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Cancer of unknown primary (CUP) is a syndrome defined by clinical absence of a primary cancer after standardised investigations. Gene expression profiling (GEP) and DNA sequencing have been used to predict primary tissue of origin (TOO) in CUP and find molecularly guided treatments; however, a detailed comparison of the diagnostic yield from these two tests has not been described. Here, we compared the diagnostic utility of RNA and DNA tests in 215 CUP patients (82% received both tests) in a prospective Australian study. Based on retrospective assessment of clinicopathological data, 77% (166/215) of CUPs had insufficient evidence to support TOO diagnosis (clinicopathology unresolved). The remainder had either a latent primary diagnosis (10%) or clinicopathological evidence to support a likely TOO diagnosis (13%) (clinicopathology resolved). We applied a microarray (CUPGuide) or custom NanoString 18-class GEP test to 191 CUPs with an accuracy of 91.5% in known metastatic cancers for high-medium confidence predictions. Classification performance was similar in clinicopathology-resolved CUPs - 80% had high-medium predictions and 94% were concordant with pathology. Notably, only 56% of the clinicopathology-unresolved CUPs had high-medium confidence GEP predictions. Diagnostic DNA features were interrogated in 201 CUP tumours guided by the cancer type specificity of mutations observed across 22 cancer types from the AACR Project GENIE database (77,058 tumours) as well as mutational signatures (e.g. smoking). Among the clinicopathology-unresolved CUPs, mutations and mutational signatures provided additional diagnostic evidence in 31% of cases. GEP classification was useful in only 13% of cases and oncoviral detection in 4%. Among CUPs where genomics informed TOO, lung and biliary cancers were the most frequently identified types, while kidney tumours were another identifiable subset. In conclusion, DNA and RNA profiling supported an unconfirmed TOO diagnosis in one-third of CUPs otherwise unresolved by clinicopathology assessment alone. DNA mutation profiling was the more diagnostically informative assay. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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RNA-seq and scRNA-seq count data and TCR contigs

Merkel cell carcinomas (MCC) are immunogenic skin cancers associated with viral infection or UV mutagenesis. To study T-cell infiltrates in MCC, we analyzed 58 MCC lesions from 39 patients using multiplex-IHC/immunofluorescence (m-IHC/IF). CD4+ or CD8+ T cells comprised the majority of infiltrating T lymphocytes in most tumors. However, almost half of the tumors harbored prominent CD4/CD8 double-negative (DN) T-cell infiltrates (>20% DN T cells), and in 12% of cases, DN T cells represented the majority of T cells. Flow cytometric analysis of single-cell suspensions from fresh tumors identified DN T cells as predominantly Vδ2− γδ T cells. In the context of γδ T–cell inflammation, these cells expressed PD-1 and LAG3, which is consistent with a suppressed or exhausted phenotype, and CD103, which indicates tissue residency. Furthermore, single-cell RNA sequencing (scRNA-seq) identified a transcriptional profile of γδ T cells suggestive of proinflammatory potential. T-cell receptor (TCR) analysis confirmed clonal expansion of Vδ1 and Vδ3 clonotypes, and functional studies using cloned γδ TCRs demonstrated restriction of these for CD1c and MR1 antigen-presenting molecules. On the basis of a 13-gene γδ T–cell signature derived from scRNA-seq analysis, gene-set enrichment on bulk RNA-seq data showed a positive correlation between enrichment scores and DN T-cell infiltrates. An improved disease-specific survival was evident for patients with high enrichment scores, and complete responses to anti–PD-1/PD-L1 treatment were observed in three of four cases with high enrichment scores. Thus, γδ T–cell infiltration may serve as a prognostic biomarker and should be explored for therapeutic interventions.See related Spotlight on p. 600

In this analysis, we systematically review and synthesize the results of two local-level studies linking various types of carbon emissions data with nationwide measures of affluence. We focus on the socio-economic dimensions of climate policy, differentiating between different sources of greenhouse gas emissions, and between different methods of collecting greenhouse gas emissions data. We demonstrate that high levels of affluence spatially displace carbon-intensive production-based emissions. We then synthesize a framework for future research on environmental policy design to explicitly consider the method of collecting data on carbon emissions by sector and activity. We offer strategies for policymakers regarding the conditions under which specific carbon emissions data collection methods may be more relevant or appropriate than other methods. We emphasize that more equitable environmental policy objectives can be achieved by recognizing the socio-economic dimensions of carbon emissions data, thus the importance of critically examining the way those data inform policy.

