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Introduction Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methods GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017.Results Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes.Conclusions This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women.Trial registration number ClinicalTrials.gov (NCT01794143)

This study examines the impact of early Algebra I coursework on advanced Carnegie credits among 12th graders from diverse racial/ethnic backgrounds, using data from the NCES HSTS (1990-2019). Findings indicate that early Algebra students, particularly Black and Latinx, earn more advanced credits, revealing a widening gap in advanced course attainment. The study underscores the importance of early Algebra in college readiness and STEM preparation, highlighting the need for interventions to address educational disparities. Future research should explore additional factors influencing college readiness.

The relationship between academic tracking and exclusionary discipline actions has only been studied in a limited number of empirical studies. By placing students at the lower strata, schools deprive them of the educational opportunities, widening the educational opportunity gap in a process we define as "opportunity stratification." Using a quantitative analysis of data from the Educational Longitudinal Study, we found students in low-track, non-college preparatory courses had higher odds of experiencing both in-school and out-of-school suspensions when compared to students in the high-track, college preparatory courses. Our findings support the intersecting role of exclusionary discipline and tracking in opportunity stratification.

Abstract Background To investigate the impact of optic disc torsion (ODT), horizontal disc tilt (HDT) angle, and ovality index (OI) on different retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) segments in healthy myopic eyes. Methods ODT and OI were measured from fundus photographs. HDT angle, peripapillary RNFL, and macular GCIPL were measured by swept-source optical coherence tomography (SS-OCT). The association between optic disc morphology and the RNFL/GCIPL thickness were evaluated, with age and axial length (AL) adjusted. Results Among 530 healthy myopic eyes of 284 participants (mean age: 41.7 years, mean spherical equivalent: − 7.70 D, and mean AL: 26.6 mm), 335 eyes (63.2%) had temporal disc torsion (temporal group) and 195 eyes (36.8%) had nasal disc torsion (nasal group). For the nasal group, a larger OI was associated with thinner superior-to-superonasal GCIPL (β = − 7.465 to − 6.972, both P = 0.024) and temporal RNFL sectors (β = − 49.596 to − 27.748, P ≤ 0.014). For the temporal group, a larger OI was associated with thinner superior-to-nasal (β = − 50.255 to − 22.093, P ≤ 0.006) and thicker temporal RNFL sectors (β = 29.015 to 56.890, P ≤ 0.003). Additionally, a larger HDT angle was associated with thinner superior-to-nasal RNFL sectors (β = − 0.559 to − 0.242, P ≤ 0.036) and thinner superior-to-superotemporal GCIPL sectors (β = − 0.084 to − 0.069, P ≤ 0.037). Conclusions The optic disc tortional direction was associated with the measurement of different RNFL and GCIPL sectors independent of the AL and age. These should be considered when constructing a myopic normative database.

Two essential questions for those leading the field of public administration are: What do we teach our students, and how do we train them? As scholars, we pay significant attention to our research, often to the detriment of recognizing the potential for merging our research with teaching through the Scholarship of Teaching and Learning (SoTL). However, given our students' leadership positions, SoTL-related work is vital to their success. In this article, we have come together to reflect on the state of SoTL's work in public administration. Through this reflection, we explore the windows of opportunity for research that we see emerging. Included among these opportunities is the need for research on how we can best serve students in and out of the classroom, as well as research the most effective way of managing our programs. We also see the need for research into faculty development, instructional design, and the return on investment for a public administration degree. Lastly, we argue for improved recognition of the value and contribution of SoTL-related work in tenure and promotion standards.

This study utilizes quantitative content analysis (QCA) and deductive qualitative approach (DQA) grounded in Ruiz's orientations of language planning to understand the landscape of bilingual educational research. This QCA included targeted counts from bilingual journal articles (n = 102) covering methodology, participants, region, and bilingual program. DQA used coding methods to infer whether programs maintained a positive or negative iteration of bilingualism. The QCA suggests that articles published are centered on qualitative methodologies, conducted in elementary dual-language classrooms, and concentrated in the northeastern and western US. The DQA demonstrates programs maintain a language-as-resource orientation. These findings provide important implications for researchers studying bilingual education.

