Daleclayton2824

Outcomes will be analysed for superiority according to intention-to-treat and per-protocol approaches. ETHICS AND DISSEMINATION Approval has been received from the relevant ethics committees. Findings will be disseminated in peer-reviewed journals and conferences, targeting those involved in managing people with COPD as well as those who develop policies and guidelines. CLINICAL TRIAL REGISTRATION ANZCTR 12618000933257. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Current literature supports cross-sectional association between childhood obstructive sleep apnoea (OSA) and elevated blood pressure (BP). However, long-term cardiovascular outcomes in children with OSA remain unexplored. OBJECTIVE To evaluate the associations of childhood OSA with BP parameters in a prospective 10 year follow-up study. METHODS Participants were recruited from a cohort established for our previous OSA epidemiological study. They were invited to undergo clinical examination, overnight polysomnography and 24-hour ambulatory BP monitoring. Multivariate linear regression was used to assess the associations of baseline childhood OSA with BP outcomes at follow-up. Multivariable log-binomial regression was used with inverse probability weighting to assess the adjusted associations of childhood OSA with hypertension and non-dipping of nocturnal BP in adulthood. RESULTS 243 participants (59% male) attended the follow-up visit. The mean age was 9.8 (SD ±1.8) and 20.2 (SD ±1.9) years at baseline and follow-up respectively, with a mean follow-up duration of 10.4 (SD ±1.1) years. Childhood moderate-to-severe OSA was associated with higher nocturnal systolic blood pressure (SBP) (difference from normal controls 6.5 mm Hg, 95% CI 2.9 to 10.1) and reduced nocturnal dipping of SBP (-4.1%, 95% CI -6.3% to 1.8%) at follow-up, adjusted for age, sex, Body Mass Index and height at baseline, regardless of the presence of OSA at follow-up. Childhood moderate-to-severe OSA was also associated with higher risk of hypertension (relative risk (RR) 2.5, 95% CI 1.2 to 5.3) and non-dipping of nocturnal SBP (RR 1.3, 95% CI 1.0 to 1.7) at follow-up. CONCLUSION Childhood OSA was found to be an independent risk factor for adverse BP outcomes in adulthood. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Key populations such as men who have sex with men (MSM), drug users and sex workers are at high risk of HIV infection, but they are marginalised and hidden. Social network strategy (SNS) is purposeful to use social networks to generate social influence, accelerate behaviour change and achieve desirable outcomes among individuals or communities and have been increasingly used for HIV interventions. This study aims to investigate the effects of SNS on HIV prevention among key populations. METHODS We searched six databases, including PubMed, Web of Science, Embase, Cochrane Library, ScienceDirect and Wiley for randomised controlled trials published between January 1999 and May 2019. Eligibility criteria included SNS conducted among key populations for HIV interventions, with a comparator group. Outcomes included changes in HIV high-risk behaviour, HIV seroconversion and other HIV outcomes. We used the risk ratio (RR) or mean difference with associated 95% confidence interval (CI) to assess the compaour and HIV incidence and increases HIV testing uptake and participant retention. TRIAL REGISTRATION NUMBER CRD42019140533. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.T-cell receptor (TCR)-modified T-cell gene therapy can target a variety of extracellular and intracellular tumor associated antigens, yet has had little clinical success. A potential explanation for limited antitumor efficacy is a lack of T-cell activation in vivo. We postulated that expression of pro-inflammatory cytokines in TCR-modified T cells would activate T cells and enhance antitumor efficacy. We demonstrate that expression of interleukin 18 (IL18) in tumor-directed TCR-modified T cells provides a superior pro-inflammatory signal than expression of interleukin 12 (IL12). Tumor-targeted T cells secreting IL18 promote persistent and functional effector T cells and a pro-inflammatory tumor microenvironment. Together, these effects augmented overall survival of mice in the pmel-1 syngeneic tumor model. find more When combined with sublethal irradiation, IL18-secreting pmel-1 T cells were able to eradicate tumors, whereas IL12-secreting pmel-1 T cells caused toxicity in mice through excessive cytokine secretion. In another xenograft tumor model, IL18 secretion enhanced the persistence and antitumor efficacy of NY-ESO-1-reactive TCR-modified human T cells as well as overall survival of tumor-bearing mice. These results demonstrate a rationale for optimizing the efficacy of TCR-modified T-cell cancer therapy through expression of IL18. Copyright ©2020, American Association for Cancer Research.Resistance to cytotoxic T cells is frequently mediated by loss of MHC class I expression or IFNγ signaling in tumor cells, such as mutations of B2M or JAK1 genes. NK cells could potentially target such resistant tumors, but suitable NK cell-based strategies remain to be developed. We hypothesized that such tumors could be targeted by NK cells if sufficient activating signals were provided. Human tumors frequently express the MICA and MICB ligands of the activating NKG2D receptor, but proteolytic shedding of MICA/B represents an important immune evasion mechanism in many human cancers. We showed that B2M- and JAK1-deficient metastases were targeted by NK cells following treatment with a monoclonal antibody (mAb) that blocks MICA/B shedding. We also demonstrated that the FDA-approved HDAC inhibitor panobinostat and a MICA/B antibody acted synergistically to enhance MICA/B surface expression on tumor cells. The HDAC inhibitor enhanced MICA/B gene expression, whereas the MICA/B antibody stabilized the synthesized protein on the cell surface.