| 1. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Bassford, Chris, et al.
(author)
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Developing an intervention around referral and admissions to intensive care : a mixed-methods study
- 2019
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Reports (other academic/artistic)abstract
- Background: Intensive care treatment can be life-saving, but it is invasive and distressing for patients receiving it and it is not always successful. Deciding whether or not a patient will benefit from intensive care is a difficult clinical and ethical challenge.Objectives: To explore the decision-making process for referral and admission to the intensive care unit and to develop and test an intervention to improve it.Methods: A mixed-methods study comprising (1) two systematic reviews investigating the factors associated with decisions to admit patients to the intensive care unit and the experiences of clinicians, patients and families; (2) observation of decisions and interviews with intensive care unit doctors, referring doctors, and patients and families in six NHS trusts in the Midlands, UK; (3) a choice experiment survey distributed to UKintensive care unit consultants and critical care outreach nurses, eliciting their preferences for factors used in decision-making for intensive care unit admission; (4) development of a decision-support intervention informed by the previous work streams, including an ethical framework for decision-making and supporting referral and decision-support forms and patient and family information leaflets. Implementation feasibility was tested in three NHS trusts; (5) development and testing of a tool to evaluate the ethical quality of decision-making related to intensive care unit admission, based on the assessment of patient records The tool was tested for inter-rater and intersite reliability in 120 patient records.Results: Influences on decision-making identified in the systematic review and ethnographic study included age, presence of chronic illness, functional status, presence of a do not attempt cardiopulmonary resuscitation order, referring specialty, referrer seniority and intensive care unit bed availability. Intensive care unit doctors used a gestalt assessment of the patient when making decisions. The choice experiment showed that age was the most important factor in consultants’ and critical care outreach nurses’ preferences for admission. The ethnographic study illuminated the complexity of the decision-making process, and the importanceof interprofessional relationships and good communication between teams and with patients and families. Doctors found it difficult to articulate and balance the benefits and burdens of intensive care unit treatment for a patient. There was low uptake of the decision-support intervention, although doctors who used it noted that it improved articulation of reasons for decisions and communication with patients.Limitations: Limitations existed in each of the component studies; for example, we had difficulty recruiting patients and families in our qualitative work. However, the project benefited from a mixed-method approachthat mitigated the potential limitations of the component studies. Conclusions: Decision-making surrounding referral and admission to the intensive care unit is complex. This study has provided evidence and resources to help clinicians and organisations aiming to improve thedecision-making for and, ultimately, the care of critically ill patients.Future work: Further research is needed into decision-making practices, particularly in how best to engage with patients and families during the decision process. The development and evaluation of trainingfor clinicians involved in these decisions should be a priority for future work.
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| 4. |
- Bassford, Christopher R., et al.
(author)
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U.K. Intensivists' Preferences for Patient Admission to ICU : Evidence From a Choice Experiment
- 2019
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In: Critical Care Medicine. - : Lippincott Williams & Wilkins. - 0090-3493 .- 1530-0293. ; 47:11, s. 1522-1530
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Deciding whether to admit a patient to the ICU requires considering several clinical and nonclinical factors. Studies have investigated factors associated with the decision but have not explored the relative importance of different factors, nor the interaction between factors on decision-making. We examined how ICU consultants prioritize specific factors when deciding whether to admit a patient to ICU.DESIGN: Informed by a literature review and data from observation and interviews with ICU clinicians, we designed a choice experiment. Senior intensive care doctors (consultants) were presented with pairs of patient profiles and asked to prioritize one of the patients in each task for admission to ICU. A multinomial logit and a latent class logit model was used for the data analyses.SETTING: Online survey across U.K. intensive care.SUBJECTS: Intensive care consultants working in NHS hospitals.MEASUREMENTS AND MAIN RESULTS: Of the factors investigated, patient's age had the largest impact at admission followed by the views of their family, and severity of their main comorbidity. Physiologic measures indicating severity of illness had less impact than the gestalt assessment by the ICU registrar. We identified four distinct decision-making patterns, defined by the relative importance given to different factors.CONCLUSIONS: ICU consultants vary in the importance they give to different factors in deciding who to prioritize for ICU admission. Transparency regarding which factors have been considered in the decision-making process could reduce variability and potential inequity for patients.
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| 5. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 6. |
- Heap, Michael J., et al.
