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Autism in Viet Nam: A systematic scoping review
No full textAutism research has predominantly focused on Western contexts, with limited studies in Vietnamese cultural settings. Through conducting a systematic scoping review, we aimed to map (a) the landscape of autism research in Vietnamese cultural contexts, (b) the quality of the research, and (c) the extent of autism community involvement in the research. A total of 137 studies met our inclusion criteria. A growing body of literature pertained to autism in Vietnamese cultural contexts, largely conducted in Viet Nam (87%). Much of the literature focused on Services and Supports (39%), as well as Interventions (20%). Key themes identified from the research were the centrality of family, the importance of school and education, and identifying a cause of autism. Quality appraisals of the studies – using the Mixed Methods Appraisal Tool, a Westernised tool – indicated that the studies were largely of low quality. There was limited autism community involvement in the research, with studies often lacking an explicit description of the nature of community involvement. Priority areas for future research include better understanding how rigour is understood in a Vietnamese research context, improving the clarity of data reporting and actively involving the Vietnamese autism community in the research process. Lay abstract: Autism research has mostly focused on Western contexts, with few studies in Vietnamese cultural contexts. In this study, we reviewed all the research we could find on autism in Vietnamese cultural contexts, to map out what this research ‘looks like’. We found 137 studies on autism in Vietnamese cultural contexts, and most of this research was conducted in Viet Nam. The studies were often focused in the areas of Services and Supports as well as Interventions. Looking for common themes in the research, we found that studies emphasised the importance of family, the importance of school and education, and the need to find the causes of autism. We used the Mixed Methods Appraisal Tool, a Westernised tool, to evaluate the quality of the research, and we found that a lot of the research was rated as ‘low quality’. There were few examples of clear autism community involvement in the research. Key areas for the field to focus on in the future include reflecting on how the quality of the research is evaluated in Global South countries such as Viet Nam, and how best to include the autism community in the research process
TSP-1 interaction with RANK and OPG: implications for bone remodeling and osteolytic bone metastasis
No full textExcessive bone disruption, driven by upregulation of bone-degrading osteoclasts, occurs in several pathologies, including breast cancer osteolytic bone metastasis, a condition associated with poor prognosis and diminished quality of life for patients. The matricellular protein thrombospondin-1 (TSP-1) plays pleiotropic roles in physiological and pathological remodeling of several tissues, including bone, and in shaping the microenvironment of primary tumors and metastasis. This study aimed to explore the role of TSP-1 in bone remodeling associated with osteolytic bone metastasis. We have identified a C-terminal fragment of TSP-1, E123CaG, that inhibited RANKL-induced osteoclast differentiation. Cleavage of TSP-1 by serine proteases released by mature osteoclasts, particularly HTRA1, generated a similar fragment, indicating a possible role as a feedback mechanism of control. E123CaG bound RANK, the RANKL receptor on osteoclast precursors, and impaired early (the MAPKs p38 and JNK) and late (NFATc1) downstream signaling. E123CaG also bound osteoprotegerin (OPG), the decoy receptor of RANKL, in this case further potentiating its inhibitory activity by protecting it from degradation by proteases, including HTRA1. In an in vivo model of osteolytic bone metastasis, the expression of E123CaG by murine breast cancer cells reduced osteolytic lesions and prolonged survival, indicating that the C-terminal TSP-1 fragment is also active in vivo and can protect the bone against metastasis-associated osteolysis. Our findings indicate that the release in the bone environment of this TSP-1 fragment, with its unique dual ability to inhibit RANK signaling while potentiating OPG activity, represents an important mechanism to control bone remodeling in osteolytic bone metastasis
Structural dynamics and immunogenicity of the recombinant and outer membrane vesicle-embedded Meningococcal antigen NadA
No full textStructural knowledge of antigens in their native state can drive the design of optimized vaccine antigens that mimic the native epitope exposure and conformation. Here, by hydrogen-deuterium exchange mass spectrometry, we assessed the structural features of Neisseria Adhesin A (NadA), a meningococcal trimeric outer membrane protein, included as soluble recombinant antigen in the 4CMenB vaccine. We propose a structural annotation of the recombinant NadA and compare its structural dynamics with NadA in situ, as embedded in meningococcal outer membrane vesicles (OMVs). The observed conformational differences suggest that OMV-embedded NadA could be more susceptible to trimer opening and display a larger antigenic surface than the soluble antigen. Accordingly, mice immunized with OMV-embedded NadA elicited antibodies with superior bactericidal activity compared to the soluble antigen. Collectively, these data support the hypothesis that protein vaccine antigens presented in native-like environments can elicit a more potent immune response than recombinant forms
Including built heritage in environmental improvement and nature recovery: exploring the challenges
No full textSignificant progress is being made to integrate the UK’s environmental improvement goals, including nature recovery, in the management and conservation of the historic environment. To date, most attention has been given to the over-arching vision and guiding principles, whilst finer scales of practice and delivery are less considered. This includes balancing management decisions and priorities for individual assets with landscape-scale environmental strategy, which may not always align or appear compatible. By reflecting on our experiences working in close partnership with national and local heritage organisations, we highlight three key challenges faced when trying to manage and enhance nature on and around built heritage assets: (1) Conflicts and trade-offs between conservation priorities, (2) uncertainty arising from a lack of knowledge and evidence, and (3) resistance to change. Underpinning these challenges in the UK is the complex diversity of built heritage assets, settings and responsible authorities, which precludes generalised approaches and solutions. In these contexts, we highlight a potential disconnect between ‘top-down’ (landscape-scale) and ‘bottom-up’ (asset-scale) decision-making. We finish with some broad suggestions for navigating these challenges in support of including built assets in the push for connected, culturally rich and biodiverse historic landscapes
AI-assisted rational decision-making
No full textAI has become a common assistant for making choices, from minor to major ones. It can inform our beliefs relevant to a decision by both helping us to find existing information and generating new information. But in what ways and to what extent is AI useful when making a rational decision? The present paper provides answers to this question for three different types of choices: easy choices, hard choices, and transformative choices. In easy choices, where the rational action is, in principle, straightforward, AI can make the decision-making process more efficient and accurate, increasing derived value (at least in the long-term). In hard choices, where options are on a par, AI can help us when we commit to an option by assisting us in the creation process of new will-based reasons. In transformative choices, where we cannot, even in principle, know by ourselves which option maximizes expected value, AI cannot fill the epistemic or metaphysical gap characteristic of such choices, and therefore cannot enable rational decision-making. Overall, the analysis shows that if the values of our options do not already allow us to determine the rational choice without AI, its assistance does not change that
Mechanistic insights into the non-equilibrium thermodynamics of nitrogen fixation via acoustic cavitation
No full textNon-equilibrium reaction environments offer a route to bypass the thermodynamic constraints that limit conventional nitrogen fixation, yet such conditions remain inaccessible in traditional thermal systems. Here, we show that rapid activation-quenching chemistry inside cavitation bubbles provides a viable non‑equilibrium pathway for nitrogen fixation. The violent collapse of ultrasound-driven bubbles generates an intense temperature pulse that enables direct nitrogen activation and subsequent redox chemistry within a transient gas phase microreactor. Nitrogen-containing products are produced with tuneable rates and selectivity controlled by feed gas composition, cavitation dynamics, and solution properties. Introduced cavitation nuclei lower the cavitation threshold and improve collapse reproducibility, while noble‑gas doping modulates collapse temperatures and shifts nitrate-nitrite distributions through enhancing the involvement of water‑derived species. Isotopic labelling and single‑bubble modelling indicate that nitrogen reaction proceeds predominantly through gas‑phase pathways during collapse, which can be described by a dynamic thermodynamic model within a temperature pulse. These findings establish cavitation‑driven non-equilibrium thermal cycling as a distinct mechanism for nitrogen fixation and underscore the broader potential of transient thermal microenvironments for chemical synthesis
If parallel lines could meet: what exactly can a poet say about the Fano plane?
No full textThis article describes our invention of a new poetic form based on projective geometry. In doing this we also explore the 'what ifs' in mathematics and poetry which spark the creative processes of poet and mathematician. In other words, throughout our collaboration we often asked one another, is this what it’s like for you? Do you think in this way, too? How does your experience of creativity compare to mine? And often, as well, what exactly do you mean when you say…? We spent a fair amount of time and energy, for example, trying to understand one another’s interpretation of ‘a line’. This collaboration resulted in three poems in the new projective plane form. We also consider what might be interesting avenues for future research, such as the incorporation of octonions in poetic form
On public commands, affections and Christian nationalism
Get PDFThis concluding paper addresses some important themes in Joan Lockwood O’Donovan’s English Public Theology, not considered in other papers in this special issue, but which take us to the heart of her contribution to public theology. The focus is upon how an evangelical community may be emancipated, especially in its desires and affections, from what O’Donovan sees as the distorting, even enslaving effects of liberalism’s preoccupation with juridical subjective rights. It proceeds by taking up O’Donovan’s challenge that theologians should be more alert to the meaning of what is ‘public’. In this regard, it considers a striking feature of her account of evangelical public authority, which is her use of the term ‘command’, when applied to the beliefs, affections, understanding and behaviour of those commanded. The connection between the church’s commands and those made by a wide variety of social institutions and influences is considered. The significance of the distinction between jurisdictional and evangelical commanding is also examined in order to develop an account of evangelical affective culture and its practical consequences. In particular, this practical focus includes consideration of Eric Gregory’s invitation to remark on what difference O’Donovan’s approach makes with respect to the discussion of Christian nationalism
Do high rheumatoid factor levels impact response to certolizumab pegol in patients with inadequately controlled rheumatoid arthritis? A post hoc analysis of the phase 3B REALISTIC trial
No full textObjectives: To assess the impact of rheumatoid factor (RF) levels and previous inadequate responses/intolerance to tumour necrosis factor inhibitors (TNFi-IR) on the efficacy of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) through a post hoc analysis of the REALISTIC trial.
Methods: In the phase 3b REALISTIC (NCT00717236) trial, patients with RA were randomised to CZP (400 mg at Weeks 0, 2, and 4, then 200 mg every two weeks) or placebo (PBO) for 12 weeks, followed by open-label CZP (minimum 16 weeks). Outcomes reported to Week 36 include Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Clinical Disease Activity Index (CDAI) scores, rates of DAS28-CRP <2.6 and CDAI remission (CDAI ≤2.8), and components of each. Data were stratified by baseline RF level (≤3rd quarter [≤Q3; <180 kU/L] versus 4th quarter [Q4; “high RF”; ≥180 kU/L]) and prior TNFi use (TNFi-naïve versus TNFi-IR).
Results: A total of 930 patients were included: 751 CZP-randomised and 179 placebo-randomised. At Week 12, CZP-randomised patients experienced marked and similar improvements in disease activity, irrespective of RF level and prior TNFi use, while PBO-randomised patients did not. Responses generally improved through Week 36 in CZP-treated patients (including PBO-randomised switchers), with similar efficacy across subgroups.
Conclusions: Patients with high and low RF levels experienced similar clinical responses to CZP treatment, irrespective of previous inadequate responses or intolerance to TNFis. These findings expand previous observations, supporting CZP as an effective treatment for patients with RA who have high RF levels and prior inadequate responses to TNFis