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Innovation systems and evolutionary economics: honoring Richard Nelson through evolutionary plasticity and insights from China
Get PDFThis article first reviews the theoretical foundations of evolutionary economics, its main critiques, and intersections with other intellectual traditions, highlighting the diffusion of this perspective into the National Innovation System (NIS) framework and Richard Nelson’s seminal contributions. It then applies this evolutionary lens to analyze China’s NIS from two complementary perspectives—historical and open-system—offering a more integrative understanding of its development. Drawing on extensive industrial- and firm-level evidence, the study introduces the concept of Evolutionary Plasticity of Innovation Systems, inspired by biological evolution, to explain how similar institutional architectures can generate divergent innovation trajectories across sectors, regions, and countries. This framework contributes to evolutionary economics by extending beyond the prevailing static, discrete categorical epistemology and essentially correlational analysis in nature by providing a generative lens for understanding how innovation systems evolve, persist, and co-adapt under varying conditions, building on Nelson’s vision of the economy as an adaptive system. Together, the study advances the evolutionary approach by emphasizing institutional expression and adaptive reconfiguration over replacement, reaffirms the explanatory power of national-level analysis in an increasingly interconnected world, and calls for more analytically sophisticated and theoretically informed examination of innovation dynamics at this level
Transcriptome profiling of intra-snail stages of the liver fluke Fasciola hepatica reveals key mediators underlying parasite development and interaction with the host
Get PDFBackground: While mammalian host invasion by the liver fluke Fasciola hepatica has been extensively studied, reports on the interaction with its intermediate host at the molecular level remain scarce. These developmental stages are particularly interesting since at least two cycles of asexual amplification occur within lymnaeid snails, leading to the production of hundreds of infective metacercariae. We analyzed transcriptomic data from miracidia and intra-molluscan stages seeking clues of these interaction and developmental processes. Results: We identified 1744 novel transcripts and several isoforms of already annotated genes. Analysis of expression across the whole life cycle resulted in five distinct gene expression clusters (egg, miracidia, intra-snail stages, invading stages and juvenile-adults). Few genes showed strict stage-specific expression, but notably most of those corresponding to miracidial and intra-snail stages were novel unannotated genes. Genes upregulated in the miracidium include enzymes involved in neurotransmitter synthesis, energy metabolism and calcium mediated signaling, consistent with the physiology of a short-lived free-living stage. Several genes associated with development and morphogenesis were characterized in early (15 days post-infection) intra-snail stages. Purine salvage pathway genes were upregulated in this time-point, consistent with a high biosynthetic demand and the absence of a complete purine synthesis pathway in F. hepatica. Mucins, glycan biosynthesis genes and aquaporins upregulated within late (30 dpi) intra-snail stages are interesting, considering their putative role in the next host transition. Conclusions: Different members of well-known protein families involved in host-parasite interaction such as cathepsin proteases, legumains, protease inhibitors and lipid transporters were detected with stage specific expression in early and late intra-snail stages. These findings suggest duplication and tunning during evolution of the same set of molecular mediators for the interactions with the intermediate and definitive hosts
Safety and efficacy of short-term ventricular assist devices in paediatric heart transplant candidates: a systematic review and single arm meta-analysis
Get PDFBackground: Safety and efficacy of short-term ventricular assist devices (VAD) remains incompletely understood, particularly in younger children. This systematic review and meta-analysis aims to evaluate outcomes, including bridging success, complications, and mortality, associated with short-term VAD support in paediatric heart transplant candidates. Methods: A systematic search of PubMed, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from inception to 2 December 2024. Eligible studies reported patients ≤ 18 years supported by short-term VADs. This review was registered in PROSPERO (ID: CRD42023468125). Results: Twelve retrospective studies met the inclusion criteria, encompassing 532 paediatric patients (mean age 10.0 years, < 0.1–18.3, mean weight 39.5 ± 30.3 kg). Pooled proportions show that with a mean support duration of 15.2 days, 50.7% were successfully bridged to transplant (95% CI 36.4%, 65.0%; I2 = 91.1%) with a 24.8% waitlist mortality (95% CI 17.6%, 31.9%; I2 = 63.8%), 14.0% (95% CI 7.2%, 20.9%; I2 = 97.5%) weaned off support and 5.4% (95% CI 2.6%, 8.3%; I2 = 39.1%) remaining on support. Complication rates were high with haemorrhage (38.9%), renal impairment (35.2%), cerebrovascular events (29.5%), infection (17.8%), and thromboembolism (9.9%) being the most reported. Conclusions: Short-term VADs offer a feasible bridge to transplant in paediatric patients, with success rates comparable to registry data. However, high rates of serious complications and waitlist mortality persist, particularly in these younger children. These findings demonstrate the need for improved patient selection, standardized outcome reporting, and development of safer, size-appropriate devices for paediatric use
Integrative epigenomic landscape of Alzheimer’s Disease brains reveals oligodendrocyte molecular perturbations associated with tau
Get PDFAlzheimer's disease (AD) brains have variable neuropathologic and biochemical changes. Capturing epigenetic factors associated with this variability can reveal novel biological insights into AD pathophysiology. Here, we conduct an epigenome-wide association study of DNA methylation in 472 AD brains with neuropathologic and biochemical brain protein levels core to AD pathogenesis. Using a novel regional methylation (rCpGm) approach, we identify 5478 significant associations, 99.7% of which associate with tau biochemical measures, and 93 concordant associations in external datasets. Transcriptome-methylome integration reveals enrichment in oligodendrocyte genes, including known AD risk gene BIN1, myelination genes MYRF, MBP and MAG previously implicated in AD, and novel genes like LDB3. Further characterization of these perturbations in independent AD and primary tauopathy datasets highlights consistent tau-related associations. In summary, we uncover the integrative epigenomic landscape of AD, demonstrate tau-related oligodendrocyte gene perturbations as a common potential pathomechanism across tauopathies and share findings via our Multiomic Atlas
