Background Temperature and rainfall patterns are known to influence seasonal patterns of dengue transmission. However, the effect of severe drought and extremely wet conditions on the timing and intensity of dengue epidemics is poorly understood. In this study, we aimed to quantify the non-linear and delayed effects of extreme hydrometeorological hazards on dengue risk by level of urbanisation in Brazil using a spatiotemporal model. MethodsWe combined distributed lag non-linear models with a spatiotemporal Bayesian hierarchical model framework to determine the exposure-lag-response association between the relative risk (RR) of dengue and a drought severity index. We fit the model to monthly dengue case data for the 558 microregions of Brazil between January, 2001, and January, 2019, accounting for unobserved confounding factors, spatial autocorrelation, seasonality, and interannual variability. We assessed the variation in RR by level of urbanisation through an interaction between the drought severity index and urbanisation. We also assessed the effect of hydrometeorological hazards on dengue risk in areas with a high frequency of water supply shortages. Findings The dataset included 12 895 293 dengue cases reported between 2001 and 2019 in Brazil. Overall, the risk of dengue increased between 0-3 months after extremely wet conditions (maximum RR at 1 month lag 1•56 [95% CI 1•41-1•73]) and 3-5 months after drought conditions (maximum RR at 4 months lag 1•43 [1•22-1•67]). Including a linear interaction between the drought severity index and level of urbanisation improved the model fit and showed the risk of dengue was higher in more rural areas than highly urbanised areas during extremely wet conditions (maximum RR 1•77 [1•32-2•37] at 0 months lag vs maximum RR 1•58 [1•39-1•81] at 2 months lag), but higher in highly urbanised areas than rural areas after extreme drought (maximum RR 1•60 [1•33-1•92] vs 1•15 [1•08-1•22], both at 4 months lag). We also found the dengue risk following extreme drought was higher in areas that had a higher frequency of water supply shortages.Interpretation Wet conditions and extreme drought can increase the risk of dengue with different delays. The risk associated with extremely wet conditions was higher in more rural areas and the risk associated with extreme drought was exacerbated in highly urbanised areas, which have water shortages and intermittent water supply during droughts. These findings have implications for targeting mosquito control activities in poorly serviced urban areas, not only during the wet and warm season, but also during drought periods.

Type 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7 signaling than males, even before puberty, but that puberty itself associated with increased production of type 1 IFN. A unique human model allows us to show that this was related to X chromosome number, and serum testosterone concentration, in a manner which differed depending on the number of X chromosomes present. In addition, we have showed that pDC were more activated in females overall, and immune cell TLR7 gene expression was higher in females after puberty. Therefore, sex hormones and X chromosome number were associated individually and interactively with the type 1 IFN response, which contributes to our understanding of why females are more likely to develop an IFN mediated disease like jSLE after puberty.

Background Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL), and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses. Method We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with two different vaccine platforms. Results Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n = 204) or adenovirus-based (n = 296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination. Conclusions These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoural protection against the globally dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.

Introduction:There is increasing evidence of the social, physical and cognitive benefits of group-singing for people living with dementia and their family carers. However, COVID-19 has necessitated the suspension of in-person group-singing globally. This study explores the impact of COVID-19 on dementia-inclusive singing groups and choirs in Ireland, and their facilitators' responses. It seeks to contribute to the limited literature on online group-singing and music telehealth for people living with dementia and family carers. It strives to provide facilitators with practical information to adapt their programmes for online delivery and continue to support the health and well-being of these populations. Method: This study adopted a qualitative methodological approach. Semi-structured interviews were conducted with facilitators of dementia-inclusive singing groups or choirs in Ireland (n = 12). Results: Four main themes were generated inductively from the data using Thematic Analysis: accessibility of online delivery; online vs in-person delivery; importance of social connection; adaptability and resilience. Discussion: This study provides a mixed picture of opportunities and challenges arising from online music programmes. Initial evidence indicates the ability of facilitators to successfully deliver online music programmes to a proportion of people living with dementia and family carers and the capacity of members of these populations to engage with them. The findings support the development of sustainable online groups and resources to increase the accessibility of dementia-inclusive singing groups and support community-dwelling people with dementia living in rural and remote areas or with health or mobility challenges. However, challenges of digital inclusion exist.