(author)
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The tensile strength of volcanic rocks : Experiments and models
- 2021
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In: Journal of Volcanology and Geothermal Research. - : Elsevier. - 0377-0273 .- 1872-6097. ; 418
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Journal article (peer-reviewed)abstract
- The tensile strength of volcanic rock exerts control over several key volcanic processes, including fragmentation and magma chamber rupture. Despite its importance, there is a paucity of laboratory data for the tensile strength of volcanic rocks, leading to an incomplete understanding of the influence of microstructural parameters, such as pore size and shape (factors that vary widely for volcanic rocks), on their tensile strength. To circumvent problems associated with the variability of natural samples, we provide here a systematic study in which we use elastic damage mechanics code "Rock Failure Process Analysis" to perform numerical experiments to better understand the influence of porosity, pore diameter, pore aspect ratio, and pore orientation on the tensile strength of volcanic rocks. We find that porosity and pore diameter exert a first-order control on the tensile strength of volcanic rocks, and that pore aspect ratio and orientation also influence tensile strength. Tensile strength is reduced by up to a factor of two as porosity is increased from 0.05 to 0.35 or as pore diameter is increased from 1 to 2 mm. Small, but systematic, reductions in tensile strength are observed as the angle between the loading direction and the major axis of an elliptical pore is increased from 0 to 90 degrees. The influence of pore aspect ratio (the ratio of the minor to major axis of an ellipse) depends on the pore angle: when the pore angle is 0 degrees, a decrease in pore aspect ratio, from 1 (a circle) to 0.2, increases the tensile strength, whereas the same decrease in pore aspect ratio does not substantially change the tensile strength when the pore angle is 90 degrees. These latter numerical experiments show that the tensile strength of volcanic rocks can be anisotropic. Our numerical data are in broad agreement with new and compiled experimental data for the tensile strength of volcanic rocks. One of the goals of this contribution is to provide better constrained constitutive models for the tensile strength of volcanic rocks for use in volcano modelling. To this end, we present a series of theoretical and semi-empirical constitutive models that can be used to determine the tensile strength of volcanic rocks, and highlight how tensile strength estimations can influence predictions of magma overpressures and assessments of the volume and radius of a magma chamber. (c) 2021 Elsevier B.V. All rights reserved.
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| 7. |
- Heidenreich, Kaja, 1973-, et al.
(author)
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The complex decision-making process of referring patients to intensive care – meanings of senior doctor’s experiences
- 2019
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In: Presented at the EACME Annual Conference 2019: Rethinking Ethics in 21st Century Europe, Oxford, UK, September 12-14, 2019.
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Conference paper (peer-reviewed)abstract
- Background: The decision whether to initiate intensive care for the critically ill patient involves ethical questions regarding what is good and right for the patient. It is not clear how referring doctors negotiate these ethical questions in practice.Objectives: To illuminate the meaning of senior referring doctors´ lived experiences of decision-making about whether to initiate intensive care treatment. Methods: Analysis, using a phenomenological hermeneutical method, of interviews with 27 senior doctors from departments regularly referring patients to intensive care in six British hospitals. The interviews were conducted as part of the larger research project ‘Understanding and improving the decision-making process surrounding admission to the intensive care unit’, funded by the National Institute of Health Research, UK.Results: Senior doctors struggle with the complex decision-making process when they are in doubt whether escalation to intensive care for the critically ill patient would be beneficial. A trusted process requires senior, mutual responsiveness between the referring doctor and the intensivist. Within the professional vulnerability created by the burdensome uncertainty of not being sure what is good and right for the patient, moral responsibility is secured through clinical proximity, and confidence is gained through responsive interaction.Conclusions: Decision-making requires a reliable process based on mutual responsiveness and proximity. To promote this, an organizational structure and culture is needed where mutual recognition and support between decision-makers are valued.
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| 8. |
- Heidenreich, Kaja, 1973-, et al.
(author)
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UK consultants’ experiences of the decision-making process around referral to intensive care : an interview study
- 2021
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:3
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Journal article (peer-reviewed)abstract
- Objective: The decision whether to initiate intensivecare for the critically ill patient involves ethical questions regarding what is good and right for the patient. It isnot clear how referring doctors negotiate these issuesin practice. The aim of this study was to describe and understand consultants’ experiences of the decision- making process around referral to intensive care.Design: Qualitative interviews were analysed according to a phenomenological hermeneutical method.Setting and participants: Consultant doctors (n=27) from departments regularly referring patients to intensive care in six UK hospitals.Results: In the precarious and uncertain situation of critical illness, trust in the decision-making process is needed and can be enhanced through the way in which the process unfolds. When there are no obvious right or wrong answers as to what ought to be done, how the decision is made and how the process unfolds is morally important. Through acknowledging the burdensome doubts in the process, contributing to an emerging, joint understanding of the patient’s situation, and respondingto mutual moral duties of the doctors involved, trust in the decision-making process can be enhanced and a shared moral responsibility between the stake holding doctors can be assumed.Conclusion: The findings highlight the importance of trust in the decision-making process and how the relationships between the stakeholding doctors are crucial to support their moral responsibility for the patient. Poor interpersonal relationships can damage trust and negatively impact decisions made on behalf of a critically ill patient. Forthis reason, active attempts must be made to foster good relationships between doctors. This is not only important to create a positive working environment, but a mechanism to improve patient outcomes.
