The Impact of Complications and Errors on Surgeons

Background Adverse events within the context of healthcare can lead to significant physician psychological distress. Contemporary research links the experience of adverse events to the prevalence of burnout, depression, and impaired quality of life. Most of the prevailing literature focuses on the impact of adverse events on all healthcare professionals. This PhD thesis recognises that some aspects of medical practice are exclusive to surgery, and the role of the surgeon. Therefore, this research investigates the unique impact of adverse events on surgeons. Furthermore, sub-types of adverse event (complication vs error) experienced within healthcare are often conflated within the literature, with very little differentiation made between a recognised complication of a surgery, and an error made by the surgeon. This research comprises a quantitative study exploring the impact of complications and errors on surgeons: Exploring the effect of type of adverse event on psychological outcomes and providing insight into the experience of surgeons following an adverse event, using surgeon responses to standardised measures to establish predictive statistical models. Methods UK Surgeons were invited to participate in an online survey. An opportunistic sampling strategy was used, involving organisations such as the Royal College of Surgeons of England and appeals at surgeons’ conferences and events. A single-factor (event: error or complication) between-groups design was used. Demographic and professional information, such as current grade and surgical specialty was collected. A detailed account of the nominated adverse event and the impact that this had on them in both a professional and personal capacity was then gathered. Standardised measures utilised within the survey, included the Work-related Acceptance and Action Questionnaire (WAAQ), the Primary Care PTSD Screen (PC-PTSD), the Brief Resilience Scale (BRS), the 21 item Depression, Anxiety and Stress Scale (DASS-21) and the Big Five Inventory personality measure (BFI). Results 445 surgeons completed the online survey. The extent to which surgeons are negatively affected by adverse events is significant. The data demonstrates that surgeons are negatively affected by adverse events, but do not possess the adaptive coping strategies to deal with them effectively. Confirmatory factor analysis confirmed five input variables within the model: event type (complication or error), nature of event (emergency or elective), severity of patient outcome (categorised by Clavien-Dindo score), timeframe of event occurring, and formal investigation. SEM identified three observed variables; feelings, PTS symptomology and worry about colleagues. The relationships between the input and observed variables were found to be moderated by training and personality factors and were mediated by resilience and psychological flexibility. Conclusion Prior to this research, it was unclear how surgeons were psychologically affected when they experienced an adverse surgical event. This gap within our understanding meant that any training, support, or intervention strategies would be unlikely to meet the specific needs of surgeons who were negatively affected. Given the mediating effects of resilience and psychological flexibility against negative outcomes, strategies should be incorporated to maximise these traits within surgeons. The findings from this research support targeted interventions focussing on the development of individual resilience and psychological flexibility. The need for changes to surgical culture are addressed, and recommendations are made to ensure that training, interventions, and support pathways within surgical training and the wider NHS are fit for purpose

Cholesterol is required for transcriptional repression by BASP1

Lipids are present within the cell nucleus, where they engage with factors involved in gene regulation. Cholesterol associates with chromatin in vivo and stimulates nucleosome packing in vitro, but its effects on specific transcriptional responses are not clear. Here, we show that the lipidated Wilms tumor 1 (WT1) transcriptional corepressor, brain acid soluble protein 1 (BASP1), interacts with cholesterol in the cell nucleus through a conserved cholesterol interaction motif. We demonstrate that BASP1 directly recruits cholesterol to the promoter region of WT1 target genes. Mutation of BASP1 to ablate its interaction with cholesterol or the treatment of cells with drugs that block cholesterol biosynthesis inhibits the transcriptional repressor function of BASP1. We find that the BASP1–cholesterol interaction is required for BASP1-dependent chromatin remodeling and the direction of transcription programs that control cell differentiation. Our study uncovers a mechanism for gene-specific targeting of cholesterol where it is required to mediate transcriptional repression

Cell density and airspace patterning in the leaf can be manipulated to increase leaf photosynthetic capacity

The pattern of cell division, growth and separation during leaf development determines the pattern and volume of airspace in a leaf. The resulting balance of cellular material and airspace is expected to significantly influence the primary function of the leaf, photosynthesis, and yet the manner and degree to which cell division patterns affect airspace networks and photosynthesis remains largely unexplored. In this paper we investigate the relationship of cell size and patterning, airspace and photosynthesis by promoting and repressing the expression of cell cycle genes in the leaf mesophyll. Using microCT imaging to quantify leaf cellular architecture and fluorescence/gas exchange analysis to measure leaf function, we show that increased cell density in the mesophyll of Arabidopsis can be used to increase leaf photosynthetic capacity. Our analysis suggests that this occurs both by increasing tissue density (decreasing the relative volume of airspace) and by altering the pattern of airspace distribution within the leaf. Our results indicate that cell division patterns influence the photosynthetic performance of a leaf, and that it is possible to engineer improved photosynthesis via this approach

Anti-Lysophosphatidic Acid Antibodies Improve Traumatic Brain Injury Outcomes

BACKGROUND: Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. FINDINGS: Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. CONCLUSIONS: This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction

Mixed-methods feasibility study of blood pressure self-screening for hypertension detection.

