3CSK4 treatment protected animals from infection and mortality. Overall, Pam3CSK4 is a bunyavirus fusion inhibitor active in primary neurons and the brain, representing a new approach toward the development of treatments for encephalitic bunyavirus infections.

Abstract Objective Cartilaginous tumors of the larynx are rare, representing less than 1% of all laryngeal tumors. Chondromas are benign mesenchymal tumors characterized by a slow‐paced growth, primarily originated in the cricoid cartilage, followed by the thyroid, arytenoid, and epiglottic cartilages. This scoping review aims to understand the extent of evidence on the epidemiology, clinical characteristics, morbidity, and recurrence of the laryngeal chondroma (LC). Data sources MEDLINE (Ovid), Embase (Elsevier), Web of Science (Clarivate), Cochrane Central Register of Controlled Trials and Systematic Reviews, Lilacs, Scopus, and Google Scholar databases. Review methods The scoping review was conducted from 1816 to 2023, for observational studies describing LC. Titles and abstracts were screened for relevance, followed by an evaluation of the full text for eligibility. The data were collected from the qualifying articles, and a narrative summary of the outcomes was prepared. Results One hundred and nineteen studies met the inclusion criteria. Ninety‐four case reports, 22 case series, and 3 cohorts. Two hundred and four participants with a diagnosis of LC were described. Male:female ratio was 2.8:1. The most common localization was the cricoid (113; 47.08%), followed by the thyroid (45; 18.75%), and the arytenoid cartilage (27; 11.25%). Dyspnea (78.85%) and hoarseness (74.28%) were the most reported symptoms. The recurrence rate was 11.25%, and complications were uncommon following the resection. Conclusion This scoping review found a low‐frequency rate over all the cartilaginous laryngeal tumors. Most patients were treated with resection, with a low rate of malignancy conversion. This population has low attributable mortality, morbidity, and recurrence according to the current literature.

Introduction Medical curricula implicitly teach that race has a biological basis. Clinical rotations reinforce this misconception as race-based algorithms are used to guide clinical decision-making. This module aims to expose the fallacy of race in clinical algorithms, using the estimated glomerular filtration rate (eGFR) equation as an example. Methods We created a 60-minute module in consultation with nephrologists. The format was an interactive, case-based presentation with a didactic section. A third-year medical student facilitated the workshops to medical students. Evaluation included pre/post surveys using 5-point Likert scales to assess awareness regarding use of race as a biological construct. Higher scores indicated increased awareness. Results Fifty-five students participated in the module. Pre/post results indicated that students significantly improved in self-perceived knowledge of the history of racism in medicine (2.6 vs. 3.2, p < .001), awareness of race in clinical algorithms (2.7 vs. 3.7, p < .001), impact of race-based eGFR on quality of life/treatment outcomes (4.5 vs. 4.8, p = .01), differences between race and ancestry (3.7 vs. 4.3, p < .001), and implications of not removing race from the eGFR equation (2.7 vs. 4.2, p < .001). Students rated the workshops highly for quality and clarity. Discussion Our module expands on others’ work to expose the fallacy of race-based algorithms and define its impact on health equity. Limitations include a lack of objective assessment of knowledge acquisition. We recommend integrating this module into preclinical and clinical curricula to discuss the use of race in medical literature and clinical practice.

Objectives In the face of unprecedented demand, the Welsh Ambulance Services University NHS Trust developed ‘Blue Light Hub’: a new app to educate primary school-aged children about emergency services. Our overarching aim was to examine the effectiveness of the app.Design Primary school-aged children from three schools in South Wales, UK, played with the app for 2 hours over 2 weeks in class time. Children completed quizzes to assess their knowledge and awareness of, and confidence in engaging with, emergency services before and after using the app.Participants Our evaluation focused on N=393 children who completed both the pre-test and post-test quizzes. On average, children were 8–9 years old (median school year, Year 4); 47.8% were male and 50.9% were female.Results After using the app, there was a significant increase in the proportion of children who knew of appropriate actions to take in non-emergency scenarios, χ2(1) = 26.01, and could provide a question a call handler would ask them if they called 999, χ2(1) = 13.79. There was also an increase in the proportion of children who could identify an National Health Service (NHS) service that could help them if they were unwell, χ2(1) = 33.31, name different roles in the NHS, χ2(1) = 12.80 and knew how dialling 111 could help them χ2(1) = 90.05 (all p values

