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The AGHQ method did not show better properties than the LA estimation in terms of convergence rate, bias, coverage, and possibility to produce very large odds ratios. In addition, although the PQL had some advantages, it was not the preferred option due to its low convergence rate in some situations, and the suboptimal point and variance estimation compared to the LA. Conclusion The GLMM is an alternative for meta-analysis of rare events and is especially useful in the presence of zero-events studies, while at least 10 total events in both arms is recommended when employing GLMM for meta-analysis. The penalized quasi-likelihood and adaptive Gauss-Hermite quadrature are not superior to the Laplace approximation for rare events and thus they are not recommended.Background Subjective measures of sedentary behaviour (SB) (i.e. questionnaires and diaries/logs) are widely implemented, and can be useful for capturing type and context of SBs. However, little is known about comparative validity and reliability. The aim of this systematic review and meta-analysis was to 1) identify subjective methods to assess overall, domain- and behaviour-specific SB, and 2) examine the validity and reliability of these methods. Methods The databases MEDLINE, EMBASE and SPORTDiscus were searched up to March 2020. Inclusion criteria were 1) assessment of SB, 2) evaluation of subjective measurement tools, 3) being performed in healthy adults, 4) manuscript written in English, and 5) paper was peer-reviewed. Data of validity and/or reliability measurements was extracted from included studies and a meta-analysis using random effects was performed to assess the pooled correlation coefficients of the validity. Results The systematic search resulted in 2423 hits. After excluding duplicates and sion number CRD42018105994.Objective To characterize long-term repopulation of peripheral immune cells following alemtuzumab-induced lymphopenia in relapsing-remitting MS (RRMS), with a focus on regulatory cell types, and to explore associations with clinical outcome measures. Methods The project was designed as a multicenter add-on longitudinal mechanistic study for RRMS patients enrolled in CARE-MS II, CARE-MS II extension at the University of Southern California and Stanford University, and an investigator-initiated study conducted at the Universities of British Columbia and Chicago. Methods involved collection of blood at baseline, prior to alemtuzumab administration, and at months 5, 11, 17, 23, 36, and 48 post-treatment. T cell, B cell, and natural killer (NK) cell subsets, chemokine receptor expression in T cells, in vitro cytokine secretion patterns, and regulatory T cell (Treg) function were assessed. Clinical outcomes, including expanded disability status score (EDSS), relapses, conventional magnetic resonance imaging (MRI) mrrelated with increases in CD3+CD8+CXCR3+ cells. Conclusions Lymphocyte repopulation after alemtuzumab treatment favors regulatory subsets in the T cell, B cell, and NK cell compartments. Clinical efficacy may reflect the sum of interactions among them, leading to control of potentially pathogenic effector cell types. Several immune measures were identified as possible biomarkers of lesion activity. Future studies are necessary to more precisely define regulatory and effector subsets and their contributions to clinical efficacy and risk for secondary autoimmunity in alemtuzumab-treated patients, and to reveal new insights into mechanisms of immunopathogenesis in MS. Trial registration Parent trials for this study are registered with ClinicalTrials.gov CARE-MS II NCT00548405, CARE-MS II extension NCT00930553 and ISS NCT01307332.Background The inclusion of 'seldom heard' groups in health and social care research is increasingly seen as important on scientific, policy and ethical grounds. British South Asians, the largest minority ethnic group in the United Kingdom (UK), are under-represented in health research yet over-represented in the incidence of certain conditions such as type 2 diabetes. With the growing requirement of patient involvement in research and the inclusion of diverse populations, methodological guidance on how to include, engage and conduct research with UK South Asian populations is essential if services and interventions are to be relevant and impactful. However, such guidance for researchers is limited. Methods The aim of the paper is to reflect on our experiences of conducting focus groups with UK South Asian communities with type 2 diabetes, which involved experienced community partners and researchers working closely together. We discuss the factors that aided the successful delivery of the project, the challe research topic and provide an insight into context-specific attitudes and views. Future research should explore British South Asian participants' views on how they would like to be involved in research, including new methods of collecting data and coproducing research.Background A proper application of the Delphi technique is essential for obtaining valid research results. Medical researchers regularly use Delphi studies, but reports often lack detailed information on methodology and controlled feedback in the medical literature, papers focusing on Delphi methodology issues are rare. Since the introduction of electronic surveys, details on response times remain scarce. We aim to bridge a number of gaps by providing a real world example covering methodological choices and response times in detail. Methods The objective of our e(lectronic)-Delphi study was to determine minimum standards for emergency departments (EDs) in the Netherlands. We opted for a two-part design with explicit decision rules. Part 1 focused on gathering and defining items; Part 2 