Little is currently known about the autism spectrum disorder (ASD)-related difficulties of females narrowly below the ASD diagnostic threshold and whether the disorder conceptualisation should be broadened to capture their presentations. We extracted fine-grained information from the assessment reports of 222 children who were either diagnosed with ASD (n = 156) or not diagnosed despite many ASD traits (n = 78). Females were less likely than males to meet Criterion B3 (restricted interests), and this was especially the case for subclinical (non-ASD) females. Non-ASD females lacked sufficient atypicality for diagnosis in several key domains, particularly Criterion A1 (social-emotional reciprocity). Evidence of sex/gender-specific restricted interests and stereotypical behaviours was found. Many behaviours differed in the extent to which they predicted the ASD diagnostic result for males and females, perhaps suggesting that sex/gender influences how ASD-related behaviours are perceived. We discuss these findings in the context of underdiagnosis of ASD in females and propose adjustments to assessment protocols.

The development of equitable grading systems that provide students with effective feedback and provide instructors with an efficient means of assessment are of deep interest to chemical educators. A recent trend in chemical education, and STEM education more broadly, has been the use of specifications, or specs, grading that emphasizes mastery of material through recursive methods and standards-based grading. Students must meet certain standards in multiple specifications to earn a particular letter grade, as opposed to more traditional points-based grading systems. However, changing from a points-based grading system to specs grading requires significant effort by the instructor, especially in courses with an integrated lab component. In this manuscript we describe the development of a hybrid-specs grading system implemented in our second semester general chemistry course over the 2021-22 academic year. We describe the development of the hybrid-specs grading system, student performance as measured by shifts in letter grade distributions and final exam scores, and student perceptions of the new grading system. Notes for practitioners on the implementation of the grading system are in the Supporting Information. Finally, we also discuss improvements of the system for implementation in future courses.

Canada thistle (Cirsium arvense (L.) Scop., CT) is one of the worst weeds threatening temperate regions of the world. A host-specific rust fungus, Puccinia punctiformis (F. Strauss) Rohl., is known to cause systemic disease of CT, ultimately killing individuals and reducing stand densities. In 2013, it was demonstrated that fall inoculation of rosettes with coarsely ground leaves bearing P. punctiformis telia can successfully initiate epiphytotics. In the same year, a cooperative project between the Colorado Department of Agriculture and United States Department of Agriculture was initiated, in which CT patches across the state of Colorado (USA) were inoculated and tracked over subsequent years for changes in stem density. Here, we report our findings from 8 years (2014–2021) of monitoring effort. At most sites (N = 87), CT stem densities declined, from a mean (±SE) of 87.9 (±6.5) stems to 44.7 (±4.2). These declines however were spatially-autocorrelated, and likely attributable to local growing conditions, as mean annual daily maximum temperature and standard deviation of elevation, as well as climatic conditions around the times of both treatment and monitoring, were found to be important predictors of CT decline. Further, we observed that the amount of inoculum deployed, timing since last release, and method in which it was spread locally at a site were also associated with the magnitude of CT stem decline. These results are indicative of the value of P. punctiformis as a CT biological control agent.

A new study considering data from 7603 households across 28 sites in 22 low- and middle-income countries show that inequality of household water security follows a Development Kuznets Curve.

Abstract Background MDT discussion is the gold standard for cancer care in the UK. With the incidence of cancer on the rise, demand for MDT discussion is increasing. The need for efficiency, whilst maintaining high standards, is therefore clear. Paper-based MDT quality assessment tools and discussion checklists may represent a practical method of monitoring and improving MDT practice. This reviews aims to describe and appraise these tools, as well as consider their value to quality improvement. Methods Medline, EMBASE and PsycInfo were searched using pre-defined terms. The PRISMA model was followed throughout. Studies were included if they described the development of a relevant tool, or if an element of the methodology further informed tool quality assessment. To investigate efficacy, studies using a tool as a method of quality improvement in MDT practice were also included. Study quality was appraised using the COSMIN risk of bias checklist or the Newcastle-Ottawa scale, depending on study type. Results The search returned 7930 results. 18 studies were included. In total 7 tools were identified. Overall, methodological quality in tool development was adequate to very good for assessed aspects of validity and reliability. Clinician feedback was positive. In one study, the introduction of a discussion checklist improved MDT ability to reach a decision from 82.2 to 92.7%. Improvement was also noted in the quality of information presented and the quality of teamwork. Conclusions Several tools for assessment and guidance of MDTs are available. Although limited, current evidence indicates sufficient rigour in their development and their potential for quality improvement. Trial registration PROSPERO ID: CRD42021234326 .

