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Background Some Canadian jurisdictions offer publicly funded HPV vaccine to gay, bisexual, and other men who have sex with men (GBM) aged ≤26 years. We characterized factors associated with being in different stages of HPV vaccination. Methods Engage is a sexual health study of GBM in the three largest Canadian cities recruited via respondent driven sampling (RDS). We categorized participants as: (1) unaware of HPV vaccine, (2) undecided/unwilling to get vaccinated, (3) willing to get vaccinated, (4) vaccinated with one or more doses. Our RDS-II weighted analyses used multinomial logistic regression to identify factors associated with being in earlier stages of the cascade compared to Stage 4. Results Across the cities, 26–40%, 7–14%, 33–39%, and 13–28% were in Stages 1 to 4, respectively. Compared to Stage 4, being in earlier stages of the cascade was associated with bisexual-identification (Stage 1: adjusted odds ratio[aOR] = 2.84, 95% confidence interval[CI] = 1.06–7.62; Stage 2: aOR = 3.09, 95%CI = 1.19–8.05), having immigrated to Canada (Stage 1: aOR = 1.79, 95%CI 1.07–2.99), preference to keep same-sex romantic relationships private (Stage 1: aOR = 1.25, 95% CI = 1.05–1.48; Stage 2: aOR = 1.24, 95%CI = 1.05–1.46), not receiving sexual health information (Stage 1: aOR = 0.31, 95% CI = 0.13–0.71; Stage 2: aOR = 0.27, 95%CI = 0.12–0.64), not accessing a health-care provider (Stage 2: aOR = 0.36, 95%CI = 0.15–0.83), and no past hepatitis A/B vaccination (Stage 1: aOR = 0.16, 95% CI = 0.09–0.30; Stage 2: aOR = 0.18, 95%CI = 0.09–0.35; Stage 3: aOR = 0.38, 95%CI = 0.21–0.61). Discussion Interventions are needed to reduce social and financial barriers, increase sexual health knowledge, and improve GBM-competent health-care access to increase vaccine uptake among GBM.

This study examined the clinical utility of the Massachusetts Youth Screening Instrument--Second Version (MAYSI-2) among African American (AA) incarcerated youth and used White incarcerated youth as a comparison group. Data were analyzed for 314 incarcerated youth (193 AA offenders and 121 White offenders) of ages 13-17 years who were adjudicated delinquent from a southeastern United States medium security residential facility. Seven logistic regression and receiver operating characteristic curve (ROC) models were built to determine whether the MAYSI-2 subscales accurately identify committed AA male incarcerated youth who have a mental illness diagnosis on file. Analyses also examined how well the MAYSI-2 subscales identify specific mental illnesses among AA-committed male incarcerated youth. Results demonstrated that no MAYSI-2 subscales accurately identified and categorized AA-committed male incarcerated youth who have mental disorders, and only two subscales (Alcohol/Drug Use, Depressed/Anxious) identified and categorized White committed male incarcerated youth who have a mental disorder. Additional results and implications for research and practice are provided.

Electron beam quality in accelerators is crucial for light source application. Here the authors demonstrate beam conditioning of laser plasma electrons thanks to a specific transport line enabling the control of divergence, energy, steering and dispersion and the application to observe undulator radiation.

Background: In Quebec, Canada, a school-based HPV vaccination for girls has been offered since 2008. The vaccine used in the program targets HPV16/18, responsible for ∼70% of cervical cancers and HPV6/11, responsible for the majority of anogenital warts. The objective of this study was to assess the prevalence of HPV in vaccinated and unvaccinated women. Methods: Women aged 17–29 years were eligible to participate. Participants' age, vaccination status and diverse risk factors were assessed by a computer-assisted questionnaire. Biological specimens were obtained by self-sampling. HPV genotyping was performed by Linear Array. Results: A total of 2,118 women were recruited. 2,042 completed the questionnaire and 1,937 provided a vaginal sample. Vaccination coverage varied from 83.5% in women aged 17–19 to 19.1% in those aged 23–29. The overall prevalence of HPV in sexually active women was 39.4% (95%CI: 37.0-41.7) and 56.7% of infected women had multiple type infections. The prevalence of vaccine HPV types varied by age and vaccination status except for women aged 23–29 for whom similar results were observed. Vaccine HPV types were detected in 0.3%, 1.4% and 10.5% of vaccinated women aged 17–19, 20–23, and 23–29 (p

A major challenge for juvenile correctional facilities (JCF) is providing literacy instruction to a transitory student population with a wide range of literacy abilities. The purpose of this study was to identify unique literacy profiles of students in long-term JCF taking into consideration their reading abilities, language abilities, intelligence quotient (IQ), disability classification, age, and grade level. Using latent profile analyses with a sample of 370 in the southeastern United States, we identified three distinct classes. Three ability groups of students (average literacy abilities, below-average literacy abilities, substantially below-average literacy abilities) were identified. Thirty-six percent performed at the average level, 55% performed below grade level; and 8% had substantial literacy deficits with an overrepresentation of students with emotional disturbance (ED) and specific learning disability (SLD). Findings provide the foundation for an evidence-based multi-tiered system of supports literacy framework within JCF. Instructional implications concerning the provision of English Language Arts in JCF are provided.