addressed the main research question using an online survey tool. A two-person consensus rule was applied throughout even after consensus on specific items was reached, panellists could reopen the discussion as long as at leastear decision rules, use a consistent lay-out and send out your reminders early. Adopting this overall approach may assist researchers in future Delphi studies and may help to improve the quality of Delphi designs in terms of improved rigor and higher response rates.Background UK government guidelines and initiatives emphasise equity in delivery of care, shared decision-making, and patient-centred care. This includes sharing information with patients as partners in health decisions and empowering them to manage their health effectively. In the UK, general practitioners (GPs) routinely receive hospital discharge letters; while patients receiving copies of such letters is seen as "good practice" and recommended, it is not standardised. The effects and consequences of whether or not this happens remains unclear. The aim of this study (one of three forming the Discharge Communication Study) was to explore patient perspectives on receiving discharge letters and their views on how this could be improved in order to optimise patient experience and outcomes. Methods Semi-structured interviews were conducted with a diverse sample of 50 patients recruited from 17 GP surgeries within the West Midlands, UK. All participants were adults with a recent episode of general hospital inpatly offered them. Patients' preferences for letter receipt could be logged in their health records. To enable positive outcomes letters should have a clear and accessible format that reflects the priorities and information needs of patients. Patients appear not to be receiving or being offered copies of letters consistently despite UK policies and guidelines supporting this practice; this suggests a need for greater standardisation of practice.Background Colon adenocarcinoma (COAD) is the most common form of colon cancer. The glutathione S-transferase Mu (GSTM) gene belongs to the GST gene family, which functions in cell metabolism and detoxification. The relationship between GSTM and COAD and the underlying mechanism remain unknown. Methods Data extracted from The Cancer Genome Atlas included mRNA expression and clinical information such as gender, age, and tumor stage. Prognostic values of GSTM genes were identified by survival analysis. Function and mechanism of prognostic GSTM genes were identified by gene set enrichment analysis. A nomogram was used to predict the contribution of risk factors to the outcome of COAD patients. Results Low expression of GSTM1 and GSTM2 was related to favorable OS (adjusted P = 0.006, adjusted HR = 0.559, 95% CI = 0.367-0.849 and adjusted P = 0.002, adjusted HR = 0.519, 95% CI = 0.342-0.790, respectively) after adjusting for tumor stage. Enrichment analysis also showed that genes involved were related to cell cycle, metabolism, and detoxification processes, as well as the Wnt signaling and NF-κB pathways. Conclusions In conclusion, low expression of GSTM1 and GSTM2 were significantly associated with favorable prognosis in COAD. These two genes may serve as potential biomarkers of COAD prognosis.Background Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by Echinococcus multilocularis larval tapeworm infections in humans that severely impairs the health of affected patients in the northern hemisphere. Methods The expression levels of 20 cytokines associated with AE infection were measured by enzyme-linked immunosorbent assay, and the correlations between these cytokines were analysed in the R programming language. Results Serum cytokine levels differed among individuals in both the AE patient and healthy control groups. The results of the correlations among the cytokines showed obvious differences between the two groups. In the AE patients group, Th1 and Th2 cytokines formed a more complicated network than that in the healthy control group. Conclusions The altered correlations between Th1 and Th2 cytokines may be closely associated with AE infection, which may provide a new explanation for the essential differences between AE patients and healthy individuals.Background Innate immune cells play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via release of cytokines. Small-molecule inhibitors of Janus kinases (JAKi) are clinically efficacious in patients with RA. However, the isoform-specific action of each JAKi is difficult to assess, since JAKs form heterodimeric complexes with cytokine receptors. We assessed the effects of several JAKi on GM-CSF-primed human innate immune cells. Results Treatment with JAKi (tofacitinib, baricitinib, upadacitinib) prevented GM-CSF-induced JAK2/STAT5 phosphorylation at higher concentrations (400 nM) in THP-1 cells. Whereas compared with baricitinib or upadacitinib, the inhibitory effects of tofacitinib on the GM-CSF-induced JAK2/STAT5 phosphorylation were weak at lower concentrations (≤ 100 nM). All JAKi inhibited GM-CSF-induced IL-1β production by human neutrophils. However, the inhibitory effects of baricitinib on IL-1β production were larger compared to those of tofacitinib or upadacitinib at lower concentrations (≤ 100 nM). Similarly, all JAKi inhibited GM-CSF-induced caspase-1(p20) production by human neutrophils. Conclusion We conclude that incubation with JAKi prevents GM-CSF-mediated JAK2/STAT5 activation in human innate immune cells. Although baricitinib and upadacitinib almost completely blocked GM-CSF-mediated JAK2/STAT5 signaling, the inhibitory effects of tofacitinib were weaker at lower concentrations suggesting that variation exists among these JAKi in the inhibition of JAK2 signaling pathways.
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