Comparative study of propofol and etomidate as intravenous induction agents for general anesthesia: hemodynamic effects, adrenal suppression, and blood glucose response in controlled hypertensive patients

Background: General anesthesia induces unconsciousness and loss of reflexes, facilitating complex medical treatments. The induction of anesthesia is crucial for patient comfort and procedural success, with propofol and etomidate being common intravenous induction agents. Propofol offers a rapid onset and short duration, while etomidate is known for cardiovascular stability. Methods: A prospective randomized controlled trial involving 100 controlled hypertensive patients compared propofol and etomidate for induction. Hemodynamic parameters and biochemical responses were monitored at various intervals. Injection site discomfort and myoclonus were assessed, and cortisol and glucose levels were measured. Results: Baseline hemodynamic values were similar. Etomidate resulted in stable hemodynamics as compared to propofol. Blood sugars were comparable. Though serum cortisol levels were reduced after etomidate was given. But it came back to normal range 24 hours after surgery. Injection site pain was reported by 20% of etomidate patients and 10% of propofol patients. No myoclonus occurred. Conclusions: Etomidate is an effective induction agent for controlled hypertensive individuals, causing transient adrenal suppression without affecting blood sugar levels

Building connections: Golden key local evaluation phase 2 report

This report summarises findings from Phase 2 of the UWE Local Evaluation of Golden Key (GK) in Bristol (March 2016 to Feb 2017). GK is one of 12 Big Lottery funded Fulfilling Lives partnerships across the UK, where local organisations are working together to improve services for people with multiple and complex needs. This is a formative evaluation that will inform learning about how, when and why change happens for individuals, groups and organisations across the City. We will be supporting the initiative throughout its 8-year duration, engaging with different stakeholders to capture a diverse range of perspectives and experiences to produce a multi-faceted understanding of the issues and to stimulate reflection and learning amongst partners.This phase of the evaluation has focused primarily on the client experience pathway, including the experiences of GK clients, Service Co-ordinators, and members of the Independent Futures (IF) Group (experts by experience). Within this report, the ‘Key findings’ sections include insights from our evaluation research, as well as our analysis of client demographics and assessment scores. ‘Activity progress summary’ sections provide a brief update on other aspects of GK’s work, such as the systems change strategy and approach, and are informed by GK documents and meetings.Findings from this phase of the evaluation will be shared with key stakeholders and used to inform the next phase of GK activity. We anticipate that the next phase of the local evaluation will involve exploring how GK is facilitating and enabling systems change (including the role of PIE and innovation pilots), capturing evidence of impact (including economic and social return on investment), and engaging with partner organisations (police, health, council, voluntary sector, etc.) to gain their perspectives on the contribution of GK

The Difference that Makes the Difference - Final evaluation of the first place-based programmes for Systems Leadership: Local Vision

1.This report outlines findings from Phase 2 of the evaluation of Systems Leadership: Local Vision, conducted by Bristol Leadership Centre on behalf of the Systems Leadership Steering Group. It is the third in a series of reports capturing the learning and outcomes of the first cohort of Local Vision projects.2.In this report we focus on the outcomes and effects of Local Vision projects in different localities and consider how local context enables or constrains the potential for sustainable change. This analysis is based on case studies, interviews and secondary data.3.Overall, the findings suggest that Local Vision has had a positive impact within each of the areas investigated, complementing existing initiatives and catalysing change and engagement amongst partners and communities. 4.There is good evidence of Local Vision projects raising awareness of systems leadership amongst stakeholders in different localities – in particular in relation to thinking systemically, working collaboratively, engaging with service users, and fostering shared leadership.5.Likewise, there is good evidence that Local Vision has been regarded as a success in most localities, producing benefits and value for a diversity of stakeholders, such as influencing strategy, generating income and opportunities, engaging professionals, and improving services and client outcomes. 6.Whilst, in many cases it is still a little too early to determine the legacy and any lasting change arising from Local Vision, there is good evidence of its ability to catalyse change, influence new ways of working, and build commitment and momentum in relation to ‘wicked’ issues. 7.The case studies conducted during this phase of the evaluation enable the identification of a number of trends across projects that suggest some important ingredients of effective systems leadership interventions. These include start-up conditions (including the nature of the problem/challenge, level of intervention, prior experience of systems working, and imperative for change); local context (including alignment with other initiatives, project ownership, dedicated project support, and senior-level organisational and political engagement); process (including choice of Enabler, engagement with local communities, memorandum of understanding, King’s Fund learning network, and scale and timing of projects); and planning for sustainability (including project leadership, Enabler exit conditions, roll-out, and evaluating outcomes).8.Alongside the collection and analysis of evidence from Local Vision project partners and Enablers, the evaluation also collated and analysed a wide range of independent metrics on localities and the nature and scale of the ‘wicked’ issues that projects were tackling. Whilst these analyses did not reveal many insights into the Local Vision projects themselves, they do illuminate the challenges of benchmarking complex change interventions, and highlight the potential value of data as a leadership tool for galvanising action in complex and contested environments. 9.The report concludes with a summary of key outcomes and recommendations for future activity on Local Vision and related systems leadership initiatives. The evidence from this evaluation suggests that Local Vision can be regarded as a successful initiative that has succeeded in developing and embedding learning about systems leadership and change in the majority of localities where it has operated. As a place-based intervention, supported by skilled ‘Enablers’, Local Vision has successfully catalysed collaboration between multiple stakeholders to address shared challenges.10.The evaluation findings prove testament to the skill and tenacity of the Local Vision Enablers, project partners and the Leadership Centre (who coordinated and supported the initiative on behalf of the Systems Leadership Steering Group) in brokering relationships, facilitating difficult conversations and (re)connecting diverse communities to a shared sense of purpose. In most localities, there are now people committed to thinking systemically, working collaboratively, engaging with service users, and fostering shared leadership that will continue to have an impact for many years to come