BackgroundThe shift toward online recruitment methods, accelerated by the COVID-19 pandemic, has brought to the forefront the growing concern of encountering fraudulent participants in health care research. The increasing prevalence of this issue poses a serious threat to the reliability and integrity of research data and subsequent findings. ObjectiveThis study aims to explore the experiences of health care researchers (HCRs) who have encountered fraudulent participants while using online recruitment methods and platforms. The primary objective was to gain insights into how researchers detect and mitigate fraudulent behavior in their work and provide prevention recommendations. MethodsA multimethod sequential design was used for this pilot study, comprising a quantitative arm involving a web-based survey followed by a qualitative arm featuring semistructured interviews. The qualitative description approach framed the qualitative arm of the study. Sample sizes for the quantitative and qualitative arms were based on pragmatic considerations that in part stemmed from encountering fraudulent participants in a concurrent study. Content analysis was used to analyze open-ended survey questions and interview data. ResultsA total of 37 HCRs participated, with 35% (13/37) of them engaging in qualitative interviews. Online platforms such as Facebook, email, Twitter (subsequently rebranded X), and newsletters were the most used methods for recruitment. A total of 84% (31/37) of participants indicated that fraudulent participation occurred in studies that mentioned incentives in their recruitment communications, with 71% (26/37) of HCRs offering physical or electronic gift cards as incentives. Researchers identified several indicators of suspicious behavior, including email surges, discrepancies in contact or personal information, geographical inconsistencies, and suspicious responses to survey questions. HCRs emphasized the need for a comprehensive screening protocol that extends beyond eligibility checks and is seamlessly integrated into the study protocol, grant applications, and research ethics board submissions. ConclusionsThis study sheds light on the intricate and pervasive problem of fraudulent participation in health care research using online recruitment methods. The findings underscore the importance of vigilance and proactivity among HCRs in identifying, preventing, and addressing fraudulent behavior. To effectively tackle this challenge, researchers are encouraged to develop a comprehensive prevention strategy and establish a community of practice, facilitating real-time access to solutions and support and the promotion of ethical research practices. This collaborative approach will enable researchers to effectively address the issue of fraudulent participation, ensuring the conduct of high-quality and ethically sound research in the digital age.

Background: COVID-19 disrupted the TB prevention programme in the UK, especially for TB infection (TBI) care. We explore whether experience of the COVID-19 pandemic impacted on patients' perceptions of TBI and its treatment. Methods: Semi-structured interviews were conducted as part of the Research to Improve Detection and Treatment of TBI (RID-TB) programme, exploring perceptual and practical barriers to TBI treatment. Nineteen people diagnosed with TBI were interviewed between August 2020 and April 2021. Recordings were transcribed and analysed using a constant comparative approach, allowing for a dynamic and iterative exploration of themes. Themes are organised using the Perceptions and Practicalities Approach. Findings: Some participants perceived TBI as a risk factor for increased susceptibility to COVID-19, while some thought that treatment for TBI might protect against COVID-19 or mitigate its effects. Adaptations to TB services (e.g., remote follow-up) and integrated practices during the COVID-19 restrictions (e.g., medication being posted) addressed some practical barriers to TBI treatment. However, we identified beliefs about TBI and COVID-19 that are likely to act as barriers to engagement with TBI treatment, including: interpreting service delays as an indication of TBI not being serious enough for treatment and concerns about contracting COVID-19 in TB clinics. Interpretation: COVID-19 and TBI service delays influence people's perceptions and practical barriers to TBI treatment adherence. Failure to address these beliefs may lead to people's concerns about their treatment not being fully addressed. Utilised service adaptations like remote consultations to address practical barriers may be relevant beyond COVID-19. Funding: NIHR RID-TB Program (RP-PG-0217-20009).

