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Quality framework for perioperative care: rapid review and participatory exercise.
Get PDFBACKGROUND: This study addresses the need for a comprehensive, evidence-informed conceptually based quality framework for structures and processes of perioperative care. METHODS: We combined a rapid review of international academic literature and UK grey literature with a participatory consultation. The review included primary studies, guidelines and grey literature identified through searches of PsycINFO, MEDLINE, CINAHL and institutional websites. Findings were synthesised across studies using an inductive process, with key concepts identified, mapped, refined and organised into a preliminary framework. We consulted with UK-based multidisciplinary professionals and patient/carer representatives (public contributors), who together formed a 14-person Expert Collaborative Group using a participatory exercise hosted on the Thiscovery online platform. Descriptive analysis was used for quantitative responses and content analysis was used for free text analysis. RESULTS: We were able to develop a 10-domain framework that encapsulates structural and process-related features important to high-quality perioperative care, using the rapid review to generate a preliminary framework and consultation with professionals and public contributors to refine it. The final framework, termed 'Perioperative Framework'(P-Frame), comprises domains covering environment and facilities, leadership and governance, organisational culture, shared decision-making, multidisciplinary working, patient optimisation, clinical protocols, post-operative support, staff education and workforce planning. Importantly, the framework integrates the perspectives of patients and carers and seeks to ensure relevance across clinical, operational and experiential dimensions of care. CONCLUSIONS: P-Frame, based on the available evidence and the views of UK clinicians and patients, offers a potentially valuable tool for monitoring and improving perioperative care quality as well as supporting research efforts. It will benefit from further evaluation and testing of use in practice in different contexts and countries
Prognostic value of admission ROTEM in trauma: enhancing 30-day all-cause mortality prediction using machine learning
Get PDFBackground: Haemorrhage is a leading cause of trauma death, yet early coagulation markers are rarely used to predict long-term outcomes. This study assessed whether a single admission rotational thromboelastometry (ROTEM) test could independently predict 30-day all-cause mortality and improve existing trauma scores. Methods: We conducted a retrospective cohort study of 1,498 adult trauma patients admitted to a Level 1 trauma centre, with ROTEM (EXTEM, INTEM, FIBTEM) acquired on admission. Machine learning models were developed to predict 30-day mortality using ROTEM alone, using conventional trauma scores (RTS, NISS, GAP, MGAP, TRISS), and their combination. Model performance was assessed through cross validation using AUROC, AUPRC, and specificity at 90% sensitivity. SHAP was used for explainability. Results: ROTEM alone predicted 30-day mortality with an AUROC of 0.80, comparable to RTS and NISS (both 0.79), and superior to PT–INR (0.63) and base excess (0.58). When combined with ROTEM, specificity significantly improved across all trauma scores, with the greatest gains observed in RTS (0.23 to 0.62) and NISS (0.36 to 0.69) (all p < 0.001). Key predictive ROTEM variables included clotting time, clot firmness time, and fibrinolysis indices. Model performance was notably lower in female patients. Conclusions: A single admission ROTEM test predicted 30-day all-cause mortality with accuracy comparable to traditional trauma scores and outperformed conventional coagulation markers. Integrating ROTEM into established scores significantly enhanced predictive performance. Viscoelastic data appears to hold prognostic information capable of improving long-term trauma outcome assessments. Graphical abstract
Parasite evolution: Coral-infecting apicomplexans disrupt our understanding of the pathways to parasitism.
No full textThe discovery of chlorophyll biosynthesis genes in a cryptic apicomplexan partner of corals has disrupted, once again, our understanding of how this infamous group of parasites evolved
Constitutional Guardians
Get PDFMPs and ministers must do more to protect and bolster the checks and balances that uphold the UK constitution – or risk damaging public trust in the governance of the UK and core democratic principles, says a new paper by the Institute for Government and Cambridge University’s Bennett Institute.