The extent of hypercholesterolemia varies considerably in patients with familial hypercholesterolemia (FH). We hypothesized that the variability of the FH phenotype might be partly explained by variation in proprotein convertase subtilisin kexin type 9 (PCSK9) activity. Individuals between 18 and 53 years of age who had been tested for a pathogenic LDLR or APOB mutation were eligible. Mutation carriers with a LDL-C level below the 75th percentile (called “FH low”) were selected, as well as those with LDL-C above the 90th percentile (called “FH high”). Relatives who tested negative for the mutation were the “controls.” PCSK9 plasma levels were assessed in 267 individuals who did not receive cholesterol-lowering treatment at the time of the study. Mean PCSK9 plasma levels (95% CI) were lower in the FH-low group compared with the FH-high group [152 (137–167) ng/ml vs. 186 (165–207) ng/ml, P= 0.010] and the control group [177 (164–190) ng/ml, P= 0.013]. Mean PCSK9 levels did not statistically differ between the FH-high and control groups (P= 0.50). Plasma PCSK9 levels are positively associated with LDL-C levels in FH patients and might contribute to the phenotypic severity in this disorder. Therefore, the results of pharmaceutical inhibition of PCSK9 in FH patients are eagerly awaited.

The original version of this Article contained an error in the last sentence of the first paragraph of the Introduction and incorrectly read ‘A proper electron beam control is one of the main challenges towards the Graal of developing a compact alternative of X-ray free-electron lasers by coupling LWFA gigaelectron-volts per centimetre acceleration gradient with undulators in the amplification regime in equation 11, nx(n-β) x β: n the two times and beta the two times should be bold since they are vectorsin Eq. 12, β should be bold as well.’ The correct version is ‘A proper electron beam control is one of the main challenges towards the Graal of developing a compact alternative of X-ray free-electron lasers by coupling LWFA gigaelectron-volts per centimetre acceleration gradient with undulators in the amplification regime.’This has been corrected in both the PDF and HTML versions of the Article.

Este artigo propõe uma nova técnica de detecção de contaminação por umidade em óleo isolante usando os sinais acústicos das descargas parciais (DP). Para demonstrá-la, um experimento é montado com um sensor piezoelétrico fixado na base de um reservatório que é preenchido com amostras de óleo isolante contaminadas com diferentes níveis de umidade. Um dispositivo gerador de descargas elétricas fica submerso no óleo para simular ocorrências de descargas parciais. Os sinais acústicos detectados são processados usando a Transformada Wavelet Discreta para extrair características de tempo e freqüência. Em seguida, é feito um processamento usando a Análise de Componentes Principais (PCA) de modo a identificar padrões de contaminação por água no óleo de transformador. Os resultados mostram que a técnica é promissora para o desenvolvimento de um sistema de monitoramento on-line de transformadores de potência.

Background: Severe malarial anemia (SMA; Hb < 5.0 g/dl) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions such as western Kenya.Methods: We investigated the relationship between two novel complement component 5 (C5) missense mutations [rs17216529:C>T, p(Val145Ile) and rs17610:C>T, p(Ser1310Asn)] and longitudinal outcomes of malaria in a cohort of Kenyan children (under 60 mos, n = 1,546). Molecular modeling was used to investigate the impact of the amino acid transitions on the C5 protein structure.Results: Prediction of the wild-type and mutant C5 protein structures did not reveal major changes to the overall structure. However, based on the position of the variants, subtle differences could impact on the stability of C5b. The influence of the C5 genotypes/haplotypes on the number of malaria and SMA episodes over 36 months was determined by Poisson regression modeling. Genotypic analyses revealed that inheritance of the homozygous mutant (TT) for rs17216529:C>T enhanced the risk for both malaria (incidence rate ratio, IRR = 1.144, 95%CI: 1.059–1.236, p = 0.001) and SMA (IRR = 1.627, 95%CI: 1.201–2.204, p = 0.002). In the haplotypic model, carriers of TC had increased risk of malaria (IRR = 1.068, 95%CI: 1.017–1.122, p = 0.009), while carriers of both wild-type alleles (CC) were protected against SMA (IRR = 0.679, 95%CI: 0.542–0.850, p = 0.001).Conclusion: Collectively, these findings show that the selected C5 missense mutations influence the longitudinal risk of malaria and SMA in immune-naïve children exposed to holoendemic P. falciparum transmission through a mechanism that remains to be defined.

There is a controversial narrative in the anaesthetic literature suggesting that anaesthetic technique (including opioids) may be detrimental to survival after tumour resection. The initial observations were retrospective. Several prospective studies are ongoing; one in breast cancer has reported no adverse outcome. The evidence for an effect of opioids stems from three pieces of information: (1) opioids depress the immune system, (2) opioids potentially promote angiogenesis, and (3) opioids potentially support tumour growth. Although the evidence for (2)/(3) is unclear, combinations of these effects are beneficial to tumours and potentially promote metastatic reseeding. Accepted wisdom suggests that opioid effects are driven by opioid receptor activation but the presence of opioid receptors on immune cells for example is unlikely. Immune cells, vascular endothelium and a range of tumour cells express Toll-like receptor 4 (TLR4) receptors (for Gram-negative bacterial wall components), and there is growing evidence for opioids interacting with this alternative receptor; and for some there is paradoxical naloxone sensitivity. Is the focus on opioid receptors and cancer the wrong target? TLR4 receptor activation produces immune activation, stimulates angiogenesis, and supports tumour survival. We know that some opioids are more immune suppressive than others (there is no such comparative information for angiogenesis and tumour survival); this may correlate with TLR4 activation. If there are clusters of opioids that have more opioid than TLR4 profiles and vice versa, this may influence outcome. If this is the case, then evidence-based advice could be given for perioperative use in the oncology–anaesthesia setting.

Nociceptin/Orphanin FQ (N/OFQ) is the endogenous opioid agonist for the N/OFQ receptor or NOP. This receptor system is involved in pain processing but also has a role in immune regulation. Indeed, polymorphonuclear cells (PMNs) express mRNA for N/OFQ precursor and are a potential source for circulating N/OFQ. Current measurements are based on ELISA and RIA techniques. In this study we have designed a bioassay to measure N/OFQ release from single PMNs. Chinese Hamster Ovary (CHO) cells transfected with the human (h) NOP receptor and Gαiq5 chimera force receptor coupling in biosensor cells to increase intracellular Ca2+; this can be measured with FLUO-4 dye. If isolated PMNs from healthy human volunteers are layered next to CHOhNOPGαiq5 biosensor cells then stimulated with the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) we hypothesise that released N/OFQ will activate the biosensor. PMNs also release ATP and CHO cells express purinergic receptors coupled to elevated Ca2+. In a system where these receptors (P2Y1, P2Y2 and P2X7) are blocked with high concentrations of PPADS and oATP, PMN stimulation with fMLP increases Ca2+ in PMNs then shortly afterwards the biosensor cells. Our data therfore reports detection of single cell N/OFQ release from immune cells. This was absent when cells were preincubated with the selective NOP antagonist; SB-612111. Collectively this is the first description of single cell N/OFQ release. We will deploy this assay with further purified individual cell types and use this to further study the role of the N/OFQ-NOP system in disease; in particular sepsis where there is strong evidence for increased levels of N/OFQ worsening outcome.

The endoplasmic reticulum (ER) is composed of sheets and tubules. Here we report that the COPII coat subunit, SEC24C, works with the long form of the tubular ER-phagy receptor, RTN3, to target dominant-interfering mutant proinsulin Akita puncta to lysosomes. When the delivery of Akita puncta to lysosomes was disrupted, large puncta accumulated in the ER. Unexpectedly, photobleach analysis indicated that Akita puncta behaved as condensates and not aggregates, as previously suggested. Akita puncta enlarged when either RTN3 or SEC24C were depleted, or when ER sheets were proliferated by either knocking out Lunapark or overexpressing CLIMP63. Other ER-phagy substrates that are segregated into tubules behaved like Akita, while a substrate (type I procollagen) that is degraded by the ER-phagy sheets receptor, FAM134B, did not. Conversely, when ER tubules were augmented in Lunapark knock-out cells by overexpressing reticulons, ER-phagy increased and the number of large Akita puncta was reduced. Our findings imply that segregating cargoes into tubules has two beneficial roles. First, it localizes mutant misfolded proteins, the receptor, and SEC24C to the same ER domain. Second, physically restraining condensates within tubules, before they undergo ER-phagy, prevents them from enlarging and impacting cell health.