Endometriosis is an estrogen dependent, chronic inflammatory disease characterized by the growth of endometrial lining outside of the uterus. Mast cells have emerged as key players in regulating not only allergic responses but also other mechanisms such as angiogenesis, fibrosis, and pain. The influence of estrogen on mast cell function has also been recognized as a potential factor driving disease pathophysiology in number of allergic and chronic inflammatory conditions. However, precise information is lacking on the cross talk between endocrine and immune factors within the endometriotic lesions and whether that contributes to the involvement of mast cells with disease pathophysiology. In this study, we observed a significant increase in mast cell numbers within endometriotic lesions compared to matched eutopic endometrium from the same patients. Compared to eutopic endometrium, endometriotic lesions had significantly higher levels of stem cell factor (SCF), a potent growth factor critical for mast cell expansion, differentiation, and survival for tissue resident mast cells. Targeted mRNA Q-PCR array revealed that the endometriotic lesions harbour microenvironment (upregulation of CPA3, VCAM1, CCL2, CMA1, CCR1, and KITLG) that is conducive to mast cells recruitment and subsequent differentiation. To examine cross-talk of mast cells within the endometriotic lesion microenvironment, endometriotic epithelial cells (12Z) and endometrial stromal cells (hESC) incubated with mast cell-conditioned media showed significantly increased production of pro-inflammatory and chemokinetic cytokines. To further understand the impact of estrogen on mast cells in endometriosis, we induced endometriosis in C57BL/6 mice. Mature mast cells were significantly higher in peritoneal fluid of estrogen-treated mice compared to untreated mice within the sham operated groups. Mouse endometriotic lesion tissue revealed several genes (qRT-PCR) relevant in mast cell biology significantly upregulated in the estrogen treated, endometriosis-induced group compared to control endometrium. The endometriotic lesions from estrogen treated mice also had significantly higher density of Alcian blue stained mast cells compared to untreated lesions or control endometrium. Collectively, these findings suggest that endometriotic lesions provide a microenvironment necessary for recruitment and differentiation of mast cells. In turn, mast cells potentially release pro-inflammatory mediators that contribute to chronic pelvic pain and endometriosis disease progression.

PurposeWe aim to develop a multi-task three-dimensional (3D) deep learning (DL) model to detect glaucomatous optic neuropathy (GON) and myopic features (MF) simultaneously from spectral-domain optical coherence tomography (SDOCT) volumetric scans.MethodsEach volumetric scan was labelled as GON according to the criteria of retinal nerve fibre layer (RNFL) thinning, with a structural defect that correlated in position with the visual field defect (i.e., reference standard). MF were graded by the SDOCT en face images, defined as presence of peripapillary atrophy (PPA), optic disc tilting, or fundus tessellation. The multi-task DL model was developed by ResNet with output of Yes/No GON and Yes/No MF. SDOCT scans were collected in a tertiary eye hospital (Hong Kong SAR, China) for training (80%), tuning (10%), and internal validation (10%). External testing was performed on five independent datasets from eye centres in Hong Kong, the United States, and Singapore, respectively. For GON detection, we compared the model to the average RNFL thickness measurement generated from the SDOCT device. To investigate whether MF can affect the model’s performance on GON detection, we conducted subgroup analyses in groups stratified by Yes/No MF. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and accuracy were reported.ResultsA total of 8,151 SDOCT volumetric scans from 3,609 eyes were collected. For detecting GON, in the internal validation, the proposed 3D model had significantly higher AUROC (0.949 vs. 0.913, p < 0.001) than average RNFL thickness in discriminating GON from normal. In the external testing, the two approaches had comparable performance. In the subgroup analysis, the multi-task DL model performed significantly better in the group of “no MF” (0.883 vs. 0.965, p-value < 0.001) in one external testing dataset, but no significant difference in internal validation and other external testing datasets. The multi-task DL model’s performance to detect MF was also generalizable in all datasets, with the AUROC values ranging from 0.855 to 0.896.ConclusionThe proposed multi-task 3D DL model demonstrated high generalizability in all the datasets and the presence of MF did not affect the accuracy of GON detection generally.

