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CellProfiler is a widely used software for creating reproducible, reusable image analysis workflows without needing to code. In addition to the >90 modules that make up the main CellProfiler program, CellProfiler has a plugins system that allows for creation of new modules which integrate with other Python tools or tools that are packaged in software containers. The CellProfiler-plugins repository contains a number of these CellProfiler modules, especially modules that are experimental and/or dependency-heavy. Here, we present an upgraded CellProfiler-plugins repository with examples of accessing containerized tools, improved documentation, and added citation/reference tools to facilitate the use and contribution of the community., 17 pages, 2 figures, 1 table

Harmonic data from a harmonic monitoring program in an Australian medium voltage (MV) distribution system containing residential, commercial and industrial customers has been analyzed using data mining techniques. Unsupervised learning, and in particular,cluster analysis using MML, which searches for the best model describing the data using a metric of an encoded message, has been shown to be able to detect anomalies and identify useful patterns within the monitored harmonic data set. The output of the clustering process has to be appropriately displayed and interpreted in relation to the problem domain so that utility engineers can provide the relevant information. The technique presented in this work allows utility engineers to detect unusual harmonic events from monitored sites, using clustering, and then to subsequently characterize the obtained clusters using the classification techniques to infer information about future harmonic performance at the monitored sites. The C5.0 algorithm has been used to generate expressible and understandable rules characterising each cluster without requiring significant data training. The optimal number of clusters in different types of data sets was investigated using a proposed method based on the trend of the exponential difference in message length between two consecutive mixture models. Testing this method using various two-weekly data sets from the harmonic monitoring data over three year period show that the suggested method is effective in

Vulnerable marine ecosystems (VMEs) are particularly susceptible to bottom-fishing activity as they are easily disturbed and slow to recover. A data-driven approach was developed to provide management options for the protection of VMEs under the European Union “deep-sea access regulations.” A total of two options within two scenarios were developed. The first scenario defined VME closure areas without consideration of fishing activity. Option 1 proposed closures for the protection of VME habitats and likely habitat, while Option 2 also included areas where four types of VME geophysical elements were present. The second scenario additionally considered fishing. This scenario used VME biomass—fishing intensity relationships to identify a threshold where effort of mobile bottom-contact gears was low and unlikely to have caused significant adverse impacts. Achieving a high level of VME protection requires the creation of many closures (> 100), made up of many small (∼50 km2) and fewer larger closures (> 1000 km2). The greatest protection of VMEs will affect approximately 9% of the mobile fleet fishing effort, while closure scenarios that avoid highly fished areas reduce this to around 4–6%. The framework allows managers to choose the level of risk-aversion they wish to apply in protecting VMEs by comparing alternative strategies., SI

Additional file 1: Figure S1. Execution times of all modules within the Cell Painting example pipeline. Measured as per-image CPU time taken for each module in the Cell Painting assay protocol (n = 48). I/O loading operations in the Images module are not recorded by these measurements.

Summary HIV-1 must replicate in cells that are equipped to defend themselves from infection through the intracellular innate immune system. Hence, HIV-1 evades innate immune sensing through encapsidated DNA synthesis and encodes accessory genes that antagonize specific antiviral effectors. Here we show that the HIV-1 Vpr protein antagonizes the stimulatory effect of a variety of pathogen associated molecular patterns, including cytoplasmic DNA, by inhibiting IRF3 and NF-κB nuclear transport. Both particle associated, and expressed Vpr, antagonized innate immune signaling. Phosphorylation of IRF3 at S396, but not S386, was also inhibited by Vpr. We provide evidence that Vpr interacts with karyopherins and disturbs their recruitment of IRF3 and NF-κB to prevent nuclear transport. Our data demonstrate Vpr rescue of HIV-1 replication in human macrophages from inhibition by cGAMP, the product of activated cGAS. We propose that Vpr inhibition of innate immune activation serves a critical function in promoting HIV-1 replication and transmission.

The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by chronic GC administration. Our results reveal a mechanism by which the circadian clock acts through REVERBa in liver on elements bound by HNF4A/HNF6 to direct GR action on energy metabolism.