Antigenotoxic Effect of Curcumin and Carvacrol against Parathion Induced DNA Damage in Cultured Human Peripheral Blood Lymphocytes and Its Relation to GSTM1 and GSTT1 Polymorphism

In recent years, the use of organophosphorus pesticides has been extensively increased and these compounds signify a major class of agricultural pesticides today. We studied antigenotoxic potential of curcumin and carvacrol against the parathion induced DNA damage in cultured peripheral blood lymphocytes using sister chromatid exchanges as a biomarker of genotoxicity. Heparinised fresh blood from healthy individuals was treated with 2.5 μg/mL concentration of parathion in presence of curcumin and carvacrol in order to observe the antigenotoxic potential of both curcumin and carvacrol. Significant reduction (P0.05) of GSTT1 and GSTM1 polymorphism on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol

Reframing, Realignment and Relationships - Interim evaluation of the first place-based programmes for Systems Leadership: Local Vision

In Autumn 2014 Bristol Leadership Centre at the University of the West of England was commissioned to undertake evaluation of the Local Vision programme.The evaluation is designed in two phases. This interim report sets out our findings for Phase 1, with a primary focus on identifying and exploring key criteria that may shape efficacy and impact. This will inform the developing evaluation framework, collective ‘sense making’ and deeper exploration of programme outcomes planned for Phase 2 of the evaluation, with a final report to be published in autumn 2015

Association of Polymorphisms of Phase I Metabolizing Genes with Sister Chromatid Exchanges in Occupational Workers Exposed to Toluene Used in Paint Thinners

This study investigated genetic damage in paint workers mainly exposed to toluene as it is a major solvent used in paint thinners. Sister chromatid exchange (SCE) assay was used as biomarker of genotoxicity. Blood samples were collected from 30 paint workers and 30 control subjects matched with respect to age and other confounding factors except for exposure to toluene. SCE frequency was found to be significantly higher in paint workers (4.81 ± 0.92) as compared to control individuals (1.73 ± 0.54) ( < 0.05). We also investigated influence of polymorphisms of CYP2E1 and CYP1A1m2 genes on SCE frequency. Our results showed that there was significant increase in frequencies of SCE among the mutant genotypes of CYP2E1 and CYP1A1m2 as compared to wild genotypes. Our study indicated that long term exposure of toluene can increase genotoxic risk in paint workers

Reaching out: Golden Key local evaluation phase 1 full report

This report presents a preliminary analysis of the evidence collated for Phase 1 of the local evaluation of Bristol Golden Key. Evidence has been collected between November 2014 and March 2016 through a variety of means, including interviews with around 40 key stakeholders, observation at over 25 key meetings and events, and review of documentation.Golden Key is a long-term, complex initiative and at this relatively early stage the evaluation is primarily formative in focus – providing observations and reflections on how Golden Key has developed since inception and emerging indicators of how it is perceived and experienced by different stakeholders. The main aim of this report is to ‘capture the learning’ so far and to raise issues and questions that should inform further development as Golden Key progresses. It does not purport to give an objective assessment of progress against project aims given the paucity of quantitative data to support such an analysis at this stage.The report is informed by the evaluation framework developed to support this investigation, which uses a realist approach to identifying how behaviours, processes, outcomes and impacts develop in relation to three main pathways: client engagement; the Golden Key partnership and processes; and citywide engagement and systems change. Chapters are presented for each of these areas, concluding with a set of key learning points and discussion questions

Reaching out: Golden Key local evaluation phase 1 summary report

This report summarises the findings from Phase 1 of the local evaluation of Golden Key though the first 18 months of initial development, progress towards delivery and operational services delivery from Autumn 2014 to Spring 2016.Bristol Golden Key is one of 12 programmes across the UK to have received funding from the Big Lottery Fund Fulfilling Lives programme to support the development and provision of services for people with multiple complex needs

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology