324139 research outputs found
Sort by
(In)significant genes: the work of genetic knowledge in the lives of people with NF1
Get PDFBy focusing on the experiences and perspectives of those with the genetic condition NF1, the purpose of this project is to investigate Britons’ thoughts on the nature and significance of genes. Genes as units of heredity are arguably central to Euro-American biomedical cosmology. However, “gene talk” is relatively rare, both in the general public and at NTUK—the London-based charity where I conducted my ethnographic research. By centring not only on participants’ health narratives but also on their choices, biosocial involvements, and philosophical reflections, my aim is to understand the fluctuating relevance of genetic information in life beyond the clinic.
This thesis’ primary contribution is to the anthropology of knowledge. Drawing on insights from the anthropology of genetics, I push forward by analysing situations where genetic knowledge provokes existential unease. An NF1 diagnosis not only generates medical uncertainty, it also compels my participants to think of themselves in genetic terms—that is, with what Carlos Novas and Nikolas Rose (2000) have described as a “molecular optic”. In my analysis, I discuss ‘temporal discipline’ and a ‘practice of emphasis’ as tactics employed by my participants to pursue a good life. The former term concerns avoiding the temptation to anticipate the future—and future generations—based on partial genetic knowledge in the present. The latter addresses how participants ‘believe in science’ yet simultaneously entertain kinder truths in which they resist seeing themselves in purely evolutionary terms.
This thesis finds that genes are avoided in everyday discourse not because of the public’s limited scientific comprehension—nor necessarily because of continuing associations with eugenics, although this plays a role—but because there exists a cultural preference for mystery. In the opinion of several of my key participants, one ought not to think too much about genes. Thus, this thesis ultimately confirms Marilyn Strathern’s (1992: 171) prediction that Euro-Americans—at least my participants with NF1—value unpredictability and unknowability when considering their genetic origin
Equality, diversity and inclusion strategies of NIHR biomedical research centres and clinical research facilities across England: a qualitative content analysis
Get PDFObjectives: The National Institute for Health and Care Research (NIHR) has 20 Biomedical Research Centres (BRCs) and 28 Clinical Research Facilities (CRFs) that work with NHS organisations and universities to translate cutting-edge research into new interventions. As mandated by NIHR, all BRCs/CRFs have an Equality, Diversity and Inclusion (EDI) strategy which details how they will implement EDI through their practices, research and organisational systems. This UK-based study aimed to conduct a pilot qualitative analysis of EDI strategies to compare all 20 NIHR BRCs/CRFs, identify common priorities and improve inclusion across research infrastructures. The analysis was presented at the first in-person seminar for NIHR EDI professionals (Birmingham, October 2024). Design: Qualitative content analysis of publicly available EDI strategy documents. Setting: 48 research infrastructures (20 BRCs and 28 CRFs). Methods: EDI strategies were collated into NVivo and Microsoft Excel where inductive coding and content analysis was executed for objectives, action plans and success measures. Both quantitative and qualitative content analyses were conducted to analyse the prevalence of categories and similarities or differences between them. Logic models were developed to map the process of implementing EDI for each main category generated. Results: The most common main category across objectives was ‘Cultural change in workplaces’ for BRCs and ‘Leadership, governance and policy’ for CRFs. For action plans, codes for ‘Collaborations and Networks’ and ‘Research development and delivery’ were most prevalent for BRCs—for CRFs, it was ‘Workforce culture change’ and ‘Research development and delivery’. Success measures for both BRCs and CRFs most often related to ‘Summary reports, feedback, audits and monitoring’. Differences between BRCs and CRFs reflected their organisational roles and strategic maturity, with BRCs tending to have more comprehensive, measurable strategies. Conclusions: This study provides the first systematic analysis of EDI strategies across all NIHR BRCs and CRFs, offering a comprehensive mapping of how EDI priorities are articulated and operationalised across objectives, action plans and success measures. While both infrastructures align with NIHR’s inclusion goals, BRCs generally showed more strategic maturity than CRFs. As the analysis was based solely on publicly available strategy documents, it could not determine the extent to which any strategy had been implemented in practice. Future research is needed to examine implementation and impact. The contribution of this work lies in demonstrating systematically and for the first time the ways in which EDI commitments are framed across NIHR infrastructures and their varying levels of depth and maturity. Our findings support the development of more measurable EDI frameworks and highlight opportunities to strengthen inclusion across NIHR-funded research infrastructures
