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Item does not contain fulltext, BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the seco

Introduction: Self-regulation is a modifiable protective factor for lifespan mental and physical health outcomes. Early caregiver-mediated interventions to promote infant and child regulatory outcomes prevent long-term developmental, emotional and behavioural difficulties and improve outcomes such as school readiness, educational achievement and economic success. To harness the population health promise of these programmes, there is a need for more nuanced understanding of the impact of these interventions. The aim of this realist review is to understand how, why, under which circumstances and for whom, early caregiver-mediated interventions improve infant and child self-regulation. The research questions guiding this review were based on consultation with families and community organisations that provide early childhood and family services. Methods and analysis: Realist reviews take a theory-driven and iterative approach to evidence synthesis, structured around continuous refinement of a programme theory. Programme theories specify context-mechanism-outcome configurations to explain what works, for whom, under which circumstances and how. Our initial programme theory is based on prior work in this field and will be refined through the review process. A working group, comprising service users, community organisation representatives, representatives from specific populations, clinicians and review team members will guide the evidence synthesis and interpretation, as well as the development and dissemination of recommendations based on the findings of the review. The review will involve searching: (i) electronic databases, (ii) connected papers, articles and citations and (iii) grey literature. Decisions to include evidence will be guided by judgements about their contribution to the programme theory and will be made by the research team, with input from the working group. Evidence synthesis will be reported using the Realist and MEta-narrative Evidence Synthesis: Evo

In this paper, and inspired by the recent discrete-time model in Parsegov et al. (2017) and Friedkin et al. (2016), we study two continuous-time opinion dynamics models (Model 1 and Model 2) where the individuals discuss opinions on multiple logically interdependent topics. The logical interdependence between the different topics is captured by a “logic” matrix, which is distinct from the Laplacian matrix capturing interactions between individuals. For each of Model 1 and Model 2, we obtain a necessary and sufficient condition for the network to reach to a consensus on each separate topic. The condition on Model 1 involves a combination of the eigenvalues of the logic matrix and Laplacian matrix, whereas the condition on Model 2 requires only separate conditions on the logic matrix and Laplacian matrix. Further investigation of Model 1 yields two sufficient conditions for consensus, and allows us to conclude that one way to guarantee a consensus is to reduce the rate of interaction between individuals exchanging opinions. By placing further restrictions on the logic matrix, we also establish a set of Laplacian matrices which guarantee consensus for Model 1. The two models are also expanded to include stubborn individuals, who remain attached to their initial opinions. Sufficient conditions are obtained for guaranteeing convergence of the opinion dynamics system, with the final opinions generally being at a persistent disagreement. Simulations are provided to illustrate the results.

Background: Sensory reweighting is important for humans to flexibly up-weigh and down-weigh sensory information in dynamic environments. There is an element of time involved in the sensory reweighting process. A longer time spent on sensory reweighting may increase the destabilizing effect of postural control. Individuals with autism spectrum disorder (ASD) are reported to have poor postural control. It is uncertain if a different sensory reweighting process underlies the postural control deficit in children and adults with ASD. Research question: To explore the sensory reweighting capability in ASD, the present study examined whether the temporal domains of postural control differed in children and adults, with and without ASD under various optic flow conditions. Methods: Thirty-three children (8–12 years old) and 33 adults (18–50 years old) with and without ASD underwent quiet standing in six radial optic flow conditions. Each condition lasted for 60 s and was shown twice to all participants. For each optic flow condition, changes in postural response within-trial and between-trials were measured. Results: Under various optic flow illusions, both children with and without ASD took a longer time to restore their posture compared with adults with and without ASD. Nonetheless, all groups demonstrated comparable abilities to adjust their posture to one that is close to the baseline position after one exposure to the optic flow stimulation. Significance: The present study showed that the temporal domains of postural control under different optic flow conditions were similar between individuals with and without ASD from the same age group. The ability to down-weigh visual information efficiently comes with the developmental progression of the sensory reweighting system. These findings suggest that the sensory reweighting process does not elucidate the postural control deficits in individuals with ASD and thus alternative explanations to determine the underlying mechanis