Influenza A virus (IAV) infection is initiated by hemagglutinin (HA), a glycoprotein exposed on the virion’s lipid envelope that undergoes cleavage by host cell proteases to ensure membrane fusion, entry into the host cells, and completion of the viral cycle. Transmembrane protease serine S1 member 2 (TMPRSS2) is a host transmembrane protease expressed throughout the porcine airway epithelium and is purported to play a major role in the HA cleavage process, thereby influencing viral pathogenicity and tissue tropism. Pigs are natural hosts of IAV and IAV disease causes substantial economic impact on the pork industry worldwide. Previous studies in mice demonstrated that knocking out expression of TMPRSS2 gene was safe and inhibited the spread of IAV after experimental challenge. Therefore, we hypothesized that knockout of TMPRSS2 will prevent IAV infectivity in the swine model. We investigated this hypothesis by comparing pathogenesis of an H1N1pdm09 virus challenge in wildtype (WT) control and in TMPRSS2 knockout (TMPRSS2−/−) pigs. We demonstrated that TMPRSS2 was expressed in the respiratory tract in WT pigs with and without IAV infection. No differences in nasal viral shedding and lung lavage viral titers were observed between WT and TMPRSS2−/− pigs. However, the TMPRSS2−/− pig group had significantly less lung lesions and significant reductions in antiviral and proinflammatory cytokines in the lung. The virus titer results in our direct challenge model contradict prior studies in the murine animal model, but the reduced lung lesions and cytokine profile suggest a possible role for TMPRSS2 in the proinflammatory antiviral response. Further research is warranted to investigate the role of TMPRSS2 in swine IAV infection and disease.

IntroductionTranscranial photobiomodulation (tPBM) is a non-invasive neuromodulation technique that improves human cognition. The effects of tPBM of the right forehead on neurophysiological activity have been previously investigated using EEG in sensor space. However, the spatial resolution of these studies is limited. Magnetoencephalography (MEG) is known to facilitate a higher spatial resolution of brain source images. This study aimed to image post-tPBM effects in brain space based on both MEG and EEG measurements across the entire human brain.MethodsMEG and EEG scans were concurrently acquired for 6 min before and after 8-min of tPBM delivered using a 1,064-nm laser on the right forehead of 25 healthy participants. Group-level changes in both the MEG and EEG power spectral density with respect to the baseline (pre-tPBM) were quantified and averaged within each frequency band in the sensor space. Constrained modeling was used to generate MEG and EEG source images of post-tPBM, followed by cluster-based permutation analysis for family wise error correction (p < 0.05).ResultsThe 8-min tPBM enabled significant increases in alpha (8–12 Hz) and beta (13–30 Hz) powers across multiple cortical regions, as confirmed by MEG and EEG source images. Moreover, tPBM-enhanced oscillations in the beta band were located not only near the stimulation site but also in remote cerebral regions, including the frontal, parietal, and occipital regions, particularly on the ipsilateral side.DiscussionMEG and EEG results shown in this study demonstrated that tPBM modulates neurophysiological activity locally and in distant cortical areas. The EEG topographies reported in this study were consistent with previous observations. This study is the first to present MEG and EEG evidence of the electrophysiological effects of tPBM in the brain space, supporting the potential utility of tPBM in treating neurological diseases through the modulation of brain oscillations.

This article addresses the English centrality in reading policy, assessment, and instructional practices in the U.S. and its implications for the educational programing for emerging bilingual students (EBs) with disabilities. A recent review of the state of practice as it relates to EBs with disabilities reveals concerns that have endured for nearly six decades: biased assessment, disproportionality issues in special education, and teachers’ lack of understanding of language acquisition and students’ potential. These concerns demonstrate a need for the field to prioritize multilingual lenses for both the identification of and programming for EBs with disabilities. We propose attention to conceptions of language that expand beyond the structuralist standpoint that prevails in the current science of reading reform. We offer guiding principles for IEP development grounded in sociocultural perspectives when designing bilingual instructional practices, which can be applied to the educational programming for EBs with disabilities. Within a sociocultural view of bilingualism and biliteracy, language, and literacy are understood by multiplicities in use, practice, form, and function, in which all communicators draw from expansive meaning-making repertoires, whether in listening, speaking, reading, writing, viewing, and multimodally representing. By expanding conceptions of a student’s linguistic repertoire, we honor their use of language as one, holistic system in which their named languages plus a multitude of linguistic practices intersect and interact.

