IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer

Breast cancer bone metastasis is currently incurable, ~75% of patients with late-stage breast cancer develop disease recurrence in bone and available treatments are only palliative. We have previously shown that production of the pro-inflammatory cytokine interleukin-1B (IL-1B) by breast cancer cells drives bone metastasis in patients and in preclinical in vivo models. In the current study, we have investigated how IL-1B from tumour cells and the microenvironment interact to affect primary tumour growth and bone metastasis through regulation of the immune system, and whether targeting IL-1 driven changes to the immune response improves standard of care therapy for breast cancer bone metastasis. Using syngeneic IL-1B/IL1R1 knock out mouse models in combination with genetic manipulation of tumour cells to overexpress IL-1B/IL1R1, we found that IL-1B signalling elicited an opposite response in primary tumours compared with bone metastases. In primary tumours, IL-1B inhibited growth, by impairing the infiltration of innate immune cell subsets with potential anti-cancer functions but promoted enhanced tumour cell migration. In bone, IL-1B stimulated the development of osteolytic metastases. In syngeneic models of breast cancer, combining standard of care treatments (Doxorubicin and Zoledronic acid) with the IL-1 receptor antagonist Anakinra inhibited both primary tumour growth and metastasis. Anakinra had opposite effects on the immune response compared to standard of care treatment, and its anti-inflammatory signature was maintained in the combination therapy. These data suggest that targeting IL-1B signalling may provide a useful therapeutic approach to inhibit bone metastasis and improve efficacy of current treatments for breast cancer patients

Exploring the role of egocentrism and fear of missing out on online risk behaviours among adolescents in South Africa

The study explored the potential for developmental and social factors to predict adolescent online risk behaviour. Employing a sample of 1184 adolescents aged 12–18 in South Africa, the study examined gender, age, egocentrism (Personal Fable and Imaginary Audience) and Fear of Missing Out (FoMO) on online risk taking. Results showed that all variables were significant predictors of online risk behaviour. Higher Imaginary Audience, higher FoMO and older age emerged as strongest predictors, and males engaged in more online risks. FoMO also correlated significantly with egocentrism constructs. The findings indicate that egocentrism is a relevant developmental construct for understanding adolescent online risk taking along with social factors like FoMO, which can inform more targeted online safety efforts at particular developmental stages

Is media multitasking good for cybersecurity? Exploring the relationship between media multitasking and everyday cognitive failures on self-reported risky cybersecurity behaviors

The current study focused on how engaging in media multitasking (MMT) and the experience of everyday cognitive failures impact on the individual's engagement in risky cybersecurity behaviors (RCsB). In total, 144 participants (32 males, 112 females) completed an online survey. The age range for participants was 18 to 43 years (M = 20.63, SD = 4.04). Participants completed three scales which included an inventory of weekly MMT, a measure of everyday cognitive failures, and RCsB. There was a significant difference between heavy media multitaskers (HMM), average media multitaskers (AMM), and light media multitaskers (LMM) in terms of RCsB, with HMM demonstrating more frequent risky behaviors than LMM or AMM. The HMM group also reported more cognitive failures in everyday life than the LMM group. A regression analysis showed that everyday cognitive failures and MMT acted as significant predictors for RCsB. These results expand our current understanding of the relationship between human factors and cybersecurity behaviors, which are useful to inform the design of training and intervention packages to mitigate RCsB

Diadoxus erythrurus (White) (Coleoptera - Buprestidae), attack of fire-damaged Callitris spp

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A left-ear disadvantage for the presentation of irrelevant sound: manipulations of task requirements and changing state

Three experiments attempted to clarify the effect of altering the spatial presentation of irrelevant auditory information. Previous research using serial recall tasks demonstrated a left-ear disadvantage for the presentation of irrelevant sounds (Hadlington, Bridges, & Darby, 2004). Experiments 1 and 2 examined the effects of manipulating the location of irrelevant sound on either a mental arithmetic task (Banbury & Berry, 1998) or a missing-item task (Jones & Macken, 1993; Experiment 4). Experiment 3 altered the amount of change in the irrelevant stream to assess how this affected the level of interference elicited. Two prerequisites appear necessary to produce the left-ear disadvantage; the presence of ordered structural changes in the irrelevant sound and the requirement for serial order processing of the attended information. The existence of a left-ear disadvantage highlights the role of the right hemisphere in the obligatory processing of auditory information. (c) 2006 Published by Elsevier Inc

Clustering Insider Threat Behaviour: An Ultrametric Anomaly Detection System

Anger, aggression and confrontational behaviour (Greitzer et al., 2012) is one of 12 psychosocial precursors linked to malicious insider threat activity. Although there is not a given threshold at which these become a cause for concern, the manifestation of anger through aggressive language becomes relevant to indicate a potential insider threat, in particular when patterns outside of normal behaviour are observed. In previous work we have shown how an ultrametric (Murtagh et al., 2008, Contreras et al., 2012) can be used to create hierarchical clusters in constant algorithmic time. In this work we introduce the use of such ultrametric applied to textual data in order to cluster anomalous aggressive behaviour. Our interest lies in detecting anomalies that can be used in conjunction with other behavioural precursors (e.g. stress, network tra c, etc.) to detect an insider threat

Impacts of temperature on metabolic rates of adult Extatosoma tiaratum

Access to balanced nutrition enables optimum health and development, body repair, fat storage, increased fecundity and longevity. In the present study, we assessed the responses of a generalist leaf feeder (the phasmid Extatosoma tiaratum) reared continuously on one of three host plants, tree lucerne (Chamaecyisus palmensis), bramble (Rubus fruticosus) and Eucalyptus species, in a low fluctuating temperature environment until adulthood. Once all individuals reached adulthood, we exposed each individual to a ramping temperature event (starting at 25 °C and ramping the temperature at 0.25 °C min⁻¹) and assessed their metabolic rates (V̇꜀ₒ₂) responses at specific temperature 'bins' (25, 30, 35, 40 and 42 °C). Sex but not diet influenced respiration and metabolic rate. Male individuals, on average, had a higher V̇꜀ₒ₂ than females. Sex and diet were significant influences on V̇꜀ₒ₂ at different temperatures. Metabolic rates at lower temperatures were not affected by sex or diet type. At 35 °C, metabolic rates were influenced by sex and diet, with males reared on bramble and tree lucerne having a higher metabolic rate than females reared on the same foodplant, whereas Eucalypt reared animals showing an opposite trend. Lifetime egg production by females was 150% higher on bramble compared with the other host plants. Incorporating fluctuating temperature ranges into experiments will further help to understand the impact that thermal stress will have on the growth, development, performance and survival of insects in a more variable climatic and nutritional landscape