Background: There are few effective interventions for dementia. Aim: To determine the clinical effectiveness and cost-effectiveness of an intervention to promote self-management, independence and self-efficacy in people with early-stage dementia. Objectives: To undertake a randomised controlled trial of the Journeying through Dementia intervention compared with usual care, conduct an internal pilot testing feasibility, assess intervention delivery fidelity and undertake a qualitative exploration of participants’ experiences. Design: A pragmatic two-arm individually randomised trial analysed by intention to treat. Participants: A total of 480 people diagnosed with mild dementia, with capacity to make informed decisions, living in the community and not participating in other studies, and 350 supporters whom they identified, from 13 locations in England, took part. Intervention: Those randomised to the Journeying through Dementia intervention (n = 241) were invited to take part in 12 weekly facilitated groups and four one-to-one sessions delivered in the community by secondary care staff, in addition to their usual care. The control group (n = 239) received usual care. Usual care included drug treatment, needs assessment and referral to appropriate services. Usual care at each site was recorded. Main outcome measures: The primary outcome was Dementia-Related Quality of Life score at 8 months post randomisation, with higher scores representing higher quality of life. Secondary outcomes included resource use, psychological well-being, self-management, instrumental activities of daily living and health-related quality of life. Randomisation and blinding: Participants were randomised in a 1 : 1 ratio. Staff conducting outcome assessments were blinded. Data sources: Outcome measures were administered in participants’ homes at baseline and at 8 and 12 months post randomisation. Interviews were conducted with participants, participating carers and interventionalists. Results: The mean Dementia-Related Quality of Life score at 8 months was 93.3 (standard deviation 13.0) in the intervention arm (n = 191) and 91.9 (standard deviation 14.6) in the control arm (n = 197), with a difference in means of 0.9 (95% confidence interval –1.2 to 3.0; p = 0.380) after adjustment for covariates. This effect size (0.9) was less than the 4 points defined as clinically meaningful. For other outcomes, a difference was found only for Diener’s Flourishing Scale (adjusted mean difference 1.2, 95% confidence interval 0.1 to 2.3), in favour of the intervention (i.e. in a positive direction). The Journeying through Dementia intervention cost £608 more than usual care (95% confidence interval £105 to £1179) and had negligible difference in quality-adjusted life-years (–0.003, 95% confidence interval –0.044 to 0.038). Therefore, the Journeying through Dementia intervention had a mean incremental cost per quality-adjusted life-year of –£202,857 (95% confidence interval –£534,733 to £483,739); however, there is considerable uncertainty around this. Assessed fidelity was good. Interviewed participants described receiving some benefit and a minority benefited greatly. However, negative aspects were also raised by a minority. Seventeen per cent of participants in the intervention arm and 15% of participants in the control arm experienced at least one serious adverse event. None of the serious adverse events were classified as related to the intervention. Limitations: Study limitations include recruitment of an active population, delivery challenges and limitations of existing outcome measures. Conclusions: The Journeying through Dementia programme is not clinically effective, is unlikely to be cost-effective and cannot be recommended in its existing format. Future work: Research should focus on the creation of new outcome measures to assess well-being in dementia and on using elements of the intervention, such as enabling enactment in the community. Trial registration: This trial is registered as ISRCTN17993825. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 24. See the NIHR Journals Library website for further project information.

Introduction The number of people living with multiple long-term conditions (MLTCs) is predicted to rise. Within this population, those also living with frailty are particularly vulnerable to poor outcomes, including decreased function. Increased physical activity, including exercise, has the potential to improve function in those living with both MLTCs and frailty but, to date, the focus has remained on older people and may not reflect outcomes for the growing number of younger people living with MLTCs and frailty. For those with higher burdens of frailty and MLTCs, physical activity may be challenging. Tailoring physical activity in response to symptoms and periods of ill-health, involving family and reducing sedentary behaviour may be important in this population. How the tailoring of interventions has been approached within existing studies is currently unclear. This scoping review aims to map the available evidence regarding these interventions in people living with both frailty and MLTCs.Methods and analysis We will use a six-stage process: (1) identifying the research questions; (2) identifying relevant studies (via database searches); (3) selecting studies; (4) charting the data; (5) collating and summarising and (6) stakeholder consultation. Studies will be critically appraised using the Mixed Methods Appraisal Tool.Ethics and dissemination All data in this project will be gathered through database searches. Stakeholder consultation will be undertaken with an established patient and public involvement group. We will disseminate our findings via social media, publication and engagement meetings.

As an environmental pollutant, cadmium (Cd) has been widely reported to induce male infertility due to its gonadotoxicity. However, the specific mechanism of Cd-induced testicular damage remains unclear. We investigated whether Cd causes testicular injury through ferroptosis. Male C57BL/6 J mice were exposed to 0, 0.5, or 5 ppm Cd via drinking water, starting in utero, and continuing through 24 weeks post-weaning. The results showed that Cd accumulated in the testes in a dose-dependent manner. Cd exposure at a concentration of 5 ppm, but not 0.5 ppm, caused a mass loss and detachment of germ cells, as well as a decreased meiotic index and testis weight. Exposure to 5 ppm Cd caused iron accumulation, increased levels of malondialdehyde (MDA) and nitro tyrosine (3-NT), and decreased expression of Nrf2, HO-1 and SOD2. We also found that exposure to 5 ppm Cd significantly decreased the expression of SLC7A11, a marker of ferroptosis in mice, along with the expression of SLC40A1 mRNA and ferritin heavy chain (FTH) protein, whereas there was no obvious change in the mRNA expression of Tfrc, ZIP8, ZIP14, and NCOA4. These findings indicate that 5 ppm Cd exposure increased testicular ferroptosis, which may be attributed to the reduction of stored iron export.

Objective To investigate the popular social media platforms Instagram and Facebook for public posts related to tympanostomy tubes in children, to discern attitudes and perceptions surrounding tympanostomy tubes, and to evaluate the content of social media posts related to tympanostomy tubes. Study Design Qualitative study. Setting Instagram and Facebook social media platforms. Methods Instagram and Facebook were searched for public posts from 2018 and 2019 including the search terms “ear tubes,”“ear tube surgery,”“tympanostomy,” and “myringotomy.” Posts were excluded if they were unrelated to pediatric tympanostomy tubes or written in a non-English language. Relevant posts underwent subgroup analysis based on 6 domains: media type, perspective, topic, timeframe, popularity, and overall tone. Results Of 1862 public social media posts, the majority (78.2%) were made by the patient’s parents/caregivers and the rest by physicians (6.0%), hospitals (8.2%), and chiropractors (6.1%), with a few posts by the patients themselves (0.4%). The majority (79.3%) of posts portrayed tympanostomy tubes positively. Most negative posts were made by chiropractors (50.8%) and the patient’s parents/caregivers (42.9%). The most common themes of posts were reassurance regarding surgery (74.9%), advertisements (12.5%), apprehension (12.4%), and education (10.3%). Conclusion Most social media posts were made by parents/caregivers in the perioperative period, and there was a low percentage of educational posts. This information could be used by otolaryngologists to optimize their interactions with patients and parents and to potentially increase physician involvement and educational material related to tympanostomy tubes on social media.

Abstract Background An association between neuroinflammation and age-related neurologic disorders has been established but the molecular mechanisms and cell types involved have not been thoroughly characterized. Activity of the proinflammatory NLRP3 inflammasome is implicated in Alzheimer’s and Parkinson’s disease and our recent studies in patients suggest that dopaminergic neurons within the degenerating mesencephalon express NLRP3 throughout the progression of PD. Here, we directly test the impact of enhanced inflammasome activity in mesencephalic neurons by characterizing motor function, tissue integrity, and neuroinflammation in aging mice harboring hyperactivating mutations within the endogenous murine Nlrp3 locus, enabled only in cells expressing the dopaminergic neuron-specific Slc6a3 promoter. Methods We compared mice harboring inducible alleles encoding the cryopyrin-associated periodic syndrome activating mutations Nlrp3 A350V and Nlrp3 L351P inserted into the endogenous mouse Nlrp3 locus. Tissue specific expression was driven by breeding these animals with mice expressing Cre recombinase under the control of the dopaminergic neuron-specific Slc6a3 promoter. The experimental mice, designed to express hyperactive NLRP3 only when the endogenous mouse Nlrp3 promotor is active in dopaminergic neurons, were analyzed throughout 18 months of aging using longitudinal motor function assessments. Biochemical and histologic analyses of mesencephalic tissues were conducted in 1- and 18-month-old animals. Results We observed progressive and significant deficits in motor function in animals expressing Nlrp3 L351P , compared with animals expressing Nlrp3 WT and Nlrp3 A350V . Age-dependent neuroinflammatory changes in the mesencephalon were noted in all animals. Analysis of GFAP-immunoreactive astrocytes in the substantia nigra revealed a significant increase in astrocyte number in animals expressing Nlrp3 L351P compared with Nlrp3 WT and Nlrp3 A350V . Further analysis of Nlrp3 L351P striatal tissues indicated genotype specific gliosis, elevated Il1b expression, and both morphologic and gene expression indicators of proinflammatory A1 astrocytes. Conclusions Dopaminergic neurons have the potential to accumulate NLRP3 inflammasome activators with age, including reactive oxygen species, dopamine metabolites, and misfolded proteins. Results indicate the Nlrp3 locus is active in dopaminergic neurons in aging mice, and that the hyperactive Nlrp3 L351P allele can drive neuroinflammatory changes in association with progressive behavioral deficits. Findings suggest neuronal NLRP3 inflammasome activity may contribute to neuroinflammation observed during normal aging and the progression of neurologic disorders.

Abstract Introduction Health-related quality of life evaluation is recognized as an important outcome in the assessment of boys with haemophilia. In fact, reliable health-related quality of life data are even more critical in developing countries to advocate for government agencies to develop national haemophilia care programmes. However, validated tools are not yet available in sub-Saharan African countries. Aims The purpose of this study was to complete the cultural adaptation and validation of the Canadian Haemophilia Outcomes-Kids’ Life Assessment Tool version2.0 (CHO-KLAT2.0) in Côte d’Ivoire. Methods The process included four steps: a linguistic adaptation, cognitive debriefing interviews with children and their parents, a validity assessment with the Pediatric Quality of Life Inventory (PedsQL) as a comparator, and a test-retest reliability assessment. Results The initial Ivoirian version of the CHO-KLAT2.0 was developed through a linguistic adaptation performed in close collaboration with members of the local medical team and haemophilia community. Cognitive debriefings were completed with five boys and their parents, with the final Ivoirian version of the CHO-KLAT2.0 developed in September 2017. The validation process included 37 boys with haemophilia (mean age: 11.4 years; 34 with severe and three with moderate forms of haemophilia, all treated on demand) and their parents. Among the child-reported population (n = 20), we observed a mean CHO-KLAT2.0 score of 51.3 ± 9.2; there was a moderate correlation between the CHO-KLAT2.0 and PedsQL scores (r = 0.581; p = 0.007) and an inverse correlation of the CHO-KLAT2.0 and PedsQL scores with the global rating of the degree to which the boys were bothered by their haemophilia. The mean parent proxy CHO-KLAT2.0 score (n = 17) was 53.5 ± 9.8. Among the parents, we found no significant correlation between the Ivoirian CHO-KLAT2.0 and PedsQL scores or between the parent-reported scores and the parent global ratings of bother. The test-retest intraclass correlation coefficient was 0.879 (95% CI: 0.673; 0.954) for the child-reported questionnaires and 0.880 (95% CI: 0.694; 0.955) for the proxy-reported questionnaires. Conclusions A cross-culturally adapted and validated version of the CHO-KLAT2.0 for Côte d’Ivoire is now available that enables baseline values to be obtained and intervention outcomes (namely, prophylaxis) to be measured in Ivoirian boys with haemophilia.