Invasion preferences suggest a possible role for Plasmodium falciparum parasites in the expansion of Duffy negativity in West and Central Africa
Get PDFDuffy antigen receptor for chemokines (DARC) is the primary red blood cell (RBC) receptor for invasion of human RBCs by Plasmodium vivax and Plasmodium knowlesi parasites. By contrast, Plasmodium falciparum parasites use multiple RBC receptors for invasion. Whether DARC is one of these receptors has never been systematically explored. We used flow cytometry and microscopy-based approaches to investigate whether P. falciparum parasites preferentially invade specific Duffy RBC phenotypes and explored 2 potential explanations for invasion preference—differences in RBC biophysical properties and surface protein composition. P. falciparum parasites showed a consistent preference for Duffy-positive RBCs, and some biophysical properties and surface protein expression varied between Duffy-positive and Duffy-negative RBCs. We then used our in vitro invasion data to parametrize an evolutionary-epidemiological model of the relationship between P. falciparum and the FYBES allele. Our model accounts for immunity against P. falciparum virulence, gained through exposure, and thus mutations that impede infection are not always advantageous. The inhibition of P. falciparum invasion that we observed in vitro leads to FYBES frequencies increasing at low levels of P. falciparum transmission but decreasing at high levels of transmission. The impact of P. falciparum on the prevalence of Duffy negativity may therefore be most apparent in lower transmission settings. Our findings show a link between Duffy negativity and P. falciparum and suggest that DARC may directly or indirectly be involved in P. falciparum invasion of human RBCs which could, together with P. vivax, explain the distribution of Duffy negativity in sub-Saharan Africa
Incidence of all-cause and vaccine-preventable, radiologically confirmed community-acquired pneumonia in hospitalised adults in Germany: a multicentre surveillance study (2021–2023)
Get PDFObjectives: Accurate estimates of the burden of vaccine-preventable community-acquired pneumonia (CAP) hospitalisations both overall and due to the most frequent and vaccine-preventable pathogens are needed to inform the use of respiratory vaccines in adults. Design and setting: This was a prospective, population-based CAP surveillance study at three hospitals in Germany. All patients admitted with clinically suspected CAP were tested for Streptococcus pneumoniae using urine antigen tests and for respiratory syncytial virus (RSV), influenza virus and SARS-CoV-2 using multiplex PCR from nasopharyngeal swabs. Incidence rate calculations for all-cause CAP were based on eligible patients, regardless of enrolment status. Participants: Individuals admitted to study hospitals within the surveillance period with suspected or confirmed diagnosis of pneumonia who provided informed consent. Outcome measures: Radiologically confirmed (RAD) CAP. Results: Active surveillance between 1 January 2021 and 30 June 2023 identified at the three study sites 4319 adults with RAD-CAP that met eligibility criteria, of which 1479 (34.2%) were enrolled and included in the analysis for pathogen distribution. The main reason for non-enrolment was the inability to provide informed consent. Incidence estimates were based on 1254 study-eligible individuals admitted at the largest study site. SARS-CoV-2, S. pneumoniae, RSV or influenza were identified in 36.5%, 9.1%, 3.7% and 1.8% of patients with RAD-CAP, respectively. Serotypes included in the 20-valent pneumococcal conjugate vaccine were detected in 6.9% of RAD-CAP and 76.0% of pneumococcal CAP. The overall adjusted annual incidence of all-cause RAD-CAP over the study period was 490/100 000 (95% CI 461 to 521). The incidence of pneumococcal and RSV-related RAD-CAP increased 8.6-fold and 10.0-fold over the study period, resulting in an incidence of 60/100 000 (95% CI 45 to 75) and 30/100 000 (95% CI 19 to 41) in 2022/2023, respectively, while SARS-CoV-2 related RAD-CAP declined by 70% to 97/100 000 (95% CI 78 to 116). Conclusions: Active pneumonia surveillance reported a high burden of RAD-CAP hospitalisations in Germany, especially among older adults. The resurgence of CAP due to RSV, S. pneumoniae or influenza, alongside maintained activity of SARS-CoV-2, was associated with an overall increase of RAD-CAP among adults
On first order amenability: On first order amenability
Get PDFWe introduce the notion of first order amenability, as a property of a first order theory T: every complete type over ∅, in possibly infinitely many variables, extends to an automorphism-invariant global Keisler measure in the same variables. Amenability of T follows from amenability of the (topological) group Aut(M) for all sufficiently large ℵ0-homogeneous countable models M of T (assuming T to be countable), but is radically less restrictive. First, we study basic properties of amenable theories, giving many equivalent conditions. Then, applying a version of the stabilizer theorem from Selecta Math. (N.S.) 28, 16 (2022), we prove that if T is amenable, then T is G-compact, namely Lascar strong types and Kim-Pillay strong types over ∅ coincide. This extends and essentially generalizes a similar result proved via different methods for ω-categorical theories in Adv. Math. 345, 1253–1299 (2019). In the special case when amenability is witnessed by ∅-definable global Keisler measures (which is for example the case for amenable ω-categorical theories), we also give a different proof, based on stability in continuous logic. Parallel (but easier) results hold for the notion of extreme amenability
Cardiac health assessment across scenarios and devices using a multimodal foundation model pretrained on data from 1.7 million individuals
Get PDFCardiovascular diseases remain a major contributor to the global burden of healthcare, highlighting the importance of accurate and scalable methods for cardiac monitoring. Cardiac biosignals, most notably electrocardiograms (ECG) and photoplethysmograms, are essential for diagnosing, preventing and managing cardiovascular conditions across clinical and home settings. However, their acquisition varies substantially across scenarios and devices, whereas existing analytical models often rely on homogeneous datasets and static bespoke models, limiting their robustness and generalizability in diverse real-world contexts. Here we present a cardiac sensing foundation model (CSFM) that leverages transformer architectures and a generative masked pretraining strategy to learn unified representations from heterogeneous health records. CSFM is pretrained on a multimodal integration of data from various large-scale datasets, comprising cardiac signals from approximately 1.7 million individuals and their corresponding clinical or machine-generated text reports. The embeddings derived from CSFM act as effective, transferable features across diverse cardiac sensing scenarios, supporting a seamless adaptation to the varied input configurations and sensor modalities. Extensive evaluations across diagnostic tasks, demographic recognition, vital sign measurement, clinical outcome prediction and ECG question answering demonstrate that CSFM consistently outperforms traditional one-modal-one-task approaches. Notably, CSFM maintains favourable performance across both 12-lead and single-lead ECGs, as well as in scenarios involving ECG only, photoplethysmogram only or a combination of both. This highlights its potential as a versatile and scalable foundation for comprehensive cardiac monitoring
Multi-scale observations and 3D modelling of inkjet printing modified carbon fibre composite
Get PDFCarbon fibre reinforced polymer (CFRP) composite is in high demand in industries such as wind turbine, automobile, and aerospace due to its exceptional strength and stiffness with low weight. However, its internal defects can lead to catastrophic failure by delamination. Therefore, enhancing interfacial resistance is critically important. Inkjet printing of polymethyl methacrylate (PMMA) or polyethylene glycol (PEG) between prepregs has shown promise in increasing fracture toughness with minor weight penalty and negligible compromise of other mechanical properties. To obtain the insight into the toughening mechanism, a series of characterizations as well as 3D finite element models were applied in this thesis.This project began with a description of manufacturing process for inkjet printing modified CFRP. The mechanical performance was then evaluated using Double Cantilever Beam (DCB) test, which verified the reported toughening effect. A series of in situ observations were conducted on the laminates to study the Mode I fracture propagation behaviour: Dual X-ray imaging and diffraction analyses were employed with the aim of monitoring the lattice strain in carbon fibres via X-ray diffraction (XRD), while tracking crack tip position through radiographs processed with Digital Image Correlation (DIC). In-situ synchrotron X ray computed tomography was used to image the 3D evolution of damage propagation. Post processing using Digital Volume Correlation (DVC), the displacement fields were resolved, and larger critical crack openings were observed for the printed specimens. The displacement field was imported into a finite element model as boundary conditions to evaluate J-integral and quantify the different modes of stress intensity factor (K), confirming the enhancement in fracture energy post printing. The fracture surface of laminates was observed by multiple characterization methods, and larger surface unevenness was observed to correspond with higher fracture toughness. Confocal microscopy revealed that PEG diffused into the epoxy matrix during curing, whereas PMMA remained separate. Fractography observed micropores and fractured particles in the PMMA-printed sample. It was deduced that the PMMA deposits facilitated crack deflection and cavitation formation, while PEG improved the matrix adhesion. Both printed laminates exhibited increased active functional groups on the fracture surfaces, suggesting enhanced bonding activity. A finite- element microstructure meshfree (FEMME) model was then applied to simulate DCB experiments with varying interfacial strength. The model replicated the wider crack opening in printed samples, consistent with XCT observations
