PACFEST : enabling technologies in the war on terrorism in the Pacific region.

On October 22-24, 2003, about 40 experts involved in various aspects of homeland security from the United States and four other Pacific region countries meet in Kihei, Hawaii to engage in a free-wheeling discussion and brainstorm (a 'fest') of the role that technology could play in winning the war on terrorism in the Pacific region. The result of this exercise is a concise and relatively thorough definition of the terrorism problem in the Pacific region, emphasizing the issues unique to Island nations in the Pacific setting, along with an action plan for developing working demonstrators of advanced technological solutions to these issues. In this approach, the participants were asked to view the problem and their potential solutions from multiple perspectives, and then to identify barriers (especially social and policy barriers) to any proposed technological solution. The final step was to create a roadmap for further action. This roadmap includes plans to: (1) create a conceptual monitoring and tracking system for people and things moving around the region that would be 'scale free', and develop a simple concept demonstrator; (2) pursue the development of a system to improve local terrorism context information, perhaps through the creation of an information clearinghouse for Pacific law enforcement; (3) explore the implementation of a Hawaii based pilot system to explore hypothetical terrorist scenarios and the development of fusion and analysis tools to work with this data (Sandia); and (4) share information concerning the numerous activities ongoing at various organizations around the understanding and modeling of terrorist behavior

Multiphase optimization of a multicomponent intervention for informal dementia caregivers: a study protocol

Abstract Background Family caregiver interventions are essential to support dementia caregiving. However, such interventions are typically complex and consist of multiple components. Existing evidence rarely delineates the effectiveness and interactions between individual components. To optimise intervention, we adopt the multiphase optimisation strategy (MOST) to test the implementation fidelity and determine the effect of each component and the interactions between each component and the corresponding outcome. Methods A prospective, assessor-blinded, randomised clinical trial with fractional factorial design using the MOST principle. Two hundred fifty family dementia caregivers will be randomised to one of 16 experimental conditions in a fractional factorial design involving six intervention components: (1) dementia and caregiving education; (2) self-care skills; (3) behavioural symptom management; (4) behavioural activation; (5) modified mindfulness-based cognitive therapy; and (6) support group. The first one is the core component, and the five remaining will be examined. Physical health, caregiver burden, stress, psychological well-being, anxiety and depressive symptoms, and social support will be assessed over the 12-month study period. Following the intention-to-treat principle, linear mixed models and regression analyses will be used to examine the specific effect of the five components and their two-way interactions to propose the most effective combination. Discussion This is the first study adopting the multiphase optimisation strategy to identify the most active and engaging components of a psychological intervention for caregivers of patients with dementia. In view that dementia caregiver interventions are increasingly diversified and complex, such knowledge is important to maximise the intervention efficacy and allow the intervention to be implemented within an efficient timeframe and dosage. The optimisation of caregiver support interventions is critical to enhance the health outcomes of caregivers and care recipients, thereby, delaying possible institutionalisation and reducing the costs of long-term dementia care. Trial registration This study was retrospectively registered in the WHO Primary Registry – Chinese Clinical Trials Registry (ChiCTR2300071235). (Protocol date 30/10/2020; version identifier 2020–2021-0045). Registered on 9 May, 2023. Reporting method SPIRIT guideline was followed. Patient or public contribution No patient or public involvement

DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibroblasts

In the search for specific genes regulated by DNA methylation in rheumatoid arthritis (RA), we investigated the expression of CXCL12 in synovial fibroblasts (SFs) and the methylation status of its promoter and determined its contribution to the expression of matrix metalloproteinases (MMPs). DNA was isolated from SFs and methylation was analyzed by bisulfite sequencing and McrBC assay. CXCL12 protein was quantified by enzyme-linked immunosorbent assay before and after treatment with 5-azacytidine. RASFs were transfected with CXCR7-siRNA and stimulated with CXCL12. Expression of MMPs was analyzed by real-time PCR. Basal expression of CXCL12 was higher in RASFs than osteoarthritis (OA) SFs. 5-azacytidine demethylation increased the expression of CXCL12 and reduced the methylation of CpG nucleotides. A lower percentage of CpG methylation was found in the CXCL12 promoter of RASFs compared with OASFs. Overall, we observed a significant correlation in the mRNA expression and the CXCL12 promoter DNA methylation. Stimulation of RASFs with CXCL12 increased the expression of MMPs. CXCR7 but not CXCR4 was expressed and functional in SFs. We show here that RASFs produce more CXCL12 than OASFs due to promoter methylation changes and that stimulation with CXCL12 activates MMPs via CXCR7 in SFs. Thereby we describe an endogenously activated pathway in RASFs, which promotes joint destruction