Background: Leukocyte-associated immunoglobulin like receptor-1 (LAIR1) is a transmembrane inhibitory receptor that influences susceptibility to a myriad of inflammatory diseases. Our recent investigations of severe malarial anaemia (SMA) pathogenesis in Kenyan children discovered that novel LAIR1 genetic variants which were associated with decreased LAIR1 transcripts enhanced the longitudinal risk of SMA and all-cause mortality. Methods: To characterize the molecular mechanism(s) responsible for altered LAIR1 signalling in severe malaria, we determined LAIR1 transcripts and protein, sLAIR1, sLAIR2, and complement component 1q (C1q) in children with malarial anaemia, followed by a series of in vitro experiments investigating the LAIR1 signalling cascade. Findings: Kenyan children with SMA had elevated circulating levels of soluble LAIR1 (sLAIR1) relative to non-SMA (1.69-fold P

Abstract Purpose To assess increased sacroiliac joint (SIJ) uptake on 18F-NaF PET/CT and to compare with MRI for inflammation and with CT scan for structural damages in a population of 23 patients with spondyloarthritis (SpA). Methods Twenty-three patients with active SpA according to the Assessment of SpondyloArthritis international Society (ASAS) and/or modified NY criteria were included. All patients had a pelvic radiograph, MRI, and CT scan of the SIJ and 18F-NaF PET/CT examinations within a month, analyzed by three blinded readers. MRIs were assessed according to the ASAS criteria and SPARCC method. On CT scans, erosion and ankylosis were quantified using the same methodology. On the 18F-NaF PET, abnormal uptake was assessed using a qualitative method inspired by the ASAS criteria and two quantitative approaches (the PET-activity score according to the SPARCC method and Maximum Standardized Uptake Value (SUVmax)). Results Structural sacroiliitis was observed on 7 radiographs and 10 CT scans; 10 MRIs showed inflammatory sacroiliitis, and 20 patients had a positive PET. The inter-reader reliability was good for the PET activity score and good to excellent for the SUVmax. A positive PET was not correlated with a positive MRI or with a structural sacroiliitis on CT scan. The PET-activity score and SUVmax were correlated with the SPARCC inflammation score but not with erosion or ankylosis scores on CT scan. Conclusion Abnormal uptake by the SIJ on 18F-NaF PET is more frequent than inflammatory and structural sacroiliitis in a population of SpA patients. The PET activity score and SUVmax had good correlations with inflammatory sacroiliitis but not with structural lesions on CT scan.

Combining secondary data from the National Center for Education Statistics National Teacher Principal Survey (NTPS) and Common Core of Data (CCD), this exploratory study examined the distribution of teacher race/ethnicity across the race/ethnicity of the schools in which they work and the extent that teacher and school race/ethnicity was associated with occupational stress. Findings indicate that teachers are more likely to work in schools with higher concentrations of students who match their own race/ethnicity. Both teacher and school race/ethnicity were unique predictors of a teacher being classified as at-risk for stress. Additional analyses suggested that teachers’ reported race/ethnicity significantly moderated the school effect association with stress risk. These findings have policy implications for how school workplace surveys are used as well as staffing and professional development considerations.

Education systems and institutions, often historically considered to be resolute, slow-moving entities transformed virtually overnight during the earlier stages of the COVID-19 pandemic, demonstrating nimbleness in adversity. This paper describes the first-hand experiences of teaching staff and students from a UK university which pivoted to emergency remote teaching for a core second-year module in engineering, focused on entrepreneurship. A range of methods are used including self-reflection, summative, formative, and focus-group student feedback. The paper provides an insight for readers who may be interested in the practical challenges associated with moving from an academic module typically delivered in a face-to-face learning environment accommodating a large student cohort (n = 177), to one that exists entirely in the digital domain. Our results show learning outcomes were fully met despite stark differences in quality of learning environments amongst students. Students reported benefits to remote learning because it offers a blended approach of both asynchronous content and synchronous sessions, with the latter enhancing engagement and providing structure to working weeks. Issues of presence emerged amongst group work: whilst it might be easier to confront some individuals for lack of contribution, it is also easier for those individuals to disengage. There was widespread support for the Microsoft Teams platform amongst students and staff but the former group reported this lacked a social environment in which relationships amongst team members could be nurtured informally, such as was experienced via social media.

Abstract Background Studies have shown that structural lesions may be present in patients with non-radiographic axial spondyloarthritis (nr-axSpA). However, the relevance of structural lesions in these patients is unclear, particularly without signs of inflammation on magnetic resonance imaging (MRI). We assessed the presence of structural lesions at baseline on MRI in the sacroiliac joints (SIJ) of patients with nr-axSpA with and without SIJ inflammation on MRI. Methods Bone marrow edema (BME) was assessed on short tau inversion recovery (STIR) scans from 185 patients with nr-axSpA, by two independent readers at baseline using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Structural lesions were evaluated on T1 weighted spin echo scans, with readers blinded to STIR scans, using the SPARCC MRI SIJ structural score. Disease characteristics and structural lesions were compared in patients with SIJ BME (score ≥2) and without SIJ BME (score