The report maps out the UK’s complex ecosystem of institutions, individuals and organisations that oversee, monitor and uphold different parts of the constitution. It identifies three types of guardians that have an important role to play: * Core guardians: the key branches of government * Auxiliary guardians: who advise those within core institutions * Tertiary guardians: individual advisors, public bodies or committees that uphold the constitution
Multi-Scale Modelling of Host-Microbe Interactions: From Cell Membranes to Multi-Cellular Gut Models
Get PDFRecently, the role of the intestinal tract in health and disease has become of increasing interest. Translation of conventional 2D in vitro and animal models, which have been the cornerstone for intestinal research, is however limited; while human studies are expensive and preclude individual mechanisms from being investigated. More tailored in vitro models therefore offer an attractive avenue to study intestinal health and disease including microbiome-gut-immune interactions. Recently, there has been much progress in the development of in vitro intestinal models with studies incorporating mechanical and biophysical cues, immune cells and supporting longer-term co-culture of microbiota, amongst others. Nevertheless, platforms which combine all of these and more faithfully represent the intestinal tract cells are still lacking. Given the complexity of the intestinal tract, however, reductionist models tailored for a specific research question still provide much utility and opportunity.
To this end, this thesis provides a brief overview of the structure of the gut and associated immune tissue to introduce the complexities involved with the gut-immune axis and how these may be challenging to recapitulate in vitro. Further, considerations for in vitro intestinal model development are introduced, together with electrochemical techniques which have been employed to monitor these models.
Three different scales of in vitro models are then presented, namely from cell-free cell membrane-based models, to traditional cell monolayers and stratified multi-cell type approaches, to address three microbe-related applications. Different electrochemical devices are used to monitor each for applications in host-pathogen interaction, microbiome differences in irritable bowel syndrome and microbe metabolite effects.
To this end, cell membrane models are first presented for the detection of whole bacteria, namely the opportunistic pathogen Vibrio vulnificus (V. vulnificus) known for its severe disease including gastroenteritis, wound infection and sepsis. Focus is given to establishing intestinal cell-derived membrane models, studying cell line susceptibility by monitoring barrier changes due to cell monolayer-V. vulnificus interactions, with results showing increased disruption of enterocytes compared to goblet cells. Enterocyte-derived membrane models are then used to validate the cell membrane models for detecting live V. vulnificus, first in a simple buffer, and then, after validating the platform’s compatibility with human blood for the first time, in human blood; demonstrating the potential of the platform for pathogen detection and point-of-care applications.
A gut-immune model comprising of an epithelial cell monolayer and an immune cell (macrophage)-laden collagen hydrogel, is next presented together with a novel conformable device which contacts cells directly. Improved sensitivity of the device on this more complex model, as well as a simple monolayer model, is confirmed compared to the gold standard EVOMTM commonly used to monitor barrier resistance. The models and devices, supported by cytokine and metabolomics analysis, are used to study how faecal matter supernatants from patients with irritable bowel syndrome affect intestinal barrier integrity, compared to faecal matter supernatants from their household controls. Not only is this studied more broadly, but subsets of IBS patients identified to harbour differing intestinal microbiota are also considered in more detail, showing how in vitro models could be used in future to identify IBS subtypes and potentially to inform treatment approaches.
Finally, a gut-immune-vasculature model is presented and utilised to investigate the potential for the conformable device to, for the first time, monitor two cell barriers within the same model independently. The model-device combination, supported by cytokine analysis, is first used to study known isolated bacterial metabolites or dietary compounds, showing changes in epithelial and endothelial barrier resistance; before being used to test more complex bacterial metabolites generated through the growth of four intestinal bacteria individually as well as a community of 25 different bacteria.
Throughout this dissertation, the potential for employing tailored in vitro intestinal models coupled with electrochemical monitoring techniques for host-microbe interactions studies is demonstrated, highlighting the potential for these platforms in research, diagnostics and clinical applications
A Bifunctional Small Molecule Degrader of the Long Noncoding RNA MALAT1 Triplex.
Get PDFThe targeted degradation of RNA, particularly long noncoding RNAs (lncRNAs), holds immense potential for therapeutic interventions in diseases associated with aberrant RNA regulation. Here, we introduce a novel Proximity-Induced Nucleic Acid Degrader (PINAD-1), a first-in-class small molecule that selectively induces the degradation of MALAT1, a lncRNA implicated in the regulation of metastatic processes. PINAD-1 is designed by conjugating a binder specific for the triple helix structure of MALAT1 to an imidazole-based RNA-degrading warhead, enabling specific cleavage of the MALAT1 transcript in vitro and in cellulo, with minimal off-target effects on the structurally similar NEAT1 lncRNA. Through mechanistic studies, we show that effective RNA degradation is not solely dependent on proximity but requires a precise structural context, as demonstrated by the differential activity of PINAD-1 compared to the structurally analogous but functionally inert conjugate PINAD-2. Our findings underscore the importance of binder-induced destabilization and RNA geometry in facilitating RNA degradation. This work lays the foundation for the design of bifunctional small-molecule RNA degraders as powerful tools for the modulation of structured noncoding RNAs, offering potential applications in RNA-based therapeutics
Integrated strategies for controlling and eliminating Neglected Tropical Diseases in Sub-Saharan Africa: a review of approaches, challenges, and opportunities.
Get PDFNeglected Tropical Diseases (NTDs) are a significant global health issue, affecting over a billion people and hindering progress in economically disadvantaged areas, particularly in Sub-Saharan Africa. This study explores the complex relationship between socioeconomic factors and health inequalities in the region, highlighting the diverse impacts of NTDs and offering forward-looking recommendations. Despite global efforts to combat these diseases, significant gaps remain in achieving eradication in endemic areas. Key strategies for progress include expanding educational initiatives, engaging broader global health communities, and addressing the stigma faced by NTD victims. Therefore, recognizing the multifaceted impact of NTDs, it is essential to integrate intersectionality into health policies and action plans to tackle the challenges these diseases pose in Sub-Saharan Africa and globally
Fieldoscopy at the quantum limit.
Get PDFWe demonstrate a novel concept for measuring time-varying electric field transients of petahertz-scale photons down to a single-photon regime. We observe a clear breakdown of the classical regime consistent with our Monte Carlo model. We reach unprecedented yoctojoule-level (10⁻²⁴ J) sensitivity and a dynamic range exceeding 90 decibels. We utilize this capability to measure intrapulse light coherence - a regime inaccessible to conventional, time-averaged spectroscopy. This opens new avenues for quantum information, cryptography, and quantum light-matter interactions on sub-cycle time scales with attosecond precision
Modelling Gas Turbine Degradation
No full textIn this thesis work will be presented which demonstrates the potential benefits and current
obstacles to the creation of a geometry morphing procedure for the computational simulation
of hot corrosion and related phenomenon in gas turbines using Reynolds-averaged Navier
Stokes (RANS) computational fluid dynamics (CFD) simulations.
Non-uniform distribution of gaseous species as a result of film coolant injection was
observed on a simple single hole test case. RANS simulation showed that the gas composition
along the centreline, downstream of a cooling hole injection site, is predominately determined
by the coolant gas composition for multiple cooling hole diameters downstream. This
observation, of interest when studying the rates of surface chemical reactions, persisted when
the same techniques where applied to an nozzle guide vane (NGV) cascade.
A simplified model for oxidation and hot corrosion of elemental nickel is suggested. This
model was used to drive a geometry morphing technique, based on a level-set geometry
representation, of an NGV cascade. The susceptibility of geometry deformation to surface
temperature and gas species concentration, being influential variable for hot corrosion,
suggests geometry-based feedback in similar scenarios.
The potential of highly data-driven hot corrosion modelling was also explored. As well
as predicting relative surface loss after a prescribed operational time, estimates of surface
roughness were performed. In locations on the model geometry susceptible to hot corrosion,
the predicted values for root mean squared roughness, between 30 µm and 48 µm, were
comparable with a representative values of 36 µm, obtained by Bons et al. (2001) through the
measurement of in-service turbine components suffering from hot corrosion. Peak to valley
roughness predictions displayed a similar agreement with published representative values.
Work was also performed on predicting material gain or loss in response to the erosion or
deposition of impacting particles over a range of particle sizes, temperature and velocities.
While particulate effects where not incorporated into the hot corrosion modelling, this is
another example of where the geometry morphing procedure used in this work could be
of use. The resulting particle impact distributions were qualitatively in line which other
published works demonstrated sensitivity to both particle size and softening temperature. However, the particle modelling was not quantitatively accurate and over-predicted particle
deposition by orders of magnitude
Remaking Public Policy in the 21st Century
Get PDFLaunch conference report | 03.09.2018 - This report follows the launch conference of the Bennett Institute for Public Policy which took place on 16 April 2018
"On 16 April 2018 we launched the Bennett Institute for Public Policy with a conference
bringing together policy-makers, business people, non-governmental organisations and
academics to discuss some of the most pressing public policy issues facing governments and
populations around the world. The conference panels were organised around four topics: poverty
and inequality; global cities; policies to combat climate change; and the goals and measurement
of public policy in the 21st century. This report builds on those discussions and collects some of
the contributions to the conference.