Potent induction of antibody-secreting B-cells by human dermal-derived CD14+ dendritic cells triggered by dual toll-like receptor ligation

Targeting CD14(+) dermal-derived dendritic cells (DDCs) is a rational approach for vaccination strategies aimed at improving humoral immune responses, because of their natural ability to stimulate naïve B-cells. Here, we show that CD14(+) DDCs express mRNA for TLRs 1–9, but respond differentially to single or paired TLR ligands. Compared to single ligands, some combinations were particularly effective at activating CD14(+) DDCs, as shown by enhanced expression of B-cell stimulatory cytokines (IL-6, IL-10 and TNF-α) and more pronounced phenotypic maturation. These combinations were Resiquimod (R-848) plus Polyinosinic:polycytidylic acid (Poly(I:C)); R-848 plus LPS; Pam3CSK4 plus Poly(I:C); LPS plus Poly(I:C). We also found that selected TLR ligand pairs (R-848 plus either LPS or Poly(I:C)) were superior to individual agents at boosting the inherent capacity of CD14(+) DDCs to induce naïve B-cells to proliferate and differentiate into CD27(+) CD38(+) B-cells that secrete high levels of IgG and IgA. When treated with the same TLR ligand combinations, CD14(+) DDCs also promoted the differentiation of Th1 (IFN-γ-secreting) CD4(+) T-cells, but not of Th2 or Th17 CD4(+) T-cells. These observations may help to identify adjuvant strategies aimed at inducing protective immune responses to various pathogens, including but not limited to HIV-1

Ocean temperature and salinity components of the Madden-Julian oscillation observed by Argo floats

New diagnostics of the Madden-Julian Oscillation (MJO) cycle in ocean temperature and, for the first time, salinity are presented. The MJO composites are based on 4 years of gridded Argo float data from 2003 to 2006, and extend from the surface to 1,400 m depth in the tropical Indian and Pacific Oceans. The MJO surface salinity anomalies are consistent with precipitation minus evaporation fluxes in the Indian Ocean, and with anomalous zonal advection in the Pacific. The Argo sea surface temperature and thermocline depth anomalies are consistent with previous studies using other data sets. The near-surface density changes due to salinity are comparable to, and partially offset, those due to temperature, emphasising the importance of including salinity as well as temperature changes in mixed-layer modelling of tropical intraseasonal processes. The MJO-forced equatorial Kelvin wave that propagates along the thermocline in the Pacific extends down into the deep ocean, to at least 1,400 m. Coherent, statistically significant, MJO temperature and salinity anomalies are also present in the deep Indian Ocean

Awareness without learning: A preliminary study exploring the effects of beachgoer's experiences on risk taking behaviours

Most drowning deaths on Australian beaches occur in locations not patrolled by lifeguards. At patrolled locations, where lifeguards supervise flagged areas in which beachgoers are encouraged to swim between, the incidence of drowning is reduced. To date, risk prevention practices on coasts focus on patrolled beaches, deploying warning signs at unpatrolled locations with the aim of raising public awareness of risk. What remains unexplored is the potential for learning and behaviour change that can transfer from patrolled to unpatrolled beaches through beachgoer's experiences and interactions with lifeguards. The aim of this preliminary study is to explore the risk perceptions of beachgoers at a patrolled beach to establish if and how their experiences of beach risk and interactions with lifeguards affect their behaviours. Data was collected in Gerroa, Australia by engaging 49 beachgoers using a mixed survey-interview methodology. Results show that beachgoers are aware that they should ‘swim between the flags’, but many did not know the basis for the positioning of safety flags. A key finding is that beachgoer's express a clear desire for a skills-based model of community engagement that enables learning with lifeguards. This demonstrates a reflective public that desires skill-development, which may transfer from patrolled to unpatrolled beaches to affect broader risk reduction on the Australian coast. Learning how to avoid site-specific rip hazards with lifeguards at the beach presents a promising, and previously unexplored model for beach drowning risk prevention that has the potential to affect behaviour at unpatrolled beaches, providing an empirically-supported alternative to prevailing deficit-based awareness raising methods

Hip joint replacement surgery for idiopathic osteoarthritis aggregates in families

In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA), we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with hip OA than in those with knee OA

Differences in trajectories of quality of life according to type of dementia: 6-year longitudinal findings from the IDEAL programme