Cancer of unknown primary (CUP) constitutes a group of metastatic cancers in which standardized clinical investigations fail to identify a tissue of origin (TOO). Gene-expression profiling (GEP) has been used to resolve TOO, and DNA sequencing to identify potential targeted treatments; however, these methods have not been widely applied together in CUP patients. To assess the diagnostic utility of DNA and RNA tests for TOO classification, we applied GEP classification and/or gene-panel DNA sequencing in 215 CUP patients. Based on a retrospective review of pathology reports and clinical data, 77% of the cohort were deemed True-CUPs (T-CUP). Among the remaining cases, a latent primary diagnosis (10%) (LP-CUP) or TOO was highly suspected based on combined clinicopathological data (13%) (histology-resolved CUP, HR-CUP). High-medium confidence GEP classifications were made for 80% of LP/HR-CUPs, and these classifications were consistent with a pathologist-assigned diagnosis in 94% of cases, while only 56% of T-CUPs had high-medium confidence predictions. The frequency of somatic mutations in cancer genes was similar to 2,785 CUPs from AACR GENIE Project. DNA features, GEP classification, and oncovirus detection assisted making a TOO diagnosis in 37% of T-CUPs. Gene mutations and mutational signatures of diagnostic utility were found in 31% T-CUPs. GEP classification was useful in 13% of cases and viral detection in 4%. Among resolved T-CUPs, lung and biliary were the most frequently identified cancer types, while kidney cancer represented another minor subset. Multivariate survival analysis showed that unresolved T-CUPs had poorer overall survival than LP/HR-CUPs (Hazard ratio=1.9, 95% CI 1.1 − 3.2, p=0.016), while the risk of death was similar in genomically-resolved T-CUPs and LP/HR-CUPs. In conclusion, combining DNA and RNA profiling with clinicopathological data supported a putative TOO diagnosis in over a third of T-CUPs. DNA sequencing benefited T-CUP tumors with atypical transcriptional patterns that hindered reliable GEP classification.

The current lack of comprehensive federal climate policy highlights the critical need for effective subnational climate policy and programs. We describe our efforts to create and cultivate a community-based multi-stakeholder group centered around local climate change planning and advocacy in a small, rural New York municipality. The literature on sustainability planning emphasizes the importance of collaborative work to build new capacities, develop knowledge, and create community commitment over the long term to advocate for municipal policies that prioritize climate change mitigation and resilience. However, case studies of rural community contexts are lacking in the literature, and rural communities may not have the planning and other resources found in the municipal offices of larger, urban communities. We argue that higher education institutions, especially those situated in small rural communities, have a vital role in supporting the climate strategies of local actors and can develop productive partnerships through research and co-curricular education. We discuss several challenges to effective campus-community partnerships, including the need to balance student engagement in community-based research with the traditional liberal arts model of education, engaging and sustaining the participation of community partners, and differential access to resources in rural spaces.

BackgroundCancer of unknown primary (CUP) is a heterogeneous group of metastatic cancers where a primary tissue of origin (TOO) is uncertain. Most patients with CUP have limited treatment options and poor survival outcomes. Immune checkpoint inhibitors (ICIs) can be efficacious in some patients with CUP, but the optimal predictive biomarkers are unknown. We therefore assessed immune and genomic biomarkers as well as predicted TOO in patients with CUP, including a subset treated with ICIs.MethodsPatients with CUP were subject to gene-expression profiling (GEP) and DNA panel sequencing. Immune and stromal-related gene expression was explored by NanoString, including genes associated with immunotherapy response (IR) in other solid malignancies. ICI responsive cancer types were assigned based on Food and Drug Administration-approved indications, and either detection of a latent primary tumor or the TOO was suspected based on genomics informed pathology review. Tumor mutation burden (TMB) and gene mutations were also assessed.ResultsA total of 219 patients with CUP were included, 215 assessed for TOO in a previous study, with the majority (163) receiving both RNA and DNA tests. Of GEP profiled cases, 33% (59/175) had a high IR gene-expression score. Of the DNA sequenced cases, 16% (32/203) had high TMB (>10 mutations/Mb), including two with mismatch repair deficiency. Low correlation was observed between TMB and an IR score (R=0.26, pConclusionsA significant fraction of CUP tumors had genomic features previously associated with ICI response. High IR score was the most sensitive predictive feature of ICI response, warranting evaluation in a larger patient series.

Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors associated with autonomic nerves. Here we use single-nuclei RNA-seq and bulk-tissue gene-expression data to characterize the cellular composition of PCPG and normal adrenal tissues, refine tumor gene-expression subtypes and make clinical and genotypic associations. We confirm seven PCPG gene-expression subtypes with significant genotype and clinical associations. Tumors with mutations in VHL, SDH-encoding genes (SDHx) or MAML3-fusions are characterized by hypoxia-inducible factor signaling and neoangiogenesis. PCPG have few infiltrating lymphocytes but abundant macrophages. While neoplastic cells transcriptionally resemble mature chromaffin cells, early chromaffin and neuroblast markers are also features of some PCPG subtypes. The gene-expression profile of metastatic SDHx-related PCPG indicates these tumors have elevated cellular proliferation and a lower number of non-neoplastic Schwann-cell-like cells, while GPR139 is a potential theranostic target. Our findings therefore clarify the diverse transcriptional programs and cellular composition of PCPG and identify biomarkers of potential clinical significance.

Drawing from the existing social science literature, we examine the relationship between fossil fuel use and the adoption of policy to address climate change at the local level. In our analysis, we incorporate direct measures of fossil fuel use in a manner that allows us to distinguish carbon emissions from consumption-based and production-based activities. Focusing on the 36 most populous and urbanized counties within the state of California, we merge these emissions, along with other political and economic measures, with an indicator of extensive policy support derived from climate agreement signatories. We then use fuzzy-set qualitative comparative analysis (QCA) to examine conditions that are sufficient for broad adoption of climate policy within a given county. Based on the results, we frame consumption-based and production-based emissions as distinctive in the way that their relationship with climate policy adoption depends on other favorable political and economic conditions. In particular, we identify several routes to extensive adoption for counties that have a combination of low emissions and a favorable political environment. In the conclusion, we discuss the QCA findings and elaborate on the theoretical and practical implications for efforts to understand and to promote carbon reduction efforts at the local level.

Background The difference in patient comfort with conscious sedation versus general anaesthesia for bronchoscopy has not been adequately assessed in a randomised trial. This study aimed to assess if patient comfort during bronchoscopy with conscious sedation is noninferior to general anaesthesia. Methods 96 subjects were randomised to receive conscious sedation or general anaesthesia for bronchoscopy. The primary outcome was subject comfort. Secondary outcomes included willingness to undergo a repeat procedure if necessary and level of sedation assessed clinically and by bispectral index (BIS) monitoring. Results There was no significant difference between subject comfort scores (difference −0.01, 95% CI −0.63–0.61 on a 10-point scale; p=0.97) or willingness to undergo a repeat procedure (97.7% versus 91.8%, 95% CI −4.8–15.5%; p=0.37). Deeper levels of sedation in the general anaesthesia cohort was confirmed with both clinical and BIS monitoring. There was no significant difference in diagnostic accuracy (conscious sedation 93.9%, 95% CI 80.4–98.3% versus general anaesthesia 86.5%, 95% CI 72.0–94.1%; p=0.43). There were more complications (29.6%, 95% CI 18.2–44.2% versus 6.1%, 95% CI 2.1–16.5%; p, Conscious sedation was noninferior to anaesthetist-controlled general anaesthesia for patient comfort during bronchoscopy in this randomised trial. Deeper sedation with general anaesthesia did not improve comfort and had increased complications. https://bit.ly/3sCDfEy

BACKGROUND: Timely access to treatment of lung cancer is dependent on efficient and appropriate patient assessment and early referral for diagnostic workup. This study assesses the impact of Cancer Care Ontario (CCO) Lung Cancer Diagnostic Pathway Guideline (LCDPG) concordance on access to treatment of stage IV lung cancer patients referred to the Diagnostic Assessment Program (DAP) at a Canadian tertiary cancer centre. METHODS: This retrospective cohort study includes patients diagnosed with clinical stage IV lung cancer referred to the DAP at a Canadian tertiary cancer centre between November 1, 2015 and May 31, 2017. Referral concordance was determined based on CCO LCDPG. The primary outcome; time to treatment from initial healthcare presentation; was compared between the concordant and discordant referrals. RESULTS: Two hundred patients were referred for clinical stage IV lung cancer during the study period. Of these referrals, 151 (75.5%) were assessed and referred in concordance with LCDPG. Guideline concordant referrals were associated with reduced time to treatment from first healthcare presentation compared with guideline discordant referrals (55.3 vs. 108.8 days, P