BACKGROUND:. Pain management is essential for postoperative surgery. Given the association of opioids with adverse outcomes, interest in the use of nonopioid analgesics, such as ketorolac, has increased. Published data on use in neonates are limited. OBJECTIVES:. To describe ketorolac dosing and safety and efficacy outcomes in the first 48 hours postcardiac surgery in neonates. DESIGN:. We performed a single-center retrospective cohort study of neonates (ages < 28 d) who received ketorolac following cardiac surgery from November 2020 to July 2023 (inclusive). The primary safety outcome was a clinically significant decline in renal function, as defined by the composite of an increase in serum creatinine by greater than or equal to 0.3 mg/dL from baseline within 96 hours of ketorolac initiation and urine output less than or equal to 0.5 mL/kg/hr for 6 hours. The secondary safety outcome was clinically significant bleeding, defined as the composite of major bleeding by the International Society on Thrombosis and Hemostasis pediatric criteria and severe/fatal bleeding by the criteria of Nellis et al (2019). Efficacy was measured by opioid utilization based on a standardized pain score-driven analgesia protocol. INTERVENTIONS:. Ketorolac was administered at 0.5 mg/kg every 6 hours as per an institutional clinical management algorithm. MEASUREMENTS AND MAIN RESULTS:. Thirty-nine patients met the eligibility criteria. The median ketorolac dose was 0.5 mg/kg/dose, and median (interquartile range [IQR]) duration of therapy was 48 hours (6–48 hr). No patients experienced a significant decline in renal function, and there were no clinically significant bleeding events. The median (IQR) IV morphine milligram equivalents (MMEs)/kg/d of opioid administration was 0.2 MME/kg/d (0.1–0.25 MME/kg/d) at the time of ketorolac initiation and 0.1 MME/kg/d (0.1–0.2 MME/kg/d) at 48 hours post-ketorolac initiation. CONCLUSIONS:. If validated prospectively, these findings suggest that a ketorolac regimen of 0.5 mg/kg/dose every 6 hours in neonates postcardiac surgery may be safe with regard to renal function and bleeding risk. Additional randomized studies would be needed to determine efficacy with regard to opioid-sparing capacity.

Ketogenic diets have been widely used for weight loss and are increasingly used in the management of type 2 diabetes. Despite evidence that ketones have multiple positive effects on kidney function, common misconceptions about ketogenic diets, such as high protein content and acid load, have prevented their widespread use in individuals with impaired kidney function. Clinical trial evidence focusing on major adverse kidney events is sparse. The aim of this review is to explore the effects of a ketogenic diet, with an emphasis on the pleiotropic actions of ketones, on kidney health. Given the minimal concerns in relation to the potential renoprotective effects of a ketogenic diet, future studies should evaluate the safety and efficacy of ketogenic interventions in kidney disease.

Abstract Octopus cyanea (Gray, 1849), abundant in the South‐West Indian Ocean (SWIO), constitutes a vital resource for both subsistence and commercial fisheries. However, despite this socioeconomic importance, and recent indications of overfishing, little is known about the population structure of O. cyanea in the region. To inform sustainable management strategies, this study assessed the spatio‐temporal population structure and genetic variability of O. cyanea at 20 sites in the SWIO (Kenya, Tanzania, Mozambique, Madagascar, Mauritius, Rodrigues, and the Seychelle Islands) by complementary analysis of mitochondrial DNA (mtDNA) noncoding region (NCR) sequences and microsatellite markers. MtDNA analysis revealed a shallow phylogeny across the region, with demographic tests suggesting historic population fluctuations that could be linked to glacial cycles. Contrary to expectations, NCR variation was comparable to other mtDNA regions, indicating that the NCR is not a hypervariable region. Both nuclear and mtDNA marker types revealed a lack of genetic structure compatible with high gene flow throughout the region. As adults are sedentary, this gene flow likely reflects connectivity by paralarval dispersal. All samples reported heterozygote deficits, which, given the overall absence of structure, likely reflect ephemeral larval recruitment variability. Levels of mtDNA and nuclear variability were similar at all locations and congruent with those previously reported for harvested Octopodidae, implying resilience to genetic erosion by drift, providing current stock sizes are maintained. However, as O. cyanea stocks in the SWIO represent a single, highly connected population, fisheries may benefit from additional management measures, such as rotational closures aligned with paralarval ecology and spanning geopolitical boundaries.