Background: People with different types of dementia may have distinct symptoms and experiences that affect their quality of life. This study investigated whether quality of life varied across types of dementia and over time. Methods: The participants were 1555 people with mild-to-moderate dementia and 1327 carers from the IDEAL longitudinal cohort study, recruited from clinical services. As many as possible were followed for up to 6 years. Diagnoses included were Alzheimer’s disease, vascular dementia, mixed Alzheimer’s and vascular dementia, Parkinson’s disease dementia, dementia with Lewy bodies, and frontotemporal dementia. Self- and informant-rated versions of the Quality of Life in Alzheimer’s Disease scale were used. A joint model, incorporating a mixed effects model with random effects and a survival model to account for dropout, was used to examine whether quality of life varied by dementia type at the time of diagnosis and how trajectories changed over time. Results: The strongest associations between dementia type and quality of life were seen around the time of diagnosis. For both self-ratings and informant ratings, people with Parkinson’s disease dementia or dementia with Lewy bodies had lower quality of life scores. Over time there was little change in self-rated scores across all dementia types (− 0.15 points per year). Informant-rated scores declined over time (− 1.63 points per year), with the greatest decline seen in ratings by informants for people with dementia with Lewy bodies (− 2.18 points per year). Conclusions: Self-rated quality of life scores were relatively stable over time whilst informant ratings showed a steeper decline. People with Parkinson’s disease dementia or dementia with Lewy bodies report particularly low levels of quality of life, indicating the importance of greater attention to the needs of these groups

Neoliberalisation and 'lad cultures' in higher education

This paper links HE neoliberalisation and ‘lad cultures’, drawing on interviews and focus groups with women students. We argue that retro-sexist ‘laddish’ forms of masculine competitiveness and misogyny have been reshaped by neoliberal rationalities to become modes of consumerist sexualised audit. We also suggest that neoliberal frameworks scaffold an individualistic and adversarial culture among young people that interacts with perceived threats to men’s privilege and intensifies attempts to put women in their place through misogyny and sexual harassment. Furthermore, ‘lad cultures’, sexism and sexual harassment in higher education may be invisibilised by institutions to preserve marketability in a neoliberal context. In response, we ask if we might foster dialogue and partnership between feminist and anti-marketisation politics

Comorbid health conditions and their impact on social isolation, loneliness, quality of life, and well-being in people with dementia: longitudinal findings from the IDEAL programme

\ua9 2024, The Author(s).Background: Most people with dementia have multiple health conditions. This study explores (1) number and type of health condition(s) in people with dementia overall and in relation to age, sex, dementia type, and cognition; (2) change in number of health conditions over two years; and (3) whether over time the number of health conditions at baseline is related to social isolation, loneliness, quality of life, and/or well-being. Methods: Longitudinal data from the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort were used. Participants comprised people with dementia (n = 1490) living in the community (at baseline) in Great Britain. Health conditions using the Charlson Comorbidity Index, cognition, social isolation, loneliness, quality of life, and well-being were assessed over two years. Mixed effects modelling was used. Results: On average participants had 1.8 health conditions at baseline, excluding dementia; increasing to 2.5 conditions over two years. Those with vascular dementia or mixed (Alzheimer’s and vascular) dementia had more health conditions than those with Alzheimer’s disease. People aged ≥ 80 had more health conditions than those aged < 65 years. At baseline having more health conditions was associated with increased loneliness, poorer quality of life, and poorer well-being, but was either minimally or not associated with cognition, sex, and social isolation. Number of health conditions had either minimal or no influence on these variables over time. Conclusions: People with dementia in IDEAL generally had multiple health conditions and those with more health conditions were lonelier, had poorer quality of life, and poorer well-being

Modelling and simulating change in reforesting mountain landscapes using a social-ecological framework

Natural reforestation of European mountain landscapes raises major environmental and societal issues. With local stakeholders in the Pyrenees National Park area (France), we studied agricultural landscape colonisation by ash (Fraxinus excelsior) to enlighten its impacts on biodiversity and other landscape functions of importance for the valley socio-economics. The study comprised an integrated assessment of land-use and land-cover change (LUCC) since the 1950s, and a scenario analysis of alternative future policy. We combined knowledge and methods from landscape ecology, land change and agricultural sciences, and a set of coordinated field studies to capture interactions and feedback in the local landscape/land-use system. Our results elicited the hierarchically-nested relationships between social and ecological processes. Agricultural change played a preeminent role in the spatial and temporal patterns of LUCC. Landscape colonisation by ash at the parcel level of organisation was merely controlled by grassland management, and in fact depended on the farmer's land management at the whole-farm level. LUCC patterns at the landscape level depended to a great extent on interactions between farm household behaviours and the spatial arrangement of landholdings within the landscape mosaic. Our results stressed the need to represent the local SES function at a fine scale to adequately capture scenarios of change in landscape functions. These findings orientated our modelling choices in the building an agent-based model for LUCC simulation (SMASH - Spatialized Multi-Agent System of landscape colonization by ASH). We discuss our method and results with reference to topical issues in interdisciplinary research into the sustainability of multifunctional landscapes