Exploring the Intensity and Continuity of Hospital Care for Patients With Long Covid: Evidence From an English Urban Healthcare System
Get PDFBackground: Long Covid (LC) is a multisystem condition leading to a wide range of symptoms and often requiring treatment by several different clinical specialties. Patients with LC have reported difficulties in accessing care and a lack of coordination of their care, particularly in a hospital setting. Objective: To determine the extent to which the intensity and continuity of hospital care changes for patients after they receive an LC diagnosis. Design: Retrospective observational cohort study using a linked primary and secondary care dataset. Setting and Participants: Routine healthcare data from North West London Integrated Care System of patients with a recorded diagnosis of LC who had attended a secondary care hospital Trust from 1 January 2019 to 30 September 2023. Main Variables Studied: The intensity of utilisation of secondary care was calculated, and the continuity of care with respect to hospitals and specialties was computed using the sequential continuity score (SeCon) before the Covid‐19 pandemic, before and after an LC diagnosis. Results: 5611 out of 6270 (90.1%) patients diagnosed with LC had a recorded secondary care interaction in the study period. Intensity of secondary care utilisation increased markedly in outpatient, inpatient and Emergency Department pathways after a diagnosis of LC but peaked in the week of diagnosis. Average hospital SeCon fell significantly after an LC diagnosis from 1.00 to 0.83, while specialty SeCon remained unchanged from after diagnosis (0.40) and before the pandemic (0.44). A notable shift in specialty activity was observed with a focus on respiratory medicine as a major hub in a densely connected patient‐sharing network with cardiology and other medical and surgical specialties. Discussion: A recorded LC diagnosis was associated with increases in the intensity of hospital activity and a reduction in hospital‐level care continuity, but no change in specialty continuity, which remains low. Conclusion: Collectively, this indicates a significant need to support LC patients as they navigate fragmented secondary care pathways. Patient and Public Contribution: This study was co‐designed with, conducted with and written in conjunction with people with long Covid
Protocol for a James Lind Alliance priority setting partnership to identify the most important research priorities addressing respiratory health disparities affecting the Black community in the UK
Get PDFIntroduction: Respiratory diseases affect millions of people in the UK, with a disproportionately high burden seen among many marginalised communities. They are the third leading cause of death in the UK and a major driver of morbidity, disability and healthcare service use. Many respiratory conditions cause debilitating symptoms and deterioration in patients’ health and quality of life over time, resulting in substantial increases in National Health Service (NHS) expenditure. Social inequalities, including occupational, housing and environmental disparities, have led to a disproportionate burden of respiratory disease among the Black community. For many Black people living in the UK, respiratory conditions have been under-recognised, misdiagnosed or inadequately treated, further contributing to disparities in health outcomes. Despite the need to address these urgent challenges, research in this area is fragmented and rarely informed by the views and opinions of those most affected. Research prioritisation provides a structured methodology to address this unmet need. The Equal Breath Priority Setting Partnership (PSP) aims to identify the 10 most urgent research priorities in respiratory health for people of Black heritage through meaningful collaboration with people with lived experience of respiratory disease, their caregivers and family members and the healthcare professionals caring for them. Methods and analysis: The top 10 research priorities for the Equal Breath PSP will be established using the James Lind Alliance (JLA) method. A steering group comprising approximately 12 people from key stakeholder groups will first be assembled to guide the PSP. Once the context and scope of the PSP has been agreed, the first survey will be developed and disseminated among stakeholder communities to identify evidence uncertainties. Data analysis of the survey responses will create summary questions and critical appraisal of available evidence will verify which of these are evidence gaps. A longlist of approximately 50 summary questions derived from the first survey will be shared with stakeholders in a second shortlisting survey. The highest ranking questions from this survey will be taken into a workshop where the top 10 research priorities will be established through a consensus process. Ethics and dissemination: This PSP employs the JLA methodology, which does not constitute research as defined by the Health Research Authority. Survey respondent data will be stored in accordance with UK General Data Protection Regulation by Asthma+Lung UK. The final 10 research priorities will be shared with funders, policymakers, professional bodies and relevant communities to inform future investment and promote equity in respiratory health
Thermostabilizing functional proteins with matrix-assisted room-temperature drying
Get PDFThis study evaluates the efficacy of the proposed matrix-assisted room-temperature (MART) drying as an alternative to freeze-drying for the thermostabilization of functional proteins in a solid state. To achieve this, protective agents are formulated with functional proteins, and the mixture is dried on a biocompatible cellulose fiber matrix. Drying is carried out at room temperature or elevated temperatures (~30 °C), either through dry air circulation (MART-DA drying) or under a vacuum (MART-V drying). The entire drying process involves no refrigeration or freezing steps. The results demonstrate the successful thermostabilization of lactate dehydrogenase (LDH), fibroblast growth factor-2 (FGF-2), and functional enzymes in reverse transcription loop-mediated isothermal amplification (RT-LAMP) reagents through the use of MART drying. The functional proteins were immobilized and effectively encapsulated in sugar glass films, preserving the proteins’ structure and functions. The sugar glass films were supported by a low-cost 3D cellulose fiber matrix. Overall, MART drying offers a simple, fast, low energy-consumption, and cost-effective strategy for drying functional proteins for long-term storage