Ultrasound devices are common in muscle physiology laboratories due to their ease of use and validity to assess skeletal muscle characteristics. The current study assessed the reliability of ultrasound skeletal muscle image analysis across multiple raters with limited experience. Vastus lateralis (VL), rectus femoris (RF), and first dorsal interosseus (FDI) images were separately analyzed by three novice raters to determine muscle thickness (MT), cross-sectional area (CSA), and echo-intensity (EI). Separate analyses of variance (ANOVA) assessed statistical differences between and within raters. Intra-class correlation coefficients (ICC) between (inter-rater) and within (intra-rater) raters, the standard error of the measurement (SEM) and minimal difference needed to be considered real were calculated. Inter-rater reliability was high for the VL and RF (ICC: 0.984-0.999), while the FDI was lower (0.614-0.962). Further, intra-rater reliability was greater than 0.961 for each rater. SEM values calculated for inter-rater reliability expressed as a percentage of the mean ranged from 0.4-5.8% across variables. Similarly, SEM values for intra-rater reliability were between 0.8-5.8%, 0.6-3.6%, and 0.4-3.2% for Raters 1, 2 and 3, respectively. Despite this, significant differences (p

Abstract Background There are few reports of the association of other cancers with Ewing sarcoma in patients and their relatives. We use a resource combining statewide genealogy and cancer reporting to provide unbiased risks. Methods Using a combined genealogy of 2.3 million Utah individuals and the Utah Cancer Registry (UCR), relative risks (RRs) for cancers of other sites were estimated in 143 Ewing sarcoma patients using a Cox proportional hazards model with matched controls; however, risks in relatives were estimated using internal cohort‐specific cancer rates in first‐, second‐, and third‐degree relatives. Results Cancers of three sites (breast, brain, complex genotype/karyotype sarcoma) were observed in excess in Ewing sarcoma patients. No Ewing sarcoma patients were identified among first‐, second‐, or third‐degree relatives of Ewing sarcoma patients. Significantly increased risk for brain, lung/bronchus, female genital, and prostate cancer was observed in first‐degree relatives. Significantly increased risks were observed in second‐degree relatives for breast cancer, nonmelanoma eye cancer, malignant peripheral nerve sheath cancer, non‐Hodgkin lymphoma, and translocation sarcomas. Significantly increased risks for stomach cancer, prostate cancer, and acute lymphocytic leukemia were observed in third‐degree relatives. Conclusions This analysis of risk for cancer among Ewing sarcoma patients and their relatives indicates evidence for some increased cancer predisposition in this population which can be used to individualize consideration of potential treatment of patients and screening of patients and relatives.

The authors discuss how Black girls can engage with literary texts through counter fairy tales (CFT) as a resistive literary strategy to reclaim Black girls' narratives and to be reflective of their experiences. The racial violence that Black girls encounter in school cannot be separated from the remnants of the afterlife of slavery within PreK-12 schools and in English language arts classrooms. When Black girls' identities, ways of learning, and leadership capacities are symbolically bonded by chains through a White-only curriculum, culturally biased literary texts, and pedagogical standards, Black female students are in fact experiencing normalized racial violence. There needs to be a (re)centering of Black girls' voices in ways that challenge the idea that "even Cinderella is white." Black girls must be exposed to and seen within the subject that they are learning while also given the opportunities for counternarratives and resistance to injustice. Early literacy experiences have enduring effects on the perceptions and aspirations of children. This is especially important for Black female learners, given the lack of representative characters in the "timeless classics" such as fairy tales. A model called counter fairy tales (CFT) was developed to leverage Black girls' experiential and communal funds of knowledge. This is necessary to support more inclusive practices in literacy instruction. The CFT model encourages these girls to take traditional fairy tales and rewrite the narrative from their perspective. Culturally responsive and/or relevant teaching in English language arts classrooms has been heightened to deconstruct biases and create safe spaces for marginalized Black girls. With culturally inclusive and supportive classroom libraries and activities that employ the CFT model, English language arts educators can empower Black girls' voices and actions to be enslaved no more.

Abstract Purpose To report the clinical outcomes of adalimumab in treating refractory Behcet’s disease (BD)-related uveitis in paediatric or adolescent patients. Methods Retrospective review of five paediatric or adolescent patients with BD-related uveitis with a minimum follow-up of 24 months. Results Disease quiescence was observed in 9 (90%) of 10 eyes at 12 months. The mean number of relapses per year per patient was 5 (range, 3–7) before initiation of adalimumab treatment. This was reduced to 0.2 relapse per patient per year among the five patients during the first 24 months after starting adalimumab treatment. At baseline, 5 eyes had active retinal vasculitis. Retinal vasculitis resolved in all cases (100%) after starting adalimumab. The mean time to complete resolution of inflammation was 3.4 weeks. The mean ± standard deviation logMAR best-corrected visual acuity was 0.711 ± 0.63 at baseline and improved to 0.172 ± 1.04 at 12 months (P < 0.001). None of the patients developed any adverse events associated with adalimumab treatment. Conclusion Adalimumab was effective in preventing irreversible sight-threatening BD-related uveitis in paediatric or adolescent patients. Adalimumab appears to be a promising treatment option for young patients with recalcitrant BD-related uveitis and has a favourable safety profile.

