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Objective The study objective was to identify differences in gene expression between treatment responders (TRs) and treatment non‐responders (TNRs) diagnosed with juvenile dermatomyositis (JDM). Methods Gene expression analyses were performed using whole blood messenger RNA sequencing in patients with JDM (n = 17) and healthy controls (HCs; n = 10). Four analyses were performed (A1‐4) comparing differential gene expression and pathways analysis exploiting the timing of sample acquisition and the treatments received to perform these comparative analyses. Analyses were done at diagnosis and follow‐up, which averaged 7 months later in the cohort. Results At diagnosis, the expression of 10 genes differed between TRs and TNRs. Hallmark and canonical pathway analysis revealed 11 and 60 pathways enriched in TRs and 3 and 21 pathways enriched in TNRs, respectively. Pathway enrichment at diagnosis in TRs was strongest in pathways involved in metabolism, complement activation, and cell signaling as mediated by IL‐8, p38/microtubule associated protein kinases (MAPK)/extracellular signal‐regulated kinases (ERK), Phosphatidylinositol 3 Kinase Gamma (PI3Kγ), and the B cell receptor. Follow‐up hallmark and canonical pathway analysis showed that 2 and 14 pathways were enriched in TRs, whereas 24 and 123 pathways were enriched in treatment TNRs, respectively. Prior treatment with glucocorticoids significantly altered expression of 13 genes in the analysis of subjects at diagnosis with JDM as compared with HCs. Conclusion Numerous genes and pathways differ between TRs and TNRs at diagnosis and follow‐up. Prior treatment with glucocorticoids prior to specimen acquisition had a small effect on the performed analyses.

Abstract Background and aim Recent UK policy has focussed on improving support for victims of domestic violence and abuse (DVA), in healthcare settings. DVA victims attending hospital are often at highest risk of harm, yet DVA support in hospitals has been inadequate. A targeted service supporting high risk DVA victims, was implemented at a hospital Trust in North West England. The service was provided by Independent Domestic Violence Advisors (IDVAs). This paper assesses the activity in the hospital-based IDVA service during the COVID-19 pandemicand addresses the research questions: What was the demand for the service? How did the service respond? What facilitated this response? Methods A mixed-methods study was undertaken. Quantitative data on referrals to the service were examined using simple descriptive statistics and compared to other DVA services. Semi-structured interviews were undertaken with IDVAs and other hospital staff involved with the service and the data subjected to thematic analysis. Results The quantitative analysis showed that referrals dropped at the start of lockdown, then increased and continued to rise; the qualitative findings reiterated this pattern. Referrals came from a range of departments across the Trust, with the majority from A&E. Pre-pandemic, the population supported by the service included higher proportions of males and people aged 40 and over than at other IDVA services; this continued during the pandemic. The qualitative findings indicated a flexible response during the pandemic, enabled by strong working relationships and by using workarounds. Conclusions The hospital-based IDVAs provided an efficient, flexible serviceduring the COVID-19 pandemic. Referrals increased during the first lockdown and subsequent relaxing of restrictions. Locating the IDVAs within a team working across the organisation, and building good working relationships facilitated an effective disclosure and referral route, which endured through social restrictions. The IDVAs supported high-risk victims who may otherwise not have been identified in traditional community-based DVA settings during the pandemic. Hospital-based IDVA services can broaden access by supporting vulnerable, at risk populations whose needs may not be identified at other services.

The gut microbiome and its associated metabolites are integral to the maintenance of gut integrity and function. There is increasing evidence that its alteration, referred to as dysbiosis, is involved in the development of a systemic conditions such as cardiovascular disease (e.g., systemic hypertension, atherosclerosis). Pulmonary hypertension (PH) is a condition characterised by progressive remodelling and vasoconstriction of the pulmonary circulation, ultimately leading to right ventricular failure and premature mortality if untreated. Initial studies have suggested a possible association between dysbiosis of the microbiome and the development of PH. The aim of this article is to review the current experimental and clinical data with respect to the potential interaction between the gut microbiome and the pathophysiology of pulmonary hypertension. It will also highlight possible new therapeutic targets that may provide future therapies.