Until recently (early 2018), there was no single coherent dataset that provided information on the spatial and temporal distribution of fishing effort at the scale of north Atlantic basin. Whilst data on fishing effort did exist for parts, e.g. the OSPAR / ICES vessel monitoring by satellite data that covers the OSPAR sea area, none extended to both the eastern and western areas simultaneously. However, in early 2018, Global Fishing Watch (GFW) released data describing fishing effort at a global scale (Kroodsma et al., 2018).

ATLAS work package 6 presentationat ATLAS 3rd General Assembly Effective Marine Spatial Planning (MSP) relies heavily on the collation of spatial data from a wide range of sources. Here we present a suite of open-source, synergistic software that can be used in an efficient workflow to store, analyse and visualise spatial data. For data storage we use PostgreSQL and PostGIS. PostgreSQL is a powerful object relational database system that has cross-platform support. It is extensible, with the PostGIS extension allowing it to store spatial data. For data visualisation and analysis we use R and QGIS. The R statistical programming language can be extended to be compatible with PostgreSQL / PostGIS. QGIS, a desktop GIS application, is similarly used in visualisation due to its intuitive interface and native support for PostgreSQL / PostGIS. Using the Rockall case study as an example we demonstrate the use of these software and their interactions in a workflow that can be used to support MSP efforts.

The bone marrow niche represents a specialized environment that regulates mesenchymal stem cell quiescence and self-renewal, yet fosters stem cell migration and differentiation upon demand. An in vitro model that embodies these features would open up the ability to perform detailed study of stem cell behavior. In this paper we present a simple bone marrow-like niche model, which comprises of nanomagnetically levitated stem cells cultured as multicellular spheroids within a type I collagen gel. The stem cells maintained are nestin positive and remain quiescent until regenerative demand is placed upon them. In response to coculture wounding, they migrate and appropriately differentiate upon engraftment. This tissue engineered regeneration-responsive bone marrow-like niche model will allow for greater understanding of stem cell response to injury and also facilitate as a testing platform for drug candidates in a multiwell plate format.

Over recent decades there has been and continues to be major advances in the imaging, diagnosis and potential treatment of medical conditions, by the use of magnetic nanoparticles. However, to date the majority of cell delivery studies employ a traditional 2D monolayer culture. This article aims to determine the ability of various sized magnetic nanoparticles to penetrate and travel through a cell seeded collagen gel model, in the presence or absence of a magnetic field. Three different sized (100, 200, and 500 nm) nanoparticles were employed in the study. The results showed cell viability was unaffected by the presence of nanoparticles over a 24-h test period. The initial uptake of the 100 nm nanoparticle into the collagen gel structure was superior compared to the larger sized nanoparticles under the influence of a magnetic field and incubated for 24 h. Interestingly, it was the 200 nm nanoparticles, which proved to penetrate the gel furthest, under the influence of a magnetic field, during the initial culture stage after 1-h incubation.

The sensory neurons innervating the urinary bladder and distal colon project to similar regions of the central nervous system and often are affected simultaneously by various diseases and disorders, including spinal cord injury. Anatomical and physiological commonalities between the two organs involve the participation of shared spinally derived pathways, allowing mechanisms of communication between the bladder and colon. Prior electrophysiological data from our laboratory suggest that the bladder also may receive sensory innervation from a nonspinal source through the vagus nerve, which innervates the distal colon as well. The present study therefore aimed to determine whether anatomical evidence exists for vagal innervation of the male rat urinary bladder and to assess whether those vagal afferents also innervate the colon. Additionally, the relative contribution to bladder and colon sensory innervation of spinal and vagal sources was determined. By using lipophilic tracers, neurons that innervated the bladder and colon in both the nodose ganglia (NG) and L6/S1 and L1/L2 dorsal root ganglia (DRG) were quantified. Some single vagal and spinal neurons provided dual innervation to both organs. The proportions of NG afferents labeled from the bladder did not differ from spinal afferents labeled from the bladder when considering the collective population of total neurons from either group. Our results demonstrate evidence for vagal innervation of the bladder and colon and suggest that dichotomizing vagal afferents may provide a neural mechanism for cross-talk between the organs.