Introduction Adolescents and young adults are susceptible population when it comes to healthy eating and dietary behaviours. The increasing use of social media by this age group presents a unique opportunity to promote healthy eating habits. Social media has become a popular platform for promoting health interventions, particularly among young people. However, there is a lack of consensus on the effectiveness of social media interventions in this population. This mixed-method systematic review aims to synthesise the available evidence on the impact of social media interventions on healthy eating behaviours among young people, their qualitative views and user experiences, and the intervention characteristics, behaviour change theories and techniques used to promote healthy eating.Methods and analysis We will conduct a comprehensive search of seven electronic databases, including ASSIA, Cochrane Library, Embase, MEDLINE, PsycINFO, Scopus and Web of Science. The search strategy will use a combination of Medical Subject Headings terms and keywords covering three domains: social media, eating behaviours and young people. The search will be limited to peer-reviewed published papers in any language, published from 2000. Three independent reviewers will screen studies based on predetermined eligibility criteria. Data will be extracted and analysed using a convergent segregated mixed-method approach. We will use random-effect meta-analysis or Synthesis Without Meta-analysis for quantitative data and thematic synthesis for qualitative data. Finally, narrative synthesis using concurrent triangulation will be used to bring together the results of the mixed-method data analysis to provide a comprehensive and integrated understanding of the impact and other features of social media interventions. This systematic review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Ethics and dissemination Ethical approval is not required since this systematic review will not collect original data. The outcomes of this review will be shared through peer-reviewed publications and conference presentations and will contribute to the PhD thesis of the primary author.PROSPERO registration number CRD42023414476.

PurposeGlare is a known side effect of intraocular lens (IOL) implantation, affected principally by IOL material and optics, although it is reported subjectively to decrease in impact with time. However, little objective data have been published on changes over time, how these relate to subjective reports, and whether those who will report greater glare symptoms can be predicted prior to IOL implantation.MethodsA total of 32 patients (aged 72.4 ± 8.0 years) with healthy eyes were implanted bilaterally with hydrophilic 600s (Rayner, Worthing, UK) or hydrophobic Acrysof (Alcon, Texas, USA) acrylic IOLs (n = 16 each, randomly assigned). Each patient reported their dysphotopsia symptoms subjectively using the validated forced choice photographic questionnaire for photic phenomena, and halo size resulting from a bright light in a dark environment was quantified objectively in eight orientations using the Aston Halometer. Assessment was performed binocularly pre-operatively and at 1, 2, 3, and 4 weeks after IOL implantation.SettingThe study was carried out at the National Health Service Ophthalmology Department, Queen Elizabeth Hospital, Birmingham, UK.ResultsVisual acuity (average 0.37 ± 0.26 logMAR) did not correlate with subjective glare (r = 0.184, p = 0.494) or objective glare (r = 0.294, p = 0.270) pre-surgery. Objective halo size (F = 112.781, p < 0.001) decreased with cataract removal and IOL implantation and continued to decreased over the month after surgery. Subjective dysphotopsia complaints (p < 0.001) were also greater pre-surgery, but did not change thereafter (p = 0.228). In neither case was there a difference with IOL material (p > 0.05). It was not possible to predict post-surgery dysphotopsia from symptoms or a ratio of symptoms to halo size pre-surgery (p > 0.05).ConclusionsSubjective dysphotopsia and objective halos caused by cataracts are greatly reduced by implantation of IOL after cataract removal causing few perceivable symptoms. However, objective measures are able to quantify a further reduction in light scatter over the first month post-IOL implantation, suggesting that any subjective effects over this period are due to the healing process and not due to neuroadaptation.