Introduction Suicide is a global health concern. Sociocultural factors have an impact on self-harm and suicide rates. In Pakistan, both self-harm and suicide are considered as criminal offence’s and are condemned on both religious and social grounds. The proposed intervention ‘Youth Culturally Adapted Manual Assisted Problem Solving Training (YCMAP)’ is based on principles of problem-solving and cognitive–behavioural therapy. YCMAP is a brief, culturally relevant, scalable intervention that can be implemented in routine clinical practice if found to be effective.Method and analysis A multicentre rater blind randomised controlled trial to evaluate the clinical and cost-effectiveness of YCMAP including a sample of 652 participants, aged 12–18 years, presenting to general physicians/clinicians, emergency room after self harm or self referrals. We will test the effectiveness of 8–10 individual sessions of YCMAP delivered over 3 months compared with treatment as usual. Primary outcome measure is repetition of self-harm at 12 months. The seconday outcomes include reduction in suicidal ideation, hopelessness and distress and improvement in health related quality of life. Assessments will be completed at baseline, 3, 6, 9 and 12 months postrandomisation. The nested qualitative component will explore perceptions about management of self-harm and suicide prevention among adolescents and investigate participants’ experiences with YCMAP. The study will be guided by the theory of change approach to ensure that the whole trial is centred around needs of the end beneficiaries as key stakeholders in the process.Ethics and dissemination Ethics approval has been obtained from the Ethics Committee of University of Manchester, the National Bioethics Committee in Pakistan. The findings of this study will be disseminated through community workshops, social media, conference presentations and peer-reviewed journals.Trial registration number NCT04131179.

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Abstract Background We designed and initiated a pilot comparative effectiveness study for juvenile localized scleroderma (jLS), for which there is limited evidence on best therapy. We evaluated the process we used, in relation to the specific protocol and to the general task of identifying strategies for implementing studies in rare pediatric diseases. Methods This was a prospective, multi-center, observational cohort study of 50 jLS patients initiating treatment, designed and conducted by the jLS group of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) from 2012 to 2015. A series of virtual and physical meetings were held to design the study, standardize clinical assessments, generate and refine disease activity and damage measures, and monitor the study. Patients were initiated on one of three standardized methotrexate-based treatment regimens (consensus treatment plans, CTPs) and monitored for 1 year. An optional bio-banking sub-study was included. Results The target enrollment of 50 patients was achieved over 26 months at 10 sites, with patients enrolled into all CTPs. Enrolled patients were typical for jLS. Study eligibility criteria were found to perform well, capturing patients thought appropriate for treatment studies. Minor modifications to the eligibility criteria, primarily to facilitate recruitment for future studies, were discussed with consensus agreement reached on them by the jLS group. There were marked differences in site preferences for specific CTPs, with half the sites treating all their patients with the same CTP. Most patients (88%) completed the study, and 68% participated in the bio-banking substudy. Conclusions We demonstrate the feasibility of our approach for conducting comparative effectiveness research in a rare pediatric disease. Multi-center collaboration by dedicated investigators who met regularly was a key factor in the success of this project. Other factors that facilitate these studies include having a sufficient number of investigators to enroll in each regimen, and streamlining study approval and management.