Mobility and strength training with and without protein supplements for pre-frail/frail older people with low protein intake
Get PDFAn analysis of Britons' preferences regarding the sociodemographic characteristics of politicians and what politicians reveal about their own sociodemographic profiles
No full textThis thesis explores political representation in contemporary Britain. Its subject is very timely, given the record low levels of electoral turnout and record high levels of political disillusionment currently plaguing the country. It focuses on the sociodemographic characteristics of politicians, which prior research has shown are closely tied to political outcomes and hold great importance for Britons. It seeks to answer three related questions: what kind of politicians do Britons want to represent them; what kind of politicians actually represent them; and what do British politicians reveal about themselves. It utilises a variety of methods, from both the quantitative and qualitative traditions, in order to do so, employing a candidate choice experiment, surveys, data collection, and content analysis.The combination of a constituency-focused candidate choice experiment which explores respondents’ views towards their own representative and surveys which explore respondents’ views towards politicians as a group is an innovative approach and it unearths important, original findings. It reveals that Britons’ views towards the sociodemographic characteristics of politicians vary by proximity of government, and that while they hold strong, statistically significant preferences with regard to the sociodemographic characteristics of their own MP, they desire a Parliament which reflects the sociodemographic profile of the wider country, not their own views. It further reveals that middle-class Britons, whilst professing a desire for more working-class representatives and fewer middle-class representatives when asked about Parliament as a whole, display a marked class affinity bias when asked about their own MP. It is suggested that this discrepancy of views among the middle-class may help explain the continued under-representation of the working class in Parliament. The candidate choice experiment and surveys not only (re)test variables which have been explored by other scholars using flawed designs, but also identify and test previously untested variables and find that they are extremely important to Britons – indeed, much more important than many of the variables which have long formed mainstays of experimental research in Britain.The collection of data on MPs’ sociodemographic characteristics complements the candidate choice experiment and surveys and allows a comparison to be made between the preferences of Britons towards their representatives and the reality. The results are troubling. British MPs are largely not the sort of people that Britons want to represent them. The content analysis of MPs’ websites finds that British MPs, perhaps cognisant of this mismatch between the preferences of Britons towards their representatives and the reality, engage in what is termed the strategic release of information. That is to say, British MPs emphasise aspects of their lives that are popular with Britons and downplay elements that are not. Further, it is noted how MPs, when they do reference possessing unpopular characteristics, frame the information in such a way as to present it in the best possible light
LICHEN enables light-chain immunoglobulin sequence generation conditioned on the heavy chain and experimental needs
Get PDFIn developing therapeutic antibodies, the heavy chain is often prioritised due to its higher variability and its central role in antigen binding. An appropriate pairing of the light sequence is however important for antibody function. Here we present LICHEN, a heavy chain conditioned light sequence generation tool that enables collaborative light sequence design by leveraging computational capabilities alongside experimental expertise. LICHEN generates light sequences which are valid (antibody-like), diverse in sequence and structure, and conditioned on a specific heavy chain. LICHEN can also condition on germline and CDRs and automatically filter generated sequences for required properties. We carry out experimental validation of the method conditioning only on the heavy sequence and on the heavy sequence and binding information. Our in vitro results show that sequences created by LICHEN have effective expression yields and can retain antigen-binding. LICHEN can thus be used across multiple antibody engineering scenarios for efficient light-chain pairing