Objectives: The aim of this study was to describe the cytological features of patients with significant occupational dust exposure presenting with benign bilateral mediastinal and hilar lymphadenopathy (BHL). Methods: A retrospective cohort study including patients undergoing EBUS-TBNA for investigation of benign BHL. Patient characteristics, dust exposure history, radiology, and cytology samples from EBUS-TBNA were assessed. Results: EBUS-TBNA cytology in patients with exposure showed a significant increase in the presence of birefringent fibers (60.7% vs 19.2%, P=0.001) and intracellular carbon pigment (75.0% vs 28.9%, P=0.001) compared with patients without exposure. The presence of these two features together yielded a sensitivity of 53.6% and a specificity of 88.5%. Conclusion: In patients with BHL and a history of occupational dust exposure, the presence of birefringent fibers and intracellular carbon pigment in EBUS-TBNA cytology samples may assist in a diagnosis of lymphadenopathy due to occupational dust exposure.

The concept of learning has long played a central role in the theories and frameworks used to understand policy processes. Findings described here aim to contribute to the theoretical and methodological understanding of individual learning in the policy process by explicitly examining belief change and belief reinforcement as products of policy learning, measuring both, as well as measuring the absence of either. The objective of this study is to use the lens of the Advocacy Coalition Framework to examine some of the factors that promote and shape policy learning, including policy actors' beliefs and the extent to which policy actors engage in various policy activities within and between belief coalitions. The results indicate that extreme beliefs are associated with belief reinforcement, relative to policy actors with more moderate beliefs, and that collaboration with individuals with differing policy views is associated with belief change. 影响政策学习的因素：一项关于参与区域气候和能源议题的政治行为者的研究 政策学习概念长期以来在研究政策过程的相关理论和框架中占据中心作用。通过将信仰改变和信仰强化（belief reinforcement）作为政策学习产物进行明确检验, 同时对二者的存在和消失都进行衡量, 本文研究结果致力从理论和方法论两方面促进（我们）理解政策过程中的个体学习。本文描述的分析方法检验了几个与政策学习相关的因素, 包括政策行为者的信仰、政策行为者参与政策活动（例如各信仰联盟内部和相互之间的协作及征求建议）的程度、以及加快的共识建立过程。与许多州相似的是, 科罗拉多州正经历与石油天然气开发和可再生能源生产相关的能源生产模式的转变。和其他30多个州一样, 这些转变正在一项用于解决气候变化的倡议背景下进行, 即 2007 年 12 月启动的科罗拉多州气候行动计划。本文目的是从倡议联盟框架（ Advocacy Coalition Framework, ACF）的视角帮助检验某些因素, 这些因素推动并影响了科罗拉多州政策行为者的政策学习, 他们参与了气候和能源政策辩论, 辩论有关前者在一系列相关政策问题上的信仰。本文结果显示, 相对于信念更加温和的政策行为者, 极端信仰（的形成）和信仰强化有关；而与持不同政策观点的个体进行协作则与信仰变化有关。 Factores que dan forma al aprendizaje politico: un estudio de los actores politicos en temas subnacionales del clima El concepto de aprendizaje ha tenido por mucho tiempo un rol central en las teorias y marcos teoricos que se usan para comprender los procesos politicos. Los hallazgos que se describen aqui buscan contribuir al entendimiento teorico y metodologico del aprendizaje individual en el proceso politico al explicitamente examinar el cambio de creencias y el fortalecimiento de creencias como productos del aprendizaje politico, midiendo los dos, asi como tambien midiendo la ausencia de ambos. El analisis descrito en este estudio examino varios factores asociados con el aprendizaje politico incluyendo: las creencias de los actores, el punto hasta el que los actores politicos participan en actividades politicas como la colaboracion y la busqueda de asesoria dentro y entre las coaliciones de creencias y procesos facilitados de construccion de consenso. Similar a muchos estados en los EE.UU., Colorado esta viendo cambios en los patrones de produccion de energia en el tema del desarrollo de hidrocarburos y la generacion de energia renovable. Asi como en mas de 30 estados, estos cambios estan sucediendo en el contexto de una iniciativa para abordar el tema del cambio climatico, el Colorado Climate Action Plan empezo en noviembre de 2007. El objetivo de este estudio es utilizar el lente del Advocacy Coalition Network (ACF) para ayudar a examinar algunos de los factores que promueven y dan forma al aprendizaje politico de los actores politicos involucrados en debates del clima y politica energetica en Colorado teniendo que ver con sus creencias en un amplio espectro de interrogantes politicas relevantes. Los resultados indican que las creencias extremas estan asociadas con el fortalecimiento de las creencias, relativo a los actores politicos con mas creencias moderadas y esa colaboracion con individuos con perspectivas politicas diferentes esta asociada con el cambio de creencias.