Objective: To investigate the predictive performance of machine learning (ML) algorithms for estimating anticoagulation control in patients with atrial fibrillation (AF) who are treated with warfarin. Methods: This was a retrospective cohort study of adult patients (≥18 years) between 2007 and 2016 using linked primary and secondary care data (Clinical Practice Research Datalink GOLD and Hospital Episode Statistics). Various ML techniques were explored to predict suboptimal anticoagulation control, defined as time in therapeutic range (TTR) 80 years and

Previously, we demonstrated in test and validation cohorts that type I IFN (T1IFN) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of non-classical and classical monocytes from RA patients defined by their pre-biologic treatment T1IFN activity. We compared single cell gene expression in purified classical (CL, n = 342) and non-classical (NC, n = 359) monocytes. In our previous work, RA patients who had either high IFNβ/α activity (>1.3) or undetectable T1IFN were likely to have EULAR non-response to TNFi. In this study comparisons were made among patients grouped according to their pre-biologic treatment T1IFN activity as clinically relevant: “T1IFN undetectable (T1IFN ND) or IFNβ/α >1.3” (n = 9) and “T1IFN detectable but IFNβ/α ≤ 1.3” (n = 6). In addition, comparisons were made among patients grouped according to their T1IFN activity itself: “T1IFN ND,” “T1IFN detected and IFNβ/α ≤ 1.3,” and “IFNβ/α >1.3.” Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the T1IFN ND or IFNβ/α >1.3 group were unlikely to express JAK1 and IFI27 (p < 0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression of IFNAR1, IRF1, TNFA, TLR4 (p ≤ 0.0001 for each) and others was enriched. Interestingly, JAK1 expression was absent in CL and NC monocytes from nine patients. This pattern most strongly associated with the IFNβ/α>1.3 group. Differences in gene expression in monocytes among the groups suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. Additional transcripts enriched in NC cells of those in the T1IFN ND and IFNβ/α >1.3 groups included MYD88, CD86, IRF1, and IL8. This work could suggest key pathways active in biologically defined groups of patients, and potential therapeutic strategies for those patients unlikely to respond to TNFi.

Information on dietary intakes of Jamaican immigrants in the United States is sparse. Understanding factors that influence diet is important since diet is associated with chronic diseases. This study examined the association between acculturation, socio-cultural factors, and dietary pattern among Jamaican immigrants in Florida. Jamaican persons 25–64years who resided in two South Florida counties were recruited for participation. A health questionnaire that assessed acculturation, dietary pattern, and risk factors for cardiovascular disease was administered to participants. Generalized Estimating Equations were used to determine associations. Acculturation score was not significantly associated with dietary intake pattern (β=−0.02 p=0.07). Age at migration was positively associated with traditional dietary pattern (β=0.02 p

Roundabouts constrain speeds and impact angles for vehicles as they approach. Therefore, they are considered to be a ‘Safe System’ solution for intersections. Though roundabouts are a positive road safety treatment for cars they do not show as dramatic a reduction in road trauma for bicyclists. New Zealand crash data for 2001-2011, found almost 28% of injury crashes at roundabouts involve cyclists, while at priority-controlled intersections and signalised intersections the proportions are 8% and 5.5% respectively. VicRoads specifies technical guidance in relation to road safety treatments at roundabouts specifically targeted for the protection of cyclists and pedestrians. In 2018 this guidance was used to design and build two cycle-friendly protected roundabouts in Moray St, South Melbourne, as part of the Metro Tunnel Project. The project upgraded the Moray Street bicycle path to provide cyclists with a safe path in the north-south route and raised pedestrian crossings at all branches of the roundabout during Metro Tunnel works on St Kilda Road. Safe System Solutions Pty Ltd evaluated the performance and found a moderate utilisation rate of cyclists on the dedicated bicycle lanes and a high utilisation rate of pedestrians using raised crossings. The evaluation also found no significant issues with near-crashes for bicycle-and-pedestrian and bicycle-and-vehicle interaction. There were no significant problems with vehicle drivers using the protected roundabout. However, it was noted that when pedestrians are crossing at the raised crossings then vehicles would sometimes stop in the middle of the roundabout thus blocking traffic.