International audience; Distribution data for elusive species are often based on detection of field signs rather than of the animal itself. However, identifying field signs can be problematic. We present here the results of a survey for American mink, , in the northern highlands of Scotland to demonstrate the importance of verifying field sign identification. Three experienced surveyors located scats, which they identified as mink scats, at seven of 147 sites surveyed and “possible” mink scats at a further 50 sites. Mitochondrial DNA was successfully extracted from 45 of 75 (60%) scats, collected from 31 of the 57 “positive” sites; sequencing of amplified DNA fragments showed that none of these scats was actually of mink origin. We consider the implications of erroneous survey data and the potential waste of resources and misdirection of conservation/management actions. We discuss potential methods that may be useful to verify field sign identification, including the use of DNA analysis, and stress that verification is crucial to ensure rigorous and reliable survey data.

The mechanical impact of a spinal cord injury (SCI) triggers a cascade of secondary damage that progressively destroys an increasing amount of tissue adjacent to the primary lesion over a period of hours to weeks. The pathophysiological changes lead to necrotic, as well as apoptotic death, inflammation, demyelination, and axonal damage. In their wake, a fluid-filled cavity often forms leaving a small rim of spared white matter. While the initial mechanically destructive events cannot be reversed, the cellular inflammatory reactions occur over several hours to weeks, a timeframe during which therapeutic intervention may be achieved. This thesis examines the efficacy of minocycline, a 2nd generation tetracycline-derivative, in attenuating secondary degeneration after SCI. The results of the first series of experiments indicate that the peak of apoptosis within the ascending sensory tracts (AST) following dorsal column transection in rats occurs at one to two weeks after injury. Numerous apoptotic profiles are located within both the proximal and distal segments of the AST after injury. Although oligodendrocytes undergo apoptosis as well as microglia, the latter are the main cell type to undergo apoptosis in this model. Importantly, minocycline administration delayed up to 30 minutes after injury, significantly reduces apoptosis, prevents corticospinal tract axonal dieback, diminishes lesion size and promotes functional recovery following a dorsal column transection. The results from the second series of experiments show that minocycline treatment reduces levels of mRNA and activation of p38 mitogen-activated protein kinase (MAPK) after SCI. In addition, p38 MAPK increases early after SCI and colocalizes with neutrophils, and microglia/macrophages. The final series of experiments assessed the efficacy of minocycline or the p38 MAPK inhibitor SB203580 in promoting neurological recovery utilizing a contusion model of SCI in rats to more closely mimic the injury seen in humans. The results from these experiments indicate that delayed minocycline treatment (1 hour after injury) administered intravenously promotes tissue preservation and functional recovery after SCI. Collectively, these findings suggest that several aspects of the secondary degeneration that occurs after SCI can be prevented by minocycline application, and supports its use as a potential neuroprotective treatment following human SCI.

Reliable quantitative evaluation of molecular pathways is critical for both drug discovery and treatment monitoring. We have modified the CAM assay to quantitatively measure vascular density, endothelial proliferation, and changes in protein expression in response to anti-angiogenic and pro-angiogenic agents. This improved CAM assay can correlate changes in vascular density with changes seen on a molecular level. We expect that these described modifications will result in a single in vivo assay system, which will improve the ability to investigate molecular mechanisms underlying the angiogenic response.

As its name suggests, this thesis is an account of the recent theory of the capacity of elements of Banach algebras. The first chapter contains a summary of the background theory, other than fundamentals, used, and consists mainly of perturbation theory of linear operators and certain properties (Jf strictly singular operators. This chapter relies heavily on the work of T„ Kato, both in his own papers and the book by S. Goldberg "Unbounded Linear Operators". Chapter 2 introduces the notion of capacity, following Halmos in his paper "Capacity in Banach algebras", and several small new results are proved, and counterexamples given, to tidy up "loose ends". The question of the capacity of the sum of two quasialgebraic elements (i.e. ones with capacity zero) is raised, and a partial solution given. The perturbation theory of Chapter 1 is applied to show the equality of the capacity of the spectrum and the Fredholn spectrum of an operator on a Banach space, whence it is shown that if J is a closed two-sided ideal of B(x) containing only Riesz operators, then perturbation by an element of J leaves the capacity invariant; this is true, in particular, for compact operators. A converse theorem is proved for Hilbert space, Chapter 3 introduces the new concept of the joint capacity of an r-tuple of elements cf a commutative Banach algebra, and develops the theory of this notion, Much of the theory parallels, xn a weaker form, that of the original concept, but there are significant differences. Finally, a perturbation theorem, similar to the original one is proved for the joint capacity.

Presentation given at the ATLAS 5th General Assembly, on using scenario-based simulations to improve marine spatial planning at Rockall Bank

Presentation given at the ATLAS 5th General Assembly, on using scenario-based simulations to improve marine spatial planning at Rockall Bank

The effect of various potential Inhibitors on methane oxidation was tested on whole-cell suspensions of Methylococcus capsulatus (strain Texas) (TRMC ) and Methylococcus capsulatus (strain Bath) (MC). Methane oxidation by TRMC was specifically inhibited by a large number of metal-chelating/binding agents and suggested the involvement of a metal ion(s) with the methane mono -oxygenase.\ud \ud The whole-cell results of MC showed a much more restricted specific inhibitor pattern for methane oxidation, which was confirmed by cell-free studies. The inhibitor pattern of MC was compared with that of TRMC and with reported patterns for other methane-utilisers. The effect of a number of acetylenic compounds on methane oxidation by MC was tested and the results discussed.\ud \ud The substrate specificity of the methane mono-oxygenase from MC was determined and found to be very non-specific. It catalysed the oxidation of various substituted methane derivatives, including methanol. C₁ -C₈ n-alkanes were hydroxylated to the corresponding 1- and 2-alcohols, carbon monoxide to carbon dioxide, terminal alkenes to the corresponding 1, 2-epoxides and internal alkenes to a variety of products. Ethers, alicyclic, aromatic and heterocyclic compounds were also oxidised. The significance of the various oxidations are discussed. Only NADPH could replace NADH as electron donor for methane mono-oxygenase activity.\ud \ud The subject of non-growth substrate oxidation by micro-organisms is discussed and the terminology of the area critically reviewed. Whole-cell oxidation studies with MC revealed five fortuitously oxidised non-growth substrates (chloromethane, bromomethane, dimethyl ether, ethene and propene) and seven cometabolic non-growth substrates (carbon monoxide, diethyl ether, ethane, propane, but-1 -ene, cis but-2-ene and trans but-2-ene). From these, dimethyl ether, bromomethane and carbon monoxide were selected to study in detail their effect on cellular metabolism of MC.\ud \ud During the oxidation studies it was suspected that an NAD(P)⁺ -linked aldehyde dehydrogenase was present. Confirmative tests proved positive. Activity in crude cell-free extracts was lost on dialysis, but could be restored by supplementing with inactive, heat-treated extract. The non-dialysable, heat-sensitive component was isolated and purified. The heat-stable component/co-factor was presumed to be a low molecular weight protein or polypeptide.\ud \ud The enzymic potential for an NAD(P)⁺ -linked cyclic scheme for the complete oxidation of formaldehyde was detected in crude cell- free extracts of MC. The relative Importance of the different formaldehyde oxidation systems found is discussed.\ud

Presentation at the 4th ATLAS General Assembly by David Stirling on progress towards deliverable 3.3: Developing case study HSM models for VME indicator taxa and key deep-sea fish species under current environmental conditions

ATLAS work package 3presentationat ATLAS 3rd General Assembly The assessment of Good Environmental Status (GES) is a cornerstone in the Marine Strategy Framework Directive (MSFD). In May 2017 a new commission decision was published (COMMISSION DECISION (EU) 2017/848 of 17 May 2017 that laid down criteria and methodological standards on GES of marine waters and specifications along with standardised methods for monitoring and assessment, repealing Decision 2010/477/EU). To explore how better to assess GES in the deep-sea is an important aspect tackled within ATLAS (WP3) and substantial progress has been made over the last year in developing indicators and thresholds to assess GES in the ATLAS Case Studies (including areas beyond national jurisdictions). GES assessment within ATLAS focuses on four out of eleven descriptors (D) included in the MSFD: D1 (Biological diversity is maintained. The quality and occurrence of habitats and the distribution and abundance of species are in line with prevailing physiographic, geographic and climatic conditions), D3 (Populations of all commercially exploited fish and shellfish are within safe biological limits, exhibiting a population age and size distribution that is indicative of a healthy stock), D6 (Sea-floor integrity is at a level that ensures that the structure and functions of the ecosystems are safeguarded and benthic ecosystems, in particular, are not adversely affected) and D10 (Properties and quantities of marine litter do not cause harm to the coastal and marine environment). The first step taken in assessing GES in the deep-sea was the selection of suitable GES indicators already included in the NEAT (Nested Environmental status Assessment Tool) Data Base generated in the EU project DEVOTES (http://www.devotes-project.eu/neat/); the second step was the addition of specific GES indicators for deep-sea ecosystems; the third step, that is currently ongoing, is the establishment of threshold values for the selected indicators. This is based on a comprehensive review of the scientific literature (more than 290 papers have been included already in a database) that has been carried out in order to extract quantitative information for the deep-sea benthic habitats and ecosystems to have a basis for the threshold selection. Next steps will be to apply the methodology described to selected ATLAS case studies, namely by assessing GES using the new data collected and the NEAT approach.

Until recently (early 2018), there was no single coherent dataset that provided information on the spatial and temporal distribution of fishing effort at the scale of north Atlantic basin. Whilst data on fishing effort did exist for parts, e.g. the OSPAR / ICES vessel monitoring by satellite data that covers the OSPAR sea area, none extended to both the eastern and western areas simultaneously. However, in early 2018, Global Fishing Watch (GFW) released data describing fishing effort at a global scale (Kroodsma et al., 2018).

Until recently (early 2018), there was no single coherent dataset that provided information on the spatial and temporal distribution of fishing effort at the scale of north Atlantic basin. Whilst data on fishing effort did exist for parts, e.g. the OSPAR / ICES vessel monitoring by satellite data that covers the OSPAR sea area, none extended to both the eastern and western areas simultaneously. However, in early 2018, Global Fishing Watch (GFW) released data describing fishing effort at a global scale (Kroodsma et al., 2018).

Presentation at the 4th ATLAS General Assembly by David Stirling on progress towards deliverable 3.3:Developingcase study HSM models for VME indicator taxa and key deep-sea fish species under current environmental conditions

ATLAS work package 3 presentation at ATLAS 3rd General Assembly The assessment of Good Environmental Status (GES) is a cornerstone in the Marine Strategy Framework Directive (MSFD). In May 2017 a new commission decision was published (COMMISSION DECISION (EU) 2017/848 of 17 May 2017 that laid down criteria and methodological standards on GES of marine waters and specifications along with standardised methods for monitoring and assessment, repealing Decision 2010/477/EU). To explore how better to assess GES in the deep-sea is an important aspect tackled within ATLAS (WP3) and substantial progress has been made over the last year in developing indicators and thresholds to assess GES in the ATLAS Case Studies (including areas beyond national jurisdictions). GES assessment within ATLAS focuses on four out of eleven descriptors (D) included in the MSFD: D1 (Biological diversity is maintained. The quality and occurrence of habitats and the distribution and abundance of species are in line with prevailing physiographic, geographic and climatic conditions), D3 (Populations of all commercially exploited fish and shellfish are within safe biological limits, exhibiting a population age and size distribution that is indicative of a healthy stock), D6 (Sea-floor integrity is at a level that ensures that the structure and functions of the ecosystems are safeguarded and benthic ecosystems, in particular, are not adversely affected) and D10 (Properties and quantities of marine litter do not cause harm to the coastal and marine environment). The first step taken in assessing GES in the deep-sea was the selection of suitable GES indicators already included in the NEAT (Nested Environmental status Assessment Tool) Data Base generated in the EU project DEVOTES (http://www.devotes-project.eu/neat/); the second step was the addition of specific GES indicators for deep-sea ecosystems; the third step, that is currently ongoing, is the establishment of threshold values for the selected indicators. This is based on a comprehensive review of the scientific literature (more than 290 papers have been included already in a database) that has been carried out in order to extract quantitative information for the deep-sea benthic habitats and ecosystems to have a basis for the threshold selection. Next steps will be to apply the methodology described to selected ATLAS case studies, namely by assessing GES using the new data collected and the NEAT approach.

Lung cancer is the leading cause of cancer related death worldwide; despite recent treatment developments survival rates remain poor and are closely related to the patient’s clinical stage. Even among patients with early-stage lung cancer, which is amenable to surgical resection, prognosis is highly variable; some go on to live disease-free for many years whereas others quickly recur. Although post-operative chemotherapy is available it has associated morbidities and it is unclear which patients would benefit; therefore, there is a need for more effective stratification of patients. The adenocarcinoma sub-type of lung cancer is known to be morphologically heterogeneous however the majority of observed growth patterns, assessed by light microscopy, can be characterised into one of five formations: lepidic, papillary, acinar, solid and micropapillary. The morphology of each tumour has been proposed as a marker of prognosis and several studies have published a link between the most prevalent growth pattern and prognosis; suggesting those with predominantly solid or micropapillary tumours to have the least favourable outcomes. Indeed, it is now recommended that the proportion of each growth pattern and the predominant growth pattern should be reported for all resected lung adenocarcinomas; although no differential treatments have been recommended based on this assessment. The aim of this study was to determine whether combining the analysis of clinicopathological; morphological; and candidate protein, molecular genetic and transcriptomic characteristics in a single cohort of 208 early-stage, resected, adenocarcinomas with clinical follow-up could be used to identify a subset of patients at high risk of recurrence. Comprehensive morphological analysis was carried out including the presence, proportion and number of individual growth patterns; the predominant growth pattern as well as features previously associated with tumour grade (the presence of large numbers of mitotic figures, apoptotic bodies, inflammatory cells, prominent nucleoli, pleomorphic tumour cells, dyscohesive tumour cells and large amounts of necrosis and scar tissue within the tumour). In addition, gene expression was assessed using a panel of 31 cell-cycle related genes, EGFR and KRAS mutation status was determined, and EGFR and TTF1 protein expression investigated. In this study the predominant growth pattern defined by histopathology showed no ability to identify a group of patients with a poorer prognosis either in univariable or multivariable analysis. Univariable analysis identified nodal status [hazard ratio of N1 compared to N0 was 2.16 (95% CI 1.48 to 3.16, p< 0.0005)], clinical stage [hazard ratios of stage IIa and IIb compared to stage Ia were 3.15 (95% CI 1.73 to 5.73, p< 0.0005) and 2.22 (95% CI 1.10 to 4.48, p= 0.025) respectively], the presence of a significant amount of the papillary growth pattern [the hazard ratio of those with less than 8.5% papillary pattern was 0.657 (95% CI 0.44 to 0.98, p= 0.035)], and overall tumour grade score (including an assessment of necrosis, mitosis, apoptosis, nucleoli, scar tissue and inflammatory cells) [hazard ratio 1.71 (95% CI 1.14 to 2.56, p= 0.008)] as significantly associated with prognosis. Multivariable analysis using Cox’s proportional hazards model identified clinical stage (p< 0.0005), the presence of a significant amount of the papillary growth pattern (p= 0.048) and the presence of large numbers of mitotic figures (p=0.029) and apoptotic bodies (p= 0.015) as independently associated with disease specific survival; although after correction for type I errors only clinical stage remained significantly associated with prognosis with patients with stage Ia disease having a significantly better outcomes [hazard ratio 0.418 (95% CI 0.20 to 0.86)]. Classification and regression tree analysis (CART) was used to further explore the data and to develop decision trees for the prognostication of early-stage lung adenocarcinoma patients. Receiver operating characteristic analysis based on 5- year survival showed a minimal improvement in the area under the curve between a model utilizing currently available clinicopathologic characteristics only [nodal status and lesion size, (area under the curve 0.704, 95% CI 0.631 to 0.777)] and one including growth pattern characteristics [area under the curve 0.725, 95% CI 0.654 to 0.796]. The greatest improvement in prognostic accuracy was observed when gene expression analysis was included in the analysis [area under the curve 0.749, 95% CI 0.673 to 0.825]; however even this showed very little impact compared to routinely used clinicopathologic variables. This analysis suggests that the recommended characterisation of lung adenocarcinoma histology is not a robust predictor of patient outcomes; even a broader model which also included indicators of tumour grade and molecular characteristics was unable to identify a model sufficiently robust to implement into clinical practice and thereby potentially alter patient treatment. Currently routinely collected clinical characteristics; including nodal status, size and clinical stage; continue to provide the most robust method of prognostication and detailed and time-consuming morphological analysis offers no significant benefit to the patient.