Background Prophylaxis reduces the frequency of bleeds in boys with severe hemophilia and is the standard care for their management in resource‐abundant countries. The effect of prophylaxis on Health‐Related Quality of Life (HRQoL) has not been established, because the sample sizes of most studies are too small to explore the relationship of multiple factors that influence HRQoL. Methods The aim of this study was to assess the impact of hemophilia severity and treatment regimen on HRQoL and to establish the minimum important difference (MID) using the international level of score distributions. HRQoL data were pooled from 7 studies across 9 countries. HRQoL was measured using the Canadian Hemophilia Outcomes–Kids’ Life Assessment Tool (CHO‐KLAT). A mixed‐effect linear regression analysis was employed to assess the impact of prophylaxis on the CHO‐KLAT score. Results Data from 401 boys with hemophilia were analyzed (57.6% severe hemophilia and 57.6% receiving prophylaxis). The model revealed that receiving prophylaxis was significantly associated with higher HRQoL (regression coefficient 8.5, 95% confidence interval [CI] 3.9‐13.1). Boys with severe hemophilia had a significantly lower HRQoL as compared to boys with moderate and mild hemophilia whose CHO‐KLAT scores were 7.0 and 6.6 points higher, respectively. There was a significant interaction between treatment and disease severity (P = 0.023), indicating prophylaxis has the most significant impact in boys with severe hemophilia. Based on these pooled data, the MID of the CHO‐KLAT was established at 6.5. Conclusions This study confirms the positive effect of prophylaxis on HRQoL in boys with hemophilia in a real‐world setting and provides initial benchmarks for interpreting HRQoL scores based on use of the CHO‐KLAT instrument.

Abstract Background Dental caries in the expanding elderly, predominantly-dentate population is an emerging public health concern. Elderly individuals with heavily restored dentitions represent a clinical challenge and significant financial burden for healthcare systems, especially when their physical and cognitive abilities are in decline. Prescription of higher concentration fluoride toothpaste to prevent caries in older populations is expanding in the UK, significantly increasing costs for the National Health Services (NHS) but the effectiveness and cost benefit of this intervention are uncertain. The Reflect trial will evaluate the effectiveness and cost benefit of General Dental Practitioner (GDP) prescribing of 5000 ppm fluoride toothpaste and usual care compared to usual care alone in individuals 50 years and over with high-risk of caries. Methods/design A pragmatic, open-label, randomised controlled trial involving adults aged 50 years and above attending NHS dental practices identified by their dentist as having high risk of dental caries. Participants will be randomised to prescription of 5000 ppm fluoride toothpaste (frequency, amount and duration decided by GDP) and usual care only. 1200 participants will be recruited from approximately 60 dental practices in England, Scotland and Northern Ireland and followed up for 3 years. The primary outcome will be the proportion of participants receiving any dental treatment due to caries. Secondary outcomes will include coronal and root caries increments measured by independent, blinded examiners, patient reported quality of life measures, and economic outcomes; NHS and patient perspective costs, willingness to pay, net benefit (analysed over the trial follow-up period and modelled lifetime horizon). A parallel qualitative study will investigate GDPs’ practises of and beliefs about prescribing the toothpaste and patients’ beliefs and experiences of the toothpaste and perceived impacts on their oral health-related behaviours. Discussion The Reflect trial will provide valuable information to patients, policy makers and clinicians on the costs and benefits of an expensive, but evidence-deficient caries prevention intervention delivered to older adults in general dental practice. Trial registration ISRCTN: 2017-002402-13 registered 02/06/2017, first participant recruited 03/05/2018. Ethics Reference No: 17/NE/0329/233335. Funding Body: Health Technology Assessment funding stream of National Institute for Health Research. Funder number: HTA project 16/23/01. Trial Sponsor: Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL. The Trial was prospectively registered.