The Trump administration cancelled US involvement in the Paris Agreement, so, despite projected devastating impacts on human communities, the US still lacks comprehensive national policies aimed at...

Much quantitative research examining the determinants of the ecological footprint has been conducted cross-nationally, where data on cross-boundary flows have been readily available. While local-level studies of the footprint do exist for specific localities, most quantitative research at this scale has examined direct environmental impacts attributed to the internal activities of the locality, for instance, carbon emissions. Our analysis builds on this previous work by exploiting a local-level carbon footprint dataset with coverage for 28,321 zip codes across the United States. Following prior research, we focus on the effect of local affluence, measured in terms of median household income. In spatial regression models, we regress the per capita carbon footprint on local affluence, controlling for a variety of other factors. Consistent with previous work, we find that affluence is positively correlated the carbon footprint and there is no evidence of an environmental Kuznets curve. In the conclusion, we review the results of the study and discuss their implications for policy, specifically in terms of cross-boundary environmental problems.

Our genes and the way in which our genetic code is read makes us who we are. Unfortunately, our genetic code can be altered or misinterpreted in cancer. The 3’ untranslated region is one such example of an important part of our genetic code that is read differently in cancer. This thesis focused on defining what changes to the 3’ untranslated region occur in breast cancer, then explored which of these changes were most associated with breast cancer outcome. Extension and validation of the work in this thesis may one day lead to a better test for breast cancer outcome.

William Hazledine (1763–1840) is a virtually forgotten figure in the history of engineering. He worked closely with Thomas Telford, and the list of their joint achievements in the UK is unmatched in the history of bridge engineering. These include the aqueducts of Chirk and Pontcysyllte; arch bridges at Bonar, Mythe, Tewkesbury and Craigellachie; lock gates and bridges for the Caledonian Canal and many smaller cast iron bridges; and, not least, the unprecedented suspension bridges at Conwy and Menai in North Wales. Hazledine's expertise also won him many other contracts, including the suspension bridge at Marlow in Buckinghamshire, and the ironwork for the first all-iron-framed multi-storey building in the world, the Flax Mill at Ditherington in his home town of Shrewsbury. Recent research has begun to reveal his importance in the production of cast and wrought iron for these valued legacy structures. The paper highlights the outstanding quality of the iron that Hazledine made and the rigorous proof tests he undertook to verify the properties of the metal. These results will be of great interest to engineers today working on heritage cast- and wrought-iron structures, if only to learn of the high-quality results that were possible 200 years ago.

Social scientists have debated how affluence impacts carbon emissions at the national level. We conduct an exploratory study at the subnational level to expose another dimension of the affluence–emissions debate. Based on the notion of aristocratic conservation, we hypothesize that affluence is positively related to carbon emissions from consumption activities but negatively related to emissions from production activities. We test these hypotheses using county-level data in the United States for the year 2002. A spatial regression analysis demonstrates that median household income is positively associated with consumption-based emissions; nevertheless, we find evidence of an environmental inequality Kuznets curve in the relationship between median household income and production-based emissions. This finding suggests that the wealthiest counties are able to displace certain types of emissions, specifically those related to energy and industrial production. We discuss the theoretical and political implicat...

