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Inflammation and obesity correlate in pulmonary hypertension but associate with diverging outcomes
No full textRationale and Objectives: Inflammation is associated with all types of pulmonary hypertension (PH), both as a known cause and as a putative confounder. The most common marker of inflammation, C-reactive protein (CRP), has not been widely studied in PH. This study set out to clarify if CRP informs clinical endotyping and outcomes.
Methods: Time-series clustering of longitudinal CRP concentrations was employed. Clinical differences between clusters were validated in three independent U.K./international cohorts using clinical cutoff values (n = 10,301; U.K. cohort, ASPIRE and FDA cohort). Associations were analyzed with functional and mortality outcomes by linear and Cox regression models including all causes of PH (groups 1–5). To add mechanistic insight, multiomics were interrogated from associated previously published arrays.
Measurements and Main Results: Patients were segregated into two stable CRP clusters (median CRP, 2 vs. 6.5 mg/L), with the high cluster exhibiting significantly higher body mass index (BMI) (difference between medians [DBM], 5.4 kg/m2), higher right atrial pressure (DBM, 2 mm Hg), and reduced 6-minute-walk distance (DBM, 55 m). Inflammation was associated with worse survival and comorbidities, higher pulmonary vascular resistance, and smoking status. CRP and BMI were associated with differing inflammatory profiles in proteomic and transcriptomic analyses. Despite the relationship with CRP, higher BMI was associated with improved survival and lower pulmonary vascular resistance and did not negatively affect 6-minute-walk distance treatment-related functional responses.
Conclusions: We establish a relationship between CRP and BMI across all-cause PH, although CRP and BMI are associated with diverging clinical outcomes. Inflammation and obesity are relevant phenotypes for consideration in clinical trial design. Understanding their impacts on outcomes is important for clinical practice
The recycling and reuse of high-value abrasively machined feedstock materials: a review
No full textDue to recent developments across the aerospace, power generation and defense sectors, the demand for flat-surfaced components with extremely high surface quality is rapidly increasing. In this regard, although abrasive machining processes often produce fine, contaminated swarf that is frequently relegated to landfill, these processes remain critical for the engineering sector. Motivated by increasing sustainability and circularity pressures, this narrative review examines the current state of the art in recycling and repurposing the chips, tooling and cutting fluids that are typically generated or consumed within grinding processes. In doing so, a number of methodologies for extracting useful materials from swarf slurries are identified, including pyrometallurgical routes (applied successfully to Ni–Co alloys, for example), hydrometallurgical strategies (e.g., iron leaching from ferrous swarf) and, in the case of non-metallic materials such as CMCs and CFRPs, chemical processing methods. Various means of separating abrasive constituents and removing contaminants from grinding swarf are also highlighted, within which centrifugation and heat treatment are found to be particularly useful for non-ferrous materials such as titanium alloys or composites, whilst ferrous materials are largely magnetically separated. Prospective applications for spent abrasive tooling are also explored, including reuse as shot, waterjet machining feedstock, road surface additives, or mortar in the context of cement production. Likewise, heat- and radiation-based strategies for prolonging cutting-fluid life are highlighted, and their associated sustainability benefits and limitations discussed, despite ultimate disposal still being relegated to fuel usage or landfill. Ultimately, this review identifies the scarcity of grinding-specific recycling process data and highlights the need for robust, publicly accessible recycling strategies for novel material systems
Packaging Signal-mediated Assembly:How Viruses Outsmart Their Hosts
Get PDFThe importance of the genetic code in virology is universally acknowledged. However, it is less known that viral genomes can harbour a second code, embedded within the genetic code, that orchestrates the efficient assembly and genome packaging in many viral systems. Since its discovery in a bacterial virus, the molecular details and function of this mechanism have been characterised in a broad range of viral families, including major human pathogens. This Perspective article reports on the hallmarks of this "assembly/packaging code", the journey of its discovery, and the enticing opportunities it brings both in antiviral therapy and in virus nanotechnology
A chequered history but positive future for British public administration
Get PDFPublic services, public servants, and the study of Public Administration are operating in a context of global turbulence. Our review of the state of the discipline suggests that a core strength of British Public Administration has been the complementarity between scholarship and practice, responding to existential threats. We analyze changing relationships between the discipline and practice in British public administration over three eras: Applied, fragmented, and impactful. The applied era saw mutual exchange, but a lack of criticality. The fragmented era was one of a retreat to over-specialization and identity crises. The impactful era has tried to revivify synergies but has struggled for coherence and criticality. Looking to the future, the nascent sub-field of Positive Public Administration is identified as providing an opportunity to radically redefine the scientific quality and social relevance of the discipline due to the way it blends constructive engagement with independent criticality.
Evidence for Practice
The history of Public Administration in the UK shows both the benefits and challenges involved in promoting knowledge exchange between research and practice.
Practitioners played a significant role in the development of the discipline in the pre-War period, and a range of mechanisms were created to facilitate knowledge exchange between research and practice.
By contrast, the latter part of the twentieth century saw a disconnect between the two communities as government embraced private sector practices and many scholars focused on theory-building.
In the last two decades, the UK government has invested in new knowledge exchange structures that are intended to re-connect public administration scholarship with practice, but there are concerns that this may compromise academic independence.
The emerging sub-field of “Positive Public Administration” seeks to fundamentally re-orientate where and how scholars focus their attention in a way that can redefine the relationship between practitioners and researchers
Do depression and anxiety symptoms vary across the adult life course and between genders? A cross-sectional cultural comparison between Indonesia and the UK
No full textBackground
Depressive and anxiety symptoms are associated with adverse physical health outcomes, and a high global prevalence is burdening healthcare systems. Understanding mental health differences across age groups, genders and cultures can help in designing effective targeted interventions. This study examined (1) if depressive and anxiety symptom levels are similar in the United Kingdom (UK) and Indonesia, (2) the age-related patterns of depressive and anxiety symptoms and whether this differs between countries, and (3) if age-related patterns of depressive and anxiety symptoms differ by gender within countries.
Methods
Convenience and purposeful sampling (to reduce potential age bias and enhance diversity) were used to recruit 1355 participants aged 18 to 91 from Indonesia (n = 706) and the UK (n = 649). Patient Health Questionnaire-9 and Generalized Anxiety Disorder Questionnaire-7 were used to measure depression and anxiety, respectively.
Results
Depressive and anxiety symptoms were higher in the UK. The association between age and mental health symptoms showed variations in non-linear patterns between countries. In the UK, both symptoms generally declined initially, with a slight upturn in middle age before continued decline. In Indonesia, symptoms declined in middle age followed by a subsequent increase for depression, whilst anxiety remained stable in later life. Country interaction increased model fit for depressive and anxiety symptoms while gender interaction increased model fit only for anxiety symptoms in the UK.
Conclusion
Mental health symptoms vary across age groups, genders and cultures. Understanding these variations can provide insights to inform tailored mental health interventions for vulnerable groups
Principles for applying AI to address the challenges of scaling digital twins
Get PDFDespite the increasing affordability of data processing and storage and the enhancement of artificial intelligence (AI) and digital technologies in recent years, scalability and adoption continue to be a challenge when it comes to digital twins (DTs). Common challenges that are often cited include the effort of designing and building DTs, high customisation, the cost to operate and maintain DTs, interoperability between DT components and DTs, and the extensive analysis and effort required to turn DT outputs into useful insights. AI has seen significant advancements and growth lately, driven by the release of popular AI products such as ChatGPT, Google Gemini and DeepSeek's R1. Many of the recent developments have the potential to address the challenges of scaling and adopting DTs. This paper examines the intersection of AI and DTs and explores how AI can be used to address some of the challenges of scaling and adopting DTs. It concludes with a set of principles that aim to apply to most DT applications, regardless of use case or industry, and proposes AI methods and techniques that can potentially be used for each principle. These principles are (1) reduce effort, cost and/or time; (2) optimise resource and system efficiency; (3) improve interaction and outcome and (4) improve interoperability, reusability and maintainability
Aggressive CSR strategy and CSR awarding: managerial opportunism versus social activism
No full textPurpose
Despite the extensive body of research on absolute corporate social responsibility (CSR) performance, limited attention has been given to the distinct concepts of optimal and aggressive CSR engagement, as well as their associations with CSR awarding. This study aims to differentiate between optimal and aggressive CSR engagement and examine their relationship with CSR awarding while considering the moderating influence of board characteristics from the perspectives of stakeholder and agency theories.
Design/methodology/approach
This empirical analysis draws on an international dataset comprising 43,803 observations from nine sectors across 41 countries. We employ a least squares dummy variable regression approach that accounts for country, industry and year effects to conduct the analysis.
Findings
The results reveal that engagement in aggressive CSR activities beyond the optimal level leads to the generation of a social reputation through CSR awarding. However, the influence of board characteristics on this relationship is significant. Specifically, the presence of a dedicated CSR committee encourages CSR awarding in the context of aggressive CSR engagement. Conversely, board independence constrains the relationship between aggressive CSR engagement and CSR awarding. Notably, board gender diversity does not have a discernible impact on this connection.
Practical implications
Our evidence provides valuable insights to help firms seeking to enhance their social reputation through CSR activities better allocate their resources and avoid unnecessary financial commitments.
Originality/value
This study advances the current understanding by exploring the relationship between aggressive CSR engagement and the recognition of CSR awards. Furthermore, it scrutinises the factors that dictate when such aggressive CSR engagement translates into enhanced social reputation, as evidenced by the attainment of CSR awards
Multi-layer process control in selective laser melting: a reinforcement learning approach
Get PDFPowder bed fusion (PBF) is an original additive manufacturing technique for creating 3D parts layer-by-layer. While there are numerous benefits to this process, the complex undergoing physical phenomena are challenging to analytically model and interpret. Hence, integrated and control-oriented 3D models are lacking in the current literature. As a result, the state of the art in process control for the powder bed fusion (PBF) process is not as advanced as in other manufacturing processes. Reinforcement learning is a machine learning, data-driven mathematical and computational framework that can be used for process control while addressing this challenge (lack of control-oriented models) effectively. Its flexible formulation and its trial-and-error nature make reinforcement learning suitable for processes where the model is intricate or even unknown. The focus of this research work is selective laser melting, which is a laser-based PBF process. For the first time in the literature we demonstrate the benefits of a reinforcement learning process control framework for multiple layers (complete 3D parts) and we highlight the importance of stability during training. The presented case studies confirm the effectiveness of the proposed control framework, directly addressing heat accumulation issues while demonstrating effective overall process control, hence opening up opportunities for further research and impact in this area
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