OBJECTIVE: To assess the feasibility of using a blood pressure (BP) self-measurement kiosk-a solid-cuff sphygmomanometer combined with technology to integrate the BP readings into patient electronic medical records- to improve hypertension detection. DESIGN: A concurrent mixed-methods feasibility study incorporating observational and qualitative interview components. SETTING: Two English general practitioner (GP) surgeries. PARTICIPANTS: Adult patients registered at participating surgeries. Staff working at these sites. INTERVENTIONS: BP self-measurement kiosks were placed in the waiting rooms for a 12-month period between 2015 and 2016 and compared with a 12-month control period prior to installation. OUTCOME MEASURES: (1) The number of patients using the kiosk and agreeing to transfer of their data into their electronic medical records; (2) the cost of using a kiosk compared with GP/practice nurse BP screening; (3) qualitative themes regarding use of the equipment. RESULTS: Out of 15 624 eligible patients, only 186 (1.2%, 95% CI 1.0% to 1.4%) successfully used the kiosk to directly transfer a BP reading into their medical record. For a considerable portion of the intervention period, no readings were transferred, possibly indicating technical problems with the transfer link. A comparison of costs suggests that at least 52.6% of eligible patients would need to self-screen in order to bring costs below that of screening by GPs and practice nurses. Qualitative interviews confirmed that both patients and staff experienced technical difficulties, and used alternative methods to enter BP results into the medical record. CONCLUSIONS: While interviewees were generally positive about checking BP in the waiting room, the electronic transfer system as tested was neither robust, effective nor likely to be a cost-effective approach, thus may not be appropriate for a primary care environment. Since most of the cost of a kiosk system lies in the transfer mechanism, a solid-cuff sphygmomanometer and manual entry of results may be a suitable alternative

Sustainability in a changing world: integrating human health and wellbeing, urbanisation, and ecosystem services

There is an urgent need to address interlinked sustainability issues in a world challenged by inequality, finite resources and unprecedented changes across Earth’s systems. As Future Earth Fellows, based on our collective expertise in a diverse range of sustainability issues, here we identify a specific need to recognise and respond appropriately to the nexus between human health and wellbeing, urbanisation, and ecosystem services (the ‘WUE nexus’). This nexus is a priority area for research, policy and practice. In particular, it provides a useful pathway to meet the challenges of successful implementation of the Sustainable Development Goals (SDGs). In this brief, we present the following policy recommendations:1. By emphasising urban-rural linkages, foster an integrated approach to ensure food security, food safety, and health promotion;2. Secure resilient livelihoods for all, in particular for vulnerable groups; and3. Integrate co-production of knowledge in science for decision-making, including the co-design of implementation frameworks, and the adoption of a nexus approach.<br/

Stomatal Function Requires Pectin De-methyl-esterification of the Guard Cell Wall

Stomatal opening and closure depends on changes in turgor pressure acting within guard cells to alter cell shape. The extent of these shape changes is limited by the mechanical properties of the cells, which will be largely dependent on the structure of the cell walls. Although it has long been observed that guard cells are anisotropic due to differential thickening and the orientation of cellulose microfibrils, our understanding of the composition of the cell wall that allows them to undergo repeated swelling and deflation remains surprisingly poor. Here, we show that the walls of guard cells are rich in unesterified pectins. We identify a pectin methylesterase gene, PME6, which is highly expressed in guard cells and required for stomatal function. pme6-1 mutant guard cells have walls enriched in methyl-esterified pectin and show a decreased dynamic range in response to triggers of stomatal opening/closure, including elevated osmoticum, suggesting that abrogation of stomatal function reflects a mechanical change in the guard cell wall. Altered stomatal function leads to increased conductance and evaporative cooling, as well as decreased plant growth. The growth defect of the pme6-1 mutant is rescued by maintaining the plants in elevated CO2, substantiating gas exchange analyses, indicating that the mutant stomata can bestow an improved assimilation rate. Restoration of PME6 rescues guard cell wall pectin methyl-esterification status, stomatal function, and plant growth. Our results establish a link between gene expression in guard cells and their cell wall properties, with a corresponding effect on stomatal function and plant physiology