One of the leading theories for understanding the policy process is the theory of social construction and policy design developed by Anne Schneider and Helen Ingram. The theory incorporates the social construction and power of target populations to understand the development and implications of policy design. In order to better understand its empirical breadth, depth, and general utility, our analysis reviews all past publications of the theory, focusing specifically on empirical applications (N = 111), from 1993 to 2013. Based on this review, we find: a recent increase in the number of applications of this theory; that these applications appear across a wide range of outlets, relate to numerous policy domains, and are conducted by a diverse group of domestic and international scholars; that the target population proposition has been applied with greater frequency than the theory’s feed-forward proposition; and that scholars have a notable interest in understanding causal mechanisms leading to changes in the positioning of target populations among advantaged, contender, dependent, and deviant target population categories. Following a descriptive review of past publications, we offer specific suggestions for theoretical development and future research.

Summary Cities are embedded within larger-scale engineered infrastructures (e.g., electric power, water supply, and transportation networks) that convey natural resources over large distances for use by people in cities. The sustainability of city systems therefore depends upon complex, cross-scale interactions between the natural system, the transboundary engineered infrastructures, and the multiple social actors and institutions that govern these infrastructures. These elements, we argue, are best studied in an integrated manner using a novel social-ecological-infrastructural systems (SEIS) framework. In the biophysical subsystem, the SEIS framework integrates urban metabolism with life cycle assessment to articulate transboundary infrastructure supply chain water, energy, and greenhouse gas (GHG) emission footprints of cities. These infrastructure footprints make visible multiple resources (water, energy, materials) used directly or indirectly (embodied) to support human activities in cities. They inform cross-scale and cross-infrastructure sector strategies for mitigating environmental pollution, public health risks and supply chain risks posed to cities. In the social subsystem, multiple theories drawn from the social sciences explore interactions between three actor categories—individual resource users, infrastructure designers and operators, and policy actors—who interact with each other and with infrastructures to shape cities toward sustainability outcomes. Linking of the two subsystems occurs by integrating concepts, theories, laws, and models across environmental sciences/climatology, infrastructure engineering, industrial ecology, architecture, urban planning, behavioral sciences, public health, and public affairs. Such integration identifies high-impact leverage points in the urban SEIS. An interdisciplinary SEIS-based curriculum on sustainable cities is described and evaluated for its efficacy in promoting systems thinking and interdisciplinary vocabulary development, both of which are measures of effective frameworks.

Human-used and managed natural resources, such as watersheds, represent complex socio-ecological systems where learning from different knowledge sources is essential for sustainable management. Guided by the advocacy coalition framework, the paper presents a set of propositions that help explain the different functional uses of expertbased information, the network position of scientific experts, and learning within and between coalitions. Most importantly, the paper investigates common assumptions about the superiority of consensus-based institutions for integrating science into policy-making by examining two collaborative and two adversarial policy subsystems. The findings show that the scientists’ centrality as coalition allies and opponents is lower in collaborative policy subsystems than in adversarial policy subsystems. The findings suggest a more hospitable setting for learning and sustainability in the management of natural resources in collaborative compared to adversarial subsystems. The paper concludes with suggestions for future research in sustainability and learning.

Aim: To determine non inferiority of conscious sedation compared with general anaesthetic (GA) for bronchoscopic procedures, in terms of patient comfort and satisfaction. Methods: Patients undergoing therapeutic and diagnostic procedures within the RBWH were considered for trial entry and randomisation. Procedures included standard diagnostic bronchoscopy, endobronchial convex probe ultrasound (EBUS) or transbronchial radial probe. Patients were randomised to either conscious sedation or GA, stratified for Charlson Comorbidity Index. Conscious sedation was by Thoracic Physicians and did not include Propofol; GA patients had Laryngeal mask airway. Patient comfort was assessed by pre and post procedural visual analogue scales. Secondary endpoints including medical staff assessment of comfort, peri-procedural complications, resource use and depth of anaesthesia as measured by Bispectral (BIS) analysis, were also measured. Results: At total of 75 patients were randomised. There was no significant difference in comfort scores between conscious sedation and GA groups for both binary (p=0.62) and 10 point visual analogue scales 2.1±0.2 vs. 2.2±0.2 (p=0.65). There was no significant difference between comfort scores as assessed by the proceduralist, however assessment by the assisting nurse showed significant improvement for the GA group (p=0.01). There were significantly higher peri-procedural complications within the GA group, 10 vs. 3 (p=0.02), as well as higher IV fluid volume requirements, 383ml±62 vs. 244ml± 27 (p=0.04), higher staff numbers 6.0±0.2 vs. 4.5±0.2 (p