In North Carolina, we analyzed cumulative data for tuberculosis (TB) from 1980 through 1999 to determine trends in incidence, population subgroups at risk, and implications for health policy-makers. The overall incidence rates declined significantly over the study period (p = 0.0001). This decline correlates strongly with an increase in TB patients receiving directly observed therapy. Males have approximately twice the risk for disease, and persons 65 years of age are at the highest risk. For every Caucasian with TB, six blacks, six Hispanics, and eight Asians have the disease. TB incidence rates are declining in all other population subgroups but increasing in foreign-born and Hispanic persons.

The substantial suppression of infrared blackbody emission from HgCdTe photoiodide arrays with cutoff wavelengths of 4.8, 5.5, and 6.0 micrometer. At room temperature, a reverse bias induces internal negative luminescence efficiencies of 95%, 93%, and 88%, respectively, which correspond to apparent cooling of the surface temperatures by 60, 59, and 49K.

Studies various InAs-on-AlSb interface structures grown by molecular beam epitaxy. Use of an atomic force microscope; Correlation between the interface configuration and the electron mobility in the InAs quantum well; Performance of transport measurements on the corresponding quantum well structures to establish the correlation between the interfacial morphology and the electron mobility in the channel.

We demonstrate the substantial suppression of infrared (IR) blackbody emission from HgCdTe photodiode arrays with cutoff wavelengths of 4.8, 5.5, and 6.0 μm. At room temperature, a reverse bias induces internal negative luminescence (NL) efficiencies of 95%, 93%, and 88%, respectively, which correspond to apparent cooling of the surface temperatures by 60, 59, and 49 K. Reverse-bias saturation current densities for the three devices were 0.11, 0.7, and 32 A/cm2. Measurement and analysis of the material transmission characteristics indicate that the small residual inefficiencies may be limited by a parasitic absorption process. The 4.8 and 5.5 pm photodiodes were fabricated into 18 × 2 arrays with total areas of 5 mm × 5 mm. In both cases, all 36 array elements were fully operable, and had similar electrical and NL properties. Effective fill factors were &ap;100%, since carrier diffusion led to the extraction of carriers from regions between the elements. These results show that efficient, low-power NL devices with active areas in the square-inch range are now feasible for such applications as the cold shielding of infrared focal-plane arrays. [ABSTRACT FROM AUTHOR]

The teaching and learning of English as a second language have always been emphasized by the Ministry of Education (MOE). In the Malaysia Education Blueprint (2013–2025), among the many goals is to produce learners who can comprehend the language for various purposes, including for information and enjoyment. Over the years, the teaching and learning of English have changed from conventional chalk-and-talk methods to modern methods that involve various platforms such as Quizizz, which is free and easy to use. This systematic literature review focuses on teachers' perception on the use of Quizizz in the teaching and learning of English. Using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) review methodology, a total of 45 articles related to the use of Quizizz in the English language classroom were identified from the ERIC and Google Scholar databases. Based on the articles from the year 2017 to 2021, the results show that the mixed-method research design was most used to gather teachers' perspectives on the use of Quizizz in the teaching and learning of English. Overall, the results of this study show that Quizizz is accepted positively among teachers due to its effectiveness, feasibility, ease of use, and motivating nature for learners. As a suggestion for future research, more focus can be put on investigating the effectiveness of Quizizz from the perspective of parents and issues related to the implementation of gamified learning, such as Internet connection and device availability. [ABSTRACT FROM AUTHOR]

We investigate a Josephson field-effect transistor in which the electron gas in an InAs quantum well serves as the weak link between superconducting Nb electrodes. We modulate the density N[sub s], of electrons and the critical current I[sub c] in the weak link by applying a voltage to an insulated gate. Measurements of the dependence of I[sub c] on N[sub s], are in good agreement with a model in which each occupied subband of the InAs quantum well makes an independent contribution to I[sub c]. Inclusion of the nonparabolic band structure in InAs is crucial to this agreement. [ABSTRACT FROM AUTHOR]