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| 9. |
- Ringqvist, Emma, et al.
(author)
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Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells
- 2008
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In: Molecular and biochemical parasitology (Print). - : Elsevier BV. - 0166-6851 .- 1872-9428. ; 159:2, s. 85-91
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Journal article (peer-reviewed)abstract
- Giardia lamblia, an important cause of diarrheal disease, resides in the small intestinal lumen in close apposition to epithelial cells. Since the disease mechanisms underlying giardiasis are poorly understood, elucidating the specific interactions of the parasite with the host epithelium is likely to provide clues to understanding the pathogenesis. Here we tested the hypothesis that contact of Giardia lamblia with intestinal epithelial cells might lead to release of specific proteins. Using established co-culture models, intestinal ligated loops and a proteomics approach, we identified three G. lamblia proteins (arginine deiminase, ornithine carbamoyl transferase and enolase), previously recognized as immunodominant antigens during acute giardiasis. Release was stimulated by cell-cell interactions, since only small amounts of arginine deiminase and enolase were detected in the medium after culturing of G. lamblia alone. The secreted G. lamblia proteins were localized to the cytoplasm and the inside of the plasma membrane of trophozoites. Furthermore, in vitro studies with recombinant arginine deiminase showed that the secreted Giardia proteins can disable host innate immune factors such as nitric oxide production. These results indicate that contact of Giardia with epithelial cells triggers metabolic enzyme release, which might facilitate effective colonization of the human small intestine.
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| 10. |
- Svantesson, Mia, 1960-, et al.
(author)
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Ethical conflicts during the process of deciding about ICU admission : an empirically driven ethical analysis
- 2021
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In: Journal of Medical Ethics. - : BMJ Publishing Group Ltd. - 0306-6800 .- 1473-4257. ; 47:12
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Journal article (peer-reviewed)abstract
- BACKGROUND: Besides balancing burdens and benefits of intensive care, ethical conflicts in the process of decision-making should also be recognised. This calls for an ethical analysis relevant to clinicians. The aim was to analyse ethically difficult situations in the process of deciding whether a patient is admitted to intensive care unit (ICU).METHODS: Analysis using the 'Dilemma method' and 'wide reflective equilibrium', on ethnographic data of 45 patient cases and 96 stakeholder interviews in six UK hospitals.ETHICAL ANALYSIS: Four moral questions and associated value conflicts were identified. (1) Who should have the right to decide whether a patient needs to be reviewed? Conflicting perspectives on safety/security. (2) Does the benefit to the patient of getting the decision right justify the cost to the patient of a delay in making the decision? Preventing longer-term suffering and understanding patient's values conflicted with preventing short-term suffering and provision of security. (3) To what extent should the intensivist gain others' input? Professional independence versus a holistic approach to decision-making. (4) Should the intensivist have an ongoing duty of care to patients not admitted to ICU? Short-term versus longer-term duty to protect patient safety. Safety and security (experienced in a holistic sense of physical and emotional security for patients) were key values at stake in the ethical conflicts identified. The life-threatening nature of the situation meant that the principle of autonomy was overshadowed by the duty to protect patients from harm. The need to fairly balance obligations to the referred patient and to other patients was also recognised.CONCLUSION: Proactive decision-making including advance care planning and escalation of treatment decisions may support the inclusion of patient autonomy. However, our analysis invites binary choices, which may not sufficiently reflect reality. This calls for a complementary relational ethics analysis.
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| 11. |
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| 12. |
- Thornton, Nicole, et al.
(author)
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Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- The clinically important MAM blood group antigen is present on haematopoietic cells of all humans except rare MAM-negative individuals. Its molecular basis is unknown. By whole-exome sequencing we identify EMP3, encoding epithelial membrane protein 3 (EMP3), as a candidate gene, then demonstrate inactivating mutations in ten known MAM-negative individuals. We show that EMP3, a purported tumour suppressor in various solid tumours, is expressed in erythroid cells. Disruption of EMP3 by CRISPR/Cas9 gene editing in an immortalised human erythroid cell line (BEL-A2) abolishes MAM expression. We find EMP3 to associate with, and stabilise, CD44 in the plasma membrane. Furthermore, cultured erythroid progenitor cells from MAM-negative individuals show markedly increased proliferation and higher reticulocyte yields, suggesting an important regulatory role for EMP3 in erythropoiesis and control of cell production. Our data establish MAM as a new blood group system and demonstrate an interaction of EMP3 with the cell surface signalling molecule CD44.
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